The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and a key cancer therapeutic target. Although first-generation allosteric and second-generation ATP-competitive mTOR inhibitors have been developed, resistance due to mTOR mutations remains a challenge. Third-generation bisteric inhibitors, which bridge both allosteric and orthosteric sites via a flexible linker, offer a promising solution, yet their atomic mechanisms and optimal linker design are not fully understood. Here, we performed microsecond molecular dynamics simulations on six mTOR-bisteric inhibitor complexes. Our results reveal that (1) steric inhibitors stabilize the catalytic cleft of mTOR, (2) inhibitor potency correlates with cleft closure, and (3) optimal linker length promotes a more closed and stable conformation, enhancing binding affinity. These findings provide atomic-level insights to guide the rational design of next-generation mTOR inhibitors.

The properties and meridian affinities of Chinese herbal medicine are closely associated with their therapeutic efficacy. This review focuses on approved antitumour Chinese medicines listed in the Pharmacopoeia of the People's Republic of China (2020 Edition, Volume I), highlighting their key components. Statistical methods were used to analyse the properties, flavours and channel tropisms of antitumour traditional Chinese medicine (TCM), including both proprietary formulations and commercially available individual herbs. Distinctive patterns were identified by comparing herb profiles with contemporary experimental studies on antitumour TCM. Analysis revealed that bitter-cold herbs represented the highest proportion of antitumour TCM, with most showing tropism towards the liver channel. These findings provide a reference framework for antitumour drug development, indicating that bitter-cold herbs merit priority as candidate ingredients.

Bone marrow mesenchymal stem cell (BMSC) lineage commitment contributes to metabolic bone diseases, but whether glucagon-like peptide-1 (GLP-1) regulates osteo-adipogenic fate remains unclear. Here, RNA sequencing was performed to identify potential pathways regulated by GLP-1 in BMSCs, followed by gain- and loss-of-function experiments. Furthermore, BMSC-specific Hif-2α knockout mice with glucocorticoid-induced osteoporosis were treated with semaglutide to evaluate skeletal effects. GLP-1 suppressed adipogenesis and promoted osteogenesis of BMSCs in a dose-dependent manner. Transcriptomic analysis identified PI3K-AKT and hypoxia signaling as major GLP-1-regulated pathways. Mechanistically, GLP-1 inhibited AKT activation during adipogenesis and reshaped AKT signaling dynamics during osteogenesis. Loss of HIF-2α largely abolished GLP-1-mediated regulation of AKT activity. In vivo, semaglutide improved trabecular bone mass in osteoporotic mice, whereas this bone-protective effect was markedly diminished in Hif-2α-knockout mice. Our findings suggest that GLP-1 modulates BMSC lineage commitment by inhibiting adipogenesis and enhancing osteogenesis through HIF-2α-associated regulation of AKT signaling.

2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) is a widely used novel brominated flame retardant with environmental persistence, yet its developmental toxicity remains poorly characterized. In this study, we investigated the developmental and cardiotoxic effects of TTBP-TAZ in zebrafish embryos/larvae. Embryos (4 hpf) were exposed to 0-20 μM TTBP-TAZ for 120 hpf. Assessments included survival, hatching kinetics, burst activity (24 hpf), heart rate (48 hpf), caudal venous blood-flow velocity (72 hpf), locomotor behavior under alternating light/dark conditions (120 hpf), cardiac morphology in Tg(myl7:EGFP), and transcription of key cardiac genes. Results indicated low mortality of embryos/ larvae across all concentrations. However, TTBP-TAZ accelerated hatching rate in a concentration-dependent manner (significant by 60 hpf) and increased burst activity. Elevated heart rate (48 hpf) and enhanced tail-vein blood flow (72 hpf) suggested tachycardia and stimulated circulation. Transgenic larvae exhibited reduced ventricular/atrial fluorescence intensity, along with enlarged cardiac size and indistinct contours, indicating structural abnormalities. qPCR analysis revealed up-regulation of nkx2.5, tbx20, and vmhc, and down-regulation of gata4, mef2, and myh7, suggesting disruption of core cardiogenic transcription and chamber-specific contractile programming. Locomotor assays demonstrated hyperactivity at higher concentrations under both light and dark conditions. These findings indicate sub-lethal TTBP-TAZ exposure induces significant developmental and cardiotoxic disturbances in zebrafish, associated with altered cardiac gene expression and functional hyperactivation. This study supports the need for further mechanistic investigation and exposure-relevant risk assessment of TTBP-TAZ.

