Genome-wide study of gene-by-sex interactions identifies risks for cleft palate.

Structural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP. CL/P is more common in males and CP is more frequently observed in females, so we hypothesized there would also be sex-specific differences for CP. Using a trio-based cohort, we performed sex-stratified genome-wide association studies (GWAS) based on proband sex followed by a genome-wide gene-by-sex (GxS) interaction testing. There were 13 loci significant for GxS interactions, with the top finding in LTBP1 (RR=3.37 [2.04 - 5.56], p=1.93x10 -6 ). LTBP1 plays a role in regulating TGF-B bioavailability, and knockdown in both mice and zebrafish lead to craniofacial anomalies. Further, there is evidence for differential expression of LTBP1 between males and females in both mice and humans. Therefore, we tested the association between the imputed genetically regulated gene expression of genes with significant GxS interactions and the CP phenotype. We found significant association for LTBP1 in cell cultured fibroblasts in female probands (p=0.0013) but not in males. Taken altogether, we show there are sex-specific risks for CP that are otherwise undetectable in a combined sex cohort, and LTBP1 is a candidate risk gene, particularly in females.

Amphiregulin secreted by umbilical cord Multipotent Stromal Cells protects against ferroptosis of macrophages via the Activating Transcription Factor 3-CD36 axis to alleviate endometrial fibrosis.

Endometrium fibrosis is the leading cause of uterine infertility. Macrophages participated in the occurrence and development of endometrial fibrosis. We previously reported that human umbilical cord multipotent stromal cells (hUC-MSCs) exerted their therapeutic effect in a macrophage-dependent manner in endometrial fibrosis. However precise mechanisms by which hUC-MSCs may influence macrophages in endometrial fibrosis remain largely unexplored. Here, we demonstrated that abnormal iron and lipid metabolism occurred in intrauterine adhesions (IUA) patients and murine models. Ferroptosis has been proven to contribute to the progression of fibrotic diseases. Our results revealed that pharmacological activation of ferroptosis by Erastin aggravated endometrial fibrosis, while inhibition of ferroptosis by Ferrostatin-1 ameliorated endometrial fibrosis in vivo. Moreover, ferroptosis of macrophages was significantly upregulated in endometria of IUA murine models. Of note, transcriptome profiles revealed that CD36 gene expression was significantly increased in IUA patients and immunofluorescence analysis showed CD36 protein was mainly located in macrophages. Silencing CD36 in macrophages could reverse cell ferroptosis. Dual luciferase reporter assay revealed that CD36 was the direct target of activation transcription factor 3 (ATF3). Furthermore, through establishing coculture system and IUA murine models, we found that hUC-MSCs had a protective role against macrophage ferroptosis and alleviated endometrial fibrosis related to decreased CD36 and ATF3. The effect of hUC-MSCs on macrophage ferroptosis was attributed to the upregulation of amphiregulin (AREG). Our data highlighted that macrophage ferroptosis occurred in endometrial fibrosis via the ATF3-CD36 pathway and hUC-MSCs protected against macrophage ferroptosis to alleviate endometrial fibrosis via secreting AREG. These findings provided a potential target for therapeutic implications of endometrial fibrosis.

Protective Interphases of Advanced Znic Anodes: Structure, Mechanisms, Fabrication Strategies and Characterization Techniques.

Aqueous zinc ion batteries (AZIBs) with metallic Zn anode have the potential for large-scale energy storage application due to their cost-effectiveness, safety, environmental-friendliness, and ease of preparation. However, the concerns regarding dendrite growth and side reactions on Zn anode surface hamper AZIB's commercialization. This review aims to give a comprehensive evaluation of the protective interphase construction and provide guildance to further improve the electrochemical performance of AZIBs. The failure behaviors of Zn metal anode including dendrite growth, corrosion, and hydrogen evolution are analyzed. Then, the applications and mechanisms of the constructed interphases are introduced, classified by the material species. The fabrication methods of the artificial interfaces are summarized and evaluated, including the in-situ strategy and ex-situ strategy. Finally, the characterization means of the interphases are discussed to give a full view for the study of Zn anode protection. Based on the analysis of this review, a stable and high-performance Zn anode could be designed by carefully choosing applied material, corresponding protective mechanism, and appropriate construction technique. Additionally, this review for Zn anode modification and construction techniques for anode protection in AZIBs may be helpful in other aqueous metal batteries with similar problems.

