Characterizing the polygenic overlap and shared loci between rheumatoid arthritis and cardiovascular diseases.

BACKGROUND: Despite substantial research revealing that patients with rheumatoid arthritis (RA) have excessive morbidity and mortality of cardiovascular disease (CVD), the mechanism underlying this association has not been fully known. This study aims to systematically investigate the phenotypic and genetic correlation between RA and CVD. METHODS: Based on UK Biobank, we conducted two cohort studies to evaluate the phenotypic relationships between RA and CVD, including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), and stroke. Next, we used linkage disequilibrium score regression, Local Analysis of [co]Variant Association, and bivariate causal mixture model (MiXeR) methods to examine the genetic correlation and polygenic overlap between RA and CVD, using genome-wide association summary statistics. Furthermore, we explored specific shared genetic loci by conjunctional false discovery rate analysis and association analysis based on subsets. RESULTS: Compared with the general population, RA patients showed a higher incidence of CVD (hazard ratio [HR] = 1.21, 95% confidence interval [CI]: 1.15-1.28). We observed positive genetic correlations of RA with AF and stroke, and a mixture of negative and positive local genetic correlations underlying the global genetic correlation for CAD and HF, with 13 ~ 33% of shared genetic variants for these trait pairs. We further identified 23 pleiotropic loci associated with RA and at least one CVD, including one novel locus (rs7098414, TSPAN14, 10q23.1). Genes mapped to these shared loci were enriched in immune and inflammatory-related pathways, and modifiable risk factors, such as high diastolic blood pressure. CONCLUSIONS: This study revealed the shared genetic architecture of RA and CVD, which may facilitate drug target identification and improved clinical management.

Short-term efficacy and safety of neoadjuvant pyrotinib plus taxanes for early HER2-positive breast cancer: a single-arm exploratory phase II trial.

Background: The effectiveness and safety of pyrotinib have been substantiated in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC). However, the role of pyrotinib as a single HER2 blockade in neoadjuvant setting among BC patients has not been studied. The objective of this study was to evaluate the efficacy and tolerability of pyrotinib plus taxanes as a novel neoadjuvant regimen in patients with HER2-positive early or locally advanced BC. Methods: In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly] for a total of four 21-day cycles before surgery. Efficacy assessment was based on pathological and clinical measurements. The primary endpoint of this study was the total pathological complete response (tpCR) rate. The secondary endpoints included breast pCR (bpCR) rate, investigator-assessed objective response rate (ORR) and adverse events (AEs) profiles. Results: From 1 September 2021 to 30 December 2022, a total of 31 patients were enrolled. One patient was withdrawn due to unbearable skin rash after the second cycle of neoadjuvant therapy. The majority of the intention-to-treat (ITT) population was premenopausal (54.8%), had large tumors (90.3%) and metastatic nodes (58.1%) at diagnosis and hormone-receptor positive tumors (64.5%). Most participants used nab-paclitaxel (74.2%) and received mastectomy (67.7%) after neoadjuvant treatment. The tpCR and bpCR rates were 48.4% [95% confidence interval (CI): 30.8-66%] and 51.6% (95% CI: 34-69.2%), respectively. Grade ≥3 treatment-related AEs were observed in 16.1% (5/31) of the ITT population, including diarrhea (n=2, 6.5%), hand and foot numbness (n=1, 3.2%), loss of appetite (n=1, 3.2%), and skin rash (n=1, 3.2%). AE related dose reduction or pyrotinib interruption was not required. Conclusions: In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification.

A high heterozygosity genome assembly of Aedes albopictus enables the discovery of the association of PGANT3 with blood-feeding behavior.

