Major Depressive Disorder Prediction Based on Sleep-Wake Disorders Symptoms in US Adolescents: A Machine Learning Approach from National Sleep Research Resource.

Background: There is substantial evidence from previous studies that abnormalities in sleep parameters associated with depression are demonstrated in almost all stages of sleep architecture. Patients with symptoms of sleep-wake disorders have a much higher risk of developing major depressive disorders (MDD) compared to those without. Objective: The aim of the present study is to establish and compare the performance of different machine learning models based on sleep-wake disorder symptoms data and to select the optimal model to interpret the importance of sleep-wake disorder symptoms to predict MDD occurrence in adolescents. Methods: We derived data for this work from 2020 to 2021 Assessing Nocturnal Sleep/Wake Effects on Risk of Suicide Phase I Study from National Sleep Research Resource. Using demographic and sleep-wake disorder symptoms data as predictors and the occurrence of MDD measured base on the center for epidemiologic studies depression scale as an outcome, the following six machine learning predictive models were developed: eXtreme Gradient Boosting model (XGBoost), Light Gradient Boosting mode, AdaBoost, Gaussian Naïve Bayes, Complement Naïve Bayes, and multilayer perceptron. The models' performance was assessed using the AUC and other metrics, and the final model's predictor importance ranking was explained. Results: XGBoost is the optimal predictive model in comprehensive performance with the AUC of 0.804 in the test set. All sleep-wake disorder symptoms were significantly positively correlated with the occurrence of adolescent MDD. The insomnia severity was the most important predictor compared with the other predictors in this study. Conclusion: This machine learning predictive model based on sleep-wake disorder symptoms can help to raise the awareness of risk of symptoms between sleep-wake disorders and MDD in adolescents and improve primary care and prevention.

Nanoconfinement of ultra-small Bi2Te3 nanocrystals on reduced graphene oxide: a pathway to high-performance sodium-ion battery anodes.

Bismuth telluride (Bi2Te3) nanomaterials have attracted considerable attention owing to their intriguing physicochemical properties and wide-ranging potential applications arising from their distinctive layered structure and nanoscale size effects. However, synthesizing sub-100 nm ultra-small Bi2Te3 nanocrystals remains a formidable challenge. To date, there has been little investigation on the performance of these ultra-small Bi2Te3 nanocrystals in sodium-ion batteries (SIBs). This study presents a general strategy for synthesizing ultra-small Bi2Te3 nanocrystals on reduced graphene oxide (Bi2Te3/rGO) through a nanoconfinement approach. First-principles calculations and electrochemical kinetic studies confirm that the ultra-small Bi2Te3/rGO composite material can effectively mitigate volumetric expansion, preserve electrode integrity, and enhance electron transfer, Na-ion adsorption, and diffusion capacity. As a result, the Bi2Te3/rGO electrode demonstrates a remarkable initial specific capacity of 521 mA h g-1 at 0.1 A g-1, showcasing outstanding rate behaviour and long-lasting cycle life exceeding 800 cycles at 1 A g-1 while preserving exceptional rate properties. The function of the battery is indicated by ex situ TEM and XPS findings, which propose a conventional dual mechanism involving conversion and alloying. This work paves the way for rapid advancements in Bi2Te3-based SIB anodes while contributing to our understanding of sodium ion storage mechanisms.

Burden of silica-attributed pneumoconiosis and tracheal, bronchus & lung cancer for global and countries in the national program for the elimination of silicosis, 1990-2019: a comparative study.

