Various poly(l-histidine) based amphiphilic copolymers have been developed for intracellular drug delivery due to the pH responsive properties and the escape from endolysosomal pathway. However, the pH induced reassembly of copolymer micelles and the assumed endolysosome membrane rupture during the copolymer facilitated endolysosomal escape have never been elucidated. To address these issues, a series of poly(ethylene glycol)-poly(d,l-lactide)-poly(l-histidine) (mPEG-PLA-PHis) with different degrees of polymerization of PLA and PHis block were synthesized. The self-assembly and reassembly behaviors of the copolymers were characterized using transmission electron microscopy (TEM), (1)H NMR, fluorescence probe technique, and dynamic light scattering (DLS). The copolymers self-assembled into micelles with PLA and unprotonated PHis blocks as hydrophobic core and PEG as hydrophilic shell at neutral pH. The changes in TEM images, (1)H NMR spectrum of PHis peak, pyrene fluorescene spectrum, and particle size as well as size distribution over the pH range from pH 8.5 to 4.5 suggest that the copolymer micelles reassembled into micelles with PLA as hydrophobic core and protonated PHis and PEG as hydrophilic shell under acidic environment. The pH induced reassembly triggered the incoporated doxorubicin (DOX) release, as indicated by the in vitro accelerated drug release and enhanced cytotoxicity. The integrity of endolysosome membrane during the copolymer facilitated DOX endolysosomal escape was observed by confocal laser scan microscopy (CLSM) and further evaluated by hemolysis test and calculation of the critical size of endolysosomal membrane. The results indicate that the endolysosomal membrane remained intact during the copolymer facilitated endolysosomal escape of DOX. It is more reasonable to ascribe the PHis based copolymer facilitation endolysosomal escape to the "proton sponge" hypothesis without rupturing the endolysosomal membrane.
Cognitive processes require working memory (WM) that involves a brief period of memory retention known as the delay period. Elevated delay-period activity in the medial prefrontal cortex (mPFC) has been observed, but its functional role in WM tasks remains unclear. We optogenetically suppressed or enhanced activity of pyramidal neurons in mouse mPFC during the delay period. Behavioral performance was impaired during the learning phase but not after the mice were well trained. Delay-period mPFC activity appeared to be more important in memory retention than in inhibitory control, decision-making, or motor selection. Furthermore, endogenous delay-period mPFC activity showed more prominent modulation that correlated with memory retention and behavioral performance. Thus, properly regulated mPFC delay-period activity is critical for information retention during learning of a WM task.
For children with stage II malignant testicular germ cell tumors (MGCT), the survival is good with chemotherapy-assisted surgery. However, there is limited data on surgical results for cases in which there was no imaging or pathologic evidence of residual tumor, but in which serum tumor markers either increased or failed to normalize after an appropriate period of half-life time post-surgery. To determine the use of chemotherapy for children with stage II germ cell tumors, we carefully analyzed the outcomes (relapse rate and overall survival) of patients who were treated at the Sun Yat-sen University Cancer Center between January 1990 and May 2013. Twenty-four pediatric patients with a median age of 20 months (range, 4 months to 17 years) were enrolled in this study. In 20 cases (83.3%), the tumors had yolk sac histology. For definitive treatment, 21 patients underwent surgery, and 3 patients received surgery and adjuvant chemotherapy. No relapse was observed in the 3 patients who received adjuvant chemotherapy, whereas relapse occurred in 16 of the 21 patients (76.2%) treated with surgery alone. There were a total of 2 deaths. Treatment was stopped for one patient, who died three months later due to the tumor. The other patient achieved complete response after salvage treatment, but developed lung and pelvic metastases 7 months later and died of the tumor after stopping treatment. For children treated with surgery alone and surgery combined with adjuvant chemotherapy, the 3-year event-free survival rates were 23.8% and 100%, respectively (P = 0.042), and the 3-year overall survival rates were 90.5% and 100%, respectively (P = 0.588). These results suggest that adjuvant chemotherapy can help to reduce the recurrence rate and increase the survival rate for patients with stage II germ cell tumors.
Longitudinal analysis of medical imaging data has become central to the study of many disorders. Unfortunately, various constraints (study design, patient availability, technological limitations) restrict the acquisition of data to only a few time points, limiting the study of continuous disease/treatment progression. Having the ability to produce a sensible time interpolation of the data can lead to improved analysis, such as intuitive visualizations of anatomical changes, or the creation of more samples to improve statistical analysis. In this work, we model interpolation of medical image data, in particular shape data, using the theory of optimal mass transport (OMT), which can construct a continuous transition from two time points while preserving "mass" (e.g., image intensity, shape volume) during the transition. The theory even allows a short extrapolation in time and may help predict short-term treatment impact or disease progression on anatomical structure. We apply the proposed method to the hippocampus-amygdala complex in schizophrenia, the heart in atrial fibrillation, and full head MR images in traumatic brain injury.
Sulfur-doped graphene quantum dots (S-GQDs) with stable blue-green fluorescence were synthesized by one-step electrolysis of graphite in sodium p-toluenesulfonate aqueous solution. Compared with GQDs, the S-GQDs drastically improved the electronic properties and surface chemical reactivities, which exhibited a sensitive response to Fe(3+). Therefore, the S-GQDs were used as an efficient fluorescent probe for highly selective detection of Fe(3+). Upon increasing of Fe(3+) concentration ranging from 0.01 to 0.70 ?M, the fluorescence intensity of S-GQDs gradually decreased and reached a plateau at 0.90 ?M. The difference in the fluorescence intensity of S-GQDs before and after adding Fe(3+) was proportional to the concentration of Fe(3+), and the calibration curve displayed linear regions over the range of 0-0.70 ?M. The detection limit was 4.2 nM. Finally, this novel fluorescent probe was successfully applied to the direct analysis of Fe(3+) in human serum, which presents potential applications in clinical diagnosis and may open a new way to the design of effective fluorescence probes for other biologically related targets.
This study aimed to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) in combination with three-dimensional conformal radiotherapy (3D-CRT) in the treatment for locally advanced unresectable hepatocellular carcinoma (HCC).
Odorant binding proteins (OBPs) are crucial for insects to detect food, mates, predators, or other purposes. They are mostly located on antennae and other olfactory sensilla. In this study, we identified an OBP from the venom of Pteromalus puparum, designated as PpOBP. The cDNA of PpOBP is 517 bp in length, encoding 132 amino acids. Phylogenetic analysis revealed that PpOBP was clustered with OBP68 and OBP67 of Nasonia vitripennis. PpOBP was highly expressed in the venom apparatus at the transcriptional and translational levels. PpOBP was located in all parts of venom apparatus including venom gland, venom reservoir, and Dufour's gland. During 0-6 days post adult eclosion, the PpOBP mRNA level peaked at 2 days in the venom apparatus, whereas the protein remained at a high level. In the venom apparatus, the PpOBP mRNA was significantly upregulated following feeding with honey and parasitization. We propose that PpOBP is involved in parasitoid-host interactions.
