Comprehensive application of AI algorithms with TCR NGS data for glioma diagnosis.

T-cell receptor (TCR) detection can examine the extent of T-cell immune responses. Therefore, the article analyzed characteristic data of glioma obtained by DNA-based TCR high-throughput sequencing, to predict the disease with fewer biomarkers and higher accuracy. We downloaded data online and obtained six TCR-related diversity indices to establish a multidimensional classification system. By comparing actual presence of the 602 correlated sequences, we obtained two-dimensional and multidimensional datasets. Multiple classification methods were utilized for both datasets with the classification accuracy of multidimensional data slightly less to two-dimensional datasets. This study reduced the TCR ß sequences through feature selection methods like RFECV (Recursive Feature Elimination with Cross-Validation). Consequently, using only the presence of these three sequences, the classification AUC value of 96.67% can be achieved. The combination of the three correlated TCR clones obtained at a source data threshold of 0.1 is: CASSLGGNTEAFF_TRBV12_TRBJ1-1, CASSYSDTGELFF_TRBV6_TRBJ2-2, and CASSLTGNTEAFF_TRBV12_TRBJ1-1. At 0.001, the combination is: CASSLGETQYF_TRBV12_TRBJ2-5, CASSLGGNQPQHF_TRBV12_TRBJ1-5, and CASSLSGNTIYF_TRBV12_TRBJ1-3. This method can serve as a potential diagnostic and therapeutic tool, facilitating diagnosis and treatment of glioma and other cancers.

Effects of lactic acid bacteria on rearing water bacterial community in Eriocheir sinensis culture.

The Chinese mitten crab (CMC, Eriocheir sinensi) culture in ponds is a unique aquaculture system. Probiotics are commonly used in the maintenance of the health of pond-cultured CMCs. However, the effects of probiotics on the bacterial community of CMC-culturing water remain unclear. This study utilized 16S rRNA gene amplicon sequencing to assess changes in the bacterial community composition, diversity, assembly, and co-occurrence patterns in CMC-culturing water following probiotic application. The results indicate that the α-diversity of the bacterial community in CMC-culturing water varied with time following probiotic application. The addition of probiotics to the water resulted in an increase in the occurrence of new operational taxonomic units (OTUs). The bacterial community assembly in the CMC-culturing water was shaped by a balance between deterministic and stochastic processes, while commercial probiotics enhanced the proportion of heterogeneous selection. In addition, including OTU2953 (Burkholderiaceae) and OTU3005 (Lactobacillaceae), from the commercial probiotics served as keystone species in the bacterial network of CMC-culturing water. Overall, probiotic application had a significant impact on the bacterial ecology of CMC-culturing water.

Mapping and candidate gene analysis of QTLs for grain shape in a rice chromosome segment substitution line Z485 and breeding of SSSLs.

Grain shape is one of the most important factors that affects rice yield. Cloning novel grain shape genes and analyzing their genetic mechanisms are crucial for high yield breeding. In this study, a slender grain CSSL-Z485 with 3-segments substitution in the genetic background of Nipponbare was constructed in rice. Cytological analysis showed that the longer grain length of Z485 was related to the increase in glume cell numbers, while the narrower grain width was associated with the decrease in cell width. Three grain shape-related quantitative trait locus (QTLs), including qGL12, qGW12, and qRLW12, were identified through the F2 population constructed from a cross between Nipponbare and Z485. Furthermore, four single segment substitution lines (SSSLs, S1-S4) carrying the target QTLs were dissected from Z485 by MAS. Finally, three candidate genes of qGL12 for grain length and qGW12 for grain width located in S3 were confirmed by DNA sequencing, RT-qPCR, and protein structure prediction. Specifically, candidate gene 1 encodes a ubiquitin family protein, while candidate genes 2 and 3 encode zinc finger proteins. The results provide valuable germplasm resources for cloning novel grain shape genes and molecular breeding by design. Supplementary information: The online version contains supplementary material available at 10.1007/s11032-024-01480-x.

Determinants of health poverty vulnerability in rural areas of Western China in the post-poverty relief era: an analysis based on the Anderson behavioral model.

