Hazard evaluation of goaf based on DBO algorithm coupled with BP neural network.

China is rich in mineral resources, and problems of goaf formed in the process of resource exploitation are serious obstacle to the development of China's economic, so it is of great significance for the assessment and management of goafs. This paper introduces emerging dung beetle optimizer (DBO) algorithm and establishes DBO-BP (back-propagation) model, at the same time, it is compared with a series of heuristic algorithms coupled with BP neural network models: PSO (particle swarm optimization) - BP model, WOA (whale optimization algorithm) - BP model, and SSA (sparrow search algorithm) - BP model. Then they are applied to evaluate the hazard of goafs, the result shows that the DBO-BP model gets the highest train set accuracy, which is at least 2.7 % higher than other models, while the DBO-BP model obtains the highest test set accuracy, meanwhile its effectiveness and stability have also been proven. Finally we apply the established DBO-BP model to evaluate the hazard of the tungsten mine goaf of Yaogangshan in Hunan Province, and its excellent practicability was confirmed. This paper may provide a reference for the solution of nonlinear engineering problems.

Seasonal-Spatial Distribution Variations and Predictions of Loliolus beka and Loliolus uyii in the East China Sea Region: Implications from Climate Change Scenarios.

Global climate change profoundly impacts the East China Sea ecosystem and poses a major challenge to fishery management in this region. In addition, closely related species with low catches are often not distinguished in fishery production and relevant data are commonly merged in statistics and fishing logbooks, making it challenging to accurately predict their habitat distribution range. Here, merged fisheries-independent data of the closely related squid Loliolus beka (Sasaki, 1929) and Loliolus uyii (Wakiya and Ishikawa, 1921) were used to explore the construction and prediction performance of species distribution models. Data in 2018 to 2019 from the southern Yellow and East China Seas were used to identify the seasonal-spatial distribution characteristics of both species, revealing a boundary line at 29.00° N for L. uyii during the autumn, with the highest average individual weight occurring during the summer, with both larvae and juveniles occurring during the autumn. Thus, the life history of L. uyii can be divided into winter-spring nursery and summer-autumn spawning periods. L. beka showed a preference for inshore areas (15-60 m) during the summer and offshore areas (32.00-78.00 m) during the winter. High-value areas of both species included inshore areas of the southern Yellow and mid-East China Seas during the autumn, enlarging during the spring to include central areas of the survey region, before significantly decreasing during the summer. Therefore, this study provides both a novel perspective for modeling biological habitat distribution with limited data and a scientific basis for the adjustment of fishery resource management and conservation measures in the context of climate change.

Development and validation of a prognostic immunoinflammatory index for patients with gastric cancer.

BACKGROUND: Studies have demonstrated the influence of immunity and inflammation on the development of tumors. Although single biomarkers of immunity and inflammation have been shown to be clinically predictive, the use of biomarkers integrating both to predict prognosis in patients with gastric cancer remains to be investigated. AIM: To investigate the prognostic and clinical significance of inflammatory biomarkers and lymphocytes in patients undergoing surgical treatment for gastric cancer. METHODS: Univariate COX regression analysis was performed to identify potential prognostic factors for patients with gastric cancer undergoing surgical treatment. Least absolute shrinkage and selection operator-COX (LASSO-COX) regression analysis was performed to integrate these factors and formulate a new prognostic immunoinflammatory index (PII). The correlation between PII and clinical characteristics was statistically analyzed. Nomograms incorporating the PII score were devised and validated based on the time-dependent area under the curve and decision curve analysis. RESULTS: Patients exhibiting elevated neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune inflammatory index displayed inferior progression-free survival (PFS) and overall survival (OS). Conversely, low levels of CD3(+), CD3(+) CD8(+), CD4(+)CD8(+), and CD3(+)CD16(+)CD56(+) T lymphocytes were associated with improved PFS and OS, while high CD19(+) T lymphocyte levels were linked to worse PFS and OS. The PII score demonstrated associations with tumor characteristics (primary tumor site and tumor size), establishing itself as an independent prognostic factor for both PFS and OS. Time-dependent area under the curve and decision curve analysis affirmed the effectiveness of the PII-based nomogram as a robust prognostic predictive model. CONCLUSION: PII may be a reliable predictor of prognosis in patients with gastric cancer undergoing surgical treatment, and it offers insights into cancer-related immune-inflammatory responses, with potential significance in clinical practice.

