The catalytic degradation of sulfur-containing volatile organic compounds (S-VOCs), especially methyl mercaptan (CH3SH), is often limited by the insufficient low-temperature activity of conventional catalysts. Herein, an inverse Cu-Ce catalyst featuring a well-defined CuO(200) facet and CuO(200)-CuO(1̅11) interface, denoted as CuO/CeO2-CP(7), is constructed through facet regulation and interfacial engineering. The catalyst enables complete conversion of CH3SH at 150 °C and exhibits a substantially lower apparent activation energy, demonstrating superior intrinsic activity compared with most reported catalysts. Structural-activity correlation reveals that the interface architecture stabilizes Cu+ species, enhances active-oxygen migration-replenishment, and significantly strengthens CH3SH adsorption and activation, thereby driving a stepwise deep-conversion route of CH3SH → CH3SSCH3 → CH3SCH3/HCOOH → CH4. In-situ FTIR confirms that Cu+-O* cooperative sites govern the coupling, rearrangement, and deep-reduction processes, while deactivation analysis identifies disrupted oxygen cycling as the primary cause of activity loss. This work highlights the critical role of CuO-CuO interfacial modulation in advancing low-temperature S-VOCs degradation and provides an effective strategy for designing highly active inverse Cu-Ce catalysts.
Proteus mirabilis is a Gram-negative uropathogenic bacterial species responsible for many catheter-associated urinary tract infections (CAUTIs). Due to the growing rates of antimicrobial resistance among CAUTI pathogens, novel antimicrobial solutions are urgently needed. Bacteriophage endolysins are an emerging class of antimicrobial agents, but no endolysins from P. mirabilis phages have been reported to date. Here, we describe two new Proteus phage endolysins, LysPM1 and LysPM2, containing Peptidase_M15_3 and CHAP domains, respectively. We experimentally confirmed their antibacterial activity against several Proteus spp. when used in combination with outer membrane permeabilizers, including EDTA, citric acid, and chloroform, as well as against frozen bacteria. Both enzymes have optimum activity at pH 7-8 and retain activity at temperatures up to 60 °C. Both endolysins completely lost their lytic activity upon treatment with EDTA, suggesting that divalent cations participate in the catalytic mechanism; the addition of Ca2⁺ and Zn2⁺ to LysPM1, and Ca2⁺ and Mn2⁺ to LysPM2 partially restored the activity. Our study confirms LysPM1 and LysPM2 as the first experimentally characterized Proteus phage endolysins, with LysPM2 also being the first experimentally characterized Gram-negative endolysin with a single CHAP domain. These findings could guide further development of phage-derived lytic enzymes for treatment of Proteus infections. KEY POINTS: • LysPM1 & LysPM2 are the first experimentally characterized Proteus phage endolysins. • Both are single-domain endolysins: Peptidase_M15_3 in LysPM1 and CHAP in LysPM2. • Metal cofactors are required for their activity: Zn2⁺ for LysPM1, Ca2⁺ for LysPM2.
Lactococcus lactis subsp. lactis strains have been widely recognized for their probiotic potential, including their immunomodulatory and anti-obesity effects. This study aims to determine the genomic basis of the health-promoting properties of L. lactis subsp. lactis CAB701 and WiKim0124 using whole-genome sequencing and comparative genomic analysis. Taxonomic classification using average nucleotide identity and digital DNA-DNA hybridization confirms both strains as L. lactis subsp. lactis. Genome alignment reveals high synteny among CAB701, WiKim0124, and the reference strains, with minor structural variations. Functional annotation identifies genes associated with carbohydrate metabolism, biofilm formation, and immune modulation. Pan-genome analysis shows a substantial proportion of strain-specific genes, suggesting niche-specific adaptation. Notably, L. lactis subsp. lactis CAB701 and WiKim0124 harbor unique biosynthetic gene clusters for nisin Z and sactipeptides, which may contribute to their antimicrobial and immunomodulatory functions. Additionally, genes involved in short-chain fatty acid metabolism are identified, highlighting their potential role in metabolic regulation. These findings provide valuable insights into the functional genetics of L. lactis subsp. lactis and their applicability as probiotics for immune modulation and obesity management. KEY POINTS: • Comparative genomics revealed strain-specific immune- and metabolism-linked genes • CAB701 and WiKim0124 uniquely harbor nisin Z and sactipeptide biosynthetic clusters • Genomic features support L. lactis application as functional probiotics.