Bisphenol M (BPM) has been increasingly used as a substitute for bisphenol A (BPA), yet its reproductive toxicity remains poorly characterized. Unlike BPA, which is well characterized as a weak estrogen receptor (ER) agonist, BPM has been identified as an ER antagonist. In this study, we systematically compared the effects of BPM and BPA on the reproductive neuroendocrine system of female mice during puberty. Five-week-old female ICR mice were exposed to BPM and BPA at doses of 1 mu g/kg bw/day, 50 mu g/kg bw/day, and 1 mg/kg bw/day for 14 days. Both chemicals induced comparable adverse reproductive outcomes at 50 mu g/kg bw/day and 1 mg/kg bw/day, including reduced uterine weight, disrupted estrous cyclicity, depletion of primordial follicles, and increased follicle atresia. However, BPM and BPA had divergent effects on molecular and hormonal end points. BPM exposure significantly elevated ovarian Cyp19a1 expression, as well as serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, whereas BPA did not significantly alter any of these parameters. Mechanistically, BPM acts as an ER antagonist, reducing functional E2-ER complexes and creating a perceived "E2 signaling deficiency". This triggers compensatory upregulation of ovarian ERs and steroidogenic genes (Star, Cyp19a1, and Hsd17b1), leading to enhanced E2 synthesis. The resulting hyperestrogenism exerts positive feedback on hypothalamic GnRH neurons, driving sustained gonadotropin secretion and creating a self-sustaining high-E2 loop that disrupts estrous cyclicity and follicle dynamics. In contrast, BPA, as a weak ER agonist, partially substitutes for endogenous E2 at ERs, preventing the perception of E2 deficiency. Consequently, no compensatory steroidogenic activation occurs, and hormone levels remain unchanged. Despite these distinct mechanisms, both compounds impair female reproductive function. Importantly, BPM exerted more pronounced endocrine disturbances than BPA, raising concerns regarding its use as a safer alternative. These findings highlight the necessity of comprehensive toxicological evaluation of BPA analogues and emphasize that ER antagonism does not necessarily imply reduced reproductive risk.

Cellular senescence is typically driven by DNA damage, telomere attrition, and metabolic/mitochondrial stress, resulting in a state of durable proliferative arrest accompanied by a senescence-associated secretory phenotype (SASP) that amplifies inflammation and paracrine remodeling across tissues, thereby accelerating functional decline and age-related pathologies. This review examines the molecular mechanisms and in vivo activities of procyanidin C1 (PCC1), a natural dualmode geroprotector. This dual behavior ostensibly allows PCC1 to function in an early or lowdose phase wherein PCC1 attenuates selected NFκB–driven SASP components while stabilizing redox and bioenergetic homeostasis; under high senescent burden or tumor-associated stress, elevated doses of PCC1 enable the selective reduction of refractory senescent cells and mitigation of pro-tumorigenic SASP outputs, concomitant with modulation of immune infiltration and metabolic reprogramming. PCC1 further exhibits pronounced anti-inflammatory and anti-tumor potential by reshaping inflammatory and chemotactic gradients within the tumor microenvironment. Reflecting broad multi-organ geroprotective potential, PCC1 can exert antioxidative, mitochondrial-supportive, and anti-fibrotic modulation in cardiovascular/metabolic tissues, skin, liver, kidney, and neural niches. Compared with BCL-2 inhibitors or multi-kinase senolytics, PCC1 shows lower cytotoxicity toward normal proliferating cells and fewer indications of platelet or hematopoietic suppression, with its staged regulatory profile and natural scaffold suggesting a wider therapeutic window. Future priorities include quantifying dose–timing transition thresholds, establishing integrated biomarker panels, and optimizing delivery strategies to define its translational potential in precision, phase-adapted geroprotective interventions.

