Epigenomic features associated with body temperature stabilize tissues during cold exposure in cold-resistant pigs.

Cold stress in low-temperature environments can trigger changes in gene expression, but epigenomics regulation of temperature stability in vital tissues, including the fat and diencephalon, is still unclear. Here, we explore the cold-induced changes in epigenomic features in the diencephalon and fat tissues of two cold-resistant Chinese pig breeds, Min and Enshi black (ES) pigs, utilizing H3K27ac CUT&Tag, RNA-seq, and selective signature analysis. Our results show significant alterations in H3K27ac modifications in the diencephalon of Min pigs and the fat of ES pigs after cold exposure. Dramatic changes in H3K27ac modifications in Min pigs are primarily associated with genes involved in energy metabolism and hormone regulation, whereas those in ES pigs are primarily associated with immunity-related genes. Moreover, transcription factors PRDM1 and HSF1, which show evidence of selection, are enriched in genomic regions presenting cold-responsive alterations in H3K27ac modification in the Min pig diencephalon and ES pig fat, respectively. Our results indicate the diversity of epigenomic response mechanisms to cold exposure between Min and ES pigs, providing unique epigenetic resources for studies of low-temperature adaptation in large mammals.

Psoralen protects neurons and alleviates neuroinflammation by regulating microglial M1/M2 polarization via inhibition of the Fyn-PKCδ pathway.

Microglia-mediated neuroinflammation is closely associated with many neurodegenerative diseases. Psoralen has potential for the treatment of many diseases, however, the anti-neuroinflammatory and neuroprotective effects of psoralen have been unclear. This study investigated the anti-neuroinflammatory and neuroprotective effects of psoralen and its regulation of microglial M1/M2 polarization. The LPS-induced mice model was used to test anti-neuroinflammatory effects, regulatory effects on microglia polarization, and neuroprotective effects of psoralen in vivo. The LPS-induced BV2 model was used to test the anti-neuroinflammatory effects and the regulatory effects and mechanisms on microglial M1/M2 polarization of psoralen in vitro. PC12 cell model induced by conditioned medium of BV2 cells was used to validate the protective effects of psoralen against neuroinflammation-induced neuronal damage. These results showed that psoralen inhibited the expression of iNOS, CD86, and TNF-α, and increased the expression of Arg-1, CD206, and IL-10. These results indicated that psoralen inhibited the M1 microglial phenotype and promoted the M2 microglial phenotype. Further studies showed that psoralen inhibited the phosphorylation of Fyn and PKCδ, thereby inhibiting activation of the MAPKs and NF-κB pathways and suppressing the expression of pro-inflammatory cytokines in microglia. Furthermore, psoralen reduced oxidative stress, neuronal damage, and apoptosis via inhibition of neuroinflammation. For the first time, this study showed that psoralen protected neurons and alleviated neuroinflammation by regulating microglial M1/M2 polarization, which may be mediated by inhibition of the Fyn-PKCδ pathway. Thus, psoralen may be a potential agent in the treatment of neuroinflammation-related diseases.

Natural products from Camellia oleifera fruit and its comprehensive utilisation.

Camellia oleifera (C. oleifera) is a woody oil plant with a good reputation of 'Oriental Olive Oil' in China. The national understanding of the health-care benefits of Camellia oil are already widespread, but the production of C. oleifera fruit has not been achieved large-scale industrialisation. In this review, we focus on the properties and commercial value of its natural products, and processing technology, performance characterisation, and novel modification strategies of its processed products. In addition, we briefly summarised the research progress of breeding and put forward the comprehensive utilisation of C. oleifera fruit based on the tandem of extraction and processing. This review might attract more researchers to make profound study regarding it as an alternative of olive oil.

Methanogen-methanotroph community has a more consistent and integrated structure in rice rhizosphere than in bulk soil and rhizoplane.

