Transcriptome- and genome-wide systematic identification of expansin gene family and their expression in tuberous root development and stress responses in sweetpotato (Ipomoea batatas).

Introduction: Expansins (EXPs) are essential components of the plant cell wall that function as relaxation factors to directly promote turgor-driven expansion of the cell wall, thereby controlling plant growth and development and diverse environmental stress responses. EXPs genes have been identified and characterized in numerous plant species, but not in sweetpotato. Results and methods: In the present study, a total of 59 EXP genes unevenly distributed across 14 of 15 chromosomes were identified in the sweetpotato genome, and segmental and tandem duplications were found to make a dominant contribution to the diversity of functions of the IbEXP family. Phylogenetic analysis showed that IbEXP members could be clustered into four subfamilies based on the EXPs from Arabidopsis and rice, and the regularity of protein motif, domain, and gene structures was consistent with this subfamily classification. Collinearity analysis between IbEXP genes and related homologous sequences in nine plants provided further phylogenetic insights into the EXP gene family. Cis-element analysis further revealed the potential roles of IbEXP genes in sweetpotato development and stress responses. RNA-seq and qRT-PCR analysis of eight selected IbEXPs genes provided evidence of their specificity in different tissues and showed that their transcripts were variously induced or suppressed under different hormone treatments (abscisic acid, salicylic acid, jasmonic acid, and 1-aminocyclopropane-1-carboxylic acid) and abiotic stresses (low and high temperature). Discussion: These results provide a foundation for further comprehensive investigation of the functions of IbEXP genes and indicate that several members of this family have potential applications as regulators to control plant development and enhance stress resistance in plants.

The Potential Mechanism of Eriodictyol in Treating Alzheimer's Disease: A Study on Computer-assisted Investigational Strategies.

BACKGROUND: At present, drug development for treating Alzheimer's disease (AD) is still highly challenging. Eriodictyol (ERD) has shown great potential in treating AD, but its molecular mechanism is unknown. OBJECTIVE: We aimed to explore the potential targets and mechanisms of ERD in the treatment of AD through network pharmacology, molecular docking, and molecular dynamics simulations. METHODS: ERD-related targets were predicted based on the CTD, SEA, PharmMapper, Swiss TargetPrediction, and ETCM databases, and AD-related targets were predicted through the TTD, OMIM, DrugBank, GeneCards, Disgenet, and PharmGKB databases. Protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomics analyses (KEGG) were used to analyse the potential targets and key pathways of the anti-AD effect of ERD. Subsequently, potential DEGs affected by AD were analysed using the AlzData database, and their relationships with ERD were evaluated through molecular docking and molecular dynamics simulations. RESULTS: A total of 198 ERD-related targets, 3716 AD-related targets, and 122 intersecting targets were identified. GO annotation analysis revealed 1497 biological processes, 78 cellular components, and 132 molecular functions of 15 core targets. KEGG enrichment analysis identified 168 signalling pathways. We ultimately identified 9 DEGs associated with AD through analysis of the AlzData data. Molecular docking results showed good affinity between the selected targets and ERD, with PTGS2, HSP90AA1, and BCL2. The interactions were confirmed by molecular dynamics simulations. CONCLUSION: ERD exerts anti-AD effects through multiple targets, pathways, and levels, providing a theoretical foundation and valuable reference for the development of ERD as a natural anti-AD drug.

METTL1-mediated tRNA m7G methylation and translational dysfunction restricts breast cancer tumorigenesis by fueling cell cycle blockade.

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

How does the ion concentration affect the functions of kinesin BimC.

BimC family proteins are bipolar motor proteins belonging to the kinesin superfamily which promote mitosis by crosslinking and sliding apart antiparallel microtubules. Understanding the binding mechanism between the kinesin and the microtubule is crucial for researchers to make advances in the treatment of cancer and other malignancies. Experimental research has shown that the ion concentration affects the function of BimC significantly. But the insights of the ion-dependent function of BimC remain unclear. By combining molecular dynamics (MD) simulations with a series of computational approaches, we studied the electrostatic interactions at the binding interfaces of BimC and the microtubule under different KCl concentrations. We found the electrostatic interaction between BimC and microtubule is stronger at 0 mM KCl compared to 150 mM KCl, which is consistent with experimental conclusions. Furthermore, important salt bridges and residues at the binding interfaces of the complex were identified, which illustrates the details of the BimC-microtubule interactions. Molecular dynamics analyses of salt bridges identified that the important residues on the binding interface of BimC are positively charged, while those residues on the binding interface of the tubulin heterodimer are negatively charged. The finding in this work reveals some important mechanisms of kinesin-microtubule binding, which helps the future drug design for cancer therapy.

