Systematical explorations of forensic feature and population genetic diversity of the Chinese Mongolian group from northwest China via a self-constructed Multi-InDel panel.

This study aimed to investigate the genetic polymorphisms and population characteristics of Chinese Mongolian group from northwest China (NCM) through a self-developed panel including 43 autosomal insertion/deletion (A-InDel) polymorphism genetic markers. Herein, 288 unrelated healthy individuals from the NCM group were employed to obtain the genetic data of 43 A-InDels through multiplex PCR amplification and InDel genotyping using capillary electrophoresis platform. In addition, multiplex population genetic analyses were performed between the NCM group and 27 reference populations. There were no deviations at 43 loci from Hardy-Weinberg equilibrium in the NCM group. The observed heterozygosity (Ho) values ranged from 0.312 8 to 0.559 2, and the combined power of discrimination (CPD) and cumulative probability of exclusion (CPE) values in the NCM group were 0.999 999 999 999 999 998 77 and 0.999 814, respectively. The forensic parameter values indicated that this panel was polymorphic and informative in the NCM group and could be used as an effective tool for forensic personal identification. Furthermore, the results of pairwise genetic distances, principal component analysis, multidimensional scaling analysis, phylogenetic tree construction, and admixture analysis among the NCM group and 27 reference populations revealed that there were closer genetic relationships between the NCM group and East Asian populations, especially Chinese Hui group (CHH) from the northwest China, which is consistent with the geographical location. These present findings contributed to the ongoing genetic explorations and insights into the genetic architecture of the NCM group.

NBS-Promoted Synthesis of Thiocyanated Aminomaleimides and Site-Selective Intramolecular Cyclization Access to 1,4-Benzothiazepines via S-CN Bond Cleavage.

A transition metal-free concise and efficient protocol for the synthesis of thiocyanated aminomaleimides and benzo[e][1,4]thiazepine derivatives has been developed. The method involves an initial α-C-H thiocyanation of aminomaleimides with KSCN and TEMPO-mediated tandem S-CN bond cleavage/intramolecular cyclization substitution processes, which enables the formation of seven-membered S/N-heterocycles. This synthetic strategy provides a reliable method for the synthesis of biologically interesting benzo[e][1,4]thiazepine derivatives by using KSCN as sulfur sources as well as expands the application of enaminones thiocyanation reactions in heterocycles synthesis.

Structure and Properties of Epoxy Resin/Graphene Oxide Composites Prepared from Silicon Dioxide-Modified Graphene Oxide.

In this study, graphene oxide (GO) was modified via electrostatic interactions and chemical grafting by silica (SiO2), and two SiO2@GO hybrids (GO-A and GO-B, respectively) with different structures were obtained and carefully characterized. Results confirmed the successful grafting of SiO2 onto the GO surface using both strategies. The distribution of SiO2 particles on the surface of GO-A was denser and more agglomerated, while it was more uniform on the surface of GO-B. Then, epoxy resin (EP)/GO composites were prepared. The curing mechanism of EP/GO composites was studied by differential scanning calorimetry and in situ infrared spectra spectroscopy. Results of tensile tests, hardness tests, dynamic mechanical analysis, and dielectric measurement revealed that EP/GO-B exhibited the highest tensile properties, with a tensile strength of 79 MPa, a 43% increase compared to raw EP. Furthermore, the addition of fillers improved the hardness of EP, and EP/GO-B showed the highest energy storage modulus of 1900 MPa. The inclusion of SiO2@GO hybrid fillers enhanced the dielectric constant, volume resistivity, and breakdown voltage of EP/GO composites. Among these, EP/GO-B displayed the lowest dielectric loss, relatively good insulation, and relatively high volume resistivity and breakdown voltage. A related mechanism was proposed.

Lycium barbarum polysaccharide mitigated methamphetamine addiction and altered methamphetamine-induced gut microbiota dysbiosis.

