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Endometrial cancer (EC) is a highly heterogeneous malignancy characterized by varied pathology and prognoses, and the heterogeneity of its cancer cells and the tumor microenvironment (TME) remains poorly understood. We conducted single-cell RNA sequencing (scRNA-seq) on 18 EC samples, encompassing various pathological types to delineate their specific unique transcriptional landscapes. Cancer cells from diverse pathological sources displayed distinct hallmarks labeled as immune-modulating, proliferation-modulating, and metabolism-modulating cancer cells in uterine clear cell carcinomas (UCCC), well-differentiated endometrioid endometrial carcinomas (EEC-I), and uterine serous carcinomas (USC), respectively. Cancer cells from the UCCC exhibited the greatest heterogeneity. We also identified potential effective drugs and confirmed their effectiveness using patient-derived EC organoids for each pathological group. Regarding the TME, we observed that prognostically favorable CD8+ Tcyto and NK cells were prominent in normal endometrium, whereas CD4+ Treg, CD4+ Tex, and CD8+ Tex cells dominated the tumors. CXCL3+ macrophages associated with M2 signature and angiogenesis were exclusively found in tumors. Prognostically relevant epithelium-specific cancer-associated fibroblasts (eCAFs) and SOD2+ inflammatory CAFs (iCAFs) predominated in EEC-I and UCCC groups, respectively. We also validated the oncogenic effects of SOD2+ iCAFs in vitro. Our comprehensive study has yielded deeper insights into the pathogenesis of EC, potentially facilitating personalized treatments for its varied pathological types.
Subject(s)
Endometrial Neoplasms , Single-Cell Analysis , Transcriptome , Tumor Microenvironment , Humans , Female , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/metabolism , Transcriptome/genetics , Gene Expression Regulation, NeoplasticABSTRACT
BACKGROUND: Irritable bowel syndrome (IBS) significantly impacts individuals due to its prevalence and negative effect on quality of life. Current genome-wide association studies (GWAS) have only identified a small number of crucial single nucleotide polymorphisms (SNPs), not fully elucidating IBS's pathogenesis. OBJECTIVE: To identify genomic loci at which common genetic variation influence IBS susceptibility. METHODS: Combining independent cohorts that in total comprise 65,840 cases of IBS and 788,652 controls, we performed a meta-analysis of genome-wide association studies (GWAS) of IBS. We also carried out gene mapping and pathway enrichment to gain insights into the underlying genes and pathways through which the associated loci contribute to disease susceptibility. Furthermore, we performed transcriptome analysis to deepen our understanding. IBS risk models were developed by combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. We detect the phenotype association for IBS utilizing PRS-based phenome-wide association (PheWAS) analyses, linkage disequilibrium score regression, and Mendelian randomization. RESULTS: The GWAS meta-analysis identified 10 IBS risk loci, seven of which were novel (rs12755507, rs34209273, rs34365748, rs67427799, rs2587363, rs13321176, rs1546559). Multiple methods identified nine promising IBS candidate gene (PRRC2A, COP1, CADM2, LRP1B, SUGT1, MED12L, P2RY14, PHF2, SHISA6) at 10 GWAS loci. Transcriptome validation also revealed differential expression of these genes. Phenome-wide associations between PRS-IBS and nine traits (neuroticism, diaphragmatic hernia, asthma, diverticulosis, cholelithiasis, depression, insomnia, COPD, and BMI) were identified. The six diseases (asthma, diaphragmatic hernia, diverticulosis, insomnia major depressive disorder and neuroticism) were found to show genetic association with IBS and only major depressive disorder and neuroticism were found to show causality with IBS. CONCLUSION: We identified seven novel risk loci for IBS and highlight the substantial influence on genetic risk harboured. Our findings offer novel insights into aetiology and phenotypic association of IBS and lay the foundation for therapeutic targets and interventional strategies.