Abnormal salience attribution is implicated in heroin addiction. Previously, combining functional magnetic resonance imaging (fMRI) and a drug cue-reactivity task, we demonstrated abnormal patterns of subjective response and brain reactivity in heroin-dependent individuals. However, whether the changes in cue-induced brain response were related to relapse was unknown. In a prospective study, we recruited 49 heroin-dependent patients under methadone maintenance treatment, a gold standard treatment (average daily dose 41.8?±?16.0?mg), and 20 healthy subjects to perform the heroin cue-reactivity task during fMRI. The patients' subjective craving was evaluated. They participated in a follow-up assessment for 3 months, during which heroin use was assessed and relapse was confirmed by self-reported relapse or urine toxicology. Differences between relapsers and non-relapsers were analyzed with respect to the results from heroin-cue responses. Compared with healthy subjects, relapsers and non-relapsers commonly demonstrated significantly increased brain responses during the processing of heroin cues in the mesolimbic system, prefrontal regions and visuospatial-attention regions. However, compared with non-relapsers, relapsers demonstrated significantly greater cue-induced craving and the brain response mainly in the bilateral nucleus accumbens/subcallosal cortex and cerebellum. Although the cue-induced heroin craving was low in absolute measures, the change in craving positively correlated with the activation of the nucleus accumbens/subcallosal cortex among the patients. These findings suggest that in treatment-seeking heroin-dependent individuals, greater cue-induced craving and greater specific regional activations might be related to reward/craving and memory retrieval processes. These responses may predict relapse and represent important targets for the development of new treatment for heroin addiction.
Methadone maintenance treatment (MMT) is safe and effective for heroin addiction, but the neural basis of the length effects of long-term MMT on brain activity during craving in former heroin addicts is unclear. This study explored it by comparing the brain activations of heroin addicts with different length of MMT during pictorial presentation of heroin-related cue. Fifteen male former heroin addicts successfully treated by MMT less than 1 year (Group A), 15 matched patients with 2-3 year MMT (Group B) and 17 healthy controls underwent functional magnetic resonance imaging while heroin-related and neutral stimuli were present to them. Subjective cue-elicited craving was measured with visual analog scale before and after imaging. Then, partial correlation analysis to reveal the relationship between drug-related blood oxygen level dependent (BOLD) signal intensity and heroin or methadone use history. Finally, self-reported craving was not different between Group A and B before and after scanning. Compared with Group A, Group B had a significant reduced brain activity to heroin-related minus neural cues in the bilateral caudate. After controlling for the variable heroin use history, the drug-related BOLD signal intensity in the bilateral caudate was negatively correlated with MMT duration and total methadone consumption. When MMT history was controlled, the drug-related activity intensity in right caudate had a positive correlation with heroin daily dosage. Long-term MMT may improve heroin-craving response by modulating the impaired function in the bilateral dorsal striatum caused by former heroin use.
To examine the dynamic maturational alterations of random amplified polymorphic DNA (RAPD) molecular marker polymorphism resulted from differential expressions of multiple fungi in the caterpillar body, stroma and ascocarp portion of Cordyceps sinensis (Cs).
Pediatric anaplastic large cell lymphoma (ALCL) has rarely been reported in Chinese pediatric patients. This study evaluated the clinical characteristics and treatment outcome of Chinese pediatric patients with ALCL. Between October 2002 and October 2012, 39 untreated pediatric patients with ALCL were enrolled at a single institution. The patients were stratified into three groups (R1, R2, and R3) based on the stage of the disease, clinical risk factors, and chemotherapeutic response, and received different intensive chemotherapy regimens based on a modified B-NHL-BFM-90 protocol. Of the 39 patients, 22 were boys, and 17 were girls, with a median age at diagnosis of 10 years (range 2-16 years), 91.2% were anaplastic lymphoma kinase (ALK)-positive. The patient groups R1, R2, and R3 accounted for 12.8%, 30.4%, and 56.4% of the total, respectively. 87.2% of patients were stage III/IV. At a median follow-up period of 52 months (range 15-136 months), seven patients relapsed and three patients died of their disease. The 5-year event-free survival for all patients was 81.4% ± 6.4%, with 100%, 83.3% ± 10% and 75.3% ± 9.8% for groups R1, R2, and R3, respectively. The overall survival for all patients was 92.2% ± 4.3%. Our study demonstrates that a risk-stratified treatment with a modified B-NHL-BFM-90 protocol is efficacious for Chinese children with ALCL.
Untargeted metabolomics analysis of rhubarb and stewed rhubarb samples shows that the determined samples clearly clustered in to two groups, indicating that the processing procedures caused changes in the composition and/or content of components in rhubarb. Ten components were identified by UHPLC-Q-TOF-MS/MS and references, which intensity declined in rhubarb after processing. Targeted metabolomics analysis of rhubarb and stewed rhubarb samples indicated that aloe-emodin, rhein, emodin and physcion were detected with lower intensity in stewed rhubarb samples than in rhubarb samples. Metabolomics analysis of rhubarb and stewed rhubarb indicated the various components of rhubarb changed after processing.
Two hybrid processes including ozonation-ceramic membrane-biological activated carbon (BAC) (Process A) and ceramic membrane-BAC (Process B) were compared to treat polluted raw water. The performance of hybrid processes was evaluated with the removal efficiencies of turbidity, ammonia and organic matter. The results indicated that more than 99% of particle count was removed by both hybrid processes and ozonation had no significant effect on its removal. BAC filtration greatly improved the removal of ammonia. Increasing the dissolved oxygen to 30.0 mg/L could lead to a removal of ammonia with concentrations as high as 7.80 mg/L and 8.69 mg/L for Processes A and B, respectively. The average removal efficiencies of total organic carbon and ultraviolet absorbance at 254 nm (UV254, a parameter indicating organic matter with aromatic structure) were 49% and 52% for Process A, 51% and 48% for Process B, respectively. Some organic matter was oxidized by ozone and this resulted in reduced membrane fouling and increased membrane flux by 25%-30%. However, pre-ozonation altered the components of the raw water and affected the microorganisms in the BAC, which may impact the removals of organic matter and nitrite negatively.
Conventional chemotherapy against hepatocellular carcinoma typically causes various side effects. Our previous study showed that cecropin of Musca domestica can induce apoptosis in human hepatocellular carcinoma BEL-7402 cells in vitro. However, whether cecropin inhibits BEL-7402 cell in vivo and the question of possible side effects remained undentified. The present study confirmed tumor-inhibitory effects of cecropin in vivo, and furthermore strongly suggested that cecropin cytotoxicity in BEL-7402 cells in vivo may be mainly derived from its pro-apoptotic action. Specifically, we found that cecropin exerted no obvious side effects in tumor-bearing mice as it had no significant hematoxicity as well as visceral toxicity. Therefore, cecropin may be a potential candidate for further investigation as an antitumor agent against hepatocellular carcinoma.
