Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

Short-term responses of soil enzyme activities and stoichiometry to litter input in Castanopsis carlesii and Cunninghamia lanceolata plantations.

Litter input triggers the secretion of soil extracellular enzymes and facilitates the release of carbon (C), nitrogen (N), and phosphorus (P) from decomposing litter. However, how soil extracellular enzyme activities were controlled by litter input with various substrates is not fully understood. We examined the activities and stoichiometry of five enzymes including ß-1,4-glucosidase, ß-D-cellobiosidase, ß-1,4-N-acetyl-glucosaminidase, leucine aminopeptidase and acidic phosphatase (AP) with and without litter input in 10-year-old Castanopsis carlesii and Cunninghamia lanceolata plantations monthly during April to August, in October, and in December 2021 by using an in situ microcosm experiment. The results showed that: 1) There was no significant effect of short-term litter input on soil enzyme activity, stoichiometry, and vector properties in C. carlesii plantation. In contrast, short-term litter input significantly increased the AP activity by 1.7% in May and decreased the enzymatic C/N ratio by 3.8% in August, and decreased enzymatic C/P and N/P ratios by 11.7% and 10.3%, respectively, in October in C. lanceolata plantation. Meanwhile, litter input increased the soil enzymatic vector angle to 53.8° in October in C. lanceolata plantations, suggesting a significant P limitation for soil microorganisms. 2) Results from partial least squares regression analyses showed that soil dissolved organic matter and microbial biomass C and N were the primary factors in explaining the responses of soil enzymatic activity to short-term litter input in both plantations. Overall, input of low-quality (high C/N) litter stimulates the secretion of soil extracellular enzymes and accelerates litter decomposition. There is a P limitation for soil microorganisms in the study area.

The status of intimate partner violence against pregnant women in contemporary China: a scoping review.

PURPOSE: This review explored the status of publications on intimate partner violence (IPV) against pregnant women in contemporary China. METHODS: The PubMed, Cochrane Library, Embase, CINAHL, and PsycInfo databases were searched using the terms "IPV," "pregnant woman," "Chinese," and synonyms in English, along with related keywords for Chinese publications. All literature pertaining to IPV during pregnancy, conducted in China, and published between 1987 and September 2023 was included. RESULTS: A total of 37 articles from 30 studies were selected. The prevalence of IPV during pregnancy ranged from 2.5% to 31.3%, with psychological violence being the most common form. Frequently identified risk factors included unintended pregnancy, poor family economic conditions, male partners engaging in health risk behaviors, poor employment status of women or their partners, low education levels among women, physical or mental health issues, strained couple relationships, and in-law conflicts. IPV during pregnancy primarily led to mental health problems for the victims and could result in adverse obstetric outcomes, as well as negative effects on the temperament and development of the offspring. Victims in China demonstrated a low willingness to seek help from professionals. Furthermore, relevant research in mainland China is scarce, with a limited number of studies and non-standardized research methodologies. CONCLUSION: Future research should investigate IPV in pregnancy from various perspectives, identify factors unique to IPV during pregnancy, and focus on high-risk groups. Considering the conditions in China, there is a pressing need to increase public awareness of IPV and to investigate interventions aimed at addressing this issue.

Mixed probiotics modulated gut microbiota to improve spermatogenesis in bisphenol A-exposed male mice.