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A novel, to the best of our knowledge, approach to generate frequency-tunable microwave sources with low-phase-noise based on a Brillouin laser frequency comb is proposed and experimentally demonstrated. The Brillouin laser frequency comb is generated by combining stimulated Brillouin scattering, frequency shifting optical injection locking, modulation sideband optical injection locking (MSOIL), and four-wave mixing effects. By beating the generated comb lines, the microwave is generated with an extremely low-level phase noise of -120 dBc/Hz at a 10-kHz offset. The frequency of the microwave signal can be finely tuned in steps of a Brillouin cavity mode spacing (i.e., 2â MHz) and coarsely adjusted to integer times the applied RF signal frequency in the MSOIL unit. Remarkably, the phase noise of the microwave source can be kept at almost the same low level during the whole tuning process over the frequency range of 30-75â GHz. The proposed tunable low-phase-noise microwave generation approach has great potential applications in communications, radars, and metrology.
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Addressing the sluggish kinetics in the alkaline hydrogen oxidation reaction (HOR) is a pivotal yet challenging step toward the commercialization of anion-exchange membrane fuel cells (AEMFCs). Here, we have successfully immobilized indium (In) atoms in an orderly fashion into platinum (Pt) nanoparticles supported by reduced graphene oxide (denoted as O-Pt3In/rGO), significantly enhancing alkaline HOR kinetics. We have revealed that the ordered atomic matrix enables uniform and optimized hydrogen binding energy (HBE), hydroxyl binding energy (OHBE), and carbon monoxide binding energy (COBE) across the catalyst. With a mass activity of 2.3066 A mg-1 at an overpotential of 50 mV, over 10 times greater than that of Pt/C, the catalyst also demonstrates admirable CO resistance and stability. Importantly, the AEMFC implementing this catalyst as the anode catalyst has achieved an impressive power output compared to Pt/C. This work not only highlights the significance of constructing ordered oxophilic sites for alkaline HOR but also sheds light on the design of well-structured catalysts for energy conversion.
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OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.
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Isolated from intertidal sediment of the Yellow Sea, China, Bremerella sp. P1 putatively represents a novel species within the genus Bremerella of the family Pirellulaceae in the phylum Planctomycetota. The complete genome of strain P1 comprises a single circular chromosome with a size of 6,955,728 bp and a GC content of 55.26%. The genome contains 5772 protein-coding genes, 80 tRNA and 6 rRNA genes. A total of 147 CAZymes and 128 sulfatases have been identified from the genome of strain P1, indicating that the strain has the capability to degrade a wide range of polysaccharides. Moreover, a gene cluster related to bacterial microcompartments (BMCs) formation containing genes encoding the shell proteins and related enzymes to metabolize fucose or rhamnose is also found in the genome of strain P1. The genome of strain P1 represents the second complete one in the genus Bremerella, expanding the understanding of the physiological and metabolic characteristics, interspecies diversity, and ecological functions of the genus.
Subject(s)
Genome, Bacterial , Polysaccharides , Polysaccharides/metabolism , Whole Genome Sequencing , ChinaABSTRACT
Background & Aims: Inflammatory bowel disease (IBD) is commonly associated with extraintestinal complications, including autoimmune liver disease. The co-occurrence of IBD and primary biliary cholangitis (PBC) has been increasingly observed, but the underlying relationship between these conditions remains unclear. Methods: Using summary statistics from genome-wide association studies (GWAS), we investigated the causal effects between PBC and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). We also analyzed the shared genetic architecture between IBD and PBC using data from GWAS, bulk-tissue RNA sequencing, and single cell RNA sequencing, and explored potential functional genes. Result: There was a strong positive genetic correlation between PBC and IBD (linkage disequilibrium score regression: rg = 0.2249, p = 3.38 × 10-5). Cross-trait analysis yielded 10 shared-risk single nucleotide polymorphisms (SNPs), as well as nine novel SNPs, which were associated with both traits. Using Mendelian randomization, a stable causal effect was established of PBC on IBD. Genetically predicted PBC was found to have a risk effect on IBD (1.105; 95% CI: 1.058-1.15; p = 1.16 × 10-10), but not vice versa. Shared tissue-specific heritability enrichment was identified for PBC and IBD (including CD and UC) in lung, spleen, and whole-blood samples. Furthermore, shared enrichment was observed of specific cell types (T cells, B cells, and natural killer cells) and their subtypes. Nine functional genes were identified based on summary statistics-based Mendelian randomization. Conclusions: This study detected shared genetic architecture between IBD and PBC and demonstrated a stable causal relationship of genetically predicted PBC on the risk of IBD. These findings shed light on the biological basis of comorbidity between IBD and PBC, and have important implications for intervention and treatment targets of these two diseases simultaneously. Impact and Implications: The discovery of novel shared single nucleotide polymorphisms (SNPs) and functional genes provides insights into the common targets between inflammatory bowel disease (IBD) and primary biliary cholangitis (PBC), serving as a basis for new drug development and contributing to the study of disease pathogenesis. Additionally, the established significant causality and genetic correlation underscore the importance of clinical intervention in preventing the comorbidity of IBD and PBC. The enrichment of SNP heritability in specific tissues and cell types reveals the role of immune factors in the potential disease mechanisms shared between IBD and PBC. This stimulates further research on potential interventions and could lead to the development of new targets for immune-based therapies.
