Depletion Strategies for Crystallized Layers of Two-Dimensional Nanosheets to Enhance Lithium-Ion Conductivity in Polymer Nanocomposites.

The assembly of long-range aligned structures of two-dimensional nanosheets (2DNSs) in polymer nanocomposites (PNCs) is in urgent need for the design of nanoelectronics and lightweight energy-storage materials of high conductivity for electricity or heat. These 2DNS are thin and exhibit thermal fluctuations, leading to an intricate interplay with polymers in which entropic effects can be exploited to facilitate a range of different assemblies. In molecular dynamics simulations of experimentally studied 2DNSs, we show that the layer-forming crystallization of 2DNSs is programmable by regulating the strengths and ranges of polymer-induced entropic depletion attractions between pairs of 2DNSs, as well as between single 2DNSs and a substrate surface, by exclusively tuning the temperature and size of the 2DNS. Enhancing the temperature supports the 2DNS-substrate depletion rather than crystallization of 2DNSs in the bulk, leading to crystallized layers of 2DNSs on the substrate surfaces. On the other hand, the interaction range of the 2DNS-2DNS depletion attraction extends further than the 2DNS-substrate attraction whenever the 2DNS size is well above the correlation length of the polymers, which results in a nonmonotonic dependence of the crystallization layer on the 2DNS size. It is demonstrated that the depletion-tuned crystallization layers of 2DNSs contribute to a conductive channel in which individual lithium ions (Li ions) migrate efficiently through the PNCs. This work provides statistical and dynamical insights into the balance between the 2DNS-2DNS and 2DNS-substrate depletion interactions in polymer-2DNS composites and highlights the possibilities to exploit depletion strategies in order to engineer crystallization processes of 2DNSs and thus to control electrical conductivity.

Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial

BACKGROUNDThe top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac). METHODSWe conducted a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the CoronaVac. A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 g/0.5 mL or 6 g /0.5mL, or placebo on Day 0,14 schedule or Day 0,28 schedule. For safety evaluation, solicited and unsolicited adverse events were collected after each vaccination within 7 days and 28 days, respectively. Blood samples were taken for antibody assay. RESULTSCoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. Pain at injection site was the most frequently reported symptoms. No Grade 3 adverse reaction or vaccine related SAEs were reported. CoronaVac showed good immunogenicity with the lower 3 g dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules. CONCLUSIONSFavorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios.

The XRCC4 rs1805377 polymorphism is not associated with the risk of cancer: An updated meta-analysis.

OBJECTIVES: A growing number of studies have reported that genes involved in the repair of DNA double-strand breaks might be cancer-susceptibility genes. The x-ray cross-complementing group 4 gene (XRCC4) encodes a protein that functions in the repair of DNA double-strand breaks, and this meta-analysis aimed to investigate the relationship between the XRCC4 rs1805377 polymorphism and cancer occurrence. METHODS: We retrieved case-control studies that met the inclusion criteria from PubMed, Web of Science, Embase, and China National Knowledge Infrastructure databases. Associations between rs1805377 and cancer risk were evaluated by odds ratios (ORs) using a random effects model and 95% confidence intervals (CIs) as well as sensitivity and subgroup analyses. RESULTS: After inclusion criteria were met, the meta-analysis involved 24 studies that included 9,633 cancer patients and 10,544 healthy controls. No significant association was found between rs1805377 and the risk of cancer (pooled OR = 1.107; 95% CI = 0.955-1.284) in the dominant genetic model. Similarly, no significant association was observed in the subgroup analysis. CONCLUSIONS: Through this meta-analysis, we found no association between the rs1805377 polymorphism and cancer occurrence. This may provide useful information for relevant future studies into the etiology of cancer.

Mahuang Fuzi Xixin Decoction Ameliorates Allergic Rhinitis in Rats by Regulating the Gut Microbiota and Th17/Treg Balance.

Mahuang Fuzi Xixin Decoction (MFXD), a Chinese traditional herbal formulation, has been used to treat allergic rhinitis (AR) in China for centuries. However, the mechanism underlying its effect on AR is unclear. This study investigated the mechanism underlying the therapeutic effects of MFXD on AR. Ovalbumin-induced AR rat models were established, which were then treated with MFXD for 14 days. Symptom scores of AR were calculated. The structure of the gut microbiota was analyzed by 16S rRNA gene sequencing and qPCR. Short-chain fatty acid (SCFA) content in rat stool and serum was determined by GC-MS. Inflammatory and immunological responses were assessed by histopathology, ELISA, flow cytometry, and western blotting. Our study demonstrated that MFXD reduced the symptom scores of AR and serum IgE and histamine levels. MFXD treatment restored the diversity of the gut microbiota: it increased the abundance of Firmicutes and Bacteroidetes and decreased the abundance of Proteobacteria and Cyanobacteria. MFXD treatment also increased SCFA content, including that of acetate, propionate, and butyrate. Additionally, MFXD administration downregulated the number of Th17 cells and the levels of the Th17-related cytokines IL-17 and RORγt. By contrast, there was an increase in the number of Treg cells and the levels of the Treg-related cytokines IL-10 and Foxp3. MFXD and butyrate increased the levels of ZO-1 in the colon. This study indicated MFXD exerts therapeutic effects against AR, possibly by regulating the gut microbial composition and Th17/Treg balance.

