Polyketides with α-glucosidase inhibitory and neuroprotective activities from Aspergillus versicolor associated with Pedicularis sylvatica.

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.

Foliar uptake screening: A promising strategy for identifying wheat varieties with low lead accumulation.

Lead (Pb) contamination in wheat grain is of great concern, especially in North China. Atmospheric deposition is a major contributor to Pb accumulation in wheat grain. Screening low Pb accumulating wheat varieties has been an effective method for addressing Pb contamination in wheat grain. However, identifying wheat varieties with low Pb accumulation based on foliar uptake of atmospheric Pb has been neglected. Therefore, two field trials with distinct atmospheric Pb deposition were conducted to screen for stable varieties with low Pb accumulation. It was verified that YB700 and CH58, which have high thousand-grain weights and stable low Pb accumulation in field 1 (0.19 and 0.13 mg kg-1) and field 2 (0.17 and 0.20 mg kg-1), respectively, were recommended for cultivation in atmospheric Pb contaminated farmlands in North China. Furthermore, indoor experiments were conducted to investigate Pb uptake by the roots and leaves of different wheat varieties. Our findings indicate that Pb accumulation in different wheat varieties is primarily influenced by foliar Pb uptake rather than root Pb uptake. Interestingly, there was a positive correlation (p < 0.05) between the Pb concentrations in leaves and the stomatal width and trichome length of the adaxial epidermal surface. Additionally, there is a positive correlation (p < 0.01) between the Pb concentration in the wheat grain and trichome length. In conclusion, the screening of wheat varieties with narrower stomatal widths or shorter trichomes based on foliar uptake pathways is an effective strategy for ensuring food safety in areas contaminated by atmospheric Pb.

Spatial and emotional distances in parent-child relationships: Impacts on human capital development in rural Chinese boarding children.

BACKGROUND: The policy of merging remote rural elementary schools into centralized villages has led to the emergence of boarding schools as an essential means of providing compulsory education in rural areas of China. As boarding children reside in schools for extended periods, parents' influence on their human capital development is inevitably specificity. The development of rural boarding children is a serious social issue in China, and parent-child distance plays a crucial role in affecting the development of children's human capital. OBJECTIVE: While previous studies have focused on the relationship between parental absence and the development of human capital in rural boarding children, this study examines the effects of both spatial and emotional distance between parents and children on the human capital of rural boarding children. PARTICIPANTS AND SETTING: A stratified, multi-stage probabilities proportional to size (PPS) sampling method was used, and self-report questionnaires were completed by 2397 rural boarding children (54.2 % males; ages 12 to 18, M = 14.66, SD = 1.30). METHODS: Children's background, family, and school and teacher characteristics were used as control variables. An OLS regression model was used to assess the effects of parent-child spatial and emotional distance on the human capital of rural boarding children, and a CMP-OLS regression model was used to address endogeneity using parents' self-assessed family economic conditions as instrumental variables. RESULTS: Parent-child spatial distance had a significant positive effect (p < 0.05, p < 0.05), and emotional distance had a significant negative effect (p < 0.05, p < 0.01) on the cognitive and non-cognitive abilities development of rural boarding children. Living with grandparents heightened the negative effect on non-cognitive abilities development. CONCLUSIONS: The findings of this study strengthen the link between parent-child distance and rural boarding children and the moderating impact of living with grandparents on the effect of parent-child distance on rural boarding children's human capital providing new insights for promoting the development of rural boarding children. It also highlights the detrimental effects of emotional neglect on rural boarding children's development. This is important for realizing China's rural revitalization strategy and the healthy development of disadvantaged children in rural areas.

Intestinal flora: New perspective of type 2 diabetes.

