Visible-Light-Promoted Radical Cascade Cyclization of 2-Vinyl Benzimidazoles: Access to Benzo[4,5]imidazo[1,2-b]isoquinolin- 11(6H)-ones.

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

Comparative study of imaging and pathology of primary mucinous adenocarcinoma with different imaging manifestations.

BACKGROUND: Pulmonary mucinous adenocarcinoma is a special type of lung cancer. Its imaging manifestations are diverse, which brings challenges to clinical diagnosis. However, its formation mechanism is unclear. OBJECTIVE: The objective of this study is to analyse the relevant mechanisms of the formation of pulmonary mucinous adenocarcinoma by observing its different imaging and pathological manifestations. DATA AND METHODS: Retrospective analysis was conducted on imaging manifestations and pathological data of 103 patients with pulmonary mucinous adenocarcinoma confirmed intraoperatively or pathologically. RESULTS: Forty-three patients had pulmonary mucinous adenocarcinoma with a solitary nodule/mass, 41 patients with localized pneumonia and 19 patients with diffuse pneumonia. Their CT manifestations included 'falling snowflake sign', ground-glass opacity close to the heart, vacuous signs/honeycombing and withered tree branches. Under the microscope, all the three types of pulmonary mucinous adenocarcinoma had visibly formed mucus lakes but were made of tumour cells with totally different shapes, which included the goblet-like shape (tall column-like shape) and quasi-circular shape. Tall column-shaped tumour cells were negative or weakly positive for thyroid transcription factor-1 (TTF-1) and strongly positive for ALK mutation, whereas quasi-circular tumour cells were positive for TTF-1 and less positive for ALK mutation. CONCLUSION: The different imaging manifestations of mucinous adenocarcinoma are possibly due to the different amounts or viscosity of mucus produced, and the mechanisms of its formation may include (1) tumour cells in different shapes have different abilities to produce mucus; (2) tumours in different stages produce different amounts or viscosity of mucus; and (3) the TTF-1 and ALK genes affect the production of mucus.

IL-22, a vital cytokine in autoimmune diseases.

Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.

Biofilm of petroleum-based and bio-based microplastics in seawater in response to Zn(II): Biofilm formation, community structure, and microbial function.

Microplastic biofilms are novel vectors for the transport and spread of pathogenic and drug-resistant bacteria. With the increasing use of bio-based plastics, there is an urgent need to investigate the microbial colonization characteristics of these materials in seawater, particularly in comparison with conventional petroleum-based plastics. Furthermore, the effect of co-occurring contaminants, such as heavy metals, on the formation of microplastic biofilms and bacterial communities remains unclear. In this study, we compared the biofilm bacterial community structure of petroleum-based polyethylene (PE) and bio-based polylactic acid (PLA) in seawater under the influence of zinc ions (Zn2+). Our findings indicate that the biofilm on PLA microplastics in the late stage was impeded by the formation of a mildly acidic microenvironment resulting from the hydrolysis of the ester group on PLA. The PE surface had higher bacterial abundance and diversity, with a more intricate symbiotic pattern. The bacterial structures on the two types of microplastics were different; PE was more conducive to the colonization of anaerobic bacteria, whereas PLA was more favorable for the colonization of aerobic and acid-tolerant species. Furthermore, Zn increased the proportion of the dominant genera that could utilize microplastics as a carbon source, such as Alcanivorax and Nitratireductor. PLA had a greater propensity to harbor and disseminate pathogenic and drug-resistant bacteria, and Zn promoted the enrichment and spread of harmful bacteria such as, Pseudomonas and Clostridioides. Therefore, further research is essential to fully understand the potential environmental effects of bio-based microplastics and the role of heavy metals in the dynamics of bacterial colonization.

