Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization.

Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-ß1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease.

Association between modifiable lifestyle factors and telomere length: a univariable and multivariable Mendelian randomization study.

BACKGROUND: Telomere length has long been recognized as a valuable biomarker of aging and is inversely correlated with chronological age. Various lifestyle factors have been implicated in telomere shortening or preservation; however, the association between lifestyle factors and telomere length remains controversial. To address this issue, we conducted a Mendelian randomization (MR) analysis to investigate the potential causal associations between multiple lifestyle factors and telomere length. METHODS: Independent genetic variants strongly associated with lifestyle factors (tobacco smoking, sleep duration, insomnia, and physical activity) were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for telomere length was obtained from a GWAS comprising 472,174 European ancestries. Univariable and multivariable MR analyses were performed to assess the relationships. RESULTS: The genetic liability to lifetime smoking was robustly associated with shorter telomere length (odd ratio [OR]: 0.882; 95% confidence interval [CI]: 0.847-0.918). Genetically predicted insomnia was also linked to shorter telomere length (OR: 0.972; 95% CI: 0.959-0.985), while no significant association was observed between sleep duration and telomere length. Furthermore, a suggestive association was found between moderate-to-vigorous physical activity and longer telomere length (OR: 1.680; 95% CI: 1.115-2.531). In multivariable MR analyses, adjusting for potential mediators such as body mass index, type 2 diabetes, alcohol consumption, and alcohol use disorder, the associations of lifetime smoking and insomnia with telomere length remained robust. CONCLUSION: Our findings suggest that smoking and insomnia may contribute to telomere shortening, while physical activity may play a role in telomere length maintenance. These findings underscore the importance of managing positive risk factors and adopting a healthy lifestyle to promote telomere health.

An novel effective and safe model for the diagnosis of nonalcoholic fatty liver disease in China: gene excavations, clinical validations, and mechanism elucidation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects. METHODS: The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice. RESULTS: Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive. CONCLUSIONS: Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415).

Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis.

Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.

Reductive Oxy-Nazarov Cyclization toward Expedient Construction of a Cyclopenta[1,2-b]pyrrolo[1,2-a]azepine Ring System: Formal Total Syntheses of Stemonamine and Cephalotaxine.

Formal total syntheses of stemonamine and cephalotaxine bearing the core cyclopenta[1,2-b]pyrrolo[1,2-a]azepine ring skeleton were achieved. The general synthetic strategy in the synthesis features the reductive oxy-Nazarov cyclization as key step, leading to the versatile construction of N-substituted spiro quaternary stereogenic centers from readily available starting materials.

Comparative pharmacokinetics of 11 major bioactive components between two dosage forms of Qixue Shuangbu Prescription in rats by ultra-high-performance liquid chromatography-tandem mass spectrometry.

Although Qixue Shuangbu Prescription (QSP) is a classic Chinese medicine prescription for treating chronic heart failure. Low bioavailability due to the insolubility and poor biofilm permeability of the main bioactive ingredients of QSP is still a key factor limiting its efficacy. In this study, a novel self-microemulsifying drug delivery system was proposed to effectively improve the bioavailability of QSP. The qualified ultra-high-performance liquid chromatography-tandem mass spectrometry methodology was established to investigate the pharmacokinetics characteristics of the QSP self-microemulsifying drug delivery system. Our results showed that 11 components in the self-microemulsifying drug delivery system group had prolonged T1/2 and MRT0-t values compared with QSP extract. The Cmax of calycosin-7-glucoside (CG), vanillic acid and paeoniflorin increased 2.5 times, 2.4 times and 2.3 times, respectively. The relative bioavailability values of CG, paeoniflorin and ononin were most significantly affected, increasing by 383.2%, 336.5% and 307.1%, respectively. This study promoted the development of new dosage forms of QSP and provided a useful reference for improving dosage forms to solve the problem of low bioavailability of traditional Chinese medicine.