Immediate and delayed placement of the intrauterine device after abortion: a systematic review and meta-analysis.

This article aims to report the comprehensive and up-to-date analysis and evidence of the insertion rate, expulsion rate, removal rate, and utilization rate of immediate placement of intrauterine devices (IUDs) versus delayed placement after artificial abortion. PubMed, Embase, Cochrane, Web of Science, CNKI, and Wanfang databases were comprehensively searched up to January 12, 2024 for studies that compared immediate versus delayed insertion of IUDs after abortion. The evaluation metrics included the number of IUD insertion after surgical or medical abortions, the frequency of expulsion and removal at 6 months or 1 year, the number of continued usage, pain intensity scores, the number of infections, the duration of bleeding, and instances of uterine perforation during or after IUD insertion. Ten randomized controlled articles were eligible, comprising 11 research projects, of which 3 projects involved the placement of an IUD after surgical abortion, and 8 projects involved the placement of an IUD after medical abortion. This included 2025 patients (977 in the immediate insertion group and 1,048 in the delayed insertion group). We summarized all the extracted evidence. The meta-analysis results indicated that for post-surgical abortions, the immediate insertion group exhibited a higher IUD placement rate than the delayed insertion group. After medical abortions, the immediate insertion group showed higher rates of IUD placement, utilization, and expulsion at 6 months or 1 year. The two groups showed no statistically significant differences in the removal rate, post-insertion infection rate, pain scores during insertion, and days of bleeding during the follow-up period. Compared to delayed placement, immediate insertion of IUDs can not only increase the usage rate at 6 months or 1 year but also enhance the placement rate.

Tunneling Proton Grotthuss Transfer Channels by Hydrophilic-Zincophobic Heterointerface Shielding for High-Performance Zn-MnO2 Batteries.

Hollandite-type manganese dioxide (α-MnO2) is recognized as a promising cathode material upon high-performance aqueous zinc-ion batteries (ZIBs) owing to the high theoretical capacities, high working potentials, unique Zn2+/H+ co-insertion chemistry, and environmental friendliness. However, its practical applications limited by Zn2+ accommodation, where the strong coulombic interaction and sluggish kinetics cause significant lattice deformation, fast capacity degradation, insufficient rate capability, and undesired interface degradation. It remains challenging to accurately modulate H+ intercalation while suppressing Zn2+ insertion for better lattice stability and electrochemical kinetics. Herein, proton Grotthuss transfer channels are first tunneled by shielding MnO2 with hydrophilic-zincophobic heterointerface, fulfilling the H+-dominating diffusion with the state-of-the-art ZIBs performance. Local atomic structure and theoretical simulation confirm that surface-engineered α-MnO2 affords to the synergy of Mn electron t2g-eg activation, oxygen vacancy enrichment, selective H+ Grotthuss transfer, and accelerated desolvation kinetics. Consequently, fortified α-MnO2 achieves prominent low current density cycle stability (≈100% capacity retention at 1 C after 400 cycles), remarkable long-lifespan cycling performance (98% capacity retention at 20 C after 12 000 cycles), and ultrafast rate performance (up to 30 C). The study exemplifies a new approach of heterointerface engineering for regulation of H+-dominating Grotthuss transfer and lattice stabilization in α-MnO2 toward reliable ZIBs.

Cis- and trans-eQTL TWASs of breast and ovarian cancer identify more than 100 susceptibility genes in the BCAC and OCAC consortia.

Transcriptome-wide association studies (TWASs) have investigated the role of genetically regulated transcriptional activity in the etiologies of breast and ovarian cancer. However, methods performed to date have focused on the regulatory effects of risk-associated SNPs thought to act in cis on a nearby target gene. With growing evidence for distal (trans) regulatory effects of variants on gene expression, we performed TWASs of breast and ovarian cancer using a Bayesian genome-wide TWAS method (BGW-TWAS) that considers effects of both cis- and trans-expression quantitative trait loci (eQTLs). We applied BGW-TWAS to whole-genome and RNA sequencing data in breast and ovarian tissues from the Genotype-Tissue Expression project to train expression imputation models. We applied these models to large-scale GWAS summary statistic data from the Breast Cancer and Ovarian Cancer Association Consortia to identify genes associated with risk of overall breast cancer, non-mucinous epithelial ovarian cancer, and 10 cancer subtypes. We identified 101 genes significantly associated with risk with breast cancer phenotypes and 8 with ovarian phenotypes. These loci include established risk genes and several novel candidate risk loci, such as ACAP3, whose associations are predominantly driven by trans-eQTLs. We replicated several associations using summary statistics from an independent GWAS of these cancer phenotypes. We further used genotype and expression data in normal and tumor breast tissue from the Cancer Genome Atlas to examine the performance of our trained expression imputation models. This work represents an in-depth look into the role of trans eQTLs in the complex molecular mechanisms underlying these diseases.