Genetic polymorphisms of 20 autosomal STR loci in the Han population of Zhangzhou City, Southeastern China.

China harbors 56 ethnic groups and Han is the largest population. It is informative and useful to explore the available population genetic characteristics of Chinese Han population from Fujian Province, Southeast China. In our study, we explored the genetic characteristics of 20 autosomal Short tandem repeat (STR) loci in 1555 unrelated Chinese Han individuals from Zhangzhou City, Southeastern China using the SureID® 21G Human STR Identification Kit. Moreover, phylogenetic analysis was performed between the Zhangzhou Han population and other relevant populations based on the shared autosomal STR genotyping. The neighbor-joining tree and multidimensional scaling analysis were analyzed based on the Nei's standard genetic distance. We found 262 alleles among 1555 unrelated individuals and the corresponding allele frequencies ranged from 0.5521 to 0.0003. The combined power of discrimination and exclusion of the 20 autosomal STR loci were 0.99999999999999999999999943 and 0.999999996166537, respectively. Population comparison revealed that the Zhangzhou Han population were lining up together with the southern Han populations in China while showed significant differences from other China populations. Our results found that the 20 autosomal STR loci in Zhangzhou Han population are meaningful for forensic medicine and human genetic. The genetics characteristic of Zhangzhou Han population is similar with the southern Han population in China.

No association between the Ser9Gly polymorphism of the dopamine receptor D3 gene and schizophrenia: a meta-analysis of family-based association studies.

BACKGROUND: Previous studies found that Ser9Gly (rs6280) might be involved in the occurrence of schizophrenia. However, no consist conclusion has yet been achieved. Compared to the case-control study, the family-based study took into account stratification bias. Thus, we conducted a meta-analysis of family-based studies to measure a pooled effect size of the association between Ser9Gly and the risk of schizophrenia. METHODS: The relevant family-based studies were screened using the electronic databases by the inclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to measure the correction between Ser9Gly polymorphism and schizophrenia susceptibility. Subgroup analysis was performed by stratification of ethnicity (i.e., East Asian, Caucasian, and other populations). Additionally, publication bias was evaluated by the funnel plot. RESULTS: After literature searching, a total of 13 family-based association studies were included, which contained 11 transmission disequilibrium test (TDT) studies with 1219 informative meiosis and 5 haplotype-based haplotype relative risk (HRR) studies. No statistical significance of the heterogeneity was detected in TDT and HRR studies. Thus, the pooled effect size was calculated under the fixed effect model. The results found that the association was significantly protective in East Asian in TDT studies (204 informative meiosis, OR = 0.744, 95% CI = 0.564-0.980, Z-value = - 2.104, p = 0.035). CONCLUSIONS: The meta-analysis based on the family study found a protective association of Ser9Gly in East Asian. In future, large sample molecular epidemiology studies are needed to validate our findings.

Population genetics of 24 Y-STR loci in Chinese Han population from Jilin Province, Northeast China.

BACKGROUND: It is meaningful to expand the available population information on forensic medicine and to investigate the genetic characteristics of Han population from Jilin Province, Northeast China. METHODS: In this study, we investigated the genetic characteristics of 24 Y-chromosomal short tandem repeat (STR) loci in 1,088 unrelated Chinese Han male individuals from Jilin Province, using DNATyperTM Y24 amplification kit. Additionally, we performed the population comparison between the Jilin population and the other nine reported populations based on the Y-STR genotyping haplotypes. RESULTS: A total of 1,067 different haplotypes were found from 1,088 unrelated individuals, of which 1,046 were unique and 21 were shared by two individuals. The gene diversity values of 22 loci ranged from 0.3870 (DYS391) to 0.9668 (DYS385ab). The random match probability was 0.0010 with the discrimination capacity of 0.9807. Population comparison showed that there were minor differences compared to Beijing Chinese Han, China Manchu, Gansu Chinese Han, and Jiangsu Chinese Han, but major differences with respect to the populations of Guangdong Chinese Han, Yunnan Chinese Han, China Hui, China Korean, and China Tibetan. CONCLUSION: Our results showed that the 24 Y-STR loci in Jilin Han population are valuable for forensic application and human genetics.

Gegen Qinlian Decoction Treats Diarrhea in Piglets by Modulating Gut Microbiota and Short-Chain Fatty Acids.