Epilepsy and childhood psychiatric disorders: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have indicated that psychiatric disorders are the most common comorbidities in pediatric epilepsy. However, the existence and direction of a causal relationship between the two remains controversial. This study aims to investigate the association between common childhood psychiatric disorders and epilepsy using a two-sample, bidirectional Mendelian randomization (MR) approach. METHODS: Genetic instruments were obtained from the most recent and largest genome-wide association studies (GWAS), including datasets for epilepsy (N_case = 29,994, N_control = 52,538), attention deficit hyperactivity disorder (ADHD) (N_case = 38,691, N_control = 186,843), autism spectrum disorder (ASD) (N_case = 18,381, N_control = 27,969), and Tourette syndrome (TS) (N_case = 4,819, N_control = 9488). MR analyses were conducted using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression. RESULTS: No reliable evidence was found to suggest a causal effect of ADHD, ASD, or TS on epilepsy, nor was there any reliable evidence indicating that epilepsy increases the risk of these three psychiatric disorders. These findings remained consistent across various sensitivity analyses. CONCLUSION: Although observational studies have highlighted a high comorbidity rate between pediatric epilepsy and psychiatric disorders like ADHD and ASD, the MR analysis did not confirm a causal relationship between them. This suggests that previous studies might have been influenced by confounding biases or other biases, potentially overestimating the true relationship. A deeper understanding of the mechanisms underlying these comorbidities is crucial for refining the treatment of pediatric epilepsy.

RBP7 functions as a tumor suppressor in HR + breast cancer by inhibiting the AKT/SREBP1 pathway and reducing fatty acid.

BACKGROUND: Increasing evidence proves that RBP7 plays a significant role in breast cancer (BC). The present study was aimed to investigate the mechanism of RBP7. METHODS: Western Blotting and qRT-PCR were performed for evaluating the expression levels. CCK8, colony forming, xenograft mouse model, wound healing and transwell assays were conducted to examine cell ability of proliferation, invasion and migration. Nile red staining and Oil red O staining were used for testing the lipid. RESULTS: RBP7 was related to overall survival (OS) in patients with HR + BC. RBP7 protein was significantly decreased in HR + BC tissues and cells. RBP7 suppressed HR + BC cell proliferation in vitro and in vivo, and inhibited migration and invasion. RBP7 reduced fatty acid in HR + BC cells by inhibiting the AKT/SREBP1 pathway. CONCLUSIONS: RBP7 may function as a tumor suppressor in HR + BC by inhibiting the AKT/SREBP1 pathway and reducing fatty acid.

New Perspectives on the Role and Therapeutic Potential of Melatonin in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide. It is essential to develop novel interventions to prevent/delay CVDs by targeting their fundamental cellular and molecular processes. Melatonin is a small indole molecule acting both as a hormone of the pineal gland and as a local regulator molecule in various tissues. It has multiple features that may contribute to its cardiovascular protection. Moreover, melatonin enters all cells and subcellular compartments and crosses morphophysiological barriers. Additionally, this indoleamine also serves as a safe exogenous therapeutic agent. Increasing evidence has demonstrated the beneficial effects of melatonin in preventing and improving cardiovascular risk factors. Exogenous administration of melatonin, as a result of its antioxidant and anti-inflammatory properties, has been reported to decrease blood pressure, protect against atherosclerosis, attenuate molecular and cellular damage resulting from cardiac ischemia/reperfusion, and improve the prognosis of myocardial infarction and heart failure. This review aims to summarize the beneficial effects of melatonin against these conditions, the possible protective mechanisms of melatonin, and its potential clinical applicability in CVDs.

CO2 utilization for methanol production: a review on the safety concerns and countermeasures.

The catalytic conversion of carbon dioxide is one of the important ways to achieve the goal of carbon neutralization, which can be further divided into electrocatalysis, thermal catalysis, and photocatalysis. Although photocatalysis and electrocatalysis have the advantages of mild reaction conditions and low energy consumption, the thermal catalytic conversion of CO2 has larger processing capacity, better reduction effect, and more complete industrial foundation, which is a promising technology in the future. During the development of new technology from laboratory to industrial application, ensuring the safety of production process is essential. In this work, safety optimization design of equipment, safety performance of catalysts, accident types, and their countermeasures in the industrial applications of CO2 to methanol are reviewed and discussed in depth. Based on that, future research demands for industrial process safety of CO2 to methanol were proposed, which provide guidance for the large-scale application of CO2 thermal catalytic conversion technology.

Characterizing advanced heart failure risk and hemodynamic phenotypes using interpretable machine learning.