Bisphenol A (BPA), an environmental endocrine disruptor (EDC), has been implicated in impairing intestinal and male reproductive dysfunction. The efficacy of gut microbiota modulation for BPA-exposed testicular dysfunction has yet to be verified through research. Therefore, this study explored the potential of mixed probiotics in restoring spermatogenesis damage through the gut-testis axis under BPA exposure. We selected two probiotics strains (Lactobacillus rhamnosus and Lactobacillus plantarum) with BPA removal properties in vitro and the BPA-exposed male mice model was established. The probiotics mixture effectively reduced BPA residue in the gut, serum, and testis in mice. Through 16 S rDNA-seq and metabolomics sequencing, we uncovered that vitamin D metabolism and bile acid levels in the gut was abolished under BPA exposure. This perturbation was linked to an increased abundance of Faecalibaculum and decreased abundance of Lachnospiraceae_NK4A136_group and Ligilactobacillus. The probiotics mixture restored this balance, enhancing intestinal barrier function and reducing oxidative stress. This improvement was accompanied by a restored balance of short-chain fatty acids (SCFAs). Remarkably, the probiotics ameliorated testicular dysfunction by repairing structures of seminiferous tubules and reversing arrested spermiogenesis. Further, the probiotics mixture enhanced testosterone-driven increases in spermatogonial stem cells and all stages of sperm cells. Testicular transcriptome profiling linked these improvements to fatty acid degradation and peroxisome pathways. These findings suggest a significant interplay between spermatogenesis and gut microbiota, demonstrating that probiotic intake could be a viable strategy for combating male subfertility issues caused by BPA exposure.

A strategy for the preparation of super-hydrophilic molybdenum disulfide composites applied to remove uranium from wastewater.

Due to the radioactivity of uranium, the discharged nuclear wastewater not only causes certain damage to the ecology, but also causes certain harm to human life and health. Adsorption is considered to be one of the most effective ways to remove uranium. In this paper, a kind of MoS2 adsorbent was prepared by the solid phase synthesis method and functionalized with NiCo-LDH. The raw materials of MoS2 are cheap and easy to obtain, and the preparation conditions are simple, and large quantities can be obtained without limitations. MoS2 functionalized with NiCo-LDH provides more adsorption sites for the adsorbent and at the same time improves the hydrophilicity of the adsorbent, so that the active sites can fully combine with uranyl ions. The maximum adsorption capacity of the Langmuir isothermal adsorption model is 492.83 mg g-1. The selective adsorption capacity of uranium can reach 76.12% in the multi-ion coexistence system. By analyzing the adsorption mechanism with FT-IR and XRD, it is believed that on the one hand, UO22+ forms a covalent bond with Mo in MoS2 and coordinates with S on the surface of MoS2. On the other hand, UO22+ enters the NiCo-LDH layer for ion exchange with NO3- and coordinates with -OH on the surface of NiCo-LDH. The successful preparation of the MoS2/NiCo-LDH composite provides a certain application prospect for the uranium adsorption field.

Clinical outcomes and predictors of bleomycin polidocanol foam sclerotherapy treatment response in venous malformations.

OBJECTIVE: To evaluate the safety and efficacy of bleomycin polidocanol foam (BPF) sclerotherapy for venous malformations (VMs) and analyze the associated clinical outcomes and predictors. METHODS: We retrospectively assessed BPF sclerotherapy outcomes in 138 patients with VMs. We analyzed pain levels, lesion volume reduction, and subjective perception of response. Logistic regression analysis was performed to identify potential predictors of treatment outcome. Additionally, we carefully monitored and recorded complications. RESULTS: There was a notable average reduction in lesion volume by 78.50% ± 15.71%. The pain numerical rating scale (NRS) score decreased from 4.17 ± 2.63 prior to treatment to 1.05 ± 1.54 afterward, and 70.3% of the patients experienced effective relief after a single BPF treatment. Multivariate analysis revealed that a high baseline NRS (odds ratio [OR]: 4.026) and elevated activated partial thromboplastin time (APTT, OR: 1.200) were positive predictors of pain reduction. Additionally, a high baseline NRS score (OR: 1.992) and elevated thrombocytocrit (PCT, OR: 2.543) were positive predictors of incomplete postoperative pain relief. Minor complications occurred in 31 (22.46%) patients. CONCLUSION: BPF sclerotherapy is safe and effective for VMs, resulting in significant reduction in lesion volume, improved symptoms, and minimal complications. APTT and PCT levels are important predictors of pain outcomes following BPF treatment.

