Melatonin alleviates brain injury in copper-laden rats: Underlying benefits for Wilson's disease.

Copper serves as an indispensable cofactor for all living organisms, and its excessive accumulation has been associated with a variety of diseases. Wilson's disease (WD) serves as an illustrative example of copper toxicity in humans, frequently presenting with liver and/or neuropsychiatric symptoms. The current therapeutic drugs, penicillamine (PA) and zinc gluconate (ZnG), have constraints, and research on their combination efficacy remains insufficient. It has been reported that melatonin (MLT) plays a vital role in binding to transition metals and exhibits strong antioxidant capacity. To investigate the therapeutic efficacy of MLT and combined treatment, rats were randomly divided into the following seven groups: the control (Con) group, copper-laden model rat (Mod) group, PA-treated group, ZnG-treated group, MLT- treated group, PA-ZnG-treated group, and PA-MLT-treated group. Then potential mechanisms and targets were investigated using a combination of metabolomics and network pharmacology and verified by molecular docking and qPCR. The findings revealed that MLT and the combination significantly improved behavior, pathology and copper levels in copper-laden rats. The results of the metabolomics study showed that profoundly altered metabolites were identified, and alanine, aspartate and glutamate metabolism, pyruvate metabolism, citrate cycle (TCA cycle), and glycolysis/gluconeogenesis were explored. In addition, molecular docking showed that MLT had high binding affinity with key targets, and qPCR results revealed that MLT could reverse the mRNA expression of targets GOT2 and PKM2. It was concluded that MLT effectively improves brain injury in copper-laden rats, and this effect was linked with the altered features of the metabolite profiles.

CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway.

Retinal vascular leakage is a major event in several retinal diseases, including diabetic retinopathy (DR). In a previous study, we demonstrated that the aqueous humor concentration of Cystatin C (CST3), a physiological inhibitor of cysteine protease, is negatively correlated with the severity of diabetic macular edema. However, its function in the retina has not been clearly elucidated. In this study, we found a significant decrease in the aqueous humor concentration of CST3 with DR progression. Furthermore, we found that CST3 was expressed in retinal endothelial cells and that its expression was significantly downregulated in high glucose-treated human retinal microvascular endothelial cells (HRMECs) and the retinal vessels of oxygen-induced retinopathy (OIR) mice. Silencing CST3 expression resulted in decreased HRMEC migration and tubule formation ability. Exogenous addition of the CST3 protein significantly improved HRMEC migration and tubular formation. In-vivo experiments demonstrated that CST3 silencing induced retinal vascular leakage in WT mice, while its intravitreal injection significantly reduced retinal leakage in OIR mice. Mechanistically, CST3 promoted the expression of the downstream adhesion molecules, claudin5, VE-cadherin, and ZO-1, in retinal vascular cells by regulating the Rap1 signaling pathway. Therefore, this study revealed a novel mechanism by which CST3 improves retinal vascular function and provided evidence that it is a potential therapeutic target for retinal vascular leakage.

Comparative analysis of internal limiting membrane peeling versus internal limiting membrane flap insertion for treating idiopathic macular holes.

OBJECTIVE: To evaluate the clinical efficacy of internal limiting membrane (ILM) peeling combined with perimacular hole massage versus ILM flap insertion in the management of patients with idiopathic macular holes was conducted. METHODS: 35 patients (total of 35 eyes) with idiopathic macular holes (with hole diameters ranging from 366 to 1430 µm) were divided into two groups-Group A consisted of 20 eyes that underwent pars plana vitrectomy (PPV) combined with ILM peeling and perimacular hole massage, while Group B comprised 15 eyes that underwent PPV combined with ILM flap insertion. Subsequent follow-up examinations were performed at 1 week, 1 month, and 3 months post-surgery. The study also involved a comparison of best corrected visual acuity (BCVA) and optical coherence tomography (OCT) classifications between both the patient groups. RESULTS: The macular hole closure rates in Group A were 60%, while in Group B, the closure rate was 93%. There was significant difference in hiatus healing rate between the two groups (t = 4.843, p = 0.048). The difference in BCVA at 3 months post-operation between the two groups was statistically significant (t = 3.221, p = 0.003). Three months post-operatively, the BCVA in Group B demonstrated improvement compared to the pre-operative BCVA, with a statistically significant difference (p > 0.05). Three months post-operatively, the BCVA in Group A demonstrated improvement compared to the pre-operative BCVA, but this difference was not statistically significant (p > 0.05). CONCLUSION: The combination of PPV with ILM flap insertion demonstrates favorable therapeutic efficacy in the treatment of idiopathic macular holes, leading to improved visual acuity.