Hydrolytic amino acids were extracted by acid hydrolysis method, then derivatized with phenyl isothiocyanate (PITC). And the samples were analysed by HPLC on an Ultimate Prime C18 (4.6 mm x 250 mm, 5 microm) column with gradient elution of 0.1 mol x L(-1) sodium acetate buffer solution (adjusted to pH 6. 5)-acetonitrile (93:7) (A) and acetonitrile-water (8:2) (B) at a flow rate of 1.0 mL x min(-1). Column temperature was 40 degrees C and the detected wavelength was 254 nm. Amino acids derivative solution remained stable in 36 hours. The response was linear for 16 amino acids with a correlation coefficient r > 0.999 5. The average recoveries were 98.01% -101.8%. The method is reliable with good accuracy and repeatability, which is useful for the determination of amino acids in Galli Gigerii Endothelium Corneum.
Active heat flow control is essential for broad applications of heating, cooling, and energy conversion. Like electronic devices developed for the control of electric power, it is very desirable to develop advanced all-thermal solid-state devices that actively control heat flow without consuming other forms of energy. Here we demonstrate temperature-gated thermal rectification using vanadium dioxide beams in which the environmental temperature actively modulates asymmetric heat flow. In this three terminal device, there are two switchable states, which can be regulated by global heating. In the "Rectifier" state, we observe up to 28% thermal rectification. In the "Resistor" state, the thermal rectification is significantly suppressed (<1%). To the best of our knowledge, this is the first demonstration of solid-state active-thermal devices with a large rectification in the Rectifier state. This temperature-gated rectifier can have substantial implications ranging from autonomous thermal management of heating and cooling systems to efficient thermal energy conversion and storage.
Superoxide dismutase (SOD) is an antioxidant enzyme involved in detoxifying reactive oxygen species. In this study, we identified genes encoding the extracellular and intracellular copper-zinc SODs (ecCuZnSOD and icCuZnSOD) and a manganese SOD (MnSOD) in the yellow mealworm beetle, Tenebrio molitor. The cDNAs for ecCuZnSOD, icCuZnSOD, and MnSOD, respectively, encode 24.55, 15.81, and 23.14 kDa polypeptides, which possess structural features typical of other insect SODs. They showed 20-94% identity to other known SOD sequences from Bombyx mori, Musca domestica, Nasonia vitripennis, Pediculus humanus corporis, and Tribolium castaneum. Expression of these genes was analyzed in selected tissues and developmental stages, and following exposure to Escherichia coli and parasitization by Scleroderma guani. We recorded expression of all three SODs in cuticle, fat body, and hemocytes and in the major developmental stages. Relatively higher expressions were detected in late-instar larvae and pupae, compared to other developmental stages. Transcriptional levels were upregulated following bacterial infection. Analysis of pupae parasitized by S. guani revealed that expression of T. molitor SOD genes was significantly induced following parasitization. We infer that these genes act in immune response and in host-parasitoid interactions.
Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.
Periductal stromal sarcoma (PSS), spindle and epithelioid types, is a rare subtype of malignant fibroepithelial tumor. The morphological characteristics of this neoplasm are different from phyllodes tumor and stromal sarcoma. PSS exhibits biphasic histology with benign ductal elements and a sarcomatous stroma composed of spindle cells and lacking phyllodes tumor architecture. The therapeutic management of PSS is based on wide surgery with free margins, and adjuvant therapies are not required. To the best of our knowledge, the recurrence of PSS in ?5 months has not been reported in the literature to date. This report describes a 43-year-old woman who presented to our hospital with a recurrence of nodules in the left breast. The patient had undergone lumpectomy at a different hospital 5 months previously, and a diagnosis of phyllodes tumor was pathologically confirmed. On presentation at our hospital, the patient underwent a second lumpectomy. Histological examination revealed PSS and the patient underwent a simple mastectomy of the left breast with no adjuvant treatment (such as chemotherapy or radiotherapy). After 9 months of close follow-up examinations, no recurrence was observed. PSS is an extremely rare disease with low-grade sarcomatous behavior, which may evolve into a phyllodes tumor or an entity of breast cancer. Therefore, frequent follow-up examinations are required.
An integrated process was specifically developed for the decentralized supply of drinking water from micro-polluted surface water in the rural areas of China. The treatment process combined ozonation with ceramic ultra-filtration (UF), coagulation for pre-treatment and granular activated carbon filtration. A flat-sheet ceramic membrane was used with a cut-off of 60 nm and the measurement of 254 mm (length) × 240 mm (width) × 6 mm (thickness). Ozonation and ceramic UF was set up whthin one reactor. The experimental results showed that the removal efficiencies of the dissolved organic carbon (DOC) and the formation potential of trihalomethanes (THMs), haloacetic acids (HAAs) and ammonia were 80%, 76%, 70% and 90%, respectively; that the turbidity of the product water was below 0.2 NTU and the particle count number (particles larger than 2 ?m) was less than 50 counts per mL. The result also showed that all the pathogenic microorganisms were retained by the ceramic and that UF. Ozonation played a critical role in the control of membrane fouling and the removal of contaminants. Exactly, the membrane fouling can be controlled in situ with 3 mg L(-1) ozone at the permeate flux of 80 L m(-2)?h(-1), yet the required dosage of ozone was dependent on the quality of the raw water. Therefore, this study is able to provide a highly compacted system for decentralized supply of high-quality drinking water in terms of both chemical and microbiological safety for the rural areas in China.
This study compared the decoction's HPLC figures of the different processed rhizomes of Cibotium barometz including the raw, the sand-baked, the wined, the steamed and the salted, on the basis of which, with the sand-baked Drynaria fortunei decoction as the positive control group, comparingall groups' decoction, concentration of which was 104.2 g x L(-1), for 4 weeks, by their effects (s-TRAP and total scores of OPG, Ca, P, IL-6, TNF-alpha and IL-1) on retinoic acid induced male rats osteoporosis. The experiment results showed the sand-baked and the wined were better than the steamed, the salted and the raw;in the processing methods' selection, the sand-baked was a better heating method than the steamed and the rice wine was the better excipient than the salt. It provided a reference to explain the processing principle of rhizomes of C. barometz and work mechanism of anti-osteoporosis.
Direct metal-free C-4-selective indolation of pyridines is achieved for the first time using TEMPO and (Boc)2O. A variety of substituents on both indoles and pyridines are tolerated to give 3-(pyridin-4-yl)-1H-indole derivatives in moderate to excellent yields. This finding provides a novel approach for developing metal-free C-H functionalization of pyridines.