BACKGROUND: Although previous risk models exist for advanced heart failure with reduced ejection fraction (HFrEF), few integrate invasive hemodynamics or support missing data. This study developed and validated a heart failure (HF) hemodynamic risk and phenotyping score for HFrEF, using Machine Learning (ML). METHODS: Prior to modeling, patients in training and validation HF cohorts were assigned to 1 of 5 risk categories based on the composite endpoint of death, left ventricular assist device (LVAD) implantation or transplantation (DeLvTx), and rehospitalization in 6 months of follow-up using unsupervised clustering. The goal of our novel interpretable ML modeling approach, which is robust to missing data, was to predict this risk category (1, 2, 3, 4, or 5) using either invasive hemodynamics alone or a rich and inclusive feature set that included noninvasive hemodynamics (all features). The models were trained using the ESCAPE trial and validated using 4 advanced HF patient cohorts collected from previous trials, then compared with traditional ML models. Prediction accuracy for each of these 5 categories was determined separately for each risk category to generate 5 areas under the curve (AUCs, or C-statistics) for belonging to risk category 1, 2, 3, 4, or 5, respectively. RESULTS: Across all outcomes, our models performed well for predicting the risk category for each patient. Accuracies of 5 separate models predicting a patient's risk category ranged from 0.896 +/- 0.074 to 0.969 +/- 0.081 for the invasive hemodynamics feature set and 0.858 +/- 0.067 to 0.997 +/- 0.070 for the all features feature set. CONCLUSION: Novel interpretable ML models predicted risk categories with a high degree of accuracy. This approach offers a new paradigm for risk stratification that differs from prediction of a binary outcome. Prospective clinical evaluation of this approach is indicated to determine utility for selecting the best treatment approach for patients based on risk and prognosis.

Postoperative interictal epileptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site.

Objective: The study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes that the concordance of IED sites with surgical sites indicates incomplete resection of epileptic focus, while non-concordance of IED sites with surgical sites indicates postoperative changes or cortical stimulation. The former has a higher risk of seizure recurrence. Methods: We retrospectively analyzed the postoperative EEG pattern of 182 consecutive children who underwent resection surgery. To identify the risk factors for seizure recurrence, we compared the attributes of seizure recurred and seizure-free groups by univariate and multivariate analyses. AED tapering was standardized, involving a 25% reduction in the dose of a single type of AED every 2 weeks, independent of the presurgical AED load. Results: We attempted AED withdrawal in 116 (63.7%) children. Twenty-eight (24.1%) children experienced seizure recurrence during or after AED withdrawal. A greater number of AEDs used at the time of surgery (p=0.005), incomplete resection (p=0.001), and presence of IED on postoperative EEG (p=0.011) are predictors of seizure recurrence. The completeness of resection and seizure recurrence after AED withdrawal were related to the presence of IED on the EEG, but not to the concordance of IED with surgical sites. Conclusion: For children with abnormal EEG, the decision to discontinue AED should be made more cautiously, regardless of the relative location of the discharge site and the surgical site.

Profiling of ERBB receptors and downstream pathways reveals selectivity and hidden properties of ERBB4 antagonists.

ERBB receptor tyrosine kinases are involved in development and diseases like cancer, cardiovascular, neurodevelopmental, and mental disorders. Although existing drugs target ERBB receptors, the next generation of drugs requires enhanced selectivity and understanding of physiological pathway responses to improve efficiency and reduce side effects. To address this, we developed a multilevel barcoded reporter profiling assay, termed 'ERBBprofiler', in living cells to monitor the activity of all ERBB targets and key physiological pathways simultaneously. This assay helps differentiate on-target therapeutic effects from off-target and off-pathway side effects of ERBB antagonists. To challenge the assay, eight established ERBB antagonists were profiled. Known effects were confirmed, and previously uncharacterized properties were discovered, such as pyrotinib's preference for ERBB4 over EGFR. Additionally, two lead compounds selectively targeting ERBB4 were profiled, showing promise for clinical trials. Taken together, this multiparametric profiling approach can guide early-stage drug development and lead to improved future therapeutic interventions.

Evaluating the performance of the language model ChatGPT in responding to common questions of people with epilepsy.

OBJECTIVE: People with epilepsy desire to acquire accurate information about epilepsy and actively engage in its management throughout the long journey of living with seizures. ChatGPT is a large language model and we aimed to assess the accuracy and consistency of ChatGPT in responding to the common concerns of people with epilepsy and to evaluate its ability to provide emotional support. METHODS: Questions were collected from the International League against Epilepsy and the China Association against Epilepsy. The responses were independently assessed by two board-certified epileptologists from the China Association against Epilepsy, and a third reviewer resolved disagreements. The reviewers assessed its ability to provide emotional support subjectively. RESULTS: A total of 378 questions related to epilepsy and 5 questions related to emotional support were included. ChatGPT provided "correct and comprehensive" answers to 68.4% of the questions. The model provided reproducible answers for 82.3% questions. The model performed poorly in answering prognostic questions, with only 46.8% of the answers rated as comprehensive. When faced with questions requiring emotional support, the model can generate natural and understandable responses. SIGNIFICANCE: ChatGPT provides accurate and reliable answers to patients with epilepsy and is a valuable source of information. It also provides partial emotional support, potentially assisting those experiencing emotional distress. However, ChatGPT may provide incorrect responses, leading users to inadvertently accept incorrect and potentially dangerous advice. Therefore, the direct use of ChatGPT for medical guidance is not recommended and its primary use at present is in patients education.

