Versatile whey acidic protein four-disulfide core domain proteins: biology and role in diseases.

The Whey acidic protein four-disulfide core (WFDC) protein family consists of proteins with one or more WFDC domains which are ubiquitously expressed throughout the body of human and perform a wide range of functions, including antiprotease, antibacterial, and immunomodulatory functions. Aberrant expression of WFDC proteins is associated with human diseases. However, review on the WFDC protein family is limited and insufficient. Furthermore, a systematic summary of the underlying mechanisms of WFDC protein activity is lacking. In this review, we give a summary of the structural basis and molecular function of these proteins and review the immune regulatory mechanisms and signaling pathways of WFDC proteins in the development of certain diseases. Furthermore, we discuss the diagnostic and prognostic potential of multiple WFDC proteins in the aforementioned conditions, as well as their prospective use. At last, we also discuss the progress of WFDC protein in clinical trials and put forward some research difficulties and the directions of follow-up research. Our review highlights the functional diversity and clinical significance of WFDC proteins family, while providing potential targets for drug development and innovative therapeutic strategies, this review lays the foundation and direction for future research on WFDC proteins.

Case report: Whole exome sequencing reveals a novel splicing variant of ANKRD17 gene in a Chinese male juvenile with developmental delay and transient tic disorder.

Background: The Ankyrin Repeat Domain Containing Protein 17 (ANKRD17, OMIM:615929) gene is a protein-coding gene associated with diseases such as Chopra-Amiel-Gordon Syndrome and Non-Specific Syndromic Intellectual Disability. The protein encoded by ANKRD17 gene belongs to the ankyrin repeat-containing protein family, which is one of the most widely existing protein domains that exclusively mediate protein-protein interactions. To date, the research and reports on the ANKRD17 gene are limited. Case presentation: Trio whole exome sequencing (Trio-WES) was conducted on the proband and his unaffected parents to elucidate the genetic etiology in the proband, who was clinically diagnosed with developmental delay and other phenotypes. Subsequently, Sanger sequencing was employed for validation of the identified candidate variant. Furthermore, RNA analysis was utilized to ascertain the impact of the variant on splicing. The WES revealed a novel heterozygous ANKRD17 splicing variant (c.7248 + 1G>A) in the proband, but not detected in his unaffected parents. And the presence of the splicing variant of the ANKRD17 gene was valided by the Sanger sequencing subsequently. And the RNA analysis confirmed that the novel variant was predicted to result in loss of donor splice site, and the analysis at mRNA level confirmed that it leads to exon 32 skipping (r.7100_7278del179) and causes premature termination of translation to the protein (p.D2357fs), therefore is classified as pathogenic. Conclusion: Our study reported a novel splicing variant in ANKRD17 gene, which may be associated with partial eating, frequent urination, and tic syndrome. This finding expands both the phenotypic and genotypic spectrum of ANKRD17 gene. Although there is currently no curative therapy available for ANKRD17 gene variants, a definitive diagnosis of its genetic etiology is significant for genetic counseling and family planning purposes. Furthermore, this is the first reported case of the ANKRD17 gene in China.

Depressive disorders in Chinese left-behind children and adolescents from Yunnan province: prevalence and association with self-harm behaviors.