Methanogenic and methanotrophic microbes together determine the net methane flux from rice fields. Despite much research on them as separate communities, there has been little study of combined community patterns, and how these vary between the rhizoplane (root surface), rhizosphere (soil surrounding the root) and bulk soil around rice plants, especially at larger spatial scale. We collected samples from 32 geographically scattered rice fields in east central China, amplicon targeting the mcrA gene for methanogenesis and pmoA gene for methanotrophy by using high-throughput sequencing. Distinct communities of both methanogens and methanotrophs occurred in each of the three compartments, and predominantly positive links were found between methanogens and methanotrophs in all compartments indicating cross-feeding or consortia relationships. Methanogens were acting as the network hub in the bulk soil, and methanotrophs in rhizoplane. Network complexity and stability was greater in the rhizosphere than rhizoplane and bulk soil, with no network hubs detected, suggesting the strongest effect of homeostatic influence by plant occurred in the rhizosphere. The proportion of determinism (homogeneous selection) and distance-decay relation (DDR) in rhizoplane was consistently lower than that in the rhizosphere for both communities, indicating weaker phylogenetic clustering in rice root surface. Our results have provided a better understanding of CH4 oxidation and emission in rice paddy fields and future agriculture management could take into consideration of the subtle variation among different soil compartments and interactions within methanogenic and methanotrophic communities.

A molecularly imprinted electrochemical sensor MIP/Cu-MOF/rGO/AuNPs/GCE for highly sensitive detection of electroneutral organophosphorus pesticide residues.

A novel electrochemical sensor, MIP/Cu-MOF/rGO/AuNPs/GCE, was developed by depositing gold nanoparticles, coating Cu-MOF/GO on the surface of glassy carbon electrode (GCE) before electroreducing graphene oxide (GO) to rGO and covering molecularly imprinted membrane by electropolymerization for highly sensitive detection of electroneutral organophosphorus pesticide residues in agricultural product. Cyclic voltammetry, differential pulse voltametry, scanning electron microscopy, energy-dispersive spectroscopy, and atomic force microscopy were used to characterize the imprinted sensor. Several key factors such as chitosan concentration, suspension volume, pH of polymerization solution, and polymerization scanning rate during preparation of the imprinted sensor were optimized in detail. When electroneutral phosmet was used as a template, the linear range of MIP/Cu-MOF/rGO/AuNPs/GCE for detecting phosmet was 1.00 × 10-14-5.00 × 10-7 mol/L with the limit of detection of 7.20 × 10-15 mol/L at working potentials of - 0.2 to 0.6 V. The selectivity, reproducibility, and repeatability of MIP/Cu-MOF/rGO/AuNPs/GCE were all acceptable. The recoveries of this method for determining phosmet in real samples ranged from 94.2 to 106.5%. The MIP/Cu-MOF/rGO/AuNPs/GCE sensor could be applied to detect electroneutral pesticide residues in organisms and agricultural products.

Radiation source terms analysis and classification of radioactive waste for the decommissioning of the first HWRR reactor in China.

Nuclear reactors will face the problem of decommissioning at the end of their operating life due to the high radioactivity of reactor components and environmental safety considerations. The Heavy Water Research Reactor (HWRR) is the first large-scale research reactor to be decommissioned in China. The second phase of HWRR decommissioning involves the main components in the reactor block, so the radiation source terms and the radioactive waste level need to be evaluated before demolition and disposal. Based on the operating history, three-dimensional geometry, materials, and other information of the HWRR, the activity of radionuclides in the main components of HWRR is calculated and analyzed, and the MCNP/ORIGEN coupling scheme is utilized for theoretical analysis. The theoretical results indicate that 14C, 54Mn, 55Fe, 60Co, 63Ni, and 152Eu are the main radioactive nuclides. The total activity of radioactive nuclides was 2.36E + 15 Bq at the end of 2007, 4.27E + 13 Bq at the end of 2021, and 1.83E + 13 Bq at the end of 2025. Furthermore, local sampling and radiometric analyses based on the HPGe gamma-ray spectrometer are also performed to verify the theoretical results, the ratio of theoretical activity values to the measured activity of the experimental sample is within 2.5 times, so the theoretical results are conservative. According to the classification standards for radioactive waste, the inner shell, outer shell, cooling water tank, sand layer, and heavy concrete shielding layer are all low-level waste. These results and conclusions can serve as a reference for the second phase decommissioning of the HWRR and the subsequent disposal of radioactive waste.

