Vertebral HU value and the pectoral muscle index based on chest CT can be used to opportunistically screen for osteoporosis.

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment. METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The T4 HU value and PMI were obtained using manual chest CT measurements. The participants were classified into normal, osteopenia, and osteoporosis groups based on the results of dual-energy X-ray (DXA) absorptiometry. We compared the clinical baseline data, T4 HU value, and PMI between the three groups of patients and analyzed the correlation between the T4 HU value, PMI, and BMD to further evaluate the diagnostic efficacy of the T4 HU value and PMI for patients with low BMD and osteoporosis. RESULTS: The study ultimately enrolled 469 participants. The T4 HU value and PMI had a high screening capacity for both low BMD and osteoporosis. The combined diagnostic model-incorporating sex, age, BMI, T4 HU value, and PMI-demonstrated the best diagnostic efficacy, with areas under the receiver operating characteristic curve (AUC) of 0.887 and 0.892 for identifying low BMD and osteoporosis, respectively. CONCLUSIONS: The measurement of T4 HU value and PMI on chest CT can be used as an opportunistic screening tool for osteoporosis with excellent diagnostic efficacy. This approach allows the early prevention of osteoporotic fractures via the timely screening of individuals at high risk of osteoporosis without requiring additional radiation.

Genetic relatedness and virulence potential of Salmonella Schwarzengrund strains with or without an IncFIB-IncFIC(FII) fusion plasmid isolated from food and clinical sources.

A total of 55 food and clinical S. Schwarzengrund isolates were assayed for plasmid content, among which an IncFIB-IncFIC(FII) fusion plasmid, conferring streptomycin resistance, was detected in 17 isolates. Among the 17 isolates, 9 were food isolates primarily collected from poultry meat, and 8 clinical isolates collected from stool, urine, and gallbladder. SNP-based phylogenetic analyses showed that the isolates carrying the fusion plasmid formed a subclade indicating the plasmid was acquired and is now maintained by the lineage. Phylogenetic analysis of the plasmid suggested it is derived from avian pathogenic plasmids and might confer an adaptive advantage to the S. Schwarzengrund isolates within birds. IncFIB-IncFIC(FII) fusion plasmids from all food and three clinical isolates were self-conjugative and successfully transferred into E. coli J53 by conjugation. Food and clinical isolates had similar virulome profiles and were able to invade human Caco-2 cells. However, the IncFIB-IncFIC(FII) plasmid did not significantly add to their invasion and persistence potential in human Caco-2 cells.

Exploring the Targets and Molecular Mechanisms of Curcumin for the Treatment of Bladder Cancer Based on Network Pharmacology, Molecular Docking and Molecular Dynamics.

Curcumin, a phenolic compound derived from turmeric, has demonstrated anti-tumor properties in preclinical models of various cancers. However, the exact mechanism of curcumin in treating bladder cancer remains unclear. This study aimed to elucidate the therapeutic targets and molecular mechanisms of curcumin in the treatment of BC through an integrated approach of network pharmacology, molecular docking, and molecular dynamics simulations. PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction were utilized to acquire targets associated with curcumin, while GeneCards, CTD, DisGeNET, OMIM, and PharmGKB databases were utilized to obtain targets related to bladder cancer. The drug-disease interaction targets were obtained using Venny 2.1.0, and GO and KEGG enrichment analyses were then conducted with the DAVID tool. We constructed a protein-protein interaction (PPI) network and identified tenkey targets. In conclusion, AutoDock Tools 1.5.7 was utilized to conduct molecular docking simulations, followed by additional analysis of the central targets through the GEPIA, HPA, cBioPortal, and TIMER databases. A total of 305 potential anticancer targets of curcumin were obtained. The analysis of GO functional enrichment resulted in a total of 1105 terms, including 786 terms related to biological processes (BP), 105 terms related to cellular components (CC), and 214 terms related to molecular functions (MF). In addition, KEGG pathway enrichment analysis identified 170 relevant signaling pathways. Treating bladder cancer could potentially involve inhibiting pathways like the PI3K-Akt signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, and IL-17 signaling pathway. Activating TNF, ALB, CASP3, and ESR1 while inhibiting AKT1, EGFR, STAT3, BCL2, SRC, and HSP90AA1 can also hinder the proliferation of bladder tumor cells. According to the results of molecular docking, curcumin binds to these central targets in a spontaneous manner, exhibiting binding energies lower than - 1.631 kJ/mol. These findings were further validated at the transcriptional, translational and immune infiltration levels. By utilizing network pharmacology and molecular docking techniques, it was discovered that curcumin possesses diverse effects on multiple targets and pathways for treating bladder cancer. It has the potential to impede the growth of bladder tumor cells by suppressing various pathways including the PI3K-Akt and MAPK signaling pathways, as well as pathways associated with EGFR tyrosine kinase inhibitor resistance and the IL-17 signaling pathway. Curcumin could potentially disrupt the cell cycle advancement in bladder cancer cells by increasing the expression of TNF, ALB, CASP3, and ESR1 while decreasing AKT1, EGFR, STAT3, BCL2, SRC, HSP90AA1, and other targeted genes. These findings reveal the possible molecular pathways through which curcumin exerts its anticancer effects in bladder cancer, and this novel research strategy not only provides an important basis for an in-depth understanding of the anticancer mechanism of curcumin, but also offers new potential drugs and targets for the clinical treatment of bladder cancer. Therefore, this study is of great scientific significance and practical application value for promoting the development of bladder cancer therapeutic field. This finding provides strong support for the development of novel, safe and effective drugs for bladder cancer treatment.

