Given the increasing demand for fruit safety assurance and environmental protection, plant essential oils have gained significant attention as natural alternatives for control of postharvest decay caused by various pathogens. In postharvest management, it is particularly important to effectively control postharvest decay without compromising the quality attributes of fruits. Although oregano essential oil (OEO) has been extensively studied for its antimicrobial properties against various postharvest pathogens, few studies have focused on its interactions with postharvest fruits. In this study, OEO was applied for management of postharvest decay of Pyrus sinkiangensis caused by Penicillium expansum, and its antifungal mechanisms and impacts on the quality attributes of pears were investigated. The OEO exhibited notable inhibitory effects, with determined MIC (0.02%) and MFC (0.04%) against P. expansum, which highlighted its potential as a viable alternative to synthetic fungicides. Our findings revealed that OEO disrupted P. expansum by compromising the integrity of the fungal plasma membrane, as evidenced by changes in plasma membrane permeability and the leakage of cellular components. The OEO treatment significantly reduced weight loss, maintained firmness, and preserved soluble-solid content in the treated pears. In addition, OEO treatment stimulated the intrinsic antioxidant mechanisms of pears, as demonstrated by elevated activities of superoxide dismutase and catalase during storage. This study provides compelling evidence for the antifungal and quality-preserving properties of OEO in the postharvest management of pears, underscoring its potential as an alternative to synthetic fungicides for controlling postharvest decay. The elucidation of the interaction between OEO and P. sinkiangensis would greatly enhance our comprehensive understanding of the biological activities of OEO and facilitate its practical application in the postharvest management of pears.

Dietary energy level plays an important role in animal growth and development. The present study investigated the effect of dietary energy on the growth performance, antioxidative state, and nutrient digestion of meat donkeys. It simultaneously explored the probable reason for cecal microbiota and metabolome. Twelve meat donkeys (male) aged 1 year with a similar weight (150 ± 25 kg) were divided into two treatment groups: low-energy group (E1) and high-energy group (E2). The experiment was divided into a 10-day pre-trial period and a 135-day trial period. Donkeys in the trial periods were fed diets with digestible energy values (in dry matter) of 12.08 and 13.38 MJ/kg (pre-fattening, 1-45 d), 13.01 and 14.27 MJ/kg (mid-fattening, 46-90 d), and 13.54 and 14.93 MJ/kg (late-fattening, 91-135 d). The results show that E1 decreases body weight, average daily gain (ADG), and the digestibility of crude protein, ether extract, neutral detergent fiber, and acid detergent fiber (p < 0.05), but increases cecal acetate and butyrate concentrations, non-esterified fatty acids (NEFAs) in serum, and the ratio of dry matter intake to ADG(F/G). E1 diminished the activities of catalase and glutathione peroxidase, while it increased the content of interleukin, tumor necrosis factor-alpha, and reactive oxygen species (ROS) (p < 0.05). Cecal microbiome showed that the abundance of Firmicutes and Actinobacteria in E1 was significantly lower than in E2 (p = 0.029, p = 0.002), whereas Bacteroidetes was higher (p = 0.005). E1 increased the genera Ruminococcaceae-UCG-004, Acinetobacter, and Rikenellaceae_RC9_gut_group. Meanwhile, cecal metabolome showed that formyl-5-hydroxykynurenamine, chorismate, 3-sulfinoalanine, and 3-isopropylmalate were upregulated in E1, while brassinolide was downregulated. The altered metabolites were mainly enriched in metabolic pathways related to energy metabolism and metabolism to mitigate oxidative stress in the meat donkeys, such as tryptophan metabolism, brassinosteroid biosynthesis metabolism, etc. In conclusion, low-energy diets resulted in a negative energy balance in meat donkeys, resulting in more nutrients being oxidized to provide energy, inducing oxidative stress, and thereby leading to decreasing growth. The reduction in meat donkey growth from low-energy diets was related to changes in cecum microbiota and metabolites.

Multiple sclerosis (MS) is an autoimmune disease mediated by T helper cells, which is characterized by neuroinflammation, axonal or neuronal loss, demyelination, and astrocytic gliosis. Histone deacetylase inhibitors (HDACis) are noted for their roles in easing inflammatory conditions and suppressing the immune response. Panobinostat, an HDACi, is now being used in treating multiple myeloma. Nevertheless, the effect of panobinostat on autoimmune diseases remains largely unclear. Thus, our research endeavored to determine if the administration of panobinostat could prevent experimental autoimmune encephalomyelitis (EAE) in mice, one of the most commonly used animal models of MS, and further explored the underlying mechanisms. The EAE mice were generated and then administered continuously with panobinostat at a dosage of 30 mg/kg for 16 days. The results indicated that panobinostat markedly alleviated the clinical symptoms of EAE mice, inhibiting demyelination and loss of oligodendrocytes in the central nervous system (CNS). Moreover, panobinostat decreased inflammation and the activation of microglia and astrocytes in the spinal cords of EAE mice. Mechanistically, treatment with panobinosat significantly suppressed M1 microglial polarization by blocking the activation of toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (MyD88)/interferon regulatory factor 5 (IRF5) pathway. Additionally, panobinostat inhibited mitochondrial dysfunction and reduced oxidative stress in the spinal cords of EAE mice. In conclusion, our findings reveal that panobinostat significantly ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting oxidative stress-linked neuroinflammation and mitochondrial dysfunction.

