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DNA mixture analysis poses a significant challenge in forensic genetics, particularly when dealing with degraded and trace amount DNA samples. Multi-SNPs (MNPs) are genetic markers similar to microhaplotypes but with smaller molecular sizes (< 75 bp), making them theoretically more suitable for analyzing degraded and trace amount samples. In this case report, we investigated a cold case involving a campstool stored for over a decade, aiming to detect and locate the suspect's DNA. We employed both conventional capillary electrophoresis-based short tandem repeat (CE-STR) analysis and next-generation sequencing-based multi-SNP (NGS-MNP) analysis. The typing results and deconvolution of the mixed CE-STR profiles were inconclusive regarding the presence of the suspect's DNA in the mixed samples. However, through NGS-MNP analysis and presence probability calculations, we determined that the suspect's DNA was present in the samples from Sect. 4-1 with a probability of 1-8.41 × 10- 6 (99.999159%). This evidence contradicted the suspect's statement and aided in resolving the case. Our findings demonstrate the significant potential of MNP analysis for examining degraded and trace amount DNA mixtures in forensic investigations.
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Microorganisms are essential in the decomposition of corpses and play a significant role in forensic science. However, previous studies have primarily focused on animal remains, specifically the gut, skin, and burial environment. Insufficient research has been conducted on the microbiota of human cadavers, especially in cases of advanced decomposition and additional tissues, resulting in a lack of relevant reference data. In this study, the microbiota of eight cadavers at different stages of decomposition were detected using 16S rRNA, metagenomic sequencing and 2bRAD-M sequencing. Nine different sites, including oral and nasal cavities, heart, liver, spleen, lung, kidney, muscle and gut, were analysed and the efficacy of these methods was evaluated. The results showed that 16S rRNA sequencing was the most cost-effective method for the study of cadavers in the early stages of decomposition, whereas for cadaveric tissues in the late stages of decomposition, 2bRAD-M could overcome host contamination more effectively than metagenomic sequencing. This paves the way for new opportunities in data retrieval and promotes in-depth investigations into the microbiota.
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Cadáver , Metagenômica , Microbiota , RNA Ribossômico 16S , Humanos , RNA Ribossômico 16S/genéticaRESUMO
The skin microbiome plays a pivotal role in human health by providing protective and functional benefits. Furthermore, its inherent stability and individual specificity present novel forensic applications. These aspects have sparked considerable research enthusiasm among scholars across various fields. However, the selection of specific 16S rRNA hypervariable regions for skin microbiome studies is not standardized and should be validated through extensive research tailored to different research objectives and targeted bacterial taxa. Notably, third-generation sequencing (TGS) technology leverages the full discriminatory power of the 16S gene and enables more detailed and accurate microbial community analyses. Here, we conducted full-length 16S sequencing of 141 skin microbiota samples from multiple human anatomical sites using the PacBio platform. Based on this data, we generated derived 16S sub-region data through an in silico experiment. Comparisons between the 16S full-length and the derived variable region data revealed that the former can provide superior taxonomic resolution. However, even with full 16S gene sequencing, limitations arise in achieving 100% taxonomic resolution at the species level for skin samples. Additionally, the capability to resolve high-abundance bacteria (TOP30) at the genus level remains generally consistent across different 16S variable regions. Furthermore, the V1-V3 region offers a resolution comparable with that of full-length 16S sequences, in comparison to other hypervariable regions studied. In summary, while acknowledging the benefits of full-length 16S gene analysis, we propose the targeting of specific sub-regions as a practical choice for skin microbial research, especially when balancing the accuracy of taxonomic classification with limited sequencing resources, such as the availability of only short-read sequencing or insufficient DNA.IMPORTANCESkin acts as the primary barrier to human health. Considering the different microenvironments, microbial research should be conducted separately for different skin regions. Third-generation sequencing (TGS) technology can make full use of the discriminatory power of the full-length 16S gene. However, 16S sub-regions are widely used, particularly when faced with limited sequencing resources including the availability of only short-read sequencing and insufficient DNA. Comparing the 16S full-length and the derived variable region data from five different human skin sites, we confirmed the superiority of the V1-V3 region in skin microbiota analysis. We propose the targeting of specific sub-regions as a practical choice for microbial research.