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A miniature laser with linear polarization is a long sought-after component of photonic integrated circuits. In particular, for multiwavelength polarization lasers, it supports simultaneous access to multiple, widely varying laser wavelengths in a small spatial region, which is of great significance for advancing applications such as optical computing, optical storage, and optical sensing. However, there is a trade-off between the size of small-scale lasers and laser performance, and multiwavelength co-gain of laser media and multicavity micromachining in the process of laser miniaturization remain as significant challenges. Herein, room-temperature linearly polarized multiwavelength lasers in the visible and near-infrared wavelength ranges are demonstrated, by fabricating random cavities scattered with silica in an Er-doped Cs2Ag0.4Na0.6In0.98Bi0.02Cl6 double-perovskite quantum dots gain membrane. By regulating the local symmetry and enabling effective energy transfer in nanocrystals, multiwavelength lasers with ultralow thresholds are achieved at room temperature. The maximum degree of polarization reaches 0.89. With their advantages in terms of miniaturization, ultralow power consumption, and adaptability for integration, these lasers offer a prospective light source for future photonic integrated circuits aimed at high-capacity optical applications.
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We proposed that the pharynx, as a common organ of the respiratory and digestive tracts, may be a respiratory and digestive tract cross cryptic transmission pathway for 2019-nCoV infection from the nasal cavities to the pharynx and lung, then to nasal cavities by aerosol (respiratory route) to the pharynx and the gastrointestinal tract, then to the oral cavity by feces (fecal-oral route) and to pharynx, lungs, or gastrointestinal tract.
Subject(s)
COVID-19 , Pharynx , SARS-CoV-2 , Humans , COVID-19/transmission , Pharynx/virology , Cross Infection/transmission , Gastrointestinal Tract/virology , Feces/virology , Feces/microbiology , Respiratory Tract Infections/transmission , Respiratory Tract Infections/virologyABSTRACT
Ferromagnets with a Curie temperature surpassing room temperature (RT) are highly sought after for advancing planar spintronics. The ultrathin CrTe2 is proposed as a promising two-dimensional (2D) ferromagnet with a Curie temperature above 300 K. However, its single-layer film is highly susceptible to specific external perturbations, leading to variable magnetic features depending on the environment. The magnetic ordering of single-layer CrTe2 remains a topic of debate, and experimental confirmation of ferromagnetic order at RT is still pending. In our study, we utilized molecular beam epitaxy to create a single-layer 1T-CrTe2 on bilayer graphene, demonstrating ferromagnetism above 300 K with in-plane magnetization through superconducting quantum interference devices (SQUID) measurements. Our density functional theory (DFT) calculations suggest that the ferromagnetic properties stem from epitaxial strain, which increases the distance between adjacent Cr atoms within the layer by about 1.6% and enhances the Cr-Te-Cr angle by approximately 1.6°. Due to its interaction with the graphene substrate, the magnetic moment transitions from an out-of-plane to an in-plane orientation, while electronic doping exceeds 1.5 e/u.c. Combining DFT calculations with in situ scanning tunneling microscopy (STM) characterizations allowed us to determine the configuration of the CrTe2 single layer on graphene. This discovery presents the first experimental proof of ferromagnetic order in single-layer CrTe2 with a Curie temperature above RT, laying the groundwork for future applications of CrTe2 single-layer-based spintronic devices.