The rapid increase in spent lithium iron phosphate (LiFePO4) batteries brings significant challenges related to environmental pollution, human health risks, and resource sustainability. Conventional recycling technologies are often hampered by high energy consumption, secondary pollution, and operational hazards. This study proposes a sustainable mechanochemical approach for recycling spent LiFePO4 black mass, based on the targeted destruction of the stable LiFePO4 crystal structure. Using sodium hydroxide as an efficient co-grinding agent in a solvent-free system, a superior lithium leaching efficiency of 98.83 % was achieved under optimized conditions, while iron co-leaching was effectively suppressed to 0.27 %. Comprehensive characterizations, including X-ray diffraction, X-ray photoelectron spectroscopy, and Mössbauer spectroscopy confirmed the destruction of the LiFePO4 crystal structure, the formation of Li3PO4, and the oxidation of Fe2+. An economic assessment demonstrates the viability of this procedure, yielding a net profit of $0.9659 per kilogram of LiFePO4 black mass. This work presents an efficient, economically viable, and environmentally benign mechanochemical strategy for LiFePO4 battery recycling, offering fundamental insights into crystal structure destruction for sustainable resource recovery.
Bovine anaplasmosis is a tick-borne rickettsial disease of significant sanitary and economic importance to livestock, particularly in tropical and subtropical regions, and is associated with high morbidity and reduced productivity. However, data on its molecular prevalence in cattle from semiarid and transitional areas of the Northeast region of Brazil remain scarce. This study aimed to determine the prevalence of Anaplasma spp. in cattle from smallholder farms located in the Sertão and Agreste mesoregions of the states of Paraíba and Pernambuco, Brazil. A total of 380 whole blood samples from cattle were analyzed by conventional PCR targeting the msp4 gene, following confirmation of DNA extraction by amplification of the endogenous GAPDH gene. Anaplasma spp. was detected in 92.1% of the cattle, with no significant association with sex, age group, breed, production system, or level of tick infestation. Positive cattle exhibited significantly lower hematocrit values compared to negative animals (p = 0.0087). These results represent the first report of molecular detection of Anaplasma spp. in cattle from the states of Pernambuco and Paraíba and suggest the presence of enzootic stability microregions in the Sertão and Agreste mesoregions of Northeast Brazil.
A current major challenge for national health systems (NHS) is the increase of obesity and overweight among populations. Subcutaneous semaglutide 2.4 mg, a glucagon-like peptide 1 analogue, has been approved by the European Medicines Agency as an adjunct to a reduced-calorie diet and increased physical activity (diet and exercise [D&E]) for the treatment of obesity. The aim of this study was to evaluate the cost-effectiveness of semaglutide 2.4 mg in combination with D&E compared with D&E alone in the treatment of patients with obesity in Spain. The analyses were performed using version 26 of the Core Obesity Model, a Markov state transition model, to project health outcomes and costs at 40 years, based on the evolution of risk factors associated with obesity. Efficacy and safety data were obtained from the STEP 1 trial (body mass index [BMI], systolic blood pressure and glycaemic status), involving a cohort of adults with an average age of 46 years and obesity (BMI ≥ 30 kg/m2). The analysis was carried out from the perspective of the Spanish NHS. The results were evaluated in terms of cost per quality-adjusted life year (QALY) gained. Only direct healthcare costs were included. Univariate and probabilistic sensitivity analyses were performed to ensure the robustness of the findings. Compared with D&E, semaglutide 2.4 mg in combination with D&E generated an additional 0.1049 QALYs and a €2685 increase in costs over 40 years, resulting in an incremental cost-effectiveness ratio of €25,589/QALY. Semaglutide 2.4 mg was shown to be cost-effective under a cost-effectiveness threshold of €30,000/QALY. The robustness of this finding was confirmed by the sensitivity analyses and scenarios evaluated. On the basis of the model-based analysis, semaglutide 2.4 mg, in combination with D&E, was estimated to be a cost-effective therapeutic alternative in Spain for adults with obesity, compared to treatment based on D&E alone. These results may be useful for optimizing decision-making.