Owing to the remarkable flexibility and reversibility of hydrogen bonds, anion-directed hydrogen-bonded organic frameworks (AOFs), serving as crystalline porous materials constructed by the interconnection of two building blocks primarily via charge-assisted hydrogen bonds (CAHBs), have emerged as promising candidates for applications in storage, separation, heterogeneous catalysis, enzyme encapsulation, proton conduction, and other related fields. Over the past three decades, a large number of hydrogen-bonded organic frameworks (HOFs) have been designed and synthesized to further explore their functionalities, accompanied by the publication of numerous research articles and a limited number of reviews focusing on HOFs. However, to the best of our knowledge, very few reviews focusing on the construction strategies, crystal engineering, and structure–property relationships of AOFs, have been reported. Therefore, the primary objective of this review is to provide a comprehensive analysis of AOFs assembled by guanidinium/amidinium cations as tectons, with a particular emphasis on representative examples of AOFs directed by organoanions. The review is organized into five main sections: (I) Di-, mono-sulfonate and organophosphate anion-directed supramolecular frameworks with guanidinium cations; (II) AOFs assembled from organopolysulfonates with guanidinium cations; (III) Organosulfonate/phosphate-directed supramolecular networks featuring amidinium cations; (IV) AOFs constructed by organocarboxylate anions and tri/tetra-amidinium cations; (v) Representative supramolecular frameworks featuring post-synthetic modification and hydrophilicity/hydrophobicity. Finally, we propose a fresh perspective on the existing prospects and potential research directions for the further advancement of dual-component AOF systems. We hope that this review could provide fundamental inspiration and guidance for supramolecular chemists to develop novel AOFs or supramolecular frameworks with potential applications in the field of materials science.

Molecular glues (MGs) represent a unique class of small molecules that modulate protein-protein interactions by altering target protein surface properties, enabling targeted degradation, pathway modulation, or functional control of proteins, including traditionally undruggable targets. Currently, 17 MG-based drugs are approved globally with over 40 in clinical trials, underscoring their therapeutic potential. Despite these advances, the lack of a dedicated database integrating structural, pharmacological, and computational data for such compounds hinders rational drug design. To address this gap, we developed MGDB, a specialized open-access repository integrating rigorously curated multidimensional data for MGs. MGDB contains 7396 curated MGs being sourced from 162 peer-reviewed publications and 156 patents. It consolidates structural data, 9728 experimental bioactivity data points (covering degradation efficiency, binding affinity, cellular/animal activity) across 201 targets and 108 effectors, 115 296 computed physicochemical properties, and 270 785 ADMET profiles. The database supports text-based and chemical structure-based queries and interoperability with external resources (e.g. PubChem, ChEMBL, DrugBank, UniProt, and WIPO) via hyperlinks. By centralizing and standardizing specialized MG information, MGDB empowers researchers to rapidly explore MG research landscapes and provides high-quality datasets for artificial intelligence-driven rational therapeutic design. MGDB is freely available at http://mgdb.idruglab.cn/.

Dietary intake is one of the major sources of per- and polyfluoroalkyl substances (PFAS) in humans. In this study, 96 samples encompassing 11 types of vegetable oils collected in Chinese markets were analyzed for 37 PFAS using a combined liquid–liquid extraction and solid-phase extraction protocol, followed by high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). Short-chain (CF2 < 7) and emerging PFAS were predominant in all oils, with a total (ΣPFAS) concentration range of < 0.00723–1454 pg/g. The concentrations of ΣPFAS in sunflower oil, camellia oil, and sesame oil were higher than those in other types of oils. Alternative PFAS, 6:2 fluorotelomer sulfonate (6:2 FTS) and hexafluoropropylene oxide dimer acid (HFPO-DA) were detected for the first time in edible oils, with maximum concentrations of 1438 pg/g and 182 pg/g, respectively. Highly refined oils contained higher average concentrations of short-chain and emerging PFAS than less refined oils, indicating that the importance of considering the impact of refining processes on PFAS contamination profiles. Meanwhile, different oil processing methods had different effects on the presence of PFAS in the oils. All estimated daily intakes of PFAS through oils for Chinese population were below the tolerable intake levels.

