SARS-CoV-2 Infection Increases High Risk Rate of Down Syndrome Screening Test by Reducing Alpha-Fetoprotein.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a significant global health issue in recent years. Numerous studies indicate that COVID-19 during pregnancy is associated with an increased likelihood of pregnancy complications. Additionally, pregnancy itself is known to elevate the risk of severe SARS-CoV-2 infection. To explore the potential impact of SARS-CoV-2 infection on the probability of Down syndrome in fetuses, we conducted serological testing of Down syndrome markers in pregnant women who had contracted the virus. METHODS: Serological experiments were conducted utilizing a particle chemiluminescence test. The cohort of pregnant women was categorized into three groups: a control group with no infection, a group infected with SARS-CoV-2 Omicron within the first six weeks of gestation, and a group infected beyond the sixth week of gestation. RESULTS: In the group of individuals infected within 6 gestational weeks, the infection resulted in a decrease in alpha-fetoprotein (AFP) levels and a higher positive rate of Down syndrome screening tests (p ˂ 0.05). However, in this study, SARS-CoV-2 infection did not lead to an increase in the occurrence of Down syndrome in the fetus. The positive rate of women infected beyond 6 gestational weeks was slightly higher than the non-infected group (6.2% vs. 5.7%), but these differences were not statistically significant (p > 0.05). Within the group infected beyond 6 gestational weeks, there was, compared to the control group, a decrease in free beta human chorionic gonadotropin (ß-hCG) levels (p < 0.05). CONCLUSIONS: This study presents a novel investigation into the impact of SARS-CoV-2 infection on AFP and ß-hCG levels. It has been observed that pregnant women who contract SARS-CoV-2 may exhibit an increased likelihood of positive results in serum tests conducted for Down syndrome screening. However, it is important to note that the occurrence of Down syndrome in the developing fetus does not appear to be elevated. To validate these findings, additional research involving larger and diverse cohorts is necessary.

Airborne signals of Pseudomonas fluorescens modulate swimming motility and biofilm formation of Listeria monocytogenes in a contactless coculture system.

Bacterial volatile compounds (BVCs) facilitate interspecies communication in socio-microbiology across physical barriers, thereby influencing interactions between diverse species. The impact of BVCs emitted from Pseudomonas on the biofilm formation characteristics of Listeria monocytogenes within the same ecological niche has been scarcely investigated under practical conditions of food processing. The objective of this study was to explore the motility and biofilm formation characteristics of L. monocytogenes under the impact of Pseudomonas BVCs. It was revealed that BVCs of P. fluorescens, P. lundensis, and P. fragi significantly promoted swimming motility of L. monocytogenes (P < 0.05). As evidenced by crystal violet staining, the L. monocytogenes biofilms reached a maximum OD570 value of approximately 3.78 at 4 d, which was 0.65 units markedly higher than that of the control group (P < 0.05). Despite a decrease in adherent cells of L. monocytogenes biofilms among the BVCs groups, there was a remarkable increase in the abundance of extracellular polysaccharides and proteins with 3.58 and 4.90 µg/cm2, respectively (P < 0.05), contributing to more compact matrix architectures, which suggested that the BVCs of P. fluorescens enhanced L. monocytogenes biofilm formation through promoting the secretion of extracellular polymers. Moreover, the prominent up-regulated expression of virulence genes further revealed the positive regulation of L. monocytogenes under the influence of BVCs. Additionally, the presence of BVCs significantly elevated the pH and TVB-N levels in both the swimming medium and biofilm broth, thereby exhibiting a strong positive correlation with increased motility and biofilm formation of L. monocytogenes. It highlighted the crucial signaling regulatory role of BVCs in bacterial interactions, while also emphasizing the potential food safety risk associated with the hitchhiking behavior of L. monocytogenes, thereby shedding light on advancements in control strategies for food processing.

Research Progress of TCM Therapy for Rotator Cuff Injury.