BACKGROUND: In industries worldwide, crystalline silica is pervasive and poses risks of pneumoconiosis and respiratory malignancies, with the latter being a knowledge gap in disease burden research that this study aims to address. By integrating both diseases, we also seek to provide an in-depth depiction of the silica-attributed disease burden. METHODS: Data from the Global Burden of Disease 2019 were extracted to analyze the disease burden due to silica exposure. The trends of age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) from 1990 to 2019, as well as the age-specific number and rate of deaths and disability-adjusted life years (DALYs) in 1990 and 2019, were presented using GraphPad Prism software. The average annual percentage changes (AAPCs) on ASMR and ASDR were calculated using joinpoint regression models. RESULTS: The global trends of disease burden due to silica exposure from 1990 to 2019 showed a significant decrease, with AAPCs on ASMR and ASDR of -1.22 (-1.38, -1.06) and - 1.18 (-1.30, -1.05), respectively. Vietnam was an exception with an unprecedented climb in ASMR and ASDR in general over the years. The age-specific deaths and DALYs mainly peaked in the age group 60-64. In comparison to 1990, the number of deaths and DALYs became higher after 45 years old in 2019, while their rates stayed consistently lower in 2019. Males experienced an elevated age-specific burden than females. China's general age-standardized burden of pneumoconiosis and tracheal, bronchus & lung (TBL) cancer ranked at the forefront, along with the highest burden of pneumoconiosis in Chilean males and South African females, as well as the prominent burden of TBL cancer in Turkish males, Thai females, and overall Vietnamese. The age-specific burden of TBL cancer surpassed that of pneumoconiosis, and a delay was presented in the pneumoconiosis pinnacle burden compared to the TBL cancer. Besides, the burden of pneumoconiosis indicated a sluggish growth trend with advancing age. CONCLUSION: Our research highlights the cruciality of continuous enhancements in occupational health legislation for countries seriously suffering from industrial silica pollution and the necessity of prioritizing preventive measures for male workers and elderly retirees.

Dynamics of platelet parameters in children with severe community-acquired pneumonia between viral and bacterial infections.

Background: Changes in platelet parameters may vary according to the different pathogens. However, little is known about the differences in platelet parameters in children with severe community-acquired pneumonia (CAP) children of viral and bacterial infections. Methods: This was a single-center retrospective study that included 156 children with severe CAP. Dynamic changes in platelet parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT), were recorded at 24 h, 48 h, 72 h, and day 7 of admission, as well as at discharge. Results: At 72 h of admission, PLT in the viral infection group was significantly lower than that in the bacterial infection and bacterial and viral coinfections group. Meanwhile, the curve of changes in PLT (ΔPLT) in the viral infection group was clearly separated from the other two groups at this time point. Receiver operating characteristic (ROC) analysis showed that PLT at 72 h of admission could assist in distinguishing bacterial and viral infections in severe pneumonia children with the area under curve (AUC) value of 0.683 [95% confidence interval (CI): 0.561-0.805, P=0.007]. However, its sensitivity and specificity were not high, at 68% and 65%, respectively. Conclusions: Although the diagnostic value of platelet parameters in bacterial and viral infection in children with severe CAP is limited, they are still expected to be combined with other indicators to provide a reference for timely treatment.

Three Birds, One Stone: An Osteo-Microenvironment Stage-Regulative Scaffold for Bone Defect Repair through Modulating Early Osteo-Immunomodulation, Middle Neovascularization, and Later Osteogenesis.

In order to repair critical-sized bone defects, various polylactic acid-glycolic acid (PLGA)-based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA-based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo-friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone-healing process, an osteo-microenvironment stage-regulative scaffold (P80/D10/M10) is fabricated by incorporating self-developed decellularized bone matrix microparticles (DBM-MPs) and multifunctional magnesium hydroxide nanoparticles (MH-NPs) into PLGA with an optimized proportion using low-temperature rapid prototyping (LT-RP) 3D-printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo-immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo-friendly microenvironment in a stage-matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo-microenvironment stage-regulative scaffold provides a promising treatment for bone defect repair.

Impact of antimicrobial stewardship 2018 on severe pneumonia with bacterial infection in PICU.

BACKGROUND: Antimicrobial stewardship (ASP) 2018 in China emphasizes the hierarchical control of antimicrobial drugs and the management of physicians' prescribing authority, especially in children. The purpose of this study was to assess the impact of implementation of ASP 2018 on antibiotic consumption, resistance and treatment outcomes in children with severe pneumonia from bacterial infections. METHODS: A single center, retrospective study was conducted on 287 children with severe bacterial pneumonia, including 165 patients before intervention (May 2016 - April 2018) and 122 patients after intervention (May 2018 - April 2020). The antimicrobial resistance rates, antibiotic consumption and clinical outcomes of the two periods were compared. RESULTS: After the implementation of ASP 2018, Staphylococcus aureus (17.9%) became the predominant Gram-positive bacterium. The resistance of Streptococcus pneumoniae to clindamycin, erythromycin, and tetracycline was significantly reduced (P < 0.001), and Staphylococcus aureus to tetracycline also decreased (P=0.034). In addition, Klebsiella pneumoniae (18.4%) replaced Pseudomonas aeruginosa (9.5%) as the most common Gram-negative bacterium. The resistance rates of Klebsiella pneumoniae to amoxicillin/clavulanic acid (AMC) and trimethoprim/sulfamethoxazole (SXT), and Acinetobacter baumannii to cefotaxime and SXT decreased significantly (P< 0.02). Total consumption (DDD/100 patient-days) of five antibiotics (cephalosporins, carbapenems, macrolides, antifungal agents, and linezolid) showed a decreasing trend, and the decrease in antifungal agents and linezolid was the most significant (27.4% and 25.6%, P < 0.001). The isolation rate of multidrug resistant (MDR) strains decreased significantly from the highest 16.8% before intervention to 6.7% after intervention (P < 0.001). CONCLUSIONS: Our data indicate that the implementation of antimicrobial management strategies has significantly reduced the consumption of antibiotics and the occurrence of antimicrobial resistance in children with severe bacterial pneumonia in PICU.

