enhancement-intestinal-recombinant-adeno-associated-virus-absorption

Enhancement of Intestinal Recombinant Adeno-Associated Virus Absorption by a Traditional Chinese Medicine Formula

Oral recombinant adeno-associated virus (rAAV) delivery holds significant therapeutic potential but is limited by inefficient intestinal absorption. ...

Naval Medical University

A two-generation reproductive toxicity study was performed to evaluate the effects of cerium nitrate on the development of the parent, offspring, and third generation of Sprague-Dawley (SD) rats. A total of 240 SD rats (30 rats/sex/group) were randomly divided into four dosage groups according to body weight: 0 mg/kg, 30 mg/kg, 90 mg/kg, and 270 mg/kg. The rats were administered different dosages of cerium nitrate by oral gavage. There were no observed changes related to cerium nitrate in body weight, food consumption, sperm survival rate, motility, mating rate, conception rate, abortion rate, uterine plus fetal weight, uterine weight, corpus luteum number, implantation rate, live fetus number (rate), stillbirth number (rate), absorbed fetus number (rate), appearance, visceral, and skeletal in rats of each generation dosage group. In addition, the pathological findings showed no significant lesions associated with cerium nitrate toxicity in all tissues and organs, including reproductive organs. In conclusion, the present study showed that long-term oral gavage of cerium nitrate at 30 mg/kg, 90 mg/kg, and 270 mg/kg had no significant effect on reproduction and the developmental ability of their offspring in rats. The no-observed-adverse-effect level (NOAEL) of cerium nitrate in SD rats was higher than 270 mg/kg.

A Two-Generation Reproductive Toxicity Study of Cerium Nitrate in Sprague-Dawley Rats.

Food waste management is an important global issue, and anaerobic digestion (AD) is a sustainable technology for treating food waste and developing a circular economy. Odor and health problems in AD plants have drawn increasing public attention. Therefore, this study investigated the odor characteristics and health risks in different workshops of food waste AD plants. At each site, the treatment capacities for kitchen and restaurant waste were 200 and 200-250 tons per day, respectively. Among the detected odorants, ethanol was the dominant component in terms of concentrations, while methanethiol, propanethiol, HS, and acetaldehyde were the major odor contributors in different workshops. The odor contribution of propanethiol had been previously overlooked in several workshops. The unloading, pretreatment, and bio-hydrolysis workshops were identified as major areas requiring odor control. Besides odor, carcinogenic and non-carcinogenic risks commonly existed in food waste AD plants. The carcinogenic risk of acetaldehyde had been underestimated previously, and it was identified as the dominant carcinogen. Furthermore, benzene was a potential carcinogen. Non-carcinogenic risks were mainly caused by acetaldehyde, HS, and ethyl acetate. The health risks were not always consistent with odor nuisance. Based on the odor and health risk assessments, several air pollution control strategies for food waste AD plants were proposed, including food waste source control, in-situ pollution control, and ex-situ pollution control.

Food waste anaerobic digestion plants: Underestimated air pollutants and control strategy.

Hydrogen sulfide (HS) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled HS and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to HS was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of HS exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, HS not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.

Chronic inhalation of HS in low concentration induces immunotoxicity and inflammatory effects in lung tissue of rats.

Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR).

Low-dose-rate induces more severe cognitive impairment than high-dose-rate in rats exposed to chronic low-dose γ-radiation.

Dengue Virus (DENV) is a life-threatening pathogen leading to dengue fever, which brings about huge public health challenges globally. However, traditional detection methods currently fail to meet the increasing demands of clinic practice in terms of speed, simplicity, and accuracy. To address these limitations, we developed a novel, rapid, and highly sensitive diagnostic method for universal DENV detection by integrating recombinase polymerase amplification (RPA) assay and the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) and associated (Cas) protein 12a (CRISPR/Cas12a) system into one-pot. This approach achieves exceptional sensitivity and specificity for DENV detection, with the entire process completed within 40 min, without the need for sophisticated equipment. The limit of detection (LOD) was determined to be 91.7 copies/test. Using this one-pot RT-RPA CRISPR/Cas12a detection system, all four serotypes of DENV (1 to 4) were successfully identified. In terms of specificity, the assay accurately detected DENV-infected positive samples without cross-reactivity with four other interfering viruses-infected samples (VSV, SeV, HSV-1 and IAV). Furthermore, we established a universal DENV RT-RPA-CRISPR/Cas12a-lateral flow dipstick (LFD) platform, which successfully identified all four serotypes of DENV with a sensitivity of approximately 250 copies/test. Collectively, our method not only provides a robust alternative for universal DENV detection but also offers valuable insights for the identification of other viruses.