Comparison of bleomycin polidocanol foam vs electrochemotherapy combined with polidocanol foam for treatment of venous malformations.

OBJECTIVE: This study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. METHODS: We conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. RESULTS: Of the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. CONCLUSIONS: Our study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.

Replacing alfalfa hay with amaranth hay: effects on production performance, rumen fermentation, nutrient digestibility and antioxidant ability in dairy cow.

OBJECTIVE: The aim of this research was to explore the effects of dietary substitution of alfalfa hay by amaranth hay on production performance, rumen fermentation, nutrient digestibility, serum biochemical parameters and antioxidant ability in dairy cows. METHODS: A total of 45 healthy Holstein cows with same parity and similar milk yield and body weight were randomly divided into 3 groups: control diet without amaranth hay (CON) or 50% and 100% alfalfa hay replaced by an equal amount of amaranth hay (dry matter basis, AH1 and AH2, respectively). All the cows were fed regularly 3 times a day at 06:30, 14:30, and 22:30 and had free access to water. The experiment lasted for 60 d. RESULTS: The dry matter intake of CON and AH1 groups was higher (p<0.05) than that of AH2 group. Compared with AH1 group, the milk yield of AH2 group was reduced (p<0.05). Moreover, dietary substitution of alfalfa hay by amaranth hay increased (p<0.05) milk fat, ammonia nitrogen and acetate concentrations. However, the crude protein digestibility of AH2 group was lower (p<0.05) than that of CON group, while an opposite tendency of serum urea nitrogen was found between two groups. The neutral detergent fiber digestibility of AH1 group was increased (p<0.05) when compared to AH2 group. Amaranth hay treatment increased (p<0.05) the serum concentration of glutathione peroxidase in dairy cows. Compared with CON group, the malonaldehyde activity of AH1 group was decreased (p<0.05). CONCLUSION: Dietary replacing alfalfa hay with amaranth hay (50% ratio) in dairy cows did not affect production performance but improved their antioxidant ability.

Bisphenol A Regulates the TNFR1 Pathway and Excessive ROS Mediated by miR-26a-5p/ADAM17 Axis to Aggravate Selenium Deficiency-Induced Necroptosis in Broiler Veins.

Selenium (Se) deficiency can affect the expression of microRNA (miRNA) and induce necroptosis, apoptosis, etc., resulting in damage to various tissues and organs. Bisphenol A (BPA) exposure can cause adverse consequences such as oxidative stress, endothelial dysfunction, and atherosclerosis. The toxic effects of combined treatment with Se-deficiency and BPA exposure may have a synergistic effect. We replicated the BPA exposure and Se-deficiency model in broiler to investigate whether the combined treatment of Se-deficiency and BPA exposure induced necroptosis and inflammation of chicken vascular tissue via the miR-26A-5p/ADAM17 axis. We found that Se deficiency and BPA exposure significantly inhibited the expression of miR-26a-5p and increased the expression of ADAM17, thereby increasing reactive oxygen species (ROS) production. Subsequently, we discovered that the tumor necrosis factor receptor (TNFR1), which was highly expressed, activated the necroptosis pathway through receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like (MLKL), and regulated the heat shock proteins-related genes expressions and inflammation-related genes expressions after exposure to BPA and selenium deficiency. In vitro, we found that miR-26a-5p knockdown and increased ADAM17 can induce necroptosis by activating the TNFR1 pathway. Similarly, both N-Acetyl-L-cysteine (NAC), Necrostatin-1 (Nec-1), and miR-26a-5p mimic prevented necroptosis and inflammation caused by BPA exposure and Se deficiency. These results suggest that BPA exposure activates the miR-26a-5p/ADAM17 axis and exacerbates Se deficient-induced necroptosis and inflammation through the TNFR1 pathway and excess ROS. This study lays a data foundation for future ecological and health risk assessments of nutrient deficiencies and environmental toxic pollution.