Atmospheric drought dominates changes in global water use efficiency.

Water use efficiency (defined as the ratio of gross primary productivity to plant transpiration, WUET) describes the tradeoff between ecosystem carbon uptake and water loss. However, a comprehensive understanding of the impact of soil and atmospheric moisture deficits on WUET across large regions remains incomplete. Solar-induced chlorophyll fluorescence (SIF) serves as an effective signal for measuring both terrestrial vegetation photosynthesis and transpiration, thereby enabling a rapid response to changes in the physiological status of plants under water stress. The objectives of this study were to: 1) mechanistically calculate WUET using top-of-canopy SIF data and meteorological information by using the revised mechanistic light response model and the Penman-Monteith equation; 2) analyze the effects of atmospheric and soil water deficits on SIF-based WUET by using decoupled soil water content (SWC) and vapor pressure deficit (VPD); 3) evaluate estimated SIF-based WUET against data from 28 eddy covariance (EC) flux sites representing eight different vegetation types. Results indicated that the model performed well in ecosystems with dense canopies, explaining 56 % of the daily variability in EC tower-based WUET. For the years 2019-2020, the global average WUET derived from SIF was 3.49 g C/kg H2O. Notably, this value exceeded 4 g C/kg H2O in tropical rainforest regions near the equator and went beyond 5 g C/kg H2O in the high-latitude regions of the Northern Hemisphere. We found that SIF-based WUET was primarily influenced by VPD rather than SWC in over 90 % of the global vegetated area. The model used in this study increased our ability to mechanistically estimate WUET with SIF at the global scale, thereby highlighting the significance of the global response of SIF-based WUET to water stress, and also enhancing our understanding of the water­carbon cycle in terrestrial ecosystems.

Phylogenetic placement and comparative analysis of the mitochondrial genomes of Idiostoloidea (Hemiptera: Heteroptera).

The classification system and the higher level phylogenetic relationships of Pentatomomorpha, the second largest infraorder of Heteroptera (Insecta: Hemiptera), have been debated and remain controversial over decades. In particular, the placement and phylogenetic relationship of Idiostoloidea are not well resolved, which hampers a better understanding of the evolutionary history of Pentatomomorpha. In this study, for the first time, we reported the complete mitochondrial genome for two narrowly distributed families of Idiostoloidea (including Idiostolidae and Henicocoridae), respectively. The length of the mitochondrial genome of Monteithocoris hirsutus and Henicocoris sp. is 16,632 and 16,013 bp, respectively. The content of AT is ranging from 75.15% to 80.48%. The mitogenomic structure of Idiostoloidea is highly conservative and there are no gene arrangements. By using the Bayesian inference, maximum likelihood, and Bayesian site-heterogeneous mixture model, we inferred the phylogenetic relationships within Pentatomomorpha and estimated their divergence times based on concatenated mitogenomes and nuclear ribosomal genes. Our results support the classification system of six superfamilies within Pentatomomorpha and confirm the monophyletic groups of each superfamily, with the following phylogenetic relationships: (Aradoidea + (Pentatomoidea + (Idiostoloidea + (Coreoidea + (Pyrrhocoroidea + Lygaeoidea))))). Furthermore, estimated divergence times revealed that most pentatomomorphan superfamilies and families diverged during the Late Jurassic to Early Cretaceous, which coincides with the explosive radiation of angiosperms.

Carbon slow-release and enhanced nitrogen removal performance of plant residue-based composite filler and ecological mechanisms in constructed wetland application.

