Laser-induced stripping defect for highly selective electrochemical quantification of dopamine: Anti-interference from other catecholamine neurotransmitters.

Detecting dopamine (DA) is critical for early diagnosis of neurological and psychiatric disorders. However, the presence of other catecholamine neurotransmitters with structural similarities to DA causes significant interference in its detection. Herein, we introduce S stripping defects via laser-induced MoS2 to functionalize MoS2 electrodes and improve their selectivity for DA electrochemical detection. The sensing results show its excellent immunity to interference from other neurotransmitters, ensuring the preservation of the DA electrochemical signal even in the mixed neurotransmitters such as acetylcholine (ACh), γ-aminobutyric acid (GABA), epinephrine (EP), norepinephrine (NP), and serotonin (5-HT). DFT calculations further reveal that the negatively charged S-stripping defects enhance DA adsorption on the surface of the functionalized MoS2 electrode, contributing to its excellent performance. Moreover, this functionalized electrodes successfully monitor DA released from living PC12 cells in the presence of other interference, highlighting its potential applicability in intercellular signaling communication.

Effects of storm events on nutrient characteristics in a stratified drinking water reservoir: Behavior, transmission pathways and management strategy.

Storm events result in nutrient fluctuations and deterioration of reservoir water supply quality. Understanding of nutrient dynamics (e.g., concentration, composition, loads and transport pathways) and adoption of effective management strategies are critical for safeguarding water quality. A comprehensive monitoring was conducted for three storm events during the rainy season in 2023. Results showed nitrogen (N) and phosphorus (P) dynamics demonstrate a significant response to hydrological process. Rainfall resulted in the highest event mean concentrations (EMCs) of total nitrogen (TN), nitrate nitrogen (NO3--N), ammonia nitrogen (NH4+-N), total phosphorus (TP), and particulate phosphorus (PP) in the runoff being 1.97, 2.15, 2.30, 44.17, and 62.38 times higher than those observed in baseflow. On average, NO3--N/PP accounted for 82 %/96 % of N/P exports. Hysteresis analyses reveal that NH4+-N and PP were mainly transported by surface runoff from over-land sources, whereas TN and NO3--N were primarily delivered by subsurface runoff. Additionally, nutrient concentrations were significantly higher in the intrusive layer in reservoir compared to the pre-storm period, which gradually decreased from the tail to the head as particulate sedimentation and water column mixing occurred. Water-lifting-aerators (WLAs) were employed to alter the reservoir thermal stratification regime via artificial mixing to affect the intrusive layer of storm runoff. Comparison of the intrusive layer for three storms reveals that WLAs triggers the storm runoff to form an underflow via increasing the reservoir bottom water temperature above that the runoff, ensuring that water quality at the intake position remains unaffected by inflows. These findings serve as a reference for the response of reservoir eutrophication levels to storm events and present practical engineering experience for enhancing water quality safety during the rainy season.

