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GOT1, a cytoplasmic glutamic oxaloacetic transaminase, plays a critical role in various metabolic pathways essential for cellular homeostasis and dysregulated metabolism. Recent studies have highlighted the significant plasticity and roles of GOT1 in metabolic reprogramming through participating in both classical and non-classical glutamine metabolism, glycolytic metabolism, and other metabolic pathways. This review summarizes emerging insights on the metabolic roles of GOT1 in cancer cells and emphasizes the response of cancer cells to altered metabolism when the expression of GOT1 is altered. We review how cancer cells repurpose cell intrinsic metabolism and their flexibility when GOT1 is inhibited and delineate the molecular mechanisms of GOT1’s interaction with specific oncogenes and regulators at multiple levels, including transcriptional and epigenetic regulation, which govern cellular growth and metabolism. These insights may provide new directions for cancer metabolism research and novel targets for cancer treatment.

Objectiveto evaluate the research status and development hotspots of fetal α-thalassemia by quantitatively analyzing the diagnostic status, key areas, related management measures and prospects of the disease by bibliometrics.MethodsThe global literature on fetal α-thalassemia and severe α-thalassemia from 2009–2023 in the Web of Science Core Collection (WOSCC) was visually analyzed by VOSviewer and CiteSpace.Results(1) The examination of the quantity of publications concerning fetal α-thalassemia indicates a rising tendency prior to 2018, followed by a decrease after 2018. (2)The United States, China, Italy, Thailand have published more papers, and the United States has more collaborating countries such as Italy and China. (3) Chiang Mai University and Harvard University are the top two institutions with the highest contribution. However, Chiang Mai University's H index (12) and citation frequency per article (8.05) are relatively low and the NC (6,342), H index (33) and citations per article (75.42) of Harvard University are higher than those of the other institutions. (4) Tongsong T, Gambari R and Fucharoen S are the top three prolific authors. Fucharoen S emerges as the most frequently cited author with 738 citations, excluding self-citations. (5) HEMOGLOBIN leading with 87 published papers (NC:601,IF: 0.82, H-index: 13), followed by BLOOD(58 papers, Nc: 3755, IF: 25.48, H-index: 40) and BLOOD CELLS MOLECULES AND DISEASES(39 papers, Nc: 729, IF: 2.37, H-index: 16). (6) The most cited article was published in science and the second and third cited articles were featured in the Proceedings of the National Academy of Sciences; the top 3 clusters of co-cited literature are “gene editing”, “polymorphisms”, “hydroxyurea”. (7) Keywords analysis showe that the top two categories of keyword cluster focus on the prenatal diagnosis and the current treatment strategy of the disease, which remain the research hotspots.ConclusionsRecent research on this topic has primarily focused on prenatal diagnosis and treatment strategies. A particular area of interest is the ongoing research on gene therapy.The advances in non-invasive diagnosis and therapeutic methods will change the current management approaches for fetal severe α-thalassemia in the future.

ObjectiveThis study aimed to investigate the association between antimony (Sb) exposure and glycated hemoglobin (HbA1c) levels in adolescents.MethodsA cross-sectional study of 751 adolescents aged 12–19 years was conducted via the National Health and Nutrition Examination Survey (NHANES, 2013–2016). Survey-weighted linear regression and restricted cubic spline (RCS) analyses were applied to evaluate the relationship of urinary Sb exposure with HbA1c.ResultsA significant relationship was observed between urinary Sb concentrations and HbA1c levels (percent change: 0.93; 95% CI: 0.42, 1.45) after full adjustment. After converting urinary Sb levels to a categorical variable by tertiles (T1–T3), the highest quantile was associated with a significant increase in HbA1c (percent change: 1.45; 95% CI: 0.38, 2.53) compared to T1. The RCS models showed a monotonically increasing relationship of urinary Sb with HbA1c. Subgroup analyses revealed a sex-specific relationship between urinary Sb exposure and HbA1c with a significant positive association in males and a non-significant positive association in females. Sensitivity analyses further confirmed the relationship between urinary Sb and HbA1c, even after excluding participants who were overweight or obese (percent change: 1.58%, 95% CI: 0.88, 2.28) and those with serum cotinine levels ≥ 1 ng/mL (percent change: 1.14%, 95% CI: 0.49, 1.80).ConclusionOur findings indicated that increased Sb exposure may correlate with higher HbA1c levels, especially in male adolescents. More studies are needed to further explore and validate the potential mechanisms.

ContextType I hypersensitivity affects approximately one-third of the global population. As the pathophysiology underlying the development of type I hypersensitivity (asthma, food allergy, and anaphylactic shock, etc.) is complex and heterogeneous, animal model studies continue to be the key to identifying novel molecular pathways and providing therapeutic strategies.ObjectiveSelection of the animal model should be done with careful consideration of the protocol variables, animal species, and strains to accurately reflect the clinical symptoms typical of humans.MethodsThe following databases were searched: PubMed and Web of Science.Results and conclusionForeign allergens include allergenic proteins and chemical haptens. This review summarizes the various methods used for designing animal models of common allergenic protein-induced type I hypersensitivity, namely, passive anaphylaxis model, active systemic anaphylaxis/anaphylaxis shock model, food allergy model, asthma model, and IgE-mediated cell models. Additionally, we summarize shrimp tropomyosin-induced type I hypersensitivity models from our previous studies and discuss their advantages and limitations compared with that of ovalbumin-induced models.

PurposeOur study utilizes Mendelian Randomization (MR) to explore the causal relationships between a range of risk factors and preeclampsia, a major contributor to maternal and perinatal morbidity and mortality.MethodsEmploying the Inverse Variance Weighting (IVW) approach, we conducted a comprehensive multi-exposure MR study analyzing genetic variants linked to 25 risk factors including metabolic disorders, circulating lipid levels, immune and inflammatory responses, lifestyle choices, and bone metabolism. We applied rigorous statistical techniques such as sensitivity analyses, Cochran’s Q test, MR Egger regression, funnel plots, and leave-one-out sensitivity analysis to address potential biases like pleiotropy and population stratification.ResultsOur analysis included 267,242 individuals, focusing on European ancestries and involving 2,355 patients with preeclampsia. We identified strong genetic associations linking increased preeclampsia risk with factors such as hyperthyroidism, BMI, type 2 diabetes, and elevated serum uric acid levels. Conversely, no significant causal links were found with gestational diabetes, total cholesterol, sleep duration, and bone mineral density, suggesting areas for further investigation. A notable finding was the causal relationship between systemic lupus erythematosus and increased preeclampsia risk, highlighting the significant role of immune and inflammatory responses.ConclusionThis extensive MR study sheds light on the complex etiology of preeclampsia, underscoring the causal impact of specific metabolic, lipid, immune, lifestyle, and bone metabolism factors. Our findings advocate for a multidimensional approach to better understand and manage preeclampsia, paving the way for future research to develop targeted preventive and therapeutic strategies.