BACKGROUND: Although China has eliminated absolute poverty, the effects of sickness still pose a threat to the prospect of returning to poverty in western rural areas. However, poverty governance extends beyond solving absolute poverty, and should enhance the family's ability to resist risks, proactively identify the existence of risks, and facilitate preventive measures to reduce the probability of falling into poverty again. This study aimed to assess the health poverty vulnerability of rural households in western China and decompose its determinants. METHODS: Based on survey data from 2022, the three-stage feasible generalized least squares method was used to calculate the health poverty vulnerability index. Then, Anderson's health behavior theory model was extended to analyse various influencing factors using binary logistic regression, and the contribution of each influencing factor was decomposed using the Shapley index. Finally, Tobit regression and the censored least absolute deviations estimation (clad) method were used to test the model's robustness. RESULTS: A total of 5455 families in the rural Ningxia region of western China were included in the study. The health poverty vulnerability index of the sample population in 2022 was 0.3000 ± 0.2223, and families with vulnerability ≥0.5 accounted for 16.9% of the sample population. From the Anderson behavioral model, the three models including propensity, enabling, and demand factors had the best fit, and the AIC and BIC values were the smallest. The Shapley decomposition showed that the dimensions of the propensity factor, number of residents, age and educational level of the household head, and dependency ratio were the most important factors influencing vulnerability to health poverty. Tobit regression and the clad method proved the reliability of the constructed model through a robustness test. CONCLUSION: Rural areas still face the risk of becoming poor or falling into poverty owing to residents' health problems. Health poverty alleviation should gradually change from a focus on treatment to prevention, and formulate a set of accurate and efficient intervention policies from a forward-looking perspective to consolidate the results of health poverty alleviation and prevent widescale poverty return.

Cleavage of HDAC6 to dampen its antiviral activity by nsp5 is a common strategy of swine enteric coronaviruses.

HDAC6, a structurally and functionally unique member of the histone deacetylase (HDAC) family, is an important host factor that restricts viral infection. The broad-spectrum antiviral activity of HDAC6 makes it a potent antiviral agent. Previously, we found that HDAC6 functions to antagonize porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus with zoonotic potential. However, the final outcome is typically a productive infection that materializes as cells succumb to viral infection, indicating that the virus has evolved sophisticated mechanisms to combat the antiviral effect of HDAC6. Here, we demonstrate that PDCoV nonstructural protein 5 (nsp5) can cleave HDAC6 at glutamine 519 (Q519), and cleavage of HDAC6 was also detected in the context of PDCoV infection. More importantly, the anti-PDCoV activity of HDAC6 was damaged by nsp5 cleavage. Mechanistically, the cleaved HDAC6 fragments (amino acids 1-519 and 520-1159) lost the ability to degrade PDCoV nsp8 due to their impaired deacetylase activity. Furthermore, nsp5-mediated cleavage impaired the ability of HDAC6 to activate RIG-I-mediated interferon responses. We also tested three other swine enteric coronaviruses (transmissible gastroenteritis virus, porcine epidemic diarrhea virus, and swine acute diarrhea syndrome-coronavirus) and found that all these coronaviruses have adopted similar mechanisms to cleave HDAC6 in both an overexpression system and virus-infected cells, suggesting that cleavage of HDAC6 is a common strategy utilized by swine enteric coronaviruses to antagonize the host's antiviral capacity. Together, these data illustrate how swine enteric coronaviruses antagonize the antiviral function of HDAC6 to maintain their infection, providing new insights to the interaction between virus and host.IMPORTANCEViral infections and host defenses are in constant opposition. Once viruses combat or evade host restriction, productive infection is achieved. HDAC6 is a broad-spectrum antiviral protein that has been demonstrated to inhibit many viruses, including porcine deltacoronavirus (PDCoV). However, whether HDAC6 is reciprocally targeted and disabled by viruses remains unclear. In this study, we used PDCoV as a model and found that HDAC6 is targeted and cleaved by nsp5, a viral 3C-like protease. The cleaved HDAC6 loses its deacetylase activity as well as its ability to degrade viral proteins and activate interferon responses. Furthermore, this cleavage mechanism is shared among other swine enteric coronaviruses. These findings shed light on the intricate interplay between viruses and HDAC6, highlighting the strategies employed by viruses to evade host antiviral defenses.