Spectroscopic and molecular docking study of three kinds of cinnamic acid interaction with pepsin.

In this work, under simulated physiological conditions (pH = 2.2, glycine hydrochloric acid buffer solution), the interactions of cinnamic acid (CA), m-hydroxycinnamic acid (m-CA) and p-hydroxycinnamic acid (p-CA) with pepsin were studied by fluorescence spectroscopy, ultraviolet-visible absorption spectroscopy, circular dichroism (CD) spectroscopy, Fourier transform infrared spectroscopy (FTIR), molecular docking and molecular dynamic simulation (MD). The spectrogram results showed that these three kinds of CA had a strong ability to quench the intrinsic fluorescence of pepsin, and the quenching effects were obvious with the increase of concentration of these three kinds of molecules. The quenching mechanism of CA, m-CA and p-CA on the fluorescence of pepsin was static quenching. In addition, a stable complex was formed between three kinds of CA with pepsin. Thermodynamic data and docking information suggested that three kinds of CA combine with pepsin were mainly driven by electrostatic force and hydrogen bond. The binding constant and the number of binding sites were determined. The interaction of CA, m-CA and p-CA with pepsin was spontaneous, and accompanied by non-radiative energy transfer. The results from CD, FTIR, UV-Vis and synchronous fluorescence spectra measurements manifested that the secondary structure of pepsin was changed by the binding of three kinds of CA. The ß-sheet of pepsin increased after the interaction with three kinds of CA. The assay results of pepsin activity showed that three kinds of CA led to a decrease in pepsin activity within the investigated concentrations. Molecular docking investigation revealed the formation of polar hydrogen bonds as well as hydrophobic interactions between three kinds of CA with pepsin, and the ligand within the binding pocket of pepsin. MD results implied the formation of a stable complex between three kinds of CA and pepsin. The research suggested that cinnamic acid and its derivatives could be a potential effect on the structure and properties of digestive enzyme.

Features of CFTR mRNA and implications for therapeutics development.

Cystic fibrosis (CF) is an autosomal recessive disease impacting ∼100,000 people worldwide. This lethal disorder is caused by mutation of the CF transmembrane conductance regulator (CFTR) gene, which encodes an ATP-binding cassette-class C protein. More than 2,100 variants have been identified throughout the length of CFTR. These defects confer differing levels of severity in mRNA and/or protein synthesis, folding, gating, and turnover. Drug discovery efforts have resulted in recent development of modulator therapies that improve clinical outcomes for people living with CF. However, a significant portion of the CF population has demonstrated either no response and/or adverse reactions to small molecules. Additional therapeutic options are needed to restore underlying genetic defects for all patients, particularly individuals carrying rare or refractory CFTR variants. Concerted focus has been placed on rescuing variants that encode truncated CFTR protein, which also harbor abnormalities in mRNA synthesis and stability. The current mini-review provides an overview of CFTR mRNA features known to elicit functional consequences on final protein conformation and function, including considerations for RNA-directed therapies under investigation. Alternative exon usage in the 5'-untranslated region, polypyrimidine tracts, and other sequence elements that influence splicing are discussed. Additionally, we describe mechanisms of CFTR mRNA decay and post-transcriptional regulation mediated through interactions with the 3'-untranslated region (e.g. poly-uracil sequences, microRNAs). Contributions of synonymous single nucleotide polymorphisms to CFTR transcript utilization are also examined. Comprehensive understanding of CFTR RNA biology will be imperative for optimizing future therapeutic endeavors intended to address presently untreatable forms of CF.

Dual-Functional Z-Scheme TiO2 @MoS2 @NC Multi-Heterostructures for Photo-Driving Ultrafast Sodium Ion Storage.