Research progress on plant-derived cardenolides(2010-2023).

Cardenolides are a class of steroidal glycoside compounds that are mainly distributed in plants, have significant physiological activity in the heart, and have been used clinically for over 200 years. To provide a reference for further research and development of these compounds, the phytochemical and biological properties of natural cardenolides (295 compounds in total) isolated between 2010 and 2023 from 17 families and hundreds of species belonging to 70-80 genera were reviewed. In vitro and in vivo studies have indicated that antitumor, antibacterial, and antiviral activities are the most commonly reported pharmacological properties of cardenolides. Antitumor activities have been thoroughly studied to understand their structure-activity relationships, revealing numerous potential anticancer molecules that lay the theoretical foundation for further development of traditional Chinese medicinal herbs and the creation of new drugs.

Association of tooth loss and gallstones: National Health and Nutrition Examination Survey 2017-2018.

Introduction: Gallstones are one of the most common digestive diseases globally, with an estimated affected population of 15% in the United States. Our aim is to assess the current association between oral health and gallstones, exploring potential mediation factors. Methods: Self-reported gallstones were determined based on medical condition questionnaires. Dental status was assessed by dental professionals and oral health questionnaire. Mediation analysis was conducted for body mass index, blood glucose, triglycerides, and cholesterol, and the percentage of mediation effects was calculated. Results: We included 444 patients with gallstones and 3565 non-gallstone participants from National Health and Nutrition Examination Survey. After fully adjusting for all covariates, the prevalence of gallstones is higher when the number of missing teeth is at T3 compared to T1 (odds ratio [OR]: 1.93, confidence interval [CI]: 1.14 - 3.26, p = 0.02, p-trend = 0.01), and there was an inverted L-shaped association between missing teeth and gallstones, with an inflection point of 17. Bone loss around mouth was also associated with gallstones (OR: 1.78, 95% CI: 1.27 - 2.48, p = 0.002), but not root caries and gum disease. Mediation analysis identified blood glucose as a crucial mediator, with a mediation effect ratio of 4.91%. Conclusions: Appropriate lifestyle interventions for patients with missing teeth may help delay the onset of gallstones, such as healthy dietary habits, trace elements supplementing, and managing weight and blood sugar levels. Further exploration of the relationship between oral health and overall health contributes to disease prevention and comprehensive medical management.

Corrigendum to "The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling".

[This corrects the article DOI: 10.1515/tnsci-2022-0334.].

Application of the Unbalanced Ensemble Algorithm for Prognostic Prediction Outcomes of All-Cause Mortality in Coronary Heart Disease Patients Comorbid with Hypertension.

