Proteomic and phosphoproteomic landscape of localized prostate cancer unveils distinct molecular subtypes and insights into precision therapeutics.

Building upon our previous investigation of genomic, epigenomic, and transcriptomic profiles of prostate cancer in China, we conducted a comprehensive analysis of proteomic and phosphoproteomic profiles of 82 tumor tissues and matched adjacent normal tissues from 41 Chinese patients with localized prostate cancer. We identified three distinct proteomic subtypes with significant difference in both molecular features and clinical prognosis. Notably, these proteomic subtypes exhibited a parallel degree of heterogeneity in the phosphoproteome, featuring unique metabolism, proliferation, and immune infiltration characteristics. We further demonstrated that a combination of proteins and phosphosites serves as the most effective biomarkers in prostate cancer to predict biochemical recurrence. Through an integrated multiomics analysis, we revealed mechanistic differences underlying different proteomic subtypes and highlighted the potential significance of Serine/arginine-rich splicing factor 1 (SRSF1) phosphorylation in promoting the malignant characteristics of prostate cancer cells. Our multiomics data provide valuable resources for understanding the molecular mechanisms of prostate cancer within the Chinese population, which have the potential to inform the development of personalized treatment strategies and enhance prognostic analyses for prostate cancer patients.

Subcellular localization and function analysis of PINK1 mitron in PD progression: Mitron modulates mitochondrial morphology to regulate neuronal death.

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder. Loss or degeneration of the dopaminergic neurons in the substantia nigra and development of Lewy bodies in dopaminergic neurons were the defining pathologic changes. MiRNAs fine-tune the protein levels by posttranscriptional gene regulation. MiR-7019-3p is encoded within the fifth intron of PD-associated protein PINK1. In present study, we firstly demonstrated miR-7019-3p expression is significantly upregulated in PD mice model and neuron cell models, miR-7019-3p mainly existed in mitochondria, miR-7019-3p could regulate the structure, and function of mitochondria in neuronal cells. We predicted and verified that mitochondria-associated protein optic atrophy 1 and 12s rRNA, 16s rRNA, and polycistronic RNA are target genes of miR-7019-3p. Finally, we proved that SP1 protein could independently regulate the expression of miR-7019-3p at the upstream. The evidences in the study suggest the role miR-7019-3p in the regulation of mitochondrial structure and function, and this kind of regulation could be implemented or promoted through the pathway of SP1-miR-7019-3p-optic atrophy 1/12s rRNA, 16s rRNA, and polycistronic RNA. Our results have suggested a promising and potential therapeutic target for reversing mitochondria dysregulation in neuronal cells during PD process.

GhGRF4/GhARF2-GhGASA24 module regulates fiber cell wall thickness by modulating cellulose biosynthesis in upland cotton (Gossypium hirsutum).

Fiber elongation rate is an essential characteristic of cotton fiber in the textile industry, yet it has been largely overlooked in genetic studies. Gibberellins (GAs) and auxin (IAA) are recognized for their role in directing numerous developmental processes in plants by influencing cell differentiation and elongation. However, the degree to which GA-IAA interaction governs cellular elongation in cotton fiber cells remains to be fully understood. In this study, we identified a causal gene, Gibberellic Acid-Stimulated in Arabidopsis 24 (GhGASA24), that appears to be responsible for fiber elongation rate via regulating fiber cell wall thickness. Subsequent experiments revealed that GhGASA24 influences cell wall formation by promoting the expression of GhCesA8 and GhCesA10. Our findings suggest that Auxin Response Factor 2 (GhARF2) regulates fiber elongation rate by directly binding to the AuxRE elements in GhGASA24 promoter. In addition, we identified Growth Regulation Factor 4 (GhGRF4) as a transcription factor that interacts with GhARF2 to form a heterodimer complex, which also transcriptionally activates GhGASA24. Intriguingly, GhGRF4 regulates GhARF2 expression by directly binding to its promoter, thereby acting as a cascade regulator to enhance the transcriptional levels of GhGASA24. We propose that the GhGRF4/GhARF2-GhGASA24-GhCesAs module may contribute to fiber cell wall thickness by modulating cellulose biosynthesis, and provide a theoretical basis for improvement of fiber quality.