Elevating PLK1 overcomes BETi resistance in prostate cancer via triggering BRD4 phosphorylation-dependent degradation in mitosis.

Bromodomain-containing protein 4 (BRD4) has emerged as a promising therapeutic target in prostate cancer (PCa). Understanding the mechanisms of BRD4 stability could enhance the clinical response to BRD4-targeted therapy. In this study, we report that BRD4 protein levels are significantly decreased during mitosis in a PLK1-dependent manner. Mechanistically, we show that BRD4 is primarily phosphorylated at T1186 by the CDK1/cyclin B complex, recruiting PLK1 to phosphorylate BRD4 at S24/S1100, which are recognized by the APC/CCdh1 complex for proteasome pathway degradation. We find that PLK1 overexpression lowers SPOP mutation-stabilized BRD4, consequently rendering PCa cells re-sensitized to BRD4 inhibitors. Intriguingly, we report that sequential treatment of docetaxel and JQ1 resulted in significant inhibition of PCa. Collectively, the results support that PLK1-phosphorylated BRD4 triggers its degradation at M phase. Sequential treatment of docetaxel and JQ1 overcomes BRD4 accumulation-associated bromodomain and extra-terminal inhibitor (BETi) resistance, which may shed light on the development of strategies to treat PCa.

Investigation on the environmental causes of tomato fruit cracking and its propagation prediction in greenhouse.

In this study, Provence tomato variety was chosen for investigating the environmental causes of tomato fruit cracking, cracks characteristics, and their propagation prediction in a greenhouse. Fruit bagging approach was used to alter the temperature and humidity and to create a microclimate around the fruit to induce fruit cracking for testing. Results showed that the fruit cracking rate increased when the environment temperature exceeded 30°C, and the difference between the highest and lowest temperature values in a day was greater than 20°C. The cracking rate was aggravated when the difference between the highest and lowest humidity values in a day was less than 20%. The proportions of top cracking, longitudinal cracking, ring cracking, radial cracking, and combined cracking were 5.4%, 16.1%, 28.3%, 26.8%, and 32.1%, respectively. The fruit shoulder was the most susceptible region to crack, followed by fruit belly and top regions, whereas longer cracks were observed in the fruit belly region indicating a higher propensity to crack propagation in that region. Finally, the measured data were used to validate an extended finite element method developed to effectively predict cracking susceptibility and propagation in tomato fruit with a relative error of 4.68%.

Intrinsic-strain-induced ferroelectric order and ultrafine nanodomains in SrTiO3.

Nano ferroelectrics holds the potential application promise in information storage, electro-mechanical transformation, and novel catalysts but encounters a huge challenge of size limitation and manufacture complexity on the creation of long-range ferroelectric ordering. Herein, as an incipient ferroelectric, nanosized SrTiO3 was indued with polarized ordering at room temperature from the nonpolar cubic structure, driven by the intrinsic three-dimensional (3D) tensile strain. The ferroelectric behavior can be confirmed by piezoelectric force microscopy and the ferroelectric TO1 soft mode was verified with the temperature stability to 500 K. Its structural origin comes from the off-center shift of Ti atom to oxygen octahedron and forms the ultrafine head-to-tail connected 90° nanodomains about 2 to 3 nm, resulting in an overall spontaneous polarization toward the short edges of nanoparticles. According to the density functional theory calculations and phase-field simulations, the 3D strain-related dipole displacement transformed from [001] to [111] and segmentation effect on the ferroelectric domain were further proved. The topological ferroelectric order induced by intrinsic 3D tensile strain shows a unique approach to get over the nanosized limitation in nanodevices and construct the strong strain-polarization coupling, paving the way for the design of high-performance and free-assembled ferroelectric devices.