Methamphetamine (MA) is a highly addictive mental stimulant, and MA abuse remains a significant public health problem worldwide, while effective treatment options are limited. Lycium barbarum polysaccharide (LBP), a major effective component extracted from Lycium barbarum, has potential health-promoting effects on the nervous system; however, its role in MA dependence remains unclear. In this study, the conditioned place preference (CPP) of MA addiction in adult male mice was established to detect changes in gut microbiota profiles after LBP treatment through 16S rRNA gene sequencing. Our results found that LBP administration could alleviate MA-induced CPP and hyperactivity. Interestingly, LBP improved MA-induced gut microbiota dysbiosis by increasing some beneficial autochthonous genus abundances, such as Allobaculum, Gordonibacter, and Ileibacterium. MA exposure induced the co-occurrence network of intestinal microbiota to become weaker and more unstable when compared with the control group, while LBP changed the above effects when compared with the MA group. Bacterial gene function prediction showed that amphetamine addiction, cocaine addiction, and short-chain fatty acid metabolism were enriched. These findings reveal that LBP might regulate MA-induced gut microbiota and behavior changes, which showed potential therapeutic applicability in treating MA addiction by regulating the gut microbiota.

Effects of chronic triclosan exposure on nephrotoxicity and gut microbiota dysbiosis in adult mice.

Triclosan (TCS), a broad-spectrum, lipophilic, and antibacterial agent, has been commonly used in cosmetics, medical devices, and household products. The toxicity of TCS has recently become a research hotspot. Emerging evidence has shown that TCS can easily migrate to humans and animals and cause adverse effects on various target organs. However, the effects of TCS exposure on nephrotoxicity and underlying mechanisms remain unknown. The aim of the present study was to explore TCS-induced nephrotoxicity. Therefore, we establish a mouse model based on adult male mice to explore the effects of 10-week TCS exposure (50 mg/kg) on kidney. After mice were sacrificed, their blood, feces, and renal tissues were harvested for further analysis. We found that TCS treatment dramatically caused kidney structural damage, and increased blood urea nitrogen (BUN) and creatinine (Cr) expression levels, which indicated renal dysfunction. In addition, TCS exposure increased the malondialdehyde (MDA) and decreased superoxide dismutase (SOD) and total cholesterol (TCHO) expression levels, which indicated oxidative stress and lipid metabolism changes. The RNA sequencing (RNA-seq) of kidney tissue identified 221 differentially expressed genes (DEGs) enriched in 50 pathways, including drug metabolism-other enzymes, oxidative phosphorylation, glutathione metabolism, and inflammatory mediator regulation of TRP channels signaling pathways. The full-length 16S rRNA gene sequencing results showed that TCS exposure altered the community of gut microbiota, which was closely related to renal function damage. The above findings provide new insights into the mechanism of TCS-induced nephrotoxicity.

Correction: Effects of graphene oxide size on curing kinetics of epoxy resin.

[This corrects the article DOI: 10.1039/D1RA05234A.].

Combined exposure to polyvinyl chloride and polystyrene microplastics induces liver injury and perturbs gut microbial and serum metabolic homeostasis in mice.

A variety of microplastics (MPs) have become ubiquitous environmental pollutants, leading to inevitable human contact and health impacts. Most previous research has explored the toxic effects of a single type of MPs exposure. However, the effects of co-exposure to both common types of MPs, polyvinyl chloride (PVC) and polystyrene (PS) MPs on mammals have not been explored. Here, adult mice were exposed to PS-PVC (1.0 µm PS and 2.0 µm PVC both at the concentration of 0.5 mg/day) for 60 days. The results showed that PS-PVC co-exposure-induced hepatotoxicity was evidenced by liver histopathological changes, the release of inflammatory cytokines, and the activation of oxidative stress. Moreover, the intestinal mucosal barrier was damaged after PS-PVC treatment. The results of 16S rRNA gene sequencing reported there was a marked shift in the gut microbial structure accompanied by decreased relative abundances of probiotics, such as Clostridium, Lachnospiraceae_UCG-006, Desulfovibrio, Clostridiales_unclassified and Ruminococcaceae_unclassified and increased the conditional pathogen abundances, such as Erysipelatoclostridium. Furthermore, the triglyceride (TG) and total cholesterol (TCH) expression levels in the serum and liver were increased after PS-PVC co-exposure. Serum metabolomics analysis showed that there were 717 differential expression metabolites found in the positive- and negative-ion modes, including 476 up-regulated and 241 down-regulated, mainly enriched in butyrate metabolism, thiamine metabolism, and phenylacetate metabolism. In addition, remarked changes in the gut microbiota and serum metabolic profiles were closely related to hepatic and intestinal injuries after PS-PVC co-exposure. These results have provided new insights into the toxic effects of PS and PVC MPs co-exposure through the gut-liver axis and the health risks of PS and PVC MPs should be paid more attention to humans.