ObjectiveThis study aimed to evaluate the efficacy of α-thalassemia gene testing as a part of an antenatal intervention program over a 10-year period.MethodsAll patients underwent α-thalassemia gene testing, which included the analysis of three types of deletions and mutations. Rare α-thalassemia gene testing was performed using Sanger sequencing, multiplex ligation-dependent probe amplification, and sequencing techniques. Prenatal diagnosis was performed in high-risk couples using chorionic villus sampling or amniocentesis.ResultsFrom 2010 to 2019, among the 91,852 patients examined, α-thalassemia mutations were identified in 41.78% of patients. The most frequent α0 gene mutation was--SEA, followed by--THAI. Two rare α0-thalassemia gene mutations at --32.8 and --230, were also observed. A total of 2,235 high-risk couples were identified, of which 562 were affected, including three with the--SEA/--THAI genotype and one with the--SEA/--230 genotype. Additionally, prenatal diagnosis revealed four cases of fetal anemia and/or mild edema, along with two cases of severe fetal edema. Chromosome and gene chip results were normal. Thalassemia gene testing showed an αCSα/αCSα genotype in four patients with anemia and/or mild edema, while two patients with severe fetal edema had one--SEA/αCSα genotype and one--SEA/--GX genotype. Using the cut-off points of 74.6 fL and 24.4 pg as criteria for identifying α0-thalassemia carriers and HbH disease, the detection rate of missed diagnoses in high-risk couples is consistent with national guidelines for standards, potentially saving 10,217,700 ¥.ConclusionRoutine molecular testing for α-thalassemia in high-risk prenatal populations effectively prevented severe α-thalassemia births. Despite the high cost, the cutoff points proposed by this study suggest that implementing screening using a new parameter has the potential to reduce current expenses.

BackgroundDespite observational links between serum uric acid (SUA), sex hormone-related phenotypes, and female infertility, the causality behind these associations remains uncertain.ObjectiveThis study utilizes Bidirectional Two-Sample and Mediation Mendelian Randomization to explore the causal relationships and mediation effects of sex hormone-binding globulin (SHBG), total testosterone (TT), and estradiol on these associations.MethodsWe analyzed single-nucleotide polymorphisms (SNPs) associated with SUA and sex hormone levels using data from large-scale GWAS of European populations. Female infertility data were sourced from 6,481 cases and 75,450 controls in the FinnGen Consortium. We employed methods including Inverse Variance Weighted (IVW), Weighted Median, and MR-Egger regression to assess causality.ResultsWe found that elevated SUA levels causally increase the risk of female infertility (IVW OR: 1.13, P=0.047). Elevated SUA levels significantly decrease SHBG levels (β=-0.261; P=2.177e-04), with SHBG mediating 27.93% of the effect of SUA on infertility (OR=0.854; 95%CI, 0.793–0.920; P=2.853e-05). Additionally, elevated TT levels, which were associated with decreased SUA levels (β=-0.127), showed an indirect effect on infertility mediated by SUA (β=-0.0187; 95% CI, -0.041 to -0.003; P=0.046).ConclusionOur findings demonstrate causal links between high SUA and increased risk of female infertility mediated by hormonal factors such as SHBG and TT. These insights suggest new avenues for infertility treatment and highlight the need for further research into these mechanisms.

Gynecologic cancers, including ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC), pose a serious threat to women’s health and quality of life due to their high incidence and lethality. Therapeutic resistance in tumors refers to reduced sensitivity of tumor cells to therapeutic drugs or radiation, which compromises the efficacy of treatment or renders it ineffective. Therapeutic resistance significantly contributes to treatment failure in gynecologic tumors, although the specific molecular mechanisms remain unclear. Exosomes are nanoscale vesicles released and received by distinct kinds of cells. Exosomes contain proteins, lipids, and RNAs closely linked to their origins and functions. Recent studies have demonstrated that exosomal ncRNAs may be involved in intercellular communication and can modulate the progression of tumorigenesis, aggravation and metastasis, tumor microenvironment (TME), and drug resistance. Besides, exosomal ncRNAs also have the potential to become significant diagnostic and prognostic biomarkers in various of diseases. In this paper, we reviewed the biological roles and mechanisms of exosomal ncRNAs in the drug resistance of gynecologic tumors, as well as explored the potential of exosomal ncRNAs acting as the liquid biopsy molecular markers in gynecologic cancers.

ObjectiveTo improve the accuracy of preimplantation genetic testing (PGT) in deletional α-thalassemia patients.DesignArticle.Patient(s)fifty-two deletional α-thalassemia couples.Intervention(s)Whole genome amplification (WGA), Next-generation sequencing (NGS) and PCR mutation loci detection.Main outcome measuresWGA, Single nucleotide polymorphism (SNP) and PCR mutation loci detection results; Analysis of embryo chromosome copy number variation (CNV).ResultsMultiple Displacement Amplification (MDA) and Multiple Annealing and Looping–Based Amplification Cycles (MALBAC) methods for PGT for deletional α-thalassemia. Blastocyst biopsy samples (n = 253) were obtained from 52 deletional α-thalassemia couples. The results of the comparison of experimental data between groups MALBAC and MDA are as follows: (i) The average allele drop-out (ADO) rate, MALBAC vs. MDA = 2.27% ± 3.57% vs. 0.97% ± 1.4%, P=0.451); (ii) WGA success rate, MALBAC vs. MDA = 98.61% vs. 98.89%, P=0.851; (iii) SNP haplotype success rate, MALBAC vs. MDA = 94.44% vs. 96.68%, P=0.409; (iv) The result of SNP haplotype analysis is consistent with that of Gap-PCR/Sanger sequencing results, MALBAC vs. MDA = 36(36/72, 50%) vs. 151(151/181, 83.43%), P=0; (v) Valid SNP loci, MALBAC vs. MDA = 30 ± 9 vs. 34 ± 10, P=0.02; (vi) The mean CV values, MALBAC vs. MDA = 0.12 ± 0.263 vs. 0.09 ± 0.40, P=0.916; (vii) The average number of raw reads, MALBAC vs. MDA =3244259 ± 999124 vs. 3713146 ± 1028721, P=0; (viii) The coverage of genome (%), MALBAC vs. MDA = 5.02 ± 1.09 vs. 5.55 ± 1.49, P=0.008.ConclusionsOur findings indicate that MDA is superior to MALBAC for PGT of deletional α-thalassemia. Furthermore, SNP haplotype analysis combined with PCR loci detection can improve the accuracy and detection rate of deletional α-thalassemia.