Comparison of Brain Gene Expression Profiles Associated with Auto-Grooming Behavior between Apis cerana and Apis mellifera Infested by Varroa destructor.

The grooming behavior of honeybees serves as a crucial auto-protective mechanism against Varroa mite infestations. Compared to Apis mellifera, Apis cerana demonstrates more effective grooming behavior in removing Varroa mites from the bodies of infested bees. However, the underlying mechanisms regulating grooming behavior remain elusive. In this study, we evaluated the efficacy of the auto-grooming behavior between A. cerana and A. mellifera and employed RNA-sequencing technology to identify differentially expressed genes (DEGs) in bee brains with varying degrees of grooming behavior intensity. We observed that A. cerana exhibited a higher frequency of mite removal between day 5 and day 15 compared to A. mellifera, with day-9 bees showing the highest frequency of mite removal in A. cerana. RNA-sequencing results revealed the differential expression of the HTR2A and SLC17A8 genes in A. cerana and the CCKAR and TpnC47D genes in A. mellifera. Subsequent homology analysis identified the HTR2A gene and SLC17A8 gene of A. cerana as homologous to the HTR2A gene and SLC17A7 gene of A. mellifera. These DEGs are annotated in the neuroactive ligand-receptor interaction pathway, the glutamatergic synaptic pathway, and the calcium signaling pathway. Moreover, CCKAR, TpnC47D, HTR2A, and SLC17A7 may be closely related to the auto-grooming behavior of A. mellifera, conferring resistance against Varroa infestation. Our results further explain the relationship between honeybee grooming behavior and brain function at the molecular level and provide a reference basis for further studies of the mechanism of honeybee grooming behavior.

Switching Hydrophobic Interface with Ionic Valves for Reversible Zinc Batteries.

Developing hydrophobic interface has proven effective in addressing dendrite growth and side reactions during zinc (Zn) plating in aqueous Zn batteries. However, this solution inadvertently impedes the solvation of Zn2+ with H2O and subsequent ionic transport during Zn stripping, leading to insufficient reversibility. Herein, an adaptive hydrophobic interface that can be switched "on" and "off" by ionic valves to accommodate the varying demands for interfacial H2O during both the Zn plating and stripping processes, is proposed. This concept is validated using octyltrimethyl ammonium bromide (C8TAB) as the ionic valve, which can initiatively establish and remove a hydrophobic interface in response to distinct electric-field directions during Zn plating and stripping, respectively. Consequently, the Zn anode exhibits an extended cycling life of over 2500 h with a high Coulombic efficiency of ≈99.8%. The full cells also show impressive capacity retention of over 85% after 1 000 cycles at 5 A g-1. These findings provide a new insight into interface design for aqueous metal batteries.

Single-cell analysis identifies PLK1 as a driver of immunosuppressive tumor microenvironment in LUAD.

PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.

Irbesartan ameliorates diabetic kidney injury in db/db mice by restoring circadian rhythm and cell cycle.

