Viral Metagenomics Analysis of Planktonic Viruses in East Lake,Wuhan,China

East Lake(Lake Donghu),located in Wuhan,China,is a typical city freshwater lake that has been experiencing eutrophic conditions and algal blooming during recent years.Marine and fresh water are considered to contain a large number of viruses.However,little is known about their genetic diversity because of the limited techniques for culturing viruses.In this study,we conducted a viral metagenomic analysis using a high-throughput sequencing technique with samples collected from East Lake in Spring,Summer,Autumn,and Winter.The libraries from four samples each generated 234,669,71,837,12,820,and 34,236 contigs(>90 bp each),respectively.The genetic structure of the viral community revealed a high genetic diversity covering 23 viral families,with the majority of contigs homologous to DNA viruses,including members of Myoviridae,Podoviridae,Siphoviridae,Phycodnaviridae,and Microviridae,which infect bacteria or algae,and members of Circoviridae,which infect invertebrates and vertebrates.The highest viral genetic diversity occurred in samples collected in August,then December and June,and the least diversity in March.Most contigs have low-sequence identities with known viruses.PCR detection targeting the conserved sequences of genes(g20,psbA,psbD,and DNApol)of cyanophages further confirmed that there are novel cyanophages in the East Lake.Our viral metagenomic data provide the first preliminary understanding of the virome in one freshwater lake in China and would be helpful for novel virus discovery and the control of algal blooming in the future.

Improving chemical and sensory quality of high-oleic peanut by application of foliar fertilizer

High-oleic peanut is favored by consumers because its a longer shelf life and benefits for cardiovascular health.Up to the high-oleic standard and with good taste is essential for peanut products in food processing.The aim of present study was to explore the effect of foliar fertilizers on chemical and eating quality of high-oleic peanuts.Three high-oleic peanut cultivars,namely Huayu 09C2,Huayu 9621,and Huayu 962,were used as materials.Huayu 09C2 and Huayu 9621 were planted in Fuxin,Liaoning,foliar sprayed with Fosforil at 2250 mL/ha,and Huayu 962 was sown in Jvnan,Shandong,foliar sprayed with Foliplus at 1500/3000 mL/ha.The chemical and sensory quality of peanut harvested from the treatment plots and controls was evaluated.Results showed that,Huayu 09C2 and Huayu 9621,foliar spraying with Fosforil in Fuxin,Huayu 962,foliar spraying with Foliplus in Jvnan,all still maintained high oleate content levels,and the Fosforil treatment was effective in raising the intensity of sweetness of roasted kernels.This study demonstrated the feasibility of improving chemical and sensory quality of high-oleic peanut through foliar fertilizer.

Improvement of the tissue culture technique for Melaleuca alternifolia

Tea tree oil is extracted from the leaves and twigs of Melaleuca alternifolia(Maiden & Betche) Cheel,and it is widely used in medicines, food preservatives,cosmetics and health care products. Traditional propagation of M. alternifolia from seeds does not necessarily transfer the desired characteristics from their mother trees,the seedlings are not uniform, and the multiplication rate from cuttings is relatively low. For these reasons, it is necessary to develop tissue culture techniques for this species. This study showed that an efficient explant initiation medium for M. alternifolia was MS 1/2 + BA0.6 mg L^(-1)+ NAA 0.1 mg L^(-1)+ sucrose 30 g L^(-1),which yielded a 75.9 % initiation rate. An efficient multiplication medium was MS + BA 0.3 mg L^(-1)+ NAA0.15 mg L^(-1)+ sucrose 30 g L^(-1), which yielded a 4.3multiplication rate and 3.2 cm shoot length. The rooting medium was MS 1/2 + IBA 0.1–0.25 mg L^(-1)+ sucrose15 g L^(-1), which yielded a 100 % rooting rate, 2.94–3.32 roots per individual and 1.36–1.44 cm root length. Local red-core soil was suitable as a transplant medium, and yielded 98 % survival. This study improved the tissue culture technique for mass-propagation of M. alternifolia,enabling the production of high quality plants for market.

VAR AND CTE BASED OPTIMAL REINSURANCE FROM A REINSURER'S PERSPECTIVE

In this article,we study optimal reinsurance design.By employing the increasing convex functions as the admissible ceded loss functions and the distortion premium principle,we study and obtain the optimal reinsurance treaty by minimizing the VaR(value at risk)of the reinsurer's total risk exposure.When the distortion premium principle is specified to be the expectation premium principle,we also obtain the optimal reinsurance treaty by minimizing the CTE(conditional tail expectation)of the reinsurer's total risk exposure.The present study can be considered as a complement of that of Cai et al.[5].