Qishen granule alleviates doxorubicin-induced cardiotoxicity by suppressing ferroptosis via nuclear erythroid factor 2-related factor 2 (Nrf2) pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical usage of doxorubicin (DOX) is greatly constrained because of its side effects, especially cardiotoxicity. Studies have suggested that ferroptosis of cardiomyocytes is one of the important causes of doxorubicin-induced cardiotoxicity (DIC). Up-regulating Nuclear erythroid factor 2-related factor 2 (Nrf2) is a potential way to prevent ferroptosis associated with DIC. Qishen granules (QSG) has been shown cardioprotective effects on various cardiovascular diseases, including DIC. However, the mechanism of QSG to prevent and treat DIC are not fully understood. AIM OF THE STUDY: The main purpose of this work is to probe whether QSG can mitigate DIC by inhibiting ferroptosis, and whether QSG suppresses ferroptosis via Nrf2 pathway. MATERIALS AND METHODS: The effects of QSG on mitigating DIC and the potential targets of QSG were investigated in a DIC mice model. The cardiac function of mice was monitored by echocardiography. Transmission electron microscopy was used to assess mitochondrial damage. ROS content was measured by dihydroethidium (DHE) staining. The glutathione (GSH) and malondialdehyde (MDA) levels in cardiac tissue were detected by kits to evaluate cellular oxidative stress. The accumulation and nuclear translocation of Nrf2 was detected by immuno-fluorescence. Ferroptosis analysis was determined by tissue iron content and key proteins in Nrf2 pathway were measured by western blotting. The anti-oxidant and anti-ferroptosis mechanisms of QSG were explored in vitro studies. Delivery of Nrf2 small interfering RNA (siRNA) to H9c2 cells aimed to investigate whether QSG could prevent DIC through Nrf2 signaling pathway. The protective effects of QSG on mito-chondrial function and free iron were measured by MitoSOX™ Red and FerroOrange staining assays, respectively. RESULTS: In vivo, QSG could improve heart function and suppress ferroptosis in DIC mice. DOX-induced ROS production decreased after QSG treatment. The accumulation of free iron and MDA induced by DOX was suppressed with QSG treatment. The level of GSH increased after QSG intervention. QSG also protected against DOX-induced mitochondrial structural damage. Meanwhile, QSG promoted the expression of Nrf2 pathway-related proteins, thereby resisting ferroptosis. In vitro, QSG exerted anti-oxidant and anti-ferroptosis effects. QSG promoted the nuclear-translocation of Nrf2. In addition, interference with Nrf2 attenuated the regulatory effect of QSG on free iron content and mitochondrial ROS production. Moreover, Nrf2 knockdown weakened the anti-ferroptosis effects of QSG and inhibited the expressions of key proteins in Nrf2 pathway. CONCLUSION: The results of this study first illustrated that QSG could alleviate DIC by suppressing ferroptosis via Nrf2 pathway. Nrf2 may be a potential key target for QSG to prevent and treat DIC.

Estimating postmortem interval based on oral microbial community succession in rat cadavers.

The accurate estimation of the postmortem interval has been one of the crucial issues to be solved in forensic research, and it is influenced by various factors in the process of decay. With the development of high-throughput sequencing technology, forensic microbiology has become the major hot topic in forensic science, which provides new research options for postmortem interval estimation. The oral microbial community is one of the most diverse of microbiomes, ranking as the second most abundant microbiota following the gastrointestinal tract. It is remarkable that oral microorganisms have a significant function in the decay process of cadavers. Therefore, we collected outdoor soil to simulate the death environment and focused on the relationship between oral microbial community succession and PMI in rats above the soil. In addition, linear regression models and random forest regression models were developed for the relationship between the relative abundance of oral microbes and PMI. We also identified a number of microorganisms that may be important to estimate PMI, including: Ignatzschineria, Morganella, Proteus, Lysinibacillus, Pseudomonas, Globicatella, Corynebacterium, Streptococcus, Rothia, Aerococcus, Staphylococcus, and so on.

Succession changes of microbial community for inferring the time since deposition of saliva.

Saliva is a common biological examination material at crime scenes and has high application value in forensic case investigations. It can reflect the suspect's time of crime at the scene and provide evidence of the suspect's criminal facts. Even though many researchers have proposed their experimental protocols for estimating the time since deposition (TsD) of saliva, there is still a relative lack of research on the use of microorganisms to estimate TsD. In the current study, the succession change of microbial community in saliva with different TsD values was explored to discern the microbial markers related to TsD of saliva. We gathered saliva samples from six unrelated healthy Han individuals living in Guizhou, China and exposed these samples to indoor conditions at six time points (0, 1, 3, 7, 15, and 28 days). Temporal changes of microbial compositions in these samples were investigated by 16S rRNA sequencing (V3-V4 regions). By assessing temporal variation patterns of microbial abundance at the genus level, four bacteria (Brucella, Prevotella, Pseudomonas, and Fusobacterium) were observed to show good time dependence in these samples. In addition, the hierarchical clustering and principal co-ordinates analysis results revealed that these saliva samples could be classified into t-short (≤7 days) and t-long (>7 days) groups. In the end, the random forest model was developed to predict the TsD of these samples. For the model, the root mean square error, R2, and mean absolute error between predicted and actual TsD values were 1.5213, 0.9851, and 1.1969, respectively. To sum up, we identified TsD-related microbial markers in saliva samples, which could be viewed as valuable markers for inferring the TsD of saliva.