Exploiting dual-functional photoelectrodes to harvest and store solar energy is a challenging but efficient way for achieving renewable energy utilization. Herein, multi-heterostructures consisting of N-doped carbon coated MoS2 nanosheets supported by tubular TiO2 with photoelectric conversion and electronic transfer interfaces are designed. When a photo sodium ion battery (photo-SIB) is assembled based on the heterostructures, its capacity increases to 399.3 mAh g-1 with a high photo-conversion efficiency of 0.71 % switching from dark to visible light at 2.0 A g-1 . Remarkably, the photo-SIB can be recharged by light only, with a striking capacity of 231.4 mAh g-1 . Experimental and theoretical results suggest that the proposed multi-heterostructures can enhance charge transfer kinetics, maintain structural stability, and facilitate the separation of photo-excited carriers. This work presents a new strategy to design dual-functional photoelectrodes for efficient use of solar energy.

Identification and analysis of differentially expressed microRNAs in gibel carp Carassius auratus gibelio responding to polyinosinic-polycytidylic acid (poly I:C) stimulation.

Polyinosinic-polycytidylic acid (poly I:C) is a synthesized analogue of viral double-strand RNA and considered as a potential immunostimulant in aquaculture. MicroRNAs (miRNAs) have been reported to play important roles in the development of the immune system and in regulation of host antiviral responses. In our earlier study, it was found that poly I:C pre-treatment could stimulate the resistance against cyprinid herpesvirus 2 (CyHV-2) infection and enhance the antiviral immune response in gibel carp. To understand the role of miRNAs in regulating the host response to poly I:C treatment, we investigated the expression profiles of miRNAs in the head kidney of poly I:C-treated gibel carp with small RNA sequencing technology. When compared with the untreated group, a total of 24 differentially expressed miRNAs were identified in the poly I:C-stimulated fish, among which, 7 and 17 miRNAs were upregulated and downregulated, respectively. Analysis of target genes of these differentially expressed miRNAs found that most targeted mRNAs were involved in catalytic activity, peptidase activity and endopeptidase activity, and were enriched in the metabolic, protein processing in endoplasmic reticulum and oxidative phosphorylation signaling pathways, suggesting that poly I:C could alter the expression of metabolism-related miRNAs in the kidney of gibel carp. Besides, it was noted that some immune-related miRNAs, including inflammation-related miRNAs (miR-192 and miR-731) and interferon-related miRNAs (miR-194a and miR-122), were downregulated after poly I:C treatment. In summary, it was found that poly I:C could regulate the cellular levels of specific miRNAs involved in metabolism and immune responses in the head kidney of gibel carp, which may increase the capacity of the immune cells to fight against pathogens infection.

Vitrectomy and ILM peeling in rhesus macaque: pitfalls and tips for success.

BACKGROUND: The non-human primate (NHP) model is ideal for pre-clinical testing of novel therapies for human retinal diseases due to its similarity to the human visual system. However, intra-ocular delivery of gene therapy or cell transplantation to the retina gets hampered by the sticky vitreous body and poorly permeable inner limiting membrane (ILM) in primates. Although vitrectomy and ILM peeling are commonly performed in patients, many pitfalls exist in carrying out these procedures in the rhesus macaque, which have not been reported previously. METHODS: We summarised common surgical pitfalls after performing vitrectomy and ILM peeling in four eyes of two rhesus macaques (one male and one female). We provided corresponding hands-on technical tips based on our surgical experience and literature search. Orbital CT scans were compared between adult rhesus macaques and humans. High-resolution surgical videos were recorded to demonstrate each critical surgical step. RESULTS: Due to size difference, poor post-operative compliance, and high-standard requirements of a controlled experiment, there were eleven common surgical pitfalls during vitrectomy and ILM peeling in rhesus macaque. Falling into these pitfalls may produce discomfort, add fatigue, cause surgical complications, or even lead to the exclusion of the NHP from an experimental group. CONCLUSION: Recognition and circumvention of these pitfalls during vitrectomy and ILM peeling in NHP are essential. By focusing on these surgical pitfalls, we can better carry out preclinical tests of novel therapies for retinal diseases in the NHP model.

Optic chiasmatic potential by endoscopically implanted skull base microinvasive biosensor: a brain-machine interface approach for anterior visual pathway assessment.