Porcine deltacoronavirus accessory protein NS6 harnesses VPS35-mediated retrograde trafficking to facilitate efficient viral infection.

IMPORTANCE: Retrograde transport has been reported to be closely associated with normal cellular biological processes and viral replication. As an emerging enteropathogenic coronavirus with zoonotic potential, porcine deltacoronavirus (PDCoV) has attracted considerable attention. However, whether retrograde transport is associated with PDCoV infection remains unclear. Our present study demonstrates that retromer protein VPS35 acts as a critical host factor that is required for PDCoV infection. Mechanically, VPS35 interacts with PDCoV NS6, mediating the retrograde transport of NS6 from endosomes to the Golgi and preventing it from lysosomal degradation. Recombinant PDCoVs with an NS6 deletion display resistance to VPS35 deficiency. Our work reveals a novel evasion mechanism of PDCoV that involves the manipulation of the retrograde transport pathway by VPS35, providing new insight into the mechanism of PDCoV infection.

Exosomes mediate the antibody-resistant intercellular transmission of porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic enteric coronavirus that causes severe enteritis and lethal watery diarrhea in suckling piglets, leading to tremendous economic losses. Exosomes have been reported to participate in intercellular communication by the transportation of a variety of biological materials, including RNAs, lipids, and proteins. However, PEDV transmission routes have not yet been fully elucidated, and whether exosomes function in PEDV transmission remains unclear. In this study, we extracted and purified exosomes from PEDV-infected Vero cells using a stringent isolation method with a combination of chemical precipitation, ultracentrifugation, and incubation with CD63-labeled magnetic beads. We found that exosomes from PEDV-infected Vero cells contain viral genomic RNA and viral nucleocapsid protein. Furthermore, we demonstrated that the purified exosomes from PEDV-infected cells are capable of transmitting the virus to both PEDV-susceptible and non-susceptible cells. Importantly, exosome-mediated PEDV infection was resistant to neutralization by PEDV-specific neutralizing antibodies that potently neutralized free PEDV. Our study reveals a potential immune evasion mechanism utilized by PEDV and provides new insight into the transmission and infection of this important pathogen.

Ethnic and geographic variations in multiple chronic conditions among community-dwelling older people in Xinjiang: a cross-sectional study.

BACKGROUND: Multiple chronic conditions (MCC) refer to the presence of two or more chronic diseases. The incidence of MCC is higher in older people, and increases with age. Studies have shown an association between MCC and increased adverse outcome, as well as the higher mortality, decline of physical function, and poor quality of life in older populations. Herein, for the first time we provide the data of ethnic and geographic variations in the prevalence of MCC among community-dwelling older people in Xinjiang, China. METHODS: A multilevel random sampling method was employed to perform an epidemiological survey in community-dwelling older adults in southern, northern, and eastern Xinjiang between January 2019 to December 2019. In total, 87,000 participants volunteered, with a response rate of 96.67%; 490 participants with incomplete data were excluded and data from 86,510 participants were analyzed. RESULTS: Our analysis demonstrated that hypertension (51.5%), obesity (27.0%), diabetes (16.9%), heart disease (8.2%), and anxiety/depression (4.5%) were the five main chronic diseases in Xinjiang. The prevalence of MCC in the population surveyed was 33.4% (95%CI, 33.1-33.7). The prevalence in females was 36.6% (95%CI, 36.1-37), which was higher than that in male (30%,95%CI, 29.5-30.4). The prevalence of MCC in older people aged 60-69, 70-79, 80-89, and ≥ 90 years was 32.7% (95%CI, 32.2-33.3), 34.3% (95%CI, 33.9-34.7), 32.5% (95% CI, 31.7-33.3), and 25.9% (95% CI, 23.5-28.3) respectively. As far as the ethnic group was concerned, the prevalence of MCC in Uygur, Han, Kazak, Hui, and Mongolian was 31.3% (95%CI, 30.9-31.7), 34.4% (95%CI, 33.9-35), 40.4% (95%CI, 39.1-41.8), 40.8% (95%CI, 38.9-42.7), 44.4% (95%CI, 38.1-50.6), respectively. The prevalence of MCC was 32.8% (95%CI, 32.1-33.5), 31.7% (95%CI, 31.2-32.1), 36.0% (95%CI, 35.3-36.7) and 39.2% (95%CI, 38.1-40.3) among uneducated, educated for 1-6, 7-9, and more than 10 years. After adjusting for age, sex, smoking, alcohol consumption, and education by level, the binary logistic analysis showed that, compared with eastern Xinjiang, the risk of MCC in the southern area was increased (odds ratio [OR], 1.418; 95% confidence interval [CI], 1.367-1.471), and it was relatively higher in northern Xinjiang (OR, 2.021; 95% CI, 1.944-2.102). Compared with Uygur, Han, Kazakh, Hui and Mongolian had an increased risk of MCC, which was (OR, 1.075; 95% CI, 1.040-1.111), (OR, 1.414; 95% CI, 1.332-1.501), (OR, 1.515; 95% CI, 1.396-1.644), (OR, 1.566; 95% CI, 1.216-2.017), respectively. CONCLUSIONS: There are ethnic and geographic variations in multiple chronic conditions among community-dwelling older people in Xinjiang. The older adults living in northern and southern Xinjiang and Han, Kazakh, Mongolian and Hui older adults have a higher risk of MCC.