Forensic validation of a combined analysis of mRNA and miRNA markers for precise tissue origin inferences of five kinds of body fluids by RT-qPCR.

Correctly inferring the tissue origin types of forensic-relevant body fluids left at a crime scene is beneficial for reconstructing a crime scene. However, it is still a challenge to accurately identify different kinds of body fluids at a crime scene. Shorter sequence length and anti-degradation microRNA (miRNA) can be used to infer the tissue sources of biological fluid traces, but a limited number of miRNAs are tissue specific. The application of messenger RNA (mRNA) has been confirmed by different studies based on its high tissue specificity. According to the differential expression features of mRNA or miRNA in forensically relevant body fluids, this study developed a simultaneously reversed mRNA and miRNA system and then used these two types of RNAs for the determinations of five common kinds of body fluids. Compared with previously reported single kind of mRNA or miRNA assay, the combined mRNA and miRNA system showed good advantages for human body fluid identifications, especially it could be applied in mixed samples. In conclusion, the obtained results indicated that this combined mRNA and miRNA system might provide a scientific and accurate reference for body fluid identifications.

Synthesis of 4-Alkylated 1,4-Dihydropyridines: Fe(II)-Mediated Oxidative Cascade Cyclization Reaction of Cyclic Ethers with Enaminones.

Syntheses of highly functionalized 4-alkylated 1,4-dihydropyridines (1,4-DHPs) from cyclic ethers and enaminones via iron(II)-mediated oxidative free radical cascade C(sp3)-H bond functionalization/C(sp3)-O bond cleavage/cyclization reaction have been first developed. This novel synthetic strategy offers an alternative method for the construction of 1,4-DHPs by using esters as the C4 sources, as well as expands the application of ethers in heterocycle synthesis.

Microwave-assisted DABCO-promoted regioselective [3 + 3] tandem cyclization: synthesis of pyrrolo[3,4-b]pyridine-4-ones from trifluoromethyl-alkynyl esters and α-aminomaleimide.

A microwave-assisted DABCO-promoted strategy for the regioselective synthesis of pyrrolo[3,4-b]pyridine-4-one derivatives has been developed from the [3 + 3] annulation of α-aminomaleimide with substituted ethyl 2-butynoate. The characteristic features of this methodology include operational simplicity, high regioselectivity, metal-free reaction conditions, and short reaction times. The potential utility of these methods in biological chemistry and medicinal science applications is highlighted.

Fe-mediated oxidative cascade [1 + 2 + 3]-cyclization/esterification reaction: synthesis of 4-alkylated 1,4-dihydropyridines.

An Fe-mediated four-component reaction of enaminones, anhydrides and tetrahydrofuran through a cascade [1 + 2 + 3]-cyclization/esterification process is presented. This protocol provides a new and effective method to construct 4-alkylated 1,4-dihydropyridines with an ester fragment. Cyclic ether is employed as the C4 source of 1,4-dihydropyridines for the first time.

A MS-feature-based medicinal plant database-driven strategy for ingredient identification of Chinese medicine prescriptions.

Identification of the individual herbs that constitute the Chinese medicine prescription (CMP) is a key step to control the quality and ensure the efficacy of traditional Chinese medicine (TCM), but also a challenging task for analysts from all over the world. In this study, a MS-feature-based medicinal plant database-driven strategy was proposed for quick and automatic interpretation of CMP ingredients. The single herb database consisting of stable ions of sixty-one common TCM medicinal herbs was first constructed. And then, the data of CMP was imported into a self-built searching program to achieve quick and automatic identification with four steps including level 1 candidate herb screening based on stable ions (step 1), level 2 candidate herb screening based on unique ions (step 2), difficult-to-distinguish herb differentiation (step 3) and results integration (step 4). The identification model was optimized and validated with homemade Shaoyaogancao Decoction, Mahuang Decoction, Banxiaxiexin Decoction, and their related negative prescriptions and homemade fakes. Another nine batches of homemade and commercial CMPs were applied to this new approach and most of composed herbs in the corresponding CMPs were correctly identified. This work provided a promising and universal strategy for the clarification of CMP ingredients.