Rotator cuff injury is a common orthopedic disease with high morbidity, which is one of the most important reasons for shoulder pain and limited movement. With the development of more research, the Traditional Chinese Medicine (TCM) therapy for rotator cuff injury is increasingly rich and has achieved a good curative effect. TCM has certain characteristics and advantages, which may become the main development trend of the treatment. By consulting the relevant literature on TCM therapy for rotator cuff injury in recent years, we found that commonly used TCM therapy include Chinese herbal therapy, Chinese herbal compounds, External treatment of Chinese herbal therapy, Acupuncture therapy, Floating needle therapy，Massage therapy, and others, which make a great clinical effect. This paper summarizes and analyzes the common TCM therapy of the rotator cuff injury, to provide new ideas for the selection of clinical treatment options.

Research Progress in Single-herb Chinese Medicine and Compound Medicine for Knee Osteoarthritis.

Due to an increase in the aging population, osteoarthritis (OA), especially knee osteoarthritis (KOA), has increasingly become one of the diseases affecting the quality of life of the elderly. As the pathogenesis of KOA is still unclear, Western medicine treatment lacks specificity, and surgical treatment is difficult to cover all patients. Therefore, in recent years, traditional Chinese medicine (TCM) for the conservative treatment of KOA has received increasing attention. The advantages of TCM are clear， such as relief of symptoms, fewer adverse reactions, and wider applicability to patients. This paper mainly discusses the research progress in single-herb TCM and TCM compounds for KOA, aiming to demonstrate the effectiveness of TCM in the treatment of KOA. It also provides ideas for future research on the treatment of KOA by TCM and the pathogenesis of knee osteoarthritis.

Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a polyphenolic compound extracted from turmeric (Curcuma longa L.), is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis. Clinical and experimental studies show that curcuminoid formulations have considerable clinical application value in the treatment of knee osteoarthritis (KOA). AIM OF THE STUDY: To evaluate the efficacy and safety of curcumin, both alone and in combination with other drugs, in KOA treatment through a Bayesian network meta-analysis (NMA). METHODS: We searched PubMed, Embase and Cochrane Library for randomized controlled trials of curcumin for KOA treatment. The time range of the search was from the establishment of each database to April 26, 2023. The NMAs of outcome indicators were all performed using a random-effects model. NMAs were calculated and graphed in R using MetaInsight and Stata 140 software. Measurement data were represented by the mean difference (MD), while count data were represented by the odds ratio (OR); the 95% confidence interval (CI) of each effect size was also calculated. RESULTS: This study included 23 studies from 7 countries, including 2175 KOA patients and 6 interventions. The NMA results showed that compared with placebo, curcumin significantly reduced the visual analogue scale pain score (MD = -1.63, 95% CI: -2.91 to -0.45) and total WOMAC score (MD = -18.85, 95% CI: -29.53 to -8.76). Compared with placebo, curcumin (OR = 0.17, 95% CI: 0.08 to 0.36), curcumin + NSAIDs (OR = 0.01, 95% CI: 0.00 to 0.13) and NSAIDs (OR = 0.11, 95% CI: 0.02 to 0.47) reduced the use of rescue medication. Compared with NSAIDs, curcumin (OR = 0.51, 95% CI: 0.25 to 0.94) and curcumin + NSAIDs (OR = 0.23, 95% CI: 0.06 to 0.9) had a reduced incidence of adverse reactions. The surface under the cumulative ranking curve results indicated that curcumin monotherapy, curcumin + chondroprotective agents, and curcumin + NSAIDs have good clinical value in KOA treatment. CONCLUSIONS: Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in KOA treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions, but this possibility still needs to be confirmed by further clinical and basic research.

J-shaped association of serum uric acid concentrations with all-cause mortality in individuals with osteoarthritis: A prospective cohort study.