SYF2, also known as CCNDBP1-interactor or p29, is reported in pre-mRNA splicing and cell cycle progression. However, the role of SYF2 in esophageal squamous cell carcinoma (ESCC) development remains elusive. In the present study, Western blot and immunohistochemistry assays demonstrated that SYF2 was overexpressed in ESCC tumor tissues and cell lines. In addition, immunohistochemistry analysis revealed that SYF2 expression was positively correlated with tumor grade and predicted poor prognosis of ESCC. In vitro studies using serum starvation-refeeding experiment and SYF2-siRNA transfection assay demonstrated that SYF2 expression promoted proliferation of ESCC cells, while SYF2 knockdown led to decreased cell growth rate and colony formation resulted from growth arrest of cell cycle at G0/G1 phase. Furthermore, our results indicated that SYF2 can down-regulate the sensitivity of ESCC cells for cisplatin. Our findings for the first time supported that SYF2 might play an important role in the regulation of ESCC proliferation and would provide a novel therapeutic strategy against human ESCC.
Ectoparasitoid wasps deposit their eggs onto the surface and inject venom into their hosts. Venoms are chemically complex and they exert substantial impact on hosts, including permanent or temporary paralysis and developmental arrest. These visible venom effects are due to changes in expression of genes encoding physiologically relevant proteins. While the influence of parasitization on gene expression in several lepidopterans has been reported, the molecular details of parasitoid/beetle relationships remain mostly unknown. This shortcoming led us to pose the hypothesis that envenomation by the ectoparasitic ant-like bethylid wasp Scleroderma guani leads to changes in protein expression in the yellow mealworm beetle Tenebrio molitor. We tested our hypothesis by comparing the proteomes of non-parasitized and parasitized host pupae using iTRAQ-based proteomics. We identified 41 proteins that were differentially expressed (32?- and 9?-regulated) in parasitized pupae. We assigned these proteins to functional categories, including immunity, stress and detoxification, energy metabolism, development, cytoskeleton, signaling and others. We recorded parallel changes in mRNA levels and protein abundance in 14 selected proteins following parasitization. Our findings support our hypothesis by documenting changes in protein expression in parasitized hosts.
Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-?B (NF-?B) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-?), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-?B activity, increased TNF-? and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-?B signaling pathway that in turn up-regulate nephrin and podocin protein expression.
As the major mechanism of plant growth and morphogenesis, cell elongation is controlled by many hormonal and environmental signals. How these signals are coordinated at the molecular level to ensure coherent cellular responses remains unclear. In this study, we illustrate a molecular circuit that integrates all major growth-regulating signals, including auxin, brassinosteroid, gibberellin, light, and temperature. Analyses of genome-wide targets, genetic and biochemical interactions demonstrate that the auxin-response factor ARF6, the light/temperature-regulated transcription factor PIF4, and the brassinosteroid-signaling transcription factor BZR1, interact with each other and cooperatively regulate large numbers of common target genes, but their DNA-binding activities are blocked by the gibberellin-inactivated repressor RGA. In addition, a tripartite HLH/bHLH module feedback regulates PIFs and additional bHLH factors that interact with ARF6, and thereby modulates auxin sensitivity according to developmental and environmental cues. Our results demonstrate a central growth-regulation circuit that integrates hormonal, environmental, and developmental controls of cell elongation in Arabidopsis hypocotyl.
A new palladium-catalyzed oxidative cyclization process leading to the functionalized bicyclo[4,3,0]nonenes is serendipitously discovered during attempts to form aza-heterocycle by the amino-Heck reaction of trans-2-vinylclohexyl phosphinyloxime. Under the influence of Pd(dba)2/Et3N/1:1 N2-O2 (1:1, v/v) (Method A) or Pd(OAc)2/Et3N/O2 (Method B), the reactions afford the substituted cis-1-hydroxyl-8-formyl-bicyclo[4,3,0]non-8(9)-enes or bicycle[4,3,0]non-1(9)-en-8-ones in varying yields with the incorporation of molecular oxygen into the structures. The 5,6-bicyclic scaffold of these products is presumably derived from tandem double intramolecular cyclization followed by the ring-opening of an aza-palladium(II) tricyclic intermediate.
Organic nanofibers are formed by simple ionic co-assembly of positively charged porphyrin (electron donor) and negatively charged perylenediimide (electron acceptor) derivatives in aqueous solution. Two kinds of electron transfer routes between electron donor and electron acceptor under light excitation in nanofibers are confirmed by DFT calculations and experimental data.
Paediatric systemic lupus erythematosus (pSLE) refers to childhood-onset systemic lupus erythematosus. pSLE has its own unique characteristics, and its pathogenesis is unclear. To study the relationship between microRNAs (miRNAs) and pSLE, we selected three pSLE patients who were newly diagnosed and had not yet been treated, and two controls were also included. We collected their peripheral blood mononuclear cells to perform Agilent human miRNA (8×15 k) 12.0 analysis. To verify the results, we next selected 12 other pSLE patients who had different disease activities and 3 healthy controls and conducted real-time PCR. The results showed high expression of miRNA-516a-3p, miRNA-629 and miRNA-525-5p in pSLE patients with active disease; these levels were normal in patients without active disease. Increased expression levels of these three miRNAs were positively correlated with the score obtained from the systemic lupus erythematosus disease activity index scoring system (SLEDAI) 2000 and C-reactive protein (CRP) levels. Furthermore, the target genes of these three miRNAs were important to the pathogenesis of pSLE. Therefore, these three miRNAs might be specific to pSLE and may be used as novel biomarkers of pSLE to diagnose and monitor the disease.
There is no consensus whether Sertoli cells express estrogen receptor 1 (Esr1). Reverse transcription-polymerase chain reaction, Western blot, and immunofluorescence demonstrated that mouse Sertoli cell lines, TM4, MSC-1, and 15P-1, and purified primary mouse Sertoli cells (PSCs) contained Esr1 messenger RNA and proteins. Incubation of Sertoli cells with 17?-estradiol (E2) or ESR1 agonist stimulated the expression of an estrogen responsive gene Greb1, which was prevented by ESR inhibitor or ESR1 antagonist. Overexpression of Esr1 in MSC-1 enhanced E2-induced Greb1 expression, while knockdown of Esr1 by small interfering RNA in TM4 attenuated the response. Furthermore, E2-induced Greb1 expression was abolished in the PSCs isolated from Amh-Cre/Esr1-floxed mice in which Esr1 in Sertoli cells were selectively deleted. Chromatin immunoprecipitation assays indicated that E2-induced Greb1 expression in Sertoli cells was mediated by binding of ESR1 to estrogen responsive elements. In summary, ligand-dependent nuclear ESR1 was present in mouse Sertoli cells and mediates a classical genomic action of estrogens.