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Bactérias , Microbiota , RNA Ribossômico 16S , Pele , Humanos , RNA Ribossômico 16S/genética , Microbiota/genética , Pele/microbiologia , Bactérias/genética , Bactérias/classificação , DNA Bacteriano/genética , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , FilogeniaRESUMO
Chronic kidney disease (CKD) has emerged as a significant public health concern. In this article, we investigated the mechanism of oat dietary fiber in regulating CKD. Our findings indicated that the gut microbiota of CKD patients promoted gut microbiota dysbiosis and kidney injury in CKD mice. Intervention with oat-resistant starch prepared by ultrasonic combined enzymatic hydrolysis (ORSU) and oat ß-glucan with a molecular weight of 5 × 104 Da (OBGM) elevated the levels of short-chain fatty acids (SCFAs) and regulated gut dysbiosis in the gut-humanized CKD mice. ORSU and OBGM also reduced CKD-related uremic toxins such as creatinine, indoxyl sulfate (IS), and p-cresol sulfate (PCS) levels; reinforced the intestinal barrier function of the gut-humanized CKD mice; and mitigated renal inflammation and fibrosis via the NF-κB/TGF-ß pathway. Therefore, ORSU and OBGM might delay the progression of CKD by modulating the gut microbiota to reduce uremic toxins levels. Our results explain the mechanism of oat dietary fiber aimed at mitigating CKD.
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OBJECTIVE: To determine the prevalence of cognitive impairment (CI) among middle-aged to older patients receiving maintenance haemodialysis (MHD) and to investigate the potential association between CI and physical performance. METHODS: This cross-sectional observational study enrolled participants aged 55-85 years who received MHD. Cognitive status was assessed using the Mini Mental State Examination (MMSE). Physical performance was measured by hand grip strength, the Timed Up and Go Test (TUGT) and the 4-m walking speed. Sociodemographic, clinical and laboratory parameters were recorded for each patient. RESULTS: The study included 592 patients (363 males); and of these, 126 (21.3%) were diagnosed with CI. Compared with patients with normal cognitive function, those with CI were significantly older and had significantly longer dialysis duration, lower educational level, higher Malnutrition Inflammation Score, higher depression and higher Charlson Comorbidity Index score. After adjustment for covariates, multiple regression analysis suggested that grip strength (odds ratio [OR] = 0.959, 95% confidence interval [CI] = 0.924, 0.996) and 4-m walking speed (OR = 0.161, 95% CI = 0.070, 0.368) were protective factors. TUGT (OR = 1.037, 95%CI = 1.003, 1.071) was a risk factor. CONCLUSION: Physical performance was correlated with CI and might be a significant indicator for the early identification of CI in middle-aged to older MHD patients.
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Disfunção Cognitiva , Força da Mão , Desempenho Físico Funcional , Diálise Renal , Humanos , Masculino , Feminino , Idoso , Estudos Transversais , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Força da Mão/fisiologia , Fatores de Risco , PrevalênciaRESUMO
BACKGROUND: Epilepsy is a nervous system disease characterized by recurrent attacks, a long disease course, and an unfavorable prognosis. It is associated with an enduring therapeutic process, and finding a cure has been difficult. Patients with epilepsy are predisposed to adverse moods, such as resistance, anxiety, nervousness, and anxiety, which compromise treatment compliance and overall efficacy. AIM: To explored the influence of intensive psychological intervention on treatment compliance, psychological status, and quality of life (QOL) of patients with epilepsy. METHODS: The clinical data of 105 patients with epilepsy admitted between December 2019 and July 2023 were retrospectively analyzed, including those of 50 patients who underwent routine intervention (control group) and 55 who underwent intensive psychological intervention (research group). Treatment compliance, psychological status based on the Self-Rating Anxiety Scale (SAS) and Depression Scale Self-Rating Depression Scale (SDS) scores, hope level assessed using the Herth Hope Scale (HHS), psychological resilience evaluated using the Psychological Resilience Scale, and QOL determined using the QOL in Epilepsy-31 Inventory (QOLIE-31) were comparatively analyzed. RESULTS: Treatment compliance in the research group was 85.5%, which is significantly better than the 68.0% of the control group. No notable intergroup differences in preinterventional SAS and SDS scores were identified (P > 0.05); however, after the intervention, the SAS and SDS scores decreased significantly in the two groups, especially in the research group (P < 0.05). The two groups also exhibited no significant differences in preinterventional HHS, Connor-Davidson Resilience Scale (CD-RISC), and QOLIE-31 scores (P > 0.05). After 6 months of intervention, the research group showed evidently higher HHS, CD-RISC, tenacity, optimism, strength, and QOLIE-31 scores (P < 0.05). CONCLUSION: Intensive psychological intervention enhances treatment compliance, psychological status, and QOL of patients with epilepsy.