OBJECTIVE: The purpose of this study was to explore the relationship between serum uric acid (SUA) concentrations and all-cause mortality in individuals with osteoarthritis (OA). METHODS: All participant data were retrieved from the National Health and Nutrition Examination Survey database. A total of 4671 participants (age range: 20 to 85 years old), including 2988 females and 1683 males, were included in this study. The determination of death outcome was based on the National Death Index (up to December 31, 2019). We explored the nonlinear relationship between SUA concentrations and all-cause mortality in OA patients by establishing a Cox proportional risk model and a two-segment Cox proportional risk model and ran an interaction test to identify the high-risk population for all-cause mortality. RESULTS: During 30,645 person-years of follow-up, the number of all-cause deaths for females and males was 736 and 516, respectively. After multivariate adjustment, we found a nonlinear relationship between SUA concentrations and all-cause mortality in both females and males with OA. In addition, we found a J-shaped relationship between SUA concentrations and all-cause mortality. The SUA concentration thresholds for all-cause mortality of females and males were stable at 5.6mg/dl and 6.2mg/dl, respectively. Compared with SUA concentrations below the inflection point, the all-cause mortality risk at higher SUA concentrations in females and males with OA increased by 20% (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 1.1 to 1.2) and 25% (HR: 1.2, 95% CI: 1.12 to 1.39), respectively. CONCLUSIONS: There is a nonlinear relationship between SUA concentrations and all-cause mortality in the American OA population (J-shaped association). The all-cause mortality thresholds for SUA concentrations in females and males are 5.6mg/dl and 6.2mg/dl, respectively.

Higher systemic immune-inflammation index is associated with sarcopenia in individuals aged 18-59 years: a population-based study.

The association between the systemic immune-inflammation index (SII) and the risk of sarcopenia has not yet been revealed. The purpose of this study was to investigate the relationship between the SII and sarcopenia in individuals aged 18-59 years. All data for this study are from the National Health and Nutrition Examination Survey (NHANES) database, including 7258 participants (age range: 18-59 years). We divided SII values by quartiles (quartiles 1-4: 0.3-3.1, 3.2-4.4, 4.4-6.2, and 6.2-58.5). We constructed a multivariate logistic regression model to assess the association between the SII and the risk of sarcopenia, and an interaction test was run to test the stability of the model and identify high-risk individuals with sarcopenia. Compared to nonsarcopenia participants, sarcopenia patients had a significantly higher SII value (weighted average: 6.65 vs. 5.16) (P = 0.002). Multivariate logistic regression results showed a positive linear relationship between the SII and sarcopenia (OR [odds ratio] = 1.12, 95% CI [confidence interval] 1.03-1.21). Compared to the quartile 1 group, the quartile 4 group was associated with a higher risk of sarcopenia (OR = 3.94, 95% CI 1.42-10.94). Compared with the quartile 1 group, the OR value of the quartile 2 to quartile 4 groups showed an upwards trend (Ptrend < 0.001) as the level of SII increased. Subgroup analysis also indicate that the correlation between higher SII values and the risk of sarcopenia was stable. There was a significant positive linear relationship between SII and sarcopenia, indicating that higher SII values can increase the risk of sarcopenia in individuals aged 18-59 in the United States. The findings of this study will be beneficial in promoting the use of SII alone or in combination with other tools for the risk screening of sarcopenia in communities or large populations.

Clinical effectiveness of krill oil supplementation on cardiovascular health in humans: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The potential role of krill oil (KO) supplementation on cardiovascular health are inconsistent in several clinical trials. Therefore, our present meta-analysis aimed to systematically evaluate the impacts of supplementation of KO on cardiovascular disease risk factors (CVDRFs). METHODS: Intervention trials assessing KO supplementation on cardiovascular disease (CVD) outcomes were systematically retrieved for pooling. The primary outcome was lipid profile. Secondary outcomes were consisted by blood pressure, glycemic indices, body composition together with inflammatory markers. We synthesized the effect sizes with 95% confidence intervals and weighted mean difference. To explore the heterogeneity source, we employed meta-regression and subgroup analysis. Quality assessment, publication bias, sensitivity-analysis and the certainty of evidence were also carried out. RESULTS: We included 14 trials (18 treatment arms) with 1458 participants. KO supplementation had beneficial effects on total cholesterol (P = 0.01), low-density lipoprotein cholesterol (P = 0.006), and triglycerides (P = 0.0005). However, no effects were found for other CVDRFs, such as blood pressure, glycemic control, body composition as well as inflammatory markers. Subgroup analyses indicated that these notably favorable effects were observed in trials with a parallel design, treatment duration <8 weeks and subjects with baseline body mass index <28 kg/m2. The above findings remained consistent in the sensitivity analysis, without obvious publication bias detected. CONCLUSIONS: The current evidence demonstrated that daily KO supplementation may as a candidate for lipid management strategies. In future, studies should pay attention to the relationships of KO intake with the incidence of CVD events or all-cause mortality.

