The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Objective To explore the protective effect of Lycium barbanun glycopeptide(LbGP)against osteogenic inhibition induced by exosomes derived from human gingival fibroblasts(HGFs)exposed to radiation.Methods Cultured HGFs with or without LbGP pretreatment were exposed to 8 Gy X-ray radiation,and the changes in cell apoptosis,senescence and α-SMA level were detected using RT-qPCR,Western blotting and β-galactosidase staining.The exosomes secreted by the treated cells were extracted,and after identification by electron microscopy,particle size analysis and Western blotting,the exosomes were added into primary cultured bone mesenchymal stem cells(BMSCs),and osteoclast activity and osteogenesis in the cell cultures were detected by Trap staining,Alizarin red staining,ALP staining,RT-qPCR and Western blotting.Results In cultured HGFs,X-ray radiation significantly increased the percentage of senescent cells,which was obviously lowered by LbGP treatment.X-ray radiation significantly reduced Bcl-2/Bax ratio and increased α-SMA expression in HGFs,and these changes were significantly suppressed by LbGP pretreatment.In rat BMSCs,incubation with the exosomes derived from HGFs with radiation exposure caused a significant increase of osteoclasts,reduced calcium nodules and lowered alkaline phosphatase expression in the cells;The opposite changes were observed in the cells treated with exosomes from LbGP-pretreated HGFs,which also significantly increased the cellular expressions of the osteogenic genes(BMP2,ALP,and RUNX2)and proteins(ALP and RUNX2)as compared with the exosomes from irradiated HGFs.Conclusion LbGP can effectively inhibit osteoclast activity and promote osteogenesis by acting on exosomes secreted by irradiated HGFs,suggesting its potential value for treatment of osteoradionecrosis of the jaw.

Objective To explore the protective effect of Lycium barbanun glycopeptide(LbGP)against osteogenic inhibition induced by exosomes derived from human gingival fibroblasts(HGFs)exposed to radiation.Methods Cultured HGFs with or without LbGP pretreatment were exposed to 8 Gy X-ray radiation,and the changes in cell apoptosis,senescence and α-SMA level were detected using RT-qPCR,Western blotting and β-galactosidase staining.The exosomes secreted by the treated cells were extracted,and after identification by electron microscopy,particle size analysis and Western blotting,the exosomes were added into primary cultured bone mesenchymal stem cells(BMSCs),and osteoclast activity and osteogenesis in the cell cultures were detected by Trap staining,Alizarin red staining,ALP staining,RT-qPCR and Western blotting.Results In cultured HGFs,X-ray radiation significantly increased the percentage of senescent cells,which was obviously lowered by LbGP treatment.X-ray radiation significantly reduced Bcl-2/Bax ratio and increased α-SMA expression in HGFs,and these changes were significantly suppressed by LbGP pretreatment.In rat BMSCs,incubation with the exosomes derived from HGFs with radiation exposure caused a significant increase of osteoclasts,reduced calcium nodules and lowered alkaline phosphatase expression in the cells;The opposite changes were observed in the cells treated with exosomes from LbGP-pretreated HGFs,which also significantly increased the cellular expressions of the osteogenic genes(BMP2,ALP,and RUNX2)and proteins(ALP and RUNX2)as compared with the exosomes from irradiated HGFs.Conclusion LbGP can effectively inhibit osteoclast activity and promote osteogenesis by acting on exosomes secreted by irradiated HGFs,suggesting its potential value for treatment of osteoradionecrosis of the jaw.

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.

Lateral epicondylitis is a common clinical disease with characteristics of lateral elbow pain, insidious onset and easy recurrence, which can cause forearm pain and decreased wrist strength, seriously affecting patients′ daily life and work. Although there are various treatment methods for lateral epicondylitis with different effects, standard treatments are still lacking nowadays. Platelet-rich plasma (PRP) has good effects on bone and tendon repair, and is now widely used in the treatment of lateral epicondylitis. However, there is a lack of a unified understanding of the technology and specifications of PRP in the treatment of lateral epicondylitis. Therefore, the Sports Medicine Branch of the Chinese Medical Association and Physical Medicine and Rehabilitation Branch of the Chinese Medical Association organized experts in the fields of sports medicine and rehabilitation medicine in China to formulate the "clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version)", and proposed suggestions based on evidence-based medicine mainly from the concept, epidemiology and pathophysiology of lateral epicondylitis, symptoms, signs and imaging manifestations of lateral epicondylitis, PRP concept and application component requirements, quality control of PRP preparation technology, indications and contraindications of PRP in the treatment of lateral epicondylitis, PRP injection in the treatment of lateral epicondylitis, application of PRP in the operation of lateral epicondylitis, related problems after PRP treatment of lateral epicondylitis, evaluation of the results after PRP treatment of lateral epicondylitis, and health and economic evaluation of PRP treatment of lateral epicondylitis, so as to provide guidance for clinical diagnosis and treatment.