The Asian tiger mosquito, Aedes albopictus, is a global invasive species, notorious for its role in transmitting dangerous human arboviruses such as dengue and Chikungunya. Although hematophagous behavior is repulsive, it is an effective strategy for mosquitoes like Aedes albopictus to transmit viruses, posing a significant risk to human health. However, the fragmented nature of the Ae. albopictus genome assembly has been a significant challenge, hindering in-depth biological and genetic studies of this mosquito. In this research, we have harnessed a variety of technologies and implemented a novel strategy to create a significantly improved genome assembly for Ae. albopictus, designated as AealbF3. This assembly boasts a completeness rate of up to 98.1%, and the duplication rate has been minimized to 1.2%. Furthermore, the fragmented contigs or scaffolds of AealbF3 have been organized into three distinct chromosomes, an arrangement corroborated through syntenic plot analysis, which compared the genetic structure of Ae. albopictus with that of Ae. aegypti. Additionally, the study has revealed a phylogenetic relationship suggesting that the PGANT3 gene is implicated in the hematophagous behavior of Ae. albopictus. This involvement was preliminarily substantiated through RNA interference (RNAi) techniques and behavioral experiment. In summary, the AealbF3 genome assembly will facilitate new biological insights and intervention strategies for combating this formidable vector of disease. The innovative assembly process employed in this study could also serve as a valuable template for the assembly of genomes in other insects characterized by high levels of heterozygosity.

Dual targetable drug delivery system based on cell membrane camouflaged liposome for enhanced tumor targeting and improved anti-tumor efficiency.

Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo. The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery.

Research trends and hotspots of ferroptosis in neurodegenerative diseases from 2013 to 2023: A bibliometrics study.

Background: With the aging population, the incidence of neurodegenerative diseases increases yearly, seriously impacting human health. Various journals have published studies on the pathogenesis of ferroptosis in neurodegenerative diseases. However, bibliometric analysis in this field is still lacking. The study aims to visually analyze global research trends in this field over the past decade. Methods: The articles and reviews regarding ferroptosis in neurodegenerative diseases were retrieved from the Web of Science on September 1, 2023. Citespace [version 6.2. R4 (64-bit)] and VOSviewer (version 1.6.18) were used to conduct the bibliometric and knowledge-map analysis. Results: In total, 370 studies were included in the paper and ranked by their citation frequency. Many articles on ferroptosis in neurodegenerative diseases have been published in the past decade. The country, institution, author, and journal with the highest publications were China, Guangzhou Medical University, Maher, Pamela, and Free Radical Biology And Medicine, respectively. The analysis of keyword co-occurrence indicated that research frontiers were molecular mechanisms of ferroptosis in neurodegenerative diseases, especially a few key pathways that triggered ferroptosis in these diseases, including lipid peroxidation signaling, iron metabolism, and GSH/GPX4 signaling. In addition, ferroptosis inhibitors such as liproxstatins and ferrostatins had protective effects in animal models of neurodegenerative diseases. Therefore, future attention should also be focused on therapeutic drugs that target ferroptosis. Conclusion: This study comprehensively analyzed the publications on ferroptosis in neurodegenerative diseases from a bibliometric perspective. Research on this topic is currently expanding at a rapid pace, and the China holds a leading position in this field by its scientific achievements and productivity. Moreover, the research frontiers were molecular mechanisms of ferroptosis in neurodegenerative diseases and developing targeted therapeutic drugs. In summary, our results showed an all-sided overview of the knowledge atlas and a valuable reference for the future research in this field.

Correlation analysis of serum TLR4 protein levels and TLR4 gene polymorphisms in gouty arthritis patients.