Effectiveness of Chinese Herbal Medicine in Postoperative Fatigue Syndrome Following Total Joint Arthroplasty or Hip Fracture Surgery: Evidence from Randomized Controlled Trials.

BACKGROUND: There is no high-quality, evidence-based protocol for the treatment of postoperative fatigue syndrome (POFS) after total joint arthroplasty (TJA) or fracture surgery with Chinese herbal medicine (CHM). PURPOSE: The purpose of this study was to explore the efficacy of CHM in the treatment of POFS after TJA or hip fracture surgery (HFS). METHODS: We searched six databases to obtain randomized controlled trials (RCTs) of CHM for the treatment of POFS after TJA or HFS. The retrieval time limit was from the establishment of each database to August, 2022. According to the Cochrane Handbook for Systematic Reviews version 5.1, we used RevMan 5.3 to evaluate the quality of the studies. Stata 14.0 software was used to merge and analyze the data. The weighted mean difference (WMD) was the effect estimate for statistical analysis. We also performed subgroup analyses according to different types of surgeries. RESULTS: A total of 11 RCTs were included in this study, comprising 430 cases in the CHM group and 432 cases in the control group (CG). The meta-analysis results showed that there was no significant difference in the Brief Profile of Mood States (BPOMS) score (WMD=0.08, 95% confidence interval (CI): -0.29 to 0.45, P=0.688), Christensen Fatigue scale (CHFS) score (WMD = 0.15, 95% CI: -0.09 to 0.39, P=0.214) or Identity-Consequence Fatigue Scale (ICFS) score (WMD=-0.40, 95% CI: -1.84 to 1.05, P=0.589) between the CHM group and the CG on the first postoperative day. The use of CHM significantly reduced the BPOMS score (WMD=-0.85 and WMD=-3.01, respectively), CHFS score (WMD=-1.01 and WMD= -1.45, respectively), and ICFS score (WMD=-3.51 and WMD=-5.26) on postoperative days 3 and 7. Compared with the CG, the CHM group had significantly increased serum transferrin and IgG levels on postoperative days 3 and 7. The subgroup analysis results suggested that the application of CHM in HFS patients improved fatigue symptoms on postoperative days 3 and 7, while the application of CHM to treat POFS in TJA patients had great inconsistency in the evaluation of different indicators. CONCLUSION: The application of CHM improved the fatigue status of POFS patients after TJA or HFS and increased the levels of transferrin and IgG in serum, which is conducive to promoting the postoperative rehabilitation process of patients. The subgroup analysis results showed that the application of CHM to intervene in POFS in HFS patients had obvious benefits.

Guidelines for the diagnosis and treatment of knee osteoarthritis with integrative medicine based on traditional Chinese medicine.

Knee osteoarthritis (KOA) is a common geriatric disease in middle-aged and elderly people. Its main pathological characteristics are articular cartilage degeneration, changes in subchondral bone reactivity, osteophyte formation at joint edges, synovial disease, ligament relaxation or contracture, and joint capsular contracture. The prevalence rate of symptomatic KOA in middle-aged and elderly people in China is 8.1%, and this is increasing. The main clinical manifestations of this disease are pain and limited activity of the knee joint, which seriously affect the quality of life of patients and may cause disability, posing a huge burden on society and the economy. Although the pathogenesis of KOA is not clear, the treatment of KOA is diverse, and Chinese medicine, which mainly relies on plant-based natural products, has a relatively stable and reliable curative effect. This guideline aims to emphasize the evidence-based staging and stepped treatment of KOA and the therapeutic effect of integrative medicine based on traditional Chinese medicine on KOA. We make recommendations that include the adoption of manual therapy, acupuncture, external application of herbs, herbal plasters, exercise therapy, and other integrative medicine based on traditional Chinese medicine. Users of the above guidelines are most likely to include clinicians and health managers in healthcare settings.