Background: Visually evoked potential (VEP) is widely used to detect optic neuropathy in basic research and clinical practice. Traditionally, VEP is recorded non-invasively from the surface of the skull over the visual cortex. However, its trace amplitude is highly variable, largely due to intracranial modulation and artifacts. Therefore, a safe test with a strong and stable signal is highly desirable to assess optic nerve function, particularly in neurosurgical settings and animal experiments. Methods: Minimally invasive trans-sphenoidal endoscopic recording of optic chiasmatic potential (OCP) was carried out with a titanium screw implanted onto the sphenoid bone beneath the optic chiasm in the goat, whose sphenoidal anatomy is more human-like than non-human primates. Results: The implantation procedure was swift (within 30 min) and did not cause any detectable abnormality in fetching/moving behaviors, skull CT scans and ophthalmic tests after surgery. Compared with traditional VEP, the amplitude of OCP was 5-10 times stronger, more sensitive to weak light stimulus and its subtle changes, and was more repeatable, even under extremely low general anesthesia. Moreover, the OCP signal relied on ipsilateral light stimulation, and was abolished immediately after complete optic nerve (ON) transection. Through proof-of-concept experiments, we demonstrated several potential applications of the OCP device: (1) real-time detector of ON function, (2) detector of region-biased retinal sensitivity, and (3) therapeutic electrical stimulator for the optic nerve with low and thus safe excitation threshold. Conclusions: OCP developed in this study will be valuable for both vision research and clinical practice. This study also provides a safe endoscopic approach to implant skull base brain-machine interface, and a feasible in vivo testbed (goat) for evaluating safety and efficacy of skull base brain-machine interface.

High-quality, large-scale, semi-thin, & ultra-thin sections of the optic nerve in large animals: An optimized procedure.

Large animal model of optic nerve (ON) injury is an essential tool for translational medicine. Perfusion fixation with paraformaldehyde is mainly used for preparing the semi-thin (1-2 µm thick) and ultra-thin (<0.5 µm thick) sections of the ON tissues. However, this conventional fixation technique in large animals needs a large volume of fixatives, which increases the risk of toxic exposure and is environmentally unfriendly. Additionally, fixed residual ON cannot be used for other tests that require fresh tissue samples. Although conventional immersion fixation is feasible for preparing a semi-thin section of the ON in small animals (0.2-0.6 mm in diameter), it faces technical challenges when fixing the ON of large animals (3 mm in diameters), as increased diameter limits the permeability of the fixatives into deeper tissue. Therefore, we optimized the immersion-fixation method to obtain high-quality, large-scale, semi-thin, and ultra-thin sections for the ON of goat and rhesus macaques. Using this optimized technique, the ON microstructure was well preserved throughout the entire area of 1.5*1.5 square millimeters, allowing confident quantification of axon density/diameter on semi-thin section and identification of specific organelles and glial cells on ultra-thin sections. Furthermore, the optimized technique is a quick, simple, and environmentally friendly fixation method. Notably, the ON regions of large animals with or without an intact neurovascular system can be prepared for light and electron microscopy. In contrast, the residual unfixed ON from the same animal can be further utilized for experiments such as tissue culture and biomolecular tests.

Copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins.

A copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins was developed, affording valuable 2,3-dihydrooxazole-spirooxindoles in moderate to good yields with excellent diastereoselectivity. The reaction sequence involves Cu(i) initiated N-O bond cleavage, 1,5-HAT and C-N bond formation. The protocol features mild reaction conditions and broad substrate scope. DFT calculations demonstrated that the [3+2] annulation pathway is more energetically favourable in both kinetics and thermodynamics.

NH4I-Triggered [4 + 2] Annulation of α,ß-Unsaturated Ketoxime Acetates with N-Acetyl Enamides for the Synthesis of Pyridines.

The NH4I-triggered formal [4 + 2] annulation of α,ß-unsaturated ketoxime acetates with N-acetyl enamides has been developed. The current protocol employs electron-rich enamides as C2 synthons and enables the efficient and straightforward construction of polysubstituted pyridines in moderate to good yields based on metal-free systems. The reaction tolerates a wide range of functional groups and represents an alternate route toward the synthesis of pyridine derivatives.

Wood dust exposure and risks of nasopharyngeal carcinoma: a meta-analysis.