Gut microbiota alterations in postmenopausal women with osteoporosis and osteopenia from Shanghai, China.

Background: The importance of the gut microbiota in maintaining bone homeostasis has been increasingly emphasized by recent research. This study aimed to identify whether and how the gut microbiome of postmenopausal women with osteoporosis and osteopenia may differ from that of healthy individuals. Methods: Fecal samples were collected from 27 individuals with osteoporosis (OP), 44 individuals with osteopenia (ON), and 23 normal controls (NC). The composition of the gut microbial community was analyzed by 16S rRNA gene sequencing. Results: No significant difference was found in the microbial composition between the three groups according to alpha and beta diversity. At the phylum level, Proteobacteria and Fusobacteriota were significantly higher and Synergistota was significantly lower in the ON group than in the NC group. At the genus level, Roseburia, Clostridia_UCG.014, Agathobacter, Dialister and Lactobacillus differed between the OP and NC groups as well as between the ON and NC groups (p < 0.05). Linear discriminant effect size (LEfSe) analysis results showed that one phylum community and eighteen genus communities were enriched in the NC, ON and OP groups, respectively. Spearman correlation analysis showed that the abundance of the Dialister genus was positively correlated with BMD and T score at the lumbar spine (p < 0.05). Functional predictions revealed that pathways relevant to amino acid biosynthesis, vitamin biosynthesis, and nucleotide metabolism were enriched in the NC group. On the other hand, pathways relevant to metabolites degradation and carbohydrate metabolism were mainly enriched in the ON and OP groups respectively. Conclusions: Our findings provide new epidemiologic evidence regarding the relationship between the gut microbiota and postmenopausal bone loss, laying a foundation for further exploration of therapeutic targets for the prevention and treatment of postmenopausal osteoporosis (PMO).

A Sinh-Cosh-Enhanced DBO Algorithm Applied to Global Optimization Problems.

The Dung beetle optimization (DBO) algorithm, devised by Jiankai Xue in 2022, is known for its strong optimization capabilities and fast convergence. However, it does have certain limitations, including insufficiently random population initialization, slow search speed, and inadequate global search capabilities. Drawing inspiration from the mathematical properties of the Sinh and Cosh functions, we proposed a new metaheuristic algorithm, Sinh-Cosh Dung Beetle Optimization (SCDBO). By leveraging the Sinh and Cosh functions to disrupt the initial distribution of DBO and balance the development of rollerball dung beetles, SCDBO enhances the search efficiency and global exploration capabilities of DBO through nonlinear enhancements. These improvements collectively enhance the performance of the dung beetle optimization algorithm, making it more adept at solving complex real-world problems. To evaluate the performance of the SCDBO algorithm, we compared it with seven typical algorithms using the CEC2017 test functions. Additionally, by successfully applying it to three engineering problems, robot arm design, pressure vessel problem, and unmanned aerial vehicle (UAV) path planning, we further demonstrate the superiority of the SCDBO algorithm.

Multi-Strategy Improved Dung Beetle Optimization Algorithm and Its Applications.