Genital herpes simplex virus (HSV) reactivation is thought to be anatomically and temporally localized, coincident with limited ganglionic infection. Short, subclinical shedding episodes are the most common form of HSV-2 reactivation, with host clearance mechanisms leading to rapid containment. The anatomic distribution of shedding episodes has not been characterized. To precisely define patterns of anatomic reactivation, we divided the genital tract into a 22-region grid and obtained daily swabs for 20 days from each region in 28 immunocompetent, HSV-2-seropositive persons. HSV was detected via PCR, and sites of asymptomatic HSV shedding were subjected to a biopsy procedure within 24 h. CD4(+) and CD8(+) T cells were quantified by immunofluorescence, and HSV-specific CD4(+) T cells were identified by intracellular cytokine cytometry. HSV was detected in 868 (7%) of 11,603 genital swabs at a median of 12 sites per person (range, 0 to 22). Bilateral HSV detection occurred on 83 (67%) days with shedding, and the median quantity of virus detected/day was associated with the number of sites positive (P < 0.001). In biopsy specimens of asymptomatic shedding sites, we found increased numbers of CD8(+) T cells compared to control tissue (27 versus 13 cells/mm(2), P = 0.03) and identified HSV-specific CD4(+) T cells. HSV reactivations emanate from widely separated anatomic regions of the genital tract and are associated with a localized cellular infiltrate that was demonstrated to be HSV specific in 3 cases. These data provide evidence that asymptomatic HSV-2 shedding contributes to chronic inflammation throughout the genital tract.
RW-Cb, the first processed product of Cibotium barometz (L.) J. Sm. (Dicksoniaceae) in TCM has been widely used to treat osteoporosis, a major worldwide health problem, influencing more and more people in the word et al. To do research on RW-Cb, one processed product of Cibotium barometz (L.) J. Sm. (Dicksoniaceae) in TCM has been widely used to treat osteoporosis, a major worldwide health problem, influencing more and more people in the word et al.
A self-assembly approach to preparing iron phthalocyanine/single-walled carbon nanotube (FePc/SWNT) heterojunction nanowires as a new oxygen reduction reaction (ORR) electrocatalyst has been developed by virtue of water-adjusted dispersing in 1-cyclohexyl-pyrrolidone (CHP) of the two components. The FePc/SWNT nanowires have a higher Fermi level compared to pure FePc (d-band center, DFT=-0.69 eV versus -0.87 eV, respectively). Consequently, an efficient channel for transferring electron to the FePc surface is readily created, facilitating the interaction between FePc and oxygen, so enhancing the ORR kinetics. This heterojunction-determined activity in ORR illustrates a new stratagem to preparing non-noble ORR electrocatalysts of significant importance in constructing real-world fuel cells.
Bai-Zhu, the dried rhizome of Atractylodes macrocephala Koidz (AMK), is widely used as a tonic herbal in eastern Asia. It is commonly used as prepared slices in clinic by stir-frying with wheat bran (processed AMK). In the theories of traditional Chinese medicine (TCM), Bai-Zhu possesses significantly different therapeutic effects before and after processing. However, the molecular mechanics of this processing is still unknown. In this paper, the strategy of metabolomics was employed to investigate the changes of chemical constituents in Atractylodes macrocephala Koidz after processing. Meanwhile, the cell activity test variation of processed and unprocessed medicine was used to interpret the processing mechanism of AMK. Using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) with the method of multivariate statistic analyses including principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA), atractylenolide I, atractylenolide II, atractylenolide III, atractylenolide VI, 7-hydroxycoumarin, 8-?-methoxy atractylenolide I and Selina-4 (14), 7 (11)-dien-8-one were rapidly explored as the potential chemical markers of raw and processed AMK, respectively. Furthermore, it could be speculated that the processing mechanism of AMK was to increase the content of atractylenolide III which could strengthen the effect on gastrointestinal function.
Brassinosteroid (BR) regulates plant development by activating the transcription factor brassinazole resistant 1 (BZR1), which activates and represses different target genes to switch cellular programmes. The mechanisms that determine BZR1's transcriptional activities remain largely unknown. Here we show that BZR1 represses target genes by recruiting the Groucho/TUP1-like transcriptional corepressor TOPLESS (TPL). Specific deletion or mutation of an evolutionarily conserved ERF-associated amphiphilic repression (EAR) motif at the carboxy terminus abolishes BZR1's abilities to regulate gene expression and cell elongation, but these defects are rescued by TPL fusion to the EAR motif-mutated BZR1. The EAR motif in BZR1 mediates recruitment of TPL to BZR1-repressed promoters. A triple tpl mutant (tpl;tpr1;tpr4) shows reduced BR sensitivity and suppresses the gain-of-function bzr1-1D mutant phenotype. BR repression of gene expression also requires histone deacetylases that interact with TPL. Our study demonstrates key roles of the EAR motif and TPL in BR regulation of gene expression and plant growth.
Thermodynamically driven self-assembly offers a direct route to organize individual nanoscopic components into three-dimensional structures over a large scale. The most thermodynamically favourable configurations, however, may not be ideal for some applications. In plasmonics, for instance, nanophotonic constructs with non-trivial broken symmetries can display optical properties of interest, such as Fano resonance, but are usually not thermodynamically favoured. Here, we present a self-assembly route with a feedback mechanism for the bottom-up synthesis of a new class of symmetry-breaking optical metamaterials. We self-assemble plasmonic nanorod dimers with a longitudinal offset that determines the degree of symmetry breaking and its electromagnetic response. The clear difference in plasmonic resonance profiles of nanorod dimers in different configurations enables high spectra selectivity. On the basis of this plasmonic signature, our self-assembly route with feedback mechanism promotes the assembly of desired metamaterial structures through selective excitation and photothermal disassembly of unwanted assemblies in solution. In this fashion, our method can selectively reconfigure and homogenize the properties of the dimer, leading to highly monodispersed aqueous metamaterials with tailored symmetries and electromagnetic responses.
Nanostructure-based photovoltaic devices have exhibited several advantages, such as reduced reflection, extraordinary light trapping, and so forth. In particular, semiconductor nanostructures provide optical modes that have strong dependence on the size and geometry. Metallic nanostructures also attract a lot of attention because of the appealing plasmonic effect on the near-field enhancement. In this study, we propose a novel design, the metal-core/semiconductor-shell nanocones with the core radius varying in a linearly gradient style. With a thin layer of semiconductor absorber coated on a metallic cone, such a design can lead to significant and broadband absorption enhancement across the entire visible and near-infrared solar spectrum. As an example of demonstration, a layer of 16 nm thick crystalline silicon (c-Si) coated on a silver nanocone can absorb 27% of standard solar radiation across a broad spectral range of 300-1100 nm, which is equivalent to a 700 nm thick flat c-Si film. Therefore, the absorption enhancement factor approaching the Yablonovitch limit is achieved with this design. The significant absorption enhancement can be ascribed to three types of optical modes, that is, Fabry-Perot modes, plasmonic modes, and hybrid modes that combine the features of the previous two. In addition, the unique nanocone geometry enables the linearly gradient radius of the semiconductor shell, which can support multiple optical resonances, critical for the broadband absorption. Our design may find general usage as elements for the low cost, high efficiency solar conversion and water-splitting devices.
A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained on-state drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.
Ovarian Stertoli-Ledig cell tumor (SLCT) is a rare type of sex cord-stromal tumor of the ovary. The present study was to evaluate clinicalopahologic features and prognosis of patients with Sertoli-Leydig cell tumor treated by surgery and adjuvant chemotherapy during short term follow-up.