A growing number of patients with early-stage cervical cancer opt for local tumor resection to preserve the uterus. Nevertheless, there is still a dearth of long-term comparisons between local tumor destruction/excision (LTD/LTE) and total hysterectomy(TH), and the optimal target population for local tumor excision remains uncertain.

Perceived discrimination constitutes an essential factor influencing the psychological crisis of college students. While prior research has examined the impact of discrimination on mental health in China, this study is the first to systematically investigate the chain mediating role of sense of life meaning and self-esteem in the relationship between perceived discrimination and psychological crisis. This approach not only enhances the theoretical framework of the relationship between discrimination and mental health but also offers a novel perspective for understanding discrimination-induced psychological crises in Chinese society.

Acute myeloid leukemia (AML) is the most prevalent kind of acute leukemia in adults. Despite the availability of new targeted therapies, AML remains connected with a poor prognosis and decreased rate of survival. Tubeimoside I (TBMS1), a critical compound extracted from Bolbostemma paniculatum, has demonstrated potential anticancer effects in lung and colorectal cancers. Nevertheless, the TBMS1 anticancer pathway against AML is still elusive. This study aimed to explore the potential role of TBMS1 in anti-AML and its molecular mechanism. In vitro, TBMS1 treatment suppressed AML cells proliferation, induced apoptosis, and mitochondrial damage, and elevated ROS levels. Network pharmacological analysis suggested, and subsequent studies confirmed, that TBMS1 induced mitophagy in AML cells by modulating the PINK1/Parkin/Mfnh2 signaling pathway, an effect that was effectively reversed following PINK1 knockdown. In vivo, TBMS1 treatment suppressed the proliferation of AML cells after 21 days, improved the survival rates of nude mice, and showed no evident organ toxicity. These evidences suggest that TBMS1 may have significant therapeutic potential in treating AML.

Mitochondrial dysfunction has been implicated in the pathogenesis of aortic aneurysms (AA); however, the causal role of mitochondrial-related proteins remains unclear. This study employs a Mendelian randomization (MR) approach to investigate the potential causal relationship between mitochondrial proteins and AA. Genetic instruments for mitochondrial proteins were obtained from the IEU Open genome-wide association study database, while AA-related genetic data were sourced from the FinnGen biobank. Inverse-variance weighting (IVW) served as the primary MR method, with MR-Egger and weighted median approaches utilized as complementary methods. Sensitivity analyses, including Cochran Q test, MR-Egger intercept, and MR-PRESSO, were performed to assess heterogeneity and pleiotropy. Reverse MR analysis was conducted to exclude the possibility of reverse causation. To enhance the robustness of the findings, replication was carried out using genome-wide association study Catalog data, and a meta-analysis was performed by integrating discovery and replication datasets. Gene expression validation was conducted using the Gene Expression Omnibus dataset, and gene set enrichment analysis (GSEA) was applied to explore relevant biological pathways. Additionally, in vitro experiments employing platelet-derived growth factor-BB-induced human aortic smooth muscle cells were performed to validate the expression patterns of mitochondrial-related proteins at both mRNA and protein levels. Through rigorous genetic variant selection, MR analysis using IVW, sensitivity analyses, replication, and meta-analysis, we identified iron-sulfur cluster assembly enzyme (ISCU), 39S ribosomal protein L14 (MRPL14), and mitochondrial peptide methionine sulfoxide reductase (MSRA) as mitochondrial proteins associated with AA. Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or pleiotropy. Reverse MR analysis ruled out reverse causation. Gene expression analysis demonstrated that ISCU was significantly upregulated, whereas MRPL14 and MSRA were downregulated in AA tissues. GSEA revealed that these proteins are involved in pathways related to inflammation, immune response, and vascular remodeling. In vitro experiments further corroborated these findings, demonstrating consistent expression patterns in platelet-derived growth factor-BB-induced human aortic smooth muscle cells. This study provides robust genetic and experimental evidence supporting the causal role of ISCU, MRPL14, and MSRA in AA pathogenesis. These mitochondrial proteins may serve as potential biomarkers and therapeutic targets for AA, warranting further investigation.