Longbie capsules reduce bone loss in the subchondral bone of rats with comorbid osteoporosis and osteoarthritis by regulating metabolite alterations.

Background and objective: With the development of global population aging, comorbidity (≥2 diseases) is a common health problem among elderly people. Osteoarthritis (OA) and osteoporosis (OP) are common in elderly individuals. There is a lack of drug therapy for OA and OP comorbidities. The purpose of this study was to explore the efficacy and mechanism of Longbie capsule (LBJN), which contains various plant herbs, in treating OA and OP comorbidities (OA + OP) in rats using metabolomics techniques. Methods: We created an OA + OP rat model through bilateral oophorectomy combined with meniscus instability surgery. Thirty SD rats were randomly divided into five groups (six in each group), namely, the sham group, OA group, OA + OP group, LBJN low-dose group (0.625 g/kg, OA + OP+LB-L group) and LBJN high-dose group (1.25 g/kg, OA + OP+LB-H group). After 8 weeks of intervention, we used micro-CT to detect bone microstructure status, ELISA to measure bone metabolism indicators, and UPLC-MS technology for metabolomics analysis. Finally, the screened differentially expressed metabolites were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and functional enrichment analysis. Results: The micro-CT results showed that LBJN significantly improved the bone mineral density (BMD) and bone quality of subchondral bone in OA + OP rats, and LBJN regulated the expression of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRACP) in serum to maintain bone metabolism balance. Metabolomics analysis showed that the metabolic trajectory of OA + OP rats after intervention in the OA + OP+LB-H group showed significant changes, and 107 potential biomarkers could be identified. Among them, 50 metabolites were upregulated (such as zeranol) and 57 were downregulated (such as vanillactic acid). The KEGG functional enrichment results indicated that the differentially expressed metabolites are mainly involved in amino acid metabolism, lipid metabolism, and carbohydrate metabolism. The KEGG pathway enrichment results indicated that LBJN may exert therapeutic effects on OA + OP rats by regulating the cAMP signaling pathway, and the FoxO signaling pathway. Conclusion: LBJN can maintain bone metabolism balance by regulating serum lipid metabolism, amino acid metabolism, carbohydrate metabolism, and estrogen, thereby reducing bone loss in subchondral bone, which may be a potential mechanism through which LBJN treats OA + OP.

Research progress on the treatment of knee osteoarthritis combined with osteoporosis by single-herb Chinese medicine and compound.

Knee osteoarthritis (KOA) is a degenerative disease with synovial inflammation, articular surface cartilage degeneration, meniscus degeneration, ligament and muscle changes, subchondral bone changes, and osteophyte formation around the joint as the main pathological changes. Osteoporosis (OP) is a disease characterized by low bone mass and deterioration of the microstructure of bone tissue. KOA and OP are both geriatric diseases, and the incidence of KOA combined with OP is high, but there is a lack of specific drugs, and the major treatments are limited to drug therapy. Most traditional Chinese medicine (TCM) treatments use plant-based natural products, and they help patients obtain good clinical benefits and at the same time provide researchers with ideas to study the mechanism of disease occurrence and the relationship between the two diseases. This article summarizes the research progress of TCM monomers and TCM compounds that are frequently used to treat KOA combined with OP to provide ideas for future clinical treatments and related basic research.

Design and analysis of a 2D grapheneplus (G+)-based gas sensor for the detection of multiple organic gases.