OBJECTIVE: The Toll-like receptor (TLR) 4-mediated nuclear factor kappa B (NF-κB) signaling pathway regulates the production of inflammatory factors and plays a key role in the pathogenesis of gouty arthritis. The aim of the present study was to investigate the link among TLR4 gene polymorphisms at various loci, protein expression, and gouty arthritis susceptibility. METHODS: Between 2016 and 2021, a case-control study was used to collect a total of 1207 study subjects, including 317 male patients with gouty arthritis (gout group) and 890 healthy males (control group). The association between gout susceptibility and different genetic models was analyzed by typing three loci of the TLR4 gene (rs2149356, rs2737191, and rs10759932) using a multiplex point mutation rapid assay, and the association between protein expression and gout was confirmed by measuring TLR4 protein concentrations using enzyme-linked immunosorbent assays (ELISAs). RESULTS: In a codominant models AA and AG, the rs2737191 polymorphism in the gout group increased the risk of gout compared to the AA genotype (OR = 2.249, 95%CI 1.010~5.008), and the risk of gout was higher for those carrying the G allele compared to the A allele (OR = 2.227, 95%CI 1.006~4.932). TLR4 protein expression was different between the two groups with different locus genotypes. The differences in TLR4 protein expression between the gout group and control group were statistically significant between the following genotypes: the GG and GT genotypes of the rs2149356 polymorphism; the AA and AG genotypes of the rs2737191 polymorphism; and the TT and TC genotypes of the rs10759932 polymorphism(P<0.05). The TLR4 protein level in the gout group (19.19±3.09 ng/ml) was significantly higher than that in the control group (15.85±4.75 ng/ml). CONCLUSION: The AG genotype of the TLR4 gene rs2737191 polymorphism may be correlated with the development of gouty arthritis. The level of TLR4 protein expression is significantly higher in patients with gouty arthritis than in controls, and there is a correlation between high TLR4 protein expression and the development of gouty arthritis.

A new TROP2-targeting antibody-drug conjugate shows potent antitumor efficacy in breast and lung cancers.

Trophoblast cell surface antigen 2 (Trop2) is considered to be an attractive therapeutic target in cancer treatments. We previously generated a new humanized anti-Trop2 antibody named hIMB1636, and designated it as an ideal targeting carrier for cancer therapy. Lidamycin (LDM) is a new antitumor antibiotic, containing an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). AE and LDP can be separated and reassembled, and the reassembled LDM possesses cytotoxicity similar to that of native LDM; this has made LDM attractive in the preparation of gene-engineering drugs. We herein firstly prepared a new fusion protein hIMB1636-LDP composed of hIMB1636 and LDP by genetic engineering. This construct showed potent binding activities to recombinant antigen with a KD value of 4.57 nM, exhibited binding to Trop2-positive cancer cells and internalization and transport to lysosomes, and demonstrated powerful tumor-targeting ability in vivo. We then obtained the antibody-drug conjugate (ADC) hIMB1636-LDP-AE by molecular reconstitution. In vitro, hIMB1636-LDP-AE inhibited the proliferation, migration, and tumorsphere formation of tumor cells with half-maximal inhibitory concentration (IC50) values at the sub-nanomolar level. Mechanistically, hIMB1636-LDP-AE induced apoptosis and cell-cycle arrest. In vivo, hIMB1636-LDP-AE also inhibited the growth of breast and lung cancers in xenograft models. Moreover, compared to sacituzumab govitecan, hIMB1636-LDP-AE showed more potent antitumor activity and significantly lower myelotoxicity in tumors with moderate Trop2 expression. This study fully revealed the potent antitumor efficacy of hIMB1636-LDP-AE, and also provided a new preparation method for LDM-based ADC, as well as a promising candidate for breast cancer and lung cancer therapeutics.

Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer.

Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.

The Chinese Clinical Sleep Database: An Innovative Database System Includes Large-Scale Clinical Data of Chinese Population.

Purpose: In this study, we established the Chinese Clinical Sleep Database (CCSD), aiming to provide a safe, scalable, and user-friendly database that includes high-quality clinical data from Chinese population to facilitate sleep research. Material and Methods: We collect individual's demographic data, scales, anthropometric measurements, clinical diagnosis, and polysomnography (PSG) recordings from the routine medical process of sleep medicine centers using standardized procedures. The distributed cluster storage technology are utilized to store these data. The structured data are stored in a high-performance MySQL database, while the unstructured data are stored in an object storage service. And we have developed an online data platform to share and manage our data. Results: The data collection has been conducted in three hospitals. In the preliminary stage of data collection (from October 18, 2022 to September 4, 2023), our database included a total of 1183 patients. Among them, 56.8% were male and their ages ranged from 3 to 88 years. These patients were diagnosed with various types of sleep disorders. Conclusion: Since the CCSD's inception, it has demonstrated good stability, security, and scalability. As an public database, the CCSD also exhibits user-friendliness. The CCSD contains comprehensive clinical data, which can contribute to the advancement of the diagnosis and treatment strategies for sleep disorders, ultimately promoting sleep health.