Establishing and applying an adaptive framework for imported malaria: a field practice in Anhui Province, China from 2012 to 2022.

BACKGROUND: Anhui Province is currently facing an increase in imported malaria cases as a result of globalization and international travel. In response, Anhui Province has implemented a comprehensive adaptive framework to effectively address this threat. METHODS: This study collected surveillance data from 2012 to 2022 in Anhui Province. Descriptive statistics were used to analyze the epidemiological characteristics of imported malaria cases. Additionally, multivariate logistic regression was employed to identify factors associated with severe malaria. Documents were reviewed to document the evolution of the adaptive framework designed to combat imported malaria. The effectiveness of the adaptive framework was evaluated based on the rates of timely medical visits, timely diagnosis, and species identification. RESULTS: During the study period, a total of 1008 imported malaria cases were reported across 77 out of 105 counties in Anhui Province, representing a coverage of 73.33%. It was found that 10.52% of imported cases went undiagnosed for more than seven days after onset. The multivariate analysis revealed several potential risk factors for severe malaria, including increasing age (OR = 1.049, 95%CI:1.015-1.083), occupation (waitperson vs. worker, OR = 2.698, 95%CI:1.054-6.906), a longer time interval between onset and the initial medical visit (OR = 1.061, 95%CI:1.011-1.114), and misdiagnosis during the first medical visit (OR = 5.167, 95%CI:2.535-10.533). Following the implementation of the adaptive framework, the rates of timely medical visits, timely diagnosis, and species identification reached 100.00%, 78.57%, and 100.00%, respectively. CONCLUSIONS: Anhui Province has successfully developed and implemented an adaptive framework for addressing imported malaria, focusing on robust surveillance, prompt diagnosis, and standardized treatment. The experiences gained from this initiative can serve as a valuable reference for other non-endemic areas.

Study on the removal effect and mechanism of calcined pyrite powder on Cr(VI).

Pyrite exhibits considerable potential as an adsorbent in wastewater treatment. However, few pyrite adsorbents are directly obtained from natural pyrite, as most are composite materials that require a complex preparation process. To develop a pyrite-based adsorbent with a simple preparation process, pyrite was processed by calcination at 400, 600, and 800 °C for 4 h and ball-milled into a fine powder. The adsorption properties of the pyrite powder were systematically explored. The calcined pyrite powder was characterized by SEM-EDS and XRD. The results revealed that the pyrite calcined at 600 °C exhibited excellent adsorption properties and was primarily composed of Fe7S8. The optimum conditions for Cr(VI) removal were a temperature of 45 °C, an adsorbent dosage of 1 g, an equilibration time of 60 min, and an initial pH of 3. Moreover, the calcined pyrite powder exhibited excellent reusability, and the Cr(VI) removal rate exceeded 65% after three cycles. The Cr(VI) adsorption on pyrite can be well described by the Freundlich model and pseudo-second-order kinetic equation. The calcination temperature is the main factor affecting the adsorption performance of pyrite. Therefore, the calcined pyrite powder is expected to be an excellent adsorbent for Cr(VI) in the wastewater treatment industry.

Pyrite has shown promising development prospects in the field of wastewater purification. However, the preparation of most pyrite-based adsorbents is complicated. Upon high-temperature calcination, pyrite is used in traditional Chinese medicine clinics to promote the healing of fractures. The efficiency and underlying mechanism of Cr(VI) adsorption from water using calcined pyrite was investigated. The adsorbent was prepared using a simple method and exhibited excellent adsorption performance, thus allowing its application in preparing ore-based adsorbents for water pollution treatment.

Epidemiology and Pattern of Pediatric Maxillofacial Trauma: A 5-Year Retrospective Study.