BACKGROUND: The prevalence of clinically diagnosed depressive disorders (DD) in Chinese left-behind children (LBC) remains unknown. We aim to estimate the prevalence of DD, discuss the associations between DD and self-harm (SH) behaviors in a large representative sample of Chinese LBCs chosen from Yunnan province. METHODS: A total of 5462 LBCs were selected from the most recent datasets of the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY), a mega population-based two-phase cross-sectional survey. Weighted prevalence rates and designed Logistic regression were adopted to estimate the prevalence of DD and the association between DD and SH. RESULTS: The weighted prevalence of lifetime and current DD were 4.22% (95% CI: 3.13-6.00%) and 3.84% (95% CI: 2.85-5.00%) in Chinese LBCs. Higher lifetime and current DD prevalence rates were observed in girls and those reported adverse parental marital status and SH behaviors. The absence of DD was associated with significantly decreased odds of SH behavior (OR = 0.06), repetitive SH (OR = 0.09), using multiple SH methods (OR = 0.09), and severe SH (OR = 0.15). Subsequently performed stratified analyses identified prominent effect modification by sex and age, as a stronger association between DD and SH was found in girls (OR = 0.02 versus OR = 0.07 in boys) and younger adolescents (OR = 0.08 versus OR = 0.22 in older adolescents). CONCLUSION: The prevalence of DD was high in Chinese LBCs. DD was associated with prominently increased risk of SH behaviors in LBCs. Attention and intervention are needed in this vulnerable population.

Unveiling the impact of cell death-related genes and immune dynamics on drug resistance in lung adenocarcinoma: a risk score model and functional insights.

Lung adenocarcinoma (LUAD), characterized by its heterogeneity and complex pathogenesis, is the focus of this study which investigates the association between cell death-related genes and LUAD. Through machine learning, a risk score model was developed using the Coxboost rsf algorithm, demonstrating strong prognostic accuracy in both validation (GSE30219, GSE31210, GSE72094) and training (TCGA-LUAD) datasets with C-indices of 0.93, 0.67, 0.68, and 0.64, respectively. The study reveals that the expression of Keratin 18 (KRT18), a key cytoskeletal protein, varies across LUAD cell lines (DV-90, PC-9, A549) compared to normal bronchial epithelial cells (BEAS-2B), suggesting its potential role in LUAD's pathogenesis. Kaplan-Meier survival curves further validate the model, indicating longer survival in the low-risk group. A comprehensive analysis of gene expression, functional differences, immune infiltration, and mutations underscores significant variations between risk groups, highlighting the high-risk group's immunological dysfunction. This points to a more intricate tumor immune environment and the possibility of alternative therapeutic strategies. The study also delves into drug sensitivity, showing distinct responses between risk groups, underscoring the importance of risk stratification in treatment decisions for LUAD patients. Additionally, it explores KRT18's epigenetic regulation and its correlation with immune cell infiltration and immune regulatory molecules, suggesting KRT18's significant role in the tumor immune landscape. This research not only offers a valuable prognostic tool for LUAD but also illuminates the complex interplay between cell death-related genes, drug sensitivity, and immune infiltration, positioning KRT18 as a potential therapeutic or prognostic target to improve patient outcomes by personalizing LUAD treatment strategies.

Chinese expert consensus on management of antifungal-resistant dermatophytoses (2024 edition).

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.

Case Report: Whole exome sequencing identifies compound heterozygous variants in the TRAPPC9 gene in a child with developmental delay.

Background: Developmental delay in children under 5 years old, which occurs globally with an incidence of 10%-15%, is caused by multiple factors including genetics, prenatal conditions, perinatal complications, postnatal influences, social factors, and nutritional deficiencies. Gene variants such as EFNB1, MECP2 and TRAPPC9 play a significant role in protein deformation and downregulation of nuclear factor κB (NF-κB) activity. Methods: A 3-year-old girl, who exhibits poor gross motor skills, personal-social development, auditory language, hand-eye coordination, and visual performance, was diagnosed with global developmental delay. Trio whole exome sequencing was conducted to identify the genetic etiology of her condition. The identified genetic etiology was then validated through Sanger sequencing and quantitative polymerase chain reaction (qPCR). Results: Genetic analysis revealed that the patient had compound heterozygous variants in the TRAPPC9 gene. These include a c.1928del frameshift variant inherited from the unaffected father and a deletion in exon 12 inherited from the unaffected mother. According to the American College of Medical Genetics (ACMG) guidelines, these variants were classified as "likely pathogenic". Conclusion: The study revealed that compound heterozygous TRAPPC9 gene variants cause developmental delay in a Chinese girl. These variants have been classified as having significant pathogenic effect according to the ACMG criteria, suggesting a recessive genetic pattern and highlighting the importance of prenatal testing for future offspring. Furthermore, our findings expand the genotype spectrum of the TRAPPC9 gene, and provide more comprehensive information regarding genetic counseling for children experiencing developmental delay.