Accurate prediction of drug-target interactions constitutes a crucial foundation for drug discovery. DualPG-DTA is presented, a general framework for binding affinity prediction that integrates two pre-trained language models to generate atomic-level molecular representations and residue-level protein embeddings. The architecture constructs dual molecular-protein graphs processed through dedicated graph neural networks equipped with dynamic attention mechanisms to extract context-aware sequence-level features, which are fused via a multimodal module for affinity predictions. Benchmark results show that DualPG-DTA consistently outperforms existing models across all metrics. Applied to CDK9 inhibitor discovery, the framework is used to develop robust regression/classification models and identified compound C1 as a novel CDK9 inhibitor with an IC50 of 1.2 nM. C1 demonstrates exceptional CDK family selectivity alongside optimal pharmacokinetic properties, including prolonged half-life, adequate clearance, robust plasma exposure, and oral bioavailability. Notably, oral C1 demonstrated potent antitumor efficacy in a Venetoclax-resistant MV4-11 acute myeloid leukemia (AML) xenograft model, with concurrent demonstration of favorable tolerability and safety profiles. Collectively, the study not only establishes a unified framework for precise binding affinity prediction but also identifies C1 as a highly promising therapeutic lead targeting CDK9 to conquer Venetoclax resistance in AML.

The C11α-hydroxyl group is essential for many steroid drugs, yet chemical synthesis suffers from complex routes and environmental issues. Here, we isolate CYP68N3_ma, a fungal cytochrome P450 from Metarhizium anisopliae EEG016, which converts 17α-hydroxyprogesterone to 11α,17α-dihydroxyprogesterone. Expressing CYP68N3_ma in Saccharomyces cerevisiae enabled the highly specific bioconversion with a concentration of 0.16 mM. Structure-guided iterative saturation mutagenesis yielded the triple mutant N3M3 (F111A/E374H/T115I), increasing the concentration 13.8-fold to 2.21 mM. Molecular dynamics and near-attack conformation analysis revealed cooperative modulation of steric hindrance and hydrogen bonding that fine-tunes substrate orientation and enhances the near-attack conformation (NAC) formation. Expression in Komagataella phaffii improved conversion 3.8-fold over that in S. cerevisiae. Overexpression of heme synthesis enzyme HEM1, cytochrome b5, an ABC transporter, and knockout of HMX1 resulted in 10.6 g/L in flask and 24.8 g/L in high-cell density bioreactor. This study establishes a versatile, sustainable, and scalable biocatalytic route for steroid functionalization.

Triple-negative breast cancer (TNBC) represents a highly aggressive breast cancer subtype characterized by a paucity of effective therapeutic options. Consequently, the development of targeted therapies constitutes a promising strategy for TNBC treatment. It has been demonstrated that combining CDK12 and PARP1 inhibitors can trigger synthetic lethality in TNBC cells. In the present study, employing a pharmacophore fusion strategy, we designed and synthesized a series of dual-target inhibitors against CDK12 and PARP1. Among them, compound 20b exerted potent inhibition activity against both CDK12 and PARP1 at nanomolar concentrations. It exhibited markedly superior antiproliferative effects compared with single-target inhibitors and effectively reduced pSer2-CTD (Ser2 phosphorylation) and PAR levels in TNBC cells. Furthermore, compound 20b produced robust colony formation inhibitory effects in TNBC cell lines, accompanied by cell cycle arrest and apoptosis induction. The dual-target CDK12/PARP1 inhibitor 20b developed herein represents a novel lead molecule for TNBC drug development.

