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Manganese-based NASICON-type compounds are promising as high-energy-density cathodes for sodium-ion batteries. However, the structural defects of Mn ions inside the crystal framework reduce the sodium storage capacity, voltage plateau, and cyclic stability of the cathodes. Here, a strategy to inhibit the Mn ion defects of Na4MnCr(PO4)3 has been proposed by using different phosphate sources. It is found that Na4MnCr(PO4)3 prepared with NH4H2PO4 (NMCP-N) exhibits less noticeable voltage hysteresis than that of Na4MnCr(PO4)3 prepared with H3PO4 (NMCP-H), indicating that the site occupation defects of Mn ions in the Na4MnCr(PO4)3 crystal structure are successfully suppressed, as confirmed by theoretical calculations and structural refinements. In the case of NMCP-N, a capacity of 109.7 mAh g-1 is delivered at 0.01 A g-1, and 54.2% capacity retention can be kept after 500 cycles at 0.5 A g-1, which is much better than that of the counterpart of NMCP-H (a lower capacity of 96.1 mAh g-1 and poorer cyclability of only 22.8% capacity retention after 500 cycles), showing that the structure defects strongly affect the sodium storage properties of Na4MnCr(PO4)3 cathodes. This work provides an effective strategy to manipulate the structure defects of Mn-based NASICON-type cathode materials to enhance their electrochemistry.

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Red Monascus pigments (MPs) are a large group of polyketides from the fungus Monascus which have been widely used as food colorants. In this study, a variety of red MPs congeners were prepared to explore promising water-soluble candidates for application in liquid food formulations. The results showed that by combining the two-stage, low-pH fermentation strategy with a downstream purification step of fractional crystallization, precursors of red MPs, namely monascorubrin and rubropunctatin, were obtained with a purity of 91.9%. Then, via the azaphilic addition reaction, 18 types of red MPs congeners carrying different amino acid moieties (MPs-aa) were semi-synthesized. Compared to rubropunctamine and monascorubramine, the water solubility, pH and thermal stability of MPs-aa were improved greatly. MPs-His, MPs-Phe, MPs-Tyr and MPs-Trp were identified to be the most resistant to pasteurization. These findings provide water-soluble red MPs candidates with high thermal stability and an attractive approach for their large scale production.

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Tremella sanguinea is a traditional Chinese medicinal and edible mushroom. Polysaccharides from Tremella mushrooms have received increasing amounts of research attention due to their diverse pharmacological activities. In this study, via the incubation of basidiospores collected from fresh artificially cultivated basidiocarps of T. sanguinea, a haploid yeast strain of T. sanguinea was obtained, and it was found to be a typical loose-slime-forming yeast capable of producing a large amount of exopolysaccharides (EPS). Using DEAE-52 cellulose column chromatography and Sephadex G-100 gel permeation chromatography, the major polysaccharide, named TSPS-1, was separated and purified from the EPS produced by the haploid yeast strain of T. sanguinea. TSPS-1 was a homogeneous polysaccharide with a molecular weight of 2.5 × 103 kDa and consisted of rhamnose, glucose, xylose, mannose and glucuronic acid at a molar ratio of 1: 0.7: 62.2: 24.6: 11.5. The bioactivity of the TSPS-1 polysaccharide was evaluated. The results show that TSPS-1 exhibited noticeable antioxidant activity by scavenging hydroxyl radicals (EC50 = 1.92 mg/mL) and superoxide radicals (EC50 = 1.33 mg/mL), and prebiotic activity by promoting the growth of different probiotic strains in the genus Lactobacillus and Bifidobacterium. These results suggest that the cultivation of the haploid yeast strain can be a promising alternative for the efficient production of valuable T. sanguinea polysaccharides with antioxidant and prebiotic potential.