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The application of molecularly imprinted material (MIM) is widely employed as a material for removing phenolic pollutants from the water environment, owing to its exceptional capacity for selective adsorption and high sensitivity. In this paper, the preparation principle, bonding types, and preparation methods of MIM have been comprehensively introduced. Meanwhile, according to the binding type of MIM with phenolic pollutants, three categories of hydroxyl bonding, hydroxyl carboxyl bonding, and hydroxyl nitro bonding were carried out to explain its application to phenolic pollutants. Strategies for addressing the challenges of selective instability, high regeneration costs, and template leakage in MIM applications were summarized. These strategies encompassed the introduction of superior carriers, enhancements in preparation processes, and the utilization of molecular dynamics simulation-assisted technology. Finally, the prospects in the three aspects of material preparation, process coupling, and recycling. In summary, this paper has demonstrated the potential of utilizing MIM for the selective treatment of phenolic pollutants from the water environment.
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Objective: The growing evidence shows that parathyroid hormone (PTH) may affect glucose metabolism. However, the relationship between them is still controversial among diabetic patients. The current study aimed to investigate the relationship between PTH and glucose metabolism in the patients with newly diagnosed type 2 diabetes (T2D). Methods: A total of 532 participants, including 387 patients with newly diagnosed T2D and 145 healthy controls, were recruited in the present study. PTH and metabolic parameters were measured in all participants. Results: The PTH levels were significantly lower in the newly diagnosed T2D patients compared with the control group (35.10 (25.90, 47.20) vs. 47.15 (35.83, 58.65) pg/ml, P < 0.001). The T2D patients with a higher glycated hemoglobin (HbA1c) tertile had lower PTH levels than the patients with a lower HbA1c tertile (32.90 (24.85, 41.40) vs. 37.50 (26.10, 54.55) pg/ml, P < 0.001). Spearman correlation analysis showed that PTH was positively correlated with the body mass index (BMI), fasting insulin (FINS), homeostasis model assessment of ß-cell function (HOMA-ß), and homeostasis model assessment of insulin resistance (HOMA-IR) and negatively correlated with HbA1c, blood calcium (Ca), blood phosphorus (P), and 25-hydroxyvitamin D3 (25-OH-D3). Multiple linear regression analysis demonstrated that PTH was significantly associated with HbA1c (ß = -1.475, P=0.003) and HOMA-ß (ß = 0.090, P=0.001) after adjusting for age, sex, BMI, season, 25-OH-D3, Ca, and P. Conclusion: PTH was negatively correlated with HbA1c in the newly diagnosed T2D patients. Our results suggested that the PTH level within the reference range is related to islet ß-cell function and hyperglycemia.
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KCNH2 (Potassium Voltage-Gated Channel Subfamily H Member) encodes a voltage-activated potassium channel role as rapidly activating-delayed rectifier potassium channel that plays an essential role in the final repolarization of the ventricular action potential. Mutations in this gene can cause long QT syndrome and short QT syndrome. Transcript variants encoding distinct isoforms were also identified. In this study, we generated induced pluripotent stem cells (iPSC) from a healthy individual by electroporation of peripheral blood mononuclear cells and generated a KCNH2 heterozygous knockout human iPSC line via CRISPR/Cas9 gene editing. The resulting iPSCs had a normal karyotype, were free of genomically integrated epitomal plasmids, expressed pluripotency markers, and maintained trilineage differentiation potential.