Background and Objectives: Irbesartan has been widely used in the clinical treatment of diabetic kidney disease (DKD). However, the molecular mechanism of its delay of DKD disease progression has not been fully elucidated. The aim of the present study was to investigate the mechanism of irbesartan in the treatment of DKD. Materials and Methods: C57BL/KsJ db/db mice were randomly divided into the model group and irbesartan-treated group. After treatment with irbesartan for 12 weeks, the effects on blood glucose, body weight, 24-h urinary albumin, and renal injuries were evaluated. Microarray was used to determine the differentially expressed genes (DEGs) in the renal cortex of mice. |Log FC| <0.5 and false discovery rate (FDR) <0.25 were set as the screening criteria. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), protein-protein interaction (PPI) network and modules, and microRNA (miRNA)-DEGs network analysis were applied to analyze the DEGs. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of microarray. Results: The present study demonstrated irbesartan could significantly improve the renal function in db/db mice through decreasing 24-h urinary albumin and alleviating the pathological injury of kidney. Irbesartan may affect the expression of numerous kidney genes involved in circadian rhythm, cell cycle, micoRNAs in cancer, and PI3K-AKT signaling pathway. In the miRNA-DEGs network, miR-1970, miR-703, miR-466f, miR-5135, and miR-132-3p were the potential targets for irbesartan treatment. The validation test confirmed that key genes regulating circadian rhythm (Arntl, Per3, and Dbp) and cell cycle (Prc1, Ccna2, and Ccnb2) were restored in db/db mice on treatment with Irbesartan. Conclusion: Generally, irbesartan can effectively treat DKD by regulating the circadian rhythm and cell cycle. The DEGs and pathways identified in the study will provide new insights into the potential mechanisms of irbesartan in the treatment of DKD.

Analysis of fungal diversity in the gut feces of wild takin (Budorcas taxicolor).

Introduction: The composition of the intestinal microbiome correlates significantly with an animal's health status. Hence, this indicator is highly important and sensitive for protecting endangered animals. However, data regarding the fungal diversity of the wild Budorcas taxicolor (takin) gut remain scarce. Therefore, this study analyzes the fungal diversity, community structure, and pathogen composition in the feces of wild B. taxicolor. Methods: To ensure comprehensive data analyses, we collected 82 fecal samples from five geographical sites. Amplicon sequencing of the internal transcribed spacer (ITS) rRNA was used to assess fecal core microbiota and potential pathogens to determine whether the microflora composition is related to geographical location or diet. We further validated the ITS rRNA sequencing results via amplicon metagenomic sequencing and culturing of fecal fungi. Results and discussion: The fungal diversity in the feces of wild Budorcas taxicolor primarily comprised three phyla (99.69%): Ascomycota (82.19%), Fungi_unclassified (10.37%), and Basidiomycota (7.13%). At the genus level, the predominant fungi included Thelebolus (30.93%), Functional_unclassified (15.35%), and Ascomycota_unclassified (10.37%). Within these genera, certain strains exhibit pathogenic properties, such as Thelebolus, Cryptococcus, Trichosporon, Candida, Zopfiella, and Podospora. Collectively, this study offers valuable information for evaluating the health status of B. taxicolor and formulating protective strategies.

Irbesartan ameliorates diabetic kidney injury in db/db mice by restoring circadian rhythm and cell cycle.

Background and Objectives: Irbesartan has been widely used in the clinical treatment of diabetic kidney disease (DKD). However, the molecular mechanism of its delay of DKD disease progression has not been fully elucidated. The aim of the present study was to investigate the mechanism of irbesartan in the treatment of DKD. Materials and Methods: C57BL/KsJ db/db mice were randomly divided into the model group and irbesartan-treated group. After treatment with irbesartan for 12 weeks, the effects on blood glucose, body weight, 24-h urinary albumin, and renal injuries were evaluated. Microarray was used to determine the differentially expressed genes (DEGs) in the renal cortex of mice. |Log FC| <0.5 and false discovery rate (FDR) <0.25 were set as the screening criteria. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), protein-protein interaction (PPI) network and modules, and microRNA (miRNA)-DEGs network analysis were applied to analyze the DEGs. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of microarray. Results: The present study demonstrated irbesartan could significantly improve the renal function in db/db mice through decreasing 24-h urinary albumin and alleviating the pathological injury of kidney. Irbesartan may affect the expression of numerous kidney genes involved in circadian rhythm, cell cycle, micoRNAs in cancer, and PI3K-AKT signaling pathway. In the miRNA-DEGs network, miR-1970, miR-703, miR-466f, miR-5135, and miR-132-3p were the potential targets for irbesartan treatment. The validation test confirmed that key genes regulating circadian rhythm (Arntl, Per3, and Dbp) and cell cycle (Prc1, Ccna2, and Ccnb2) were restored in db/db mice on treatment with Irbesartan. Conclusion: Generally, irbesartan can effectively treat DKD by regulating the circadian rhythm and cell cycle. The DEGs and pathways identified in the study will provide new insights into the potential mechanisms of irbesartan in the treatment of DKD.