Potential Mechanism by which Eriodictyol Protects against Doxorubicininduced Cardiotoxicity based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

BACKGROUND: The clinical use of doxorubicin (DOX), an anthracycline antibiotic with broad-spectrum applications against various malignant tumors, is limited by doxorubicininduced cardiotoxicity (DIC). Eriodictyol (ERD) has shown cardioprotective effects, but the mechanism of its protective effect on DIC remains unknown. AIMS: This study aimed to explore the potential mechanisms by which ERD confers protection against DIC. METHODS: ERD and DIC targets were identified from the TCMSP, PharmMaper, SwissTargetPrediction, TargetNet, BATMAN, GeneCards, and PharmGKB databases. Differential gene expression data between DIC and normal tissues were extracted from the GEO database. A protein‒ protein interaction (PPI) network of the intersecting ERD-DIC targets was constructed using the STRING platform and visualized with Cytoscape 3.10.0 software. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for ERD-DIC cross-targets were conducted. Validation included molecular docking with AutoDock Tools software and molecular dynamics simulations with Gromacs 2019.6 software. RESULTS: Network pharmacology analysis revealed 43 intersecting ERD-DIC targets, including 6 key targets. GO functional enrichment analysis indicated that the intersecting targets were enriched in 550 biological processes, 45 cell components, and 41 molecular functions. KEGG pathway enrichment analysis identified 114 enriched signaling pathways. Molecular docking revealed a strong binding affinity between ERD and 6 key targets, as well as multiple targets within the ROS pathway. Molecular dynamics simulations indicated that ERD has favorable binding with 3 crucial targets. CONCLUSION: The systematic network pharmacology analysis suggests that ERD may mitigate DIC through multiple targets and pathways, with the ROS pathway potentially playing a crucial role. These findings provide a reference for foundational research and clinical applications of ERD in treating DIC.

Effects of 15% Azelaic Acid Gel in the Management of Post-Inflammatory Erythema and Post-Inflammatory Hyperpigmentation in Acne Vulgaris.

INTRODUCTION: The aim of this study was to assess the efficacy and safety of 15% azelaic acid (AzA) gel in treating acne-induced post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH). The effects of 15% AzA gel on acne, skin barrier function, and quality of life were also evaluated. METHODS: A total of 72 patients with mild to moderate acne were enrolled in a randomized, double-blind, placebo-controlled trial. Patients were divided into two groups: patients in the AzA group applied 15% AzA gel twice daily for 12 weeks, and those in the placebo group applied AzA-free gel. Clinical evaluations using non-invasive skin detection technologies, including VISIA skin analysis, dermoscopy, and skin physiological function tests, were performed at 0, 4, 8, and 12 weeks. Main outcome measures included the post-acne hyperpigmentation index (PAHPI), melanin, hemoglobin, individual typology angle, water content, transepidermal water loss, and sebum. Investigator Global Assessment) and Dermatology Life Quality Index (DLQI) assessments were conducted at weeks 0 and 12. Adverse reactions were recorded. RESULTS: Of the 72 patients at study initiation, 60 completed the trial. At 8 and 12 weeks, patients in the AzA group showed significantly reduced PAHPI for PIE lesions compared to baseline and patients receiving placebo (P < 0.05). Patients in both groups exhibited reduced PIH lesions at weeks 8 and 12 that differed significantly from baseline (P < 0.05). Hemoglobin content decreased significantly in AzA-treated PIE lesions compared to those treated with placebo at week 12 (P < 0.05). Melanin content decreased significantly in AzA-treated PIH lesions at week 12 (P < 0.05). The AzA group showed higher improvement in DLQI (P < 0.05), and greater overall satisfaction (P < 0.05) compared to placebo. CONCLUSION: The results indicate that 15% AzA gel effectively improved acne-induced PIE and PIH with minimal adverse reactions, making it a viable clinical application. In the study population, it had no adverse effects on skin barrier function and contributed positively to acne improvement and patient quality of life. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (ChiCTR.org.cn) under the identifier ChiCTR2300076959. The registration date was 25 October 2023, retrospectively registered.