Forensic features and phylogenetic structure survey of four populations from southwest China via the autosomal insertion/deletion markers.

Insertion/Deletion (InDel) polymorphisms, characterized by their smaller amplicons, reduced mutation rates, and compatibility with the prevalent capillary electrophoresis (CE) platforms in forensic laboratories, significantly contribute to the advancement and application of genetic analysis. Guizhou province in China serves as an important region for investigating the genetic structure, ethnic group origins, and human evolution. However, DNA data and the sampling of present-day populations are lacking, especially about the InDel markers. Here, we reported data on 47 autosomal InDels from 592 individuals from four populations in Guizhou (Han, Dong, Yi, and Chuanqing). Genotyping was performed with the AGCU InDel 50 kit to evaluate their utility for forensic purposes and to explore the population genetic structure. Our findings showed no significant deviations from Hardy-Weinberg and linkage equilibriums. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) for each population demonstrated that the kit could be applied to forensic individual identification and was an effective supplement for parentage testing. Genetic structure analyses, including principal component analysis, multidimensional scaling, genetic distance calculation, STRUCTURE, and phylogenetic analysis, highlighted that the genetic proximity of the studied populations correlates with linguistic, geographical, and cultural factors. The observed genetic variances within four research populations were less pronounced than those discerned between populations across different regions. Notably, the Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi. These results underscore the potential of InDel markers in forensic science and provide insights into the genetic landscape and human evolution in multi-ethnic regions like Guizhou. Key points: InDel markers show promise for forensic individual identification and parentage testing via the AGCU InDel 50 kit.Genetic analysis of Guizhou populations reveals correlations with linguistic, geographical, and cultural factors.Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi.

Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism.

INTRODUCTION: Valerenic acid (VA) is a unique and biologically active component in Valeriana officinalis L., which has been reported to have a regulatory effect on the cardiovascular system. However, its therapeutic effects on pathological myocardial hypertrophy (PMH) and the underlying mechanisms are undefined. OBJECTIVES: Our study aims to elucidate how VA improves PMH, and preliminarily discuss its mechanism. METHODS: The efficacy of VA on PMH was confirmed by in vivo and in vitro experiments and the underlying mechanism was investigated by molecular dynamics (MD) simulations and specific siRNA interference. RESULTS: VA enhanced cardiomyocyte fatty acid oxidation (FAO), inhibited hyper-activated glycolysis, and improved the unbalanced pyruvate-lactate axis. VA could significantly improve impaired mitochondrial function and reduce the triglyceride (TG) in the hypertrophic myocardium while reducing the lactate (LD) content. Molecular mechanistic studies showed that VA up-regulated the expression of peroxisome proliferator-activated receptor-α (PPARα) and downstream FAO-related genes including CD36, CPT1A, EHHADH, and MCAD. VA reduced the expression of ENO1 and PDK4, the key enzymes in glycolysis. Meanwhile, VA improved the pyruvate-lactate axis and promoted the aerobic oxidation of pyruvate by inhibiting LDAH and MCT4. MD simulations confirmed that VA can bind with the F273 site of PPARα, which proposes VA as a potential activator of the PPARα. CONCLUSION: Our results demonstrated that VA might be a potent activator for the PPARα-mediated pathway. VA directly targets the PPARα and subsequently promotes energy metabolism to attenuate PMH, which can be applied as a potentially effective drug for the treatment of HF.