To examine the maturational changes in proteomic polymorphisms resulting from differential expression by multiple intrinsic fungi in the caterpillar body and stroma of natural Cordyceps sinensis (Cs), an integrated micro-ecosystem.
This study is to investigate the effects of vitamin D on renal fibrosis in rat diabetic nephropathy models, as well as the changes and interactions in the expressions of renal fibrogenesis- and inflammation-related genes. Rat diabetic nephropathy models were established by high-fat diets, which were subjected to TGF-?1 manipulation, as well as vitamin D treatment. H&E staining, Masson staining, and TEM detection were performed to assess the effects of vitamin D treatment and/or TGF-?1 manipulation on pathological changes in the renal tissues in these rat diabetic nephropathy models. Immunohistology and real-time PCR were used to evaluate the expressions of TGF-?1, MCP-1, CTGF, and VDR. Histological staining and TEM detection showed that, in both TGF-?1 over-expressed and interfered groups, vitamin D administration alleviated the renal fibrosis, compared with the vehicle treatment. Similar results were observed with the immunohistological staining. Real-time PCR analysis indicated that, when TGF-?1 was over-expressed in diabetic nephropathy, the expressions of MCP-1 and CTGF were also up-regulated, which would be decreased by the treatment of vitamin D. On the other hand, when TGF-?1 was interfered in DN, the expressions of MCP-1 and CTGF were relatively down-regulated, which would be further lowered by vitamin D administration. The mRNA expression of VDR was elevated by vitamin D treatment in these diabetic nephropathy models. Active vitamin D3 and lentivirus-mediated TGF-?1 interference could effectively reduce the renal fibrosis and protect the renal function in diabetic nephropathy rat models, which makes a promising therapeutic strategy for the disease.
Fourier transform infrared (FTIR) microspectroscopy was applied to in-situ analyse the chemical change of tibial articular subchondral bone of female Hartley guinea pigs with age increase. Three infrared absorption regions (a, b, c) of trabecular bone and central marrow region of the subchondral bone were measured for guinea pigs of different ages (1 months, 2 months and 3 months) using the infrared spectrum. Results show that (1) with months increasing, the total area of trabecular bone is increasing, meanwhile, the region a which is similar to normal trabecular bone spectra is decreasing, and region d waveform has the same trend as region a. (2) In the second and third month, region b & c show amide Ill redshift and the red shift in region c shows a shoulder peak, showing the absorption peak intensity on behalf of nucleic acid and polysaccharide in region b & c is 7 times that in region a. (3) beta glycosidic bond absorption peak appears at region c in 3 different old pigs. (4) I(amide III) / I(amide II) is the highest in region b in the second month but lowest in the third month; I(amide III) / I(amide II) reduces from a to c in the second and third month; I(upsilon3)PO2- / I(amide II) in region b & c is 7 times higher than region a in the second and third Month These results are consistent with the regular pattern of change rule of osteoarthritis subchondral bones organization structure and chemical composition in different stages. Our primary result illustrated that FTIR microspectroscopy can be used for in-situ analysis of the molecular organization of subchondral trabecular bone and bone marrow. It provides reliable pathology information for osteoarthritis subchondral bone tissue at molecular level.
Methylation abnormalities in T lymphocytes have been reported to correlate with systemic lupus erythematosus (SLE). Previous studies identified hypomethylation in the promoter of several genes linked to SLE. Long interspersed nucleotide element-1 (LINE-1) constitutes 17-25% of the human genome, and LINE-1 hypomethylation has been reported in SLE. Limited information is available regarding LINE-1 methylation in juvenile SLE (JSLE).
Cobalt is a promising soft metallic magnetic material used for important applications in the field of absorbing stealth technology, especially for absorbing centimeter waves. However, it frequently presents a weak dielectric property because of its instability, aggregation, and crystallographic form. A method for enhancing the electromagnetic property of metal Co via phase-controlled synthesis of Co nanostructures grown on graphene (GN) networks has been developed. Hexagonal close-packed cobalt (?-Co) nanocrystals and face-centered cubic cobalt (?-Co) nanospheres with uniform size and high dispersion have been successfully assembled on GN nanosheets via a facile one-step solution-phase strategy under different reaction conditions in which the exfoliated graphite oxide (graphene oxide, GO) nanosheets were reduced along with the formation of Co nanocrystals. The as-synthesized Co/GN nanocomposites showed excellent microwave absorbability in comparison with the corresponding Co nanocrystals or GN, especially for the nanocomposites of GN and ?-Co nanocrystals (the reflection loss is -47.5 dB at 11.9 GHz), which was probably because of the special electrical properties of the cross-linked GN nanosheets and the perfect electromagnetic match in their microstructure as well as the small particle size of Co nanocrystals. The approach is convenient and effective. Some magnetic metal or alloy materials can also be prepared via this route because of its versatility.
A general and efficient method for the cross-coupling of indoles with ?-keto esters by using TEMPO/CuSO4·5H2O in air as oxidant has been developed. This reaction features high functional-group compatibility and an excellent selectivity. This methodology provides an alternative approach for the ketonization-olefination of indoles in moderate to good yields.
Doxorubicin-loaded PLGA nanoparticles (DOX-PLGA NPs) was prepared by double emulsion (W/O/W) solvent evaporation method with the biodegradable materials-poly (lactic-co-glycolic acid) (PLGA) used as carrier materials. Single-factor test was used to investigate the influence of the type and ratio of the organic phase, the amount of surfactant, PLGA concentration, the ratio of external water phase and oil phase (W/O), the ratio of doxorubicin and PLGA, ultrasonic time and stirring time on the preparation of nanoparticles. The best formulation and preparation conditions were optimized by orthogonal test based on single-factor test, evaluation indicator as particle size and entrapment efficiency, and the results were analyzed by overall desirability. And the in vitro release behaviors of the nanoparticles were studied as well. The size distribution, zeta potential, morphology of DOX-PLGA NPs were characterized by laser light scattering and transmission electron microscopy; encapsulation efficiency and releasing behavior of DOX-PLGA NPs in vitro were investigated by ultraviolet spectrophotometry. The results show that the DOX-PLGA NPs are regularly spherical in shape with the mean size of (189.2 +/- 5.3) nm, and the zeta-potential of the NPs is about (-28.32 +/- 0.52) mV. Drug loading and encapsulation efficiency are estimated to be (73.16 +/- 0.43) % and (1.51 +/- 0.07) %, respectively. The cumulative percentage of the drug released is 90.34%, and the in vitro release behavior made up of initial burst release and sustained-release could be described by the bidirectional kinetic equation. The results indicate that hydrophilic small-molecule drugs could be successfully entrapped into PLGA-NPs. With optimization of the formulation and preparation conditions, we obtained uniform and stable DOX-PLGA NPs with sustained release character in vitro and pH-sensitive property, which could provide the experimental basis for the development of a new anti-tumor sustained-release formulation.