AkNBS-LRR43 and AkNBS-LRR100 positively regulate immunity in Amorphophallus konjac against Pectobacterium carotovorum subsp. carotovorum by enhancing antioxidant activity and reducing oxidative damage. Amorphophallus konjac, an economically important Araceae species rich in konjac glucomannan (KGM), faces production losses from biotic/abiotic stresses. Nucleotide-binding-site leucine-rich repeat (NBS-LRR) genes, crucial for plant immunity, remain understudied in A. konjac. Here, we comprehensively analyzed 146 AkNBS-LRR genes, characterizing their structure, chromosomal distribution, phylogeny, cis-elements and expression patterns. Furthermore, two candidate genes (AkNBS-LRR43/100) were functionally validated. The AkNBS-LRRs showed chromosomal preference (chr1/2/3/5/9/11) and clustered into five phylogenetic subclasses (CNL_E predominant). These genes harbored abundant cis-elements associated with growth and stress responses. Functional annotation implicated their roles in signal transduction, development, and biotic/abiotic stress responses. Transcriptome profiling revealed pathogen-responsive differential expression patterns. RT-qPCR revealed differential AkNBS-LRR expression during Pectobacterium carotovorum subsp. carotovorum (Pcc) infection, with AkNBS-LRR43/100 showing pronounced upregulation. Subcellular localization confirmed their nuclear targeting. Transgenic A. konjac plants transiently overexpressing AkNBS-LRR43/100 showed significantly reduced lesion expansion under pathogen infection compared to controls. Concurrently, these transgenic plants exhibited increased activities of peroxidase (POD) and superoxide dismutase (SOD), along with decreased malondialdehyde (MDA) content, which may lead to enhanced reactive oxygen species (ROS) scavenging capacity and consequently to reduced disease symptom development. These findings suggest that AkNBS-LRR43/100 may function as positive regulators in A. konjac disease resistance by enhancing antioxidant capacity.
In this study, β-glucan (β-gluM16) was obtained from the cell wall of the probiotic yeast strain Pichia kudriavzevii M16 and chemically altered through carboxymethylation (CMβ-gluM16) to improve its solubility in water. Using gel permeation chromatography, the molecular weight of CMβ-gluM16 was found to be 232 kDa. Structural modification was confirmed by FTIR, with shifts linked to carboxymethyl functional groups. The 1,1-Diphenyl-2-Picrylhydrazyl (DPPH) radical, hydroxyl radical, and superoxide anion scavenging assays were used to measure antioxidant activity. DPPH activity reached 96% at 100 mg/mL, while hydroxyl radical scavenging reached 69.65% at the same concentration. At 100 mg/mL, the superoxide anion scavenging gradually reached 76%. CMβ-gluM16 effectively reduced biofilm formation in all tested pathogens. The strongest inhibition was observed for Escherichia coli (80% at 1 mg/mL), followed by Pseudomonas aeruginosa (71% at 0.5 mg/mL) and Staphylococcus aureus (67% at 10 mg/mL), depending on the applied concentration. Cytotoxicity tests showed that L929 fibroblast cells stayed alive at 500 µg/mL after 36 h (≥ 64% viability), demonstrating a nontoxic effect. However, at the same concentration and hour, HT-29 colorectal adenocarcinoma cell viability decreased in a dose- and time-dependent manner, reaching 60%. CMβ-gluM16 enhanced the adhesion of Lactiplantibacillus plantarum LP1 to intestinal epithelial cells and increased adhesion from 83% (probiotic alone) to 92% (synbiotic application) at 500 mg/mL. Cytokine levels (IL-1β, IL-6, IL-10, and TNF-α) were assessed for immunomodulatory activity; these levels changed with dose and application time. IL-1β ranged from 1341 to 3371 pg/mL, IL-6 from 169 to 280 pg/mL, IL-10 from 220 to 859 pg/mL, and TNF-α from 126 to 263 pg/mL across the tested conditions. This study is a preliminary investigation into the potential biotechnological applications of CMβ-gluM16, indicating its promise for further research.