Purpose: This study sought to develop an unbalanced-ensemble model that could accurately predict death outcomes of patients with comorbid coronary heart disease (CHD) and hypertension and evaluate the factors contributing to death. Patients and Methods: Medical records of 1058 patients with coronary heart disease combined with hypertension and excluding those acute coronary syndrome were collected. Patients were followed-up at the first, third, sixth, and twelfth months after discharge to record death events. Follow-up ended two years after discharge. Patients were divided into survival and nonsurvival groups. According to medical records, gender, smoking, drinking, COPD, cerebral stroke, diabetes, hyperhomocysteinemia, heart failure and renal insufficiency of the two groups were sorted and compared and other influencing factors of the two groups, feature selection was carried out to construct models. Owing to data unbalance, we developed four unbalanced-ensemble prediction models based on Balanced Random Forest (BRF), EasyEnsemble, RUSBoost, SMOTEBoost and the two base classification algorithms based on AdaBoost and Logistic. Each model was optimised using hyperparameters based on GridSearchCV and evaluated using area under the curve (AUC), sensitivity, recall, Brier score, and geometric mean (G-mean). Additionally, to understand the influence of variables on model performance, we constructed a SHapley Additive explanation (SHAP) model based on the optimal model. Results: There were significant differences in age, heart rate, COPD, cerebral stroke, heart failure and renal insufficiency in the nonsurvival group compared with the survival group. Among all models, BRF yielded the highest AUC (0.810; 95% CI, 0.778-0.839), sensitivity (0.990; 95% CI, 0.981-1.000), recall (0.990; 95% CI, 0.981-1.000), and G-mean (0.806; 95% CI, 0.778-0.827), and the lowest Brier score (0.181; 95% CI, 0.178-0.185). Therefore, we identified BRF as the optimal model. Furthermore, red blood cell count (RBC), body mass index (BMI), and lactate dehydrogenase were found to be important mortality-associated risk factors. Conclusion: BRF combined with advanced machine learning methods and SHAP is highly effective and accurately predicts mortality in patients with CHD comorbid with hypertension. This model has the potential to assist clinicians in modifying treatment strategies to improve patient outcomes.

Creating large-scale genetic diversity in Arabidopsis via base editing-mediated deep artificial evolution.

BACKGROUND: Base editing is a powerful tool for artificial evolution to create allelic diversity and improve agronomic traits. However, the great evolutionary potential for every sgRNA target has been overlooked. And there is currently no high-throughput method for generating and characterizing as many changes in a single target as possible based on large mutant pools to permit rapid gene directed evolution in plants. RESULTS: In this study, we establish an efficient germline-specific evolution system to screen beneficial alleles in Arabidopsis which could be applied for crop improvement. This system is based on a strong egg cell-specific cytosine base editor and the large seed production of Arabidopsis, which enables each T1 plant with unedited wild type alleles to produce thousands of independent T2 mutant lines. It has the ability of creating a wide range of mutant lines, including those containing atypical base substitutions, and as well providing a space- and labor-saving way to store and screen the resulting mutant libraries. Using this system, we efficiently generate herbicide-resistant EPSPS, ALS, and HPPD variants that could be used in crop breeding. CONCLUSIONS: Here, we demonstrate the significant potential of base editing-mediated artificial evolution for each sgRNA target and devised an efficient system for conducting deep evolution to harness this potential.

The pharmacokinetics/pharmacodynamics integration of tilmicosin against Mycoplasma synoviae in vitro and in vivo.

Mycoplasma synoviae (MS) infection is a serious threat to poultry industry in China. Tilmicosin is a semisynthetic macrolide antibiotic used only in animals and has shown potential efficacy against MS, but there were no reported articles concerning the pharmacokinetics/pharmacodynamics (PK/PD) interactions of tilmicosin against MS in vitro and vivo. This study aimed to assess the antibacterial activity of tilmicosin against MS in vitro and in vivo using PK/PD model to provide maximal efficacy. The minimum inhibitory concentration (MIC) and killing rates of different drug concentrations were measured using the microdilution method in vitro. Then, tilmicosin was administered orally to the MS-infected chickens at doses of 7.5 and 60 mg/kg, and the PK parameters of tilmicosin in joint dialysates were determined using high-pressure liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) combined with the microdialysis technique. The antibacterial effect (△E) was calculated when the infected chickens were administered a single oral dose of tilmicosin at 4, 7.5, 15, 30, and 60 mg/kg b.w. The PK and PD data were fitted using the Sigmoid Emax model to evaluate the PK/PD interactions of tilmicosin against MS. The bactericidal activity of tilmicosin against MS was concentration dependent. Furthermore, the PK/PD index of AUC0-72h/MIC exhibited the most optimal fitting results (R2 = .98). The MS load decreased by 1, 2, and 3 Log10 CFU/mL, then AUC/MIC was determined as 13.99, 20.53, and 28.23 h, respectively, and the bactericidal effect can be achieved when the dose of MS-infected chickens is at 31.64 mg/kg b.w. The findings of this study hold significant implications for optimizing the treatment regimen for MS infection.