Combination therapy is a widely used clinical strategy to enhance treatment efficacy against solid tumors. However, the diversity of medicinal drugs and the complexity of in vivo delivery processes present significant challenges for the rational selection and efficient delivery of drug combinations. As a proof of concept, we herein developed an omics-based high-throughput drug screening platform, pharmacotranscriptomic signature enrichment analysis (PSEA), for the prediction of drug combinations of resiquimod (R848) to improve macrophage-mediated cancer immunotherapy. By comparing the critical transcriptional signatures of R848 with chemical perturbation signatures from the LINCS database, PSEA identified mitoxantrone (MIT) as a promising candidate. We then engineered an MIT/R848 co-loaded hydrogel (MIT/R848@Gel) and tested its therapeutic effect in multiple tumor models including the MMTV-PyMT transgenic mouse tumor and VX2 rabbit tumor. Local injection of MIT/R848@Gel not only suppressed the growth of primary tumors but also potently inhibited tumor recurrence and metastasis by eliciting durable and robust systemic antitumor immune responses, resulting in long-term remission in a high percentage of animals. Transcriptional and flow cytometry results indicated that MIT/R848@Gel remarkably reprogrammed immunosuppressive macrophages toward an antitumor phenotype and effectively activated the antitumor effect of cytotoxic T cells. This study establishes a novel framework integrating omics-driven drug discovery with localized combination therapy for enhanced cancer immunotherapy.

Diminished ovarian reserve (DOR) is a major cause of female infertility. In recent years, traditional Chinese medicine has displayed unique ameliorating effects on DOR. This study aims to investigate the therapeutic efficacy and molecular mechanisms of Bushen Zhuluan Decoction (BSZLD) in DOR. A rat model of DOR was established and treated with either BSZLD or Progynova (positive control). Estrous cycle monitoring, ovarian index calculation, hematoxylin-eosin staining, and enzyme-linked immunosorbent assay were performed to assess ovarian reserve function. TUNEL staining, immunohistochemistry, and Western blotting were conducted to evaluate ovarian cell apoptosis. To elucidate the pharmacological basis of BSZLD, ultra-high-performance liquid chromatography-tandem mass spectrometry was applied. Network pharmacology analysis, machine learning algorithms, and molecular docking were integrated to predict key active compounds and pathways. The role of the sirtuin 1 (SIRT1) and its downstream target hypoxia-inducible factor 1alpha (HIF-1α) signaling in BSZLD-mediated effects was verified using short hairpin RNA (shRNA) lentiviral-mediated interference. BSZLD significantly restored estrous cycle disturbances, increased ovarian index and follicle counts, and reduced atretic follicles and ovarian cell apoptosis in DOR rats. Serum anti-Müllerian hormone and estradiol levels were elevated, while follicle-stimulating hormone and luteinizing hormone levels were reduced. The SIRT1/HIF-1α signaling pathway was a core regulatory axis for BSZLD action. BSZLD markedly upregulated SIRT1 expression while suppressing HIF-1α expression. Silencing SIRT1 using shRNA reduced SIRT1 levels, elevated HIF-1α expression, and significantly attenuated the therapeutic effects of BSZLD. BSZLD attenuates DOR in rats by activating the SIRT1/HIF-1α signaling, thereby suppressing ovarian cell apoptosis and restoring ovarian reserve function.