A new member of the 2D carbon family, grapheneplus (G+), has demonstrated excellent properties, such as Dirac cones and high surface area. In this study, the electronic transport properties of G+, NG+, and BG+ monolayers in which the NG+/BG+ can be obtained by replacing the center sp3 hybrid carbon atoms of the G+ with N/B atoms, were studied and compared using density functional theory and the non-equilibrium Green's function method. The results revealed that G+ is a semi-metal with two Dirac cones, which becomes metallic upon doping with N or B atoms. Based on the electronic structures, the conductivities of the 2D G+, NG+ and BG+-based nanodevices were analyzed deeply. It was found that the currents of all the designed devices increased with increasing the applied bias voltage, showing obvious quasi-linear current-voltage characteristics. IG+ was significantly higher than ING+ and IBG+ at the same bias voltage, and IG+ was almost twice IBG+, indicating that the electron mobility of G+ can be controlled by B/N doping. Additionally, the gas sensitivities of G+, NG+, and BG+-based gas sensors in detecting C2H4, CH2O, CH4O, and CH4 organic gases were studied. All the considered sensors can chemically adsorb C2H4 and CH2O, but there were only weak van der Waals interactions with CH4O and CH4. For chemical adsorption, the gas sensitivities of these sensors were considerably high and steady, and the sensitivity of NG+ to adsorb C2H4 and CH2O was greater as compared to G+ and BG+ at higher bias voltages. Interestingly, the maximum sensitivity difference for BG+ toward C2H4 and CH2O was 17%, which is better as compared to G+ and NG+. The high sensitivity and different response signals of these sensors were analyzed by transmission spectra and scattering state separation at the Fermi level. Gas sensors based on G+ monolayers can effectively detect organic gases such as C2H4 and CH2O, triggering their broad potential application prospects in the field of gas sensing.

Global Publication Trends and Research Hotspots of the Immune System and Osteoporosis: A Bibliometric and Visualization Analysis from 2012 to 2022.

BACKGROUND: Osteoporosis (OP) is a systemic bone metabolism disorder in which the immune system and bone metabolism interact. OBJECTIVE: The purpose of this study was to explore the research status, hot spots and trends regarding the influence of the immune system on OP and to provide a basis for research directions and applications in this field. METHODS: We searched and collected literature about the immune system and OP published from 2012 to 2022 in the Web of Science Core Collection database. All the included studies were subjected to bibliometrics analysis using Hiplot Pro, VOSviewer and CiteSpace software to produce statistics and visual analyses of the literature output, countries, institutions, authors, keywords and journals. RESULTS: A total of 1201 papers were included, and the number of citations of these articles reached 31,776. The number of publications and citations on the immune system and OP has increased year by year. The top three countries with the greatest number of papers published were China, the United States of America (USA) and Italy. The two institutions with the largest number of papers published were Sichuan University and Soochow University, both located in China. De Martinis Massimo (Italy) and Ginaldi Lia (Italy) are prolific authors in this field. The representative academic journals are Osteoporosis International, Frontiers in Immunology, Journal of Bone and Mineral Research, PloS One and Bone. The results of the keyword cooccurrence analysis showed that the research topics in this field mainly focused on T cells, cytokines, signaling pathways, vitamin D, postmenopausal OP and immune diseases. The keyword burst results showed that zoledronic acid, chain fatty acids and gut microbiota are the frontiers and trends of future research on this topic. CONCLUSION: The influence of the immune system on OP has been widely studied, and the current research in this field focuses on the effect or mechanism of immune-related cytokines, signaling pathways and vitamin D on OP. Future research trends in this field should focus on the immune regulation mechanism and clinical transformation of zoledronic acid, chain fatty acids and the gut microbiota in OP.

MicroRNA-194-3p impacts autophagy and represses rotavirus replication via targeting silent information regulator 1.