Porcine deltacoronavirus resists antibody neutralization through cell-to-cell transmission.

ABSTRACTPorcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that has been reported to infect a variety of animals and even humans. Cell-cell fusion has been identified as an alternative pathway for the cell-to-cell transmission of certain viruses, but the ability of PDCoV to exploit this transmission model, and the relevant mechanisms, have not been fully elucidated. Herein, we provide evidence that cell-to-cell transmission is the main mechanism supporting PDCoV spread in cell culture and that this efficient spread model is mediated by spike glycoprotein-driven cell-cell fusion. We found that PDCoV efficiently spread to non-susceptible cells via cell-to-cell transmission, and demonstrated that functional receptor porcine aminopeptidase N and cathepsins in endosomes are involved in the cell-to-cell transmission of PDCoV. Most importantly, compared with non-cell-to-cell infection, the cell-to-cell transmission of PDCoV was resistant to neutralizing antibodies and immune sera that potently neutralized free viruses. Taken together, our study revealed key characteristics of the cell-to-cell transmission of PDCoV and provided new insights into the mechanism of PDCoV infection.

Development of actein derivatives as potent anti-triple negative breast cancer agents.

Actein is a natural triterpenoid glycoside, isolated from the rhizomes of Cimicifuga foetida, which have been demonstrated to be potential in the treatment of breast cancer previously. Herein, we described the design and synthesis of a series of actein derivatives as anti-triple negative breast cancer (TNBC) inhibitors. Of which, the most promising derivative 27 exhibited significant inhibitory activity against human TNBC cell lines HCC1806 and MDA-MB-231, with IC50 values of 2.78 and 9.11 µM, respectively. Structure-activity relationships of actein derivatives were also discussed. Moreover, preliminary mechanism investigation revealed that 27 significantly inhibited cancer cell proliferation via cell cycle arrest at S phase. In addition, western blot analysis showed that the activation of MAPK signaling pathway might contribute to derivative 27 induced cell death. Overall, these results indicate that 27 has the potential to be developed as a lead compound and compounds with the actein scaffold are a promising novel class of inhibitors to treat TNBC.

Design, synthesis, and anti-triple negative breast cancer activity of novel Toosendanin derivatives.

Toosendanin (TSN) is a natural anti-cancer compound that is isolated from the traditional Chinese herbal Melia toosendan Sieb et Zucc. However, the research effect of TSN in the treatment of Triple negative breast cancer (TNBC) is still far from ideal. In this work, we investigated TSN and its derivatives in terms of their actions against MDA-MB-231 and HCC1806 TNBC cell lines. The results indicated that TSN and its derivative 11 showed excellent antitumor activity. Preliminary mechanistic studies showed that both compounds TSN and 11 induced S-phase arrest and G2/M phase cell number decrease in HCC1806 cells. Also, TSN and 11 significantly reduced the protein level of the well-known cancer suppressor gene p53, reduced the phosphorylation of AKT and ERK, and also induced the accumulation of phosphorylated p38 and p21.