Infected wounds pose a significant clinical challenge, not only because of bacterial colonization (e.g., Staphylococcus aureus) but also because of the formation of a dysregulated wound microenvironment. Effective wound treatment requires strategies that simultaneously suppress bacterial growth and dynamically regulate the wound microenvironment for the biofluid transport. Here, we report a self-pumping wound dressing that autonomously regulates the wound microenvironment while providing a mechanism-specific antibacterial activity. The dressing is constructed by laminating a hydrophobic polyvinylidene fluoride layer with hydrophilic carbon cloth, forming an asymmetric wettability gradient that drives spontaneous and unidirectional exudate transport. To integrate antibacterial function, a novel fluorinated polyphenolic compound (FPC, C27H22F2O3) with selective activity against Staphylococcus aureus and low mammalian cytotoxicity is incorporated into the dressing, enabling effective bacterial inhibition under conditions compatible with tissue repair. Importantly, dynamic regulation of wound biofluid enhances the availability of FPC at the wound site rather than relying on sustained exposure. In a murine full-thickness Staphylococcus aureus-infected wound model, this integrated system accelerates wound closure, reduces inflammatory responses, and promotes organized collagen deposition and re-epithelialization. These results demonstrate that coupling autonomous microenvironment regulation with mechanism-specific antibacterial chemistry offers an effective strategy for treating infected wounds through the active control of the wound microenvironment.

Hepatocellular carcinoma (HCC) is characterized by poor prognosis and limited effective treatment options, necessitating a deeper understanding of its pathogenesis. This study focuses on tumor necrosis factor-α-induced protein 1 (TNFAIP1) and cytochrome P450 3A4 (CYP3A4) in HCC, aiming to investigate their association and functional roles in tumor progression. Bioinformatics analyses and experimental validation revealed that both TNFAIP1 and CYP3A4 are downregulated in HCC, and that TNFAIP1 positively regulates CYP3A4 expression. TNFAIP1 knockout not only decreased CYP3A4 expression but also significantly impaired the ability of rifampicin (RIF), an upstream nuclear receptor-pregnane X receptor (PXR) agonist, to induce CYP3A4, indicating that TNFAIP1 is an essential regulator of PXR/CYP3A4 pathway. Co-immunoprecipitation (Co-IP) experiment further confirmed the direct interaction between TNFAIP1 and PXR. TNFAIP1 knockout promoted HCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while suppressing apoptosis; these effects were partially attenuated by pharmacological activation of PXR or genetic overexpression of CYP3A4. In vivo experiments demonstrated that overexpression of Tnfaip1 upregulated the Pxr/Cyp3a11 pathway and inhibited tumor growth, whereas Tnfaip1 knockout suppressed this pathway. This study identified TNFAIP1-PXR-CYP3A4 as a novel tumor-suppressive axis in HCC, providing potential molecular targets for HCC diagnosis and treatment.

Perfluorohexane sulfonate (PFHxS) is a persistent perfluoroalkyl substance with bioaccumulative properties, yet its chronic and parental transmission toxicity in aquatic vertebrates remains insufficiently characterized. Here, adult zebrafish (Danio rerio) were exposed to 0, 0.01, or 0.1 μmol/L PFHxS for 56 days, and both parental (F0) reproductive endpoints and offspring (F1) development were assessed. In F0 adults, PFHxS altered somatic and gonadal indices in a sex-dependent manner and induced clear gonadal histopathology. Sperm kinematic parameters (VAP, VSL, VCL) were reduced by 15 % in the 0.01 μmol/L group and were further decreased in the 0.1 μmol/L group, indicating impaired sperm motility. PFHxS exposure also affected gonadal hormone levels in zebrafish and significantly altered the expression of multiple hypothalamic-pituitary-gonadal (HPG) axis-related genes in testes and ovaries. F0 fish exposed to 0.1 μmol/L PFHxS produced fewer and poorer-quality embryos, with spawning number decreasing and fertilization rates declining. Although overall survival of F1 larvae was unaffected, parental PFHxS exposure advanced hatching, increased heart rate at 48 hpf, and significantly reduced average swimming distance and speed at 120 hpf. At 7 dpf, the F1 offspring of PFHxS-exposed parents exhibited a trend toward elevated liver triglyceride levels, accompanied by significant alterations in lipid-metabolism genes. In summary, these findings indicate that long-term low-dose PFHxS exposure impairs reproductive function in adult zebrafish and induces developmental and metabolic alterations in offspring across one generation (F0–F1). This work provides phenotypic and endocrine evidence for the parental transmission of toxicity of PFHxS and highlights the need for future mechanistic and epigenetic studies.