Long-time mobile phone use (LTMPU) has been linked to emotional issues such as anxiety and depression while the enlarged perivascular spaces (EPVS), as marker of neuroinflammation, is closely related with mental disorders. In the current study, we aim to develop a predictive model utilizing MRI-quantified EPVS metrics and machine learning algorithms to assess the severity of anxiety and depression symptoms in patients with LTMPU.

Tuberculosis (TB) diagnostic monitoring is paramount to clinical decision-making and the host biomarkers appears to play a significant role. The currently available diagnostic technology for TB detection is inadequate. In the present study, we aimed to identify biomarkers for diagnosis of pulmonary tuberculosis (PTB) using urinary metabolomic and proteomic analysis.

Aberrant N6-methyladenosine (m6A) modification on mRNA results in dysregulated mRNA translation and cancer progression; however, the role of m6A modification on rRNA remains unclear in cancers. Here, we show that ZCCHC4 and its mediated m6A modification on 28S rRNA are upregulated in various cancers and correlated with poor survival. Functionally, ZCCHC4 promotes intrahepatic cholangiocarcinoma (ICC) progression via its catalytic activity. Mechanistically, tether of the N6-adenineMIase domain of ZCCHC4 to the m6A site on 28S rRNA facilitates the binding of the zf-GRF-containing domain to eIF3G in the translation initiation complex and the binding of zf-DHHC-containing domain to the 3' UTR of mRNA, therefore facilitating mRNA circularization and translation. Further analysis reveals that HPD mediates ZCCHC4's functions on tyrosine catabolism and ICC progression, and targeting HPD inhibits ICC progression in vivo. Overall, our findings uncover insights underlying mRNA translation control and provide a molecular basis for targeting the ZCCHC4-HPD axis in ICC.

The neurotransmitter gamma-aminobutyric acid (GABA) has been thought to be involved in the development of some types of cancer. Yet, the de novo synthesis of GABA and how it functions in hepatocellular carcinoma (HCC) remain unclear. Here, we report that SLC6A12 acts as a transporter of GABA, and that aldehyde dehydrogenase 9 family member A1 (ALDH9A1), not glutamate decarboxylase 1 (GAD1), generates GABA in human HCC. Interestingly, SLC6A12 and ALDH9A1 are upregulated during lung metastases of HCC, and depletion of either of them leads to impaired HCC metastasis. Mechanistically, GABA directly binds and stabilizes β-catenin, resulting in activated Wnt/β-catenin signaling, and thereby enhancing HCC metastasis. Reciprocally, β-catenin transcriptionally upregulates SLC6A12 to import more GABA to stabilize β-catenin. Thus, our findings identify ALDH9A1 as the major GABA synthetase in HCC, demonstrate a positive-feedback regulatory mechanism for sustaining Wnt/β-catenin signaling, and reveal a role for β-catenin in sensing GABA, which contributes to HCC metastasis.

Despite its association with high mortality rates and negative fetal outcomes, large-scale epidemiological studies on scrub typhus (ST) during pregnancy remain scarce.

Phragmites australis is a globally distributed grass species (Poaceae) recognized for its vast biomass and exceptional environmental adaptability, making it an ideal model for studying wetland ecosystems and plant stress resilience. However, genomic resources for this species have been limited. In this study, we assembled a chromosome-level reference genome of P. australis containing one B chromosome. An explosion of LTR-RTs, centered on the Copia family, occurred during the late Pleistocene, driving the expansion of P. australis genome size and subgenomic differentiation. Comparative genomic analysis showed that P. australis underwent two whole gene duplication events, was segregated from Cleistogenes songorica at 34.6 Mya, and that 41.26% of the gene families underwent expansion. Based on multi-tissue transcriptomic data, we identified structural genes in the biosynthetic pathway of pharmacologically active Phragmitis rhizoma polysaccharides with essential roles in rhizome development. This study deepens our understanding of Arundinoideae evolution, genome dynamics, and the genetic basis of key traits, providing essential data and a genetic foundation for wetland restoration, bioenergy development, and plant stress.

The global health challenge of ulcerative colitis (UC) has been classified by the WHO as a modern refractory disease, commonly referred to as green cancer, with limited treatment options still available, highlighting the urgent need for the development of new therapeutic strategies. Recent pharmacological research has shown that traditional Chinese medicine saussurea costus (SC) possesses beneficial antibacterial and anti-inflammatory properties. Nevertheless, its underlying mechanism remains elusive.