The genetic basis of leaf hair development in upland cotton (Gossypium hirsutum).

Trichomes, which originate from the epidermal cell of aerial organs, provide plants with defense and secretion functions. Although numerous genes have been implicated in trichome development, the molecular mechanisms underlying trichome cell formation in plants remain incompletely understood. Here, we using genome-wide association study (GWAS) across 1037 diverse accessions in upland cotton (Gossypium hirsutum) to identify three loci associated with leaf pubescence (hair) amount, located on chromosome A06 (LPA1), A08 (LPA2) and A11 (LPA3), respectively. GhHD1, a previously characterized candidate gene, was identified on LPA1 and encodes an HD-Zip transcription factor. For LPA2 and LPA3, we identified two candidate genes, GhGIR1 and GhGIR2, both encoding proteins with WD40 and RING domains that act as inhibitors of leaf hair formation. Expression analysis revealed that GhHD1 was predominantly expressed in hairy accessions, whereas GhGIR1 and GhGIR2 were expressed in hairless accessions. Silencing GhHD1 or overexpressing GhGIR1 in hairy accessions induced in a hairless phenotype, whereas silencing GhGIR2 in hairless accessions resulted in a hairy phenotype. We also demonstrated that GhHD1 interact with both GhGIR1 and GhGIR2, and GhGIR1 can interact with GhGIR2. Further investigation indicated that GhHD1 functions as a transcriptional activator, binding to the promoters of the GhGIR1 and GhGIR2 to active their expression, whereas GhGIR1 and GhGIR2 can suppress the transcriptional activation of GhHD1. Our findings shed light on the intricate regulatory network involving GhHD1, GhGIR1 and GhGIR2 in the initiation and development of plant epidermal hairs in cotton.

Epoxyeicosatrienoic Acids Prevent Cardiac Dysfunction in Viral Myocarditis via Interferon Type I Signaling.

Myocarditis is a challenging inflammatory disease of the heart, and better understanding of its pathogenesis is needed to develop specific drug therapies. Epoxyeicosatrienoic acids (EETs), active molecules synthesized by CYP (cytochrome P450) enzymes from arachidonic acids and hydrolyzed to less active dihydroxyeicosatrienoic acids by sEH (soluble epoxide hydrolase), have been attributed anti-inflammatory activity. Here, we investigated whether EETs have immunomodulatory activity and exert protective effects on coxsackie B3 virus-induced myocarditis. Viral infection altered eicosanoid epoxide and diol levels in both patients with myocarditis and in the murine heart and correlated with the increased expression and activity of sEH after coxsackie B3 virus infection. Administration of a sEH inhibitor prevented coxsackie B3 virus-induced cardiac dysfunction and inflammatory infiltration. Importantly, EET/sEH inhibitor treatment attenuated viral infection or improved viral resistance by activating type I IFN (interferon) signaling. At the molecular level, EETs enhanced the interaction between GSK3ß (glycogen synthase kinase-3 beta) and TBK1 (TANK-binding kinase 1) to promote IFN-ß production. Our findings revealed that EETs and sEH inhibitors prevent the progress of coxsackie B3 virus-induced myocarditis, particularly by promoting viral resistance by increasing IFN production.

Sensitivity of triple negative breast cancer cells to ATM-dependent ferroptosis induced by sodium selenite.