Multi-omics characterization of esophageal squamous cell carcinoma identifies molecular subtypes and therapeutic targets.

Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer and is characterized by an unfavorable prognosis. To elucidate the distinct molecular alterations in ESCC and investigate therapeutic targets, we performed a comprehensive analysis of transcriptomics, proteomics, and phosphoproteomics data derived from 60 paired treatment-naive ESCC and adjacent nontumor tissue samples. Additionally, we conducted a correlation analysis to describe the regulatory relationship between transcriptomic and proteomic processes, revealing alterations in key metabolic pathways. Unsupervised clustering analysis of the proteomics data stratified patients with ESCC into 3 subtypes with different molecular characteristics and clinical outcomes. Notably, subtype III exhibited the worst prognosis and enrichment in proteins associated with malignant processes, including glycolysis and DNA repair pathways. Furthermore, translocase of inner mitochondrial membrane domain containing 1 (TIMMDC1) was validated as a potential prognostic molecule for ESCC. Moreover, integrated kinase-substrate network analysis using the phosphoproteome nominated candidate kinases as potential targets. In vitro and in vivo experiments further confirmed casein kinase II subunit α (CSNK2A1) as a potential kinase target for ESCC. These underlying data represent a valuable resource for researchers that may provide better insights into the biology and treatment of ESCC.

Relationship between Dietary Inflammatory Index and Blood Glucose Changes in Patients with Pre-diabetes Mellitus.

Objective: The objective of this study was to assess the association between the dietary inflammatory index (DII) and blood glucose changes in patients diagnosed with pre-diabetes mellitus (Pre-DM). Methods: The study participants were 111 patients diagnosed with Pre-DM at Taizhou People's Hospital of Jiangsu Province Hospital between January 2019 and December 2021. Patients' initial BG data were collected and recorded. A dietary assessment was performed on all Pre-DM patients, and the DII of each participant was calculated to explore the relationship between DII and BG changes. DII was calculated based on the relation between food and interleukin serum IL-1ß, IL-4, IL-6, IL-10 and CRP. Results: The fasting (FBG), 1-hour postprandial (1hPBG) and 2-hour postprandial blood glucose (2hPBG) levels were (5.43±0.88) mmol/L, (10.67±3.05) mmol/L, and (8.65±2.89) mmol/L, respectively, with statistical significance among them (n=111, F=222.987, P < .001). Multivariate linear regression models were established with FBG, 1hPBG, 2hPBG, and BG changes (2hPBG-FBG and 1hPBG-FBG) as dependent variables. In Model 5, the coefficient (B value) of DII and its 95% (CI) were 0.324 (0.018~0.658) (P = .031), indicating a positive correlation between DII and BG concentration that the change of BG concentration increased by 0.456 mmol/L for every 1 unit increase in DII. Conclusions: DII is a risk factor for Pre-DM patients, so attention should be paid to the content of inflammatory components in the diet, and more intake of anti-inflammatory components is helpful to prevent the occurrence of diabetes further.

Single-Cell RNA-Sequencing Reveals Heterogeneity and Transcriptional Dynamics in Porcine Circulating CD8+ T Cells.

Pigs are the most important source of meat and valuable biomedical models. However, the porcine immune system, especially the heterogeneity of CD8 T cell subtypes, has not been fully characterized. Here, using single-cell RNA sequencing, we identified 14 major cell types from peripheral blood circulating cells of pigs and observed remarkable heterogeneity among CD8 T cell types. Upon re-clustering of CD8+ T cells, we defined four CD8 T cell subtypes and revealed their potential differentiation trajectories and transcriptomic differences among them. Additionally, we identified transcription factors with potential regulatory roles in maintaining CD8 T cell differentiation. The cell-cell communication analysis inferred an extensive interaction between CD8 T cells and other immune cells. Finally, cross-species analysis further identified species-specific and conserved cell types across different species. Overall, our study provides the first insight into the extensive functional heterogeneity and state transitions among porcine CD8 T cell subtypes in pig peripheral blood, complements the knowledge of porcine immunity, and enhances its potential as a biomedical model.