Untargeted metabolomics reveals that declined PE and PC in obesity may be associated with prostate hyperplasia.

BACKGROUND: Recent studies have shown that obesity may contribute to the pathogenesis of benign prostatic hyperplasia (BPH). However, the mechanism of this pathogenesis is not fully understood. METHODS: A prospective case-control study was conducted with 30 obese and 30 nonobese patients with BPH. Prostate tissues were collected and analyzed using ultra performance liquid chromatography ion mobility coupled with quadrupole time-of-flight mass spectrometry (UPLC-IMS-Q-TOF). RESULTS: A total of 17 differential metabolites (3 upregulated and 14 downregulated) were identified between the obese and nonobese patients with BPH. Topological pathway analysis indicated that glycerophospholipid (GP) metabolism was the most important metabolic pathway involved in BPH pathogenesis. Seven metabolites were enriched in the GP metabolic pathway. lysoPC (P16:0/0:0), PE (20:0/20:0), PE (24:1(15Z)/18:0), PC (24:1(15Z)/14:0), PC (15:0/24:0), PE (24:0/18:0), and PC (16:0/18:3(9Z,12Z,15Z)) were all significantly downregulated in the obesity group, and the area under the curve (AUC) of LysoPC (P-16:0/0/0:0) was 0.9922. The inclusion of the seven differential metabolites in a joint prediction model had an AUC of 0.9956. Thus, both LysoPC (P-16:0/0/0:0) alone and the joint prediction model demonstrated good predictive ability for obesity-induced BPH mechanisms. CONCLUSIONS: In conclusion, obese patients with BPH had a unique metabolic profile, and alterations in PE and PC in these patients be associated with the development and progression of BPH.

Gegen Qinlian Decoction Modulates Atherosclerosis and Lipid Metabolism Through Cellular Interplay and Signaling Pathways.

OBJECTIVE: The objective of this study is to investigate Gegen Qinlian decoction (GQD) effects on lipid metabolism and explore its mechanism for preventing and treating atherosclerosis. METHODS: An atherosclerotic rat model was established;, and after an 8-week high-fat diet, atherosclerosis and non-alcoholic fatty liver disease were assessed. Subsequently, GQD was administered at low and high doses. Histopathological aortic wall changes, hepatic lipid deposition, and blood lipid changes were evaluated. ELISA indicated the influence of TNF-α and IL-13, and Western blotting revealed MerTK, ABCA1, and LXR-α expression. A foam macrophage model was established, and Cell activity was detected by the MTT method. ELISA indicated the influence of PPAR-γ. The expression of ABCA1, ABCA7, ABCG1, GAS6, MerTK, SCARB1, LXR- α and LXR-ß mRNA were detected by qPCR， and Western blotting revealed MerTK and LXR-α expression. The impact of drug-containing serum of GQD on efferocytosis-related factors was studied. RESULTS: GQD improved atherosclerosis and non-alcoholic fatty liver disease and reduced serum low-density lipoprotein levels in the high-dose group. The high- and low-dose groups showed upregulated ABCA1, MerTK, and LXR-α expression in blood vessels and the liver, respectively. GQD decreased serum TNF-α and increased IL-13 levels. PPAR-γ expression was elevated in the high-, and low-dose groups. In the high-and low-dose groups, ABCA7, GAS6, SCARB1, and LXR-α, ABCA1 and MerTK, and ABCG1 gene expression were upregulated, respectively. Both low- and high-dose serum-containing drugs promoted LXR-ß gene expression, and LXR-α protein expression was improved in the high-dose group. CONCLUSION: GQD improves rat atherosclerosis and hepatic lipid metabolism by regulating PPAR-γ, LXR-α, LXR-ß, ABCA1, ABCA7, and ABCG1 expression and augmenting cellular intercalation through the GAS6/TAM pathway.