Stable carbon release and coupled microbial efficacy of external carbon source solid fillers are the keys to enhanced nitrogen removal in constructed wetlands. The constructed wetland plant residue Acorus calamus was cross-linked with poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to create composite solid carbon source fillers (Ac-BDPs). The study demonstrated the slow release of carbon sources from Ac-BDPs with 35.27 mg/g under an average release rate of 0.88 mg/(g·d). Excellent denitrification was also observed in constructed wetlands with Ac-BDPs. Moreover, the average removal rate of nitrate nitrogen (NO3--N) was increased by 1.94 and 3.85 times of the blank groups under initial NO3--N inputs of 5 and 15 mg/L, respectively. Furthermore, the relatively high abundances of nap, narG, nirKS, norB, qnorZ and nosZ guaranteed efficient denitrification performance in constructed wetlands with Ac-BDPs. The study introduced a reliable technique for biological nitrogen removal by using composite carbon source fillers in constructed wetlands.

Characterization of extrachromosomal circular DNAs in plasma of patients with clear cell renal cell carcinoma.

BACKGROUND AND PURPOSE: Extrachromosomal circular DNAs (eccDNAs) have been recognized for their significant involvement in numerous biological processes. Nonetheless, the existence and molecular characteristics of eccDNA in the peripheral blood of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have not yet been reported. Our aim was to identify potentially marked plasma eccDNAs in ccRCC patients. METHODS AND MATERIALS: The detection of plasma eccDNA in ccRCC patients and healthy controls was performed using the Tn5-tagmentation and next-generation sequencing (NGS) method. Comparisons were made between ccRCC patients and healthy controls regarding the distribution of length, gene annotation, pattern of junctional nucleotide motif, and expression pattern of plasma eccDNA. RESULTS: We found 8,568 and 8,150 plasma eccDNAs in ccRCC patients and healthy controls, respectively. There were no statistical differences in the length distribution, gene annotation, and motif signature of plasma eccDNAs between the two groups. A total of 701 differentially expressed plasma eccDNAs were identified, and 25 plasma eccDNAs with potential diagnostic value for ccRCC have been successfully screened. These up-regulated plasma eccDNAs also be indicated to originate from the genomic region of the tumor-associated genes. CONCLUSION: This work demonstrates the characterization of plasma eccDNAs in ccRCC and suggests that the up-regulated plasma eccDNAs could be considered as a promising non-invasive biomarker in ccRCC.

Efficacy and safety of consolidation chemotherapy after adjuvant therapy in stage IB-IIA cervical cancer patients with risk factors: a retrospective single-center study.

Objective: Accumulated evidence has suggested a relatively high recurrence rate in early-stage cervical cancer (CC) patients with risk factors. This study aimed to assess the efficacy and safety of consolidation chemotherapy following adjuvant therapy (concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone) in stage IB-IIA CC patients with risk factors. Methods: A total of 237 stage IB-IIA CC patients who received radical surgery between January 2014 and December 2021 were included in the retrospective study. According to the types of adjuvant therapies, the patients were classified into the control group (CCRT or RT alone) and the study group (consolidation chemotherapy following CCRT or RT alone). The propensity score matching (PSM) was used to balance baseline characteristics between the two groups. The primary end points of the study were disease-free survival (DFS) and overall survival (OS). Results: For the entire cohort, no significant difference was observed in the DFS or OS between the study and control group, which was also confirmed in the PSM cohort (n=124). The multivariate analysis identified the high-risk factor type was an independent adverse prognostic factor for the patients. In patients with high risk factors, consolidation chemotherapy following adjuvant therapy was significantly associated with better clinical outcomes and identified as an independent prognostic favorable factor. Moreover, this association remained statistically significant in high-risk patients with ≥2 metastatic lymph nodes. In patients with intermediate risk factors, consolidation chemotherapy following adjuvant therapy was unrelated to DFS or OS. The safe assessment demonstrated consolidation chemotherapy following adjuvant therapy was significantly correlated with higher rates of ≥ grade 3 hematologic toxicities in both the global and subgroup analysis stratified by risk factor type. Conclusion: Consolidation chemotherapy after adjuvant therapy provided survival benefits in stage IB-IIA CC patients with high risk factors, particularly those with ≥2 metastatic lymph nodes. However, related hematologic toxicities should be alerted in patient management. The actual efficacy and safety of consolidation chemotherapy still need to be investigated in more well-designed clinical trials.

Zinc finger Protein207 orchestrates glioma migration through regulation of epithelial-mesenchymal transition.