3D-Printed Flexible Microfluidic Health Monitor for In Situ Sweat Analysis and Biomarker Detection.

Wearable sweat biosensors have shown great progress in noninvasive, in situ, and continuous health monitoring to demonstrate individuals' physiological states. Advances in novel nanomaterials and fabrication methods promise to usher in a new era of wearable biosensors. Here, we introduce a three-dimensional (3D)-printed flexible wearable health monitor fabricated through a unique one-step continuous manufacturing process with self-supporting microfluidic channels and novel single-atom catalyst-based bioassays for measuring the sweat rate and concentration of three biomarkers. Direct ink writing is adapted to print the microfluidic device with self-supporting structures to harvest human sweat, which eliminates the need for removing sacrificial supporting materials and addresses the contamination and sweat evaporation issues associated with traditional sampling methods. Additionally, the pick-and-place strategy is employed during the printing process to accurately integrate the bioassays, improving manufacturing efficiency. A single-atom catalyst is developed and utilized in colorimetric bioassays to improve sensitivity and accuracy. A feasibility study on human skin successfully demonstrates the functionality and reliability of our health monitor, generating reliable and quantitative in situ results of sweat rate, glucose, lactate, and uric acid concentrations during physical exercise.

Rhei Radix et Rhizoma and its anthraquinone derivatives: Potential candidates for pancreatitis treatment.

BACKGROUND: Pancreatitis is a common exocrine inflammatory disease of the pancreas and lacks specific medication currently. Rhei Radix et Rhizoma (RR) and its anthraquinone derivatives (AQs) have been successively reported for their pharmacological effects and molecular mechanisms in experimental and clinical pancreatitis. However, an overview of the anti-pancreatitis potential of RR and its AQs is limited. PURPOSE: To summarize and analyze the pharmacological effects of RR and its AQs on pancreatitis and the underlying mechanisms, and discuss their drug-like properties and future perspectives. METHODS: The articles related to RR and its AQs were collected from the Chinese National Knowledge Infrastructure, Wanfang data, PubMed, and the Web of Science using relevant keywords from the study's inception until April first, 2024. Studies involving RR or its AQs in cell or animal pancreatitis models as well as structure-activity relationship, pharmacokinetics, toxicology, and clinical trials were included. RESULTS: Most experimental studies are based on severe acute pancreatitis rat models and a few on chronic pancreatitis. Several bioactive anthraquinone derivatives of Rhei Radix et Rhizoma (RRAQs) exert local protective effects on the pancreas by maintaining pancreatic acinar cell homeostasis, inhibiting inflammatory signaling, and anti-fibrosis, and they improve systemic organ function by alleviating intestinal and lung injury. Pharmacokinetic and toxicity studies have revealed the low bioavailability and wide distribution of RRAQs, as well as hepatotoxicity and nephrotoxicity. However, there is insufficient research on the clinical application of RRAQs in pancreatitis. Furthermore, we propose effective strategies for subsequent improvement in terms of balancing effectiveness and safety. CONCLUSION: RRAQs can be developed as either candidate drugs or novel lead structures for pancreatitis treatment. The comprehensive review of RR and its AQs provides references for optimizing drugs, developing therapies, and conducting future studies on pancreatitis.

A rapid and sensitive one-pot platform integrating fluorogenic RNA aptamers and CRISPR-Cas13a for visual detection of monkeypox virus.