Chemical Synthesis Enables the Configurational Determination of Myristriol, a Highly Oxygenated Phenylpropanoid from Myristica fragrans Houtt.

A new phenylpropanoid, myristriol (1), along with 11 known ones were isolated from the seed kernel of Myristica fragrans Houtt. Their chemical structures were clearly elucidated by extensive spectroscopic analysis. In which, the relative configuration of 1 was finally determined as erythro-1 by comparison the NMR data of two synthetic erythro- and threo-diastereoisomers with that of natural 1.

Porcine deltacoronavirus uses heparan sulfate as an attachment receptor.

Porcine deltacoronavirus (PDCoV) is a newly emerging swine enteropathogenic coronavirus with extensive tissue tropism and cross-species transmission potential. Heparan sulfate (HS) is a complex polysaccharide ubiquitously expressed on cell surfaces and the extracellular matrix and acts as an attachment factor for many viruses. However, whether PDCoV uses HS as an attachment receptor is unclear. In this study, we found that treatment with heparin sodium or heparinase Ⅱ significantly inhibited PDCoV binding and infection among LLC-PK1 and IPI-2I cells. Attenuation of HS sulfuration by sodium chlorate also impeded PDCoV binding and infection. Moreover, we demonstrated that HS functioned independently of amino peptidase N (APN), a functional PDCoV receptor, in PDCoV infection. Molecular docking revealed that the S1 subunit of the PDCoV spike protein might be a putative region for HS binding. Taken together, these results firstly confirmed that HS is an attachment receptor for PDCoV infection, providing new insight into better understanding the mechanisms of PDCoV-host interactions.

Genome-Wide CRISPR/Cas9 Screen Reveals a Role for SLC35A1 in the Adsorption of Porcine Deltacoronavirus.

Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, not only causes diarrhea in piglets but also possesses the potential to infect humans. To better understand host-virus genetic dependencies and find potential therapeutic targets for PDCoV, we used a porcine single-guide RNA (sgRNA) lentivirus library to screen host factors related to PDCoV infection in LLC-PK1 cells. The solute carrier family 35 member A1 (SLC35A1), a key molecule in the sialic acid (SA) synthesis pathway, was identified as a host factor required for PDCoV infection. A knockout of SLC35A1 caused decreases in the amounts of cell surface sialic acid (SA) and viral adsorption; meanwhile, trypsin promoted the use of SA in PDCoV infection. By constructing and assessing a series of recombinant PDCoV strains with the deletion or mutation of possible critical domain or amino acid residues for SA binding in the S1 N-terminal domain, we found that S T182 might be a PDCoV SA-binding site. However, the double knockout of SLC35A1 and amino peptidase N (APN) could not block PDCoV infection completely. Additionally, we found that different swine enteric coronaviruses, including transmissible gastroenteritis coronavirus, porcine epidemic diarrhea virus, and swine acute diarrhea syndrome coronavirus, are differentially dependent on SA. Overall, our study uncovered a collection of host factors that can be exploited as drug targets against PDCoV infection and deepened our understanding of the relationship between PDCoV and SA. IMPORTANCE Identifying the host factors required for replication will be helpful to uncover the pathogenesis mechanisms and develop antivirals against the emerging coronavirus porcine deltacoronavirus (PDCoV). Herein, we performed a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout screen, the results of which revealed that the solute carrier family 35 member A1 (SLC35A1) is a host factor required for PDCoV infection that acts by regulating cell surface sialic acid (SA). We also identified the T182 site in the N-terminal domain of PDCoV S1 subunit as being associated with the SA-binding site and found that trypsin promotes the use of cell surface SA by PDCoV. Furthermore, different swine enteric coronaviruses use SLC35A1 differently for infection. This is the first study to screen host factors required for PDCoV replication using a genome-wide CRISPR-Cas9 functional knockout, thereby providing clues for developing antiviral drugs against PDCoV infection.