Targeting ferroptosis, a type of cell death elicited by Fe2+ and lipid reactive oxygen species (L-ROS), provides a novel strategy for cancer therapy. Selenium has the potential to treat cancers by acting as a pro-oxidative agent, thus leading to cancer cell death. Here, we found that the triple negative breast cancer (TNBC) MDA-MB-231 cells were more sensitive to ferroptosis induced by sodium selenite (Na2SeO3) than that of non-TNBC MCF-7 cells. Na2SeO3 significantly elevated the level of L-ROS, MDA and Fe2+, decreased the content of GSH and the enzyme activity of GPx, disrupted the expression of ferroptosis related proteins such as GPx4 and FTH1, as well as compromised mitochondrial morphology in MDA-MB-231 cells. Moreover, ATM was activated by Na2SeO3 in MDA-MB-231 cells. Notably, Na2SeO3-induced ferroptosis was inhibited by ATM kinase inhibitor KU55933 or siATM, suggesting that Na2SeO3-induced ferroptosis was mediated by ATM protein in MDA-MB-231 cells. Our findings suggest a therapeutic strategy by ferroptosis against TNBC and deepened our understanding of ATM function.

Artemisinins: Promising drug candidates for the treatment of autoimmune diseases.

Autoimmune diseases are characterized by the immune system's attack on one's own tissues which are highly diverse and diseases differ in severity, causing damage in virtually all human systems including connective tissue (e.g., rheumatoid arthritis), neurological system (e.g., multiple sclerosis) and digestive system (e.g., inflammatory bowel disease). Historically, treatments normally include pain-killing medication, anti-inflammatory drugs, corticosteroids, and immunosuppressant drugs. However, given the above characteristics, treatment of autoimmune diseases has always been a challenge. Artemisinin is a natural sesquiterpene lactone initially extracted and separated from Chinese medicine Artemisia annua L., which has a long history of curing malaria. Artemisinin's derivatives such as artesunate, dihydroartemisinin, artemether, artemisitene, and so forth, are a family of artemisinins with antimalarial activity. Over the past decades, accumulating evidence have indicated the promising therapeutic potential of artemisinins in autoimmune diseases. Herein, we systematically summarized the research regarding the immunoregulatory properties of artemisinins including artemisinin and its derivatives, discussing their potential therapeutic viability toward major autoimmune diseases and the underlying mechanisms. This review will provide new directions for basic research and clinical translational medicine of artemisinins.

The mechanical journey of primordial germ cells.

Primordial germ cells (PGCs) are the earliest progenitors of germline cells of the gonads in animals. The tissues that arise from primordial germ cells give rise to the male as well as female gametes and are thus responsible for transmitting genetic information to subsequent generations. Their development from single cells to fully formed tissues has thus been of great importance. In most higher animals, PGCs are initially specified at a site away from the gonads. They then migrate across multiple tissue contexts to reach a mesodermal mass of cells called the genital ridge, where they associate with somatic cells to form the sex-specific reproductive organs. This migratory behavior has been studied extensively to identify the various tissues PGCs interact with and how this might affect their development. A crucial point overlooked by classical studies has been the physical environment experienced by PGCs as they migrate and the mechanical challenges they might encounter. It has long been understood that migrating cells can sense and adapt to physical forces around them via a variety of mechanisms. Studies have also shown that these mechanical signals can guide stem cell fate. In this review, we summarize the mechanical microenvironment of migrating PGCs in different organisms. We describe how cells can adapt to this environment and how this adaptation can influence cell fate. We propose that mechanical signals play a crucial role in normal development of the germline and shed light on this unexplored area of developmental biology.

NAD+ supplementation prevents STING-induced senescence in CD8+ T cells by improving mitochondrial homeostasis.