Polarized photoluminescence spectroscopy in WS_(2),WSe_(2) atomic layers and heterostructures by cylindrical vector beams

Due to the large exciton binding energy,two-dimensional(2D)transition metal dichalcogenides(TMDCs)provide an ideal platform for studying excitonic states and related photonics and optoelectronics.Polarization states lead to distinct light-matter interactions which are of great importance for device applications.In this work,we study polarized photoluminescence spectra from intralayer exciton and indirect exciton in WS_(2) and WSe_(2) atomic layers,and interlayer exciton in WS_(2)/WSe_(2) heterostructures by radially and azimuthally polarized cylindrical vector laser beams.We demonstrated the same in-plane and out-of-plane polarization behavior from the intralayer and indirect exciton.Moreover,with these two laser modes,we obtained interlayer exciton in WS_(2)/WSe_(2) heterostructures with stronger out-of-plane polarization,due to the formation of vertical electric dipole moment.

Pharmacokinetics of Arctigenin in Fructus Arctii Extract in Piglets

[Objectives]This study was conducted to investigate the pharmacokinetic characteristics of arctigenin from water extract of Fructus Arctii in piglets,understand its absorption,distribution,transformation and excretion in piglets,and provide theoretical reference for the development and clinical use of new veterinary drugs.[Methods]Six healthy piglets,weighing(30.0±5.0)kg,were selected and administered by gavage with a Fructus Arctii water extract at 1.0 g/kg·bw.Blood was collected from the anterior vena cava at different time points.The concentration of arctigenin in pig plasma was determined by HPLC.The main pharmacokinetic parameters were:absorption half-life(t1/2 ka)(0.098±0.006)h,distribution half-life(t1/2α)(0.208±0.009)h,elimination half-life(t1/2β)(23.816±2.151)h,apparent volume of distribution(Vd)(32.212±4.033)L/kg,apparent volume of distribution(Vd)(32.212±4.033)L/kg,clearance(CLb)(2.384±1.589)L/(h·kg),peak time(tmax)(0.251±0.011)h,peak concentration(Cmax)(0.560±0.063)μg/ml,and the area under the curve(AUC)at the time of drug administration(9.620±0.752)μg·h/ml.[Results]After oral administration of the water extract powder of Fructus Arctii,arctigenin showed a two-compartment model with absorption in piglets,with the characteristics of fast absorption,wide distribution and slow elimination.Arctigenin might have a hepatoenteral circulation in piglets,and the drug effect could last for a long time.[Conclusions]This study provides a theoretical basis and reference for the development and clinical use of new veterinary drugs.

B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation

Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role of anti-phosphatidylserine (PS) autoantibodies in the development of LN. Elevated serum PS-specific IgG levels were measured in model mice and SLE patients, especially in those with LN. PS-specific IgG accumulation was found in the kidney biopsies of LN patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type that secretes PS-specific IgG in both lupus model mice and patients. Adoptive transfer of PS-specific B1a cells accelerated the PS-specific autoimmune response and renal damage in recipient lupus model mice, whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components, while blockade of TLR signal cascades by DNase I digestion and inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of the TLR/Syk signaling cascade inhibits PS-specific B1-cell expansion provide new insights into lupus pathogenesis and may facilitate the development of novel therapeutic targets for the treatment of LN in SLE.

Transcriptome analysis of Saposhnikovia divaricata and mining of bolting and fowering genes