The application of artificial intelligence (AI) to summarize a whole-brain magnetic resonance image (MRI) into an effective “brain age” metric can provide a holistic, individualized, and objective view of how the brain interacts with various factors (e.g., genetics and lifestyle) during aging. Brain age predictions using deep learning (DL) have been widely used to quantify the developmental status of human brains, but their wider application to serve biomedical purposes is under criticism for requiring large samples and complicated interpretability. Animal models, i.e., rhesus monkeys, have offered a unique lens to understand the human brain - being a species in which aging patterns are similar, for which environmental and lifestyle factors are more readily controlled. However, applying DL methods in animal models suffers from data insufficiency as the availability of animal brain MRIs is limited compared to many thousands of human MRIs. We showed that transfer learning can mitigate the sample size problem, where transferring the pre-trained AI models from 8,859 human brain MRIs improved monkey brain age estimation accuracy and stability. The highest accuracy and stability occurred when transferring the 3D ResNet [mean absolute error (MAE) = 1.83 years] and the 2D global-local transformer (MAE = 1.92 years) models. Our models identified the frontal white matter as the most important feature for monkey brain age predictions, which is consistent with previous histological findings. This first DL-based, anatomically interpretable, and adaptive brain age estimator could broaden the application of AI techniques to various animal or disease samples and widen opportunities for research in non-human primate brains across the lifespan.

IntroductionNumerous studies have suggested a connection between circadian rhythm and neurological disorders with cognitive and consciousness impairments in humans, yet little evidence stands for a causal relationship between circadian rhythm and the brain cortex.MethodsThe top 10,000 morningness-related single-nucleotide polymorphisms of the Genome-wide association study (GWAS) summary statistics were used to filter the instrumental variables. GWAS summary statistics from the ENIGMA Consortium were used to assess the causal relationship between morningness and variates like cortical thickness (TH) or surficial area (SA) on the brain cortex. The inverse-variance weighted (IVW) and weighted median (WM) were used as the major estimates whereas MR-Egger, MR Pleiotropy RESidual Sum and Outlier, leave-one-out analysis, and funnel-plot were used for heterogeneity and pleiotropy detecting.ResultsRegionally, morningness decreased SA of the rostral middle frontal gyrus with genomic control (IVW: β = −24.916 mm, 95% CI: −47.342 mm to −2.490 mm, p = 0.029. WM: β = −33.208 mm, 95% CI: −61.933 mm to −4.483 mm, p = 0.023. MR Egger: β

BackgroundBirth defects (BDs) are associated with many potential risk factors, and its causes are complex.ObjectivesThis study aimed to explore the epidemiological characteristics of BDs in Guangxi of China and the associated risk factors of BDs.MethodsBDs data of perinatal infants (PIs) were obtained from the Guangxi birth defects monitoring network between 2016 and 2020. Univariate Poisson regression was used to calculate the prevalence-rate ratios (PRR) to explore the changing trends of BDs prevalence by year and the correlation between the regarding of characteristics of BDs (including infant gender, maternal age, and quarter) and BDs. Clinical characteristics of PIs with BDs and general characteristics of their mothers were documented, and Spearman correlation analysis was used to explore the potential associated risk factors of BDs.ResultsBetween 2016 and 2020, 44,146 PIs with BDs were monitored, with an overall BDs prevalence of 121.71 (95% CI: 120.58–122.84) per 10,000 PIs, showing a significant increase trend (PRR = 1.116, 95% CI: 1.108–1.123), especially the prevalence of congenital heart defects (CHDs) that most significantly increased (PRR = 1.300, 95% CI: 1.283–1.318). The 10 most common BDs were CHDs, polydactyly, congenital talipes equinovarus, other malformation of external ear, syndactyly, hypospadias, cleft lip with cleft palate, cleft lip, hemoglobin Bart's hydrops fetalis syndrome (BHFS), and congenital atresia of the rectum and anus. BDs were positively correlated with pregnant women's age (R = 0.732, P

A healthy urban environment is considered as an important issue for the amenity and equity of migrants. China has one of the largest internal population movements in the world, and the environmental health of its migrants becomes a growing concern. Based on the 1‰ microdata from the 2015 1% population sample survey, this study uses the spatial visualization and spatial econometric interaction model to reveal intercity population migration patterns and the role of environmental health in China. The results are as follows. First, the main direction of population migration is toward economically developed high class cities, especially the eastern coast where the intercity population migration is most active. However, these major destinations are not necessarily the healthiest areas for the environment. Second, environmentally friendly cities are mainly located in the southern region. Among them, the areas with less serious atmospheric pollution are mainly distributed in the south, climate comfort zones are mainly located in the southeastern region, but areas with more urban green space are mainly distributed in the northwestern region. Third, compared with socioeconomic factors, environmental health factors have not yet become a major driver of population migration. Migrants often place higher value on income than on environmental health. The government should focus not only on the public service wellbeing of migrant workers, but also on their environmental health vulnerability.

Background: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia–reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia–reperfusion injury (IRI-AKI).Method: Two public datasets (GSE39548 and GSE131288) originating from the NCBI Gene Expression Omnibus (GEO) database were analyzed using the R software limma package, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) and gene set enrichment analysis (GSEA) were performed using the differentially expressed genes. Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes, and transcription factor (TF)–hub gene and miRNA–hub gene networks were constructed. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb.Result: A total of 323 common differentially expressed genes were identified in the renal ischemia–reperfusion injury group compared with the control group. Among these, 260 differentially expressed genes were upregulated and 66 differentially expressed genes were downregulated. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis results showed that these common differentially expressed genes were enriched in positive regulation of cytokine production, muscle tissue development, and other biological processes, indicating that they were involved in mitogen-activated protein kinase (MAPK), PI3K-Akt, TNF, apoptosis, and Epstein–Barr virus infection signaling pathways. Protein-protein interaction analysis showed 10 hub genes, namely, Jun, Stat3, MYC, Cdkn1a, Hif1a, FOS, Atf3, Mdm2, Egr1, and Ddit3. Using the STRUST database, starBase database, and DGIdb database, it was predicted that 34 transcription factors, 161 mi-RNAs, and 299 drugs or molecular compounds might interact with hub genes.Conclusion: Our findings may provide novel potential biomarkers and insights into the pathogenesis of ischemia–reperfusion injury–acute kidney injury through a comprehensive analysis of Gene Expression Omnibus data, which may provide a reliable basis for early diagnosis and treatment of ischemia–reperfusion injury–acute kidney injury.

With the upgrade and development of the high-throughput sequencing technology, multi-omics data can be obtained at a low cost. However, mapping tools that existed for microbial multi-omics data analysis cannot satisfy the needs of data description and result in high learning costs, complex dependencies, and high fees for researchers in experimental biology fields. Therefore, developing a toolkit for multi-omics data is essential for microbiologists to save effort. In this work, we developed MicrobioSee, a real-time interactive visualization tool based on web technologies, which could visualize microbial multi-omics data. It includes 17 modules surrounding the major omics data of microorganisms such as the transcriptome, metagenome, and proteome. With MicrobioSee, methods for plotting are simplified in multi-omics studies, such as visualization of diversity, ROC, and enrichment pathways for DEGs. Subsequently, three case studies were chosen to represent the functional application of MicrobioSee. Overall, we provided a concise toolkit along with user-friendly, time-saving, cross-platform, and source-opening for researchers, especially microbiologists without coding experience. MicrobioSee is freely available at https://microbiosee.gxu.edu.cn.