BACKGROUND: Rotavirus (RV) is the main cause of serious diarrhea in infants and young children worldwide. Numerous studies have demonstrated that RV use host cell mechanisms to motivate their own stabilization and multiplication by degrading, enhancing, or hijacking microRNAs (miRNAs). Therefore, exploring the molecular mechanisms by which miRNAs motivate or restrain RV replication by controlling different biological processes, including autophagy, will help to better understand the pathogenesis of RV development. This study mainly explored the effect of miR-194-3p on autophagy after RV infection and its underlying mechanism of the regulation of RV replication. METHODS: Caco-2 cells were infected with RV and used to measure the expression levels of miR-194-3p and silent information regulator 1 (SIRT1). After transfection with plasmids and RV infection, viral structural proteins, RV titer, cell viability, and autophagy-linked proteins were tested. The degree of acetylation of p53 was further investigated. A RV-infected neonatal mouse model was constructed in vivo and was evaluated for diarrhea symptoms and lipid droplet formation. RESULTS: The results showed that miR-194-3p was reduced but SIRT1 was elevated after RV infection. Elevation of miR-194-3p or repression of SIRT1 inhibited RV replication through the regulation of autophagy. The overexpression of SIRT1 reversed the effects of miR-194-3p on RV replication. The upregulation of miR-194-3p or the downregulation of SIRT1 repressed RV replication in vivo. MiR-194-3p targeted SIRT1 to decrease p53 acetylation. CONCLUSION: These results were used to determine the mechanism of miR-194-3p in RV replication, and identified a novel therapeutic small RNA molecule that can be used against RV.

Effects of resveratrol in an animal model of osteoporosis: a meta-analysis of preclinical evidence.

Background: Resveratrol is a natural polyphenol compound that is widely present in herbal medicines such as Reynoutria japonica Houtt., Veratrum nigrum L., and Catsiatora Linn and is used in traditional Chinese medicine to treat metabolic bone deseases. Animal experiments have shown that resveratrol may have a strong treatment effect against osteoporosis (OP). The purpose of this study was to explore the efficacy of resveratrol in treating OP animal models based on preclinical research data. Methods: This study was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases from inception to May 8, 2023, to identify animal experiments on the treatment of OP with resveratrol. The effect sizes of bone mineral density (BMD), parameters of micro-CT, serum calcium, phosphorus, alkaline phosphatase (ALP) and osteocalcin were expressed as the mean differences (MDs) and 95% confidence intervals (CIs). RevMan 5.4 software was used for data analysis. Results: This meta-analysis included a total of 15 animal experiments, including 438 OP rats. The meta-analysis results showed that compared with the control group, resveratrol (<10, 10-25, 40-50, ≥ 60 mg/kg/day) significantly increased femoral and lumbar bone mineral density (BMD) in OP rats (p < 0.05). Resveratrol (<10 mg/kg/day) significantly increased the BMD of the total body (MD = 0.01, 95% CI: 0.01 to 0.01, p < 0.001). In terms of improving the parameters related to micro-CT, resveratrol (40-50 mg/kg/day) can increase trabecular thickness and trabecular number and reduce trabecular spacing (p < 0.05). Compared with the control group, resveratrol can reduce the concentration of calcium and phosphorus in serum but has no significant effect on serum ALP and osteocalcin (p > 0.05). The results of subgroup analysis showed that resveratrol increased the whole-body BMD of SD rats (p = 0.002) but did not improve the whole-body BMD of 3-month-old rats (p = 0.17). Conclusion: Resveratrol can increase BMD in OP rat models, and its mechanism of action may be related to improving bone microstructure and regulating calcium and phosphorus metabolism. The clinical efficacy of resveratrol in the treatment of OP deserves further research.

Arctigenin hinders the invasion and metastasis of cervical cancer cells via the FAK/paxillin pathway.