A long cold storage protocol for Anisopteromalus calandrae based on promoting prepupal development and arresting early pupal growth under low temperature.

Anisopteromalus calandrae (Howard) shows great promise as an ectoparasitoid for controlling various coleopteran pests in warehouses. However, for a large-scale release, it is crucial to establish an ample supply of A. calandrae while carefully maintaining their quality and effectiveness. Appropriate cold storage techniques are the key to achieving these goals. Previous studies on cold storage have focused on specific developmental stages and explored cold storage conditions that can be applied only to those stages. Herein, we examined the development, survival and reproductive capacity of A. calandrae at different temperatures (13, 16, and 19 °C) and storage durations (30, 60, and 90 d) and evaluated the fitness of the offspring. A. calandrae completed its egg-to-larva development and pupated at 16 °C, but its development was arrested at an early pupal stage. Even after 90 d of cold storage at 16 °C, the survival rate of A. calandrae remained high at 77%, with no significant impact on reproductive capacity. Furthermore, cold storage showed no negative effect on the F1 generation. In contrast, eggs stored at 13 °C failed to hatch, whereas those stored at 19 °C developed. Adults emerged after > 60 d. This indicates that storage at 19 °C is only suitable for short durations. Our findings highlight the developmental pattern of A. calandrae at 16 °C, indicating that the parasitic wasp can be stored for a long time at this temperature across all stages of development before pupation, substantially facilitating its mass reproduction and industrial production.

The chlamydial transcriptional regulator Euo is a key switch in cell form developmental progression but is not involved in the committed step to the formation of the infectious form.

Bacteria in the genus Chlamydia are a significant health burden worldwide. They infect a wide range of vertebrate animals, including humans and domesticated animals. In humans, C. psittaci can cause zoonotic pneumonia, while C. pneumoniae causes a variety of respiratory infections. Infections with C. trachomatis cause ocular or genital infections. All chlamydial species are obligate intracellular bacteria that replicate exclusively inside of eukaryotic host cells. Chlamydial infections are dependent on a complex infection cycle that depends on transitions between specific cell forms. This cycle consists of cell forms specialized for host cell invasion, the elementary body (EB), and a form specialized for intracellular replication, the reticulate body (RB). In addition to the EB and RB, there is a transitionary cell form that mediates the transformation between the RB and the EB, the intermediate body (IB). In this study, we ectopically expressed the regulatory protein Euo and showed that high levels of expression resulted in reversible arrest of the development cycle. The arrested chlamydial cells were trapped phenotypically at an early IB stage of the cycle. These cells had exited the cell cycle but had not shifted gene expression from RB like to IB/EB like. This arrested state was dependent on continued expression of Euo. When ectopic expression was reversed, Euo levels dropped in the arrested cells which led to the repression of native Euo expression and the resumption of the developmental cycle. Our data are consistent with a model where Euo expression levels impact IB maturation to the infectious EB but not the production of the IB form. IMPORTANCE: Bacterial species in the Chlamydiales order infect a variety of vertebrate animals and are a global health concern. They cause various diseases in humans, including genital and respiratory infections. The bacteria are obligate intracellular parasites that rely on a complex infectious cycle involving multiple cell forms. All species share the same life cycle, transitioning through different states to form the infectious elementary body (EB) to spread infections to new hosts. The Euo gene, encoding a DNA-binding protein, is involved in regulating this cycle. This study showed that ectopic expression of Euo halted the cycle at an early stage. This arrest depended on continued Euo expression. When Euo expression was reversed, the developmental cycle resumed. Additionally, this study suggests that high levels of Euo expression affect the formation of the infectious EB but not the production of the cell form committed to EB formation.

Interferon Gamma Inducible Protein 30: from biological functions to potential therapeutic target in cancers.