Alizarin-embedded γ-cyclodextrin-based metal-organic framework in a methylcellulose/polyvinyl alcohol film for maintaining and monitoring grass carp freshness.

Multifunctional packaging films that monitor and maintain fish freshness hold significant potential for use in the food industry. This study introduces a multifunctional intelligent packaging film comprising alizarin (ALI)-embedded cubic γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) (denoted as γ-CD-MOFs@ALI) in a methylcellulose/polyvinyl alcohol (MP)-based matrix to achieve colorimetric monitoring and enhanced preservation of fish freshness. The MP/γ-CD-MOFs@ALI reveals a rapid color transition in 3 min from yellow color progressively darkens to purple as the pH increases from 2.0 to 10.0. And it is proved that the as-prepared film owns high antibacterial activity against Gram-positive bacteria (S. aureus), impressive ABTS+ radical scavenging rates of 85.54 ± 1.25 %, and effective ALI sustained-release properties. The intelligent packaging film exhibits an excellent colorimetric response to total volatile basic nitrogen and provides exceptional freshness preservation performance, effectively prolonging the shelf life of Ctenopharyngodon idella (grass carp) under 25 °C to 42 h.

Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate. METHODS: A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone. RESULTS: After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC. CONCLUSION: Collectively, these findings suggest that domperidone serves as an effective "multi-target" inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

Peptide derived from RAGE efficiently improves oocyte development through attenuating oxidative stress in oocytes of mice with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in reproductive-aged women that frequently leads to infertility due to poor oocyte quality. In this study, we identified a new active peptide (advanced glycation end products receptors RAGE344-355 ) from PCOS follicular fluid using mass spectrometry. We found that supplementing PCOS-like mouse oocytes with RAGE344-355 attenuated both meiotic defects and oxidative stress levels, ultimately preventing developmental defects. Additionally, our results suggest that RAGE344-355 may interact with eEF1a1 to mitigate oxidative meiotic defects in PCOS-like mouse oocytes. These findings highlight the potential for further clinical development of RAGE344-355 as a potent supplement and therapeutic option for women with PCOS. This research addresses an important clinical problem and offers promising opportunities for improving oocyte quality in PCOS patients.

Ubiquitous protein lactylation in health and diseases.

For decades, lactate has been considered a byproduct of glycolysis. The lactate shuttle hypothesis shifted the lactate paradigm, demonstrating that lactate not only plays important roles in cellular metabolism but also cellular communications, which can transcend compartment barriers and can occur within and among different cells, tissues and organs. Recently, the discovery that lactate can induce a novel post-translational modification, named lysine lactylation (Kla), brings forth a new avenue to study nonmetabolic functions for lactate, which has inspired a 'gold rush' of academic and commercial interest. Zhang et al. first showed that Kla is manifested in histones as epigenetic marks, and then mounting evidences demonstrated that Kla also occurs in diverse non-histone proteins. The widespread Kla faithfully orchestrates numerous biological processes, such as transcription, metabolism and inflammatory responses. Notably, dysregulation of Kla touches a myriad of pathological processes. In this review, we comprehensively reviewed and curated the existing literature to retrieve the new identified Kla sites on both histones and non-histone proteins and summarized recent major advances toward its regulatory mechanism. We also thoroughly investigated the function and underlying signaling pathway of Kla and comprehensively summarize how Kla regulates various biological processes in normal physiological states. In addition, we also further highlight the effects of Kla in the development of human diseases including inflammation response, tumorigenesis, cardiovascular and nervous system diseases and other complex diseases, which might potentially contribute to deeply understanding and interpreting the mechanism of its pathogenicity.