Genetic analysis of a pedigree with MECP2 duplication syndrome in China.

BACKGROUND: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males. It is characterized by delayed or absent speech development, severe motor and cognitive impairment, and recurrent respiratory infections. MDS is caused by the duplication of a chromosomal region located on chromosome Xq28, which contains the methyl CpG binding protein-2 (MECP2) gene. MECP2 functions as a transcriptional repressor or activator, regulating genes associated with nervous system development. The objective of this study is to provide a clinical description of MDS, including imaging changes observed from the fetal period to the neonatal period. METHODS: Conventional G-banding was employed to analyze the chromosome karyotypes of all pedigrees under investigation. Subsequently, whole exome sequencing (WES), advanced biological information analysis, and pedigree validation were conducted, which were further confirmed by copy number variation sequencing (CNV-seq). RESULTS: Chromosome karyotype analysis revealed that a male patient had a chromosome karyotype of 46,Y,dup(X)(q27.2q28). Whole-exon duplication in the MECP2 gene was revealed through WES results. CNV-seq validation confirmed the presence of Xq27.1q28 duplicates spanning 14.45 Mb, which was inherited from a mild phenotype mother. Neither the father nor the mother's younger brother carried this duplication. CONCLUSION: In this study, we examined a male child in a family who exhibited developmental delay and recurrent respiratory tract infections as the main symptoms. We conducted thorough family investigations and genetic testing to determine the underlying causes of the disease. Our findings will aid in early diagnosis, genetic counseling for male patients in this family, as well as providing prenatal diagnosis and reproductive guidance for female carriers.

Analysis of maternal genetic structure of mitochondrial DNA control region from Tai-Kadai-speaking Buyei population in southwestern China.

BACKGROUND: Even though the Buyei are a recognised ethnic group in southwestern China, there hasn't been much work done on forensic population genetics, notably using mitochondrial DNA. The sequences and haplogroups of mitochondrial DNA control regions of the Buyei peoples were studied to provide support for the establishment of a reference database for forensic DNA analysis in East Asia. METHODS AND RESULTS: The mitochondrial DNA control region sequences of 200 Buyei individuals in Guizhou were investigated. The haplotype frequencies and haplogroup distribution of the Buyei nationality in Guizhou were calculated. At the same time, the paired Fst values of the study population and other populations around the world were computed, to explore their genetic polymorphism and population relationship. A total of 179 haplotypes were detected in the Buyei population, with frequencies of 0.005-0.015. All haplotypes were assigned to 89 different haplogroups. The haplotype diversity and random matching probability were 0.999283 and 0.0063, respectively. The paired Fst genetic distances and correlation p-values among the 54 populations revealed that the Guizhou Buyei was most closely related to the Henan Han and the Guizhou Miao, and closer to the Hazara population in Pakistan and the Chiang Mai population. CONCLUSIONS: The study of mitochondrial DNA based on the maternal genetic structure of the Buyei nationality in Guizhou will benefit the establishment of an East Asian forensic DNA reference database and provide a reference for anthropological research in the future.

Exploring the Mechanism of Si-miao-yong-an Decoction in the Treatment of Coronary Heart Disease based on Network Pharmacology and Experimental Verification.