BACKGROUND: Glioma represents the predominant primary malignant brain tumor. For several years, molecular profiling has been instrumental in the management and therapeutic stratification of glioma, providing a deeper understanding of its biological complexity. Accumulating evidence unveils the putative involvement of zinc finger proteins (ZNFs) in cancer. This study aimed to elucidate the role and significance of ZNF207 in glioma. METHODS: Utilizing online data such as The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx) project, the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases, in conjunction with bioinformatics methodologies including GO, KEGG, GSEA, CIBERSORT immune cell infiltration estimation, and protein-protein interaction (PPI) analysis, enabled a comprehensive exploration of ZNF207's involvement in gliomagenesis. Immunohistochemistry and RT-PCR techniques were employed to validate the expression level of ZNF207 in glioma samples. Subsequently, the biological effects of ZNF207 on glioma cells were explored through in vitro assays. RESULTS: Our results demonstrate elevated expression of ZNF207 in gliomas, correlating with unfavorable patient outcomes. Stratification analyses were used to delineate the prognostic efficacy of ZNF207 in glioma with different clinicopathological characteristics. Immunocorrelation analysis revealed a significant association between ZNF207 expression and the infiltration levels of T helper cells, macrophages, and natural killer (NK) cells. Utilizing ZNF207 expression and clinical features, we constructed an OS prediction model and displayed well discrimination with a C-index of 0.861. Moreover, the strategic silencing of ZNF207 attenuated glioma cell advancement, evidenced by diminished cellular proliferation, weakened cell tumorigenesis, augmented apoptotic activity, and curtailed migratory capacity alongside the inhibition of the epithelial-mesenchymal transition (EMT) pathway. CONCLUSIONS: ZNF207 may identify as a prospective biomarker and therapeutic candidate for glioma prevention, providing valuable insights into understanding glioma pathogenesis and treatment strategies.

Development of a haematological indices-based nomogram for prognostic prediction and immunotherapy response assessment in primary pulmonary lymphoepithelioma-like carcinoma patients.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare yet aggressive malignancy. This study aims to investigate a deep learning model based on hematological indices, referred to as haematological indices-based signature (HIBS), and propose multivariable predictive models for accurate prognosis prediction and assessment of therapeutic response to immunotherapy in PPLELC. Methods: This retrospective study included 117 patients with PPLELC who received immunotherapy and were randomly divided into a training (n=82) and a validation (n=35) cohort. A total of 41 hematological features were extracted from routine laboratory tests and the least absolute shrinkage and selection operator (LASSO) algorithm were utilized to establish the HIBS. Additionally, we developed a nomogram using the HIBS and clinical characteristics through multivariate Cox regression analysis. To evaluate the nomogram's predictive performance, we used calibration curves and calculated the time-dependent area under the curve (AUC). Kaplan-Meier survival analysis was performed to estimate progression-free survival (PFS) in both cohorts. Results: The proposed HIBS comprised 14 hematological features and showed that patients who experienced disease progression had significantly higher HIBS scores compared to those who did not progress (P<0.001). Five prognostic factors, including HIBS, tumor-node-metastasis (TNM) stage, presence of bone metastasis and the specific immunotherapy regimen, were found to be independent factors and were used to construct a nomogram, which effectively categorized PPLELC patients into a high-risk and a low-risk group, with patients in the high-risk patients demonstrating worse PFS (7.0 vs. 18.0 months, P<0.001) and lower overall response rates (22.2% vs. 52.7%, P<0.001). The nomogram showed satisfactory discrimination for PFS, with AUC values of 0.837 and 0.855 in the training and validation cohorts, respectively. Conclusions: The HIBS-based nomogram could effectively predict the PFS and response of patients with PPLELC regarding immunotherapy and serve as a valuable tool for clinical decision making.

A novel PD-1/PD-L1 pathway-related seven-gene signature for the development and validation of the prognosis prediction model for breast cancer.