Subject(s)
ERG1 Potassium Channel , Heterozygote , Induced Pluripotent Stem Cells , Long QT Syndrome , Induced Pluripotent Stem Cells/metabolism , Humans , ERG1 Potassium Channel/genetics , ERG1 Potassium Channel/metabolism , Long QT Syndrome/genetics , Long QT Syndrome/metabolism , Long QT Syndrome/pathology , Cell Line , CRISPR-Cas Systems , Gene Knockout Techniques , Cell Differentiation , Gene Editing , Arrhythmias, CardiacABSTRACT
The pit mud in the Baijiu fermentation cellar is an abundant microbial resource that is closely related to the quality of baijiu. However, many naturally existing species might be in a viable but nonculturable (VBNC) state, posing challenges to the isolation and application of functional species. Herein, a previously isolated strain from baijiu mash, Umezawaea beigongshangensis, was found to contain the rpf gene that encodes resuscitation promotion factor (Rpf). Therefore, the gene was cloned and heterologously expressed, and the recombinant protein (Ub-Rpf 2) was purified. Ub-Rpf 2 was found to significantly promote the growth of resuscitated VBNC state Corynebacterium beijingensis and Sphingomonas beigongshangensis. To determine the resuscitation effect of Ub-Rpf 2 on real ecological samples, the protein was supplemented in pit mud for enrichment culture. Results revealed that specific families and genera were enriched in abundance upon Ub-Rpf 2 incubation, including a new family of Symbiobacteraceae and culturable Symbiobacterium genus. Furthermore, 14 species belonging to 12 genera were obtained in Ub-Rpf 2 treated samples, including a suspected novel species. This study lays a foundation for applying Rpf from U. beigongshangensis to exploit microbial resources in baijiu pit mud.
Subject(s)
Actinomycetales , Lactobacillales , Bacteria/genetics , Actinomycetales/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Fermentation , Lactobacillales/metabolismABSTRACT
Beneficial bacteria remain largely unexplored. Lacking systematic methods, understanding probiotic community traits becomes challenging, leading to various conclusions about their probiotic effects among different publications. We developed language model-based metaProbiotics to rapidly detect probiotic bins from metagenomes, demonstrating superior performance in simulated benchmark datasets. Testing on gut metagenomes from probiotic-treated individuals, it revealed the probioticity of intervention strains-derived bins and other probiotic-associated bins beyond the training data, such as a plasmid-like bin. Analyses of these bins revealed various probiotic mechanisms and bai operon as probiotic Ruminococcaceae's potential marker. In different health-disease cohorts, these bins were more common in healthy individuals, signifying their probiotic role, but relevant health predictions based on the abundance profiles of these bins faced cross-disease challenges. To better understand the heterogeneous nature of probiotics, we used metaProbiotics to construct a comprehensive probiotic genome set from global gut metagenomic data. Module analysis of this set shows that diseased individuals often lack certain probiotic gene modules, with significant variation of the missing modules across different diseases. Additionally, different gene modules on the same probiotic have heterogeneous effects on various diseases. We thus believe that gene function integrity of the probiotic community is more crucial in maintaining gut homeostasis than merely increasing specific gene abundance, and adding probiotics indiscriminately might not boost health. We expect that the innovative language model-based metaProbiotics tool will promote novel probiotic discovery using large-scale metagenomic data and facilitate systematic research on bacterial probiotic effects. The metaProbiotics program can be freely downloaded at https://github.com/zhenchengfang/metaProbiotics.