Polystyrene micro- and nanoparticles exposure induced anxiety-like behaviors, gut microbiota dysbiosis and metabolism disorder in adult mice.

Plastics have been proven to be a potential threat to the ecosystem, and their toxicity mechanism is still uncertain. In the ecological environment, plastics can be degraded into microplastics (MPs) and nanoplastics (NPs), which can be contaminated and ingested through the food chain. MPs and NPs are associated with severe intestinal injury, intestinal microbiota disorder, and neurotoxicity, but it is still unclear whether MPs- and NPs-induced intestinal microbiota dysbiosis will affect the brain through the gut-brain axis. In the current study, we determined the effects of exposure to polystyrene (PS)-MPs and PS-NPs on anxiety-like behaviors and explored the underlying mechanisms. This study explored the behavioral effects of 30-day and 60-day exposure to PS-NPs and PS-MPs using the open field test (OFT) and elevated plus maze (EPM) test. Behavioral tests showed PS-NPs and PS-MPs treatment remarkedly induced anxiety-like behaviors compared with the control group. Using 16 S rRNA gene sequencing and untargeted metabolomics analyses, we observed that PS-MPs and PS-NPs exposure reduced the beneficial gut microbiota expression level, such as Lachnoclostridium and Lactobacillus, and increased the conditionally pathogenic bacteria expressions level, such as Proteobacteria, Actinobacteria, and Desulfovibrio. In addition, PS-NPs and PS-MPs reduce intestinal mucus secretion and increase intestinal permeability. The results of serum metabonomics suggested that the metabolic pathways, such as ABC transporter pathways, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, and bile secretion were enriched after PS-NPs and PS-MPs treatment. Besides, neurotransmitter metabolites were also altered by PS-NPs and PS-MPs. It is noteworthy that the correlation analysis showed that the disorder of intestinal microbiota was related to anxiety-like behaviors and neurotransmitter metabolites disorder. The regulation of intestinal microbiota may be a promising treatment strategy for PS-MPs- and PS-NPs-induced anxiety disorder.

Systematical characterization of gypenosides in Gynostemma pentaphyllum and the chemical composition variation of different origins.

Gynostemma pentaphyllum (Thunb.) Makino is an herbaceous plant of Cucurbitaceae family, which has been widely used as an herbal tea and traditional Chinese medicine. Since its saponins are similar to ginsenosides and have a wide range of activities, it has attracted wide interest. However, there are still a large number of unknown saponins that have not been isolated, especially some trace gypenosides. In the present study, a HILIC × RP offline two-dimensional liquid separation combined with a multimode data acquisition was developed for the systematical characterization of gypenosides. On top of the negative mode information, considering that saponins are prone to in-source fragmentations in positive ion mode, a precursor ion list data acquisition method was used for the targeted acquisition of multistage positive data. Reference herbal drug was taken as a golden sample to probe the chemical composition of G. pentaphyllum. The mixed sample of commercially available samples were also analyzed in parallel. Furthermore, the chemical compositions of commercially available samples from different sources were compared. In total, 1108 saponins were characterized, among which 588 were accurately characterized, with 574 identified in the reference herbal drug and 700 in the mixed commercially available samples. The commercially available samples showed great composition variation. These findings clarified the material basis and provided clues for quality control of G. pentaphyllum.

Rare, fatal pulmonary fat embolism after acupuncture therapy: A case report and literature review.