Mo-doping and construction of the heterostructure between NiFe LDH and NiSx co-trigger the activity enhancement for overall water splitting.

To reduce the preparation cost of high-purity hydrogen, it is necessary to search suitable non-precious metal catalysts with high activity and robust stability. Herein, two means (heteroatom-doping and the heterostructure construction) were adopted together to improve the dual-function activity of NiFe LDH which was widely used in water electrolysis. Mo doped NiFe LDH nanoflowers were firstly generated by hydrothermal reaction, and then NiSx was modified on the petals via electrodeposition. Finally, the obtained NF/Mo-NiFe LDH/NiSx with large electrochemical active area exhibits the expected electrochemical performance with the overpotential at 100 mA cm-2 of 169 and 249 mV for hydrogen evolution (HER) and oxygen evolution reaction (OER) respectively. Assembling NF/Mo-NiFe LDH/NiSx into a two-electrode device for the integral water electrolysis, it just requires a cell voltage of 1.69 V to drive a current density of 100 mA cm-2, and keeps stable after 50-hour continuous operation in 1.0 M KOH. Mo-doping not only regulates the electronic structure of the transition metals and reduces the energy barrier of HER intermediates, but also facilitates the generation of reactive sites for OER. Meanwhile, the construction of heterointerface ensures the synergism between NiSx and Mo-NiFe LDH and accelerates the electron transfer across interfaces, thus enhancing the bifunctional performance.

Metabolic engineering of Escherichia coli for high-level production of the biodegradable polyester monomer 2-pyrone-4,6-dicarboxylic acid.

2-Pyrone-4,6-dicarboxylic acid (PDC), a chemically stable pseudo-aromatic dicarboxylic acid, is a promising building block compound for manufacturing biodegradable polyesters. This study aimed to construct high-performance cell factories enabling the efficient production of PDC from glucose. Firstly, the effective enzymes of the PDC biosynthetic pathway were overexpressed on the chromosome of the 3-dehydroshikimate overproducing strain. Consequently, the one-step biosynthesis of PDC from glucose was achieved. Further, the PDC production was enhanced by multi-copy integration of the key gene PsligC encoding 4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase and co-expression of Vitreoscilla hemoglobin. Subsequently, the PDC production was substantially improved by redistributing the metabolic flux for cell growth and PDC biosynthesis based on dynamically downregulating the expression of pyruvate kinase. The resultant strain PDC50 produced 129.37 g/L PDC from glucose within 78 h under fed-batch fermentation conditions, with a yield of 0.528 mol/mol and an average productivity of 1.65 g/L/h. The findings of this study lay the foundation for the potential industrial production of PDC.

Boosting Visible-Light Photocatalytic Activity of BiOCl Nanosheets via Synergetic Effect of Oxygen Vacancy Engineering and Graphene Quantum Dots-Sensitization.