Gut microbiota and its metabolites, short-chain fatty acids (SCFAs), play important roles in diarrheal diseases. Gegen Qinlian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries. However, little is known about the mechanism underlying its efficacy and whether it is mediated by gut microbiota and SCFAs. In this study, the composition of gut microbiota from bacterial diarrheal piglets was assessed using 16S rRNA analysis. The concentrations of fecal SCFAs were determined using a gas chromatography-mass spectrometer (GC-MS). The expression of mucosal pro-inflammatory cytokines in the colon was ascertained. Results showed that GQD reverses the reduction in the richness of gut microbiota, changes its structure, and significantly increases the relative abundances of SCFA-producing bacteria, including Akkermansia, Bacteroides, Clostridium, Ruminococcus, and Phascolarctobacterium. Moreover, GQD increased the levels of fecal SCFAs, including acetic acid, propionic acid, and butyric acid. GQD thus attenuates diarrhea in piglets. Further, our results suggest that the SCFAs could help to attenuate mucosal pro-inflammatory responses following GQD treatment by inhibiting histone deacetylase and the NF-κB pathway. We thus suggseted that gut microbiota play an important role during diarrhea treatment, an effect may be promoted by the GQD-induced structural changes of the gut microbial community and production of SCFAs. The increased levels of SCFAs probably provide further help to attenuate mucosal inflammation and diarrhea. In conclusion, our study might provide evidence that GQD treats diarrhea maybe involved in modulating gut microbiota and increasing SCFA levels.

Comparative metabolism of the eight main bioactive ingredients of gegen qinlian decoction by the intestinal flora of diarrhoeal and healthy piglets.

Diarrhoeal diseases alter the composition of intestinal flora, thereby affecting the efficacy of herbal medicinal formulations. Gegen Qinlian decoction (GQD), a Chinese traditional herbal formulation, is widely used to treat infectious diarrhoea. However, little is known about the microbial disposition of GQD in the diarrhoeal state. In this study, the comparative metabolism of components of GQD by diarrhoeal and normal intestinal flora was investigated in vitro. UPLC-MS/MS was performed for simultaneous analysis of eight ingredients of GQD in bacterial solution. The type, activities, and sources of microbial enzymes were also investigated. Microbial metabolism of daidzin, genistin and liquiritin (metabolized by ß-glucosidase); baicalin, wogonoside and glycyrrhizin (metabolized by ß-glucuronidase); and berberine and coptisine (metabolized via nitroreductase) was faster in the diarrhoeal group than in the normal group. Moreover, the activities of these enzymes in the diarrhoeal group were higher than those in the normal group. This difference might be associated with the increase in Escherichia spp. Thus, a change in the metabolism of components by diarrhoeal intestinal flora is associated with a preponderance of Escherichia spp., which might improve the efficacy of GQD. These findings have implications for understanding the action mechanism of GQD for diarrhoea treatment in terms of the microbial milieu.

Comparative pharmacokinetics of major bioactive components from Puerariae Radix-Gastrodiae Rhizome extracts and their intestinal absorption in rats.

Puerariae Radix (PR) and Gastrodiae Rhizome (GR) is frequently used in traditional herbal formulas to treat cardio-cerebral vascular diseases due to their synergistic effects. In this study, to elucidate the action mechanism of PR-GR in vivo, a simple and reliable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of nine bioactive ingredients from PR-GR in plasma was developed and applied to a comparative pharmacokinetic study following oral administration of PR, GR, and PR-GR aqueous extracts in rats. The effect of GR on the absorption of components of PR was also investigated by single-pass intestinal perfusion study. Results showed that comparing to the single herbs, PR-GR extract significantly increased the systemic exposure of puerarin, 3'-hydroxypuerarin, 3'-methoxypuerarin, 6″-O-xylosylpuerarin, daidzin, genistein, and gastrodin. Moreover, the intestinal absorption of puerarin and daidzin could be improved by GR extract and inhibitors of P-glycoprotein and multidrug resistanceassociated protein 2, respectively. These results indicate that the combination of PR and GR increases the levels of their bioactive ingredients exposed in the blood, and GR increases the absorption of ingredients of PR may by inhibition of the efflux mediated by P-glycoprotein and multidrug resistanceassociated protein 2. This is the first report for the pharmacokinetics and intestinal absorption of PR-GR, which may explain their synergetic effects in the treatment of circulatory systematic diseases and provide a meaningful insight for their clinical applications.

Clinical study of chronic pain after breast cancer surgery / 军事医学

Objective To study the epidemiological characteristics of chronic pain following breast cancer surgery and analyze the related factors.Methods Nine hundred and twelve patients following breast cancer surgery were enrolled in the Department of Breast Surgery,Affiliated Hospital,Academy of Military Medical Sciences.The Douleur Neuropathique-4 (DN-4) questionnaire was used to identify neuropathic pain,and the related factors were statistically analyzed.Results The follow-up was completed in 821 patients,including 263 (32％) patients with chronic pain.DN-4 score of 47 (17.9％)patients was over 4 points.There was significant difference between the painful group and the non-painful group in methods of surgery and axillary lymph node dissection (P ＜ 0.05).Conclusion Findings suggest that chronic pain after breast cancer surgery is a significant problem clinically.Proper surgery and psychological buildup are of clinical value in preventing post-surgery chronic pain.