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The goal of the following study is to clarify whether the skeletal remains over 70 years old from missing persons and their alleged relatives shared identical Y-STR loci. Nowadays, advances in ancient DNA extraction techniques and approaches of using multiple different Y-STRs have significantly increased the possibility of obtaining DNA profiles from highly degraded skeletal remains. Given the ages and conditions of the skeletal remains, ancient DNA extraction methods can be used to maximize the probability of DNA recovery. Considering that information about distant relatives is more relevant for long-term missing persons and alleged family members are male, Y-STR loci analysis is considered the most appropriate and informative approach for determining paternal lineage relationship. In this study, Y-STR genotypes obtained from these alleged relatives were identical to each other and to the alleles of missing persons' consensus profiles at more than 22 loci examined, whilst not being found in Y-STR population database from Y-Chromosome STR Haplotype Reference Database. Therefore, Missing Person No.7 and Missing Person No.18 have a patrilineal relationship with reference samples from Family1 and Family2, respectively. In addition, the fact that Y-STR haplotypes obtained from skeletal remains of missing persons and reference samples are not found in the Han Chinese people from East Asian demonstrates its rarity and further supports a paternal lineage relationship amongst them.
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The testes are the organs of gamete production and testosterone synthesis. Up to date, no model system is available for mammalian testicular development, and only few studies have characterized the mouse testis transcriptome from no more than three postnatal ages. To describe the transcriptome landscape of the developing mouse testis and identify the potential molecular mechanisms underlying testis maturation, we examined multiple RNA-seq data of mouse testes from 3-week-old (puberty) to 11-week-old (adult). Sperm cells appeared as expected in 5-week-old mouse testis, suggesting the proper sample collection. The principal components analysis revealed the genes from 3w to 4w clustered away from other timepoints, indicating they may be the important nodes for testicular development. The pairwise comparisons at two adjacent timepoints identified 7,612 differentially expressed genes (DEGs), resulting in 58 unique mRNA expression patterns. Enrichment analysis identified functions in tissue morphogenesis (3-4w), regulation of peptidase activity (4-5w), spermatogenesis (7-8w), and antigen processing (10-11w), suggesting distinct functions in different developmental periods. 50 hub genes and 10 gene cluster modules were identified in the testis maturation process by protein-protein interaction (PPI) network analysis, and the miRNA-lncRNA-mRNA, miRNA-circRNA-mRNA and miRNA-circRNA-lncRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed. The results suggest that testis maturation is a complex developmental process modulated by various molecules, and that some potential RNA-RNA interactions may be involved in specific developmental stages. In summary, this study provides an update on the molecular basis of testis development, which may help to understand the molecular mechanisms of mouse testis development and provide guidance for mouse reproduction.
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Perfilação da Expressão Gênica , Testículo , Animais , Masculino , Testículo/metabolismo , Testículo/crescimento & desenvolvimento , Camundongos , Regulação da Expressão Gênica no Desenvolvimento , Transcriptoma , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
INTRODUCTION: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by bone abnormalities, vascular calcification, and some other complications. Although there are diagnostic criteria for CKD-MBD, in situations when conducting target feature examining are unavailable, there is a need to investigate and discover alternative biochemical criteria that are easy to obtain. Moreover, studying the correlations between the newly discovered biomarkers and the existing ones may provide insights into the underlying molecular mechanisms of CKD-MBD. METHODS: We collected a cohort of 116 individuals, consisting of three subtypes of CKD-MBD: calcium abnormality, phosphorus abnormality, and PTH abnormality. To identify the best biomarker panel for discrimination, we conducted six machine learning prediction methods and employed a sequential forward feature selection approach for each subtype. Additionally, we collected a separate prospective cohort of 114 samples to validate the discriminative power of the trained prediction models. RESULTS: Using machine learning under cross validation setting, the feature selection method selected a concise biomarker panel for each CKD-MBD subtype as well as for the general one. Using the consensus of these features, best area under ROC curve reached up to 0.95 for the training dataset and 0.74 for the perspective dataset, respectively. DISCUSSION/CONCLUSION: For the first time, we utilized machine learning methods to analyze biochemical criteria associated with CKD-MBD. Our aim was to identify alternative biomarkers that could serve not only as early detection indicators for CKD-MBD, but also as potential candidates for studying the underlying molecular mechanisms of the condition.