The dung beetle optimization (DBO) algorithm, a swarm intelligence-based metaheuristic, is renowned for its robust optimization capability and fast convergence speed. However, it also suffers from low population diversity, susceptibility to local optima solutions, and unsatisfactory convergence speed when facing complex optimization problems. In response, this paper proposes the multi-strategy improved dung beetle optimization algorithm (MDBO). The core improvements include using Latin hypercube sampling for better population initialization and the introduction of a novel differential variation strategy, termed "Mean Differential Variation", to enhance the algorithm's ability to evade local optima. Moreover, a strategy combining lens imaging reverse learning and dimension-by-dimension optimization was proposed and applied to the current optimal solution. Through comprehensive performance testing on standard benchmark functions from CEC2017 and CEC2020, MDBO demonstrates superior performance in terms of optimization accuracy, stability, and convergence speed compared with other classical metaheuristic optimization algorithms. Additionally, the efficacy of MDBO in addressing complex real-world engineering problems is validated through three representative engineering application scenarios namely extension/compression spring design problems, reducer design problems, and welded beam design problems.

Improvement of Phased Antenna Array Applied in Focused Microwave Breast Hyperthermia.

Focused microwave breast hyperthermia (FMBH) employs a phased antenna array to perform beamforming that can focus microwave energy at targeted breast tumors. Selective heating of the tumor endows the hyperthermia treatment with high accuracy and low side effects. The effect of FMBH is highly dependent on the applied phased antenna array. This work investigates the effect of polarizations of antenna elements on the microwave-focusing results by simulations. We explore two kinds of antenna arrays with the same number of elements using different digital realistic human breast phantoms. The first array has all the elements' polarization in the vertical plane of the breast, while the second array has half of the elements' polarization in the vertical plane and the other half in the transverse plane, i.e., cross polarization. In total, 96 sets of different simulations are performed, and the results show that the second array leads to a better focusing effect in dense breasts than the first array. This work is very meaningful for the potential improvement of the antenna array for FMBH, which is of great significance for the future clinical applications of FMBH. The antenna array with cross polarization can also be applied in microwave imaging and sensing for biomedical applications.

Surface Nanostructures Promote Droplet Splash on Hot Substrates.

Splash, one of the most visually apparent droplet dynamics, can manifest on any surface above a certain impact velocity, regardless of surface wettability. Previous studies demonstrate that elevating the substrate temperature can suppress droplet splash, which is unfavorable for many practical applications, such as spray cooling and combustion. Here, we report that the suppression effect of substrate temperature on splash is nullified by utilizing surfaces with nanostructures. By manipulating air evacuation time through surface nanostructures, we have identified a pathway for precise control over the splash threshold and the ability to tailor the dependence of the splash onset on surface temperature. We further propose a theoretical criterion to determine different splash regimes by considering the competition between air evacuation and the development of flow instabilities. Our findings underscore the crucial role of nanostructures in splash dynamics, offering valuable insights for the control of splash in various industrial scenarios.

Male reproductive function before and after the adjustment of the COVID-19 prevention policy: a multicenter study in China.

At the end of 2022, the adjustment of the coronavirus disease 2019 (COVID-19) pandemic control policy in China resulted in a large-scale increase in public infection. To compare the fertility parameters of male patients before and after the adjustments of the COVID-19 pandemic control policy in China, we collected data on patients' medical histories and laboratory examinations on their first visits between June 2022 and March 2023 in five different hospitals. Data were divided into five groups according to the timeline of the policy adjustment. The data we collected from male patients included semen quality and serum reproductive hormone levels, and intergroup comparisons were made using the Mann-Whitney U and Chi-square tests. In total, 16 784 cases underwent regular semen analysis, 11 180 had sperm morphology assessments, and 7200 had reproductive hormone analyses. The data showed declining trends in semen volume, sperm motility, and the progressive sperm motility rate after the policy adjustment. Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate. Sperm morphology analysis showed increased neck and tail abnormalities after the policy adjustment. No significant change in hormone levels was observed. Following the adjustment of the COVID-19 prevention policy in China, a decline in sperm motility and morphology was observed. This trend may gradually recover over 2 months. After the policy adjustment, reproductive hormone levels were relatively stable throughout, except for an increase in luteinizing hormone (LH). These changes in semen parameters suggest that the policy adjustment had a short- to medium-term impact on male reproductive function.