Case report: Genetic diagnoses in a pediatric patient with retinoblastoma and comorbid global developmental delay: three distinct entities diagnosed by whole exome sequencing in a single patient.

Background: The objective of this study was to explore the genetic etiology and propose a genetic diagnosis and counseling strategy for children with retinoblastoma (RB) and global developmental delay (GDD). Case presentation: We report on a 2 years and 4 months old boy with binocular retinoblastoma and global developmental delay (included intellectual disability, language development delay, motor development delay, etc.). Genomic DNA was extracted from peripheral blood mononuclear cells isolated from the proband and his parents. Whole exome sequencing (WES) was carried out for the proband and his parents to identify genetic etiology, which was subsequently verified by quantitative polymerase chain reaction (qPCR).The WES revealed a gross heterozygous deletion in the RB transcriptional corepressor 1 (RB1, OMIM:614041) gene, including exon 7-8, in the affected proband but not in his parents. Additionally, two pathogenic copy number variations (CNVs) were identified: a duplication at 7q11.23 and a microdeletion at 16p11.2-p12.2, respectively. Furthermore, the genomic qPCR analysis demonstrated a 50% reduction in the copy numbers of exon 7 and exon 8 in the RB1 gene of the proband, as compared to those detected in his parents. Simultaneous variants in the RB1 gene and two pathogenic CNVs can precisely explain the genetic etiology of the proband. Conclusion: The present study firstly reports a novel gross deletion variant of the RB1 gene coexisting with two pathogenic CNVs in a pediatric patient with retinoblastoma and comorbid global developmental delay in China. Additionally, our findings strongly support the use of WES in pediatric patients with RB comorbid GDD, and WES is recommended as the first-tier test.

Childhood maltreatment associated suicidal risk in Chinese children and adolescents: a mediation of resilience.

BACKGROUND: Existing evidence suggests that children and adolescents who had experienced childhood maltreatment (CM) are at higher suicidal risk. However, the mediation role of resilience in this association remains unclear. We aim to investigate the mediation via resilience in the associations between CM and three suicidal risk indicators (suicidal ideation, SI; suicidal plan, SP; suicidal attempt, SA) among a large sample of Chinese children and adolescents. METHODS: A population-based cross-sectional survey was conducted in southwestern China Yunnan province. A total of 9723 children and adolescents were included and analyzed by using a multi-stage stratified cluster sampling design. Univariate and multivariate logistic regression models were fitted to explore the associations between CM, resilience, and the three suicidal risk indicators, dose-response trends further elucidated by using the restricted cubic splines. Path models were adopted to estimate the mediation of resilience. RESULTS: The estimated prevalence rates for one-year SI, SP and SA were 32.86% (95% CI: 31.93-33.80%), 19.36% (95% CI: 18.57-20.16%) and 9.07% (95% CI: 8.51-9.66%). After adjustment, CM significantly associated with all 3 suicidal risk indicators, and the odds ratios (ORs) were 2.13 (95% CI: 1.91-2.37), 2.45 (95% CI: 2.13-2.81), and 3.61 (95% CI: 2.90-4.52) for one-year SI, SP, and SA, respectively. Path models revealed that resilience significantly mediated the associations between CM and the three suicidal risk indicators, and among all dimensions of resilience, family support presented the strongest mediation consistently. CONCLUSIONS: Our study results suggest that intervention measures which focusing on improving psychological resilience might be effective in reducing suicidal risk for children and adolescents who had experienced maltreatment. Prospective studies should be done to corroborate our findings.

Anisodamine hydrobromide ameliorates acute lung injury via inhibiting pyroptosis in murine sepsis model.