The recent global upsurge in Monkeypox virus (MPXV) outbreaks underscores the critical need for rapid and precise diagnostic solutions, particularly in resource-constrained settings. The gold standard diagnostic method, qRT-PCR, is hindered by its time-consuming nature, requirement for nucleic acid purification, expensive equipment, and the need for highly trained personnel. Traditional CRISPR/Cas fluorescence assays, relying on trans-cleavage of ssDNA/RNA reporters labeled with costly fluorophores and quenchers, pose challenges that limit their widespread application, especially for point-of-care testing (POCT). In this study, we utilized a cost-effective and stable fluorogenic RNA aptamer (Mango III), specifically binding and illuminating the fluorophore TO3-3 PEG-Biotin Fluorophore (TO3), as a reporter for Cas13a trans-cleavage activity. We propose a comprehensive strategy integrating RNA aptamer, recombinase-aided amplification (RAA), and CRISPR-Cas13a systems for the molecular detection of MPXV target. Leveraging the inherent collateral cleavage properties of the Cas13a system, we established high-sensitivity and specificity assays to distinguish MPXV from other Orthopoxviruses (OPVs). A streamlined one-pot protocol was developed to mitigate aerosol contamination risks. Our aptamer-coupled RAA-Cas13a one-pot detection method achieved a Limit of Detection (LoD) of 4 copies of target MPXV DNA in just 40 min. Validation using clinical MPX specimens confirmed the rapid and reliable application of our RAA-Cas13a-Apt assays without nucleic acid purification procedure, highlighting its potential as a point-of-care testing solution. These results underscore the user-friendliness and effectiveness of our one-pot RAA-Cas13a-Apt diagnostic platform, poised to revolutionize disease detection and management.

[Effects of tetramethylpyrazine on pharmacokinetics in plasma and brain dialysate and neuropathic pain in rat model of spared sciatic nerve injury].

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.

A novel approach to study multi-domain motions in JAK1's activation mechanism based on energy landscape.

The family of Janus Kinases (JAKs) associated with the JAK-signal transducers and activators of transcription signaling pathway plays a vital role in the regulation of various cellular processes. The conformational change of JAKs is the fundamental steps for activation, affecting multiple intracellular signaling pathways. However, the transitional process from inactive to active kinase is still a mystery. This study is aimed at investigating the electrostatic properties and transitional states of JAK1 to a fully activation to a catalytically active enzyme. To achieve this goal, structures of the inhibited/activated full-length JAK1 were modelled and the energies of JAK1 with Tyrosine Kinase (TK) domain at different positions were calculated, and Dijkstra's method was applied to find the energetically smoothest path. Through a comparison of the energetically smoothest paths of kinase inactivating P733L and S703I mutations, an evaluation of the reasons why these mutations lead to negative or positive regulation of JAK1 are provided. Our energy analysis suggests that activation of JAK1 is thermodynamically spontaneous, with the inhibition resulting from an energy barrier at the initial steps of activation, specifically the release of the TK domain from the inhibited Four-point-one, Ezrin, Radixin, Moesin-PK cavity. Overall, this work provides insights into the potential pathway for TK translocation and the activation mechanism of JAK1.

Nutrient availability regulates the secretion and function of immune cell-derived extracellular vesicles through metabolic rewiring.

Extracellular vesicle (EV)-based immunotherapeutics have emerged as promising strategy for treating diseases, and thus, a better understanding of the factors that regulate EV secretion and function can provide insights into developing advanced therapies. Here, we report that nutrient availability, even changes in individual nutrient components, may affect EV biogenesis and composition of immune cells [e.g., macrophages (Mφs)]. As a proof of concept, EVs from M1-Mφ under glutamine-depleted conditions (EVGLN-) had higher yields, functional compositions, and immunostimulatory potential than EVs from conventional GLN-present medium (EVGLN+). Mechanistically, the systemic metabolic rewiring (e.g., altered energy and redox metabolism) induced by GLN depletion resulted in up-regulated pathways related to EV biogenesis/cargo sorting (e.g., ESCRT) and immunostimulatory molecule production (e.g., NF-κB and STAT) in Mφs. This study highlights the importance of nutrient status in EV secretion and function, and optimizing metabolic states and/or integrating them with other engineering methods may advance the development of EV therapeutics.

The Preparation of Acryloxyl Group Functionalized Siloxane Polymers and the Study of Their Ultra Violet Curing Properties.