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Digestive system malignant tumor is one of the common malignant tumors in humans,and its high morbidity and low survival rate at advanced stages bring heavy disease burden to patients,families and society.However,current tumor screening technologies are not suitable for screening in large-scale populations and long-term follow-up because of the invasiveness or complexity.Thus,liquid biopsy,which based on biomarkers such as circulating tumor DNA,circulating tumor cells,exosomes and other new biomarkers,has broad prospects for development in tumor screening.Exosome,secreted by living cells,is a type of extracellular vesicle with the lipid bilayer.Compared to other biomarkers,exosome has the advantages of high stability,wide distribution,and high quantity.The various proteins carried by exosome can reflect the characteristics of the origin cells,and exosome has important research value for the early diagnosis of tumors.This article reviews the studies of exosomal proteins as biomarkers for early diagnosis of digestive system malignant tumors in the past five years,and summarizes the characteristics and limitations of the above studies,so as to provide reference for promoting the clinical transformation of exosomal proteins.

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Osteoarthritis has become the fourth cause of disability in the world and its occurrence and development are caused by apoptosis and extracellular matrix (ECM) degradation of chondrocytes. Asiaticoside (ASI) is a triterpene saponin compound obtained from Centella Asiatica and has anti-inflammatory and anti-apoptotic effects in various diseases. However, its effects on OA are not clear. In this study, we reported that ASI has a protective effect on the occurrence and progression of OA in vivo and in vitro, and demonstrated its potential molecular mechanism. In vitro, ASI treatment inhibited the release of pro-apoptotic factors induced by TBHP and promoted the release of the anti-apoptotic proteins. In addition, ASI promotes the expression of Aggrecan and Collagen II, while inhibiting the expression of thrombospondin motifs 5 (ADAMTS5) and matrix metalloproteinase-13 (MMP-13), which causes extracellular matrix (ECM) degradation. Mechanistically, ASI exerts its anti-apoptotic effect by activating the Nrf2/HO-1 pathway and preventing p65 from binding to DNA. Similarly, in vivo, ASI has been shown to have a protective effect in a mouse OA model. The conclusion is that our research shows that ASI can be used as a potential drug for the treatment of OA.

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Objective:To investigate the epidemiological characteristics of influenza-like illnesses (ILI) and the etiological characteristics of influenza viruses in Minhang District of Shanghai from 2010 to 2021.Methods:The surveillance data collected by influenza surveillance sentinel hospitals and the influenza laboratory network from the first week of 2010 to the 52 nd week of 2021 were used for a statistical analysis. Results:A total of 122 903 cases with ILI were reported by the national influenza surveillance sentinel hospitals in Minhang during 2010 to 2021, and the average percentage of ILI cases was 0.94%, showing an increasing trend ( P<0.001). Among them, those aged 0-4, 5-14, 15-24, 25-59 and ≥60 years accounted for 4.35%, 13.30%, 14.30%, 54.32% and 13.73%, respectively. The percentage of ILI showed obvious periodicity. The seasonal incidence of ILI peaked from December to February and from July to September. But the winter peak at the beginning of 2013 was postponed. There was no significant peak in 2021. A total of 11 625 samples were tested from 2010 to 2021, in which the detection rate of influenza viruses was 20.92% (2 432/11 625). The positive rate was 12.83% (1 492/11 625) for influenza A viruses and 8.09% (940/11 625) for influenza B viruses, indicating that the epidemic intensity caused by influenza A viruses was greater than that caused by influenza B viruses. The overall positive rates for influenza A/H3N2 virus, influenza A/H1N1 virus, influenza B/Victoria lineage and influenza B/Yamagata lineage were 9.04% (1 051/11 625), 3.79% (441/11 625), 2.69% (313/11 625) and 2.19% (255/11 625) during 2010 to 2021. The predominant circulating strains altered between influenza A and influenza B viruses in Minhang District of Shanghai during 2010 to 2019. It generally took six months for an epidemic strain to be replaced by a new one. No obvious regularity was observed in 2020 or 2021. The tendency of the incidence of ILI reported from 2010 to 2019 was basically the same as that of the positive rate of influenza viruses, while there were significant differences in 2020 and 2021. Conclusions:Influenza viruses circulated seasonally in Minhang District of Shanghai with alternating prevalent viral subtypes and the infections mostly occurred in the winter and summer seasons. During the epidemic of COVID-19, the intensity of influenza was decreased, but with the normalization of prevention and control measures, the influenza epidemic showed an obvious upward trend. Therefore, it was important to strengthen the prevention and monitoring of influenza and analyze the virus variations in time.