Function of FT in Flowering Induction in Two Camellia Species.

FLOWERING LOCUS T (FT), belonging to the FT/TFL1 gene family, is an important gene regulating the flowering transition and inflorescence architecture during plant development. Given its importance to plant adaptation and crop improvement, FT has been extensively studied in related plant research; however, the specific role and underlying molecular mechanisms of FT in the continuous flowering of perennial plants remains elusive. Here, we isolated and characterized homologous FT genes from two Camellia species with different flowering-period phenotypes: CaFT was isolated from Camellia azalea, a precious species blooming in summer and flowering throughout the year, and CjFT was isolated from C. japonica, which blooms in winter and spring. The major difference in the genes between the two species was an additional five-amino acid repeat sequence in C. japonica. FT showed high expression levels in the leaves in both species from January to August, especially in April for C. japonica and in May for C. azalea. CaFT was expressed throughout the year in C. azalea, whereas CjFT was not expressed from September to December in C. japonica. The expression levels of FT in the floral buds were generally higher than those in the leaves. Overexpression of CaFT and CjFT in Arabidopsis indicated that both genes can activate downstream genes to promote flowering. Transgenic callus tissue was obtained by introducing the two genes into C. azalea through Agrobacterium-mediated transformation. Transcriptome and quantitative real-time polymerase chain reaction analyses indicated that both florigen FT genes promoted the expression of downstream genes such as AP1, FUL, and SEP3, and slightly up-regulated the expression of upstream genes such as CO and GI. The above results indicated that CaFT and CjFT played a role in promoting flowering in both camellia species. The expression pattern of CaFT in leaves suggested that, compared to CjFT, CaFT may be related to the annual flowering of C. azalea.

Clinical Analysis and Mental Health Survey of Hemophilia Carriers: a Cross-sectional Study.

OBJECTIVE: Hemophilia carriers (HCs), who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene (F8 or F9), may have a wide range of clotting factor levels, from very low, similar to afflicted males, to the upper limit of normal, and may experience mental health issues. The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs. Additionally, we aimed to investigate the mental health status of HCs in China. METHODS: A total of 127 hemophilia mothers, including 93 hemophilia A (HA) mothers and 34 hemophilia B (HB) mothers, were enrolled in this study. Long distance PCR, multiplex PCR, and Sanger sequencing were used to analyze mutations in F8 or F9. Coagulation factor activity was detected by a one-stage clotting assay. The Symptom Checklist 90 (SCL-90, China/Mandarin version) was given to HCs at the same time to assess their mental health. RESULTS: A total of 90.6% of hemophilia mothers were diagnosed genetically as carriers, with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers, respectively. The median clotting factor level in carriers was 0.74 IU/mL (ranging from 0.09 to 1.74 IU/mL) compared with 1.49 IU/mL (ranging from 0.93 to 1.89 IU/mL) in noncarriers, of which 14.3% of HCs had clotting factor levels of 0.40 IU/mL or below. A total of 53.8% (7/13) of HA carriers with low clotting factor levels (less than 0.50 IU/mL) had a history of bleeding, while none of the HB carriers displayed a bleeding phenotype. The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00 (±60.37) and 1.78 (±0.59), respectively. A total of 67.7% of the respondents had psychological symptoms, with obsessive-compulsive disorder being the most prevalent and severe. The pooled estimates of all nine factors were significantly higher than those in the general population (P<0.05). CONCLUSIONS: The detection rate of gene mutations in hemophilia mothers was 90.6%, with a median clotting factor level of 0.74 IU/mL, and 14.3% of HCs had a clotting factor level of 0.40 IU/mL or below. A history of bleeding was present in 41.2% of HCs with low clotting factor levels (less than 0.50 IU/mL). Additionally, given the fragile mental health status of HCs in China, it is critical to develop efficient strategies to improve psychological well-being.

Near-field coupling of interlayer excitons in MoSe2/WSe2 heterobilayers to surface plasmon polaritons.