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Distúrbio Mineral e Ósseo na Doença Renal Crônica , Insuficiência Renal Crônica , Humanos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Estudos Prospectivos , Biomarcadores , Cálcio , Insuficiência Renal Crônica/diagnósticoRESUMO
BACKGROUND: In recent years, biosafety and green food safety standards have increased the demand for immune enhancers and adjuvants. In the present study, recombinant food-grade Lactococcus lactis (r-L. lactis-Tα1-IFN) expressing thymosin Tα1 and chicken interferon fusion protein was constructed. RESULTS: The in vitro interactions with macrophages revealed a mixture of recombinant r-L. lactis-Tα1-IFN could significantly activate both macrophage J774-Dual™ NF-κB and interferon regulator (IRF) signaling pathways. In vitro interactions with chicken peripheral blood mononuclear cells (PBMCs) demonstrated that a mixture of recombinant r-L. lactis-Tα1-IFN significantly enhanced the expression levels of interferon (IFN)-γ, interleukin (IL)-10, CD80, and CD86 proteins in chicken PBMCs. Animal experiments displayed that injecting a lysis mixture of recombinant r-L. lactis-Tα1-IFN could significantly activate the proliferation of T cells and antigen-presenting cells in chicken PBMCs. Moreover, 16S analysis of intestinal microbiota demonstrated that injection of the lysis mixture of recombinant r-L. lactis-Tα1-IFN could significantly improve the structure and composition of chicken intestinal microbiota, with a significant increase in probiotic genera, such as Lactobacillus spp. Results of animal experiments using the lysis mixture of recombinant r-L. lactis-Tα1-IFN as an immune adjuvant for inactivated chicken Newcastle disease vaccine showed that the serum antibody titers of the experimental group were significantly higher than those of the vaccine control group, and the expression levels of cytokines IFN-γ and IL-2 were significantly higher than those of the vaccine control group. CONCLUSION: These results indicate that food-safe recombinant r-L. lactis-Tα1-IFN has potential as a vaccine immune booster and immune adjuvant. This study lays the foundation for the development of natural green novel animal immune booster or immune adjuvant.
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Lactococcus lactis , Timosina , Vacinas , Animais , Interferons/metabolismo , Lactococcus , Leucócitos Mononucleares , Adjuvantes Imunológicos/metabolismo , Proteínas Recombinantes/metabolismo , Timosina/metabolismo , Vacinas/metabolismo , Galinhas , Lactococcus lactis/metabolismoRESUMO
Currently, the most commonly used method for human identification and kinship analysis in forensic genetics is the detection of length polymorphism in short tandem repeats (STRs) using polymerase chain reaction (PCR) and capillary electrophoresis (CE). However, numerous studies have shown that considerable sequence variations exist in the repeat and flanking regions of the STR loci, which cannot be identified by CE detection. Comparatively, massively parallel sequencing (MPS) technology can capture these sequence differences, thereby enhancing the identification capability of certain STRs. In this study, we used the ForenSeq™ DNA Signature Prep Kit to sequence 58 STRs and 94 individual identification SNPs (iiSNPs) in a sample of 220 unrelated individuals from the Eastern Chinese Han population. Our aim is to obtain MPS-based STR and SNP data, providing further evidence for the study of population genetics and forensic applications. The results showed that the MPS method, utilizing sequence information, identified a total of 486 alleles on autosomal STRs (A-STRs), 97 alleles on X-chromosome STRs (X-STRs), and 218 alleles on Y-chromosome STRs (Y-STRs). Compared with length polymorphism, we observed an increase of 260 alleles (157, 31, and 72 alleles on A-STRs, X-STRs, and Y-STRs, respectively) across 36 STRs. The most substantial increments were observed in DYF387S1 and DYS389II, with increases of 287.5% and 250%, respectively. The most increment in the number of alleles was found at DYF387S1 and DYS389II (287.5% and 250%, respectively). The length-based (LB) and sequence-based (SB) combined random match probability (RMP) of 27 A-STRs were 6.05E-31 and 1.53E-34, respectively. Furthermore, other forensic parameters such as total discrimination power (TDP), cumulative probability of exclusion of trios (CPEtrio), and duos (CPEduo) were significantly improved when using the SB data, and informative data were obtained for the 94 iiSNPs. Collectively, these findings highlight the advantages of MPS technology in forensic genetics, and the Eastern Chinese Han genetic data generated in this study could be used as a valuable reference for future research in this field.