Interferon Gamma Inducible Protein 30 (IFI30), also known as Gamma-Interferon-Inducible Lysosomal Thiol Reductase (GILT), is predominantly found in lysosomes and the cytoplasm. As the sole enzyme identified to catalyze disulfide bond reduction in the endocytic pathway, IFI30 contributes to both major histocompatibility complex (MHC) class I-restricted antigen cross-presentation and MHC class II-restricted antigen processing by decreasing the disulfide bonds of endocytosed proteins. Remarkably, emerging research has revealed that IFI30 is involved in tumorigenesis, tumor development, and the tumor immune response. Targeting IFI30 may provide new strategies for cancer therapy and improve the prognosis of patients. This review provided a comprehensive overview of the research progress on IFI30 in tumor progression, cellular redox status, autophagy, tumor immune response, and drug sensitivity, with a view to providing the theoretical basis for pharmacological intervention of IFI30 in tumor therapy, particularly in immunotherapy.

Reference Ranges and Comparison of Pepsinogen by Chemiluminescence Immunoassay and Enzyme-Linked Immunosorbent Assay in Chinese Population.

Objective: Serum pepsinogen (PG) is a good indicator of atrophic changes in the gastric mucosa. Gastric mucosal atrophy is a high-risk factor for gastric cancer. Serological testing for PG combined with endoscopy can help to improve gastric cancer screening. In this study, we established the reference ranges of serum PG-I, PG-II, and the PG-I/II ratio (PGR) in the Chinese population by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). Besides, in the real world, doctors are often confused by the results of different testing platforms. Thus, a comparison of methods CLIA and ELISA was performed. Methods: 2904 individuals were enrolled from six regions in China as part of the Chinese Adult Digestive Diseases Surveillance (2016) program. The individuals completed questionnaires and volunteered to undergo examinations, including gastroscopy, urea breath test, abdominal ultrasound examination and routine serologic tests. Serum was collected to measure PGs (including PG-I, PG-II and PGR) by CLIA and ELISA. Participants who were found obvious abnormalities or absent from the examinations were excluded. Ultimately, 747 healthy individuals were enrolled in this study. The Kolmogorov-Smirnov test was used to assess the distribution of variables. The Kruskal-Wallis H or Mann-Whitney U-tests were used to compare different sex, age, and geographical groups. The 95% reference ranges of PGs obtained by the two methods were established according to document CLSI-EP28-A3, with covariates of sex, age, and region. Spearman correlation analysis, linear regression analysis and allowable total error (ATE) zone analysis were utilized for comparing the two methods. Results: On overall, the 95% reference ranges of PG-I, PG-II, and PGR measured by CLIA were 23.00-110.64 ng/mL, 2.50-19.13 ng/mL, and 3.87-13.30, respectively. Meanwhile, the reference ranges of PG-I, PG-II, and PGR measured by ELISA were 36.93-205.06 ng/mL, 1.65-17.96 ng/mL, and 7.50-33.60, respectively. Both PG-I and PG-II levels measured by the two platforms were found to be influenced by sex and age. PGR measured by CLIA was influenced by age but not by sex, while PGR measured by ELISA was not affected by either age or sex. Regional factors did not significantly impact the PG results, except for PG-I detected by ELISA. Ultimately, reference ranges for PGs were established based on age and sex stratification. Additionally, the Spearman correlation analysis revealed that the correlation coefficients for PG-I, PG-II, and PGR detected by the two methods were 0.899, 0.887, and 0.777, respectively, indicating a strong correlation between the two methods. The regression equation for the PG levels detected by two methods was obtained through linear regression analysis. The ATE analysis provided a visual depiction of the consistency between the two methods, clearly indicating the poor agreement between them. Conclusion: This study established the reference ranges of PGs by strict and intact enrollment standard. In addition, the results indicated a strong linear relationship between the two methods, yet with a clear bias, which was valuable for laboratory interpretation.

Genome-wide expression analysis in a Fabry disease human podocyte cell line.