Understanding the connection between senescence phenotypes and mitochondrial dysfunction is crucial in aging and premature aging diseases. Loss of mitochondrial function leads to a decline in T cell function, which plays a significant role in this process. However, more research is required to determine if improving mitochondrial homeostasis alleviates senescence phenotypes. Our research has shown an association between NAD+ and senescent T cells through the cGAS-STING pathway, which can lead to an inflammatory phenotype. Further research is needed to fully understand the role of NAD+ in T-cell aging and how it can be utilized to improve mitochondrial homeostasis and alleviate senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in senescent T cells and tumor-bearing mice. Senescence is mediated by a stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD+ levels with nicotinamide mononucleotide (NMN) prevents senescence and SASP by promoting mitophagy. NMN treatment also suppresses senescence and neuroinflammation and improves the survival cycle of mice. Encouraging mitophagy may be a useful strategy to prevent CD8+ T cells from senescence due to mitochondrial dysfunction. Additionally, supplementing with NMN to increase NAD+ levels could enhance survival rates in mice while also reducing senescence and inflammation, and enhancing mitophagy as a potential therapeutic intervention.

Multilocus Distance-Regulated Sensor Array for Recognition of Polyphenols via Machine Learning and Indicator Displacement Assay.

Developing new strategies to construct sensor arrays that can effectively distinguish multiple natural components with similar structures in mixtures is an exceptionally challenging task. Here, we propose a new multilocus distance-modulated indicator displacement assay (IDA) strategy for constructing a sensor array, incorporating machine learning optimization to identify polyphenols. An 8-element array, comprising two fluorophores and their six dynamic covalent complexes (C1-C6) formed by pairing two fluorophores with three distinct distance-regulated quenchers, has been constructed. Polyphenols with diverse spatial arrangements and combinatorial forms compete with the fluorophores by forming pseudocycles with quenchers within the complexes, leading to varying degrees of fluorescence recovery. The array accurately and effectively distinguished four tea polyphenols and 16 tea varieties, thereby demonstrating the broad applicability of the multilocus distance-modulated IDA array in detecting polyhydroxy foods and natural medicines.

Single extracellular vesicle research: From cell population to a single cell.

Extracellular vesicles (EVs) are secreted by cells with a membrane structure and complex components such as DNA, RNA and proteins. These biomolecules play an important role in cell communication, cell proliferation, cell migration, vascularization, immune response and other physiological and pathological processes. Most current research on EVs focused on populations of EVs. Heterogeneity of EVs is neglected. Considering the heterogeneity of single EVs may offer critical molecular insights into cell-cell interactions, it is necessary to enhance our understanding about molecular characteristics from EVs derived from cell population to a single EV of derived from a single cell. This transformation is expected to provide a new insight into the understanding of cellular biology and the accurate description of the law of disease progress. In this article, we review the current research progress of single EV analysis technology for single EVs derived from cell population (SECP) and discuss its main applications in biological and clinical medicine research. After that, we propose the development direction, main difficulties and application prospect of single EV analysis technology for single EVs derived from single cells (SESC) according to our own research work, to provide new perspectives for the field of EV research.

Conductive MXene/Polymer Composites for Transparent Flexible Supercapacitors.

Transparent flexible energy storage devices are limited by the trade-off among flexibility, transparency, and charge storage capability of their electrode materials. Conductive polymers are intrinsically flexible, but limited by small capacitance. Pseudocapacitive MXene provides high capacitance, yet their opaque and brittle nature hinders their flexibility and transparency. Herein, the development of synergistically interacting conductive polymer Ti3C2Tx MXene/PEDOT:PSS composites is reported for transparent flexible all-solid-state supercapacitors, with an outstanding areal capacitance of 3.1 mF cm-2, a high optical transparency of 61.6%, and excellent flexibility and durability. The high capacitance and high transparency of the devices stem from the uniform and thorough blending of PEDOT:PSS and Ti3C2Tx, which is associated with the formation of O─H…O H-bonds in the composites. The conductive MXene/polymer composite electrodes demonstrate a rational means to achieve high-capacity, transparent and flexible supercapacitors in an easy and scalable manner.

Decoupling the roles of Ni and Co in anionic redox activity of Li-rich NMC cathodes.