Diabetes comprises a group of metabolic diseases characterized by hyperglycemia stemming from various factors. Current diabetes management primarily focuses on blood glucose control, yet it is inherently progressive, necessitating increased reliance on exogenous blood glucose control methods over time. Therefore, there is an urgent need to explore novel intervention strategies addressing both diabetes and its complications. The human intestinal microbiota, often referred to as the "second genome", exhibits significant diversity and plays a pivotal role in insulin resistance, glucose and lipid metabolism, and inflammatory response. Notably, Li and Guo have elucidated the involvement of intestinal flora in the pathogenesis of type 2 diabetes mellitus (T2DM) and proposed a novel therapeutic approach targeting intestinal microbes. This advancement enhances our comprehension of the multifaceted and multi-target regulation of T2DM by intestinal microflora, thereby offering fresh avenues for understanding its pathogenesis and clinical management. This letter briefly summarizes the role of intestinal flora in T2DM based on findings from animal experiments and clinical studies. Additionally, it discusses the potential clinical applications and challenges associated with targeting intestinal flora as therapeutic interventions.

The construction of a nomogram to predict the prognosis and recurrence risks of UPJO.

Objective: This study was conducted to explore the risk factors for the prognosis and recurrence of ureteropelvic junction obstruction (UPJO). Methods: The correlation of these variables with the prognosis and recurrence risks was analyzed by binary and multivariate logistic regression. Besides, a nomogram was constructed based on the multivariate logistic regression calculation. After the model was verified by the C-statistic, the ROC curve was plotted to evaluate the sensitivity of the model. Finally, the decision curve analysis (DCA) was conducted to estimate the clinical benefits and losses of intervention measures under a series of risk thresholds. Results: Preoperative automated peritoneal dialysis (APD), preoperative urinary tract infection (UTI), preoperative renal parenchymal thickness (RPT), Mayo adhesive probability (MAP) score, and surgeon proficiency were the high-risk factors for the prognosis and recurrence of UPJO. In addition, a nomogram was constructed based on the above 5 variables. The area under the curve (AUC) was 0.8831 after self cross-validation, which validated that the specificity of the model was favorable. Conclusion: The column chart constructed by five factors has good predictive ability for the prognosis and recurrence of UPJO, which may provide more reasonable guidance for the clinical diagnosis and treatment of this disease.

Targeting estrogen mediated CYP4F2/CYP4F11-20-HETE metabolic disorder decelerates tumorigenesis in ER+ breast cancer.

Purpose: As the most common subset of breast cancer (BC), estrogen receptor positive (ER+) BC accounting for 80% of cases, has become a global public health concern. The female hormone estrogen (E2) unequivocally drives ER + breast malignancies. The reasons that estrogen affects BC development has long been considered, yet further study remains to be conducted of the molecular events in the E2-estrogen receptor α (ERα) signaling pathway in ER + BC progression, especially lipid metabolism, so providing more options for tailored and individualized therapy. Our aim is to find out new targets and clinical biomarkers for ER + breast cancer treatment from the perspective of lipid metabolism. Methods: Lipid metabolomics profiling was used to examine the membrane phospholipid stimulated by E2. Clinical BC samples were used to assess the association of CYP4F2, CYP4F11 expression with clinicopathological characteristics and patient outcomes. Some inhibitors of main enzymes in AA metabolism were used combined with E2 to assess roles of CYP4F2/CYP4F11 in the progression of ER + BC. CYP4F2, CYP4F11 overexpression and knockdown BC cell lines were employed to examine the effects of CYP4F2, CYP4F11 on cellular proliferation, apoptosis and tumor growth. Western blotting, qPCR, Immunohistochemical staining and flow cytometry were also conducted to determine the underlying mechanisms related to CYP4F2, CYP4F11 function. Results: The activation of the CYP450 signaling pathway in arachidonic acid metabolism contributed to ER + BC tumorigenesis. In ER + BC, CYP4F2 and CYP4F11 overexpression induced by E2 could promote cancer cell proliferation and resistance to apoptosis by producing the metabolite 20-HETE and activating the antiapoptotic protein Bcl-2. CYP4F2 and CYP4F11 elevation correlates with poorer overall survival and disease-free survival in ER + BC patients. Conclusion: CYP4F2, CYP4F11 and their metabolite 20-HETE could serve as effective prognostic markers and attractive therapeutic targets for novel anticancer drug development about ER + BC.

Identification and analysis of MSC-Exo-derived LncRNAs related to the regulation of EMT in hypospadias.