Objective: Early bolting of Saposhnikovia divaricata has seriously hindered its medicinal value and sustainable development of resources. The molecular mechanism of bolting and fowering of S. divaricata is still unclear and worth of research. In our study, we explored the transcriptome of the genes related to the bolting and fowering of S. divaricata.Methods: The transcriptome library was constructed, sequenced, assembled and annotated from the bolting and unbolting leaves of S. divaricata by high-throughput sequencing at the bud and fowering stage.Focus on the pathways related to bolting and fowering in plants, and exploring genes. The expression of seven candidate genes was verified by real-time fuorescence quantitative PCR(qRT-PCR).Results: Transcriptome results showed that 249 889 422 high-quality clean reads were obtained. A total of 67 866 unigenes were assembled with an average length of 948.1 bp. Trinity de Novo assembly produced 67 866 unigenes with an average length of 948.1 bp. Among 993 differentially expressed genes,484 genes were significantly up-regulated and 509 genes were down-regulated in the SdM group. A total of 79 GO terms were significantly enriched for differentially expressed genes. KEGG results showed that 11 154 unigenes were enriched in 89 pathways. And 21 candidate genes related to bolting and fowering of S. divaricata were excavated. The qRT-PCR results showed that expression trends of HDA9, PHYB, AP2,TIR1, Hsp90, CaM, and IAA7 were consistent with transcriptomic sequencing results. In addition, RNA-seq had identified 10 740 transcription factors and classified them into 58 families by their conserved domains. Further studies showed that the transcription factors regulating the fowering of S. divaricata were mainly distributed in the NAC, MYB_related, HB-other, ARF, and AP2 families.Conclusion: Based on the results of this study, it was found that the plant hormone signal transduction pathway was one of the decisive factors to control bolting and fowering. Among them, auxin related genes IAA and TIR1 are the key genes in the bolting and fowering process of S. divaricata.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR)

Background:The clinical features of enthesitis in patients with psoriatic arthritis(PsA)have been reported in some Western countries,but data in China are very limited.This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts.Methods:Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis(CREPAR)(December 2018 to June 2021)were included.Data including demographics,clinical characteristics,disease activity measures,and treatment were collected at enrollment.Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada(SPARCC),Maastricht ankylosing spondylitis enthesitis score(MASES),and Leeds enthesitis index(LEI)indices.A multivariable logistic model was used to identify factors related to enthesitis.We also compared our results with those of other cohorts.Results:In total,1074 PsA patients were included,308(28.7%)of whom had enthesitis.The average number of enthesitis was 3.3±2.8(range:1.0–18.0).More than half of the patients(165,53.6%)had one or two tender entheseal sites.Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis,reported a higher proportion of PsA duration over 5 years,and had a higher percentage of axial involvement and greater disease activity.Multivariable logistic regression showed that axial involvement(odds ratio[OR]2.21,95%confidence interval[CI],1.59–3.08;P<0.001),psoriasis area and severity index(PASI)(OR:1.03,95%CI:1.01–1.04;P=0.002),and disease activity score 28-C reactive protein(DAS28-CRP)(OR:1.25,95%CI:1.01–1.55;P=0.037)were associated with enthesitis.Compared with the results of other studies,Chinese patients with enthesitis had a younger age,lower body mass index(BMI),a higher rate of positive human leukocyte antigen(HLA)-B27,more frequent dactylitis,and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs’(csDMARDs)use.Conclusions:Enthesitis is a common condition among Chinese patients with PsA.It is important to evaluate entheses in both peripheral and axial sites.

结节性多动脉炎诊疗规范

结节性多动脉炎(PAN)是主要累及中小动脉的一种少见的血管炎,好发于血管的分叉处,导致微动脉瘤、血栓形成、动脉瘤破裂出血及器官梗死。约1/3的患者与乙型肝炎病毒(HBV)感染相关。全身各组织器官均可受累,以皮肤、关节、外周神经最常见。病理改变急性期为血管壁纤维蛋白样坏死,炎性细胞浸润和管腔内血栓形成,慢性期为血管壁纤维性增生。近几十年来,PAN的总体预后得到了改善,主要反映了早期诊断和更有效的治疗方法。PAN治疗主要是糖皮质激素和环磷酰胺,而HBV相关PAN患者应接受抗病毒治疗和血浆置换。中华医学会风湿病学分会组织有关专家,在借鉴国内外诊治经验和指南的基础上,制定了本规范,旨在规范PAN的诊断和治疗,以降低致死率及严重并发症的发生率,更好地控制病情,改善患者预后。

Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure in human–hamster hybrid cells