Li[LixNiyMnzCo1-x-y-z]O2 (lithium-rich NMCs) are benchmark cathode materials receiving considerable attention due to the abnormally high capacities resulting from their anionic redox chemistry. Although their anionic redox mechanisms have been much investigated, the roles of cationic redox processes remain underexplored, hindering further performance improvement. Here we decoupled the effects of nickel and cobalt in lithium-rich NMCs via a comprehensive study of two typical compounds, Li1.2Ni0.2Mn0.6O2 and Li1.2Co0.4Mn0.4O2. We discovered that both Ni3+/4+ and Co4+, generated during cationic redox processes, are actually intermediate species for triggering oxygen redox through a ligand-to-metal charge-transfer process. However, cobalt is better than nickel in mediating the kinetics of ligand-to-metal charge transfer by favouring more transition metal migration, leading to less cationic redox but more oxygen redox, more O2 release, poorer cycling performance and more severe voltage decay. Our work highlights a compositional optimization pathway for lithium-rich NMCs by deviating from using cobalt to using nickel, providing valuable guidelines for future high-capacity cathode design.

Eco-Friendly Sustainable and Responsive High-Performance Benzotriazole-Metal Organic Frameworks/Silica Composite Coating with Active/Passive Corrosion Protection on Copper.

Coatings with only passive protection cannot offer long-term anticorrosion on metals. Eco-friendly sustainable and responsive coating for active/passive corrosion protection is desirable to extend the service life of metals. Here, benzotriazole (BTA)-metal organic frameworks (Cu-MOFs, UiO-66) were embedded in silica (SiO2) coating by one-step electrodeposition on copper. Combined with passive capability of MOFs and active protection of BTA inhibitor, the composite coating (BTA-MOF/SiO2) exhibited high and stable corrosion resistance, confirmed by microstructure characterizations and electrochemical tests. As a result, the as-prepared composite coating exhibited superhydrophobicity with a water contact angle of 154.2°. With loading of BTA-MOF in SiO2 coating, the impedance modulus at 0.01 Hz increased by ∼10-fold and the corrosion current density decreased to 3.472 × 10-9 A·cm-2. Immersion and salt spray tests confirmed the long-term protection of the composite coating. The responsive release of BTA inhibitor endows the coating with a responsively anticorrosive behavior. The active-passive ability makes the coating a good candidate for protection on metals used in highly salty environments.

A modified nucleoside O6-methyl-2'-deoxyguanosine-5'-triphosphate exhibits anti-glioblastoma activity in a caspase-independent manner.

Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties through the activation of AIF-mediated apoptosis and the parthanatos pathway. In vivo studies using U251 and Ln229 cell xenografts supported the robust tumor-inhibitory capacity of O6-methyl-dGTP. In an orthotopic transplantation model with U87MG cells, O6-methyl-dGTP showcased marginally superior tumor-suppressive activity compared to TMZ. In summary, our research, for the first time, underscores the potential of O6-methyl-dGTP as an effective candidate against GBM, laying a robust scientific groundwork for its potential clinical adoption in GBM treatment regimens.

Protocol for Evaluating the Efficacy and Safety of Radiotherapy for Prostate and Oligometastatic Lesions in Patients With Low-Burden Sensitive Oligometastatic Prostate Cancer: An Open, Exploratory Pilot Clinical Trial.