BACKGROUND: To investigate the active ingredients and the mechanisms of Si-miaoyong- an Decoction (SMYA) in the treatment of coronary heart disease (CHD) by using network pharmacology, molecular docking technology, and in vitro validation. METHODS: Through the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Uniprot database, GeneCards database, and DAVID database, we explored the core compounds, core targets and signal pathways of the effective compounds of SMYA in the treatment of CHD. Molecular docking technology was applied to evaluate the interactions between active compounds and key targets. The hypoxia-reoxygenation H9C2 cell model was applied to carry out in vitro verification experiments. A total of 109 active ingredients and 242 potential targets were screened from SMYA. A total of 1491 CHD-related targets were retrieved through the Gene- Cards database and 155 overlapping CHD-related SMYA targets were obtained. PPI network topology analysis indicated that the core targets of SMYA in the treatment of CHD include interleukin- 6 (IL-6), tumor suppressor gene (TP53), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), phosphorylated protein kinase (AKT1) and mitogen-activated protein kinase (MAPK). KEGG enrichment analysis demonstrated that SMYA could regulate Pathways in cancer, phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hypoxiainducible factor-1(HIF-1) signaling pathway, VEGF signaling pathway, etc. Results: Molecular docking showed that quercetin had a significant binding activity with VEGFA and AKT1. In vitro studies verified that quercetin, the major effective component of SMYA, has a protective effect on the cell injury model of cardiomyocytes, partially by up-regulating expressions of phosphorylated AKT1 and VEGFA. CONCLUSION: SMYA has multiple components and treats CHD by acting on multiple targets. Quercetin is one of its key ingredients and may protect against CHD by regulating AKT/VEGFA pathway.

Insertion/deletion polymorphism for genetic background and forensic performance exploration of the Sui group from Guizhou.

Insertion/deletion polymorphisms (InDels) as ideal genetic markers for forensic genetics are appreciated by scholars both nationally and internationally because they integrated the favorable features of single nucleotide polymorphisms (SNPs) and short tandem repeats (STRs). Nevertheless, with the limited identification efficiency of InDels, the multiplex amplification systems of InDels might just be applied as the supplementary methods in paternity testing with respect to commonly used STRs. In the current research, we successfully genotyped 105 unrelated individuals from the Guizhou Sui population based on a six-color fluorescence multiplex panel that could simultaneously detect 64 genetic markers (59 autosomal InDels, two autosomal miniSTRs and three Y chromosomal genetic markers). In addition, frequency distributions and forensic statistical parameters of these loci in the Sui group were assessed using the STRAF software. Phylogenetic relationships among the Sui group and other reference populations were dissected by two methods (principal component analysis and phylogenetic trees) based on 59 InDels. The combined discrimination power and probability of exclusion values of 61 autosomal genetic markers in the Sui group were nearly equal to 1-1.90063 × 10-27 and 0.999998272, respectively. Furthermore, we observed that the Sui group from Guizhou had closer genetic affinities with East Asian populations with respect to other continental populations. In summary, we stated that the multiplex amplification system might be utilized as a prospective independent tool for human individual identification and parentage testing in the Sui group residing in Guizhou.

Genomic formation of Tibeto-Burman speaking populations in Guizhou, Southwest China.

Sino-Tibetan is the most prominent language family in East Asia. Previous genetic studies mainly focused on the Tibetan and Han Chinese populations. However, due to the sparse sampling, the genetic structure and admixture history of Tibeto-Burman-speaking populations in the low-altitude region of Southwest China still need to be clarified. We collected DNA from 157 individuals from four Tibeto-Burman-speaking groups from the Guizhou province in Southwest China. We genotyped the samples at about 700,000 genome-wide single nucleotide polymorphisms. Our results indicate that the genetic variation of the four Tibeto-Burman-speaking groups in Guizhou is at the intermediate position in the modern Tibetan-Tai-Kadai/Austronesian genetic cline. This suggests that the formation of Tibetan-Burman groups involved a large-scale gene flow from lowland southern Chinese. The southern ancestry could be further modelled as deriving from Vietnam's Late Neolithic-related inland Southeast Asia agricultural populations and Taiwan's Iron Age-related coastal rice-farming populations. Compared to the Tibeto-Burman speakers in the Tibetan-Yi Corridor reported previously, the Tibeto-Burman groups in the Guizhou region received additional gene flow from the southeast coastal area of China. We show a difference between the genetic profiles of the Tibeto-Burman speakers of the Tibetan-Yi Corridor and the Guizhou province. Vast mountain ranges and rivers in Southwest China may have decelerated the westward expansion of the southeast coastal East Asians. Our results demonstrate the complex genetic profile in the Guizhou region in Southwest China and support the multiple waves of human migration in the southern area of East Asia.