OBJECTIVE: Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered ALI and elucidate the fundamental mechanisms involved. MATERIALS AND METHOD: The protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. RESULTS: Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1ß in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines. CONCLUSION: These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.

Effects of vaginal microbiota on human papillomavirus infection and its related diseases.

With the knowledge of female reproductive tract microbiota gradually increasing, the connection between vaginal microbiota (VMB) and its related diseases is increasingly highlighted. Manifestation of VMB keeps changing with various dominated bacteria, which can affect the immune response of mucosal barrier and the entrance of pathogens. Human papillomavirus (HPV), as an oncogenic virus, is closely related to viral-associated cancer, such as cervical cancer. According to HPV infection status, VMB can transform into different types, and result in accelerating or restraining the progression of diseases, which have exposed the inner link between VMB and HPV. Therefore, probiotics therapy promises to be a new complementary therapy to rebuild a healthy VMB for patients, but there's still a long way to go before its ready for the clinic. This review focuses on composition, immune response, and application of VMB in HPV and its associated diseases and aims to provide the new ideas and directions for the research on VMB.

Automated Skeleton Network Generation for ReaxFF Molecular Dynamics Simulations of Hydrocarbon Fuel Pyrolysis and Oxidation via a Rate-Based Algorithm.

In this study, we present an automated approach of rate-based skeleton network generation for ReaxFF MD simulation (RxMD-SN) for deriving the reaction kinetic mechanism of large hydrocarbon fuels in pyrolysis and oxidation from large-scale ReaxFF MD simulations. The approach contains the statistical calculation of reaction rate constants and the generation of skeleton reaction networks using a rate-based algorithm. The RxMD-SN method takes advantage of reaction flux ranking at a small time interval in terms of temporal reaction rate to extract the core reaction networks, which allows for keeping the rare reaction events that may be dominant in a certain period of the reaction network. The kinetic models derived from ReaxFF MD simulation in CH4 oxidation can reproduce what was obtained in the ReaxFF MD simulation, which demonstrates the capability of RxMD-SN in capturing the global reaction kinetics. An evaluation of reaction rate constants indicates that close kinetic parameters are shared for n-octane oxidation of similar reaction classes, shared oxidation reactions of CH4 against n-heptane, and shared pyrolysis reactions of the RP-3 surrogate fuel against n-heptane. This capability of RxMD-SN is particularly beneficial in meeting the challenges in characterizing the oxidation reaction kinetics of large hydrocarbon molecules. RxMD-SN approach is potentially a general approach in chemical kinetics modeling on the basis of ReaxFF MD simulations.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

MHBase: A comprehensive database of short microhaplotypes for advancing forensic genetic analysis.

Microhaplotypes (MHs) were first recommended by Prof. Kidd for use in forensics because they can improve human identification, kinship analysis, mixture deconvolution, and ancestry prediction. Since their introduction, extensive research has demonstrated the advantages of MHs in forensic applications and provided useful data for different populations. Currently, two databases, ALFRED (ALlele FREquency Database) and MicroHapDB (MicroHaplotype DataBase), house the published MH information and population data. We previously constructed a single nucleotide polymorphism SNP-SNP MH database (D-SNPsDB) of MHs within 50 bp on the whole human genome for 26 populations integrating basic data such as physical genome positions, mapping of variant identifiers (rsIDs), allele frequencies, and basic variant information. Building upon the previous research, we further selected MHs containing at least two variants (SNPs and/or insertions/deletions [InDels]) within a short DNA fragment (≤ 50 bp) in 26 populations based on the 1000 Genomes Project dataset (Phase 3) to construct a more comprehensive database. Subsequently, we established a user-friendly website that allows users to search the MH database (MHBase) based on their research objectives and study population to find suitable loci and provides other functions such as querying reported loci, performing online calculations using the PHASE software, and calculating ancestral-related parameters. The loci in the database are classified as SNP-based MHs, which include only SNPs, and InDel-including MHs, which contain at least one InDel. Here, we provide a detailed overview of the MHBase and an analysis of shared loci at the global and continental levels, ancestral markers, the genetic distance within loci, and mapping with the genome annotation file. The website is an accessible and useful tool for researchers engaged in marker discovery, population studies, assay development, and panel design.

Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches.

Clostridioides difficile (C. difficile), as the major pathogen of diarrhea in healthcare settings, has become increasingly prevalent within community populations, resulting in significant morbidity and mortality. However, the therapeutic options for Clostridioides difficile infection (CDI) remain limited, and as of now, no authorized vaccine is available to combat this disease. Therefore, the development of a novel vaccine against C. difficile is of paramount importance. In our study, the complete proteome sequences of 118 strains of C. difficile were downloaded and analyzed. We found four antigenic proteins that were highly conserved and can be used for epitope identification. We designed two vaccines, WLcd1 and WLcd2, that contain the ideal T-cell and B-cell epitopes, adjuvants, and the pan HLA DR-binding epitope (PADRE) sequences. The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications. Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors (TLRs) than WLcd2. Furthermore, molecular dynamics (MD) simulations, performed using Gmx_MMPBSA v1.56, confirmed the binding stability of WLcd1 with TLR2 and TLR4. The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI; however, experimental studies are necessary to confirm these predictions.

Characterization of posterior circulation blood perfusion in patients with different degrees of basilar artery tortuosity.

OBJECTIVE: The morphology of basilar artery (BA) may affect posterior circulation blood perfusion. We aimed to investigate whether different degrees of BA tortuosity could lead to the alterations of posterior circulation perfusion. METHODS: We collected 138 subjects with different BA tortuosity scores, including 32 cases of score 0, 45 cases of score 1, 43 cases of score 2, and 18 cases of score 3. A higher score represented a higher degree of BA tortuosity. Ordered logistic regression analysis was performed to investigate the risk factors for BA tortuosity. We quantitatively measured the cerebral blood flow (CBF) in eight posterior circulation brain regions using arterial spin labeling. SPSS 25.0 was used for statistical analysis. The correlation between the CBF and BA tortuosity was corrected by the Bonferroni method. The significance level was set at 0.006 (0.05/8). RESULTS: Hypertension (HR: 2.39; 95%CI: 1.23-4.71; P = 0.01) and vertebral artery dominance (HR: 2.38; 95%CI: 1.10-4.67; P = 0.03) were risk factors for BA tortuosity. CBF in occipital gray matter (R = -0.383, P < 0.001), occipital white matter (R = -0.377, P < 0.001), temporal gray matter (R = -0.292, P = 0.001), temporal white matter (R = -0.297, P < 0.001), and cerebellum (R = -0.328, P < 0.001) were negatively correlated with BA tortuosity degree. No significant correlation was found between the BA tortuosity degree and CBF in hippocampus (R = -0.208, P = 0.014), thalamus (R = -0.001, P = 0.988) and brainstem (R = -0.204, P = 0.016). CONCLUSIONS: BA tortuosity could affect posterior circulation blood perfusion. CBF was negatively correlated with BA tortuosity degree. The morphology of BA may serve as a biomarker for posterior circulation and the severity of posterior circulation ischemia.

Childhood maltreatment, parenting style and anxiety in Chinese youths: A case-control study.