Hepatic regulator of G protein signaling 14 ameliorates NAFLD through activating cAMP-AMPK signaling by targeting Giα1/3.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is an emerging public health threat as the most common chronic liver disease worldwide. However, there remains no effective medication to improve NAFLD. G protein-coupled receptors (GPCRs) are the most frequently investigated drug targets family. The Regulator of G protein signaling 14 (RGS14), as an essential negative modulator of GPCR signaling, plays important regulatory roles in liver damage and inflammatory responses. However, the role of RGS14 in NAFLD remains largely unclear. METHODS AND RESULTS: In this study, we found that RGS14 was decreased in hepatocytes in NAFLD individuals in a public database. We employed genetic engineering technique to explore the function of RGS14 in NAFLD. We demonstrated that RGS14 overexpression ameliorated lipid accumulation, inflammatory response and liver fibrosis in hepatocytes in vivo and in vitro. Whereas, hepatocyte specific Rgs14-knockout (Rgs14-HKO) exacerbated high fat high cholesterol diet (HFHC) induced NASH. Further molecular experiments demonstrated that RGS14 depended on GDI activity to attenuate HFHC-feeding NASH. More importantly, RGS14 interacted with Guanine nucleotide-binding protein (Gi) alpha 1 and 3 (Giα1/3, gene named GNAI1/3), promoting the generation of cAMP and then activating the subsequent AMPK pathways. GNAI1/3 knockdown abolished the protective role of RGS14, indicating that RGS14 binding to Giα1/3 was required for prevention against hepatic steatosis. CONCLUSIONS: RGS14 plays a protective role in the progression of NAFLD. RGS14-Giα1/3 interaction accelerated the production of cAMP and then activated cAMP-AMPK signaling. Targeting RGS14 or modulating the RGS14-Giα1/3 interaction may be a potential strategy for the treatment of NAFLD in the future.

Baicalin - 2- ethoxyethyl ester alleviates renal fibrosis by inhibiting PI3K/AKT/NF-κB signaling pathway.

With the increasing incidence of chronic kidney disease (CKD), the development of safe and effective anti-renal fibrosis drugs is particularly urgent. Recently, Baicalin has been considered to have a renal protective effect, but its bioavailability is too low. Therefore, we synthesized baicalin-2-ethoxyethyl ester (BAE) by esterification of baicalin. We hope that this experiment will demonstrate the anti-renal fibrosis effect of BAE and explain its molecular mechanism. In this study, the chronic kidney injury model of SD rats was established by 5/6 nephrectomy, and BAE was given for 28 days. The results showed that after BAE treatment, the serum creatinine and urea nitrogen levels decreased significantly, and the pathological changes in kidneys were improved. In addition, RNA-seq analysis showed that the mechanism of BAE in relieving renal fibrosis was related to the ECM receptor, PI3K/AKT signaling pathway, and inflammatory reaction. The western blotting analysis confirmed that BAE could inhibit the expression of α-SMA, TGF-ß1, p-PI3K, p-AKT, p-IκBα, and NF-κB p65. We found that BAE can inhibit the inflammatory reaction and promote the degradation of the extracellular matrix by inhibiting the activation of the PI3K/AKT/NF-κB pathway, thus alleviating the symptoms of renal fibrosis in 5/6Nx rats, which revealed BAE was a potential compound to relieve renal fibrosis effect.

Bavachin ameliorates neuroinflammation and depressive-like behaviors in streptozotocin-induced diabetic mice through the inhibition of PKCδ.