Highly sensitive electrochemical immunosensor based on electrodeposited platinum nanostructures confined in silica nanochannels for the detection of the carcinoembryonic antigen.

In this study, we report a highly sensitive electrochemical immunosensor for carcinoembryonic antigen (CEA) detection based on the electrodeposited platinum nanoparticles (Pt NPs) confined in the ultrasmall nanochannels of vertically ordered mesoporous silica film (VMSF). VMSF bearing amine groups (NH2-VMSF) can be prepared on the indium tin oxide electrode surface via a one-step co-condensation route using an electrochemically assisted self-assembly method, which renders a strong electrostatic effect for [PtCl6]2- and leads to the spatial confinement of Pt NPs inside the silica nanochannels after electrodeposition. The external surface of NH2-VMSF is functionalized with CEA antibodies using glutaraldehyde as a coupling agent, resulting in an electrochemical immunosensing interface with good specificity for CEA detection. Under optimal experimental conditions, high affinity between the CEA antibody and CEA produces a steric hindrance effect for the accessibility of the electrochemical probe ([Fe(CN)6]3-) in the bulk solution to the underlying indium tin oxide surface, eventually resulting in the attenuated electrochemical signal and enabling the detection of the CEA with a wide linear range of 0.01 pg/mL∼10 ng/mL and a pretty low limit of detection of 0.30 fg/mL. Owing to the signal amplification ability of Pt NPs and the anti-biofouling property of NH2-VMSF, the as-prepared electrochemical immunosensor based on the Pt NPs@NH2-VMSF displays an accurate analysis of the CEA in human serum samples, holding significant promise for health monitoring and clinical diagnosis.

TP induces hepatic intolerance to FasL-mediated hepatocyte apoptosis by inhibiting XIAP.

Triptolide (TP) is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook. F. (TWHF). Its severe toxic side effects, especially hepatotoxicity, have limited the clinical application of TP-related drugs. In this study, we investigated the mechanism of the hepatotoxic effects of TP from the perspective that TP inhibited the expression of the pro-survival protein X-linked inhibitor of apoptosis protein (XIAP) and enhanced FasL-mediated apoptosis of hepatocytes. TP and CD95/Fas antibody (Jo-2) were administered by gavage to C57BL/6 mice for 7 consecutive days. After co-administration of TP and Jo-2, mouse livers showed large areas of necrosis and apoptosis and significantly increased Caspase-3 activity. KEGG pathway enrichment analysis indicated that TP may cause the development of liver injury through the apoptotic signaling pathway. Proteinprotein interaction networks showed that XIAP played an essential role in this process. TP reduced the protein expression of XIAP after combination treatment with Jo-2/FasL in vivo/in vitro. TP and FasL co-stimulation significantly increased microRNA-137 (miR-137) levels in AML12 cells, while inhibition of miR-137 expression induced a rebound in XIAP protein expression. In conclusion, TP presensitizes hepatocytes and enhances the sensitivity of hepatocytes to the Fas/FasL pathway by inhibiting the protein expression of XIAP, leading to hepatocyte apoptosis.

Research progress in biological control of tomato bacterial wilt.

Bacterial wilt caused by the infection of Ralstonia solanacearum, is one of the most harmful diseases to tomatoes, one of the most important greenhouse vegetables in China. R. solanacearum can survive and remain active in the deep soil for a long time, and the chemical control of tomato bacterial wilt is consequently limited. In this study, we introduced the characteristics of tomato bacterial wilt disease and the types of R. solanacearum, and systematically reviewed the research progresses of biological control methods from the aspects of botanical insecticides, agricultural antibiotics, biocontrol bacteria. We emphatically introduced the principle and current status of these methods, discussed the limitations and the improvement strategies, and prospected a new environmental protection and efficient biological control system based on micro-ecological regulation would be the development direction of biological control of tomato bacterial wilt.