Porcine deltacoronavirus accessory protein NS7a possesses the functional characteristics of a viroporin.

Viroporins are virus-encoded proteins that mediate ion channel (IC) activity, playing critical roles in virus entry, replication, pathogenesis, and immune evasion. Previous studies have shown that some coronavirus accessory proteins have viroporin-like activity. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus that encodes three accessory proteins, NS6, NS7, and NS7a. However, whether any of the PDCoV accessory proteins possess viroporin-like activity, and if so which, remains unknown. In this study, we analyzed the biochemical properties of the three PDCoV-encoded accessory proteins and found that NS7a could enhance the membrane permeability of both mammalian cells and Escherichia coli cells. Indirect immunofluorescence assay and co-immunoprecipitation assay results further indicated that NS7a is an integral membrane protein and can form homo-oligomers. A bioinformation analysis revealed that a putative viroporin domain (VPD) is located within amino acids 69-88 (aa69-88) of NS7a. Experiments with truncated mutants and alanine scanning mutagenesis additionally demonstrated that the amino acid residues 69FLR71 of NS7a are essential for its viroporin-like activity. Together, our findings are the first to demonstrate that PDCoV NS7a possesses viroporin-like activity and identify its key amino acid residues associated with viroporin-like activity.

Plasma tumor necrosis factor-α is associated with sarcopenia in elderly individuals residing in agricultural and pastoral areas of Xinjiang, China.

Background: Inflammatory reactions play a significant role in the occurrence and development of sarcopenia. Determining the association between specific cytokines and sarcopenia may reveal the disease's pathophysiological mechanism(s). Accordingly, the present study aimed to investigate the association between sarcopenia and inflammatory cytokines among the elderly natural population in agricultural and pastoral areas of Xinjiang. Methods: We conducted a cross-sectional epidemiological survey of the community-dwelling older people using a multi-stage random sampling method in Mulei County in northern Xinjiang and Luopu County in southern Xinjiang from September 2017 to May 2018. Of the 2,100 participants, the statistical analyses included 1,838 participants with complete data. Comparisons of living habits, disease status, biochemical indexes, and levels of interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in sarcopenia and non-sarcopenia participants were made in this study. Results: Our study revealed no significant differences (i.e., P > 0.05) in sex, age, ethnicity, smoking and drinking habits, serum renal function, total cholesterol, and diabetes in the elderly between the sarcopenia and non-sarcopenia groups in Xinjiang. However, triglyceride levels (P = 0.004), hypertension (P = 0.019), and abdominal obesity (P < 0.001) in the sarcopenia group were significantly higher than those in the non-sarcopenia group. Moreover, the levels of IL-10 (P < 0.001), IL-4 (P < 0.001), and TNF-α (P < 0.001) in the sarcopenia group were higher than those in the non-sarcopenia group after adjusting for sex, age, hypertension, blood lipid concentration, and obesity. Furthermore, after adjusting for sex, age, hypertension, obesity, and IL-10, IL-4, and IL-6 levels, an increased TNF-α level was also significantly associated with sarcopenia. Conclusion: The results of the present study suggest that an increased plasma level of TNF-α is significantly associated with sarcopenia among elderly individuals residing in Xinjiang's agricultural and pastoral areas. Further study is still needed to determine the physiological role of "immune aging" in the pathogenesis of sarcopenia.

Heat maps of cardiovascular disease risk factor clustering among community-dwelling older people in Xinjiang: a cross-sectional study.