PURPOSE: To analyze the epidemiology, pattern, and prevent measurement of pediatric maxillofacial trauma in Xinjiang, China. PATIENTS AND METHODS: Clinical records of patients aged 0 to 18 years with maxillofacial trauma over the 5 years were reviewed. Epidemiological features of data were collected for the cause of injury, age and sex distribution, frequency and type of injury, localization and frequency of soft tissue injuries, facial bone fractures, and presence of associated injuries. Statistical analyses performed included descriptive analysis, χ 2 test, and logistic regression analyses. RESULTS: Among the 450 patients, 333 were male and 117 were female, with a male-to-female ratio of 3.8:1, the mean age was 9.2±5.4 years; 223 cases were soft tissue injuries and 227 cases were maxillofacial fractures. The 16 to 18-year-old group was the highest, with the prevalence of maxillofacial fractures. The most common cause of pediatric maxillofacial trauma was traffic injuries. CONCLUSION: The incidence of maxillofacial trauma in pediatric patients correlates with a number of factors, including age, sex, and etiology of trauma. The 16 to 18-year-old group is the most prevalent group for maxillofacial trauma in pediatric patients, and traffic accidents are the leading cause of maxillofacial trauma in pediatric patients.

Feasibility of using Vis-NIR spectroscopy and PXRF spectrometry to estimate regional soil cadmium concentration.

Conventionally, soil cadmium (Cd) measurements in the laboratory are expensive and time-consuming, involving complex processes of sample preparation and chemical analysis. This study aimed to identify the feasibility of using sensor data of visible near-infrared reflectance (Vis-NIR) spectroscopy and portable X-ray fluorescence spectrometry (PXRF) to estimate regional soil Cd concentration in a time- and cost-saving manner. The sensor data of Vis-NIR and PXRF, and Cd concentrations of 128 surface soils from Yunnan Province, China, were measured. Outer-product analysis (OPA) was used for synthesizing the sensor data and Granger-Ramanathan averaging (GRA) was applied to fuse the model results. Artificial neural network (ANN) models were built using Vis-NIR data, PXRF data, and OPA data, respectively. Results showed that: (1) ANN model based on PXRF data performed better than that based on Vis-NIR data for soil Cd estimation; (2) Fusion methods of both OPA and GRA had higher predictive power (R2) = 0.89, ratios of performance to interquartile range (RPIQ) = 4.14, and lower root mean squared error (RMSE) = 0.06, in ANN model based on OPA fusion; R2 = 0.88, RMSE = 0.06, and RPIQ = 3.53 in GRA model) than those based on either Vis-NIR data or PXRF data. In conclusion, there exists a great potential for the combination of OPA fusion and ANN to estimate soil Cd concentration rapidly and accurately.

Identification of unique transcriptomic signatures through integrated multispecies comparative analysis and WGCNA in bovine oocyte development.

BACKGROUND: Cattle (Bos taurus) are a major large livestock, however, compared with other species, the transcriptional specificity of bovine oocyte development has not been emphasised. RESULTS: To reveal the unique transcriptional signatures of bovine oocyte development, we used integrated multispecies comparative analysis and weighted gene co-expression network analysis (WGCNA) to perform bioinformatic analysis of the germinal follicle (GV) and second meiosis (MII) gene expression profile from cattle, sheep, pigs and mice. We found that the expression levels of most genes were down-regulated from GV to MII in all species. Next, the multispecies comparative analysis showed more genes involved in the regulation of cAMP signalling during bovine oocyte development. Moreover, the green module identified by WGCNA was closely related to bovine oocyte development. Finally, integrated multispecies comparative analysis and WGCNA picked up 61 bovine-specific signature genes that participate in metabolic regulation and steroid hormone biosynthesis. CONCLUSION: In a short, this study provides new insights into the regulation of cattle oocyte development from a cross-species comparison.

Ultrafast and scalable variant annotation and prioritization with big functional genomics data.