Central nervous system (CNS) metastases are a frequent and ominous scenario in patients with breast cancer. CNS metastases (CNSm) are typically classified as brain metastases (BrMs) or leptomeningeal disease (LMD). Although the coexistence of BrMs and LMD (BrMs + LMD) is commonly encountered in clinical practice, its true prevalence and prognostic implications remain insufficiently characterized. This study aimed to characterize the distribution of CNSm and compare outcomes in patients with breast cancer BrMs with and without LMD. We retrospectively analyzed a prospectively maintained database of patients with breast cancer and magnetic resonance imaging (MRI)-confirmed CNSm treated at a single tertiary cancer center between January 2010 and January 2023. Among 659 patients with breast cancer CNSm, 292 (44%) had BrMs, 169 (26%) had LMD, and 198 (30%) had BrMs + LMD. The CNSm survival for the entire cohort was 9.6 months (95% CI, 8.0-11.2); 12.2 months (95% CI, 9.9-14.5) in the BrMs group; 5.8 months (95% CI, 4.3-7.2) in the LMD group; and 10.3 months (95% CI, 8.0-12.7 months) in the BrMs + LMD group (P < 0.001). After adjustment for performance status, number of brain metastases, and molecular subtype, the risk of mortality remained higher in the BrMs + LMD group (HR 1.24; 95% CI, 1.01-1.52; P = 0.032) compared with the BrMs group. In patients with breast cancer and brain metastases, concomitant leptomeningeal involvement is common and independently associated with worse survival. These findings support the need to incorporate leptomeningeal disease status into prognostic models and clinical decision-making for CNSm in patients with breast cancer.
Optic nerve sheath diameter (ONSD) is increasingly used as a non-invasive indicator of intracranial pressure and neurological status in both human and veterinary medicine, although physiological factors affecting ONSD measurements in dogs remain insufficiently defined. This study investigated the relationships among body mass (BM), age, serum estradiol (E2) and progesterone (P4) levels, and ultrasonographically measured ONSD in clinically healthy female dogs. Thirty-four female dogs of different ages and BM presented for routine clinical examination were included. ONSD was measured ultrasonographically via a transorbital approach using a microconvex probe, and the mean value of bilateral measurements was used for analysis. Serum E2 and P4 concentrations were determined using ELISA. Correlation analyses (Pearson or Spearman, depending on distribution) and power-law regression models were applied to evaluate associations between variables. Age and E2 were expressed as median (IQR) values [2.5 (1) years and 90.43 (85.03)], whereas BM, P4, and ONSD were reported as mean ± SD (23.15 ± 9.72 kg, 9.04 ± 1.96 ng/mL, and 2.42 ± 0.44 mm, respectively). A moderate negative correlation was observed between P4 and ONSD (r = - 0.41, p < 0.05), while no significant relationships were detected between age, BM, E2, and ONSD (p > 0.05). These findings suggest that P4 may show a modest inverse association with ONSD in clinically healthy female dogs, whereas BM, age, and E2 appear to have minimal influence. Further studies with larger populations are warranted to confirm these findings.
Surface passivation has played an essential role in the rapid advancement of power conversion efficiency (PCE) in perovskite solar cells (PSCs). However, conventional passivation strategies predominantly rely on small molecules such as ammonium-based ligands, which are prone to deprotonation under light exposure and thermal stress, leading to compromised device stability. Here, we report a polymerizable surface passivation material, vinylphosphonic acid (VPA). The vinyl group enables in situ polymerization, while the phosphate group passivates uncoordinated metallic defects. Both theoretical and experimental results confirmed that the polymerized-VPA (PVPA) forms a more robust and stable passivation layer than conventional organoammonium-based small molecules. Consequently, we achieved a PCE of 26.54% (certified as 26.24%). Benefiting from the more stable polymerized passivation layer, our devices demonstrate remarkable operational durability, retaining over 90% of their initial PCE after 1600 h at maximum power point operation under continuous 1-sun illumination. This approach provides a promising passivation layer strategy to enhance the stability and efficiency of perovskite solar cells.