Context: Cervical cancer is the most common gynecological pernicious tumor with high morbidity and mortality worldwide, especially in developing countries. Arctigenin (ARG), a nature-derived component, has exhibited anti-tumor activity in various tumors. Objective: To explore the effect of ARG on cervical cancer. Materials and methods: The effect and mechanism of ARG on cervical cancer cells were explored by cell counting kit-8 (CCK-8), flow cytometry, transwell and Western blot assays. Additionally, in vivo experiment was conducted in xenografted mice by immunohistochemistry (IHC), terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) and Western blot assays. Results: ARG treatment induced both concentration-dependent and time-dependent reductions in the cell viability of SiHa and HeLa cells with a IC50 value of 9.34 µM and 14.45 µM, respectively. ARG increased the apoptosis rate and the protein levels of cleaved-caspase 3 and E-cadherin, but decreased the invaded cell numbers and the protein levels of Vimentin and N-cadherin in vitro. Mechanically, ARG inhibited the expression of focal adhesion kinase (FAK)/paxillin pathway, which was confirmed by the overexpression of FAK in SiHa cells. The inhibitory role of overexpression of FAK in proliferation and invasion, as well as its promoted role in apoptosis were reversed with ARG treatment. Meanwhile, ARG suppressed growth and metastasis, and enhanced apoptosis in vivo. Consistently, ARG administration reduced the relative protein level of p-FAK/FAK and p-paxillin/paxillin in tumor tissues of xenografted mice. Conclusion: ARG inhibited proliferation, invasion and metastasis, but enhanced apoptosis of cervical cancer via the FAK/paxillin axis.

Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial.

BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

hKLK alleviates myocardial fibrosis in mice with viral myocarditis.

Myocardial fibrosis is the most serious complication of viral myocarditis (VMC). This study aimed to investigate the therapeutic benefits and underlying mechanisms of lentivirus-mediated human tissue kallikrein gene transfer in myocardial fibrosis in VMC mice. We established VMC mouse model via intraperitoneal injection with Coxsackie B3 virus. The effect was then assessed after treatment with vehicle, the empty lentiviral vectors (EZ.null), and the vectors expressing hKLK1 (EZ.hKLK1) via tail vein injection for 30 days, respectively. The results showed that administering EZ.hKLK1 successfully induced hKLK1 overexpression in mouse heart. Compared with EZ.null treatment, EZ.hKLK1 administration significantly reduced the heart/weight ratio, improved cardiac function, and ameliorated myocardial inflammation in VMC mice, suggesting that hKLK1 overexpression alleviates VMC in mice. EZ.hKLK1 administration also significantly abrogated the increased myocardial collagen content, type I/III collagen ratio, TGF-ß1 mRNA and protein expression in VMC mice, suggesting that hKLK1 overexpression reduces collagen accumulation and blunts TGF-ß1 signaling in the hearts of VMC mice. In conclusion, our results suggest that hKLK1 alleviates myocardial fibrosis in VMC mice, possibly by downregulating TGF-ß1 expression.

Nonvolatile Electrical Control and Reversible Gas Capture by Ferroelectric Polarization Switching in 2D FeI2/In2S3 van der Waals Heterostructures.

Nonvolatile electrical control is the core of future magnetoelectric nanodevices. In this work, we systematically explore both the electronic structures and transport properties of multiferroic van der Waals (vdW) heterostructures consisting of a ferromagnetic FeI2 monolayer and a ferroelectric In2S3 monolayer using density functional theory and the nonequilibrium Green's function method. The results reveal that the FeI2 monolayer can be reversibly switched between semiconducting and half-metallic properties by nonvolatile control of the In2S3 ferroelectric polarization states. Correspondingly, the proof-of-concept two-probe nanodevice based on the FeI2/In2S3 vdW heterostructure exhibits a significant valving effect by modulating the ferroelectric switching. Moreover, it is also found that the preference of nitrogen-containing gases such as NH3, NO, and NO2 for adsorption on the surface of FeI2/In2S3 vdW heterostructures strongly depends on the polarization direction of the ferroelectric layer. In particular, the FeI2/In2S3 heterostructure shows reversible capture behavior for NH3. As a result, the FeI2/In2S3 vdW heterostructure-based gas sensor demonstrates high selectivity and sensitivity. These findings may open up a new route for the application of multiferroic heterostructures to spintronics, nonvolatile memories, and gas sensors.