Fabry disease (FD) is an X-linked lysosomal disease caused by an enzyme deficiency of alpha-galactosidase A (α-gal A). This deficiency leads to the accumulation of glycosphingolipids in lysosomes, resulting in a range of clinical symptoms. The complex pathogenesis of FD involves lysosomal dysfunction, altered autophagy, and mitochondrial abnormalities. Omics sciences, particularly transcriptomic analysis, comprehensively understand molecular mechanisms underlying diseases. This study focuses on genome-wide expression analysis in an FD human podocyte model to gain insights into the underlying mechanisms of podocyte dysfunction. Human control and GLA-edited podocytes were used. Gene expression data was generated using RNA-seq analysis, and differentially expressed genes were identified using DESeq2. Principal component analysis and Spearman correlation have explored gene expression trends. Functional enrichment and Reporter metabolite analyses were conducted to identify significantly affected metabolites and metabolic pathways. Differential expression analysis revealed 247 genes with altered expression levels in GLA-edited podocytes compared to control podocytes. Among these genes, 136 were underexpressed, and 111 were overexpressed in GLA-edited cells. Functional analysis of differentially expressed genes showed their involvement in various pathways related to oxidative stress, inflammation, fatty acid metabolism, collagen and extracellular matrix homeostasis, kidney injury, apoptosis, autophagy, and cellular stress response. The study provides insights into molecular mechanisms underlying Fabry podocyte dysfunction. Integrating transcriptomics data with genome-scale metabolic modeling further unveiled metabolic alterations in GLA-edited podocytes. This comprehensive approach contributes to a better understanding of Fabry disease and may lead to identifying new biomarkers and therapeutic targets for this rare lysosomal disorder.

High-Order Harmonic Generation in Photoexcited Three-Dimensional Dirac Semimetals.

High-order harmonic generation (HHG) in condensed matter is highly important for potential applications in various fields, such as materials characterization, all-optical switches, and coherent light source generation. Linking HHG to the properties or dynamic processes of materials is essential for realizing these applications. Here, a bridge has been built between HHG and the transient properties of materials through the engineering of interband polarization in a photoexcited three-dimensional Dirac semimetal (3D-DSM). It has been found that HHG can be efficiently manipulated by the electronic relaxation dynamics of 3D-DSM on an ultrafast time scale of several hundred femtoseconds. Furthermore, time-resolved HHG (tr-HHG) has been demonstrated to be a powerful spectroscopy method for tracking electron relaxation dynamics, enabling the identification of electron thermalization and electron-phonon coupling processes and the quantitative extraction of electron-phonon coupling strength. This demonstration provides insights into the active control of HHG and measurements of the electron dynamics.

Timing the first emergence and disappearance of global water scarcity.

Alleviating water scarcity is at the core of Sustainable Development Goal 6. Yet the timing of water scarcity in its onset and possible relief in different regions of the world due to climate change and changing human population dynamics remains poorly investigated. Here we assess the timing of the first emergence of water scarcity (FirstWS) and disappearance of water scarcity (EndWS), by using ensembles of simulations with six Global Hydrological Models under two representative concentration pathways (i.e., RCP2.6, RCP6.0) combined with two shared socioeconomic pathways (i.e., SSP2, SSP3) for 1901-2090. Historically (1901-2020), FirstWS occurred predominantly in Asia (e.g., China and India) and Africa (e.g., East Africa); the peak time of emerging water scarcity began around the 1980s. Under all the four future RCPs-SSPs scenarios (2021-2090), FirstWS will likely occur mainly in some regions of Africa, for which the newly added area is double that in Asia. On the other hand, EndWS will mostly occur in China after 2050, primarily due to the projected declining population. We, therefore, call for specific attention and effort to adapt to the looming water scarcity in Africa.

Integrative catalytic pairs for efficient multi-intermediate catalysis.

Single-atom catalysts (SACs) have attracted considerable research interest owing to their combined merits of homogeneous and heterogeneous catalysts. However, the uniform and isolated active sites of SACs fall short in catalysing complex chemical processes that simultaneously involve multiple intermediates. In this Review, we highlight an emerging class of catalysts with adjacent binary active centres, which is called integrative catalytic pairs (ICPs), showing not only atomic-scale site-to-site electronic interactions but also synergistic catalytic effects. Compared with SACs or their derivative dual-atom catalysts (DACs), multi-interactive intermediates on ICPs can overcome kinetic barriers, adjust reaction pathways and break the universal linear scaling relations as the smallest active units. Starting from this active-site design principle, each single active atom can be considered as a brick to further build integrative catalytic clusters (ICCs) with desirable configurations, towards trimer or even larger multi-atom units depending on the requirement of a given reaction.