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Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.

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Clostridium perfringens (C. perfringens) is a zoonotic microorganism and rarely reported in duck production chain. This study aimed to investigate prevalence, serotype distribution, antibiotic resistance and genetic diversity of C. perfringens at different stages of a duck production chain. In total, 319 samples were collected from a large-scale rearing and slaughter one-stop enterprise in Weifang, China, of which 42.95% of samples were positive for C. perfringens. All isolates were genotype A. Cpe and cpb2 genes were found in 2.54% and 24.87% of the isolates, respectively. Antimicrobial susceptibility testing revealed that 55.47% of the isolates resistant to at least 5 classes of commonly used antibiotics. Multilocus sequence typing (MLST) results showed that 65 representative isolates were divided into 47 sequences types (STs), 33.85% of them were included into four clonal complexes (CC). Some of isolates from breeding and slaughtering stages were distributed in the same CC or ST, indicating duck products may be contaminated by C. perfringens originated from the breeding stage. Part of duck isolates were distributed in the same CC as human isolates and systemically close with human isolates. The high contamination rates of duck products, the isolates with multi-drug antibiotic resistance or the cpe gene, and the close relationship between strains from human and ducks, indicated potential public health risks, not only control measures at slaughtering stage but also at rearing stage should be considered to reduce this risks.

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The yellow Monascus pigments (YMPs) named monascin and ankaflavin and the orange Monascus pigments (OMPs) named rubropunctatin and monascorubrin are two groups of bioactive components in a mixture state in the Monascus fermented products. In order to separate these two groups of bioactive pigments, a facile macroporous resin-based method was developed. The weak-polar resin CAD-40 was selected from the seven tested macroporous resins as it revealed better properties for the adsorption and desorption of the YMPs and OMPs. Then, CAD-40 resin was used for column-chromatographic separation. After eluted by 4 bed volumes of ethanol, the yellow group (monascin and ankaflavin) and the orange group (rubropunctatin and monascorubrin) were successfully separated and purified, with an increased content from 49.3% and 44.2% in the crude pigment extract to 85.2% and 83.0% in the final products, respectively. This method would be helpful for the large-scale separation and purification of Monascus pigment products with specific bioactivity.

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Controlling the reactivity of reactive intermediates is essential to achieve selective transformations. Due to the facile 1,5-hydrogen atom transfer (HAT), alkoxyl radicals have been proven to be important synthetic intermediates for the δ-functionalization of alcohols. Herein, we disclose a strategy to inhibit 1,5-HAT by introducing a silyl group into the α-position of alkoxyl radicals. The efficient radical 1,2-silyl transfer (SiT) allows us to make various α-functionalized products from alcohol substrates. Compared with the direct generation of α-carbon radicals from oxidation of α-C-H bond of alcohols, the 1,2-SiT strategy distinguishes itself by the generation of alkoxyl radicals, the tolerance of many functional groups, such as intramolecular hydroxyl groups and C-H bonds next to oxygen atoms, and the use of silyl alcohols as limiting reagents.