Excessive extracellular glutamate leads to neuronal death in central nervous system. Excitatory glutamate transporter subtype 2 (GLT-1) carries bulk of glutamate reuptake in cerebral ischemia. Although GLT-1 expression fluctuates during the period of ischemia, little is known about its regulatory mechanism. Here we show an up-regulation of GLT-1 via mammalian target of rapamycin (mTOR)-Akt-nuclear factor-?B (NF-?B) signaling cascade in oxygen glucose deprivation (OGD). We found that brief rapamycin treatment significantly increased GLT-1 expression in cultured astrocytes. Rapamycin increased phosphorylation of raptor at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1 expression. This conclusion was further confirmed by raptor and rictor disruption experiments. Akt was activated by mTORC1 inhibition and required for GLT-1 expression because triciribine, a specific inhibitor of Akt, blocked the increase of GLT-1 expression. mTOR-Akt cascade then activated NF-?B and increased ?B-motif-binding phosphoprotein (KBBP) expression and GLT-1 transcription. We next demonstrated that mTOR-Akt-NF-?B cascade was activated in OGD and subsequently caused the upregulation of GLT-1. Supporting evidence included: (1) inhibition of Akt or NF-?B occluded OGD-induced GLT-1 upregulation; (2) Raptor knock-down plus OGD did not add to the increase of GLT-1 expression; (3) Intact mTORC2 was required for GLT-1 enhancement. In summary, our data first showed that mTOR-Akt-NF-?B cascade played critical roles to up-regulate GLT-1 in OGD. This signaling cascade may work to promote glutamate uptake in brain ischemia and neurodegenerative diseases.
Intensive research has demonstrated that extracellular matrix (ECM) molecules and growth factors (GF) collaborate at many different levels. The ability of ECM to modulate GF signals has important implications in tissue formation and homeostasis as well as novel therapies for acute and chronic wounds. Recently, a number of GF-binding sites was identified in fibronectin (FN) and was shown to provide another layer of regulation on GF signaling. Here, we review these new findings on FN interaction with GF in the context of general ways ECM molecules regulate GF signaling.Journal of Investigative Dermatology advance online publication, 12 December 2013; doi:10.1038/jid.2013.484.
Growth factor-binding domains identified in various extracellular matrix proteins have been shown to regulate growth factor activity in many ways. Recently, we identified a fibronectin peptide (P12) that can bind platelet-derived growth factor BB (PDGF-BB) and promote adult human dermal fibroblast (AHDF) survival under stress. In vivo experiments in a porcine burn injury model showed that P12 limited burn injury progression, suggesting an active role in tissue survival. In this report, we explored the molecular mechanism of this peptide in ADHF under nutrient deprivation. Our results showed that P12 acted like some cell-penetrating peptides in that it redirected ligand-bound PDGF receptor (PDGFR) from the clathrin-dependent endocytic pathway to a slower, macropinocytosis-like pathway. P12 slowed internalization and degradation of PDGF-BB, augmented its survival signals, and promoted cell survival after nutrient removal. Our findings demonstrate a mechanism for a potential therapeutic peptide that increases cell and tissue survival by acting as a cofactor to PDGF-BB.Journal of Investigative Dermatology advance online publication, 5 December 2013; doi:10.1038/jid.2013.463.
A pilot-scale ballasted flocculation system was used to remove fluoride from one type of industrial wastewater. The system included the formation of calcium fluoride (CaF2) using calcium hydroxide followed by coagulation sedimentation. Calcium fluoride was recycled as nuclei for enhancing CaF2 precipitation and as a ballasting agent for improving fluoride removal and flocculation efficiency. Factors affecting fluoride and turbidity removal efficiencies, including pH in the CaF2-reacting tank and coagulation-mixing tank, sludge recycling ratio, and dosages of FeCl3 and polyacrylamide (PAM), were investigated in the pilot-scale system. The recycled CaF2 precipitates improved CaF2 formation kinetics, enhanced fluoride removal and flocculation performance. Under the optimized condition, the ballast flocculation process reduced fluoride concentration from 288.9 to 10.67 mg/L and the turbidity from 129.6 NTU to below 2.5 NTU.
Lymphoma is seen in up to 30% of patients with X-linked lymphoproliferative disease (XLP), but cerebral vasculitis related with XLP after cure of Burkitt lymphoma is rarely reported. We describe a case of a 5-year-old boy with XLP who developed cerebral vasculitis two years after cure of Burkitt lymphoma. He had Burkitt lymphoma at the age of 3 years and received chemotherapy (non-Hodgkins lymphoma-Berlin-Frankfurt-Milan-90 protocol plus rituximab), which induced complete remission over the following two years. At the age of 5 years, the patient first developed headache, vomiting, and then intellectual and motorial retrogression. His condition was not improved after anti-infection, dehydration, or dexamethasone therapy. No tumor cells were found in his cerebrospinal fluid. Magnetic resonance imaging showed multiple non-homogeneous, hypodense masses along the bilateral cortex. Pathology after biopsy revealed hyperplasia of neurogliocytes and vessels, accompanied by lymphocyte infiltration but no tumor cell infiltration. Despite aggressive treatment, his cognition and motor functions deteriorated in response to progressive cerebral changes. The patient is presently in a vegetative state. We present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system.
Stressors after injury from a multitude of factors can lead to cell death. We have identified four fibronectin (FN) peptides: two from the first FN type III repeat (FNIII1), one from the 13th FN type III repeat (FNIII13), and one from FN variable region (IIICS), which when tethered to a surface acted as platelet-derived growth factor-BB (PDGF-BB) enhancers to promote cell survival. One of the FNIII1 peptides and its smallest (14-mer) bioactive form (P12) were also active in solution. Specifically, P12 bound PDGF-BB (KD=200?nM), enhanced adult human dermal fibroblast (AHDF) survival under serum starvation, oxidative or endoplasmic reticulum stressors, and limited burn-injury progression in a rat hot comb model. Furthermore, P12 inhibited endoplasmic reticulum stress-induced c-Jun N-terminal kinase (JNK) activation. Although many growth factors have been found to bind FN directly or indirectly, here we identify peptide sequences of growth factor-binding sites in FN. The finding of these peptides further delineated how the extracellular matrix protein FN can support cell survival. As the peptide P12 is active in either soluble form or tethered to a substrate, it will have multifactorial uses as a bioactive peptide by itself or in tissue engineering.Journal of Investigative Dermatology advance online publication, 7 November 2013; doi:10.1038/jid.2013.420.
Insulin is a secreted peptide hormone identified in human pancreas to promote glucose utilization. Insulin has been observed to induce cell proliferation and myogenesis in C2C12 cells. The precise mechanisms underlying the proliferation of C2C12 cells induced by insulin remain unclear. In this study, we observed for the first time that 10 nM insulin treatment promotes C2C12 cell proliferation. Additionally, 50 and 100 nM insulin treatment induces C2C12 cell apoptosis. By utilizing real-time PCR and Western blotting analysis, we found that the mRNA levels of cyclinD1 and BAD are induced upon 10 and 50 nM/100 nM insulin treatment, respectively. The similar results were observed in C2C12 cells expressing GATA-6 or PPAR?. Our results identify for the first time the downstream targets of insulin, cyclin D1, and BAD, elucidate a new molecular mechanism of insulin in promoting cell proliferation and apoptosis.