The advances of large-scale genomics studies have enabled compilation of cell type-specific, genome-wide DNA functional elements at high resolution. With the growing volume of functional annotation data and sequencing variants, existing variant annotation algorithms lack the efficiency and scalability to process big genomic data, particularly when annotating whole-genome sequencing variants against a huge database with billions of genomic features. Here, we develop VarNote to rapidly annotate genome-scale variants in large and complex functional annotation resources. Equipped with a novel index system and a parallel random-sweep searching algorithm, VarNote shows substantial performance improvements (two to three orders of magnitude) over existing algorithms at different scales. It supports both region-based and allele-specific annotations and introduces advanced functions for the flexible extraction of annotations. By integrating massive base-wise and context-dependent annotations in the VarNote framework, we introduce three efficient and accurate pipelines to prioritize the causal regulatory variants for common diseases, Mendelian disorders, and cancers.

Comprehensive analysis of metabolome and transcriptome reveals the mechanism of color formation in different leave of Loropetalum Chinense var. Rubrum.

BACKGROUND: Loropetalum chinense var. rubrum (L. chinense var. rubrum) is a precious, coloured-leaf native ornamental plant in the Hunan Province. We found an L. chinense var. rubrum tree with three different leaf colours: GL (green leaf), ML (mosaic leaf), and PL (purple leaf). The mechanism of leaf coloration in this plant is still unclear. Therefore, this study aimed to identify the metabolites and genes involved in determining the colour composition of L. chinense var. rubrum leaves, using phenotypic/anatomic observations, pigment content detection, and comparative metabolomics and transcriptomics. RESULTS: We observed that the mesophyll cells in PL were purple, while those in GL were green and those in ML were a mix of purple-green. The contents of chlorophyll a, b, carotenoids, and total chlorophyll in PL and ML were significantly lower than those in GL. While the anthocyanin content in PL and ML was significantly higher than that in GL. The metabolomics results showed the differences in the content of cyanidin 3-O-glucoside, delphinidin 3-O-glucoside, cyanidin 3,5-O-diglucoside, pelargonidin, and petunidin 3,5-diglucoside in ML, GL, and PL were significant. Considering that the change trend of anthocyanin content change was consistent with the leaf colour difference, we speculated that these compounds might influence the colour of L. chinense var. rubrum leaves. Using transcriptomics, we finally identified nine differentially expressed structural genes (one ANR (ANR1217); four CYP75As (CYP75A1815, CYP75A2846, CYP75A2909, and CYP75A1716); four UFGTs (UFGT1876, UFGT1649, UFGT1839, and UFGT3273) and nine transcription factors (two MYBs (MYB1057 and MYB1211), one MADS-box (MADS1235), two AP2-likes (AP2-like1779 and AP2-like2234), one bZIP (bZIP3720), two WD40s (WD2173 and WD1867) and one bHLH (bHLH1631) that might be related to flavonoid biosynthesis and then impacted the appearance of colour in L. chinense var. rubrum leaves. CONCLUSION: This study revealed potential molecular mechanisms associated with leaf coloration in L. chinense var. rubrum by analyzing differential metabolites and genes related to the anthocyanin biosynthesis pathway. It also provided a reference for research on leaf colour variation in other ornamental plants.

Different Methods of Minimally Invasive Esophagojejunostomy After Total Gastrectomy for Gastric Cancer: Outcomes from Two Experienced Centers.