Recent years have witnessed significant advances in neuromodulation techniques for stroke rehabilitation, especially in ameliorating motor deficits, positioning them as a key focus in both research and clinical practice. The selection of stimulation targets is crucial, as different sites engage distinct neural mechanisms and yield varied therapeutic outcomes. This review systematically synthesizes evidence from neuromodulation studies that target key regions, including the cerebral hemispheres, sensorimotor cortex, cerebellum, and vagus nerve. By analyzing the stimulation protocols, therapeutic effects, and optimal parameters associated with each target, we aim to provide a theoretical foundation and practical guidance for refining neuromodulation strategies in stroke rehabilitation.

Organic fluorescent dyes have become an indispensable research tool in modern science and medicine. Rhodamine B (RhB) is a representative of organic fluorescent dyes, and its combination with semiconductors can provide more possibilities for the development of optoelectronics. The emerging organic photoelectrochemical transistor (OPECT) biosensing technology applied to organic electronics and photoelectrochemical bioanalysis is a promising technological frontier in this field. However, research on the combination of gate electrodes in OPECT with organic fluorescent dyes still needs to be expanded. In this study, a biosensor based on RhBsensitized ZnIn2S4/FTO gate electrode combined with OPECT was developed to achieve the ultrasensitive detection of cholesterol oxidase (ChOx). The sensitizing effect of RhB on ZnIn2S4 and the enhancement of photocurrent were found for the first time. Besides, cholesterol was catalyzed by ChOx to generate H2O2, which reacted with I- under acidic conditions, leading to a significant decrease in the sensitization ability of RhB towards the gate electrode. A corresponding gate-gated poly (ethylene dioxythiophene): polystyrene sulfonate modulated channel current at a specific drain voltage was regulated accordingly, thus establishing a sensitive and specific biosensing platform for assaying ChOx with the detection limit of 6.53 x 10(-10) U center dot mL(-1). This sensing platform performs innovative experiments for the combination of organic fluorescent dyes with OPECT and applies the combined sensors to bio-detection, providing a proof-of-concept study for the overall development of organic fluorescent dye-sensitized semiconductor gated electronics and beyond.

In recent years, there has been an escalating incidence of recurrent pregnancy loss (RPL), imposing substantial psychosocial and economic burdens on families. Despite extensive investigations, approximately 50% of cases remain idiopathic, underscoring the intricate nature of potential pathogenic mechanisms. Quercetin (QUE), a prevalent flavonoid compound, exhibits potential in the therapeutic modulation of RPL by influencing endocrine, coagulation, oxidative stress, inflammation, and immune responses. This review aims to elucidate the potential role of QUE in RPL, explore its molecular mechanisms, and delineate its therapeutic significance. Herein, we synthesize existing evidence on the impact of QUE in RPL, particularly in traditional Chinese medicine, accentuating areas necessitating further exploration. QUE demonstrates regulatory prowess over RPL by modulating endocrine functions, encompassing thyroid functionality, diabetes, polycystic ovary syndrome, and luteal phase defects. It exhibits anti-inflammatory and antioxidant properties, influences coagulation functions, and affects immune cells such as T cells, T helper cells, macrophages, and natural killer cells. QUE also interacts with maternal-fetal interface cells, including myeloid-derived suppressor cells, stromal cells, and extravillous trophoblast cells, highlighting its multifaceted role in the modulation of RPL. Despite promising preclinical data, clinical trials directly targeting RPL remain limited. We emphasize the need for rigorous human studies to validate QUE's efficacy and safety in pregnancy. By elucidating the mechanistic underpinnings of QUE in treating RPL, this research may contribute to developing targeted interventions for RPL and other adverse pregnancy conditions, ultimately ameliorating reproductive health and well-being for affected individuals and families.