Early antiseizure medication withdrawal and risk of seizure recurrence in children after epilepsy surgery: A retrospective study.

OBJECTIVE: The timing of antiseizure medication (ASM) withdrawal in children after epilepsy surgery remains controversial and lacks recognized standards. Given the various negative effects of ASM on development in children, this study aimed to evaluate the safety and feasibility of early ASM withdrawal after epileptic resection surgery. METHODS: We retrospectively assessed the seizure outcomes and ASM profiles of children who had undergone epileptic resection surgery between August 2015 and August 2020 and attempted ASM reduction in the early postoperative phase. Tapering the dose of ASM was attempted when children were seizure-free with no interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) for at least 6 months postoperatively. RESULTS: This study included 145 children with a median follow-up duration of 40 months. Early ASM tapering was attempted postoperatively in 99 (68.3 %) children. Postoperative ASM discontinuation was attempted in 87 (60.0 %) children. Nine (9.1 %) children experienced seizure recurrence during the ASM reduction stage, and 10 (11.5 %) experienced recurrence after ASM discontinuation. Incomplete resection (P = 0.003) and postoperative seizures before ASM tapering (P = 0.003) were independent predictors of seizure recurrence during and after early ASM withdrawal. SIGNIFICANCE: ASM withdrawal is viable and safe to be initiated in children who are seizure-free postoperatively and have no IEDs on the scalp EEG for at least 6 months. Children with incomplete resection and postoperative seizures before ASM withdrawal are at a higher risk of seizure recurrence and may need to continue ASM for a longer period.

Comprehensive split TEV based protein-protein interaction screening reveals TAOK2 as a key modulator of Hippo signalling to limit growth.

The conserved Hippo signalling pathway plays a crucial role in tumour formation by limiting tissue growth and proliferation. At the core of this pathway are tumour suppressor kinases STK3/4 and LATS1/2, which limit the activity of the oncogene YAP1, the primary downstream effector. Here, we employed a split TEV-based protein-protein interaction screen to assess the physical interactions among 28 key Hippo pathway components and potential upstream modulators. This screen led us to the discovery of TAOK2 as pivotal modulator of Hippo signalling, as it binds to the pathway's core kinases, STK3/4 and LATS1/2, and leads to their phosphorylation. Specifically, our findings revealed that TAOK2 binds to and phosphorylates LATS1, resulting in the reduction of YAP1 phosphorylation and subsequent transcription of oncogenes. Consequently, this decrease led to a decrease in cell proliferation and migration. Interestingly, a correlation was observed between reduced TAOK2 expression and decreased patient survival time in certain types of human cancers, including lung and kidney cancer as well as glioma. Moreover, in cellular models corresponding to these cancer types the downregulation of TAOK2 by CRISPR inhibition led to reduced phosphorylation of LATS1 and increased proliferation rates, supporting TAOK2's role as tumour suppressor gene. By contrast, overexpression of TAOK2 in these cellular models lead to increased phospho-LATS1 but reduced cell proliferation. As TAOK2 is a druggable kinase, targeting TAOK2 could serve as an attractive pharmacological approach to modulate cell growth and potentially offer strategies for combating cancer.

Potential and Limitations of ChatGPT 3.5 and 4.0 as a Source of COVID-19 Information: Comprehensive Comparative Analysis of Generative and Authoritative Information.