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Impressões Digitais de DNA , Etnicidade , Humanos , Impressões Digitais de DNA/métodos , Etnicidade/genética , Genética Populacional , Polimorfismo de Nucleotídeo Único/genética , Repetições de Microssatélites/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , China , DNA , Análise de Sequência de DNA/métodosRESUMO
BACKGROUND: The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. METHODS: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. RESULTS: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = -0.356, p < 0.001 and r = -0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73-1.81), 1.69 (1.07-2.70), and 2.87 (1.69-4.88) (p for trend = 0.005). CONCLUSION: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.
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BACKGROUND: Pheochromocytoma (PCC) crisis is a rare life-threatening endocrine emergency. The diagnosis and treatment of PCC crisis, with acute respiratory distress syndrome (ARDS) as the first manifestation, is highly challenging, and traditional PCC management strategies are no longer suitable for these patients. CASE PRESENTATION: A 46-year-old female patient was admitted to the Intensive Care Unit (ICU) following sudden-onset acute respiratory distress and subsequent initiation of mechanical ventilation via endotracheal intubation. She was initially suspected of having a PCC crisis through the bedside critical care ultrasonic examination protocol. The computed tomography examination revealed a left adrenal neoplasm of 6.5cm × 5.9cm. The plasma-free metanephrine level was 100 times higher than the reference value. These findings were compatible with her PCC diagnosis. Alpha-blockers and fluid intake were started immediately. The endotracheal intubation was removed on the 11th day after admission to the ICU. The patient progressed to severe ARDS again, and invasive ventilation and continuous renal replacement therapy were needed. Despite aggressive therapy, her condition deteriorated. Therefore, she underwent veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-assisted emergency adrenalectomy after multidisciplinary discussion. Postoperatively, the patient was supported by VA-ECMO for 7days. She was discharged from the hospital on day 30 after tumor resection. CONCLUSIONS: This case highlighted the challenges in diagnosing and managing ARDS associated with PCC crisis. The traditional preoperative preparation protocol and optimal operation timing for patients with PCC are not suitable for patients with PCC crisis. Patients with life-threatening PCC crisis may benefit from early tumor removal, and VA-ECMO could maintain hemodynamic stability during and after surgery.
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Neoplasias das Glândulas Suprarrenais , Oxigenação por Membrana Extracorpórea , Metoclopramida , Feocromocitoma , Síndrome do Desconforto Respiratório , Cardiomiopatia de Takotsubo , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Metoclopramida/efeitos adversos , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Dysfunctional lens index (DLI) changing is rarely reported after implantable collamer lens (ICL) implantation. In the current research, we hope to investigate the changes of DLI by ray-tracing aberrometry before and after implantation of the posterior chamber phakic implantable collamer lens with a central artificial hole for patients with moderate-to-high myopia. METHODS: This retrospective, observational case series included 206 eyes of 104 patients with moderate-to-high myopia who underwent ICL V4c implantation. Data were collected on ocular indicators preoperatively and at 1 day, 1, 3, and 6 months postoperatively. The i-Trace Visual Functional Analyzer was used to assess the DLI measurement. RESULTS: The overall values of safety index and efficacy index were both more than 1. Preoperatively, the mean spherical equivalent (SE) of included 206 eyes was - 10.77 ± 3.46 diopter (D). Then at 1-day postoperation, the mean SE was - 0.22 ± 0.55 D, and barely changed from 1 day to 6 months postoperatively. Although the endothelial parameters had no significant differences between preoperation and postoperation, the mean loss of endothelial cells was 0.74 ± 0.98% at 6 months. Regarding the vault, there was a significant difference between each time of follow-up (P < 0.001). The mean of the vault decreased 109.6 ± 13.5 µm from 1-day post-op to 6 months post-op. The DLI values were 3.70, 9.26, 10.00, and 9.68 at baseline, 1, 3, and 6 months, respectively (P < 0.001), but no significant differences were found between 1, 3, and 6 months postoperatively (P > 0.05). The preoperative lnDLI showed a significant positive linear correlation (r = 0.621, P < 0.001) with the preoperative spherical equivalent (SE). The lnDLI was negatively correlated with the axial length (r = - 0.462, P < 0.001), corneal thickness (r = - 0.207, P = 0.003), preoperative LogMAR UDVA (r = - 0.189, P = 0.006), and preoperative LogMAR CDVA (r = - 0.306, P < 0.001). CONCLUSIONS: The postoperative refractive parameters were confirmed excellent in efficacy, predictability, and stability in half a year. The DLI was significantly improved after the ICL V4c implantation in patients with moderate-to-high myopia and showed good stability during the follow-up periods. The DLI deserves a more comprehensive understanding and application in clinical services.
