real-time-label-free-imaging-quantitative-analysis-macrophage

Real-Time Label-Free Imaging and Quantitative Analysis of Macrophage Morphodynamics Using Optical Diffraction Tomography

This study establishes a label-free optical diffraction tomography (ODT)-based workflow for live-cell imaging and analysis to observe time-dependent ...

Peking University

Ecological migration serves as an important measure for poverty eradication as well as for the protection, inheritance, and utilization of traditional ecological knowledge. This study investigated and cataloged the traditional forage plant resources and recorded the associated traditional knowledge of immigrant villages in Hongsibu District of Ningxia, China. The diversity of traditional forage plant resources and the changes in associated traditional ecological knowledge were compared among ecological immigrant villages from different emigration areas, with a hope of providing a reference for forage development, the conservation of wild forage plant resources, and the development of regional animal husbandry.

Changes in traditional ecological knowledge of forage plants in immigrant villages of Ningxia, China.

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.

CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells.

Regulatory T cell (Treg) stability is necessary for the proper control of immune activity and tissue homeostasis. However, it remains unclear whether Treg stability must be continually reinforced or is established during development under physiological conditions. Foxp3 has been characterized as a central mediator of the genetic program that governs Treg stability. Here, we demonstrate that to maintain Foxp3 protein expression, Tregs require cell-to-cell contact, which is mediated by the CD147-CD98 interaction. As Tregs are produced, CD147, which is expressed on their surface, is stimulated by CD98, which is widely expressed in the physiological environment. As a result, CD147's intracellular domain binds to CDK2 and retains it near the membrane, leading to Foxp3 dephosphorylation and the prevention of Foxp3 degradation. In addition, the optimal distribution of Foxp3+ Tregs under both pathological and physiological conditions depends on CD98 expression. Thus, our study provides direct evidence that Foxp3-dependent Treg stability is reinforced in the periphery by the interaction between CD147 and CD98 in the surrounding environment. More importantly, Tregs with high CD147 expression effectively inhibit inflammatory responses and maintain Foxp3 stability, which has guiding significance for the application of Tregs in immunotherapy.

CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis.

: Non-small cell lung cancer (NSCLC), a malignant tumor with high global incidence and mortality rates, urgently requires more effective targeted drug delivery systems for its treatment. As an EGFR tyrosine kinase inhibitor, gefitinib has its clinical efficacy limited by poor solubility and low bioavailability. This study aimed to develop a gefitinib-salicylic acid salt (Gef-Sa) and its nano-formulation (Gef-Sa-NPs) via a combined strategy of crystal engineering and nanotechnology to improve its pharmaceutical properties. : Gef-Sa was prepared using a suspension method, and its salt formation and thermal stability were predicted by the ΔpKa rule and confirmed by various solid-state characterization techniques, including single crystal/powder X-ray diffraction, thermal analysis, and infrared spectroscopy. Gef-Sa-NPs were prepared via an ultrasound-assisted anti-solvent precipitation method. Their performance was evaluated through in vitro dissolution tests, pharmacokinetic studies, and in vitro antitumor experiments. : Gef-Sa-NPs with a particle size of 31 nm (PDI = 0.15) were successfully prepared. In vitro dissolution tests demonstrated that the nano-formulation exhibited a significantly higher dissolution rate in pH 1.2, pH 4.5, pH 6.8 and pure water when compared with the raw drug ( < 0.01). Pharmacokinetic studies revealed that Gef-Sa and Gef-Sa-NPs increased the oral bioavailability in rats to 1.5-fold and 1.9-fold that of the raw drug, respectively. In vitro antitumor experiments confirmed that the Gef-Sa-NPs increased the inhibition rate against A549 cells compared with the Gef. : This study innovatively combines salt formation and nanonization technologies to systematically address the key issue of the poor solubility of Gef. The resulting nano-formulation demonstrates excellent dissolution characteristics, pharmacokinetic behavior, and antitumor efficacy. This strategy not only provides a novel drug delivery system with translational potential for NSCLC treatment but also offers a paradigm for the formulation design of poorly soluble drugs. Subsequent research will focus on scaling up production and evaluating pre-clinical safety.

Article	Year
Changes in traditional ecological knowledge of forage plants in immigrant villages of Ningxia, China. Journal of ethnobiology and ethnomedicine\| PubMed ID: 31842902	2019
CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal transduction and targeted therapy\| PubMed ID: 33277466	2020
CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis. Cellular & molecular immunology\| PubMed ID: 34759371	2021
Development and In Vitro Evaluation of Gefitinib-Salicylic Acid Nanocrystals for Improved Bioavailability. Pharmaceutics\| PubMed ID: 42198266	2026

Jie-jie Zhu

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