Subject(s)
Metagenome , Probiotics , Humans , Algorithms , Metagenomics/methods , Bacteria/genetics , LanguageABSTRACT
Despite the differences in disease outcomes and pathological features between cervical squamous cell carcinoma (CSCC) and adenocarcinoma (ADC), the molecular characteristics in immune heterogeneity of the tumor microenvironment remain unclear. Here, we explored the immune landscape and heterogeneity between CSCC and ADC. Gene expression and clinical characteristics of cervical carcinoma from The Cancer Genome Atlas (TCGA) were downloaded. Differentially expressed genes (DEGs), immune cell infiltration, and pathway enrichment analyses were used to explore the immune landscape and heterogeneity between CSCC and ADC. Furthermore, distinct immune signatures between CSCC and ADC were validated based on clinical samples. In total, 4,132 upregulated DEGs and 2,307 down-regulated DEGs were identified between CSCC and ADC, with enrichments in immune related-pathways in CSCC. In addition, 54 hub DEGs correlated with patients' prognosis and immunocytes infiltration were identified. The CSCC patients had a higher ImmuneScore and more abundant immunocytes infiltration compared to ADC patients, as validated by immunohistochemistry (IHC) and multicolor immunofluorescence (mIF) analyses of collected samples. Furthermore, CSCC displayed higher inhibitory immune checkpoints expression, tumor mutation burden (TMB), and microsatellite instability (MSI) compared to ADC, which indicated CSCC patients were more likely to benefit from immunotherapy. In summary, our results revealed the huge immune heterogeneity between CSCC and ADC, and provided guidance for immunotherapy selection for different pathological types of cervical cancer.
Subject(s)
Adenocarcinoma , Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/pathology , Carcinoma, Squamous Cell/metabolism , Prognosis , Adenocarcinoma/genetics , Tumor Microenvironment/geneticsABSTRACT
BACKGROUND: Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. METHODS: A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. RESULTS: Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. CONCLUSION: This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells.
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Water contamination irritated by Cd(II) brings about severe damage to the ecosystem and to human health. The decontamination of Cd(II) by the adsorption method is a promising technology. Here, we construct aminomethylpyridine-functionalized polyamidoamine (PAMAM) dendrimer/apple residue biosorbents (AP-G1.0-AMP and AP-G2.0-AMP) for adsorbing Cd(II) from aqueous solution. The adsorption behaviors of the biosorbents for Cd(II) were comprehensively evaluated. The maximum adsorption capacities of AP-G1.0-AMP and AP-G2.0-AMP for Cd(II) are 1.40 and 1.44 mmol·g-1 at pH 6. The adsorption process for Cd(II) is swift and can reach equilibrium after 120 min. The film diffusion process dominates the adsorption kinetics, and a pseudo-second-order model is appropriate to depict this process. The uptake of Cd(II) can be promoted by increasing concentration and temperature. The adsorption isotherm follows the Langmuir model with a chemisorption mechanism. The biosorbents also display satisfied adsorption for Cd(II) in real aqueous media. The adsorption mechanism indicates that C-N, NâC, C-O, CONH, N-H, and O-H groups participate in the adsorption for Cd(II). The biosorbents display a good regeneration property and can be reused with practical value. The as-prepared biosorbents show great potential for removing Cd(II) from water solutions with remarkable significance.
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Drought stress profoundly hampers both plant growth and crop yield. To combat this, plants have evolved intricate transcriptional regulation mechanisms as a pivotal strategy. Through a genetic screening with rice genome-scale mutagenesis pool under drought stress, we identified an APETALA2/Ethylene Responsive Factor, namely OsERF103, positively responds to drought tolerance in rice. Combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we pinpointed c. 1000 genes directly influenced by OsERF103. Further results revealed that OsERF103 interacts with Stress-responsive NAC1 (SNAC1), a positive regulator of drought tolerance in rice, to synergistically regulate the expression of key drought-related genes, such as OsbZIP23. Moreover, we found that OsERF103 recruits a Su(var)3-9,enhancer of zeste and trithorax-domain group protein 705, which encodes a histone 3 lysine 4 (H3K4)-specific methyltransferase to specifically affect the deposition of H3K4me3 at loci like OsbZIP23 and other genes linked to dehydration responses. Additionally, the natural alleles of OsERF103 are selected during the domestication of both indica and japonica rice varieties and exhibit significant geographic distribution. Collectively, our findings have unfurled a comprehensive mechanistic framework underlying the OsERF103-mediated cascade regulation of drought response. This discovery not only enhances our understanding of drought signaling but also presents a promising avenue for the genetic improvement of drought-tolerant rice cultivars.