OBJECTIVE: This study aims to screen the differentially expressed long non-coding RNAs (DELncRNAs) related to the regulation of epithelial-mesenchymal transition (EMT) in hypospadias in mesenchymal stem cell-derived exosomes (MSC-Exons) and explore the potential mechanism of these lncRNAs for the EMT in hypospadias. METHODS: In this study, the microarray data related to MSC-Exos and hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the lncRNAs highly expressed in MSC-Exos and the differentially expressed mRNAs and lncRNAs in children with hypospadias were screened, respectively. In addition, the lncRNAs enriched in MSC-Exos and differentially expressed lncRNAs in hypospadias were intersected to obtain the final DElncRNAs. Moreover, the co-expression interaction pairs of differentially expressed lncRNAs and mRNAs were analyzed to construct a Competing Endogenous RNA (ceRNA) network. Finally, the candidate lncRNAs in exosomes were subjected to in vitro cell function verification. RESULTS: In this study, a total of 4 lncRNAs were obtained from the microarray data analysis. Further, a ceRNA regulatory network of MSC-Exo-derived lncRNAs related to the regulation of EMT in hypospadias was constructed, including 4 lncRNAs, 2 mRNAs, and 6 miRNAs. The cell function verification results indicated that the exosomes secreted by MSCs may transport HLA complex group 18 (HCG18) into target cells, which promoted the proliferation, migration, and EMT of these cells. CONCLUSION: MSC-Exo-derived lncRNA HCG18 can enter target cells, and it may be involved in the regulation of EMT in hypospadias through the ceRNA network.

Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms.

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.

Regulation of VEGF gene expression by bisacridine derivative through promoter i-motif for cancer treatment.

BACKGROUND: Vascular endothelial growth factor (VEGF) is overexpressed in most malignant tumors, which has important impact on tumor angiogenesis and development. Its gene promoter i-motif structure formed by C-rich sequence can regulate gene expression, which is a promising new target for anti-tumor therapy. METHODS: We screened various compounds and studied their effects on VEGF through extensive experiments, including SPR, MST, TO displacement, FRET, CD, ESI-MS, NMR, MTT, clone formation, qPCR, Western blot, dual-luciferase reporter assay, immunofluorescence, cell scrape, apoptosis, transwell assay, and animal model. RESULTS: After extensive screening, bisacridine derivative B09 was found to have selective binding and stabilization to VEGF promoter i-motif, which could down-regulate VEGF gene expression. B09 showed potent inhibition on MCF-7 and HGC-27 cell proliferation and metastasis. B09 significantly inhibited tumor growth in xenograft mice model with HGC-27 cells, showing decreased VEGF expression analyzed through immunohistochemistry. CONCLUSION: B09 could specifically regulate VEGF gene expression, possibly through interacting with promoter i-motif structure. As a lead compound, B09 could be further developed for innovative anti-cancer agent targeting VEGF.

Nephroblastoma-specific dysregulated gene SNHG15 with prognostic significance: scRNA-Seq with bulk RNA-Seq data and experimental validation.

Wilms tumor (WT) is the most common malignancy of the genitourinary system in children. Currently, the Integration of single-cell RNA sequencing (scRNA-Seq) and Bulk RNA sequencing (RNA-Seq) analysis of heterogeneity between different cell types in pediatric WT tissues could more accurately find prognostic markers, but this is lacking. RNA-Seq and clinical data related to WT were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Small nucleolar RNA host gene 15 (SNHG15) was identified as a risk signature from the TARGET dataset by using weighted gene co-expression network analysis, differentially expressed analysis and univariate Cox analysis. After that, the functional mechanisms, immunological and molecular characterization of SNHG15 were investigated at the scRNA-seq, pan-cancer, and RNA-seq levels using Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), ESTIMATE, and CIBERSORT. Based on scRNA-seq data, we identified 20 clusters in WT and annotated 10 cell types. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing M2 macrophages as hubs for intercellular communication. In addition, in vitro cellular experiments showed that siRNAs interfering with SNHG15 significantly inhibited the proliferation and migration of G401 cells and promoted the apoptosis of G401 cells compared with the control group. The effect of siRNAs interfering with SNHG15 on EMT-related protein expression was verified by Western blotting assay. Thus, our findings will improve our current understanding of the pathogenesis of WT, and they are potentially valuable in providing novel prognosis markers for the treatment of WT.