Background: Hong Kong's construction industry currently faces a manpower crisis. Blue-collar workers are a disadvantaged group and suffer higher levels of chronic diseases, for example, cancer, than the wider population. Cancer risk factors are likely to cluster together. We documented prevalence of cancer-associated lifestyle risk behaviors and their correlates among Hong Kong construction workers. Methods: Data were collected from workers at 37 railway-related construction worksites throughout Hong Kong during May 2014. Tobacco use, alcohol consumption, unbalanced nutrition intake, and physical inactivity were included in the analysis. Latent class analysis and multivariable logistic regression were performed to identify the patterns of risk behaviors related to cancer, as well as their impact factors among construction workers in Hong Kong. Results: Overall, 1,443 workers participated. Latent class analysis identified four different behavioral classes in the sample. Fully adjusted multiple logistic regression identified age, gender, years of Hong Kong residency, ethnicity, educational level, and living status differentiated behavioral classes. Conclusion High levels of lifestyle-related cancer-risk behaviors were found in most of the Hong Kong construction workers studied. The present study contributes to understanding how cancer-related lifestyle risk behaviors cluster among construction workers and relative impact factors of risk behaviors. It is essential to tailor health behavior interventions focused on multiple risk behaviors among different groups for further enlarging the effects on cancer prevention.

A proportion of patients experience acute or even prolonged cognitive impairment after surgery, a condition known as postoperative cognitive dysfunction (POCD). It is characterized by impairment in different cognitive domains and neuroinflammation has been implicated as one of the inciting factors as strategies targeting inflammation tend to improve cognitive performance. Siegesbeckia Orientails L. (S. Orientails) is a common Chinese medicinal herb used for managing chronic inflammatory diseases. We investigated if pretreatment with S. Orientails before surgery confers any neuroprotective effects in postoperative animals in terms of reducing inflammation and mitigating cognitive impairment. Three-month-old male C57BL/6N mice were fed different doses of S. Orientails extract for 14 days before they underwent a laparotomy. After cognitive testing they were sacrificed on postoperative day (POD) 3. Our results showed that animals with extract pretreatment demonstrated memory improvement in a dose-dependent manner compared with control. Further, evidence for the attenuation of systemic and neuroinflammation was found in the pretreated animals, along with the inhibition of inflammatory pathways and significantly reduced tau phosphorylation in the hippocampus. Taken together, these results demonstrated a neuroprotective effect of S. Orientails in postoperative animals, indicating a therapeutic potential of S. Orientails in minimizing POCD and the possibility of utilizing this traditional Chinese medicine perioperatively.
Animals ; Asian Continental Ancestry Group ; Cognition Disorders ; Hippocampus ; Humans ; Inflammation* ; Laparotomy ; Male ; Medicine, Chinese Traditional ; Memory ; Mice ; Neuroprotective Agents ; Phosphorylation ; Plants, Medicinal

Bat is nature reservoir hosts of some important viruses.It has been confirmed that bats were infected by many viruses in nature in Yunnan Province,China during 2010-2015,such as SARS-like coronavirus and another coronaviruses (Alphacoronavirus and Betacoronavirus) as well as novel reovirus,rotavirus,orthohepadnavirus,filovirus,paramyxovirus,adenovirus,bocavirus and circovirus.This paper presents a review about natural infection of bat with zoonosis-related viral pathogens in Yunnan Province,China,and its public health importance.

Antineoplastic Agents ; adverse effects ; Arterial Occlusive Diseases ; chemically induced ; Breast Neoplasms ; drug therapy ; Carotid Artery Diseases ; chemically induced ; Carotid Artery, Internal ; Female ; Humans ; Middle Aged ; Nitriles ; adverse effects ; Postmenopause ; Triazoles ; adverse effects