Predicting TCM patterns in PCOS patients: An exploration of feature selection methods and multi-label machine learning models.

Background: Traditional Chinese Medicine (TCM) offers individualized treatment for Polycystic Ovary Syndrome (PCOS) through pattern differentiation, but the subjectivity of TCM diagnoses can lead to inconsistent outcomes. Integrating machine learning (ML) offers an objective basis to support TCM diagnoses. This study aims to evaluate various feature selection techniques and multi-label ML algorithms to develop an effective predictive model for classifying TCM patterns in PCOS patients, thereby enhancing diagnostic standardization and treatment personalization. Methods: The study utilized a dataset comprising 432 patients with PCOS, exhibiting one or more of five TCM patterns. Feature selection began with Variance Thresholding (VT), followed by a comparison of five advanced techniques: Statistical Analysis Test, Recursive Feature Elimination with Cross-Validation (RFECV), Least Absolute Shrinkage and Selection Operator Regression, BorutaShap, and ReliefF. To ascertain the most effective model for predicting PCOS TCM patterns, four ML algorithms-Support Vector Machine, Logistic Regression, Extreme Gradient Boosting (XGBoost), and Artificial Neural Networks-were evaluated against the identified feature set. Results: VT reduced the feature count from 224 to 174. RFECV emerged as the most effective feature selection method, identifying 67 key features. XGBoost emerged as the top-performing model, demonstrating superior testing accuracy (0.7870), F1 score (0.9519), and Hamming loss (0.0481) with RFECV-optimized features. Conclusions: The RFECV-XGBoost model proved effective for classifying TCM patterns in PCOS. It emphasizes the necessity of precise feature selection and the significant capabilities of ML in advancing TCM pattern diagnostics, marking a significant step toward enhancing precise and personalized healthcare in biomedical studies.

Electroacupuncture attenuates depressive-like behaviors in poststroke depression mice through promoting hippocampal neurogenesis and inhibiting TLR4/NF-κB/NLRP3 signaling pathway.

The aim of this study was to investigate the impact and underlying molecular mechanisms of electroacupuncture on mice with poststroke depression (PSD). Mice were randomly allocated into sham, PSD, and electroacupuncture groups. Mice in the PSD and electroacupuncture groups underwent middle cerebral artery occlusion (MCAO) surgery following with sedentary behavior. Electroacupuncture targeting Zusanli (ST36) acupoint was performed 24 h after MCAO for 4 weeks in electroacupuncture group. The sucrose preference test, forced swimming test, open field test, tail suspension test, elevated plus maze, Catwalk analysis, RNA sequencing, Nissl staining, Golgi staining, TUNEL staining, Edu labeling, and doublecortin staining were performed. Lymphocyte subsets in peripheral blood and the levels of IL-1ß, IL-6, TNF-α, and expression of Iba1/CD86, Iba1/NLRP3, TLR4/p38/NF-κB/NLRP3 pathways in the hippocampus were detected. Electroacupuncture effectively protected against the development of depression-like symptoms. The number of granulosa cells and doublecortin-positive cells in the dentate gyrus (DG) were significantly decreased in PSD group, which were significantly upregulated (P < 0.01) by electroacupuncture. Electroacupuncture also significantly reduced (P < 0.05) TUNEL-positive cells in the DG and CA1. RNA-seq revealed that electroacupuncture may exert antidepressant effect by regulating the inflammation mediated by TLR4/NF-κB/NLRP3 pathway in hippocampus. Electroacupuncture remarkably elevated (P < 0.01) the ratio of CD4+ to CD8+ T cells and percentage of CD3-CD49b+ cells in CD45+CD49b+ cells in the peripheral blood. Electroacupuncture significantly reduced (P < 0.05) the high levels of IL-1ß, IL-6, TNF-α, iba1, TLR4, p-p38, p-NF-κB, and NLRP3 and sedentary behavior. Electroacupuncture was observed to mitigate depression symptoms and increase hippocampal neurogenesis in mice with PSD, possibly by inhibiting TLR4/p38/NF-κB/NLRP3 pathways and improving the microglia-mediated inflammatory microenvironment in the hippocampus.