The Poirier–Bienvenu neurodevelopmental syndrome is an autosomal dominant disorder characterized by intellectual disability and epilepsy. The disease is caused by mutations in the CSNK2B gene, which encodes the beta subunit of casein kinase II, and it has important roles in neuron development and synaptic transmission. In this study, five Chinese patients were diagnosed with Poirier–Bienvenu neurodevelopmental syndrome caused by CSNK2B mutations by whole exome sequencing. We detected four different de novo variants of the CSNK2B gene in these five unrelated Chinese patients: two novel mutations, namely, c.100delT (p.Phe34fs*16) and c.158_159insA (p.Asp55fs*4), and two recurrent mutations, namely, c.1A>G (p.Met1?) and c.332 G >C (p.R111P). All five patients showed mild-to-profound intellectual disabilities/or learning disabilities and developmental delays, with or without seizures. Although intellectual disability/developmental delay and epilepsy are the most common manifestations of CSNK2B deficiency, the clinical phenotypes of probands are highly variable, and there is no significant correlation between genotype and phenotype. An abnormal stature may be another common manifestation of CSNK2B deficiency. Here, we report the effects of growth hormone (GH) therapy on the patients' linear height. In conclusion, Poirier–Bienvenu neurodevelopmental syndrome is a highly heterogeneous disease caused by mutations in the CSNK2B gene. The phenotype was highly variable, and no significant correlation of genotype and phenotype was found. Patients with short-stature and CSNK2B deficiency may benefit from GH therapy. The identification and characterization of these novel variants will expand the genotypic and phenotypic spectrum of Poirier–Bienvenu neurodevelopmental syndrome.

Investigating microbial lipid regulation contributes to understanding the lipid-dependent signal transduction process of cells and helps to improve the sensitivity of microorganisms to environmental factors by interfering with lipid metabolism, thus beneficial for constructing advanced cell factories of novel molecular drugs. Integrated omics technology was used to systematically reveal the lipid metabolism mechanism of a marine Meyerozyma guilliermondii GXDK6 under high NaCl stress and test the sensitivity of GXDK6 to antibiotics when its lipid metabolism transformed. The omics data showed that when GXDK6 perceived 10% NaCl stress, the expression of AYR1 and NADPH-dependent 1-acyldihydroxyacetone phosphate reductase was inhibited, which weaken the budding and proliferation of cell membranes. This finding was further validated by decreased 64.39% of OD600 under 10% NaCl stress when compared with salt-free stress. In addition, salt stress promoted a large intracellular accumulation of glycerol, which was also verified by exogenous addition of glycerol. Moreover, NaCl stress remarkably inhibited the expression of drug target proteins (such as lanosterol 14-alpha demethylase), thereby increasing sensitivity to fluconazole. This study provided new insights into the molecular mechanism involved in the regulation of lipid metabolism in Meyerozyma guilliermondii strain and contributed to developing new methods to improve the effectiveness of killing fungi with lower antibiotics.

Background: Thalassemia is one of the most common genetic diseases in southern China. Howerver, population in different regions or different population has their own spectrums of thalassemia. To investigate the prevalence and spectrum features of thalassemia among children in Guangxi. Hematology and genetic analysis were performed on 71,459 children aged 1–10 years in various regions of Guangxi.Results: A total of 11,821 children were diagnoses with thalassemia including 7,615 (10.66%) subjects of α-thalassemia, 3,507 (4.90%) subjects of β-thalassemia, and 699 (0.98%) cases with both α- and β-thalassemia. Nine α-thalassemia mutations and 30 genotypes were identified among the α-thalassemia children. The - -SEA and - -SEA/αα were the most frequent mutation and genotype, respectively. One α-thalassemia fusion gene and a rare 2.4 kb deletion both causing α+-thalassemia were identified, respectively. Thirteen β-thalassemia mutations and 31 genotypes were characterized among the β-thalassemia children, with the most common mutation CD41-42 (-CTTT) accounting for 46.05% of the β-mutations. Two rare mutations IVS-II-5 (G>C), and IVS-I-2 (T>C) were firstly identified. Furthermore, 92 genotypes were identified among 699 children with both α- and β-thalassemia.Conclusions: Our findings highlight the great heterogeneity and the extensive spectrum of thalassemia among children in Guangxi, which provide an available reference for prevention of thalassemia in this area.

BackgroundIn animal models of ventilation-induced lung injury, mitophagy triggers mitochondria damage and the release of mitochondrial (mt) DNA, which activates inflammation. However, the mechanism of this process is unclear.MethodsA model of cyclic stretching (CS)-induced lung epithelial cell injury was established. The genetic intervention of phosphatase and tensin homolog-induced kinase 1 (PINK1) expression via lentivirus transfection was used to identify the relationship between PINK1-mediated mitophagy and mtDNA release in stretching-induced inflammatory response and injury. Pharmacological inhabitation of Toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88) expression was performed via their related inhibitors, while pre-treatment of exogenous mtDNA was used to verify the role of mtDNA in stretching-induced inflammatory response and injury.ResultsUsing a cell culture model of CS, we found that knocking down PINK1 in lung epithelial cells reduced mitophagy activation and mtDNA release, leading to milder inflammatory response and injury; conversely, up-regulating PINK1 exacerbated stretching-induced inflammation and injury, and similar effects were observed by upregulating TLR9 to induce expression of MyD88 and nuclear factor-κB (NF-κB)/p65. Down-regulating MyD88 protected lung epithelial cells from stretching injury and decreased NF-κB/p65 expression.ConclusionThese findings suggest that PINK1-dependent mitophagy and associated TLR9 activation is indeed a major factor in stretch-induced cell injury via a mechanism in which released mtDNA activates TLR9 and thereby the MyD88/NF-κB pathway. Inhibiting this process may be a therapeutic approach to prevent inflammation and cell injury in patients on mechanical ventilation.

Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to induce proinflammatory cytokine production and modulate the host interferon (IFN) system. Proinflammatory cytokines and type I IFNs contribute to the prevention of viral infection. Lipopolysaccharide (LPS), a specific agonist to Toll-like receptor 4 (TLR4), provokes signal transduction and activates immune response in vivo and in vitro. Here we identified LPS inhibited PRRSV infection in porcine alveolar macrophages (PAMs) and in Marc-145 cells. To investigate the possible mechanism, we found TLR4-NF-κB pathway was obviously activated in LPS-treated PAMs at the early stage of PRRSV infection. As a result, the expression of proinflammatory cytokines was strongly induced following LPS and PRRSV co-treatment. Due to the enhanced proinflammatory response, CD163 expression was significantly reduced and a disintegrin and metalloproteinase 17 was activated, which promotes the cleavage of membrane CD163. Ultimately, CD163 down-regulation led to the suppression of PRRSV replication. Our data demonstrate that LPS has an impact on PRRSV infection via inflammation response, which provides a new insight of inflammation-mediated antiviral immunity and a new strategy to control PRRSV infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) 1 and 2 differ in their recognition of CD163. Substitution of porcine CD163 SRCR5 domain with a human CD163-like SRCR8 confers resistance to PRRSV 1 but not PRRSV 2. The deletion of CD163 SRCR5 has been shown to confer resistance to PRRSV 1 in vivo and both PRRSV 1 and 2 in vitro. However, the anti-PRRSV 2 activity of modifying the CD163 SRCR5 domain has not yet been reported. Here, we describe the highly efficient generation of two pig breeds (Liang Guang Small Spotted and Large White pigs) lacking a short region of CD163 SRCR5, including the ligand-binding pocket. We generated a large number of gene-edited Large White pigs of the F0 generation for use in viral challenge studies. The results of this study show that these pigs are completely resistant to infection by species 2 PRRSV, JXA1, and MY strains. There were no clinical symptoms, pathological abnormalities, viremia, or anti-PRRSV antibodies in the CD163 SRCR5-edited pigs compared to wild-type controls after viral challenge. Porcine alveolar macrophages (PAMs) isolated from CD163 SRCR5-edited Large White pigs also displayed resistance to PRRSV in vitro. In addition, CD163 SRCR5-edited PAMs still exhibited a cytokine response to PRRSV infection, and no significant difference was observed in cytokine expression compared to wild-type PAMs. Taken together, these data suggest that CD163 SRCR5-edited pigs are resistant to PRRSV 2, providing a basis for the establishment of PRRSV-resistant pig lines for commercial application and further investigation of the essential region of SRCR5 involved in virus infection.