Two-dimensional (2D) transition metal dichalcogenides have emerged as promising quantum functional blocks benefitting from their unique combination of spin, valley, and layer degrees of freedom, particularly for the tremendous flexibility of moiré superlattices formed by van der Waals stacking. These degrees of freedom coupled with the enhanced Coulomb interaction in 2D structures allow excitons to serve as on-chip information carriers. However, excitons are spatially circumscribed due to their low mobility and limited lifetime. One way to overcome these limitations is through the coupling of excitons with surface plasmon polaritons (SPPs), which facilitates an interaction between remote quantum states. Here, we showcase the successful coupling of SPPs with interlayer excitons in molybdenum diselenide/tungsten diselenide heterobilayers. Our results indicate that the valley polarization can be efficiently transferred to SPPs, enabling preservation of polarization information even after propagating tens of micrometers.

Islr regulates satellite cells asymmetric division through the SPARC/p-ERK1/2 signaling pathway.

Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.

XPO1 inhibition displays anti-leukemia efficacy against DNMT3A-mutant acute myeloid leukemia via downregulating glutathione pathway.

Acute myeloid leukemia (AML) patients with DNA methyltransferase 3A (DNMT3A) mutation display poor prognosis, and targeted therapy is not available currently. Our previous study identified increased expression of Exportin1 (XPO1) in DNMT3AR882H AML patients. Therefore, we further investigated the therapeutic effect of XPO1 inhibition on DNMT3AR882H AML. Three types of DNMT3AR882H AML cell lines were generated, and XPO1 was significantly upregulated in all DNMT3AR882H cells compared with the wild-type (WT) cells. The XPO1 inhibitor selinexor displayed higher potential in the inhibition of proliferation, promotion of apoptosis, and blockage of the cell cycle in DNMT3AR882H cells than WT cells. Selinexor also significantly inhibited the proliferation of subcutaneous tumors in DNMT3AR882H AML model mice. Primary cells with DNMT3A mutations were more sensitive to selinexor in chemotherapy-naive AML patients. RNA sequencing of selinexor treated AML cells revealed that the majority of metabolic pathways were downregulated after selinexor treatment, with the most significant change in the glutathione metabolic pathway. Glutathione inhibitor L-Buthionine-(S, R)-sulfoximine (BSO) significantly enhanced the apoptosis-inducing effect of selinexor in DNMT3AWT/DNMT3AR882H AML cells. In conclusion, our work reveals that selinexor displays anti-leukemia efficacy against DNMT3AR882H AML via downregulating glutathione pathway. Combination of selinexor and BSO provides novel therapeutic strategy for AML treatment.

Identification and Validation of T-Cell Exhaustion Signature for Predicting Prognosis and Immune Response in Pancreatic Cancer by Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data.

PURPOSE: Pancreatic cancer (PACA) is one of the most fatal malignancies worldwide. Immunotherapy is largely ineffective in patients with PACA. T-cell exhaustion contributes to immunotherapy resistance. We investigated the prognostic potential of T-cell exhaustion-related genes (TEXGs). METHODS: A single-cell RNA (scRNA) sequencing dataset from Tumor Immune Single-Cell Hub (TISCH) and bulk sequencing datasets from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to screen differentially expressed TEXGs. Kaplan-Meier survival, LASSO regression, and univariate/multivariate Cox regression analyses were performed to construct a TEXG risk model. This model was used to predict the prognosis, tumor immune microenvironment, and immunotherapy response. The PACA cohorts from the ICGC and GSE71729 datasets were used to validate the risk model. Pan-cancer expression of SPOCK2 was determined using the TISCH database. RESULTS: A six-gene (SPOCK2, MT1X, LIPH, RARRES3, EMP1, and MEG3) risk model was constructed. Patients with low risk had prolonged survival times in both the training (TCGA-PAAD, n = 178) and validation (ICGC-PACA-CA, ICGC-PAAD-US, and GSE71729, n = 412) datasets. Multivariate Cox regression analysis demonstrated that the risk score was an independent prognostic variable for PACA. High-risk patients correlated with their immunosuppressive status. Immunohistochemical staining confirmed the changes in TEXGs in clinical samples. Moreover, pan-cancer scRNA sequencing datasets from TISCH analysis indicated that SPOCK2 may be a novel marker of exhausted CD8+ T-cells. CONCLUSION: We established and validated a T-cell exhaustion-related prognostic signature for patients with PACA. Moreover, our study suggests that SPOCK2 is a novel marker of exhausted CD8+ T cells.

VRK1 promotes DNA-induced type I interferon production.