BACKGROUND: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has necessitated reliable and authoritative information for public guidance. The World Health Organization (WHO) has been a primary source of such information, disseminating it through a question and answer format on its official website. Concurrently, ChatGPT 3.5 and 4.0, a deep learning-based natural language generation system, has shown potential in generating diverse text types based on user input. OBJECTIVE: This study evaluates the accuracy of COVID-19 information generated by ChatGPT 3.5 and 4.0, assessing its potential as a supplementary public information source during the pandemic. METHODS: We extracted 487 COVID-19-related questions from the WHO's official website and used ChatGPT 3.5 and 4.0 to generate corresponding answers. These generated answers were then compared against the official WHO responses for evaluation. Two clinical experts scored the generated answers on a scale of 0-5 across 4 dimensions-accuracy, comprehensiveness, relevance, and clarity-with higher scores indicating better performance in each dimension. The WHO responses served as the reference for this assessment. Additionally, we used the BERT (Bidirectional Encoder Representations from Transformers) model to generate similarity scores (0-1) between the generated and official answers, providing a dual validation mechanism. RESULTS: The mean (SD) scores for ChatGPT 3.5-generated answers were 3.47 (0.725) for accuracy, 3.89 (0.719) for comprehensiveness, 4.09 (0.787) for relevance, and 3.49 (0.809) for clarity. For ChatGPT 4.0, the mean (SD) scores were 4.15 (0.780), 4.47 (0.641), 4.56 (0.600), and 4.09 (0.698), respectively. All differences were statistically significant (P<.001), with ChatGPT 4.0 outperforming ChatGPT 3.5. The BERT model verification showed mean (SD) similarity scores of 0.83 (0.07) for ChatGPT 3.5 and 0.85 (0.07) for ChatGPT 4.0 compared with the official WHO answers. CONCLUSIONS: ChatGPT 3.5 and 4.0 can generate accurate and relevant COVID-19 information to a certain extent. However, compared with official WHO responses, gaps and deficiencies exist. Thus, users of ChatGPT 3.5 and 4.0 should also reference other reliable information sources to mitigate potential misinformation risks. Notably, ChatGPT 4.0 outperformed ChatGPT 3.5 across all evaluated dimensions, a finding corroborated by BERT model validation.

The genome assembly and annotation of the Chinese cobra, Naja atra.

In China, 65 types of venomous snakes exist, with the Chinese Cobra Naja atra being prominent and a major cause of snakebites in humans. Furthermore, N. atra is a protected animal in some areas, as it has been listed as vulnerable by the International Union for Conservation of Nature. Recently, due to the medical value of snake venoms, venomics has experienced growing research interest. In particular, genomic resources are crucial for understanding the molecular mechanisms of venom production. Here, we report a highly continuous genome assembly of N. atra, based on a snake sample from Huangshan, Anhui, China. The size of this genome is 1.67 Gb, while its repeat content constitutes 37.8% of the genome. A total of 26,432 functional genes were annotated. This data provides an essential resource for studying venom production in N. atra. It may also provide guidance for the protection of this species.

Varietal Authenticity Assessment of QTMJ Tea Using Non-Targeted Metabolomics and Multi-Elemental Analysis with Chemometrics.

In this paper, a combination of non-targeted metabolomics and multi-element analysis was used to investigate the impact of five different cultivars on the sensory quality of QTMJ tea and identify candidate markers for varietal authenticity assessment. With chemometric analysis, a total of 54 differential metabolites were screened, with the abundances significantly varied in the tea cultivars. By contrast, the QTMJ tea from the Yaoshan Xiulv (XL) monovariety presents a much better sensory quality as result of the relatively more abundant anthocyanin glycosides and the lower levels of 2'-o-methyladenosine, denudatine, kynurenic acid and L-pipecolic acid. In addition, multi-elemental analysis found 14 significantly differential elements among the cultivars (VIP > 1 and p < 0.05). The differences and correlations of metabolites and elemental signatures of QTMJ tea between five cultivars were discussed using a Pearson correlation analysis. Element characteristics can be used as the best discriminant index for different cultivars of QTMJT, with a predictive accuracy of 100%.

Impact of storage time on non-volatile metabolites and fungal communities in Liupao tea using LC-MS based non-targeted metabolomics and high-throughput sequencing.