BACKGROUND: Although evidence in supporting the associations between childhood maltreatment (CM), parenting style and anxiety in children and adolescents exists, few high-quality analytical epidemiological studies which focusing on clinically diagnosed anxiety disorders (AD) had been published. OBJECTIVE: The aim of this study was to further corroborate the associations between CM, parenting style, and AD in a large representative sample of Chinese children and adolescents. PARTICIPANTS AND SETTING: Study subjects were derived from the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY), a population-based cross-sectional program. METHODS: Individually matched case-control study design was adopted. Univariate and multivariate conditional binary logistic regression models were used to estimate the associations between CM, parenting style and AD. Dose-response trends were estimated using the Cochran-Armitage Chi-square test. A series of stratified analyses were conducted to explore effect modification on exposure-outcome association by some important features. RESULTS: Totally we screened out 202 cases and 404 matched controls, with an age mean of 14.43 years. Conditional logistic regression models revealed that EA and a higher level of parental over-protection were significantly associated with increased risk of AD, with adjusted ORs of 3.39 (95 % CI: 2.07-5.56) and 1.93 (95 % CI: 1.28-2.90). Stratified analysis identified noticeable effect modification by sex, age, and whether the only child in the family. CONCLUSIONS: Major findings of this study suggested that children and adolescents who had experienced EA or raised up by over-protective parents are at increased risk of AD. Targeted intervention measures should be developed and implemented for these high-risk youths.

Developmental validation of an mRNA kit: A 5-dye multiplex assay designed for body-fluid identification.

Identifying the sources of biosamples found at crime scenes is crucial for forensic investigations. Among the markers used for body fluid identification (BFI), mRNA has emerged as a well-studied marker because of its high specificity and remarkable stability. Despite this potential, commercially available mRNA kits specifically designed for BFI are lacking. Therefore, we developed an mRNA kit that includes 21 specific mRNA markers of body fluids, along with three housekeeping genes for BFI, to identify four forensic-relevant fluids (blood, semen, saliva, and vaginal fluids). In this study, we tested 451 single-body-fluid samples, validated the universality of the mRNA kit, and obtained a gene expression profile. We performed the validation studies in triplicates and determined the sensitivity, specificity, stability, precision, and repeatability of the mRNA kit. The sensitivity of the kit was found to be 0.1 ng. Our validation process involved the examination of 59 RNA mixtures, 60 body fluids mixtures, and 20 casework samples, which further established the reliability of the kit. Furthermore, we constructed five classifiers that can handle single-body fluids and mixtures using this kit. The classifiers output possibility values and identify the specific body fluids of interest. Our results showed the reliability and suitability of the BFI kit, and the Random Forest classifier performed the best, with 94% precision. In conclusion, we developed an mRNA kit for BFI which can be a promising tool for forensic practice.

Analysis of cantharidin-induced kidney injury and the protective mechanism of resveratrol in mice determined by liquid chromatography/mass spectrometry-based metabonomics.

Cantharidin (CTD) is the main active component in the traditional Chinese medicine Mylabris and an effective anti-tumor agent. However, it is relatively toxic and exhibits nephrotoxicity, which limits its clinical use. However, its toxic mechanism is not clear. The toxic effects of CTD exposure on the kidney and the protective effect of resveratrol (RES) were studied in a mouse model, by determination of serum biochemical and renal antioxidant indicators, histopathological and ultrastructural observation, and metabonomics. After CTD exposure, serum uric acid, creatinine, and tissue oxidative stress indicators increased, and the renal glomerular and tubular epithelial cells showed clear pathological damage. Ultrastructure observation revealed marked mitochondrial swelling, endoplasmic reticulum dilation, and the presence of autophagy lysosomes in glomerular epithelial cells. RES ameliorated the renal injury induced by CTD. Metabonomics analysis indicated that CTD can induce apoptosis and oxidative damage in kidney cells, mainly by disrupting sphingolipid and glutathione metabolism, increasing sphingosine and sphingomyelin levels, and decreasing glutathione levels. RES counteracts these effects by regulating renal cell proliferation, the inflammatory response, oxidative stress, and apoptosis, by improving the levels of phosphatidylcholine (PC), LysoPC, and lysophosphatidyl glycerol in the glycerophospholipid metabolism pathway, thereby reducing CTD-induced nephrotoxicity. The mechanisms of CTD-induced renal injury and the protective effect of RES were revealed by metabonomics, providing a basis for evaluating clinical treatment regimens to reduce CTD-induced nephrotoxicity.