Background: Breast cancer (BC/BRCA) is the most common carcinoma in women. The average 5-year survival rate of BC patients with stage IV disease is 26%. A considerable proportion of patients still do not receive effective therapy. It is an unmet need to identify novel biomarkers for BC patients. Herein, we evaluated whether the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) status is associated with the clinical outcomes of BC, based on data from The Cancer Genome Atlas (TCGA). Methods: Clinical and transcriptome data of BC patients were obtained from TCGA dataset, and prognostic genes in BC patients were identified, as well as the PD-1/PD-L1 pathway mainly associating with the BC patients. Following the execution of the consensus clustering algorithm, BC patients were segregated into two clusters, and subsequent investigation of the potential mechanisms between them was carried out. A comparison of ferroptosis and N6-methyladenosine (m6A) was conducted between the two groups with the greatest difference in prognosis. Based on least absolute shrinkage and selection operator (LASSO) analysis, a signature associated with the PD-1/PD-L1 pathway was developed, and the prognosis outcome and the predictive accuracy of the signature model were further assessed. Results: Prognostic genes in BC patients were studied using TCGA data and it was found that the PD-1/PD-L1 pathway was most associated with the BC patients. Then, a low-risk (C1) group and a high-risk (C2) group of BC patients were constructed based on a PD-1/PD-L1 pathway-related signature. The functional analyses suggested that the underlying mechanisms between these groups were mainly associated with immune-related pathways. We found that ferroptosis and m6A were significantly different between the two groups. A PD-1/PD-L1 pathway-related gene signature was further developed to predict survival of BC patients, including 7 genes [mitogen-activated protein kinase kinase 6 (MAP2K6), NF-kappa-B inhibitor alpha (NFKBIA), NFKB Inhibitor Epsilon (NFKBIE), Interferon gamma (IFNG), Toll/interleukin-1 receptor domain-containing adapter protein (TIRAP), IkappaB kinase (CHUK), and Casein kinase 2 alpha 3 gene (CSNK2A3)]. The receiver operating characteristic (ROC) curves were analyzed to further assess the prognostic values of these 7 genes. The 1-, 3-, and 5-year values of the areas under the curve (AUCs) for overall survival were 0.651, 0.658, and 0.653 in this seven gene signature model, respectively. Conclusions: PD-1/PD-L1 pathway-related subtypes of BC were identified, which were closely associated with the immune microenvironment, the ferroptosis status, and m6A in BC patients. The gene signature involved in the PD-1/PD-L1 pathway might help to make a distinction and predict prognosis in BC patients.

Proteome-wide association studies using summary proteomic data identified 23 risk genes of Alzheimer's disease.

Characterizing the genetic mechanisms underlying Alzheimer's disease (AD) dementia is crucial for developing new therapeutics. Proteome-wide association study (PWAS) integrating proteomics data with genome-wide association study (GWAS) summary data was shown as a powerful tool for detecting risk genes. The identified PWAS risk genes can be interpretated as having genetic effects mediated through the genetically regulated protein abundances. Existing PWAS analyses of AD often rely on the availability of individual-level proteomics and genetics data of a reference cohort. Leveraging summary-level protein quantitative trait loci (pQTL) reference data of multiple relevant tissues is expected to improve PWAS findings for studying AD. Here, we applied our recently developed OTTERS tool to conduct PWAS of AD dementia, by leveraging summary-level pQTL data of brain, cerebrospinal fluid (CSF), and plasma tissues, and multiple statistical methods. For each target protein, imputation models of the protein abundance with genetic predictors were trained from summary-level pQTL data, estimating a set of pQTL weights for considered genetic predictors. PWAS p-values were obtained by integrating GWAS summary data of AD dementia with estimated pQTL weights. PWAS p-values from multiple statistical methods were combined by the aggregated Cauchy association test to yield one omnibus PWAS p-value for the target protein. We identified significant PWAS risk genes through omnibus PWAS p-values and analyzed their protein-protein interactions using STRING. Their potential causal effects were assessed by the probabilistic Mendelian randomization (PMR-Egger). As a result, we identified a total of 23 significant PWAS risk genes for AD dementia in brain, CSF, and plasma tissues, including 7 novel findings. We showed that 15 of these risk genes were interconnected within a protein-protein interaction network involving the well-known AD risk gene of APOE and 5 novel findings, and enriched in immune functions and lipids pathways including positive regulation of immune system process, positive regulation of macrophage proliferation, humoral immune response, and high-density lipoprotein particle clearance. Existing biological evidence was found to relate our novel findings with AD. We validated the mediated causal effects of 14 risk genes (60.8%). In conclusion, we identified both known and novel PWAS risk genes, providing novel insights into the genetic mechanisms in brain, CSF, and plasma tissues, and targeted therapeutics development of AD dementia. Our study also demonstrated the effectiveness of integrating public available summary-level pQTL data with GWAS summary data for mapping risk genes of complex human diseases.

Childhood Mycoplasma pneumoniae: epidemiology and manifestation in Northeast and Inner Mongolia, China.