Comprehensive analyses of genetic diversities and population structure of the Guizhou Dong group based on 44 Y-markers.

Background: The non-recombining region of the human Y chromosome (NRY) is a strictly paternally inherited genetic marker and the best material to trace the paternal lineages of populations. Y chromosomal short tandem repeat (Y-STR) is characterized by high polymorphism and paternal inheritance pattern, so it has been widely used in forensic medicine and population genetic research. This study aims to understand the genetic distribution of Y-STRs in the Guizhou Dong population, provide reference data for forensic application, and explore the phylogenetic relationships between the Guizhou Dong population and other comparison populations. Methods: Based on the allele profile of 44 Y-markers in the Guizhou Dong group, we estimate their allele frequencies and haplotype frequencies. In addition, we also compare the forensic application efficiency of different Y-STR sets in the Guizhou Dong group. Finally, genetic relationships among Guizhou Dong and other reference populations are dissected by the multi-dimensional scaling and the phylogenetic tree. Results: A total of 393 alleles are observed in 312 Guizhou Dong individuals for these Y-markers, with allele frequencies ranging from 0.0032 to 0.9679. The haplotype diversity and discriminatory capacity for these Y-markers in the Guizhou Dong population are 0.99984 and 0.97440, respectively. The population genetic analyses of the Guizhou Dong group and other reference populations show that the Guizhou Dong group has the closest genetic relationship with the Hunan Dong population, and followed by the Guizhou Tujia population. Conclusions: In conclusion, these 44 Y-markers can be used as an effective tool for male differentiation in the Guizhou Dong group. The haplotype data in this study not only enrich the Y-STR data of different ethnic groups in China, but also have important significance for population genetics and forensic research.

MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation.

Langerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-ß and related downstream signaling pathways are known to control numerous aspects of LC biology, little is known about the epigenetic signals that coordinate cell signaling during LC ontogeny, maintenance, and function. Our previous studies in a total miRNA deletion mouse model showed that miRNAs are critically involved in embryonic LC development and postnatal LC homeostasis; however, the specific miRNA(s) that regulate LCs remain unknown. miR-23a is the first member of the miR-23a-27a-24-2 cluster, a direct downstream target of PU.1 and TGF-b, which regulate the determination of myeloid versus lymphoid fates. Therefore, we used a myeloid-specific miR-23a deletion mouse model to explore whether and how miR-23a affects LC ontogeny and function in the skin. We observed the indispensable role of miR-23a in LC antigen uptake and inflammation-induced LC epidermal repopulation; however, embryonic LC development and postnatal homeostasis were not affected by cells lacking miR23a. Our results suggest that miR-23a controls LC phagocytosis by targeting molecules that regulate efferocytosis and endocytosis, whereas miR-23a promotes homeostasis in bone marrow-derived LCs that repopulate the skin after inflammatory insult by targeting Fas and Bcl-2 family proapoptotic molecules. Collectively, the context-dependent regulatory role of miR-23a in LCs represents an extra-epigenetic layer that incorporates TGF-b- and PU.1-mediated regulation during steady-state and inflammation-induced repopulation.

A flexible electrochemical glucose sensing platform based on an electrospun PVA mat covered with in situ grown silver nanoparticles and a mixed self-assembled monolayer of glucose oxidase and ferrocene.