INTRODUCTION: The existing large prospective study demonstrates the benefits of primary radiotherapy in patients with low-volume oligometastatic prostate cancer (OMPC), and there is additional evidence of the benefits of local metastasis-directed therapy (MDT) for metastatic lesions. However, there are no results from a prospective study to demonstrate the efficacy of radiotherapy for prostate and oligometastases. Therefore, the aim of the protocol is to illustrate the efficacy of radiotherapy for prostate and oligometastatic lesions in patients with low-volume de novo hormone-sensitive OMPC. METHODS AND ANALYSIS: This study involves a prospective, single-center, limited-sample, single-arm exploration of radiotherapy for prostate and oligometastatic lesions in patients diagnosed with low-volume hormone-sensitive OMPC. Eligible participants undergo thorough assessments and treatment involving endocrine therapy alongside radiation targeting metastatic lesions and the pelvic region. The primary site is treated with volumetric modulated arc therapy (VMAT), while metastatic sites are treated with either VMAT or stereotactic body radiation therapy (SBRT) depending on their location. All patients received radiation therapy for both the primary and metastatic lesions combined with endocrine therapy. Endocrine therapy with an antiandrogen (bicalutamide, for 4 weeks) androgen deprivation therapy combined with novel hormonal agents (acetate abiraterone) will be continued for 2 years. The primary objective is to evaluate progression-free survival-2 (PFS-2), while secondary endpoints include androgen deprivation therapy (ADT)-free survival, quality of life (QoL), overall survival, time to castration-resistant prostate cancer (CRPC), radiation-related complications, and endocrine therapy-related adverse events. ETHICS AND DISSEMINATION: Approval was obtained from the ethics committee of the First Affiliated Hospital of Naval Medical University (CHEC2023-220). This is a single-arm exploration pilot trial evaluating radiotherapy for prostate and oligometastatic lesions in patients with OMPC. It aims to disseminate its findings through peer-reviewed journals and relevant medical conferences, with the intention of publication and presentation at these events. TRIAL REGISTRATION NUMBERS: Clinicaltrials.gov identifier NCT06198387.

Efficient detection of Streptococcus pyogenes based on recombinase polymerase amplification and lateral flow strip.

PURPOSE: This article aims to establish a rapid visual method for the detection of Streptococcus pyogenes (GAS) based on recombinase polymerase amplification (RPA) and lateral flow strip (LFS). METHODS: Utilizing speB of GAS as a template, RPA primers were designed, and basic RPA reactions were performed. To reduce the formation of primer dimers, base mismatch was introduced into primers. The probe was designed according to the forward primer, and the RPA-LFS system was established. According to the color results of the reaction system, the optimum reaction temperature and time were determined. Thirteen common clinical standard strains and 14 clinical samples of GAS were used to detect the selectivity of this method. The detection limit of this method was detected by using tenfold gradient dilution of GAS genome as template. One hundred fifty-six clinical samples were collected and compared with qPCR method and culture method. Kappa index and clinical application evaluation of the RPA-LFS were carried out. RESULTS: The enhanced RPA-LFS method demonstrates the ability to complete the amplification process within 6 min at 33 °C. This method exhibits a high analytic sensitivity, with the lowest detection limit of 0.908 ng, and does not exhibit cross-reaction with other pathogenic bacteria. CONCLUSIONS: The utilization of RPA and LFS allows for efficient and rapid testing of GAS, thereby serving as a valuable method for point-of-care testing.

Short-Term PM2.5 Exposure and DNA Methylation Changes of Circadian Rhythm Genes: Evidence from Two Experimental Studies.

The circadian rhythm regulates many crucial physiological processes, impacting human aging and aging-related outcomes. Observational evidence links circadian rhythm disturbance to PM2.5 exposure, yet the underlying DNA methylation mechanisms remain unclear due to limited PM2.5-dominated experimental settings. Therefore, we investigated the associations between short-term PM2.5 exposure and DNA methylation changes of 1188 CpG candidates across circadian genes among 32 young adults in the FDU study, with the validation in 26 individuals from the PKU study. Further mediation analyses tested whether DNA methylation of circadian genes could mediate the influence of PM2.5 on aging measured by three epigenetic ages: DNAmGrimAge, DunedinPoAm, and the mortality risk score. We identified three CpG sites associated with personal PM2.5 exposure: cg01248361 (CSNK2A2), cg17728065 (RORA), and cg22513396 (PRKAG2). Acute effects of PM2.5 on the three loci could be mediated by several circulating biomarkers, including MDA and EGF, with up to ∼30% of mediated proportions. Three loci further showed varying potentials in mediating the aging acceleration effect of PM2.5. Locus cg17728065 is the key site exhibiting a robust mediating effect (7.54-12.52%) on PM2.5-induced aging acceleration. Our findings demonstrated that PM2.5, even short-term peaks, could leave imprints on human aging via inducing aberrant temporal fluctuation in circadian homeostasis captured by DNA methylation profiles.