Depression and diabetes are closely linked; however, the pathogenesis of depression associated with diabetes is unclear, and there are no clinically effective antidepressant drugs for diabetic patients with depression. Bavachin is an important active ingredient in Fructus Psoraleae. In this study, we evaluated the anti-neuroinflammatory and antidepressant effects associated with diabetes and the molecular mechanisms of bavachin in a streptozotocin-induced diabetes mouse model. We found that bavachin clearly decreased streptozotocin (STZ)-induced depressive-like behaviors in mice. It was further found that bavachin significantly inhibited microglia activation and the phosphorylation level of PKCδ and inhibited the activation of the NF-κB pathway in vivo and in vitro. Knockdown of PKCδ with siRNA-PKCδ partially reversed the inhibitory effect of bavachin on the NF-κB pathway and the level of pro-inflammatory factors. We further found that PKCδ directly bound to bavachin based on molecular docking and pull-down assays. We also found that bavachin improved neuroinflammation-induced neuronal survival and functional impairment and that this effect may be related to activation of the ERK and Akt pathways mediated by the BDNF pathway. Taken together, these data suggested that bavachin, by targeting inhibition PKCδ to inhibit the NF-κB pathway, further reduced the inflammatory response and oxidative stress and subsequently improved diabetic neuronal survival and function and finally ameliorated diabetes-induced depressive-like behaviors in mice. For the first time, we found that bavachin is a potential agent for the treatment of diabetes-associated neuroinflammation and depression and that PKCδ is a potential target for the treatment of diabetes-associated neuroinflammation, including depression.

Distinct biogeographic patterns in Glomeromycotinian and Mucoromycotinian arbuscular mycorrhizal fungi across China: A meta-analysis.

Fine root endophytes, recently reclassified as Mucoromycotinian arbuscular mycorrhizal fungi (M-AMF), are now recognized as functionally important as Glomeromycotinian AMF (G-AMF). However, little is known about the biogeography and ecology of M-AMF and G-AMF communities, particularly on a large scale, preventing a systematic assessment of ecosystem diversity and functioning. Here, we investigated the biogeographic assemblies and ecological diversity patterns of both G-AMF and M-AMF, using published 18S rDNA amplicon datasets and associated metadata from 575 soil samples in six ecosystems across China. Contrasting with G-AMF, putative M-AMF were rare in natural/semi-natural sites, where their communities were a subset of those in agricultural sites characterized by intensive disturbances, suggesting different ecological niches that they could occupy. Spatial and environmental factors (e.g., vegetation type) significantly influenced both fungal communities, with soil total­nitrogen and mean-annual-precipitation being the strongest predictors for G-AMF and M-AMF richness, respectively. Both groups exhibited a strong spatial distance-decay relationship, shaped more by environmental filtering than spatial effects for M-AMF, and the opposite for G-AMF, presumably because stochasticity (e.g., drift) dominantly structured G-AMF communities; while the narrower niche breadth (at community-level) of M-AMF compared to G-AMF suggested its more susceptibility to environmental differences. Furthermore, co-occurrence network links between G-AMF and M-AMF were prevalent across ecosystems, and were predicted to play a key role in stabilizing overall communities harboring both fungi. Based on the macroecological spatial scale datasets, this study provides solid evidence that the two AMF groups have distinct ecological preferences at the continental scale in China, and also highlights the potential impacts of anthropogenic activities on distributions of AMF. These results advance our knowledge of the ecological differences between the two fungal groups in terrestrial ecosystems, suggesting the need for further field-based investigation that may lead to a more sophisticated understanding of ecosystem function and sustainable management.

Electro-catalytic adsorption mechanism of acetonitrile in water using a ME-ACFs system.

Acetonitrile wastewater is difficult to treat due to its high salinity and toxicity to microorganisms. In this paper, a micro electro-activated carbon fiber coupled system (ME-ACF) was established to treat simulated acetonitrile wastewater. In the 200 ml system, the concentration of acetonitrile adsorbed by ACF was 91.3 mg/L, while that of acetonitrile adsorbed by ME-ACF was 150.6 mg/L, and the removal efficiency was increased by 65 % in comparison. The activated carbon fibers before and after the reaction were subjected to a series of characterization, and it was found that the SABET decreased from 1393.48 m2/g to 1114.93 m2/g and 900.23 m2/g, respectively, but the oxygen on the surface of the activated carbon fibers was increased, and the effect of the micro electrolytic system on the activated carbon fibers was then analyzed. The possible reasons for the formation of acetic acid contained in the products were also discussed using DFT simulations. The removal mechanism of acetonitrile by ME-ACF was considered to be electrically enhanced adsorption and electro-catalytic hydrolysis.