Identification and characterization of a fungal cutinase-like enzyme CpCut1 from Cladosporium sp. P7 for polyurethane degradation.

Plastic degradation by biological systems emerges as a prospective avenue for addressing the pressing global concern of plastic waste accumulation. The intricate chemical compositions and diverse structural facets inherent to polyurethanes (PU) substantially increase the complexity associated with PU waste management. Despite the extensive research endeavors spanning over decades, most known enzymes exhibit a propensity for hydrolyzing waterborne PU dispersion (i.e., the commercial Impranil DLN-SD), with only a limited capacity for the degradation of bulky PU materials. Here, we report a novel cutinase (CpCut1) derived from Cladosporium sp. P7, which demonstrates remarkable efficiency in the degrading of various polyester-PU materials. After 12-h incubation at 55°C, CpCut1 was capable of degrading 40.5% and 20.6% of thermoplastic PU film and post-consumer foam, respectively, while achieving complete depolymerization of Impranil DLN-SD. Further analysis of the degradation intermediates suggested that the activity of CpCut1 primarily targeted the ester bonds within the PU soft segments. The versatile performance of CpCut1 against a spectrum of polyester-PU materials positions it as a promising candidate for the bio-recycling of waste plastics.IMPORTANCEPolyurethane (PU) has a complex chemical composition that frequently incorporates a variety of additives, which poses significant obstacles to biodegradability and recyclability. Recent advances have unveiled microbial degradation and enzymatic depolymerization as promising waste PU disposal strategies. In this study, we identified a gene encoding a cutinase from the PU-degrading fungus Cladosporium sp. P7, which allowed the expression, purification, and characterization of the recombinant enzyme CpCut1. Furthermore, this study identified the products derived from the CpCut1 catalyzed PU degradation and proposed its underlying mechanism. These findings highlight the potential of this newly discovered fungal cutinase as a remarkably efficient tool in the degradation of PU materials.

Hypoxia-activated selectivity-improved anti-PKM2 antibody combined with prodrug TH-302 for potentiated targeting therapy in hepatocellular carcinoma.

Background: Hypoxia induces hepatocellular carcinoma (HCC) malignancies; yet it also offers treatment opportunities, exemplified by developing hypoxia-activated prodrugs (HAPs). Although HAP TH-302 combined with therapeutic antibody (Ab) has synergistic effects, the clinical benefits are limited by the on-target off-tumor toxicity of Ab. Here, we sought to develop a hypoxia-activated anti-M2 splice isoform of pyruvate kinase (PKM2) Ab combined with TH-302 for potentiated targeting therapy. Methods: Codon-optimized and hypoxia-activation strategies were used to develop H103 Ab-azo-PEG5k (HAP103) Ab. Hypoxia-activated HAP103 Ab was characterized, and hypoxia-dependent antitumor and immune activities were evaluated. Selective imaging and targeting therapy with HAP103 Ab were assessed in HCC-xenografted mouse models. Targeting selectivity, systemic toxicity, and synergistic therapeutic efficacy of HAP103 Ab with TH-302 were evaluated. Results: Human full-length H103 Ab was produced in a large-scale bioreactor. Azobenzene (azo)-linked PEG5k conjugation endowed HAP103 Ab with hypoxia-activated targeting features. Conditional HAP103 Ab effectively inhibited HCC cell growth, enhanced apoptosis, and induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) functions. Analysis of HCC-xenografted mouse models showed that HAP103 Ab selectively targeted hypoxic HCC tissues and induced potent tumor-inhibitory activity either alone or in combination with TH-302. Besides the synergistic effects, HAP103 Ab had negligible side effects when compared to parent H103 Ab. Conclusion: The hypoxia-activated anti-PKM2 Ab safely confers a strong inhibitory effect on HCC with improved selectivity. This provides a promising strategy to overcome the on-target off-tumor toxicity of Ab therapeutics; and highlights an advanced approach to precisely kill HCC in combination with HAP TH-302.