When two different images are presented to the two eyes dichoptically, observers usually experience a perceptual alternation between the two images. This phenomenon, known as binocular rivalry, has been used as a powerful tool to investigate mechanisms of visual awareness. It was also found that the rates of perceptual alternation are slower in patients with bipolar disorder than in healthy controls (Pettigrew and Miller, 1998; Miller et al., 2003). To investigate the broader clinical relevance of binocular rivalry in psychiatric disorders, we measured the perceptual alternation rates during rivalry in healthy controls (n = 39) and in patients with different types of psychiatric disorders, including bipolar disorder type I (BD, n = 28), obsessive–compulsive disorder (OCD, n = 22), major depression (MD, n = 50), schizophrenia (SCZ, n = 44), and first-degree relatives (FDRs) of SCZ patients (n = 32). Participants viewed competing red–green images on a computer monitor through red–green anaglyph glasses and pressed buttons to record their perceptual alternations. The distributions of the rivalry rates were well described by a lognormal function in all groups. Critically, the median rate of perceptual alternation was 0.27 Hz for BD patients, 0.26 Hz for the OCD patients, 0.25 Hz for the MD patients, and 0.23 Hz and 0.27 Hz for the SCZ patients and their FDRs, respectively. All of which were significantly slower than the rate of 0.41 Hz obtained for the healthy controls, suggesting there may be shared genotypes between these different disorders. While rivalry alternations were generally slower in different types of psychiatric disorders compared to healthy controls, adding variance of rivalry rates in the analysis helped to partially separate among the different patient groups. Our results suggest that the slowing of binocular rivalry is likely due to certain common factors among the patient groups, but more subtle differences between different patient groups could be revealed when additional properties of rivalry dynamics are considered.

In bistable perception, constant input leads to alternating perception. The dynamics of the changing perception reflects the intrinsic dynamic properties of the “unconscious inferential” process in the brain. Under the same condition, individuals differ in how fast they experience the perceptual alternation. In this study, testing many forms of bistable perception in a large number of observers, we investigated the key question of whether there is a general and common mechanism or multiple and independent mechanisms that control the dynamics of the inferential brain. Bistable phenomena tested include binocular rivalry, vase-face, Necker cube, moving plaid, motion induced blindness, biological motion, spinning dancer, rotating cylinder, Lissajous-figure, rolling wheel, and translating diamond. Switching dynamics for each bistable percept was measured in 100 observers. Results show that the switching rates of subsets of bistable percept are highly correlated. The clustering of dynamic properties of some bistable phenomena but not an overall general control of switching dynamics implies that the brain’s inferential processes are both shared and independent – faster in constructing 3D structure from motion does not mean faster in integrating components into an objects.

The COVID-19 pandemic has resulted in the implementation of strict mitigation measures that have impacted the transmission dynamics of human respiratory syncytial virus (HRSV). The measures also have the potential to influence the evolutionary patterns of the virus. In this study, we conducted a comprehensive analysis comparing genomic variations and evolving characteristics of its neutralizing antigens, specifically F and G proteins, before and during the COVID-19 pandemic. Our findings showed that both HRSV A and B exhibited an overall chronological evolutionary pattern. For the sequences obtained during the pandemic period (2019-2022), we observed that the HRSV A distributed in A23 genotype, but formed into three subclusters; whereas the HRSV B sequences were relatively concentrated within genotype B6. Additionally, multiple positively selected sites were detected on F and G proteins but none were located at neutralizing antigenic sites of the F protein. Notably, amino acids within antigenic site III, IV, and V of F protein remained strictly conserved, while some substitutions occurred over time on antigenic site Ø, I, II and VIII; substitution S389P on antigenic site I of HRSV B occurred during the pandemic period with nearly 50% frequency. However, further analysis revealed no substitutions have altered the structural conformations of the antigenic sites, the vial antigenicity has not been changed. We inferred that the intensive public health interventions during the COVID-19 pandemic did not affect the evolutionary mode of HRSV. [ABSTRACT FROM AUTHOR]

The genus Rimicaris is the dominant organism living in hydrothermal vents. However, little research has been done on the functions of their intestinal flora. Here, we investigated the potential functions of Deferribacterota, which is dominant in the intestine of Rimicaris kairei from the Central Indian Ridge. In total, six metagenome-assembled genomes (MAGs) of Deferribacterota were obtained using the metagenomic approach. The six Deferribacterota MAGs (Def-MAGs) were clustered into a new branch in the phylogenetic tree. The six Def-MAGs were further classified into three species, including one new order and two new genera, based on the results of phylogenetic analysis, relative evolutionary divergence (RED), average nucleotide identity (ANI), average amino acid identity (AAI) and DNA–DNA hybridization (DDH) values. The results of the energy metabolism study showed that these bacteria can use a variety of carbon sources, such as glycogen, sucrose, salicin, arbutin, glucose, cellobiose, and maltose. These bacteria have a type II secretion system and effector proteins that can transport some intracellular toxins to the extracellular compartment and a type V CRISPR–Cas system that can defend against various invasions. In addition, cofactors such as biotin, riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) synthesized by R. kairei gut Deferribacterota may also assist their host in surviving under extreme conditions. Taken together, the potential function of Deferribacterota in the hydrothermal R. kairei gut suggests its long-term coevolution with the host. [ABSTRACT FROM AUTHOR]