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The current study is undertaken to characterize the prevalence, genotypes distribution, antibiotic resistance and genetic diversity of Clostridium perfringens (C. perfringens) collected from different stages of a chicken production chain. In total, 579 samples from a broiler farm and 378 samples from the slaughterhouse were collected from a large-scale rearing and slaughter one-stop enterprise in Weifang, China, between June and July 2019, of which 30.40% of the samples from farm and 54.50% of samples from slaughterhouse were determined to be positive for C. perfringens, respectively. The contamination of chicken products was relatively serious, with the total positive rate of carcasses at 59.73%; the positive rate of carcass samples was the highest in the evisceration process, which might be the critical point of C. perfringens contamination. A total of 476 isolates of C. perfringens were recovered; and 99.58% of recovered isolates were identified as type A, with the remaining isolates being type G. Antimicrobial susceptibility testing revealed that 97.15% of the isolates showed multiple antibiotic resistance and 67.89% of them were resistant to at least five classes of commonly used antibiotics. Multilocus sequence typing results of 91 representative isolates showed that the isolates can be divided into 74 sequences types (STs); 40.66% of the isolates can be included into seven clonal complexes (CCs). Although most of the isolates were classified as type A, considerable genetic diversity was observed, with the Simpson's diversity index of ST up to 0.9902. Some isolates from farm stage and slaughter stage were distributed in the same ST or CC, indicating that chicken products may be contaminated by the same ST or CC of C. perfringens originated from the farm stage. The high contamination rates of chicken products and the widespread multiple antibiotic resistance of isolates indicated potential public health risks, control measures at rearing and slaughtering stage should be considered to reduce this risk.

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BackgroundPre-pandemic psychiatric disorders have been associated with an increased risk of COVID-19. However, the underlying mechanisms remain unknown, e.g. to what extent genetic predisposition to psychiatric disorders contributes to the observed association. MethodsThe analytic sample consisted of white British participants of UK Biobank registered in England, with available genetic data, and alive on Jan 31, 2020 (i.e., the start of the COVID-19 outbreak in the UK) (n=346,554). We assessed individuals genetic predisposition to different psychiatric disorders, including substance misuse, depression, anxiety, and psychotic disorder, using polygenic risk score (PRS). Diagnoses of psychiatric disorders were identified through the UK Biobank hospital inpatient data. We performed a GWAS analysis for each psychiatric disorder in a randomly selected half of the study population who were free of COVID-19 (i.e., the base dataset). For the other half (i.e., the target dataset), PRS was calculated for each psychiatric disorder using the discovered genetic variants from the base dataset. We then examined the association between PRS of each psychiatric disorder and risk of COVID-19, or severe COVID-19 (i.e., hospitalization and death), using logistic regression models. The ascertainment of COVID-19 was through the Public Health England dataset, the UK Biobank hospital inpatient data and death registers, updated until July 26, 2020. For validation, we repeated the PRS analyses based on publicly available GWAS summary statistics. Results155,988 participants (including 1,451 COVID-19 cases), with a mean age of 68.50 years at COVID-19 outbreak, were included for PRS analysis. Higher genetic liability forwards psychiatric disorders was associated with increased risk of both any COVID-19 and severe COVID-19, especially genetic risk for substance misuse and depression. The adjusted odds ratios (ORs) for any COVID-19 were 1.15 (95% confidence interval [CI] 1.02-1.31) and 1.26 (1.11-1.42) among individuals with a high genetic risk (above the upper tertile of PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Largely similar ORs were noted for severe COVID-19 and similar albeit slightly lower estimates using PRSs generated from GWAS summary statistics from independent samples. ConclusionIn the UK Biobank, genetic predisposition to psychiatric disorders was associated with an increased risk of COVID-19, including severe course of the disease. These findings suggest the potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19, underscoring the need of increased medical surveillance of for this vulnerable population during the pandemic.

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Esophageal squamous cell carcinoma （ESCC） is a malignant tumor caused by both environmental and genetic factors. Epidemiology studies have identified smoking as a major environmental risk factor. In recent years， the advancement of genomics research has led to the recognition of the influence of genetic variation in ESCC. We reviewed the research progress in smoking， genetic polymorphism and their interaction on susceptibility to ESCC. Reducing exposure time to tobacco was found to be the most effective way to reduce the risk. At the genetic level， mutations in DNA repair genes， regulation genes of carcinogen-metabolizing enzymes， cell cycle regulation genes， folate metabolism related genes， and alcohol metabolism related genes were found to significantly increase the risk of ESCC. However， studies on the interaction between smoking and genetic polymorphisms in ESCC risk are still limited， more studies are needed for better screening of the high-risk populations and the prevention.