Grape Seed Extract as a Feed Additive Improves the Growth Performance, Ruminal Fermentation and Immunity of Weaned Beef Calves.

The purpose of this research was to evaluate effects of grape seed extract (Gse) supplementation on the growth performance; ruminal fermentation; nutrient digestibility; and serum biochemical, antioxidative, and immune parameters of weaned beef calves. A total of 30 Simmental crossbred male calves with similar age and body weight were randomly allocated to two groups: a control group with no Gse (CON) and a Gse supplementation group (GSE) (4 g/d Gse per animal). The results show that, compared with the CON group, the average daily gain significantly increased (p = 0.043) in the GSE group. The ruminal contents of microbial protein and butyrate in GSE group were higher (p < 0.05) than those in the CON group. Additionally, calves fed Gse displayed increased (p < 0.05) dry matter and neutral detergent fiber digestibility. Moreover, the serum concentrations of triglyceride, catalase, superoxide dismutase, immunoglobulin G and immunoglobulin M were higher (p < 0.05) in the GSE group than those in the CON group. However, opposite tendencies of non-esterified fatty acid, malondialdehyde, tumor necrosis factor-α and interleukin-6 were found between the two groups. Overall, the supplementation of Gse can improve ruminal fermentation, nutrient digestibility, antioxidant ability, and immunity, as well as promoting the healthy growth of weaned cross-breed beef calves.

Genetic analysis of fundic gland­type gastric adenocarcinoma.

This study aimed to analyze the molecular characteristics of gastric adenocarcinoma of the fundic-gland type (GAFG) and explore the possible mechanism of tumor development. Samples from 10 Chinese patients with GAFG were collected at the Peking University International Hospital and Liaocheng People's Hospital between January 2015 and March 2022. The nucleic acid sequence of Epstein Barr virus-encoded RNA (EBV-EBER) was detected by in situ hybridization. Genetic mutation information for GNAS, KRAS, NRAS, BRAF, PIK3CA, TP53, APC, CTNNB1, HER2, MLH1, MSH2, MSH6, and PMS2 was obtained by Next-Generation Sequencing, and the relevant literature was reviewed. A total of eight instances of missense mutations were detected, consisting of seven cases with GNAS mutations, two cases with KRAS mutations, and one case with a TP53 mutation. Additionally, two patients had simultaneous missense mutations in GNAS and KRAS. Nonsynonymous mutations in APC, CTNNB1, NRAS, BRAF, PIK3CA, HER2, MLH1, MSH2, MSH6, or PMS2 were not observed in any cases. In addition, all tumors were EBER-negative. GAFG exhibits diversity at the molecular level, and GNAS mutations are more common than KRAS mutations, TP53 mutations, and microsatellite instability. To date, no association between EBV/HER2 and GAFG has been found.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

Silage additives improve fermentation quality, aerobic stability and rumen degradation in mixed silage composed of amaranth and corn straw.

The objective of this research was to investigate effects of different additives on the fermentation quality, aerobic stability and rumen degradation of mixed silage composed of amaranth and corn straw. The mixture ratio of amaranth to corn straw was 78%: 22%. Three additives were selected in this study and five groups were as follows: control group (CON, without additive), lactic acid bacteria group (LAB, 5 mg/kg, Lactobacillus plantarum ≥ 1.6×1010 CFU/g and L. buchneri ≥ 4.0×109 CFU/g), glucose group (GLU, 30 g/kg), cellulase group (CEL, 2 mg/kg) and lactic acid bacteria, glucose and cellulase group (LGC, added at the same levels as in individual group). The period of ensiling was 60 days. Fermentation quality, chemical composition and aerobic stability of mixed silage were analyzed. Four cows with permanent ruminal fistula were selected as experimental animals. Nylon bag technique was used to study rumen degradation characteristic of dry matter (DM), crude protein (CP), neutral detergent fiber (NDF) and acid detergent fiber (ADF) of mixed silage. Compared with CON group, the addition of different silage additives could improve mixed silage quality of amaranth and corn straw to some extent. Combining three additives significantly increased (P < 0.05) the DM, CP and lactic acid contents, whereas decreased (P < 0.05) the ADF and NDF contents as well as pH and ammonia nitrogen/total nitrogen. Moreover, the aerobic stability and rumen degradation of DM, CP and NDF were significantly improved (P < 0.05) in LGC group when compared to other groups. In conclusion, the combined addition of lactic acid bacteria, glucose and cellulase increased DM, CP and lactic acid contents as well as lactic acid bacteria count, decreased NDF and ADF contents and aerobic bacteria and mold counts, improved aerobic stability and rumen degradation of amaranth and corn straw mixed silage.

Therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on ovarian functions through the PI3K/Akt cascade in mice with premature ovarian failure.

Premature ovarian failure (POF) mainly refers to ovarian dysfunction in females younger than forty. Mesenchymal stem cells (MSCs) are considered an increasingly promising therapy for POF. This study intended to uncover the therapeutic effects of human umbilical cord MSC-derived extracellular vesicles (hucMSCEVs) on POF. hucMSCs were identified by observing morphology and examining differentiation capabilities. EVs were extracted from hucMSCs and later identified utilizing nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. POF mouse models were established by injecting D-galactose (Dgal). The estrous cycles were assessed through vaginal cytology, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), estradiol (E2), and progesterone (P) were measured by ELISA. The human ovarian granulosa cell line KGN was used for in vitro experiments. The uptake of hucMSC-EVs by KGN cells was detected. After D-gal treatment, cell proliferation and apoptosis were assessed via CCK-8 assay and flow cytometry. The PI3K/Akt pathway-related proteins were determined by Western blotting. Our results revealed that POF mice had prolonged estrous cycles, increased FSH and LH levels, and decreased AMH, E2, and P levels. Treatment with hucMSC-EVs partially counteracted the above changes. D-gal treatment reduced proliferation and raised apoptosis in KGN cells, while hucMSC-EV treatment annulled the changes. D-gal-treated cells exhibited downregulated p-PI3K/PI3K and p-Akt/Akt levels, while hucMSC-EVs activated the PI3K/Akt pathway. LY294002 suppressed the roles of hucMSC-EVs in promoting KGN cell proliferation and lowering apoptosis. Collectively, hucMSC-EVs facilitate proliferation and suppress apoptosis of ovarian granulosa cells by activating the PI3K/Akt pathway, thereby alleviating POF.

Repurposing Niclosamide as a Therapeutic Drug against Acute Liver Failure by Suppressing Ferroptosis.

Acute liver failure (ALF) is a severe liver disease with a high mortality rate without effective therapeutic drugs. Ferroptosis is a form of programmed cell death that plays an important role in ALF. In this study, we aimed to identify ferroptosis-related genes in ALF, thereby predicting promising compounds to treat ALF. First, mRNA microarray data were utilized to identify the ferroptosis-related differentially expressed genes (DEGs). Hub genes were screened in the protein-protein interaction network and validated. Subsequently, potential drugs to treat ALF were predicted. One of the predicted drugs was tested in an ALF model of mice. Ferroptosis examination and molecular docking were analyzed to explore the mechanism. A total of 37 DEGs were identified, ten hub genes were extracted, and their expression in ALF was validated. The predicted drug niclosamide mitigated lipopolysaccharide/D-galactosamine-induced hepatotoxicity, and decreased mortality of mice in the ALF model. Mechanically, niclosamide may combine with signal transducer and activator of transcription 3 to inhibit ALF progression by suppressing ferroptosis. This study may help advance our understanding of the role of ferroptosis in ALF, and niclosamide may be promising for therapeutic efficacy in patients with ALF.