The subgenus Cerasus, one of the most important groups in the genus Prunus sensu lato, comprises over 100 species; however, the taxonomic classification and phylogenetic relationships of Cerasus remain controversial. Therefore, it is necessary to reconstruct the phylogenetic tree for known Cerasus species. Here, we report the chloroplast (cp) genome sequences of 11 Cerasus species to provide insight into evolution of the plastome. The cp genomes of the 11 Cerasus species (157,571-158,830 bp) displayed a typical quadripartite circular structure. The plastomes contain 115 unique genes, including 80 protein-coding genes, four ribosomal RNAs, and 31 transfer RNAs. Twenty genes were found to be duplicated in inverted repeats as well as at the boundary. The conserved noncoding sequences showed significant divergence compared with the coding regions. We found 12 genes and 14 intergenic regions with higher nucleotide diversity and more polymorphic sites, including matK, rps16, rbcL, rps16-trnQ, petN-psbM, and trnL-trnF. During cp plastome evolution, the codon profile has been strongly biased toward the use of A/T at the third base, and leucine and isoleucine codons appear the most frequently. We identified strong purifying selection on the rpoA, cemA, atpA, and petB genes; whereas ccsA, rps19, matK, rpoC2, ycf2 and ndhI showed a signature of possible positive selection during the course of Cerasus evolution. In addition, we further analyzed the phylogenetic relationships of these species with 57 other congenic related species. Through reconstructing the Cerasus phylogeny tree, we found that true cherry is similar to the flora of China forming a distinct group, from which P. mahaleb was separated as an independent subclade. Microcerasus was genetically closer to Amygdalus, Armeniaca, and Prunus (sensu stricto) than to members of true cherry, whereas P. japonica and P. tomentosa were most closely related to P. triloba and P. pedunculata. However, P. tianshanica formed a clade with P. cerasus, P. fruticosa, P. cerasus × P. canescens 'Gisela 6', and P. avium as a true cherry group. These results provide new insights into the plastome evolution of Cerasus, along with potential molecular markers and candidate DNA barcodes for further phylogenetic and phylogeographic analyses of Cerasus species. [ABSTRACT FROM AUTHOR]

Human respiratory syncytial virus (RSV) is a ubiquitous pediatric pathogen causing serious lower respiratory tract disease worldwide. No licensed vaccine is currently available. In this work, the coding gene for mDS-Dav1, the fulllength and prefusion conformation RSV fusion glycoprotein (F), was designed by introducing the stabilized prefusion F (preF) mutations from DS-Cav1 into the encoding gene of wild-type RSV (wtRSV) F protein. The recombinant adenovirus encoding mDS-Cav1, rChAd63-mDS-Cav1, was constructed based on serotype 63 chimpanzee adenovirus vector and characterized in vitro. After immunizing mice via intranasal route, the rChAd63-mDS-Cav1 induced enhanced neutralizing antibody and F-specific CD8+ T cell responses as well as good immune protection against RSV challenge with the absence of enhanced RSV disease (ERD) in BALB/c mice. The results indicate that rChAd63-mDS-Cav1 is a promising mucosal vaccine candidate against RSV infection and warrants further development. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to determine whether residual dizziness (RD) after successful repositioning treatment in benign paroxysmal positional vertigo (BPPV) patients could be predicted by red blood cell distribution width (RDW). Materials andmethods: In this study, a total of 303 BBPV patients hospitalized at the neurology department were investigated. The enrolled patients were divided into two groups after successful repositioning treatment: non-RD group included patients who were completely cured, and RD group included patients with RD. We collected data on all subjects, including general information, blood routine examination, blood biochemical examination, and magnetic resonance imaging tests. Results: The mean RDW values of patients in the RD group were significantly higher than that in the non-RD group (13.63 ± 1.8 vs. 12.5 ± 0.8; p < 0.001). In subsequent multivariate analysis, elevated RDW levels were a statistically significant risk factor associated with the occurrence of RD [odds ratio = 2.62, 95% confidence interval (CI) 1.88-3.64, p < 0.001]. The area under the ROC curve was 0.723 in terms of its predictive ability to distinguish patients with RD. A cut-off point of 12.95% of RDW predicted RD with a sensitivity of 75.6% and a specificity of 69.5%. Moreover, the AUC for the ability of the RDW to predict recurrence were 0.692 (95% CI = 0.561-0.831; p < 0.014). Conclusions: Elevated RDW level was related to increased risk of RD among BPPV patients, requiring further efforts to clarify the actual underlying pathophysiology. [ABSTRACT FROM AUTHOR]

Soil eutrophication from atmospheric deposition and fertilization threatens biodiversity and the functioning of terrestrial ecosystems worldwide. Increases in soil nitrogen (N) and phosphorus (P) content can alter the biomass and structure of plant communities in grassland ecosystems; however, the impact of these changes on plant–pollinator interactions is not yet clear. In this study, we tested how changes in flowering plant diversity and composition due to N and P enrichment affected pollinator communities and pollination interactions. Our experiments, conducted in a Tibetan alpine grassland, included four fertilization treatments: N (10 g N m−2 year−1 ), P (5 g P m−2 year−1 ), a combination of N and P (N + P), and control. We found that changes in flowering plant composition and diversity under the N and P treatments did not alter the pollinator richness or abundance. The N and P treatments also had limited effects on the plant–pollinator interactions, including the interaction numbers, visit numbers, plant and pollinator species dissimilarity, plant–pollinator interaction dissimilarity, average number of pollinator species attracted by each plant species (vulnerability), and average number of plant species visited by each pollinator species (generality). However, the N + P treatment increased the species and interaction dissimilarity in flowering plant and pollinator communities and decreased the generality in plant–pollinator interactions. These data highlight that changes in flowering plants caused by N + P enrichment alter pollination interactions between flowering plants and pollinators. Owing to changes in flowering plant communities, the plant– pollinator interactions could be sensitive to the changing environment in alpine regions. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) causes dengue fever, which is prevalent in the tropical and subtropical regions, and in recent years, has resulted in several major epidemics. Vimentin, a cytoskeletal component involved in DENV infection, is significantly reorganized during infection. However, the mechanism underlying the association between DENV infection and vimentin is still poorly understood. We generated vimentin-knockout (Vim-KO) human brain microvascular endothelial cells (HBMECs) and a Vim-KO SV129 suckling mouse model, combining the dynamic vimentin changes observed in vitro and differences in disease course in vivo , to clarify the role of vimentin in DENV-2 infection. We found that the phosphorylation and solubility of vimentin changed dynamically during DENV-2 infection of HBMECs, suggesting the regulation of vimentin by DENV-2 infection. The similar trends observed in the phosphorylation and solubility of vimentin showed that these characteristics are related. Compared with that in control cells, the DENV-2 viral load was significantly increased in Vim-KO HBMECs, and after DENV-2 infection, Vim-KO SV129 mice displayed more severe disease signs than wild-type SV129 mice, as well as higher viral loads in their serum and brain tissue, demonstrating that vimentin can inhibit DENV-2 infection. Moreover, Vim-KO SV129 mice had more disordered cerebral cortical nerve cells, confirming that Vim-KO mice were more susceptible to DENV-2 infection, which causes severe brain damage. The findings of our study help clarify the mechanism by which vimentin inhibits DENV-2 infection and provides guidance for antiviral treatment strategies for DENV infections. [ABSTRACT FROM AUTHOR]

Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) is critical for the pathogenesis of Escherichia coli (E. coli) K1 meningitis, a severe central nervous system infection of the neonates. However, little is known about how E. coli K1 manipulates α7 nAChR signaling. Here, through employing immortalized cell lines, animal models, and human transcriptional analysis, we showed that E. coli K1 infection triggers releasing of secreted Ly6/Plaur domain containing 1 (SLURP1), an endogenous α7 nAChR ligand. Exogenous supplement of SLURP1, combined with SLURP1 knockdown or overexpression cell lines, showed that SLURP1 is required for E. coli K1 invasion and neutrophils migrating across the blood-brain barrier (BBB). Furthermore, we found that SLURP1 is required for E. coli K1-induced α7 nAChR activation. Finally, the promoting effects of SLURP1 on the pathogenesis of E. coli K1 meningitis was significantly abolished in the α7 nAChR knockout mice. These results reveal that E. coli K1 exploits SLURP1 to activate α7 nAChR and facilitate its pathogenesis, and blocking SLURP1-α7 nAChR interaction might represent a novel therapeutic strategy for E. coli K1 meningitis. [ABSTRACT FROM AUTHOR]

Bacterial infection remains one of the leading causes of death worldwide due to the continuous rise of multiple antibiotic-resistant bacteria. Focusing solely on bacteria as the drug targets is a major limitation inherent in the conventional antibiotic therapy. Recently, host-directed therapies have become such an innovative approach to modulate the host defense system and the interplay of innate and adaptive immunity. Our previous studies showed that memantine (MEM), an α7 nAChR antagonist, could efficiently block multi-drug resistant Escherichia coli -caused bacteremia and meningitis in a mouse model. However, the underlying mechanisms that govern the antibacterial effects of MEM are still unknown. In this study, we demonstrated that MEM is able to significantly suppress E. coli infection by enhancing E. coli -induced formation and release of NETs in vitro and in vivo. MEM could promote the trapping and bactericidal activities of the polymorphonuclear neutrophils (PMNs) in a manner dependent on α7 nAChR, since knockdown of this receptor noticeably reduces the survival ability of bacteria in PMNs while MEM no longer affects the survival of bacteria in PMNs. Our results also showed that when the expression of S100A9, an antiseptic protein, is inhibited, pathogen survival rates in PMNs increase significantly. MEM reverses this effect in a concentration-dependent manner. MEM stimulates the production of MPO, S100A9, and DNA in PMNs and accelerates the release of depolymerized chromatin fibers into the extracellular space, suggesting the formation of NETs. Taken together, our data suggest that MEM effectively blocks bacterial infection through the promotion of the antibacterial function of NETs induced by E. coli. [ABSTRACT FROM AUTHOR]

It has long been known that probiotics can be used to maintain intestinal homeostasis and treat a number of gastrointestinal disorders, but the underlying mechanism has remained obscure. Recently, increasing evidence supports the notion that certain probiotic-derived components, such as bacteriocins, lipoteichoic acids, surface layer protein and secreted protein, have a similar protective role on intestinal barrier function as that of live probiotics. These bioactive components have been named 'postbiotics' in the most recent publications. We previously found that the Lactobacillus rhamnosus GG (LGG) culture supernatant is able to accelerate the maturation of neonatal intestinal defense and prevent neonatal rats from oral Escherichia coli K1 infection. However, the identity of the bioactive constituents has not yet been determined. In this study, using liquid chromatography-tandem mass spectrometry analysis, we identified a novel secreted protein (named HM0539 here) involved in the beneficial effect of LGG culture supernatant. HM0539 was recombinated, purified, and applied for exploring its potential bioactivity in vitro and in vivo. Our results showed that HM0539 exhibits a potent protective effect on the intestinal barrier, as reflected by enhancing intestinal mucin expression and preventing against lipopolysaccharide (LPS)- or tumor necrosis factor α (TNF-α)-induced intestinal barrier injury, including downregulation of intestinal mucin (MUC2), zonula occludens-1 (ZO-1) and disruption of the intestinal integrity. Using a neonatal rat model of E. coli K1 infection via the oral route, we verified that HM0539 is sufficient to promote development of neonatal intestinal defense and prevent against E. coli K1 pathogenesis. Moreover, we further extended the role of HM0539 and found it has potential to prevent dextran sulfate sodium (DSS)-induced colitis as well as LPS/D-galactosamine-induced bacterial translocation and liver injury. In conclusion, we identified a novel LGG postbiotic HM0539 which exerts a protective effect on intestinal barrier function. Our findings indicated that HM0539 has potential to become a useful agent for prevention and treatment of intestinal barrier dysfunction- related diseases. [ABSTRACT FROM AUTHOR]

The brain's functional organization can be altered by visual deprivation. This is observed by comparing blind and sighted people's activation response to tactile discrimination tasks, like braille reading. Where, the blind have higher activation than the sighted upon tactile discrimination tasks, especially high activation difference is seen in ventral occipitotemporal (vOT) cortex. However, it remains unknown, whether this vOT hyperactivation is related to alteration of spontaneous activity. To address this question, we examined 16 blind subjects, 19 low-vision individuals, and 21 normally sighted controls using functional magnetic resonance imaging (fMRI). Subjects were scanned in resting-state and discrimination tactile task. In spontaneous activity, when compared to sighted subjects, we found both blind and low vision subjects had increased local signal synchronization and increased temporal variability. During tactile tasks, compared to sighted subjects, blind and low-vision subject's vOT had stronger tactile task-induced activation. Furthermore, through inter-subject partial correlation analysis, we found temporal variability is more related to tactile-task activation, than local signal synchronization's relation to tactile-induced activation. Our results further support that vision impairment induces vOT cortical reorganization. The hyperactivation in the vOT during tactile stimulus processing in the blind may be related to their greater dynamic range of spontaneous activity. [ABSTRACT FROM AUTHOR]

Soil microbial communities are influenced by climate change drivers such as warming and altered precipitation. These changes create abiotic stresses, including desiccation and nutrient limitation, which act on microbes. However, our understanding of the responses of microbial communities to co-occurring climate change drivers is limited. We surveyed soil bacterial and fungal diversity and composition after a 1-year warming and altered precipitation manipulation in the Tibetan plateau alpine grassland. In isolation, warming and decreased precipitation treatments each had no significant effects on soil bacterial community structure; however, in combination of both treatments altered bacterial community structure (p = 0.03). The main effect of altered precipitation specifically impacted the relative abundances of Bacteroidetes and Gammaproteobacteria compared to the control, while the main effect of warming impacted the relative abundance of Betaproteobacteria. In contrast, the fungal community had no significant response to the treatments after 1-year. Using structural equation modeling (SEM), we found bacterial community composition was positively related to soil moisture. Our results indicate that short-term climate change could cause changes in soil bacterial community through taxonomic shifts. Our work provides new insights into immediate soil microbial responses to short-term stressors acting on an ecosystem that is particularly sensitive to global climate change. [ABSTRACT FROM AUTHOR]