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Esophageal squamous cell carcinoma （ESCC） is a malignant tumor caused by both environmental and genetic factors. Epidemiology studies have identified smoking as a major environmental risk factor. In recent years， the advancement of genomics research has led to the recognition of the influence of genetic variation in ESCC. We reviewed the research progress in smoking， genetic polymorphism and their interaction on susceptibility to ESCC. Reducing exposure time to tobacco was found to be the most effective way to reduce the risk. At the genetic level， mutations in DNA repair genes， regulation genes of carcinogen-metabolizing enzymes， cell cycle regulation genes， folate metabolism related genes， and alcohol metabolism related genes were found to significantly increase the risk of ESCC. However， studies on the interaction between smoking and genetic polymorphisms in ESCC risk are still limited， more studies are needed for better screening of the high-risk populations and the prevention.

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Stereoselectively-fluorinated analogs of pipecolic acid have been investigated through a combined theoretical and experimental approach. Three of the four possible diastereoisomers of 4,5-difluoropipecolic acid were successfully synthesized via deoxyfluorination chemistry, navigating a complex reaction network that included neighboring group participation, rearrangement, and elimination pathways. A DFT-based conformational study, supported by NMR J-based analysis, revealed that the different diastereoisomers of 4,5-difluoropipecolic acid preferentially adopt different puckers of the six-membered ring. These findings could have future relevance for the conformational control of biologically active peptides.

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BACKGROUND: Effective management of imported cases is an important part of epidemic prevention and control. Hainan Province, China reported 168 coronavirus disease 2019 (COVID-19), including 112 imported cases on February 19, 2020, but successfully contained the epidemic within 1 month. We described the epidemiological and clinical characteristics of COVID-19 in Hainan and compared these features between imported and local cases to provide information for other international epidemic areas. METHODS: We included 91 patients (56 imported and 35 local cases) from two designated hospitals for COVID-19 in Haikou, China, from January 20 to February 19, 2020. Data on the demographic, epidemiological, clinical and laboratory characteristics were extracted from medical records. Patients were followed until April 21, 2020, and the levels of antibodies at the follow-ups were also analysed by the Wilcoxon matched-pairs signed ranks test. RESULTS: Of the 91 patients, 78 (85.7%) patients were diagnosed within the first three weeks after the first case was identified (Day 1: Jan 22, 2020), while the number of local cases started to increase during the third week. No new cases occurred after Day 29. Fever and cough were two main clinical manifestations. In total, 15 (16.5%) patients were severe, 14 (15.4%) had complicated infections, nine (9.9%) were admitted to the intensive care unit, and three died. The median duration of viral shedding in feces was longer than that in nasopharyngeal swabs (19 days vs 16 days, P = 0.007). Compared with local cases, imported cases were older and had a higher incidence of fever and concurrent infections. There was no difference in outcomes between the two groups. IgG was positive in 92.8% patients (77/83) in the follow-up at week 2 after discharge, while 88.4% patients (38/43) had a reduction in IgG levels in the follow-up at week 4 after discharge, and the median level was lower than that in the follow-up at week 2 (10.95 S/Cut Off (S/CO) vs 15.02 S/CO, P <  0.001). CONCLUSION: Imported cases were more severe than local cases but had similar prognoses. The level of IgG antibodies declined from week 6 to week 8 after onset. The short epidemic period in Hainan suggests that the epidemic could be quickly brought under control if proper timely measures were taken.