This study aims to investigate the effects of UV-C irradiation on photosynthetic processes of Microcystis aeruginosa to unravel the mechanism(s) involved in how and in what ways UV-C mediates growth suppression and cellular recovery. Changes in the concentration of photosynthetic pigments, photochemical efficiency, PS II core protein (D1) content, and the coding genes expressions were measured. The results indicate that UV-C doses at 20-200 mJ cm(-2) lead to rapid reduction in gene expression of both psbA (for D1) and cpc (for phycocyanin), but the suppression was short term and recoverable within 3 d of post-UV incubation. Conversely, UV-C doses at ?50 mJ cm(-2) could induce marked decline in photochemical efficiency (represented by the optimal PS II quantum yield, FV/FM, and the effective PS II quantum yield, Y) as well as decreases in D1 content and water soluble pigments (phycoerythrins, phycocyanins, allophycocyanins) in M. aeruginosa during the post UV-C incubation period. The results suggest that interruption of both the light energy harvesting apparatus (especially the water soluble pigments) and the photochemical process mainly accounted for the growth suppression effect in UV-C irradiated M. aeruginosa.
Exposure to addictive drugs has been associated with disrupted brain white matter integrity. A few studies have examined the white matter deficits in heroin users; however, the results were influenced by the use of substitution drugs such as methadone and buprenorphine. The present study assessed the alteration in white matter integrity and heroin-related neuropathology in heroin dependents who had not received any replacement therapy using quantitative diffusion tensor imaging (DTI). The study comprised 17 heroin-dependent (HD) subjects and 15 matched healthy controls (HC). Fractional anisotropy (FA) and eigenvalues (??, ?||) of white matter in the whole brain were measured and compared using a voxel-based analysis. The correlation between DTI measurements in identified regions and history of heroin exposure was tested by partial correlation analysis. Compared with HCs, HD subjects displayed decreased FA in the bilateral frontal lobe sub-gyrus, cingulate gyrus, medial frontal gyrus, extra-nuclear, left temporal lobe sub-gyrus and right superior frontal gyrus. Among these regions, the HD group had significantly increased ?? in the bilateral frontal lobe sub-gyrus, cingulate gyrus and extra-nuclear relative to the HC group. There were no group differences in ?||. In addition, there were no significant correlations between duration of heroin use or accumulated dosage and FA or ?? values. In conclusion, chronic heroin-dependent subjects had widespread disruption of white matter structural connectivity located mainly in anterior and superior regions of the brain. Damage to myelin other than axons was the primary pathological feature in the brain of the heroin user.
This article presents a highly integrated hybrid process for the advanced treatment of drinking water in dealing with the micro-polluted raw water. A flat sheet ceramic membrane with the pore size of 50?60 nm for ultrafiltration (UF) is used to integrate coagulation and ozonation together. At the same time, biological activated carbon filtration (BAC) is used to remove the ammonia and organic pollutants in raw water. A pilot study in the scale of 120 m(3)/d has been conducted in Southern China. The mainly-analyzed parameters include turbidity, particle counts, ammonia, total organic carbon (TOC), UV254, biological dissolved organic carbon (BDOC), dissolved oxygen (DO) as well as trans-membrane pressure (TMP). The experiments demonstrated that ceramic UF-membrane was able to remove most of turbidity and suspended particulate matters. The final effluent turbidity reached to 0.14 NTU on average. BAC was effective in removing ammonia and organic matters. Dissolved oxygen (DO) is necessary for the biodegradation of ammonia at high concentration. The removal efficiencies reached to 90% for ammonia with the initial concentration of 3.6 mg/L and 76% for TOC with the initial concentration of 3.8 mg/L. Ozonation can alter the molecular structure of organics in terms of UV254, reduce membrane fouling, and extend the operation circle. It is believed the hybrid treatment process developed in this article can achieve high performance with less land occupation and lower cost compared with the conventional processes. It is especially suitable for the developing countries in order to obtain high-quality drinking water in a cost-effective way.
In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.
Pediatric diffuse large B-cell lymphoma (DLBCL) is a highly aggressive disease with unique clinical characteristics. This study analyzed the germinal-center type B-cell (GCB) classification and clinical characteristics of Chinese pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat-sen University Cancer Center between February 2000 and May 2011, with an age younger than 18 years, were included in the analysis. The male/female ratio was 3.47:1. The median age was 12 years (range, 2 to 18 years), and 47 (61.8%) patients were at least 10 years old. Of the 76 patients, 48 (63.2%) had stage III/IV disease, 9 (11.8%) had bone marrow involvement, 1 (1.3%) had central nervous system (CNS) involvement, and 5 (6.6%) had bone involvement. The GCB classification was assessed in 45 patients: 26 (57.8%) were classified as GCB subtype, and 19 (42.2%) were classified as non-GCB subtype. The modified B-NHL-BFM-90/95 regimen was administered to 50 patients, and the 4-year event-free survival (EFS) rate was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification: 17 (54.8%) were classified as GCB subtype, with a 4-year EFS rate of 88.2%; 14 (45.2%) were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our data indicate that bone marrow involvement and stage III/IV disease are common in Chinese pediatric DLBCL patients, whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype. The modified B-NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.
The brassinosteroid (BR) class of steroid hormones regulates plant development and physiology. The BR signal is transduced by a receptor kinase-mediated signal transduction pathway, which is distinct from animal steroid signalling systems. Recent studies have fully connected the BR signal transduction chain and have identified thousands of BR target genes, linking BR signalling to numerous cellular processes. Molecular links between BR and several other signalling pathways have also been identified. Here, we provide an overview of the highly integrated BR signalling network and explain how this steroid hormone functions as a master regulator of plant growth, development and metabolism.
Neurons critically depend on the long-distance transport of mitochondria. Motor proteins kinesin and dynein control anterograde and retrograde mitochondrial transport, respectively in axons. The regulatory molecules that link them to mitochondria need to be better characterized. Nuclear distribution (Nud) family proteins LIS1, Ndel1 and NudCL are critical components of cytoplasmic dynein complex. Roles of these Nud proteins in neuronal mitochondrial transport are unknown. Here we report distinct functions of LIS1, Ndel1 and NudCL on axonal mitochondrial transport in cultured hippocampal neurons. We found that LIS1 interacted with kinsein family protein KIF5b. Depletion of LIS1 enormously suppressed mitochondrial motility in both anterograde and retrograde directions. Inhibition of either Ndel1 or NudCL only partially reduced retrograde mitochondrial motility. However, knocking down both Ndel1 and NudCL almost blocked retrograde mitochondrial transport, suggesting these proteins may work together to regulate retrograde mitochondrial transport through linking dynein-LIS1 complex. Taken together, our results uncover novel roles of LIS1, Ndel1 and NudCL in the transport of mitochondria in axons.
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