To evaluate intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for preoperative diagnosis of perineural invasion (PNI) in rectal cancer (RC). A total of 148 patients with pathology-confirmed RC (PNI+, n = 72; PNI-, n = 76) were enrolled. Parameters from mono-exponential (ADC), bi-exponential (D, D*, f), and stretched-exponential (DDC, α) IVIM models were analyzed. Univariate and multivariate logistic regression analyses were used to construct diagnostic models. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. The DeLong test was used to compare the AUC of the models. Internal validation was employed to assess model performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI), along with calibration metrics and decision curve analysis, were used to further evaluate model performance. P-value < 0.05 was considered statistically significant. ADC, D, f, and DDC differed significantly between groups. Multivariate analysis identified ADC and D as independent PNI predictors. The D value yielded the highest AUC (0.84), while ADC showed the highest sensitivity (81.94%). A combined model (ADC + D) achieved an AUC of 0.85, sensitivity of 86.10%, specificity of 73.70%, and accuracy of 77.00%. The fivefold internal validation mean AUC was 0.84 ± 0.04. No significant AUC differences were found among parameters or models (DeLong test, P > 0.05). Further analyses revealed that the combined model provided significant improvements over the ADC model in individual risk reclassification (continuous NRI = 0.65, 95% CI 0.33-0.95), overall predictive accuracy (IDI = 0.07, 95% CI excluding 0), and calibration (Brier score: 0.16 vs. 0.17; MAE: 0.01 vs. 0.04; MSE: 2.3×10⁻⁴ vs. 1.91×10⁻³). Decision curve analysis demonstrated consistently higher net benefit for the combined model across threshold probabilities of 0-0.50. IVIM-DWI demonstrates potential value for the preoperative assessment of PNI status in rectal cancer and may facilitate individualized treatment planning.
Limited genetic and genomic resources in citronella necessitate the use of novel breeding methods to develop advanced breeding material that taps into genetic variability. Identify superior and highly variable half sibs besides identifying their pollen donors, to be used in citronella breeding programs. In this study, we used four commercial citronella cultivars (CIM-Bio-13, CIM-Jeeva, Medini and Jal Pallavi) as parents in a polycross breeding scheme. This resulted in 60 half-sib progenies. We evaluated herb yield, essential oil content and various biochemical components across two harvests. From this evaluation, eleven superior half-sibs were identified. Notably, half-sib progeny B25 6-10 consistently outperformed others and showed the greatest divergence in both harvests. Principal component analysis accounted for 60-70% of observed variability with two components, highlighting the diversity within the progenies. SSR markers confirmed the highest amplification from Cymbopogon flexuous (54.26%), followed by C. winterianus (42.85%) and C. citratus (41.17%). Genetic diversity metrics confirmed moderate polymorphism and marker informativeness. SSR-based UPGMA clustering corroborated morphological differentiation, and unique pollen donors were identified for 5 of 11 half-sib progenies. The identified variable progenies are valuable resources for further genetic studies and potential population improvement. Marker-based paternity results demonstrate the value of this approach for precise selection in citronella breeding.
Climate change and population growth present significant challenges to global food security, underscoring the critical importance of sustainable and efficient agricultural production. Crop rotation is a key agricultural practice that enhances food production, improves soil fertility, reduces pest and disease pressure, and maintains agro-ecological balance. The complexity and diversity of cropping patterns, particularly in the fragmented farmland of southern China, limit the availability of high-resolution crop rotation maps in precision agriculture. To improve the consistency between cropping intensity (CI) estimation and crop pattern (CP) mapping, this study developed a hierarchical framework for extracting cropland, CI, and CP from remotely sensed images. Using the Google Earth Engine (GEE) platform, a 10-m binary cropland/non-cropland map was first generated from the time-series Normalized Difference Vegetation Index (NDVI). Then, CI was derived within cropland regions using an intelligent algorithm that counts the number of growth cycles. Finally, taking advantage of crop phenology and CI constraints, nine cropping patterns were extracted from a diversified cropping region. Comparing with field survey data, the results revealed overall accuracies of 98.97%, 96.47%, and 87.92% for the cropland/non-cropland map, cropping intensity map, and cropping pattern map, respectively. These findings demonstrate the reliability of the generated maps and the potential of the proposed framework for revealing diverse cropping patterns in complex cropping regions.