Long-term storage of Liupao tea (LPT) is usually believed to enhance its quality and commercial value. The non-volatile metabolites variations and the fungal succession play a key role for organoleptic qualities during the storage procedure. To gain in-depth understanding the impact of storage time on the quality of LPT, two different brands of LPT with different storage time, including Maosheng LPTs (MS) with 0, 5, 10 and 15 years and Tianyu LPTs (TY) with 0, 3, 5, 8 and 10 years, were resorted to investigate the changes of non-volatile metabolites and fungi as well as their correlation by multi-omics. A total of 154 and 119 differential metabolites were identified in these two different brands of MS and TY, respectively, with the aid of high-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry. In both categories of LPTs, the transformation of differential metabolites in the various stages referred to the formation of alkaloids, increase of organic acids, biosynthesis of terpenoids as well as glycosylation and methylation of flavonoids. Thereinto, glycosylation and methylation of flavonoids were the critical stages for distinguishing MS and TY, which were discovered in MS and TY stored for about 10 and 8 years, respectively. Moreover, the results of high-throughput sequencing showed that the key fungal genera in the storage of LPTs consisted of Eurotium, Aspergillus, Blastobotrys, Talaromyces, Thermomyces and Trichomonascus. It was confirmed on the basis of multivariate analysis that the specific fungal genera promoted the transformation of metabolites, affecting the tea quality to some extent. Therefore, this study provided a theoretical basis for the process optimization of LPT storage.

[Meta-analysis of the relationship between maternal arsenic exposure and preterm birth].

OBJECTIVE: To systematic evaluate the association between maternal arsenic exposure and preterm birth. METHODS: A literature search was conducted through Pubmed, Web of Science, Embase, China Knowledge Network(CNKI), WanFang Data, Vip Chinese Journal Service Platform(VIP) with a time frame of November 2022 from the beginning of database construction. Meta-analysis of dichotomous variables was performed using Stata MP15 software, and a random or fixed effects model was chosen for the meta-analysis based on the heterogeneity result, with the ratio of ratios(OR) as the effect indicator; subgroup analysis was used to find characteristic changes; funnel plots were used to evaluate publication bias. RESULTS: A total of 15 papers with a sample size of(n=9 892 256 279), 10 prospective cohort studies, 3 retrospective cohort studies, and 2 cross-sectional studies, were included in 6 Chinese and 9 English papers. By Meta-analysis, the combined OR of preterm birth outcome was 1.06(95%CI 1.03-1.09); the result of subgroup analysis by exposure factors and region, the combined OR(95%CI) of hair, blood, urine, drinking water, and placenta were 0.97(0.56-1.69), 1.40(1.22-1.60), 1.04(0.93-1.17), 1.14(1.04-1.24) and 0.69(0.07-6.38). The combined OR(95%CI) were 1.17(1.04-1.31), 1.10(1.05-1.14), 0.69(0.07-6.38) and 1.17(1.01-1.36) for Asia, Americas, Europe and Africa, respectively. For subgroup analysis based on study type, the combined OR(95%CI) was 1.16(1.05-1.28), 1.01(1.01-1.02) and 1.65(0.73-3.74) for prospective cohort studies, retrospective cohort studies, and cross-sectional studies, respectively. CONCLUSION: Maternal arsenic exposure may contribute to the occurrence of preterm birth, and drinking water arsenic levels may be an important indicator for assessing human arsenic exposure and risk of causing preterm birth.

Comprehensive genome-wide analysis of the DREB gene family in Moso bamboo (Phyllostachys edulis): evidence for the role of PeDREB28 in plant abiotic stress response.

Dehydration response element binding (DREB) proteins are vital for plant abiotic stress responses, but the understanding of DREBs in bamboo, an important sustainable non-timber forest product, is limited. Here we conducted a comprehensive genome-wide analysis of the DREB gene family in Moso bamboo, representing the most important running bamboo species in Asia. In total, 44 PeDREBs were identified, and information on their gene structures, protein motifs, phylogenetic relationships, and stress-related cis-regulatory elements (CREs) was provided. Based on the bioinformatical analysis, we further analyzed PeDREBs from the A5 group and found that four of five PeDREB transcripts were induced by salt, drought, and cold stresses, and their proteins could bind to stress-related CREs. Among these, PeDREB28 was selected as a promising candidate for further functional characterization. PeDREB28 is localized in nucleus, has transcriptional activation activity, and could bind to the DRE- and coupling element 1- (CE1) CREs. Overexpression of PeDREB28 in Arabidopsis and bamboo improved plant abiotic stress tolerance. Transcriptomic analysis showed that broad changes due to the overexpression of PeDREB28. Furthermore, 628 genes that may act as the direct PeDREB28 downstream genes were identified by combining DAP-seq and RNA-seq analysis. Moreover, we confirmed that PeDREB28 could bind to the promoter of pyrabactin-resistance-like gene (DlaPYL3), which is a homolog of abscisic acid receptor in Arabidopsis, and activates its expression. In summary, our study provides important insights into the DREB gene family in Moso bamboo, and contributes to their functional verification and genetic engineering applications in the future.