Polysiloxane with multiple acryloxyl groups at the terminal site of the polymer chain was synthesized by the condensation reaction between hydroxyl-terminated polysiloxane and acryloyl chloride and used to improve the cross-linking density of UV-curable silicone materials initiated from dual acryloxy-terminated symmetric polysiloxane or single acryloxy-terminated asymmetric polysiloxane with the mixture of Irgacure 1173 and Irgacure 184 at a mass ratio of 1:1 as the photoinitiator. The effects of factors such as initiator composition, UV irradiation time, structure, and molecular weight of linear dual acryloxy-terminated or single acryloxy-terminated asymmetric siloxane oligomers on the gelation yield, thermal properties, water absorption, and water contact angle of UV-cured film were investigated. The synthesized cross-linking density modifier can be copolymerized with acryloxy-functionalized linear polysiloxanes under the action of a photoinitiator to increase the cross-link density of UV-cured products effectively. Both linear dual acryloxy-terminated or single acryloxy-terminated asymmetric siloxane oligomers can be copolymerized with cross-link density modifiers within 20 s of UV irradiation. The gelation yields of the UV-cured products obtained from the dual acryloxy-terminated siloxane oligomers were greater than 85%, and their surface water contact angles increased from 72.8° to 95.9° as the molecular weight of the oligomers increased. The gelation yields of UV-cured products obtained from single acryloxy-terminated asymmetric siloxane oligomers were less than 80%, and their thermal stabilities were inferior to those obtained from the dual acryloxy-terminated siloxane oligomers. However, the water contact angles of UV-cured products obtained from these single acryloxy-terminated asymmetric siloxane oligomers were all greater than 90°.

Age-, sex- and proximal-distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates.

The incidence of intestinal diseases increases with age, yet the mechanisms governing gut aging and its link to diseases, such as colorectal cancer (CRC), remain elusive. In this study, while considering age, sex and proximal-distal variations, we used a multi-omics approach in non-human primates (Macaca fascicularis) to shed light on the heterogeneity of intestinal aging and identify potential regulators of gut aging. We explored the roles of several regulators, including those from tryptophan metabolism, in intestinal function and lifespan in Caenorhabditis elegans. Suggesting conservation of region specificity, tryptophan metabolism via the kynurenine and serotonin (5-HT) pathways varied between the proximal and distal colon, and, using a mouse colitis model, we observed that distal colitis was more sensitive to 5-HT treatment. Additionally, using proteomics analysis of human CRC samples, we identified links between gut aging and CRC, with high HPX levels predicting poor prognosis in older patients with CRC. Together, this work provides potential targets for preventing gut aging and associated diseases.

The Potential Mechanism of Liujunzi Decoction in the Treatment of Breast Cancer based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND: Liujunzi Decoction (LJZD) is a potential clinical treatment for Breast Cancer (BC), but the active ingredients and mechanisms underlying its effectiveness remain unclear. OBJECTIVE: The study aimed to investigate the target gene of LJZD compatibility and the possible mechanism of action in the treatment of breast cancer by using network pharmacology and molecular docking. METHODS: Based on TCMSP, ETCM, and BATMAN database searching and screening to obtain the ingredients of LJZD, the related targets were obtained. Breast cancer-related targets were collected through GEO, Geencards, OMIM, and other databases, and drug-disease Venn diagrams were drawn by R. The PPI network map was constructed by using Cytoscape. The intersecting targets were imported into the STRING database, and the core targets were analyzed and screened. The intersected targets were analyzed by the DAVID database for GO and KEGG enrichment. AutoDock Vina and Gromacs were used for molecular docking and simulation of the core targets and active ingredients. RESULTS: 126 active ingredients of LJZD were obtained; 241 targets related to breast cancer were sought after screening, and 180 intersection targets were identified through Venn diagram analysis. The core targets were FOS and ESR1. KEGG enrichment analysis mainly involved PI3K/Akt, MAPK, and other signaling pathways. CONCLUSION: This study has explored the possible targets and signaling pathways of LJZD in treating breast cancer through network pharmacology and bioinformatics analysis. Molecular docking and simulation have further validated the potential mechanism of action of LJZD in breast cancer treatment, providing essential experimental data for future studies.

Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility.

BACKGROUND: Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia. METHODS: We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation. RESULTS: Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein. CONCLUSIONS: Our research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.

Assessment of the Reliability and Clinical Applicability of ChatGPT's Responses to Patients' Common Queries About Rosacea.

Objective: Artificial intelligence chatbot, particularly ChatGPT (Chat Generative Pre-trained Transformer), is capable of analyzing human input and generating human-like responses, which shows its potential application in healthcare. People with rosacea often have questions about alleviating symptoms and daily skin-care, which is suitable for ChatGPT to response. This study aims to assess the reliability and clinical applicability of ChatGPT 3.5 in responding to patients' common queries about rosacea and to evaluate the extent of ChatGPT's coverage in dermatology resources. Methods: Based on a qualitative analysis of the literature on the queries from rosacea patients, we have extracted 20 questions of patients' greatest concerns, covering four main categories: treatment, triggers and diet, skincare, and special manifestations of rosacea. Each question was inputted into ChatGPT separately for three rounds of question-and-answer conversations. The generated answers will be evaluated by three experienced dermatologists with postgraduate degrees and over five years of clinical experience in dermatology, to assess their reliability and applicability for clinical practice. Results: The analysis results indicate that the reviewers unanimously agreed that ChatGPT achieved a high reliability of 92.22% to 97.78% in responding to patients' common queries about rosacea. Additionally, almost all answers were applicable for supporting rosacea patient education, with a clinical applicability ranging from 98.61% to 100.00%. The consistency of the expert ratings was excellent (all significance levels were less than 0.05), with a consistency coefficient of 0.404 for content reliability and 0.456 for clinical practicality, indicating significant consistency in the results and a high level of agreement among the expert ratings. Conclusion: ChatGPT 3.5 exhibits excellent reliability and clinical applicability in responding to patients' common queries about rosacea. This artificial intelligence tool is applicable for supporting rosacea patient education.

Multimodal evaluation of the effects of low-intensity ultrasound on cerebral blood flow after traumatic brain injury in mice.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and destruction of the cerebrovascular system is a major factor in the cascade of secondary injuries caused by TBI. Laser speckle imaging (LSCI)has high sensitivity in detecting cerebral blood flow. LSCI can visually show that transcranial focused ultrasound stimulation (tFUS) treatment stimulates angiogenesis and increases blood flow. To study the effect of tFUS on promoting angiogenesis in Controlled Cortical impact (CCI) model. tFUS was administered daily for 10 min and for 14 consecutive days after TBI. Cerebral blood flow was measured by LSCI at 1, 3, 7 and 14 days after trauma. Functional outcomes were assessed using LSCI and neurological severity score (NSS). After the last test, Nissl staining and vascular endothelial growth factor (VEGF) were used to assess neuropathology. TBI can cause the destruction of cerebrovascular system. Blood flow was significantly increased in TBI treated with tFUS. LSCI, behavioral and histological findings suggest that tFUS treatment can promote angiogenesis after TBI.

Malakoplakia of urinary bladde: 3 cases reports and review.

OBJECTIVE: This study aims to explore the clinical diagnosis and treatment methods of bladder malakoplakia (MUB) to enhance the understanding of the disease. METHODS: A retrospective analysis of the diagnosis and treatment processes of three cases of MUB treated in our department was conducted. Relevant literature from both domestic and international sources was reviewed to provide a comprehensive analysis. RESULTS: All three patients underwent transurethral resection of bladder lesions combined with antibiotic therapy, and two of them received transurethral instillation of gemcitabine. There were two cases with two recurrences each, and one case with four recurrences, with the latter also concurrently presenting with unilateral ureteral malakoplakia. Postoperative pathology confirmed MUB in all three cases. Close follow-up revealed no significant recurrence in the patients. CONCLUSION: The effective diagnosis rate is increased by conducting multiple deep, repetitive, and randomly selected live tissue examinations. The definitive diagnosis of MUB relies on pathological histological examination. Treatment involving a combination of antibiotics and transurethral resection of bladder lesions proves to be effective. Exploring the use of bladder instillation of gemcitabine widens the spectrum of MUB treatment methods.