Mycoplasma pneumoniae (MP) is commonly detected in children. However, the epidemiological trends of MP in Northeast (NE) China are unclear. This retrospective study aimed to investigate the prevalence of MP infections in this understudied region. The clinical manifestations and bronchoscopic findings observed in hospitalized patients with severe Mycoplasma pneumoniae pneumonia (SMPP) were collected from comprehensive data obtained from six tertiary hospitals in NE and Inner Mongolian (IM) China, from 1 January 2017 to 31 December 2023. A total of 5,593,530 children who visited the outpatient and emergency departments, and 412,480 inpatient hospitalized children were included in the study. The positivity rate of MP immunoglobulin M (IgM) in the children who visited the outpatient and emergency departments varied from 7.80% to 10.12%, whereas that of MP infection in hospitalized children ranged from 27.18% to 30.10%. Children hospitalized for MP infection were mainly concentrated in the 1- to 4-year (41.39%) and 4- to 7-year (24.25%) age groups. Before 2020, the season with the highest incidence of MP was winter. After the implementation of non-pharmaceutical interventions (NPIs), the MP epidemic season changed, and the number of children with MP infections decreased; however, the proportion of MP infections in hospitalized children did not change significantly. Starting from August 2023, the MP infection rate in outpatient, emergency, and hospitalized children increased sharply, with SMPP and its complications (e.g., plastic bronchitis and pleural effusion) increasing significantly. MP is prevalent in NE and IM, China. When the NPIs ended, MP infection showed a delayed outbreak trend, and the number of children with severe infection increased significantly. IMPORTANCE: In Northeastern (NE) and Inner Mongolia (IM), the incidence of Mycoplasma pneumoniae (MP) infections, including severe Mycoplasma pneumoniae pneumonia (SMPP), is high, posing health risks and imposing substantial economic burdens on the local population. Therefore, it is imperative to prioritize the study of MP prevalence and address the research gaps in MP epidemiology in these areas of China. We obtained a comprehensive collection of pediatric outpatient, emergency, and inpatient data from six public Grade III hospitals. We believe that our study makes a significant contribution to the literature because understanding regional variations in MP infections can help healthcare professionals tailor prevention and treatment strategies, and studying bronchoscopic manifestations can provide insights into the impact of the disease on the respiratory system, potentially leading to a more effective clinical management.

Crystal phase and nanoscale size regulation utilizing the in-situ catalytic pyrolysis of bamboo sawdust in the recycling of spent lithium batteries.

Current Li-ion battery (LIB) recycling methods exhibit the disadvantages of low metal recovery efficiencies and high levels of pollution and energy consumption. Here, products generated via the in-situ catalytic pyrolysis of bamboo sawdust (BS) were utilized to regulate the crystal phase and nanoscale size of the NCM cathode to enhance the selective Li extraction and leaching efficiencies of other valuable metals from spent LIBs. The catalytic effect of the NCM cathode significantly promoted the release of gases from BS pyrolysis. These gases (H2, CO, and CH4) finally transformed the crystal phase of the NCM cathode from LiNixCoyMnzO2 into (Ni-Co/MnO/Li2CO3)/C. The size of the spent NCM cathode material was reduced approximately 31.7-fold (from 4.1 µm to 129.2 nm) after roasting. This could be ascribed to the in-situ catalytic decomposition of aromatic compounds generated via the primary pyrolysis of BS into C and H2 on the surface of the cathode material, resulting in the formation of the nanoscale composite (Ni-Co/MnO/Li2CO3)/C. This process enabled the targeted control of the crystal phase and nanoscale size of the material. Water leaching studies revealed a remarkable selective Li extraction efficiency of 99.27 %, and sulfuric acid leaching experiments with a concentration of 2 M revealed high extraction efficiencies of 99.15 % (Ni), 93.87 % (Co), and 99.46 % (Mn). Finally, a novel mechanism involving synergistic thermo-reduction and carbon modification for crystal phase regulation and nanoscale control was proposed. This study provides a novel concept for use in enhancing the recycling of valuable metals from spent LIBs utilizing biomass waste and practices the concept of "treating waste with waste".

CPEB2 inhibits preeclampsia progression by regulating SSTR3 translation through polyadenylation.

