Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Lipid metabolism relates to tumor proliferation, progression, and immune escape. With the rapid development of immunotherapy, the relationship between immunotherapy and lipid metabolism has been constantly explored. On the one hand, immunotherapy can cause dyslipidemia and accelerate the progression of atherosclerosis, which has been neglected by clinicians. On the other hand, lipid metabolism can affect antitumor immunity at multiple levels and potentially influence the efficacy of immunotherapy. Lipid metabolism-regulating drugs also have the potential to synergize with immunotherapy. This review summarizes relevant research evidence to inspire further exploration.

Objective　To detect clustered regularly interspaced short palindromic repeats (CRISPR) in Listeria monocytogenes, and analyze the structure and homology of CRISPR loci. Methods Totally 34 strains of Listeria monocytogenes isolated in our laboratory were identified, PCR amplified and sequenced. The repeat sequence structure and spacer sequence homology in CRISPR loci were analyzed by bioinformatics software. Results A total of 7 CRISPR loci were detected in 34 strains. The mutation rate of the first 2 and last 2 bases of the Repeat sequence of CRISPR loci was higher, while the mutation rate of the middle part was lower. Seven CRISPR sites form eight CRISPR structural types, among which the Repeat sequences of CRISPR1 and CRISPR2 are relatively conserved, while the Repeat sequences of CRISPR1 and CRISPR5 can form dumbbell shaped secondary structures. The number of Spacer sequences contained in each CRISPR site ranges from 2 to 15, with an average of 2.43. The 136 Spacer sequences detected were not only homologous to Listeria plasmids and bacteriophages, but also homologous to uncultured virus sequences, staphylococcal bacteriophages, and Listeria innocua. The same CRISPR genotype did not show large-scale clustering, but some strains in the same year were in the same evolutionary cluster with close genetic relationships. Conclusion The CRISPR structure of Listeria monocytogenes in this study exhibits high specificity, and its homology with bacteriophages provides a theoretical basis for the application of bacteriophages in the control and prevention of Listeria monocytogenes.

Cancer is a serious global health problem and a major cause of human death. Conventional cancer treatments often run the risk of impairing vital organ functions. Anticancer peptides (ACPs) are considered to be one of the most promising therapeutic agents against common human cancers due to their small sizes, high specificity, and low toxicity. Since ACP recognition is highly limited to the laboratory, expensive, and time-consuming, we proposed pLM4ACP, a model for predicting ACPs based on machine learning and protein language models. In this model, the protein language model ProtT5 was used to extract the features of ACPs, and the extracted features were input into the support vector machine (SVM) classification algorithm for optimization and performance evaluation. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 0.763, F1-score of 0.767, Matthews correlation coefficient of 0.527, and area under the curve of 0.827 on the independent test set. This study constructs an efficient anticancer peptide prediction model based on protein language models, further advancing the application of artificial intelligence in the biomedical field and promoting the development of precision medicine and computational biology.
Machine Learning ; Antineoplastic Agents/chemistry* ; Humans ; Peptides/chemistry* ; Support Vector Machine ; Algorithms ; Computational Biology/methods* ; Neoplasms/drug therapy*