Microcystin-LR(MC-LR) is the most abundant and toxic microcystin congener and has been classified as a potential human carcinogen(Group 2B) by the International Agency for Research on Cancer. However, the mechanisms underlying the genotoxic effects of MC-LR during chronic exposure are still poorly understood. In the present study, human–hamster hybrid(AL) cells were exposed to MC-LR for varying lengths of time to investigate the role of nitrogen radicals in MC-LR-induced genotoxicity. The mutagenic potential at the CD59 locus was more than 2-fold higher(p < 0.01) in ALcells exposed to a cytotoxic concentration(1 μmol/L) of MC-LR for 30 days than in untreated control cells, which was consistent with the formation of micronucleus. MC-LR caused a dose-dependent increase in nitric oxide(NO) production in treated cells. Moreover, this was blocked by concurrent treatment with the NO synthase inhibitor NG-methyl-L-arginine(L-NMMA), which suppressed MC-LRinduced mutations as well. The survival of mitochondrial DNA-depleted(ρ0) ALcells was markedly decreased by MC-LR treatment compared to that in ALcells, while the CD59 mutant fraction was unaltered. These results provided clear evidence that the genotoxicity associated with chronic MC-LR exposure in mammalian cells was mediated by NO and might be considered as a basis for the development of therapeutics that prevent carcinogenesis.

Avian Influenza A(H7N9) Virus in a Wild Land Bird in Central China,Late 2015

Dear Editor,In early 2013,the first case of a human infection with avian influenza A(H7N9)virus was reported in the Yangtze River Delta region of China(Liu et al.2013).Since early2013,a total of 1533 laboratory-confirmed human infections with avian H7N9 viruses have been reported to

Assessment of the cytotoxic and mutagenic potential of the Jialu River and adjacent groundwater using human-hamster hybrid cells

The Jialu River in China has been seriously polluted by the direct discharge of industrial and domestic wastewater. The predominant contaminants of the Jialu River and its adjacent groundwater were recently investigated. However, the potential genotoxic impact of polluted water on human health remains to be clarified. Here, we used human–hamster hybrid(A_L) cells, which are sensitive for detecting environmental mutagens. We found that the cytotoxicity and mutagenicity of the groundwater in the Jialu River basin were influenced by the infiltration of the Jialu River. Hydrological periods significantly affected the cytotoxicity, but not the mutagenic potential, of surface and groundwater. Further, the mutagenic potential of groundwater samples located < 1 km from the Jialu River(S_(M-2) water samples) was detected earlier than that of groundwater samples located approximately 20 km from the Jialu River(S_N water samples). Because of high cytotoxicity, the mutagenic potential of water samples from the Jialu River(S_(M-1) water samples) was not significantly enhanced compared with that of untreated controls. To further assess the mutagenic dispersion potential, an artificial neural network model was adopted. The results showed that the highest mutagenic potential of groundwater was observed approximately 10 km from the Jialu River. Although further investigation of mutagenic spatial dispersion is required, our data are significant for advancing our understanding of the origin, dispersion,and biological effects of water samples from polluted areas.

Chinese registry of rheumatoid arthritis(CREDIT)V:sex impacts rheumatoid arthritis in Chinese patients

Background: The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients.Methods: Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits.Results: A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0vs. 6.7 mg/L), pain visual analogue scale (4.8vs. 4.5), patient’s and physician’s global assessment (4.9vs. 4.5 and 4.9vs. 4.5), 28-joint disease activity score using DAS28-CRP (4.3vs. 4.0) simplified disease activity index (21.9vs. 19.9), and clinical disease activity index (19.3vs. 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4%vs. 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women.Conclusions: In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.

Fabrication of layered structure VS4 anchor in 3D graphene aerogels as a new cathode material for lithium ion batteries

VS4 has gained more and more attention for its high theoretical capacity (449 mAh/g with 3e^- transfer) in lithium ion batteries (LIBs). Herein, a layered structure VS4 anchored in graphene aerogels is prepared and first reported as cathode material for LIBs. VS4@GAs composite exhibits an exceptional high initial reversible capacity (511 mAh/g), an excellent high-rate capability (191 mAh/g at the 5 C), and an excellent cyclic stability (239 mAh/g after 15 cycles).

Sex differences in systemic lupus erythematosus(SLE):an inception cohort of the Chinese SLE Treatment and Research Group(CSTAR)registry XVII