BACKGROUND: Type I interferons (IFNs) are an essential class of cytokines with antitumor, antiviral and immunoregulatory effects. However, over-productive the type I IFNs are tightly associated with autoimmune disorders. Thus, the induction of type I interferons is precisely regulated to maintain immune hemostasis. This study aimed to identify a novel regulator of type I interferon signaling. METHODS AND RESULTS: Primary BMDMs, isolated from mice, and human cell lines (HEK293 cells, Hela cells) and murine cell line (MEF cells) were cultured to generate in vitro models. After knockdown VRK1, real-time PCR and dual-luciferase reporter assay were performed to determine the expression level of the type I IFNs and ISGs following HTDNA and Poly (dA:dT) stimulation. Additionally, cells were treated with the VRK1 inhibitor, and the impact of VRK1 inhibition was detected. Upon HTDNA and Poly (dA:dT) stimulation, knockdown of VRK1 attenuated the induction of the type I IFNs and ISGs. Consistently, VRK-IN-1, a potent and selective VRK1 inhibitor, significantly suppressed the induction of the type I IFNs and ISGs in human and murine cell lines. Further, VRK-IN-1 inhibited induction of the type I IFNs in mouse primary BMDMs. Intriguingly, VRK1 potentiated the cGAS-STING- IFN-I axis response at STING level. CONCLUSIONS: Our study reveals a novel function of VRK1 in regulating the production of type I IFNs. VRK-IN-1 might be a potential lead compound for suppressing aberrant type I IFNs in autoimmune disorders.

Anthropogenic-induced ecological risks on marine ecosystems indicated by characterizing emerging pollutants in Pearl River Estuary, China.

Anthropogenic Contaminants of Emerging Concern (CECs) in marine environments have raised significant concerns. Yet, analyses detailing their origins, fate, and environmental effects are limited. This study employs an integrated non-target screening methodology to elucidate CECs existence across 46 sampling sites in the Pearl River Estuary (PRE) of the South China Sea. Assisted by advanced liquid chromatography-high resolution mass spectrometry, we discovered 208 chemicals in six usage categories, with pesticides (33 %) and pharmaceuticals (29 %) predominating. Several CECs drew attention for their consistent detections, profound abundance, and significant ecotoxicities. The wide detection of them at offshore sites further implies that anthropogenic activities may contribute to large-scale contamination. Meanwhile, distinct distribution patterns of CECs across PRE are evident in semi-quantitative results, indicating regional anthropogenic influences. Identified transformation products may establish a novel and non-negligible negative contribution to ecology through elevated environmental toxicities, exemplified by HMMM and atrazine. Based on the ecological risks, we compiled a prioritized list of 21 CECs warranting intensified scrutiny. Our findings indicate the introduction of various CECs into the South China Sea via PRE, emphasizing the urgent necessity for ongoing surveillance of discharged CECs at estuary areas and assessment of their marine ecological consequences.

Pan-cancer analysis reveals potential immunological and prognostic roles of METTL7A in human cancers.

Methyltransferase-like protein 7A (METTL7A) is an m6A RNA methyltransferase that has been linked to cancer prognosis and drug resistance. However, a comprehensive analysis of METTL7A is lacking. The expression of METTL7A, prognostic performance, correlation with microsatellite instability (MSI), tumor mutational burden (TMB), and immune infiltration was investigated in The Cancer Genome Atlas (TCGA). Immunohistochemistry staining was applied to detect METTL7A in 6 tumors. METTL7A was significantly decreased in 19 cancers in TCGA including LUAD. Alterations of METTL7A include amplification and mutation, and epigenetic alterations revealed increased promoter methylation may result in down-regulation of METTL7A in LUAD. We also found that METTL7A was linked to both TMB and MSI in LUAD. METTL7A was increasingly correlated with invasive immune cells, while being negatively associated with Macrophages M0, Mast cells activated, activated memory CD4 T cells, CD8 T cells, and follicular helper T cells in several tumors. Additionally, METTL7A showed similar correlation with immune therapy-related genes across cancers. Our biological validation found that the protein levels of METTL7A were down-regulated in breast cancer (BRCA), endometrioid cancer (UCEC), colon cancer (COAD), prostate cancer (PRAD), and kidney clear cell carcinoma (KIRC), as detected by immunohistochemistry staining. Overall, our work indicates that METTL7A may serve as promising diagnostic and prognostic indicator of LUAD, and our work sheds light on the potential immunological and prognostic roles of METTL7A in human cancers.