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

Objective:To investigate the effects of Yangxue Qingnao granules combined with oxiracetam on cognitive function, psychiatric symptoms, and levels of inflammatory factors in patients with Alzheimer's disease. Methods:This study used a prospective design and included 100 patients with Alzheimer's disease who received treatment at the Department of Neurology, Shangluo Traditional Chinese Medicine Hospital, from January 2021 to June 2023. The patients were randomly divided into two groups: a control group and an observation group ( n = 50 per group). The control group received oxiracetam treatment, while the observation group received Yangxue Qingnao granules in addition to oxiracetam. All patients underwent treatment for 12 weeks and were followed up for 24 weeks. Levels of inflammatory factors (C-reactive protein, amyloid-β1-42, interleukin σ), oxidative stress responses (superoxide dismutase, malondialdehyde, glutathione peroxidase, heme oxygenase-1), psychiatric symptoms (assessed by the Behavioral Pathology in Alzheimer's Disease Rating Scale), and cognitive function (measured using the Alzheimer's Disease Assessment Scale-Cognitive Subscale and the Mini-Mental State Examination) were compared between the two groups before and after treatment. The response rate was also compared between the two groups. Data were statistically analyzed using SPSS 24.0, using t-tests for measurement data and chi-square tests for categorical data. Results:After treatment, the serum levels of C-reactive protein, amyloid-β1-42, interleukin σ, superoxide dismutase, and malondialdehyde as well as Alzheimer's Disease Assessment Scale-Cognitive Subscale and Behavioral Pathology in Alzheimer's Disease Rating Scale scores in the observation group were (2.50 ± 0.31) mg/L, (83.77 ± 19.77) ng/L, (80.10 ± 30.11) ng/L, (55.10 ± 4.42) kU/L, (3.33 ± 0.32) μmol/L, (13.26 ± 2.62), and (5.86 ± 1.14), respectively. All of these values were significantly lower than those in the control group [(4.53 ± 0.50) mg/L, (109.31 ± 24.19) ng/L, (148.53 ± 42.00) ng/L, (63.51 ± 4.25) kU/L, (4.87 ± 0.24) μmol/L, (17.90 ± 3.35), (10.16 ± 2.49), t = 24.40, -5.78, 9.36, 9.69, -27.22, -7.71, 11.10, all P<0.01]. The serum levels of glutathione peroxidase and heme oxygenase-1 as well as Mini-Mental State Examination scores in the observation group were (95.21 ± 5.43) U, (14.33 ± 1.58) μg/L, and (26.40 ± 1.11), respectively, which were significantly higher than those in the control group [(80.24 ± 5.33) U, (10.87 ± 1.24) μg/L, (23.53 ± 3.32) points, t = 13.91, 12.18, 5.79, all P<0.01]. Conclusions:Yangxue Qingnao granules combined with oxiracetam shows positive effects on improving behavioral symptoms, cognitive function, and overall clinical efficacy in patients with Alzheimer's disease.

To investigate the protective effect of Lycium barbarum glycopeptide(LbGp)on testicu-lar injury induced by D-galactose(D-gal)in aging rats,male SD rats were randomly divided into 6 groups:the blank control group(Control),aging model group(Model),positive control group(β-nicotinamide mononucleotide,NMN),low dose LbGp group(LLbGp),medium dose LbGp group(MLbGp)and high dose LbGp group(HLbGp).The testicular mass of rats was counted,the morphological changes of testicular tissue were observed by hematoxylin-eosin(HE)staining,the testicular senescence was detected by β-galactosidase(SA-β-gal)staining,and the levels of testos-terone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)in serum were de-tected.The levels of oxidative factors such as glutathione peroxidase(GSH-Px),superoxide dis-mutase(SOD),malondialdehyde(MDA),catalase(CAT)and inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in rat tissues were measured.TUNEL staining was used to detect the apoptosis of testicular cells,epididymal sperm quality,and the expression of Keap1,Nrf2 and Nqo1 mRNA were analyzed.The results showed that compared with the Model group,the testicular coefficient of Lycium barbarum glycopeptide rats in MLbGp and HLbGp groups increased(P＜0.01),the level of T in serum and sperm quality increased(P＜0.05),the structural degeneration and aging of testicular tissue decreased(P＜0.01),the level of antioxidant factors increased,and the levels of inflammatory factors and apopto-sis decreased(P＜0.05).The expression of Keap1 decreased significantly(P＜0.01),while the ex-pression of Nrf2 and Nqo1 mRNA increased(P＜0.05).The above results indicate that Lycium barbarum glycopeptide can improve D-gal-induced testicular senescence,attenuate oxidative stress,reduce inflammatory response,decrease apoptosis,and exert a protective effect on testicular injury in rats due to senescence through the Keap1-Nrf2 signaling pathway.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
Humans ; Cell Movement ; Transcription Factors/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Cycle Proteins ; Azepines/pharmacology* ; Epithelial-Mesenchymal Transition ; Carcinoma, Squamous Cell/metabolism* ; Esophageal Squamous Cell Carcinoma ; Triazoles/pharmacology* ; Nuclear Proteins/genetics* ; Cell Proliferation ; Acetyl-CoA Carboxylase/genetics* ; Transfection ; Autophagy ; Bromodomain Containing Proteins