In recent years, oxygen vacancy (VO) engineering has become a research hotspot in the field of photocatalysis. Herein, an efficient GQDs/BiOCl-VO heterojunction photocatalyst was fabricated by loading graphene quantum dots (GQDs) onto BiOCl nanosheets containing oxygen vacancies. ESR and XPS characterizations confirmed the formation of oxygen vacancy. Combining experimental analysis and DFT calculations, it was found that oxygen vacancy promoted the chemical adsorption of O2, while GQDs accelerated electron transfer. Benefiting from the synergistic effect of oxygen vacancy, GQDs, and dye sensitization, the as-prepared GQDs/BiOCl-VO sample exhibited improved efficiency for RhB degradation under visible-light irradiation. A 2 wt% GQDs/BiOCl-VO composite effectively degraded 98% of RhB within 20 min. The main active species were proven to be hole (h+) and superoxide radical (·O2-) via ESR analysis and radical trapping experiments. This study provided new insights into the effective removal of organic pollutants from water by combining defect engineering and quantum dot doping techniques in heterojunction catalysts.

Effects of exogenous melatonin on the osmotic regulation and antioxidant capacity of Ginkgo biloba seedlings under salt stress.

We investigated the effects of exogenous melatonin on the osmotic regulation and antioxidant capacity of 4-year-old Ginkgo biloba seedlings under salt stress. There were three treatments, with low (50 mmol·L-1), medium (100 mmol·L-1), and high (200 mmol·L-1) NaCl stress. Leaves were sprayed and the soil was watered with melatonin solution (0, 0.02, 0.1, 0.5 mmol·L-1). The results showed that saline stress significantly inhibited the osmoregulation and antioxidant capacities of G. biloba seedlings. Application of exogenous melatonin at appropriate concentrations (0.02, 0.1 mmol·L-1) under salt stress could promote plant growth, reduce the rate of electrolyte leakage, decrease the content of flavonoids and malonic dialdehyde, and enhance peroxidase and superoxide dismutase activities in leaves. High concentration (0.5 mmol·L-1) of exogenous melatonin would aggravate the oxidative and osmotic stresses. The 0.02 and 0.1 mmol·L-1 exogenous melatonin alleviated osmotic stress and oxidative stress in G. biloba seedlings under salt stress, while the 0.02 mmol·L-1 exogenous melatonin treatment had the best effect on NaCl stress alleviation. Ground diameter, branch width, branch length, electrolyte leakage rate, superoxide dismutase activity, and flavonoids content could be used as the key indices for rapid identification of the degree of salt stress in G. biloba seedlings.

Spatiotemporal assembly and functional composition of planktonic microeukaryotic communities along productivity gradients in a subtropical lake.

Microeukaryotes play crucial roles in the microbial loop of freshwater ecosystems, functioning both as primary producers and bacterivorous consumers. However, understanding the assembly of microeukaryotic communities and their functional composition in freshwater lake ecosystems across diverse environmental gradients remains limited. Here, we utilized amplicon sequencing of 18S rRNA gene and multivariate statistical analyses to examine the spatiotemporal and biogeographical patterns of microeukaryotes in water columns (at depths of 0.5, 5, and 10 m) within a subtropical lake in eastern China, covering a 40 km distance during spring and autumn of 2022. Our results revealed that complex and diverse microeukaryotic communities were dominated by Chlorophyta (mainly Chlorophyceae), Fungi, Alveolata, Stramenopiles, and Cryptophyta lineages. Species richness was higher in autumn than in spring, forming significant hump-shaped relationships with chlorophyll a concentration (Chl-a, an indicator of phytoplankton biomass). Microeukaryotic communities exhibited significant seasonality and distance-decay patterns. By contrast, the effect of vertical depth was negligible. Stochastic processes mainly influenced the assembly of microeukaryotic communities, explaining 63, 67, and 55% of community variation for spring, autumn, and both seasons combined, respectively. Trait-based functional analysis revealed the prevalence of heterotrophic and phototrophic microeukaryotic plankton with a trade-off along N:P ratio, Chl-a, and dissolved oxygen (DO) gradients. Similarly, the mixotrophic proportions were significantly and positively correlated with Chl-a and DO concentrations. Overall, our findings may provide useful insights into the assembly patterns of microeukaryotes in lake ecosystem and how their functions respond to environmental changes.

Description of Fuscovulum ytuae sp. nov, a facultative autotroph isolated from the intertidalite of Yangma island, China.