Background:The onset and clinical presentation of systemic lupus erythematosus(SLE)are sex-related.Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort.This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort.Methods:Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group,a total of 8713 patients(795 men and 7918 women)with newly diagnosed SLE were enrolled between April 2009 and March 2021.Of these,2900 patients(347 men and 2553 women)were eligible for lupus nephritis(LN).A cross-sectional analysis of the baseline demographic characteristics,clinical manifestations,laboratory parameters,organ damage,initial treatment regimens,and renal pathology classification was performed according to sex.Results:In the SLE group,as compared to female patients,male patients had a later age of onset(male vs.female:37.0±15.8 years vs.35.1±13.7 years,P=0.006)and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score(male vs.female:0.47±1.13 vs.0.34±0.81,P=0.015),LN(male vs.female:43.6%vs.32.2%,P<0.001),fever(male vs.female:18.0%vs.14.6%,P=0.010),thrombocytopenia(male vs.female:21.4%vs.18.5%,P=0.050),serositis(male vs.female:14.7%vs.11.7%,P=0.013),renal damage(male vs.female:11.1%vs.7.4%,P<0.001),and treatment with cyclophosphamide(CYC)(P<0.001).The frequency of leukopenia(male vs.female:20.5%vs.25.4%,P=0.002)and arthritis(male vs.female:22.0%vs.29.9%,P<0.001)was less in male patients with SLE.In LN,no differences were observed in disease duration,SLE Disease Activity Index score,renal biopsy pathological typing,or 24-h urine protein quantification among the sexes.In comparisons with female patients with LN,male patients had later onset ages(P=0.026),high serum creatinine(P<0.001),higher end-stage renal failure rates(P=0.002),musculoskeletal damage(P=0.023),cardiovascular impairment(P=0.009),and CYC use(P=0.001);while leukopenia(P=0.017),arthritis(P=0.014),and mycophenolate usage(P=0.013)rates were lower.Conclusions:Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients;therefore,they may require more aggressive initial treatment compared to female patients.

Affinity maturation of anti-TNF-alpha scFv with somatic hypermutation in non-B cells

Activation-induced cytidine deaminase(AID)is required for the generation of antibody diversity through initiat-ing both somatic hypermutation(SHM)and class switch recombination.A few research groups have success-fully used the feature of AID for generating mutant li-braries in directed evolution of target proteins in B cells in vitro.B cells,cultured in suspension,are not con-venient for transfection and cloning.In this study,we established an AID-based mutant accumulation and sorting system in adherent human cells.Mouse AID gene was first transfected into the human non-small cell lung carcinoma H1299 cells,and a stable cell clone(H1299-AID)was selected.Afterwards,anti-hTNF-αscFv(ATscFv)was transfected into H1299-AID cells and ATscFv was displayed on the surface of H1299-AID cells.By 4-round amplification/flow cytometric sorting for cells with the highest affinities to hTNF-alpha,two ATscFv mutant gene clones were isolated.Compared with the wild type ATscFv,the two mutants were much more efficient in neutralizing cytotoxicity of hTNF-alpha.The results indicate that directed evolution by somatic hypermutation can be carried out in adherent non-B cells,which makes directed evolution in mammalian cells easier and more efficient.

Enhanced radiosensitivity by 6-thio-dG via increasing telomere dysfunction and ataxia telangiectasia mutated inhibition in non-small cell lung cancer

Objective:To investigate the radiosensitivity of 6-thio-dG and its underlying molecular mechanisms in non-small cell lung cancer(NSCLC).Methods:H1299 and A549 NSCLC cells were pretreated with 6-thio-dG for one week and then exposed toγ-irradiation.Cell proliferation and survival were quantified using clonogenic assays.DNA damage was assessed using immunofluorescence forγH2AX.Telomere dysfunction-induced foci analysis was performed by the colocalization of telomere signals(FISH)andγH2AX.Telomere fusion was defined as two telomere signals merged into one at the chromosome by immuno-FISH in metaphase spreads.Proteins related to the DNA damage response were detected using Western blot analysis.Apoptosis wasanalyzed using flow cytometry and Western blot.Results:The presence of 6-thio-dG increased the radio sensitivity of H1299 and A549 cells(P<0.05),but had no effect on the normal human lung fibroblast line,MRC5.6-thio-dG pretreatment significantly reduced the clonogenic potential induced byγ-ray irradiation and aggravated genomic DNA and telomeric DNA damage(P<0.05).In addition,6-thio-dG pretreatment effectively increasedγ-ray irradiation induced telomere dysfunction(P<0.05),resulting in disruption of chromosome stability and inhibition of the ATM pathway,thereby impairing genomic DNA and telomeric DNA repair,which was closely associated with enhanced drug-mediated radiation-induced apoptosis.Conclusions:6-thio-dG increases the radiosensitivity of NSCLC by inhibiting ATM and inducing telomere dysfunction,which can potentially be used as a strategy for radiotherapy for NSCLC.