Multifactor assessment of ovarian cancer reveals immunologically interpretable molecular subtypes with distinct prognoses.

Background: Ovarian cancer (OC) is a highly heterogeneous and malignant gynecological cancer, thereby leading to poor clinical outcomes. The study aims to identify and characterize clinically relevant subtypes in OC and develop a diagnostic model that can precisely stratify OC patients, providing more diagnostic clues for OC patients to access focused therapeutic and preventative strategies. Methods: Gene expression datasets of OC were retrieved from TCGA and GEO databases. To evaluate immune cell infiltration, the ESTIMATE algorithm was applied. A univariate Cox analysis and the two-sided log-rank test were used to screen OC risk factors. We adopted the ConsensusClusterPlus algorithm to determine OC subtypes. Enrichment analysis based on KEGG and GO was performed to determine enriched pathways of signature genes for each subtype. The machine learning algorithm, support vector machine (SVM) was used to select the feature gene and develop a diagnostic model. A ROC curve was depicted to evaluate the model performance. Results: A total of 1,273 survival-related genes (SRGs) were firstly determined and used to clarify OC samples into different subtypes based on their different molecular pattern. SRGs were successfully stratified in OC patients into three robust subtypes, designated S-I (Immunoreactive and DNA Damage repair), S-II (Mixed), and S-III (Proliferative and Invasive). S-I had more favorable OS and DFS, whereas S-III had the worst prognosis and was enriched with OC patients at advanced stages. Meanwhile, comprehensive functional analysis highlighted differences in biological pathways: genes associated with immune function and DNA damage repair including CXCL9, CXCL10, CXCL11, APEX, APEX2, and RBX1 were enriched in S-I; S-II combined multiple gene signatures including genes associated with metabolism and transcription; and the gene signature of S-III was extensively involved in pathways reflecting malignancies, including many core kinases and transcription factors involved in cancer such as CDK6, ERBB2, JAK1, DAPK1, FOXO1, and RXRA. The SVM model showed superior diagnostic performance with AUC values of 0.922 and 0.901, respectively. Furthermore, a new dataset of the independent cohort could be automatically analyzed by this innovative pipeline and yield similar results. Conclusion: This study exploited an innovative approach to construct previously unexplored robust subtypes significantly related to different clinical and molecular features for OC and a diagnostic model using SVM to aid in clinical diagnosis and treatment. This investigation also illustrated the importance of targeting innate immune suppression together with DNA damage in OC, offering novel insights for further experimental exploration and clinical trial.

Fiber-reinforced gelatin/ß-cyclodextrin hydrogels loaded with platelet-rich plasma-derived exosomes for diabetic wound healing.

Diabetic complications with high-glucose status (HGS) cause the dysregulated autophagy and excessive apoptosis of multiple-type cells, leading to the difficulty in wound self-healing. Herein, we firstly developed fiber-reinforced gelatin (GEL)/ß-cyclodextrin (ß-CD) therapeutic hydrogels by the modification of platelet-rich plasma exosomes (PRP-EXOs). The GEL fibers that were uniformly dispersed within the GEL/ß-CD hydrogels remarkably enhanced the compression strengths and viscoelasticity. The PRP-EXOs were encapsulated in the hydrogels via the covalent crosslinking between the PRP-EXOs and genipin. The diabetic rat models demonstrated that the GEL/ß-CD hydrogels and PRP-EXOs cooperatively promoted diabetic wound healing. On the one hand, the GEL/ß-CD hydrogels provided the biocompatible microenvironments and active components for cell adhesion, proliferation and skin tissue regeneration. On the other hand, the PRP-EXOs in the therapeutic hydrogels significantly activated the autophagy and inhibited the apoptosis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). The activation of autophagy and inhibition of apoptosis in HUVECs and HSFs induced the blood vessel creation, collagen formation and re-epithelialization. Taken together, this work proved that the incorporation of PRP-EXOs in a wound dressing was an effective strategy to regulate autophagy and apoptosis, and provide a novel therapeutic platform for diabetic wound healing.