Dietary copper requirement of broilers fed a corn-soybean meal diet during 22-42 d of age.

This research was to assess the dietary copper (Cu) requirement of broiler chickens fed a practical corn-soybean meal diet during 22-42 d of age. A total of 288 numbered Arbor Acres male broilers at 22 d of age were randomly allotted 6 treatments with 8 replicate cages (6 broilers per cage) per treatment. Broilers were fed a Cu-unsupplemented corn-soybean meal basal diet (control, containing 7.36 mg Cu/kg) or the basal diet added with 3, 6, 9, 12, or 15 mg Cu/kg from CuSO4·5H2O for 21 d. Quadratic, asymptotic and broken-line models were fitted and the best fitted models were selected to determine dietary Cu requirements. The results revealed that the contents of Cu in serum and liver, mRNA expression levels of Cu- and zinc-containing superoxide dismutase (CuZnSOD) in liver and monoamine oxidase b (MAO B) in heart, as well as protein expression level of CuZnSOD in liver were affected (P < 0.05) by supplemental Cu levels, and the above indices varied linearly and quadratically (P < 0.05) with increasing Cu levels. Dietary Cu requirements assessed according to the best fitted broken-line models (P < 0.05) of the above indexes were 10.45-13.81 mg/kg. It was concluded that mRNA expression levels of CuZnSOD in liver and MAO B in heart, as well as liver CuZnSOD protein expression level were new specific sensitive biomarkers for estimating dietary Cu requirements, and the dietary Cu requirement was recommended to be 14 mg/kg to support Cu metabolic needs related to key Cu-containing enzymes in broilers fed the corn-soybean meal diet during 22-42 d of age, which was higher than the dietary Cu requirement (8 mg/kg) for broilers at the corresponding stage suggested by the Chinese Feeding Standard of Chicken.

Case report: remedial microdissection testicular sperm extraction after onco-microdissection testicular sperm extraction failure.

BACKGROUND: Testicular cancer (TC) mostly occurs in men aged 14 to 44. Studies have shown that TC seriously damages male fertility, and 6% to 24% of patients with TC were even found to suffer from azoospermia when they are diagnosed. At present, some studies have pointed out that onco-microdissection testicular sperm extraction (mTESE) can extract sperm from tumor testicles. However, there are almost no reports on remedial measures after onco-mTESE failure. Given the valuable opportunity for fertility preservation in patients with TC and azoospermia, it is necessary to provide effective remedial methods for patients with failed onco-mTESE. METHODS: Two young men, who were diagnosed with TC and also found to have azoospermia, tried onco-mTESE while undergoing radical orchiectomy for fertility preservation. However, sperm extraction failed in both patients. Subsequently, the isolated testicular tissue of the patient in case 1 suffered from TC again, and the patient in case 2 was scheduled to receive multiple cycles of gonadotoxic chemotherapy. Because both had a plan to have a birth in the future, we performed remedial mTESE. RESULTS: Sperm was successfully extracted from both patients. The patient recovered well, without complications. The patient couple in case 1 underwent 1 intracytoplasmic sperm injection (ICSI) cycle but did not achieve clinical pregnancy. CONCLUSIONS: There is still an opportunity to extract sperm successfully using onco-mTESE, despite the difficulty of fertility preservation in TC patients with azoospermia. If sperm extraction from the tumor testis fails, implementing remedial mTESE as early as possible would likely preserve the last chance of fertility for these patients.

Effects of butyl paraben on behavior and molecular mechanism of Chinese striped-necked turtle (Mauremys sinensis).