A one-pot method for universal Dengue virus detection by combining RT-RPA amplification and CRISPR/Cas12a assay.

Sepsis is a life-threatening disease caused by the dysregulation of the immune response. It is important to identify influential genes modulating the immune response in sepsis. In this study, we used P-NET, a biologically informed explainable artificial intelligence model, to evaluate the gene importance for sepsis. About 688 important genes were identified, and these genes were enriched in pathways involved in inflammation and immune regulation, such as the PI3K-Akt signalling pathway, necroptosis and the NF-κB signalling pathway. We further selected differentially expressed genes both at bulk and single-cell levels and found TIMP1, GSTO1 and MYL6 exhibited significant different expressions in multiple cell types. Moreover, the expression levels of these 3 genes were correlated with the abundance of important immune cells, such as M-MDSC cells. Further analysis demonstrated that these three genes were highly expressed in sepsis patients with worse outcomes, such as severe, non-survived and shock sepsis patients. Using a drug repositioning strategy, we found navitoclax, curcumin and rotenone could down-regulate and bind to these genes. In conclusion, TIMP1, GSTO1 and MYL6 may serve as promising biomarkers and targets for sepsis treatment.

Sepsis Important Genes Identification Through Biologically Informed Deep Learning and Transcriptomic Analysis.

The high prevalence of pre-existing neutralizing antibodies (NAbs) against adeno-associated virus (AAV) poses a major obstacle to in vivo gene therapy. Current immunosuppressive (IS) strategies, such as corticosteroids, are limited by toxicity and adverse effects. To explore safer alternatives, we evaluated dihydroartemisinin (DHA), a synthetic derivative of artemisinin inspired by traditional Chinese medicine (TCM), as a potential IS agent.

Dihydroartemisinin decreases pre-existing neutralizing antibodies against adeno-associated virus in challenged mice.

Pancreatic ductal adenocarcinoma (PDAC) is a prevalent and lethal form of cancer. According to clinical trials results, immunotherapy has not been successful in PDAC so far, which may be due to the high heterogeneity of the tumour immune microenvironment (TIME) of PDAC patients. This study aimed to identify significant genes associated with the prognosis and immune microenvironment of PDAC using interpretive deep learning.

Identification of key genes in pancreatic ductal adenocarcinoma with biologically informed deep neural network.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death around the world, with therapy resistance posing a substantial obstacle to enhancing patient outcomes. Cancer-associated fibroblasts (CAFs), the predominant stromal cells within the tumor microenvironment (TME), have been identified as pivotal contributors to HCC progression and therapeutic resistance. CAFs have direct or indirect interactions with cancer cells, leading to immune evasion and drug resistance. This review mostly concentrates on the role of CAFs in HCC, particularly how CAFs influence chemotherapy, targeted therapy, and immunotherapy. Additionally, it explores synergistic therapeutic strategies targeting CAFs. It has been found that targeting CAFs or disrupting their interactions with other cells offers promising avenues for dealing with drug resistance and improving the effectiveness of therapies in HCC.

Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.

Article	Year
A Two-Generation Reproductive Toxicity Study of Cerium Nitrate in Sprague-Dawley Rats. Biological trace element research\| PubMed ID: 37148403	2024
Food waste anaerobic digestion plants: Underestimated air pollutants and control strategy. The Science of the total environment\| PubMed ID: 37572914	2023
Chronic inhalation of HS in low concentration induces immunotoxicity and inflammatory effects in lung tissue of rats. Ecotoxicology and environmental safety\| PubMed ID: 38581906	2024
Low-dose-rate induces more severe cognitive impairment than high-dose-rate in rats exposed to chronic low-dose γ-radiation. Frontiers in public health\| PubMed ID: 38841686	2024
A one-pot method for universal Dengue virus detection by combining RT-RPA amplification and CRISPR/Cas12a assay. BMC microbiology\| PubMed ID: 40128655	2025
Sepsis Important Genes Identification Through Biologically Informed Deep Learning and Transcriptomic Analysis. Clinical and experimental pharmacology & physiology\| PubMed ID: 40356040	2025
Dihydroartemisinin decreases pre-existing neutralizing antibodies against adeno-associated virus in challenged mice. Frontiers in pharmacology\| PubMed ID: 40822466	2025
Identification of key genes in pancreatic ductal adenocarcinoma with biologically informed deep neural network. Journal of gastrointestinal oncology\| PubMed ID: 41220726	2025
Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies. Cancer gene therapy\| PubMed ID: 41691133	2026

Jingjing Fang

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