BackgroundAlthough several studies linked the sugary beverages to chronic kidney disease (CKD), the role of different types of sugary beverages in the development of CKD remained inconsistent. This study aimed to examine the associations of sugar-sweetened beverages (SSBs), artificially-sweetened beverages (ASBs), and natural juices (NJs) with CKD risk, and assess the extent to which the associations were mediated through metabolic syndrome (MetS).MethodsThis is a prospective analysis of 191,956 participants from the UK Biobank. Participants with information on beverage consumption and no history of CKD at recruitment were included. Daily consumptions of SSBs, ASBs and NJs were measured via 24-h dietary recall. Cox models were fitted to calculate the hazard ratios (HRs) and confidence intervals (CIs) of sugary beverages intakes on CKD risk. The causal mediation analyses were conducted to investigate whether MetS explained the observed associations.ResultsWe documented 4,983 CKD cases over a median of 10.63 years follow-up. Higher consumption of SSBs and ASBs (>1 units/d compared with none) was associated with an elevated risk of CKD (HR: 1.45; 95% CI: 1.30–1.61, P-trend < 0.001 for SSBs and 1.52, 95% CI: 1.36–1.70 for ASBs). In contrast, we observed a J-shaped association between NJs and CKD with the with lowest risk at 0–1 unit/day (0–1 unit/d vs. 0, HR 0.86; 95% CI 0.81–0.91). The proportions of the observed association of higher intakes of SSBs and ASB with CKD mediated by MetS were 12.5 and 18.0%, respectively.ConclusionsHigher intakes of ASBs and SSBs were positively associated with the development of CKD, while moderate consumption of NJs was inversely associated with CKD risk. More intensified policy efforts are warranted to reduce intake of SSBs and ASBs for CKD prevention.

Sponges are widely distributed in the global ocean and harbor diverse symbiotic microbes with mutualistic relationships. However, sponge symbionts in the deep sea remain poorly studied at the genome level. Here, we report a new glass sponge species of the genus Bathydorus and provide a genome-centric view of its microbiome. We obtained 14 high-quality prokaryotic metagenome-assembled genomes (MAGs) affiliated with the phyla Nitrososphaerota, Pseudomonadota, Nitrospirota, Bdellovibrionota, SAR324, Bacteroidota, and Patescibacteria. In total, 13 of these MAGs probably represent new species, suggesting the high novelty of the deep-sea glass sponge microbiome. An ammonia-oxidizing Nitrososphaerota MAG B01, which accounted for up to 70% of the metagenome reads, dominated the sponge microbiomes. The B01 genome had a highly complex CRISPR array, which likely represents an advantageous evolution toward a symbiotic lifestyle and forceful ability to defend against phages. A sulfur-oxidizing Gammaproteobacteria species was the second most dominant symbiont, and a nitrite-oxidizing Nitrospirota species could also be detected, but with lower relative abundance. Bdellovibrio species represented by two MAGs, B11 and B12, were first reported as potential predatory symbionts in deep-sea glass sponges and have undergone dramatic genome reduction. Comprehensive functional analysis indicated that most of the sponge symbionts encoded CRISPR–Cas systems and eukaryotic-like proteins for symbiotic interactions with the host. Metabolic reconstruction further illustrated their essential roles in carbon, nitrogen, and sulfur cycles. In addition, diverse putative phages were identified from the sponge metagenomes. Our study expands the knowledge of microbial diversity, evolutionary adaption, and metabolic complementarity in deep-sea glass sponges.

ObjectiveEmerging evidence has highlighted the possible links of environmental pollution with several cardiovascular diseases (CVDs). The current study aimed to explore the impact of short-term air pollution exposure on CHD hospitalization in Hefei.MethodsData about the daily number of CHD admissions (from 2014 to 2021) were retrieved from the First Affiliated Hospital of Anhui Medical University. Air pollutants and meteorological data were obtained from the China Environmental Monitoring Station and the China Meteorological Data Service Center, respectively. The correlation between air pollution and CHD hospitalization was assessed using distributed lag non-linear model (DLNM) and Poisson generalized linear regression.ResultsIn the single-pollutant model, NO2, O3, and CO strongly correlated with CHD hospitalization rate. Specifically, exposure to NO2 (lag0, relative risk [RR]: 1.013, 95%CI: 1.002–1.024, per 10 μg/m3 increase) and CO (lag13, RR: 1.035, 95%CI: 1.001–1.071, per 1 μg/m3 increase) revealed a positive correlation with an increased rate of CHD hospitalization. Interestingly, O3 had a protective association with hospitalization of CHD (lag0, RR: 0.993, 95%CI: 0.988–0.999, per 10 μg/m3 increase). Similar results, to those of the single-pollutant model, were revealed following verification using two-pollutant models. Subgroup analyses indicated that young people, women, and people in hot seasons were more susceptible to NO2 exposure, while the elderly, women, and people in cold seasons were more susceptible to O3. Furthermore, the elderly were more susceptible to CO exposure.ConclusionOverall, exposure to NO2 and CO increases the rate of CHD hospitalization, but exposure to O3 shows a protective association with the rate of CHD hospitalization. Therefore, early preventive measures against air pollutants should be applied to protect vulnerable patients with CHD.

Porcine enteric coronaviruses are pathogens that cause viral diarrhea in pigs and are widely prevalent worldwide. Moreover, studies have shown that some porcine enteric coronaviruses can infect humans and poultry. In order to effectively monitor these viruses, it is necessary to establish a multiple detection method to understand their prevalence and conduct in-depth research. Common porcine enteric coronaviruses include Porcine epidemic diarrhea virus (PEDV), Porcine transmissible gastroenteritis virus (TGEV), Porcine delta coronavirus (PDCoV), and Swine acute diarrhea syndrome coronavirus (SADS-CoV). Pigs infected with these viruses have the common clinical symptoms that are difficult to distinguish. A quadruplex RT-PCR (reverse transcription-polymerase chain reaction) method for the simultaneous detection of PEDV, PDCoV, TGEV and SADS-CoV was developed. Four pairs of specific primers were designed for the PEDV M gene, PDCoV N gene, TGEV S gene and SADS-CoV RdRp gene. Multiplex RT-PCR results showed that the target fragments of PDCoV, SADS-CoV, PEDV and TGEV could be amplified by this method. and the specific fragments with sizes of 250 bp, 368 bp, 616 bp and 801 bp were amplified, respectively. This method cannot amplify any fragment of nucleic acids of Seneca Valley virus (SVV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Atypical Porcine Pestivirus (APPV), and has good specificity. The lowest detection limits of PDCoV, PEDV, TGEV and SADS-CoV were 5.66 × 105 copies/μL, 6.48 × 105 copies/μL, 8.54 × 105 copies/μL and 7.79 × 106 copies/μL, respectively. A total of 94 samples were collected from pig farms were analyzed using this method. There were 15 positive samples for PEDV, 3 positive samples for mixed infection of PEDV and PDCoV, 2 positive samples for mixed infection of PEDV and TGEV, and 1 positive sample for mixed infection of PEDV, TGEV, and PDCoV. Multiplex RT-PCR method could detect four intestinal coronaviruses (PEDV, PDCoV, TGEV, and SADS-CoV) in pigs efficiently, cheaply and accurately, which can be used for clinical large-scale epidemiological investigation and diagnosis.