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Cristalino , Lentes Intraoculares , Miopia , Humanos , Células Endoteliais , Estudos Retrospectivos , Miopia/cirurgiaRESUMO
Y-chromosome short tandem repeats (Y-STRs) have a unique role in forensic investigation. However, low-medium mutating Y-STRs cannot meet the requirements for male lineage differentiation in inbred populations, whereas rapidly mutating (RM) high-resolution Y-STRs might cause unexpected exclusion of paternal lineages. Thus, combining Y-STRs with low and high mutation rates helps to distinguish male individuals and lineages in family screening and analysis of genetic relationships. In this study, a novel 6-dye, 41-plex Y-STR panel was developed and validated, which included 17 loci from the Yfiler kit, nine RM Y-STR loci, 15 low-medium mutating Y-STR loci, and three Y-InDels. Developmental validation was performed for this panel, including size precision testing, stutter analysis, species specificity analysis, male specificity testing, sensitivity testing, concordance evaluation, polymerase chain reaction inhibitors analysis, and DNA mixture examination. The results demonstrated that the novel 41-plex Y-STR panel, developed in-house, was time efficient, accurate, and reliable. It showed good adaptability to directly amplify a variety of case-type samples. Furthermore, adding multiple Y-STR loci significantly improved the system's ability to distinguish related males, making it highly informative for forensic applications. In addition, the data obtained were compatible with the widely used Y-STR kits, facilitating the search and construction of population databases. Moreover, the addition of Y-Indels with short amplicons improves the analyses of degraded samples. Key Points: A novel multiplex comprising 41 Y-STR and 3 Y-InDel was developed for forensic application.The multiplex included rapidly mutating Y-STRs and low-medium mutating Y-STRs, which is compatible with many commonly used Y-STR kits.The multiplex is a powerful tool for distinguishing related males, familial searching, and constructing DNA databases.
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Despite recent advances in the prevention of coronary heart disease, the mortality rate of sudden cardiac death (SCD) remains high, which has become a substantial public health issue. Methyltransferase-like protein 16 (METTL16), as a newly discovered m6A methyltransferase, may be related to cardiovascular diseases. In the present study, a 6-base-pair insertion/deletion (del) polymorphism (rs58928048) in the METTL16 3'untranslated region (3'UTR) region was chosen as a candidate variant based on the findings of systematic screening. Then, the association between rs58928048 and susceptibility to SCD originating from coronary artery disease (SCD-CAD) in the Chinese population was investigated by conducting a case-control study that included 210 SCD-CAD cases and 644 matched healthy controls. Logistic regression analysis showed that the del allele of rs58928048 significantly reduced the SCD risk (odds ratio 0.69, 95% confidence interval 0.55 to 0.87, p = 0.00177). Genotype-phenotype correlation studies in human cardiac tissue samples demonstrated that the lower messenger RNA and protein expression levels of METTL16 were associated with the del allele of rs58928048. In the dual-luciferase activity assay, the del/del genotype exhibited lower transcriptional competence. Further bioinformatic analysis showed that the rs58928048 del variant may create transcription factor binding sites. Finally, pyrosequencing showed that the genotype of rs58928048 was related to the methylation status of the 3'UTR region of METTL16. Taken together, our findings provide evidence that rs58928048 may affect the methylation status of the 3'UTR region of METTL16 and subsequently affect its transcriptional activity thus as a potential genetic risk marker for SCD-CAD.
