[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 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.

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.

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°.

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.

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.

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.

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.

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.

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.

Manufacturing non-sintered ceramsite from dredged sediment, steel slag, and fly ash for lightweight aggregate: production and characterization.

Green and low-carbon materialization for dredged sediment (DS) is limited due to its low pozzolanic activity. In this study, a novel DS-based non-sintered lightweight aggregate (LWA) is developed by steel slag (SS) and fly ash (FA) activation. Process optimization is performed by the response surfaces, and the basic properties and characterization of the optimal product are investigated. Results indicated that the optimized design ceramic aggregate (ODCA) was prepared as follows: raw pellets comprising of 59.2% DS, 5% SS, 35.8% FA, 5% MK, 5% H2O2, and 2‰ foam stabilizer were activated by alkali activator (1.5 weight ratio of 14 M NaOH to water glass) and then cured at 80 °C and 95% humidity for 24 h. The basic and environmental performances of ODCA were in accordance with standards, whose bulk density was as low as 665.8 kg/m3, the high cylinder compressive strength was 6.143 MPa, and leaching concentrations of heavy metals were controllable. The regulation mechanism of LWA performances could be summarized as follows. SS and FA additives played the role for the mechanical strength enhancement and passivation of heavy metals, which promoted the formation of sillimanite, chabazite, and C-S-H / C-S-A-H gels in ODCA. The bulk density of ODCA was greatly reduced by H2O2 addition, where ODCA had an open-pore structure with a median pore size of 4969.75 nm. Note that C-S-H/C-S-A-H were the key hydration products to give ODCA light density and high mechanical strength, simultaneously.

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.

Serum Albumin for Short-Term Poor Prognosis in Patients With Acute Pulmonary Embolism: A Clinical Study Based on a Database.

The relationship between serum albumin (ALB) and short-term prognosis in patients with acute pulmonary embolism (APE) remains unclear. We investigated the predictive value of ALB for short-term prognosis in APE patients using our hospital pulmonary embolism (PE) database (384 patients consecutively collected). Logistic regression analysis and nomograms were applied to construct the predictive model, and validation was assessed. A total of 340 APE patients were included, with a 30-day all-cause mortality rate of 8.5%. The incidence of hypoalbuminemia was 15.9%. The odds ratio (OR) for short-term mortality in patients with high ALB was 0.89 (0.886, 95% CI: 0.812-0.967). Additionally, we created a nomogram for individualized mortality risk prediction. Receiver operating characteristic (ROC) curve analysis showed that the diagnostic area under the curve (AUC) of ALB was 0.758 (95% CI 0.683-0.833), and the best cut-off value was 33.85 g/L. Optimal simplified Pulmonary Embolism Severity Index (sPESI) (ALB combined sPESI) AUC was 0.835 (95% CI 0.775-0.896). Baseline hypoalbuminemia may be an independent prognostic indicator of short-term mortality in patients with APE.

Integrated bioinformatics analysis identifies a Ferroptosis-related gene signature as prognosis model and potential therapeutic target of bladder cancer.

Background: Bladder cancer (BLCA) is one of the most prevalent cancers worldwide. Ferroptosis is a newly discovered form of non-apoptotic cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRGs) in BLCA has not yet been well studied. Method and materials: In this study, we performed consensus clustering based on FRGS and categorized BLCA patients into 2 clusters (C1 and C2). Immune cell infiltration score and immune score for each sample were computed using the CIBERSORT and ESTIMATE methods. Functional annotation of differentially expressed genes were performed by Gene Ontology (GO) and KEGG pathway enrichment analysis. Protein expression validation were confirmed in Human Protein Atlas. Gene expression validation were performed by qPCR in human bladder cancer cell lines lysis samples. Result: C2 had a significant survival advantage and higher immune infiltration levels than C1. Additionally, C2 showed substantially higher expression levels of immune checkpoint markers than C1. According to the Cox and LASSO regression analyses, a novel ferroptosis-related prognostic signature was developed to predict the prognosis of BLCA effectively. High-risk and low-risk groups were divided according to risk scores. Kaplan-Meier survival analyses showed that the high-risk group had a shorter overall survival than the low-risk group throughout the cohort. Furthermore, a nomogram combining risk score and clinical features was developed. Finally, SLC39A7 was identified as a potential target in bladder cancer. Discussion: In conclusion, we identified two ferroptosis-clusters with different prognoses using consensus clustering in BLCA. We also developed a ferroptosis-related prognostic signature and nomogram, which could indicate the outcome.

Atomic-level design of metalloenzyme-like active pockets in metal-organic frameworks for bioinspired catalysis.

Natural metalloenzymes with astonishing reaction activity and specificity underpin essential life transformations. Nevertheless, enzymes only operate under mild conditions to keep sophisticated structures active, limiting their potential applications. Artificial metalloenzymes that recapitulate the catalytic activity of enzymes can not only circumvent the enzymatic fragility but also bring versatile functions into practice. Among them, metal-organic frameworks (MOFs) featuring diverse and site-isolated metal sites and supramolecular structures have emerged as promising candidates for metalloenzymes to move toward unparalleled properties and behaviour of enzymes. In this review, we systematically summarize the significant advances in MOF-based metalloenzyme mimics with a special emphasis on active pocket engineering at the atomic level, including primary catalytic sites and secondary coordination spheres. Then, the deep understanding of catalytic mechanisms and their advanced applications are discussed. Finally, a perspective on this emerging frontier research is provided to advance bioinspired catalysis.