Butyl paraben (BuP) is widely used in cosmetics, drugs, and food preservation. Recently it is an identified new pollutant that affects various aspects of reproduction, lipid metabolism, and nervous system. Behavioral activity serves as a pre-warning biomarker for predicting water quality. So, in this study, the changes in some behaviors and its neurotransmitters and cell apoptosis in the brain of Chinese striped-necked turtles (Mauremys sinensis) were studied when the turtles were exposed to BuP concentrations of 0, 5, 50, 500, and 5000 µg/L for 21 weeks. The results showed that, the basking time and altering scores to external stimuli in the groups of 50, 500, and 5000 µg/L were significantly reduced, while the time for body-righting was significantly increased, compared with the control (0 µg/L), indicating that the turtles exhibited depression and inactive behavior. The analysis of neurotransmitter in the brain showed that 5-hydroxytryptamine (5-HT) contents in the groups of 500 and 5000 µg/L were significantly higher than the other groups, which was due to an increase in the mRNA relative expression levels of the 5-HT receptor gene (5-HTR), neurotransmitter transporter genes (Drd4, Slc6a4), and neurotransmitter synthase tryptophan hydroxylase (TPH). Furthermore, GABA transaminase (GABA-T) activity increased in the 500 and 5000 µg/L groups, and tyrosine hydroxylase (TH) activity increased dramatically in the 5000 µg/L group. However, acetyl-CoA (AChE) activity was significantly reduced in these four BuP exposure groups. These changes could be attributed to decreased movement velocity and increased inactivity. Meanwhile, the mRNA expression level of BAX, Bcl-2, caspase-9 and TUNEL assay indicated the occurrence of cell apoptosis in the brains of the higher BuP exposed groups, which may play an important role in neuronal death inducing behavior change. In summary, these findings offer fundamental insights into turtle ecotoxicology and serve as a foundation for a comprehensive assessment of the ecological and health risks associated with BuP.

Activating nickel foam with trace titanium oxide for enhanced water oxidation.

Nickel-based electrocatalysts for water oxidation suffer from low activity and poor stability. In this work, 0.015 mg cm-2 TiO2 nanosheets anchored on Ni foam addressed these problems after electrochemical activation. In situ investigations, including Raman spectra, corroborated the enhanced generation of highly active Ni(III)-O-O species on Ni foam in the presence of trace TiO2.

Applications of Raman spectroscopy in the diagnosis and monitoring of neurodegenerative diseases.

Raman scattering is an inelastic light scattering that occurs in a manner reflective of the molecular vibrations of molecular structures and chemical conditions in a given sample of interest. Energy changes in the scattered light can be assessed to determine the vibration mode and associated molecular and chemical conditions within the sample, providing a molecular fingerprint suitable for sample identification and characterization. Raman spectroscopy represents a particularly promising approach to the molecular analysis of many diseases owing to clinical advantages including its instantaneous nature and associated high degree of stability, as well as its ability to yield signal outputs corresponding to a single molecule type without any interference from other molecules as a result of its narrow peak width. This technology is thus ideally suited to the simultaneous assessment of multiple analytes. Neurodegenerative diseases represent an increasingly significant threat to global public health owing to progressive population aging, imposing a severe physical and social burden on affected patients who tend to develop cognitive and/or motor deficits beginning between the ages of 50 and 70. Owing to a relatively limited understanding of the etiological basis for these diseases, treatments are lacking for the most common neurodegenerative diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The present review was formulated with the goal of briefly explaining the principle of Raman spectroscopy and discussing its potential applications in the diagnosis and evaluation of neurodegenerative diseases, with a particular emphasis on the research prospects of this novel technological platform.

A novel model for predicting deep-seated candidiasis due to Candida glabrata among cancer patients: A 6-year study in a cancer center of China.

Followed by Candida albicans, Candida glabrata ranks as the second major species contributing to invasive candidiasis. Given the higher medical burden and lower susceptibility to azoles in C. glabrata infections, identifying these infections is critical. From 2016 to 2021, patients with deep-seated candidiasis due to C. glabrata and non-glabrata Candida met the criteria to be enrolled in the study. Clinical data were randomly divided into training and validation cohorts. A predictive model and nomogram were constructed using R software based on the stepwise algorithm and logistic regression. The performance of the model was assessed by the area under the receiver operating characteristic curve and decision curve analysis (DCA). A total of 197 patients were included in the study, 134 of them infected with non-glabrata Candida and 63 with C. glabrata. The predictive model for C. glabrata infection consisted of gastrointestinal cancer, co-infected with bacteria, diabetes mellitus, and kidney dysfunction. The specificity was 84.1% and the sensitivity was 61.5% in the validation cohort when the cutoff value was set to the same as the training cohort. Based on the model, treatment for patients with a high-risk threshold was better than 'treatment for all' in DCA, while opting low-risk patients out of treatment was also better than 'treatment for none' in opt-out DCA. The predictive model provides a rapid method for judging the probability of infections due to C. glabrata and will be of benefit to clinicians making decisions about therapy strategies.