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Clostridium perfringens is an important zoonotic microorganism. The present study was undertaken to investigate prevalence, serotype distribution, antibiotic resistance, and genetic diversity of C. perfringens isolates from 4 duck farms in Shandong, China. In total, 424 samples of cloacal swabs and environment were collected from 3 commercial meat-type duck farms in Tai'an, Liaocheng, and Weifang and one breeder duck farm in Liaocheng between December 2018 and June 2019, of which, 207 (48.82%) samples were determined to be positive for C. perfringens; a total of 402 isolates of C. perfringens were recovered, all of which were identified as type A; 30.85% of the isolates were positive for cpb2 gene; and cpe gene was found in 0.5% of the isolates. Antimicrobial susceptibility testing revealed that some of the isolates exhibited high antibiotic resistance, and 39.14% of the isolates were resistant to at least 5 classes of commonly used antibiotics. Multilocus sequence typing analysis showed that 85 representative isolates encompassed 54 different sequences types (STs), clustered in 5 clonal complexes (CCs) and 40 singletons. ST3, the most common ST in 54 STs, constituting 15.29% of all isolates, was also the most prevalent ST of isolates from the Liaocheng breeder duck farm (farm 3). CC1, the most prolific CC, containing 15.29% of the analyzed isolates, was the popular subtype of isolates from Liaocheng meat duck farm (farm 2). Although all the isolates belong to type A, the genetic diversity varied greatly in different regions; the Simpson's Diversity Index of STs for Liaocheng, Tai'an, and Weifang were 0.5941, 0.9198, and 0.9627, respectively. Some of cloacal isolates and environmental isolates were distributed in the same ST or CC, indicating close genetic relationship between cloacal isolates and environmental isolates. A portion of the strains from humans and ducks was found to be phylogenetically close. The close relationship between strains from humans and ducks, the high antibiotic resistance of C. perfringens, and the cpe-positive isolates indicated potential public health risks.

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Molecular tools of double or multimeric G-quadruplexes have been given higher requirements on detection sensitivity, thermal stabilization and cell imaging to establish functions of these G-quadruplex aggregates and biological mechanisms as anticancer reagents. Here, two smart berberine-bisquinolinium conjugates (Ber-360A and Ber-PDS) by linking the berberine fluorophore ligand and an established G-quadruplex binder (i.e. bisquinolinium scaffold), have been designed and evaluated their activities and mechanisms for G-quadruplex aggregation. Two conjugates, especially Ber-PDS, are two highly selective, sensitive and fluorescent sensors which can distinguish human telomere double G-quadruplexes from other type G-quadruplexes and ds DNA. These two ligands could be the first example to stack two adjacent G-quadruplex units and fluorescently recognize human telomere double G-quadruplexes. Furthermore, conjugate Ber-PDS could enter the nucleoli and target G-quadruplex DNA through microscopy experiments, and also display strong telomerase inhibition and antitumor activities.

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We have realized the first Ullmann type coupling reaction of tri(di)fluoroethylamine with (hetero)aromatic bromides, employing 5-20 mol% Cu2O and an oxalamide ligand [N-(2,4,6-trimethoxyphenyl)acetamide]. This efficient and practical method has the following features: (i) avoids the use of an expensive catalyst; (ii) does not require anhydrous solvent and strict air extrusion; (iii) uses bench stable and inexpensive (hetero)aromatic bromides; (iv) is suitable for the synthesis of fluoroalkylated hetero-aromatic substrates; (v) is suitable for gram-scale synthesis. This work also shows the "negative fluorine effect" for the alkylamines in the copper catalysed coupling reactions.

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The influence of pH on the biosynthesis of orange Monascus pigments (OMPs) in Monascus ruber M7 was investigated. Under acidic fermentation conditions, pigment mixtures predominantly rich in OMPs were obtained. HPLC analysis revealed the presence of four orange components (O1-O4) and four yellow components (Y1-Y4) in the mixtures, and the dominant ones were O1 and O3, which accounted for 56.0% to 75.9% of the total pigments in the pH range 3-6. Subsequently, O1 and O3 were identified by LC-DAD-ESI/MS as Rubropunctatin and Monascorubrin, respectively. The yield of OMPs was observed to be inversely dependent on pH. At pH 3, large amounts of OMPs with high purity (79.1%) were accumulated. A real-time quantitative PCR analysis revealed that the expression of genes related to the biosynthesis of OMPs in M. ruber M7 was upregulated at acidic pH as compared to neutral pH, and the variation in the level of expression of these genes with pH was consistent with the production of OMPs. These results indicated that the large accumulation of OMPs under acidic condition involved the acidic pH-induced transcription of genes related to the biosynthesis of OMPs. These results would contribute towards the development of an efficient technology for large-scale production of OMPs.

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