The Pediatric Quality of Life Inventory™ (PedsQL™ 4.0) is widely used to assess quality of life (QoL) in children, yet evidence on the reliability and validity of young children's self-reports is inconsistent. We evaluated whether self-reported QoL in young children varies by parental presence during administration and whether parent-child agreement differed between mothers and fathers. Secondary analyses were conducted using data from primary schools (n = 303, children aged 5-7 years) including at least one participating parent. Children completed the PedsQL self-report either at school with a trained research assistant (parent-absent) or at home with a parent who read items aloud and recorded answers (parent-present). Mothers and fathers completed parallel proxy-reports. Multilevel modeling was used to estimate mean differences and correlations between reporters and conditions, with age and sex as covariates. Internal consistency of child self-reports was limited across the four subdomains, with somewhat lower values in the parent-absent condition. Parent ratings showed no systematic differences between conditions, whereas children scored higher when a parent was present, yielding smaller parent-child gaps and higher correlations. These patterns were similar for mothers and fathers. In this school-based community sample, improved agreement with a parent present was driven by higher child scores, consistent with brief, non-leading parental assistance (clarification/recall). Self-reports of young children obtained without a parent present warrant caution. Clear, age-appropriate guidance on administration and structured parental support is needed.
Global developmental delay is a common pediatric condition that affects multiple developmental domains. Emerging evidence suggests that iron deposition in the deep gray matter nuclei may play a critical role in neurodevelopmental processes. However, brain iron deposition in children with global developmental delay remains insufficiently characterized. This study aimed to investigate abnormal brain iron deposition patterns on neuroimaging in children with global developmental delay, with the goal of facilitating early detection, timely diagnosis, and targeted intervention. This study enrolled 71 children with global developmental delay and 31 typically developing controls. Quantitative susceptibility mapping (QSM) data were acquired using a 3.0-T magnetic resonance imaging scanner and post-processed on the MATLAB platform. Between-group comparisons of susceptibility values in the deep gray matter nuclei were performed, followed by correlation analyses between regional susceptibility values and Gesell Developmental Scale scores in the differentially affected brain regions. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic performance of quantitative susceptibility mapping. The Benjamini-Hochberg false discovery rate (FDR) method was applied, with significance set at corrected P<0.05. Children in the global developmental delay group exhibited significantly lower magnetic susceptibility in the bilateral thalamus, substantia nigra, and dentate nucleus (all P<0.05). Susceptibility values of the bilateral dentate nucleus were positively correlated with gross motor and personal-social Gesell sub-scores (right dentate nucleus: r=0.41, P<0.001 and r=0.26, P=0.027; left dentate nucleus: r=0.36, P=0.002 and r=0.26, P=0.026). ROC analysis showed that the right dentate nucleus had the highest area under the curve (AUC=0.83). Children with global developmental delay demonstrate decreased magnetic susceptibility within the deep gray matter nuclei, which supports imaging-based inference of dysregulated brain iron metabolism, potentially reflecting underlying pathophysiological mechanisms of neurodevelopment.
Congenital tuberculosis (CTB) is a rare disease with high mortality in neonates. Early diagnosis is crucial but often delayed due to atypical clinical and imaging manifestations. We report a 36-day-old female infant presenting with recurrent fever. Laboratory data showed leukocytosis and neutrophilia with mildly elevated C-reactive protein. Chest computed tomography revealed extensive ground-glass opacities, multiple subpleural nodules, and necrotic hilar and mediastinal lymphadenopathy. The asymptomatic mother was subsequently found to have diffuse miliary nodules on chest CT. Conventional tuberculosis tests (acid-fast smear, culture, GeneXpert, T-SPOT.TB) were negative in both the infant and mother. Metagenomic next-generation sequencing (mNGS) of the placental tissue detected 10 specific Mycobacterium tuberculosis sequences, and Ziehl-Neelsen staining confirmed acid-fast bacilli. Both mother and infant responded well to anti-tuberculosis therapy. CTB should be considered in neonates with persistent pulmonary infection unresponsive to broad-spectrum antibiotics. Examination of placental tissue using mNGS is a valuable diagnostic tool for confirming transplacental tuberculosis transmission.