Multi-dimensional metabolomic profiling reveals dysregulated ornithine metabolism hallmarks associated with a severe acute pancreatitis phenotype.

To reveal dysregulated metabolism hallmark that was associated with a severe acute pancreatitis (SAP) phenotype. In this study, LC-MS/MS-based targeted metabolomics was used to analyze plasma samples from 106 acute pancreatitis (AP) patients (34 mild, 38 moderate, and 34 severe) admitted within 48 hours from abdominal pain onset and 41 healthy controls. Temporal metabolic profiling was performed on days 1, 3, and 7 after admission. A random forest (RF) was performed to significantly determine metabolite differences between SAP and non-SAP (NSAP) groups. Mass spectrometry imaging (MSI) and immunohistochemistry were conducted for the examination of pancreatic metabolite and metabolic enzyme alterations, respectively, on necrosis and paracancerous tissues. Simultaneously determination of serum and pancreatic tissue metabolic alterations using an L-ornithine-induced AP model to discover metabolic commonalities. Twenty-two significant differential metabolites screened by RF were selected to build an accurate model for the prediction of SAP from NSAP (AUC = 0.955). Six of 22 markers were found by MSI with significant alterations in pancreatic lesions, reduced ornithine-related metabolites were also identified. The abnormally expressed arginase2 and ornithine transcarboxylase were further discovered in combination with time-course metabolic profiling in the SAP animal models, the decreased ornithine catabolites were found at a late stage of inflammation, but ornithine-associated metabolic enzymes were activated during the inflammatory process. The plasma metabolome of AP patients is distinctive, which shows promise for early SAP diagnosis. AP aggravation is linked to the activated ornithine metabolic pathway and its inadequate levels of catabolites in in-situ lesion.

Role of solute carrier transporters in regulating dendritic cell maturation and function.

Dendritic cells (DCs) are specialized antigen-presenting cells that initiate and regulate innate and adaptive immune responses. Solute carrier (SLC) transporters mediate diverse physiological functions and maintain cellular metabolite homeostasis. Recent studies have highlighted the significance of SLCs in immune processes. Notably, upon activation, immune cells undergo rapid and robust metabolic reprogramming, largely dependent on SLCs to modulate diverse immunological responses. In this review, we explore the central roles of SLC proteins and their transported substrates in shaping DC functions. We provide a comprehensive overview of recent studies on amino acid transporters, metal ion transporters, and glucose transporters, emphasizing their essential contributions to DC homeostasis under varying pathological conditions. Finally, we propose potential strategies for targeting SLCs in DCs to bolster immunotherapy for a spectrum of human diseases.

Drug-Induced Acute Pancreatitis: A Real-World Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database.

Timely identification and discontinuation of culprit-drug is the cornerstone of clinical management of drug-induced acute pancreatitis (AP), but the comprehensive landscape of AP culprit-drugs is still lacking. To provide the current overview of AP culprit-drugs to guide clinical practice, we reviewed the adverse event (AE) reports associated with AP in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from 2004 to 2022, and summarized a potential AP culprit-drug list and its corresponding AE report quantity proportion. The disproportionality analysis was used to detect adverse drug reaction (ADR) signals for each drug in the drug list, and the ADR signal distribution was integrated to show the risk characteristic of drugs according to the ADR signal detection results. In the FAERS database, a total of 62,206 AE reports were AP-related, in which 1,175 drugs were reported as culprit-drug. On the whole, metformin was the drug with the greatest number of AE reports, followed by quetiapine, liraglutide, exenatide, and sitagliptin. Drugs used in diabetes was the drug class with the greatest number of AE reports, followed by immunosuppressants, psycholeptics, drugs for acid-related disorders, and analgesics. In disproportionality analysis, 595 drugs showed potential AP risk, whereas 580 drugs did not show any positive ADR signal. According to the positive-negative distribution of the ADR signal for drug classes, the drug class with the greatest number of positive drugs was antineoplastic agents. In this study, we provided the current comprehensive landscape of AP culprit-drugs from the pharmacovigilance perspective, which can provide reference information for clinical practice.

Multi-MSIProcessor: Data Visualizing and Analysis Software for Spatial Metabolomics Research.

Mass spectrometry imaging (MSI) has emerged as a revolutionary analytical strategy in biomedical research for molecular visualization. By linking the characterization of functional metabolites with tissue architecture, it is now possible to reveal unknown biological functions of tissues. However, due to the complexity and high dimensionality of MSI data, mining bioinformatics-related peaks from batch MSI data sets and achieving complete spatially resolved metabolomics analysis remain a great challenge. Here, we propose novel MSI data processing software, Multi-MSIProcessor (MMP), which integrates the data read-in, MSI visualization, processed data preservation, and biomarker discovery functions. The MMP focuses on the AFADESI-MSI data platform but also supports mzXML and imzmL data input formats for compatibility with data generated by other MSI platforms such as MALDI/SIMS-MSI. MMP enables deep mining of batch MSI data and has flexible adaptability with the source code opened that welcomes new functions and personalized analysis strategies. Using multiple clinical biosamples with complex heterogeneity, we demonstrated that MMP can rapidly establish complete MSI analysis workflows, assess batch sample data quality, screen and annotate differential MS peaks, and obtain abnormal metabolic pathways. MMP provides a novel platform for spatial metabolomics analysis of multiple samples that could meet the diverse analysis requirements of scholars.