Silicon Hybridization for the Preparation of Room-Temperature Curing and High-Temperature-Resistant Epoxy Resin.

Specialized epoxy resin, capable of achieving room-temperature profound curing and sustaining prolonged exposure to high-temperature environments, stands as a pivotal material in modern high-end manufacturing sectors including aerospace, marine equipment fabrication, machinery production, and the electronics industry. Herein, a silicon-hybridized epoxy resin, amenable to room-temperature curing and designed for high-temperature applications, was synthesized using a sol-gel methodology with silicate esters and silane coupling agents serving as silicon sources. Resin characterization indicates a uniform distribution of silicon elements in the obtained silicon hybrid epoxy resin. In comparison to the non-hybridized epoxy resin, notable improvements are observed in room-temperature curing performance, heat resistance, and mechanical strength.

Genome-Wide Identification and Characterization of the Medium-Chain Dehydrogenase/Reductase Superfamily of Trichosporon asahii and Its Involvement in the Regulation of Fluconazole Resistance.

The medium-chain dehydrogenase/reductase (MDR) superfamily contains many members that are widely present in organisms and play important roles in growth, metabolism, and stress resistance but have not been studied in Trichosporon asahii. In this study, bioinformatics and RNA sequencing methods were used to analyze the MDR superfamily of T. asahii and its regulatory effect on fluconazole resistance. A phylogenetic tree was constructed using Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans, and T. asahii, and 73 MDRs were identified, all of which contained NADPH-binding motifs. T. asahii contained 20 MDRs that were unevenly distributed across six chromosomes. T. asahii MDRs (TaMDRs) had similar 3D structures but varied greatly in their genetic evolution at different phylum levels. RNA-seq and gene expression analyses revealed that the fluconazole-resistant T. asahii strain upregulates xylitol dehydrogenase, and downregulated alcohol dehydrogenase and sorbitol dehydrogenase concluded that the fluconazole-resistant T. asahii strain was less selective toward carbon sources and had higher adaptability to the environment. Overall, our study contributes to our understanding of TaMDRs, providing a basis for further analysis of the genes associated with drug resistance in T. asahii.

Comprehensive review on the elaboration of payloads derived from natural products for antibody-drug conjugates.

Antibody-drug conjugates (ADCs) have arisen as a promising class of biotherapeutics for targeted cancer treatment, combining the specificity of monoclonal antibodies with the cytotoxicity of small-molecule drugs. The choice of an appropriate payload is crucial for the success development of ADCs, as it determines the therapeutic efficacy and safety profile. This review focuses on payloads derived from natural products, including cytotoxic agents, DNA-damaging agents, and immunomodulators. These offer several advantages such as diverse chemical structures, unique mechanism of actions, and potential for improved therapeutic index. Challenges and opportunities associated with their development were highlighted. This review underscores the significance of natural product payloads in the elaboration of ADCs, which serves as a valuable resource for researchers involved in developing and optimizing next-generation ADCs for cancer treatment.

Straw with different fermentation degrees mediate Se/Cd bioavailability by governing the putative iron reducing bacteria.