MicroRNA (miRNA) dysregulation contributes to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), but the role of specific miRNAs in tau-mediated toxicity remains unclear. Here, we investigated the contribution of hsa-miR-125b to tau-induced cellular dysfunction using a stable neuronal cell line overexpressing mutant tau (P301L). We found that hsa-miR-125b levels were significantly elevated in tau-expressing cells compared to controls. Using bioinformatic tools, we identified a strong enrichment of predicted hsa-miR-125b targets involved in mitochondrial function. We validated several of these targets by RT-qPCR and confirmed the downregulation of mitochondrial-related transcripts, including genes encoding components of complexes I, IV, and V of the electron transport chain. To assess functional consequences, we performed Seahorse metabolic flux analysis and observed impaired mitochondrial respiration in tau-overexpressing cells, including reduced basal respiration, ATP production, and spare respiratory capacity. Our findings demonstrate that hsa-miR-125b contributes to tau-induced mitochondrial dysfunction by repressing transcripts essential for mitochondrial homeostasis. We propose that hsa-miR-125b acts as a mechanistic link between tau pathology and metabolic impairment in AD and may represent a promising target for therapeutic intervention.
We aimed to assess the prognostic role of untreated moderate-to-severe tricuspid regurgitation (TR) by a systematic review and meta-analysis. We searched Pubmed from database inception to 14 August 2025. Studies reporting data on clinical outcomes associated with different TR grades not receiving treatment were considered eligible. The primary endpoint was all-cause mortality; secondary endpoints included cardiovascular (CV) mortality and heart failure (HF) hospitalization. Pooled estimates were calculated using random-effects models. Our literature search yielded 2,727 articles, of which 225 were assessed for full-text eligibility. A total of 106 studies (107 comparisons) comprising 961,136 patients, were included in the quantitative synthesis. The overall prevalence of untreated moderate-to-severe TR was 13.5%, but varied widely across population subgroups. Moderate-to-severe TR was associated with a significantly higher all-cause mortality compared with none-to-mild TR (unadjusted HR 2.07; 95% CI 1.89-2.26; p < 0.001). The association was confirmed in adjusted models and among different subgroups (i.e., patients performing a general echocardiographic irrespective of indication, patients with left-side valvular heart disease [LSVHD], HF without LSVHD, patients undergoing cardiac implantable electronic device implantation, left ventricular assist device recipients and in patients with pulmonary artery hypertension), but not after heart transplantation. A stepwise increase in mortality was observed with increasing TR severity. Moderate-to-severe TR was also associated with higher risk of CV mortality and HF hospitalization (HR 1.92 [1.64-2.26] and HR 1.63[1.44-1.84], respectively). Untreated moderate-to-severe TR is associated with higher risk of all-cause mortality, CV mortality and HF hospitalization, underlying the role of timely diagnosis and appropriate management.
Polycystic ovarian syndrome (PCOS) is an intricate endocrine and metabolic disorder affecting reproductive-age women. This research focused on assessing the therapeutic potential of harmine in letrozole-induced PCOS rat model. PCOS was induced in all the groups except normal control by oral administration of letrozole (1 mg/kg) for consecutive 28 days. After confirmation of PCOS, normal and disease controls were treated with vehicle, clomiphene citrate (5.25 mg/kg) was administered as a standard drug, and harmine as treatment compound at 2.5, 5.0, and 10 mg/kg orally for 28 days daily. Letrozole administration in diseased rats displayed disrupted estrous cycle irregularity, insulin resistance, cystic ovarian morphology, and hyperandrogenism along with upregulation of metabolic and lipid profile and alteration in hormonal and hematological parameters. Treatment with harmine (2.5-10 mg/kg) was remarkably (p < 0.05) normalize the metabolic and lipid profile, restored the hormonal imbalance, and improved ovarian histology. Treatment with harmine (2.5-10 mg/kg) notably reduced the serum level TNF-α, and IL-6 in contrast to disease control. Harmine-treated rats exhibited the down regulation of mRNA expression of TNF-α, IL-6, PGR, and Keap-1 while upregulated FSHR, CYP19A1, and Nfr-2 as equated to disease control. However, harmine demonstrated dose-dependent improvement in mRNA expression that linked with ovarian function. These findings concluded that harmine exhibited promising therapeutic potential for PCOS by modulating metabolic, endocrine, anti-oxidant, anti-inflammatory, and steroidogenic markers. Besides, harmine was safe in acute usage and LD50 > 2000 mg/kg.