BACKGROUND: Esophagojejunostomy after minimally invasive total gastrectomy (MITG) for gastric cancer (GC) is technically challenging. Failure of the esophagojejunal anastomosis can lead to significant morbidity, leading to short- and long-term quality of life (QoL) impairment or mortality. The optimal reconstruction method following MITG remains controversial. We evaluated outcomes of minimally invasive esophagojejunostomy after laparoscopic or robotic total gastrectomies. METHODS: We retrospectively reviewed MITG patients between 2015 and 2020 at two high-volume centers in China and the United States. Eligible patients were divided into groups by different reconstruction methods. We compared clinicopathologic characteristics, postoperative outcomes, including complication rates, overall survival rate (OS), disease-free survival rate (DFS), and patient-reported QoL. RESULTS: GC patients (n = 105) were divided into intracorporeal esophagojejunostomy (IEJ, n = 60) and extracorporeal esophagojejunostomy (EEJ, n = 45) groups. EEJ had higher incidence of wound infection (8.3% vs 13.3%, P = 0.044) and pneumonia (21.7% vs 40.0%, P = 0.042) than IEJ. The linear stapler (LS) group was inferior to the circular stapler (CS) group in reflux [50.0 (11.1-77.8) vs 44.4 (0.0-66.7), P = 0.041] and diarrhea [33.3 (0.0-66.7) vs 0.0 (0.0-66.7), P = 0.045] while LS was better than CS for dysphagia [22.2 (0.0-33.3) vs 11.1 (0.0-33.3), P = 0.049] and eating restrictions [33.3 (16.7-58.3) vs 41.7 (16.7-66.7), P = 0.029] at 1 year. OS and DFS did not differ significantly between LS and CS. CONCLUSIONS: IEJ anastomosis generated better results than EEJ. LS was associated with a better patient eating experience, but more diarrhea and reflux compared with CS. Clinical and patient-reported outcomes show the superiority of IEJ with the LS reconstruction method in MITG for GC.

Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner.

BACKGROUND: CXC chemokine ligand 3 (CXCL3) is a member of CXC-type chemokine family that is identified as a major regulator in immune and inflammation responses. Recently, numerous evidence indicated that CXCL3 is broadly expressed in various human tumor types, and it is also known to play a critical role in mediating tumor development and progression. However, the expression profile of CXCL3 and the exact molecular mechanism behind the role of CXCL3 in colon adenocarcinoma (COAD) has not been fully elucidated. METHODS: The expression and clinical significance of CXCL3 mRNA and protein in the tissues from COAD patients were estimated using bioinformatics and immunohistochemistry assays. The expression and roles of exogenous administration or overexpression of CXCL3 in HT-29 and SW480 COAD cells were determined using enzyme-linked immunosorbent assay(ELISA), Cell Counting Kit-8 (CCK-8) and Transwell assays. Mechanically, CXCL3-induced malignant behaviors were elucidated using western blotting assay and extracellular signal-regulated protein kinase 1/2 (ERk1/2) inhibitor PD98059. RESULTS: The cancer genome atlas (TCGA)-COAD data analysis revealed that CXCL3 mRNA is highly expressed and has high clinical diagnostic accuracy in COAD. Increased expression of CXCL3 mRNA was associated with patient's clinical stage, race, gender, age, histological subtype, nodal mestastasis and tumor protein 53 (TP53) mutation status. Similarly, immunohistochemistry assay also exhibited that CXCL3 protein in COAD tissues was significantly up-regulated. Gene expression associated assay implied that CXC chemokine ligand 1 (CXCL1) and CXC chemokine ligand 2 (CXCL2) were markedly correlated with CXCL3 in COAD. Protein-protein interaction (PPI) analysis revealed that cyclin B1 (CCNB1), mitotic arrest deficient 2 like 1 (MAD2L1), H2A family member Z (H2AFZ) and CXCL2 may be the important protein molecules involved in CXCL3-related tumor biology. Gene set enrichment analysis (GSEA) analysis revealed that CXCL3 was mainly enriched in the cell cycle, DNA replication, NOD-like receptors, NOTCH and transforming growth factor-ß (TGF-ß) Signal pathways. In vitro, exogenous administration or overexpression of CXCL3 resulted in increased malignant behaviors of HT-29 and SW480 cells, and down-regulation of CXCL3 expression inhibited the malignant behaviors of these tumor cells. In addition, overexpression of CXCL3 affected the expression of genes related to extracellular signal regulated kinase (ERK) pathway, including ERK1/2, p-ERK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cyclin D1. Finally, CXCL3-induced malignant behaviors in HT-29 and SW480 cells were obviously attenuated following treatment with ERK inhibitor PD98059. CONCLUSION: CXCL3 is upregulated in COAD and plays a crucial role in the control of malignant behaviors of tumor cells, which indicated its involvement in the pathogenesis of COAD.