An electrochemical glucose sensor based on flexible materials is significant for wearable devices used for real-time health monitoring and diagnosis. However, applying flexible electrodes involves complex fabrication processes and might reduce detection sensitivity. To overcome these obstacles, we herein report a novel strategy for preparing a highly flexible enzyme electrode based on an electrospun poly(vinyl alcohol) (PVA) mat decorated with in situ grown silver nanoparticles (nano-Ag) for electrochemical glucose sensing. Ferrocene (Fc) was selected as an electron acceptor for glucose oxidase (GOD) in order to minimize the influence of oxygen. Electron transfer between GOD and Fc was facilitated by confining them within a mixed self-assembled monolayer (SAM) formed on a thin layer of gold deposited on top of the PVA/nano-Ag film. Nano-Ag was found to significantly increase the surface area of the electrode and improve the stability of electrode conductivity during tensile deformation. Electrochemical glucose detection was performed by chronoamperometry in the electroactivity domain of ferrocene, and good linearity (R2 = 0.993) was obtained in the range of 0.2-7 mM with a detection limit of 0.038 mM and a relative standard deviation (RSD) of 1.45% (n = 6). After being stuck to a bendable PDMS slice and bent, respectively, at 30° and 60° 50 times, the electrode showed slight changes in detection results (<4.78%), which remained within 8% when the bending angle increased to 90°. With its high flexibility, good detection performance, and convenient fabrication process, the proposed enzyme electrode showed good potential as a flexible platform for wearable glucose sensing systems.

Systematic selection of ancestry informative SNPs for differentiating Han, Japanese, Dai, and Kinh populations.

Biogeographical origin inferences of different populations can provide valuable clues in the forensic investigation by narrowing down the detection scope. However, much research mainly focuses on forensic ancestral origin analyses of major continental populations, which may provide limited information in forensic practice. To improve the ancestral resolution of East Asian populations, we systematically selected ancestry informative single-nucleotide polymorphisms (AISNPs) for differentiating Han, Dai, Japanese, and Kinh populations. In addition, we evaluated the performance of the selected AISNPs to differentiate these populations via multiple methods. Totally 116 AISNPs were selected from the genome-wide data to infer the population origins of these four populations. Results of principle component analysis and population genetic structure of these populations indicated that the selected 116 AISNPs could achieve ancestral resolution of most individuals. Furthermore, the machine learning model built by 116 AISNPs unveiled that most individuals from these four populations could be assigned to correct population origins. To sum up, the selected 116 SNPs could be available for ancestral origin predictions of Han, Dai, Japanese, and Kinh populations, which could provide valuable information for forensic research and genome-wide association study in East Asian populations to some extent.

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques.

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

Genetic features and phylogenetic relationship analyses of Guizhou Han population residing in Southwest China via 38 X-InDels.

Background: The insertion/deletion polymorphism (InDel), an ideal forensic genetic marker with a low spontaneous mutation rate and small amplification product fragments, is widely distributed in the genome, combining the advantages of STR and SNP genetic markers. The X-chromosome has high application value in complex paternity testing, and it is an excellent system for evaluating population admixture and studying evolutionary anthropology. However, further research is needed on the population genetics of X-chromosome InDels (X-InDels). Methods: In this article, a system composed of 38 X-InDel loci was utilized to analyse and evaluate the forensic parameters of the Guizhou Han population in order to explore its forensic application efficiency. Results: The results showed that expected heterozygosities spanned from 0.0189 to 0.5715, and the cumulative power of discrimination of the 32 X-InDels and three linkage blocks was 0.9999999954 and 0.999999999999741 for males and females, respectively. The combined mean exclusion chance of these loci for trios and duos is 0.999999 and 0.999747, respectively. Multiple methods like principal component analysis, Fst genetic distance, and phylogenetic reconstruction were employed for dissecting the genetic structure of the Guizhou Han population by comparing it with previously reported populations. As expected, the studied Han population displayed relatively close genetic affinities with the East Asian populations. At the same time, there were obvious genetic differentiations between the Guizhou Han population and other continental populations that were discerned, especially for the African populations. Conclusions: This study further verified the applicability of 38 X-InDels for human personal identification and kinship analyses of Han Chinese, and also showed the application potential of X-InDels in population genetics.