Clock genes regulate physiological and metabolic processes by responding to changes in environmental light and temperature, and genetic variations in these genes may facilitate environmental adaptation, offering opportunities for resilience to climate change. However, the genetic and molecular mechanisms remain unclear in marine organisms. In this study, we investigated the role of a key clock gene, the circadian locomotor output cycles kaput (Clock), in thermal adaptation using DNA affinity purification sequencing (DAP-Seq) and RNA interference (RNAi)-based transcriptome analysis. In cold-adapted Crassostrea gigas and warm-adapted Crassostrea angulata, Clock was subject to environmental selection and exhibited contrasting expression patterns. The transcriptome analysis revealed 2054 differentially expressed genes (DEGs) following the knockdown of the Clock expression, while DAP-Seq identified 150,807 genes regulated by Clock, including 5273 genes located in promoter regions. The combined analyses identified 201 overlapping genes between the two datasets, of which 98 were annotated in public databases. These 98 genes displayed distinct expression patterns in C. gigas and C. angulata under heat stress, which were potentially regulated by Clock, indicating its role in a molecular regulatory network that responds to heat stress. Notably, a heat-shock protein 70 family gene (Hsp12b) and a tripartite motif-containing protein (Trim3) were significantly upregulated in C. angulata but showed no significant changes in C. gigas, further highlighting their critical roles in thermal adaptation. This study preliminarily constructs a thermal regulatory network involving Clock, providing insights into the molecular mechanisms of clock genes in thermal adaptation.

Percutaneous coronary intervention (PCI) can effectively restore myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, STEMI patients may still experience a "no-reflow" phenomenon after PCI. Accordingly, this study focused on the clinical value of low-dose dobutamine stress myocardial contrast echocardiography (MCE) for evaluating myocardial microcirculation perfusion and long-term prognosis in STEMI patients after PCI.

Obesity can contribute to infertility, but the exact relationship between infertility risk and obesity-related measurements like waist-to-height ratio (WHtR), body roundness index (BRI), conicity index (CoI), and A body shape index (ABSI) in women is uncertain. We investigated the association between these indices and female infertility.

Repairing critical bone defects remains a formidable challenge in regenerative medicine. Scaffolds that can fill defects and facilitate bone regeneration have garnered considerable attention. However, scaffolds struggle to provide an ideal microenvironment for cell growth and differentiation at the interior of the bone defect sites. The scaffold's structure must meet specific requirements to support endogenous bone regeneration. Here, we introduce a novel 3D-printed nanocolloidal gelatin methacryloyl (GelMA) hydrogel, namely, the nG hydrogel, that was derived from the self-assembly of GelMA in the presence of Pluronics F68, emphasizing its osteoinductive capability conferred solely by the specific nanocolloidal structure. The nG hydrogel, exhibiting remarkable pore connectivity and cell-adaptable microscopic structure, induced the infiltration and migration of rat bone mesenchymal stem cells (rBMSCs) into the hydrogel with a large spreading area in vitro. Moreover, the nG hydrogel with interconnected nanospheres promoted the osteogenic differentiation of rBMSCs, leading to up-regulated expression of ALP, RUNX2, COL-1, and OCN, as well as augmented formation of calcium nodules. In the critical-sized rat calvarial defect model, the nG hydrogel demonstrated improved repair of bone defects, with enhanced recruitment of endogenous CD29+ and CD90+ stem cells and increased bone regeneration, as indicated by significantly higher bone mineral density (BMD) in vivo. Mechanistically, the integrin β1/focal adhesion kinase (FAK) mechanotransduction signaling pathway was up-regulated in the nG hydrogel group both in vitro and in vivo, which may partially account for its pronounced osteoinductive capability. In conclusion, the cell-adaptable nG hydrogel shows great potential as a near-future clinical translational strategy for the customized repair of critical-sized bone defects.

Insulin-like Growth Factor 2 mRNA-binding Protein 1 (IGF2BP1) is a candidate gene of significant interest for modulating economically important traits in livestock and poultry. The second intron of IGF2BP1 has been implicated in growth-related traits, though its precise mechanistic role remains elusive. Initial resequencing analyses in our laboratory indicated strong selective pressures on the IGF2BP1 genomic region, prompting the selection and identification of several single nucleotide polymorphisms (SNPs). Seven SNPs were mapped to the conserved region of the second intron, necessitating further investigation into their functional relevance and association with growth traits. In this study, 348 Nanjiang Yellow goats were analyzed, and the association analysis via the GLM program in SAS 9.4 identified five SNPs significantly correlated with growth traits. Notably, rs652062749(A > G) emerged as a critical locus influencing later-stage growth traits. Furthermore, strong linkage disequilibrium was observed among three SNPs, with the rs638185407 (T > A) variant markedly enhancing luciferase activity in H293T cells. Combination genotypes TTAACT, TTCCCC, and ATCACT were identified as superior for growth traits, offering theoretical insights for genetic co-breeding. This study underscores the potential utility of IGF2BP1 as a functional genetic marker in Nanjiang Yellow goat breeding programs.

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Infiltration and alterations in non-cardiomyocytes of the human heart involve crucially in the occurrence of DCM and associated immunotherapeutic approaches.