MEIOK21 regulates oocyte quantity and quality via modulating meiotic recombination.

The reproductive life span of females is largely determined by the number and quality of oocytes. Previously, we identified MEIOK21 as a meiotic recombination regulator required for male fertility. Here, we characterize the important roles of MEIOK21 in regulating female meiosis and oocyte number and quality. MEIOK21 localizes at recombination sites as a component of recombination bridges in oogenesis like in spermatogenesis. Meiok21-/- female mice show subfertility. Consistently, the size of the primordial follicle pool in Meiok21-/- females is only ~40% of wild-type females because a great number of oocytes with defects in meiotic recombination and/or synapsis are eliminated. Furthermore, the numbers of primordial and growing follicles show a more marked decrease in an age-dependent manner compared with wild-type females. Further analysis shows Meiok21-/- oocytes also have reduced rates of germinal vesicle breakdown and the first polar body extrusion when cultured in vitro, indicating poor oocyte quality. Additionally, Meiok21-/- oocytes have more chromosomes bearing a single distally localized crossover (chiasmata), suggesting a possible defect in crossover maturation. Taken together, our findings indicate critical roles for MEIOK21 in ensuring the number and quality of oocytes in the follicles.

A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity.

ARID4A plays an important role in regulating gene expression and cell proliferation. ARID4A belongs to the AT-rich interaction domain (ARID)-containing family, and a PWWP domain immediately precedes its ARID region. The molecular mechanism and structural basis of ARID4A are largely unknown. Whole-exome sequencing (WES) revealed that a novel heterozygous missense variant, ARID4A c.1231 C > G (p.His411Asp), was associated with schizophrenia (SCZ) in this study. We determined the crystal structure of the PWWP-ARID tandem at 2.05 Å, revealing an unexpected mode in which ARID4A assembles with its PWWP and ARID from a structural and functional supramodule. Our results further showed that compared with the wild type, the p.His411Asp ARID mutant protein adopts a less compact conformation and exhibits a weaker dsDNA-binding ability. The p.His411Asp mutation decreased the number of cells that were arrested in the G0-G1 phase and caused more cells to progress to the G2-M phase. In addition, the missense mutation promoted the proliferation of HEK293T cells. In conclusion, our data provide evidence that ARID4A p.His411Asp could cause a conformational change in the ARID4A ARID domain, influence the DNA binding function, and subsequently disturb the cell cycle arrest in the G1 phase. ARID4A is likely a susceptibility gene for SCZ; thus, these findings provide new insight into the role of ARID4A in psychiatric disorders.

Re-exploration of dietary iodine intake in Chinese adult males using a modified iodine balance study.

There is still controversy about optimal dietary iodine intake as the Universal Salt Iodization policy enforcement in China. A modified iodine balance study was thus conducted to explore the suitable iodine intake in Chinese adult males using the iodine overflow hypothesis. In this study, thirty-eight apparently healthy males (19·1 (sd 0·6) years) were recruited and provided with designed diets. After the 14-d iodine depletion, daily iodine intake gradually increased in the 30-d iodine supplementation, consisting of six stages and each of 5 d. All foods and excreta (urine, faeces) were collected to examine daily iodine intake, iodine excretion and the changes of iodine increment in relation to those values at stage 1. The dose-response associations of iodine intake increment with excretion increment were fitted by the mixed effects models, as well as with retention increment. Daily iodine intake and excretion were 16·3 and 54·3 µg/d at stage 1, and iodine intake increment increased from 11·2 µg/d at stage 2 to 118·0 µg/d at stage 6, while excretion increment elevated from 21·5 to 95·0 µg/d. A zero iodine balance was dynamically achieved as 48·0 µg/d of iodine intake. The estimated average requirement and recommended nutrient intake were severally 48·0 and 67·2 µg/d, which could be corresponded to a daily iodine intake of 0·74 and 1·04 µg/kg per d. The results of our study indicate that roughly half of current iodine intakes recommendation could be enough in Chinese adult males, which would be beneficial for the revision of dietary reference intakes.