AIMS: Trophoblast cell dysfunction is one of the important factors leading to preeclampsia (PE). Cytoplasmic polyadenylation element-binding 2 (CPEB2) has been found to be differentially expressed in PE patients, but whether it mediates PE process by regulating trophoblast cell function is unclear. METHODS: The expression of CPEB2 and somatostatin receptor 3 (SSTR3) was detected by quantitative real-time PCR, Western blot (WB) and immunofluorescence staining. Cell functions were analyzed by CCK-8 assay, EdU assay, flow cytometry and transwell assay. Epithelial-mesenchymal transition (EMT)-related protein levels were detected by WB. The interaction of CPEB2 and SSTR3 was confirmed by RIP assay, dual-luciferase reporter assay and PCR poly(A) tail assay. Animal experiments were performed to explore the effect of CPEB2 on PE progression in vivo, and the placental tissues of rat were used for H&E staining, immunohistochemical staining and TUNEL staining. RESULTS: CPEB2 was lowly expressed in PE patients. CPEB2 upregulation accelerated trophoblast cell proliferation, migration, invasion and EMT, while its knockdown had an opposite effect. CPEB2 bound to the CPE site in the 3'-UTR of SSTR3 mRNA to suppress SSTR3 translation through reducing poly(A) tails. Besides, SSTR3 overexpression suppressed trophoblast cell proliferation, migration, invasion and EMT, while its silencing accelerated trophoblast cell functions. However, these effects could be reversed by CPEB2 upregulation and knockdown, respectively. In vivo experiments, CPEB2 overexpression relieved histopathologic changes, inhibited apoptosis, promoted proliferation and enhanced EMT in the placenta of PE rat by decreasing SSTR3 expression. CONCLUSION: CPEB2 inhibited PE progression, which promoted trophoblast cell functions by inhibiting SSTR3 translation through polyadenylation.

[Prognostic Value of IGF2BP3 Gene Expression Levels in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia (AML). METHODS: High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center, the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML. The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML. The expression of IGF2BP3 in two anthracycline-resistant cell lines (HL60/ADR, K562/ADR) was detected by RT-qPCR and Western blot, and the expression difference of IGF2BP3 was compared with that in sensitive cells (HL60, K562). The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML, and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis. RESULTS: In the bone marrow primary leukemia cells of 27 AML patients in our center, the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients (P =0.0343). The expression of IGF2BP3 in leukemia patients with extramedullary infiltration (EMI) was significantly higher than that in AML patients without extramedullary infiltration (P =0.0049). Compared with healthy subjects (n=20), IGF2BP3 expression in AML patients (n=26) was higher (P =0.0009). The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines (HL60/ADR, K562/ADR) was significantly higher than that in the sensitive cell lines (K562/ADR vs K562,P =0.0430; HL60/ADR vs HL60, P =0.7369). Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells (P < 0.001). qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive (P =0.002). High expression of IGF2BP3 was associated with poor prognosis in AML (P < 0.05) in 3 large sample cohorts of AML patients. Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival (EFS, HR=1.887, P =0.024) and overall survival (OS, HR=1.619, P =0.016). CONCLUSION: The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML, suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.

Catalytic ozonation of reverse osmosis concentrate from coking wastewater reuse by surface oxidation over Mn-Ce/γ-Al2O3: Effluent organic matter transformation and its catalytic mechanism.

Degradation of organics in high-salinity wastewater is beneficial to meeting the requirement of zero liquid discharge for coking wastewater treatment. Creating efficient and stable performance catalysts for high-salinity wastewater treatment is vital in catalytic ozonation process. Compared with ozonation alone, Mn and Ce co-doped γ-Al2O3 could remarkably enhance activities of catalytic ozonation for chemical oxygen demand (COD) removal (38.9%) of brine derived from a two-stage reverse osmosis treatment. Experimental and theoretical calculation results indicate that introducing Mn could increase the active points of catalyst surface, and introducing Ce could optimize d-band electronic structures and promote the electron transport capacity, enhancing HO• bound to the catalyst surface ([HO•]ads) generation. [HO•]ads plays key roles for degrading the intermediates and transfer them into low molecular weight organics, and further decrease COD, molecular weights and number of organics in reverse osmosis concentrate. Under the same reaction conditions, the presence of Mn/γ-Al2O3 catalyst can reduce ΔO3/ΔCOD by at least 37.6% compared to ozonation alone. Furthermore, Mn-Ce/γ-Al2O3 catalytic ozonation can reduce the ΔO3/ΔCOD from 2.6 of Mn/γ-Al2O3 catalytic ozonation to 0.9 in the case of achieving similar COD removal. Catalytic ozonation has the potential to treat reverse osmosis concentrate derived from bio-treated coking wastewater reclamation.