EPHB2 as a key mediator of glioma progression: Insights from microenvironmental receptor ligand-related prognostic gene signature.

Malignant gliomas, characterized by pronounced heterogeneity, a complex microenvironment, and a propensity for relapse and drug resistaniguree, pose significant challenges in oncology. This study aimed to investigate the prognostic value of Ligand and Receptor related genes (LRRGs) within the glioma microenvironment. An intersection of 71 ligand-related genes (LRGs) and 2628 receptor-related genes (RRGs) yielded a total of 69 LRRGs. Utilizing the least absolute shrinkage and selection operator (LASSO) regression analysis, a prognostic RiskScore model comprising 28 LRRGs was constructed. The model demonstrated robust prognostic value, further validated in the TCGA-GBMLGG dataset. Subsequent analyses included differential gene expression, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment (GSEA), and gene set variation (GSVA) within RiskScore groups. Additionally, evaluations of PPI, mRNA-RBP, mRNA-TF, and mRNA-drug interaction networks were conducted. Four hub genes were identified through differential expression analysis of the 28 LRRGs across various GSE datasets. A multivariate Cox prognostic model was constructed for nomogram analysis, gene mutation analysis, and related expression distribution. This study underscores the role of LRRGs in intercellular communication within the glioma microenvironment and identifies four hub genes crucial for prognostic assessment in clinical glioma patients. These findings offer a potential evaluation framework for glioma patients, enhancing our understanding of the disease and informing future therapeutic strategies.

Betaine supplementation alleviates corticosterone-induced hepatic cholesterol accumulation through epigenetic modulation of HMGCR and CYP7A1 genes in laying hens.

Excessive corticosterone (CORT) exposure could cause hepatic cholesterol accumulation in chickens and maternal betaine supplementation could decrease hepatic cholesterol deposition through epigenetic modifications in offspring chickens. Nevertheless, it remains uncertain whether providing betaine to laying hens could protect CORT-induced hepatic cholesterol accumulation via epigenetic mechanisms. This study aimed to examine the effects of dietary betaine on plasma and hepatic cholesterol contents, expression of cholesterol metabolic genes, as well as DNA methylation on their promoters in the liver of laying hens exposed to CORT. A total of 72 laying hens at 130 d of age were randomly divided into 3 groups: control (CON), CORT, and CORT+betaine (CORT+BET) groups. The experiment lasted for 35 d. Chickens in CON and CORT groups were fed a basal diet, whereas the CORT+BET group chickens were fed the basal diet supplemented with 0.1% betaine for 35 d. On d 28 of the experiment, chickens in CORT and CORT+BET groups received daily subcutaneous injections of CORT (4.0 mg/kg body weight), whereas the CON group chickens were injected with an equal volume of solvent for 7 d. The results showed that CORT administration led to a significant increase (P < 0.05) in the contents of cholesterol in plasma and liver, associated with activation (P < 0.05) of sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), lecithin-cholesterol acyltransferase (LCAT) and low-density lipoprotein receptor (LDLR) genes expression, and inhibition of cholesterol-7-alpha hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) genes expression in the liver compared to the CON. In contrast, CORT-induced up-regulation of HMGCR mRNA and protein abundances and downregulation of CYP7A1 mRNA and protein abundances were completely normalized (P < 0.05) by betaine supplementation. Besides, CORT injection led to significant hypomethylation (P < 0.05) on HMGCR promoter and hypermethylation (P < 0.05) on CYP7A1 promoter. Moreover, dietary betaine rescued (P < 0.05) CORT-induced changes in methylation status of HMGCR and CYP7A1 genes promoters. These results indicate that dietary betaine addition protects laying hens from CORT-induced hepatic cholesterol accumulation via epigenetic modulation of HMGCR and CYP7A1 genes.