Straw returning is a crucial agronomic practice in fields due to its various benefits. However, effects and mechanisms of straw with different fermentation degrees on Se and Cd bioavailability have not been sufficiently investigated. In this study, straw with different fermentation degrees were applied to a Cd-contaminated seleniferous soil to investigate their effects on Se and Cd bioavailability. Results revealed that the effects of straw application on Se/Cd bioavailability in soil depended on the fermentation degrees of straw. Both original and slightly fermented straw had pronounced impacts on microbial iron reduction compared to fully fermented straw, and thus led to a significant increase in Se and Cd bioavailability. The linear discriminant analysis effect size (LEfSe) showed that norank_f_Symbiobacteraceae, Micromonospora, WCHB1-32, Ruminiclostrdium, and Cellulomonas were the major biomarkers at genus level in straw application soils, additional network analysis and random forest analysis suggested that Ruminiclostrdium and Cellulomonas might be implicated in microbial iron reduction. Furthermore, the microbial iron reduction had negative effects on mineral-associated Se with coefficient of -0.81 and positive effects on mineral-associated Cd with coefficient of 0.72, while Mn fractions exhibited positive effects on mineral-associated Se with a coefficient of 0.53 and negative effects on mineral-associated Cd. In conclusion, straw with different fermentation degrees governed Se and Cd mobility by regulating abundance of Ruminiclostrdium and Cellulomonas, subsequently affecting Fe and Mn fractions and consequently influencing Se and Cd bioavailability.

Mitochondrial Artificial K+ Channel Construction Using MPTPP@5F8 Nanoparticles for Overcoming Cancer Drug Resistance via Disrupting Cellular Ion Homeostasis.

Mitochondrial potassium ion channels have become a promising target for cancer therapy. However, in malignant tumors, their low expression or inhibitory regulation typically leads to undesired cancer therapy, or even induces drug resistance. Herein, this work develops an in situ mitochondria-targeted artificial K+ channel construction strategy, with the purpose to trigger cancer cell apoptosis by impairing mitochondrial ion homeostasis. Considering the fact that cancer cells have a lower membrane potential than that of normal cells, this strategy can selectively deliver artificial K+ channel molecule 5F8 to the mitochondria of cancer cells, by using a mitochondria-targeting triphenylphosphine (TPP) modified block polymer (MPTPP) as a carrier. More importantly, 5F8 can further specifically form a K+ -selective ion channel through the directional assembly of crown ethers on the mitochondrial membrane, thereby inducing mitochondrial K+ influx and disrupting ions homeostasis. Thanks to this design, mitochondrial dysfunction, including decreased mitochondrial membrane potential, reduced adenosine triphosphate (ATP) synthesis, downregulated antiapoptotic BCL-2 and MCL-1 protein levels, and increased reactive oxygen species (ROS) levels, can further effectively induce the programmed apoptosis of multidrug-resistant cancer cells, no matter in case of pump or nonpump dependent drug resistance. In short, this mitochondria-targeted artificial K+ -selective ion channel construction strategy may be beneficial for potential drug resistance cancer therapy.

Fibroblasts in immune-mediated inflammatory diseases: The soil of inflammation.

As one of the most abundant stromal cells, fibroblasts are primarily responsible for the production and remodeling of the extracellular matrix. Traditionally, fibroblasts have been viewed as quiescent cells. However, recent advances in multi-omics technologies have demonstrated that fibroblasts exhibit remarkable functional diversity at the single-cell level. Additionally, fibroblasts are heterogeneous in their origins, tissue locations, and transitions with stromal cells. The dynamic nature of fibroblasts is further underscored by the fact that disease stages can impact their heterogeneity and behavior, particularly in immune-mediated inflammatory diseases such as psoriasis, inflammatory bowel diseases, and rheumatoid arthritis, etc. Fibroblasts can actively contribute to the disease initiation, progression, and relapse by responding to local microenvironmental signals, secreting downstream inflammatory factors, and interacting with immune cells during the pathological process. Here we focus on the development, plasticity, and heterogeneity of fibroblasts in inflammation, emphasizing the need for a developmental and dynamic perspective on fibroblasts.