BACKGROUND: Wood dust has been confirmed as one kind of human carcinogen. However, there are inconsistent study results of exploring the relationship of exposure to wood dust and occurrence of nasopharyngeal cancer (NPC). For a greater clarification, the authors systemically reviewed the relevant published articles on the relationship of exposure to wood dust and occurrence of NPC. And meta-analysis was conducted. METHODS: The databases of PubMed, U.S. National Library of Medicine (MEDLINE), Embase and Science Direct were searched for the relevant publications. And Newcastle-Ottawa scale was employed for judging the quality of articles. Random-effect model was utilized for meta-analysis. RESULTS: Among a total of 583 retrieved items, 10 case-control studies and 1 cohort study were selected. The ratio of maximal/minimal exposure concentration of wood dust yielded a pooled odd ratio (OR) of 2.18 (95% CI = 1.62-2.93, P = 0.063) with a moderate heterogeneity (I2: 43.0%; P = 0.001). And subgroup analysis was performed for such factors as exposure status, exposure population and geographic region. No publishing bias was noted. Exposing to a high concentration of wood dust was positively proportional to occurring risk of NPC. CONCLUSION: It hints at the contributing effect of wood dust upon NPC. For eliminating the effects of other confounding factors, larger prospective cohort studies are required for further elucidating the relationship of exposure to wood dust and occurrence of NPC.

Copper-Catalyzed N-O Cleavage of α,ß-Unsaturated Ketoxime Acetates toward Structurally Diverse Pyridines.

The copper-catalyzed [4 + 2] annulation of α,ß-unsaturated ketoxime acetates with 1,3-dicarbonyl compounds for the synthesis of three classes of structurally diverse pyridines has been developed. This method employs 1,3-dicarbonyl compounds as C2 synthons and enables the synthesis of multifunctionalized pyridines with diverse electron-withdrawing groups in moderate to good yields. The mechanistic investigation suggests that the reactions proceed through an ionic pathway.

Population-based study of environmental/occupational lead exposure and amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Lead is a known risk factor for amyotrophic lateral sclerosis (ALS). However, the results of studies exploring the relationship between lead exposure and the occurrence of ALS are inconsistent. To clarify this issue, we conducted a systematic review and meta-analysis of relevant published articles on the relationship between lead exposure and the occurrence of ALS. We searched the PubMed, MEDLINE, Embase, and Science Direct databases for relevant publications. The quality of the articles was judged according to the Newcastle-Ottawa scale, and the meta-analysis was conducted using a random effect model. A total of 583 items were retrieved of which 11 case-control studies were selected. The ratio of maximal/minimal lead exposure yielded a pooled odds ratio (OR) of 1.46 (95% confidence interval (CI) 1.16-1.83) with moderate heterogeneity (I2 = 51.8%; p = 0.019). Subgroup and sensitivity analyses showed stable results. There was evidence of publication bias, but the recalculated OR after employing the "fill and trim" method was 1.28 (95% CI 1.02-1.63). These results indicated that environmental/occupational lead exposure was positively proportional to the risk of ALS.

WPMIAS: Whole-degradome-based Plant MicroRNA-Target Interaction Analysis Server.

A critical aspect for exploring the biological function of a microRNA (miRNA) lies on exact detection and validation of its target mRNAs. However, no convenient and efficient web-based server is available for plant biologists to identify the experimentally verified target mRNAs of miRNAs. In this work, we built a comprehensive web-based platform for miRNA-target analysis, named as Whole-degradome-based Plant MiRNA-target Interaction Analysis Server (WPMIAS), for validation of predicted interactions of miRNAs and their target mRNAs (MTIs) by user-submitted data or all available pre-loaded degradome data. Besides, the server can construct degradome-based miRNA regulatory networks (MRNs) based on the validated MTIs to help study the functions and relations among miRNAs and target mRNAs. WPMIAS is also suitable for other small RNAs (sRNAs), such as 21-nt phased siRNAs (phasiRNAs) and natural antisense siRNAs (nat-siRNAs), which direct cleavage of target mRNAs. Currently, WPMIAS supports 64 plant species with ∼200 cDNA libraries and 274 pre-loaded plant degradome datasets. The user can identify all validated MTIs by analyzing all degradome data at a time and understand when and where MTIs take place and their cleavage levels. With the data obtained from WPMIAS, the user can build a plant miRNA-target map, where it is convenient to find interesting research ideas on miRNAs. In summary, WPMIAS is able to support a comprehensive web-based plant miRNA-target analysis and expected to greatly promote future research on plant miRNAs. AVAILABILITY: It can be freely accessed at https://cbi.njau.edu.cn/WPMIAS/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.