In this study, we reported a Gram-stain-negative, ovoid to rod-shaped, atrichous, and facultative anaerobe bacteria strain named YMD61T, which was isolated from the intertidal sediment of Yangma island, China. Growth of strain YMD61T occurred at 10.0-45.0 °C (optimum, 30.0 °C), pH 7.0-10.0 (optimum, 8.0) and with 0-3.0% (w/v) NaCl (optimum, 2.0%). Phylogenetic tree analysis based on 16 S rRNA gene or genomic sequence indicated that strain YMD61T belonged to the genus Fuscovulum and was closely related to Fuscovulum blasticum ATCC 33,485T (96.6% sequence similarity). Genomic analysis indicated that strain YMD61T contains a circular chromosome of 3,895,730 bp with DNA G + C content of 63.3%. The genomic functional analysis indicated that strain YMD61T is a novel sulfur-metabolizing bacteria, which is capable of fixing carbon through an autotrophic pathway by integrating the processes of photosynthesis and sulfur oxidation. The predominant respiratory quinone of YMD61T was ubiquinone-10 (Q-10). The polar lipids of YMD61T contained phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, five unidentified lipids, unidentified aminolipid and unidentified aminophospholipid. The major fatty acids of strain YMD61T contained C18:1ω7c 11-methyl and summed feature 8 (C18:1 ω 7c or/and C18:1 ω 6c). Phylogenetic, physiological, biochemical and morphological analyses suggested that strain YMD61T represents a novel species of the genus Fuscovulum, and the name Fuscovulum ytuae sp. nov. is proposed. The type strain is YMD61T (= MCCC 1K08483T = KCTC 43,537T).

Alternative polyadenylation quantitative trait methylation mapping in human cancers provides clues into the molecular mechanisms of APA.

Genetic variants are involved in the orchestration of alternative polyadenylation (APA) events, while the role of DNA methylation in regulating APA remains unclear. We generated a comprehensive atlas of APA quantitative trait methylation sites (apaQTMs) across 21 different types of cancer (1,612 to 60,219 acting in cis and 4,448 to 142,349 in trans). Potential causal apaQTMs in non-cancer samples were also identified. Mechanistically, we observed a strong enrichment of cis-apaQTMs near polyadenylation sites (PASs) and both cis- and trans-apaQTMs in proximity to transcription factor (TF) binding regions. Through the integration of ChIP-signals and RNA-seq data from cell lines, we have identified several regulators of APA events, acting either directly or indirectly, implicating novel functions of some important genes, such as TCF7L2, which is known for its involvement in type 2 diabetes and cancers. Furthermore, we have identified a vast number of QTMs that share the same putative causal CpG sites with five different cancer types, underscoring the roles of QTMs, including apaQTMs, in the process of tumorigenesis. DNA methylation is extensively involved in the regulation of APA events in human cancers. In an attempt to elucidate the potential underlying molecular mechanisms of APA by DNA methylation, our study paves the way for subsequent experimental validations into the intricate biological functions of DNA methylation in APA regulation and the pathogenesis of human cancers. To present a comprehensive catalog of apaQTM patterns, we introduce the Pancan-apaQTM database, available at https://pancan-apaqtm-zju.shinyapps.io/pancanaQTM/.

Study of factors affecting the remediation of contaminated soil through pneumatic fracturing and soil vapor extraction.