OBJECTIVE: The clustering of multiple cardiovascular disease (CVD) risk factors (CRFs) increases the risk of CVD prevalence and mortality. Little is known about CRF clustering among community-dwelling older people in Xinjiang. The objective of this study was to explore the prevalence of CRF clustering in this population. DESIGN: Cross-sectional study. SETTING: Xinjiang, China. PARTICIPANTS: Multilevel random sampling was used to survey individuals aged ≥60 in six regions of Xinjiang. In total, 87 000 participants volunteered, with a response rate of 96.67%; 702 participants with incomplete data were excluded and data from 86 298 participants were analysed. OUTCOME MEASURES: The prevalence of smoking, hypertension, diabetes, dyslipidaemia and overweight/obesity was 9.4%, 52.1%, 16.8%, 28.6% and 62.7%, respectively. The prevalence of CRF clusters among people of different ages, regions and ethnic groups differed significantly. The 85.7% of the participants presented at least one CRFs and 55.9% of the participants presented clustering of CRFs. The proportion of CRF clusters tended to be higher in men, 60-69-year-old group, northern Xinjiang and the Kazakh population. After adjusting for age and sex, logistic regression analysis revealed that men, 60-69-year-old group, northern Xinjiang and the Kazakh population were more likely to have clustering of CRFs, compared with their counterparts. CONCLUSIONS: The prevalence of CRFs in the older Xinjiang population is high and their clustering differs by sex, age, region and ethnicity. CRF prevention and management should be active in this population, and strategies to reduce CVD risk based on sex, age, ethnic group and region are warranted.

The APC/CTAD1-WIDE LEAF 1-NARROW LEAF 1 pathway controls leaf width in rice.

Leaf morphology is one of the most important features of the ideal plant architecture. However, the genetic and molecular mechanisms controlling this feature in crops remain largely unknown. Here, we characterized the rice (Oryza sativa) wide leaf 1 (wl1) mutant, which has wider leaves than the wild-type due to more vascular bundles and greater distance between small vascular bundles. WL1 encodes a Cys-2/His-2-type zinc finger protein that interacts with Tillering and Dwarf 1 (TAD1), a co-activator of the anaphase-promoting complex/cyclosome (APC/C) (a multi-subunit E3 ligase). The APC/CTAD1 complex degrades WL1 via the ubiquitin-26S proteasome degradation pathway. Loss-of-function of TAD1 resulted in plants with narrow leaves due to reduced vascular bundle numbers and distance between the small vascular bundles. Interestingly, we found that WL1 negatively regulated the expression of a narrow leaf gene, NARROW LEAF 1 (NAL1), by recruiting the co-repressor TOPLESS-RELATED PROTEIN and directly binding to the NAL1 regulatory region to inhibit its expression by reducing the chromatin histone acetylation. Furthermore, biochemical and genetic analyses revealed that TAD1, WL1, and NAL1 operated in a common pathway to control the leaf width. Our study establishes an important framework for understanding the APC/CTAD1-WL1-NAL1 pathway-mediated control of leaf width in rice, and provides insights for improving crop plant architecture.

Estimating the effects of policies on infertility prevalence worldwide.

BACKGROUND: Infertility has troubled millions of people worldwide while always being an ignored issue. The high cost of treatment or lack of services placed a barrier to the alleviation of infertility status. Governments play a significant role to promote infertility-related policies for better access to infertility services and comprehensive supports for infertile people. METHODS: Data of infertility status indicators and infertility-related policies in ten representative countries were collected. An infertility-related policy system was established, then classification and quantification were processed according to specific criteria, and different policy implementation patterns were identified. The effectiveness of specific infertility-related policy and various patterns on infertility prevalence relief between 1990 and 2017 were evaluated via generalized linear models and analyses of covariance for the first time. RESULTS: Economic support policies would be less prioritized compared with social security policies, while economic support policy had a significant positive role in the decline of female infertility prevalence (ß = -2·16, p = 0·042). In detail, insurance coverage and economic reward policies were crucial (ß = -3·31, p = 0·031; ß = -4·10, p = 0·025) with adjusted with covariates. The effect of economic support-oriented pattern was relatively better than other patterns for both male and female infertility prevalence relief. Nevertheless, the effectiveness of gradual-promotion pattern seemed preferable for male infertility prevalence relief while was similar with simultaneous-promotion pattern for females. CONCLUSIONS: Our data-driven analysis revealed that insurance coverage and economic reward policies played the pivotal role in moderation of female infertility status. Economic support-oriented pattern and gradual-promotion pattern were preferable when promoting infertility-related policies.