Associations of environmental cadmium exposure with kidney damage: Exploring mediating DNA methylation sites in Chinese adults.

Environmental exposure is widely recognized as the primary sources of Cadmium (Cd) in the human body, and exposure to Cd is associated with kidney damage in adults. Nevertheless, the role of DNA methylation in Cd-induced kidney damage remains unclear. This study aimed to investigate the epigenome-wide association of environmental Cd-related DNA methylation changes with kidney damage. We included 300 non-smoking adults from the China in 2019. DNA methylation profiles were measured with Illumina Infinium MethylationEPIC BeadChip array. Linear mixed-effect model was employed to estimate the effects of urinary Cd with DNA methylation. Differentially methylated positions (DMPs) associated with urinary Cd were then tested for the association with kidney damage indicators. The mediation analysis was further applied to explore the potential DNA methylation based mediators. The prediction model was developed using a logistic regression model, and used 1000 bootstrap resampling for the internal validation. We identified 27 Cd-related DMPs mapped to 20 genes after the adjustment of false-discovery-rate for multiple testing among non-smoking adults. 17 DMPs were found to be associated with both urinary Cd and kidney damage, and 14 of these DMPs were newly identified within the Chinese. Mediation analysis revealed that DNA methylation of cg26907612 and cg16848624 mediated the Cd-related reduced kidney damage. In addition, ten variables were selected using the LASSO regression analysis and were utilized to develop the prediction model. It found that the nomogram model predicted the risk of kidney damage caused by environmental Cd with a corrected C-index of 0.779. Our findings revealed novel DMPs associated with both environmental Cd exposure and kidney damage among non-smoking adults, and developed an easy-to-use nomogram-illustrated model using these novel DMPs. These findings could provide a theoretical basis for formulating prevention and control strategies for kidney damage from the perspective of environmental pollution and epigenetic regulation.

Improving on mapping long-term surface water with a novel framework based on the Landsat imagery series.

Surface water plays a crucial role in the ecological environment and societal development. Remote sensing detection serves as a significant approach to understand the temporal and spatial change in surface water series (SWS) and to directly construct long-term SWS. Limited by various factors such as cloud, cloud shadow, and problematic satellite sensor monitoring, the existent surface water mapping datasets might be short and incomplete due to losing raw information on certain dates. Improved algorithms are desired to increase the completeness and quality of SWS datasets. The present study proposes an automated framework to detect SWS, based on the Google Earth Engine and Landsat satellite imagery. This framework incorporates implementing a raw image filtering algorithm to increase available images, thereby expanding the completeness. It improves OTSU thresholding by replacing anomaly thresholds with the median value, thus enhancing the accuracy of SWS datasets. Gaps caused by Landsat7 ETM + SLC-off are respired with the random forest algorithm and morphological operations. The results show that this novel framework effectively expands the long-term series of SWS for three surface water bodies with distinct geomorphological patterns. The evaluation of confusion matrices suggests the good performance of extracting surface water, with the overall accuracy ranging from 0.96 to 0.97, and user's accuracy between 0.96 and 0.98, producer's accuracy ranging from 0.83 to 0.89, and Matthews correlation coefficient ranging from 0.87 to 0.9 for several spectral water indices (NDWI, MNDWI, ANNDWI, and AWEI). Compared with the Global Reservoirs Surface Area Dynamics (GRSAD) dataset, our constructed datasets promote greater completeness of SWS datasets by 27.01%-91.89% for the selected water bodies. The proposed framework for detecting SWS shows good potential in enlarging and completing long-term global-scale SWS datasets, capable of supporting assessments of surface-water-related environmental management and disaster prevention.