In low-permeability soils, the effectiveness of soil vapor extraction (SVE) is often constrained, resulting in increased time and operational expenses. In this study, pneumatic fracturing and the SVE were combined to remediate low-permeability clay contaminated with ammonia gas. The soil parameters, pneumatic fracturing parameters, extraction mode, and other influencing factors were investigated via laboratory testing. The results indicated that: (1) Pneumatically induced fracturing disrupts soil structure, forming cracks and providing new pathways for ammonium gas migration; (2) the soil crack area exhibits a quadratic function relationship with both the fracturing pressure and frequency, and the soil crack area increases with higher pneumatic frequencies, leading to a faster pneumatic pressure decline; (3) a denser network of pathways emerges within the soil due to the reduced distance between the two pneumatic fracturing points, consequently enhancing soil permeability and increasing pollutant elimination efficiency; (4) the ammonium gas removal efficiency gradually increases with an increase in the extracted vapor flow rate, but there is an optimal extraction flow rate (9 L/min); (5) continuous extraction combined with gas injection effectively ameliorates the issue of prolonged fluctuations in ammonium gas concentration during the later stages of extraction. (6) Fracturing and extraction reduce the moisture content of the surrounding soil. The results demonstrated the feasibility and superiority of pneumatic pre-fracturing extraction in low-permeability soils.

Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis.

Effects of charged polystyrene microplastics on the bioavailability of dufulin in tomato plant.

Microplastics (MPs) and pesticides commonly exist in the environment, yet the interactions between them and their subsequent impacts on plants remain poorly understood. Thus, this study aimed to investigate the impacts of differently charged polystyrene (PS) MPs, including PS-COO-, PS and PS-NH3+ MPs, on the fate of 14C-labelled new antiviral pesticide Dufulin (DFL) in a hydroponic tomato system. The results showed that MPs greatly reduced the growth of tomato plants, with suppression of 18.4-30.2%. Compared to the control group, PS-COO-, PS and PS-NH3+ MPs also reduced the bioaccumulation of DFL in whole tomato plants by 40.3%, 34.5%, and 26.1%, respectively. Furthermore, MPs influenced the translocation of DFL in plant tissues, and the values decreased at the rates of 38.7%, 26.5% and 15.7% for PS-COO-, PS and PS-NH3+, respectively. Interestingly, compared to the control group, PS-COO- exhibited a profound inhibitory effect on DFL concentrations in tomatoes, potentially resulting in a lower dietary risk in the hydroponic tomato system. This may be due to the strong adsorption between PS-COO- and DFL, and PS-COO- may also inhibit the growth of tomato plants. Overall, our study could provide valuable insights into the risk assessment of DFL in the presence of MPs in plant systems.

Performance and mechanism of amphiphilic polymeric chelator for enhanced removal of high concentrations of Cu(II) from wastewater.

An amphiphilic polymeric chelator (APC16-g-SX) grafted with sodium xanthate (SX) groups was successfully prepared for the efficient removal of high concentrations of Cu(II) from wastewater. The ordinary polymeric chelator (PAM-g-SX) based on linear polyacrylamide (PAM) was also prepared for comparative studies. The polymeric chelators were characterized by Fourier transform infrared spectroscopy (FT-IR), solid-state nuclear magnetic resonance (13C-NMR), gel permeation chromatography (GPC), elemental analyzer, and scanning electron microscope (SEM). The chelating performance of these polymeric chelators was investigated, and the mechanism of APC16-g-SX for enhanced removal of Cu(II) from wastewater was proposed based on fluorescence spectroscopy, cryo-scanning electron microscope (Cryo-SEM), energy-dispersive spectrometer (EDS), and X-ray photoelectron spectroscopy (XPS) tests. The results show that as the initial Cu(II) concentration in the wastewater increases, APC16-g-SX shows more excellent chelating performance than ordinary PAM-g-SX. For the wastewater with an initial Cu(II) concentration of 200 mg/L, the removal rate of Cu(II) was 99.82% and 89.34% for both 500 mg/L APC16-g-SX and PAM-g-SX, respectively. The pH of the system has a very great influence on the chelating performance of the polymeric chelators, and the increase in pH of the system helps to improve the chelating performance. The results of EDS and XPS tests also show that N, O, and S atoms in APC16-g-SX were involved in the chelation of Cu(II). The mechanism of enhanced removal of Cu(II) by APC16-g-SX can be attributed to the spatial network structure constructed by the self-association of hydrophobic groups that enhances the utilization of chelation sites.