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Doença da Artéria Coronariana , Morte Súbita Cardíaca , Predisposição Genética para Doença , Metiltransferases , Humanos , Regiões 3' não Traduzidas , Estudos de Casos e Controles , Doença da Artéria Coronariana/genética , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , População do Leste Asiático , Metiltransferases/genética , Polimorfismo GenéticoRESUMO
Background: The purpose of this study is to establish a novel nomogram model for accurate detection of non-alcoholic fatty liver disease (NAFLD) in the Chinese population based on sex hormone binding globulin (SHBG) and other routine laboratory tests. Methods: A total of 1417 participants (1003 testing and 414 validations) were enrolled into the study. Risk factors independently associated with NAFLD were identified and incorporated in the new nomogram, SFI. The performance of nomogram was assessed by analysis of receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results: We formulated a new nomogram incorporating four independent factors: SHBG, body mass index (BMI), ALT/AST, and triglycerides (TG). The nomogram achieved good indexes of area under ROC 0.898 (95% confidence interval 0.865-0.926) in predicting NAFLD, which was significantly superior to previously reported models of FLI, HSI, LFS, and LAP. The calibration curve and decision curve demonstrated high performance and clinical utility of the nomogram in predicting NAFLD. Conclusion: The nomogram SFI has high performance in predicting NAFLD in Chinese population and may be used as a cost-effective screening model to assess NAFLD in the general population.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Nomogramas , Globulina de Ligação a Hormônio Sexual , População do Leste Asiático , Fatores de RiscoRESUMO
This experiment aimed to analyze the salidroside effect on lipopolysaccharide (LPS)-induced inflammatory activation in young rats with acute lung injury (ALI) via PI3K/Akt signaling pathway. In this study, sixty SD young rats were divided into 5 groups (control, model, salidroside low-dose, salidroside medium-dose and salidroside high-dose), with 12 rats in each group. ALI rat model was established. In the control and model group, rats were intraperitoneally injected with normal saline, while the salidroside low-, medium-, and high-dose groups were intraperitoneally injected with 5, 20, and 40 mg/kg salidroside, then the pathological changes of lung tissue, lung injury score, wet/dry lung weight ratio, neutrophils and TNF-α, MPO, MDA, NO, p-PI3K and p-AKT were detached and compared between these groups. Results showed that the ALI rat model was successfully established. The lung injury score, wet/dry lung weight ratio, neutrophils and TNF-α in alveolar lavage fluid, MPO, MDA, NO, p-PI3K and p-AKT in the lung tissue of the model group were increased than the control group. With the increase of salidroside dose, lung injury score, wet lung weight/dry lung weight ratio, neutrophils and TNF-α in alveolar lavage fluid, and the levels of MPO, MDA, NO, p-PI3K and p-AKT in lung tissues of the salidroside group were decreased then model group (P < 0.05). In conclusion, salidroside may reduce the activation of inflammatory cells in the lung tissue of young rats with LPS-induced ALI by activating PI3K/AKT signaling pathway, thereby exerting a certain protective effect on the lung tissue with LPS-induced ALI.
Assuntos
Lesão Pulmonar Aguda , Glucosídeos , Animais , Ratos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Glucosídeos/uso terapêuticoRESUMO
Income inequality is a good indicator reflecting the quality of people's livelihood. There are many studies on the determinants of income inequality. However, few studies have been conducted on the impacts of industrial agglomeration on income inequality and their spatial correlation. The goal of this paper is to investigate the impact of China's industrial agglomeration on income inequality from a spatial perspective. Using data on China's 31 provinces from 2003 to 2020 and the spatial panel Durbin model, our results show that industrial agglomeration and income inequality present an inverted "U-shape" relationship, proving that they are the non-linear change. As the degree of industrial agglomeration increases, income inequality will rise, after it reaches a certain value, income inequality will drop. Therefore, Chinese government and enterprises had better pay attention to the spatial distribution of industrial agglomeration, thereby reducing China's regional income inequality.
Assuntos
Povo Asiático , Renda , Desenvolvimento Industrial , Indústrias , Humanos , China , Governo , Indústrias/economia , Indústrias/organização & administração , Fatores Econômicos , Status Econômico , Qualidade de VidaRESUMO
Blau syndrome (BS) is a rare genetic immune disease which commonly presents in childhood. Currently, the miss-rate of BS diagnosis is very high, and an effective clinical management of BS has not been well established. This case report depicts a 54-year-old male Chinese patient presenting with hand malformation, fever, skin rash and joint pain. His diagnosis was ultimately confirmed according to typical medical history and genetic analysis. This case report will further help clinicians to be aware of this rare clinical entity for correct diagnosis and proper treatment.