Re-exploring the requirement of dietary iodine intake in Chinese female adults based on 'iodine overflow theory'.

PURPOSE: We re-explored the basal iodine requirement based on healthy Chinese female and a new iodine overflow theory was proposed for iodine balance study. METHODS: Thirty-six Chinese healthy female adults (age 20.7 ± 1.1) were recruited for this study, which included 40 days low iodine depletion period and six stages of 30 days supplementation period. Uniform diets with low iodine were provided and the content of iodine in the diet was regulated by dairy products. The total iodine intake from food and the total iodine excretion through 24-h urine and staged feces were completely gathered and monitored. The incremental (Δ) intake and excretion over the range were calculated. RESULTS: The iodine intake and excretion were 13.6 µg/day and 48.6 µg/day at the first stage, respectively. The incremental iodine intakes and excretions were 21.1 µg/day to 120.3 µg/day and 25.8 µg/day to 105.4 µg/day for the supplementation stages, respectively. According to the 'iodine overflow theory', the zero iodine balance (Δ iodine intake = Δ iodine excretion) derived from a mixed effect model indicated a mean iodine intake of 52.2 µg/d (1.0 µg/d kg). The RNI for iodine to healthy Chinese female adult was 73.1 µg/d (1.4 µg/d kg). CONCLUSION: A daily iodine intake of 52.2 µg/d may meet the basal iodine requirement for healthy Chinese female adults, and Chinese female may need more than 20% iodine intake than male based on the 'iodine overflow theory'. The trial was registered at the Chinese Clinical Trial Registry in May 2018 (No: ChiCTR1800016184).

Simultaneous immobilization of lead and arsenic and improved phosphorus availability in contaminated soil using biochar composite modified with hydroxyapatite and oxidation: Findings from a pot experiment.

Multi-metals/metalloids contaminated soil has received extensive attention because of their adverse health effects on the safety of the food chain and environmental health. In order to provide additional insight and aid in mitigating environmental risks, a pot experiment was directed to assess the impacts of biochars derived from rice straw (BC), and modified biochars i-e., hydroxyapatite modified (HAP-BC) and oxidized biochars (Ox-BC) on the redistribution, phytoavailability and bioavailability of phosphorus (P), lead (Pb), and Arsenic (As), as well as their effects on the growth of maize (Zea mays L.) in a Lead (Pb)/Arsenic (As) contaminated soil. The results showed that HAP-BC increased the soil total and available P, compared with raw biochar and control treatment. HAP-BC improved soil properties by elevating soil pH and electric conductivity (EC). The Hedley fractionation scheme revealed that HAP-BC enhanced the labile and moderately labile P species in soil. Both HAP-BC and Ox-BC assisted in the P build-up in plant roots and shoots. The BCR (European Community Bureau of Reference) sequential extraction data for Pb and As in soil showed the pronounced effects of HAP-BC towards the transformation of labile Pb and As forms into more stable species. Compared with control, HAP-BC significantly (P ≤ 0.05) decreased the DTPA-extractable Pb and As by 55% and 28%, respectively, subsequently, resulting in reduced Pb and As plant uptakes. HAP-BC application increased the plant fresh and dry root/shoot biomass by 239%, 72%, 222% and 190%, respectively. The Pb/As immobilization by HAP-BC was mainly driven by precipitation, ion exchange and surface complexation mechanisms in soil. In general, HAP-BC application indicated a great capability to be employed as an effective alternative soil amendment for improving P acquisition in soil, simultaneously immobilizing Pb and As in the soil-plant systems.