BACKGROUND: Death from nontraumatic pulmonary fat embolism associated with minor soft tissue contusion, surgery, cancer chemotherapy, hematologic disorders and so on has been reported. Patients often present with atypical manifestations and rapid deterioration, making diagnosis and treatment difficult. However, there are no reported cases of death from pulmonary fat embolism after acupuncture therapy. This case emphasizes that the stress induced by acupuncture therapy, a mild soft tissue injury, plays an important role in pulmonary fat embolism. In addition, it suggests that in such cases, pulmonary fat embolism as a complication of acupuncture therapy needs to be taken seriously, and autopsy should be used to identify the source of fat emboli. CASE PRESENTATION: The patient was 72 years old female and experienced dizziness and fatigue after silver-needle acupuncture therapy. She experienced a significant drop in blood pressure and died 2 h later despite treatment and resuscitation. A systemic autopsy and histopathology examination (H&E and Sudan Ⅲ staining) were performed. More than 30 pinholes were observed in the lower back skin. Focal hemorrhages were seen surrounding the pinholes in the subcutaneous fatty tissue. Microscopically, numerous fat emboli were observed in the interstitial pulmonary arteries and alveolar wall capillaries, in addition to the vessels of the heart, liver, spleen and thyroid gland. The lungs showed congestion and edema. The cause of death was identified as pulmonary fat embolism. CONCLUSION: This article suggests that high vigilance for risk factors and the complication of pulmonary fat embolism following silver-needle acupuncture therapy should be exercised. In postmortem examinations, it should be pay attention that the peripheral arterial system and the venous system draining from non-injured sites should be examined for the formation of fat emboli, which can help distinguish posttraumatic and nontraumatic pulmonary fat embolism.

The Role of Non-coding RNAs in Methamphetamine-Induced Neurotoxicity.

Methamphetamine (METH) is an amphetamine-type stimulant that is highly toxic to the central nervous system (CNS). Repeated intake of METH can lead to addiction, which has become a globalized problem, resulting in multiple public health and safety problems. Recently, the non-coding RNA (ncRNA) has been certified to play an essential role in METH addiction through various mechanisms. Herein, we mainly focused on three kinds of ncRNAs including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), which are involved in neurotoxicity effects such as cognitive impairment, behavioral abnormalities, and psychiatric disorders due to METH abuse. In addition, differential expression (DE) ncRNAs also suggest that specific responses and sensitivity to METH neurotoxicity exist in different brain regions and cells. We summarized the relationships between the ncRNAs and METH-induced neurotoxicity and psychiatric disturbances, respectively, hoping to provide new perspectives and strategies for the prevention and treatment of METH abuse. Schematic diagram of the non-coding RNAs (ncRNAs) was involved in methamphetamine (METH)-induced neurotoxicity. The ncRNAs were involved in METH-induced blood-brain barrier disruption, neuronal, astrocyte, and microglial damage, and synaptic neurotransmission impairment. The study of ncRNAs is a hot spot in the future to further understand the neurotoxicity of METH and provide more favorable scientific support for clinical diagnosis and innovation of related treatments.

Comparative identification of phytoecdysteroids in Achyranthes bidentata Blume and its three analogous species and application in differentiation between processing products from different species.

The differentiation of raw herbal products from similar species have been achieved by plant metabolomics. However, the distinguishment on various processed products with improved activities and wide clinical utilization from similar species is still tricky due to obscure composition variations during processing. In this study, a comprehensive analysis of phytoecdysteroids in Achyranthes bidentata Blume (AB) and its three analogous species, which were all called Niuxi in Chinese, was conducted on UPLC-HRMS by integrating dynamic exclusion acquisition with data post-processing of targeted multilateral mass defect filter. Two most frequently used species, AB and Cyathula officinalis Kuan (CO) were systematically compared with plant metabolomics methods. And the differential components from the raw materials were evaluated on the ability of distinguishing processed products. The substitution of hydroxyl groups on C-21, C-20, C-22 and C-25 were determined by characteristic mass differences, leading to systematical characterization of 281 phytoecdysteroids. In plant metabolomics studies of raw AB and CO, 16 potential markers were filtered by VIP value > 1, and displayed satisfactory differentiation on the processed AB and CO. The results facilitated the quality control of the four species, especially the processed products of AB and CO, also provided a reference method for the quality control of other processed products.

Comprehensive Understanding the Forensic Systematic Effectiveness in Chinese Yunnan Hani Group and Intercontinental Population Architecture Differentiation Analyses via a Novel Set of Autosomal InDel Markers.

BACKGROUND: Chinese Yunnan Hani group is an East Asian ethnic group mainly distributed in China, Thailand, Laos, Vietnam, and Burma. The genetic makeup of Chinese Yunnan Hani ethnic group remains to be further investigated. The insertion/deletion (InDel) polymorphism genetic markers are highlighted by their merits such as shorter amplified fragments, lower mutation rates, and are considered effective tools for population genetic investigations. METHODS: The 221 individuals of Chinese Yunnan Hani group were enrolled to obtain the genetic data and polymorphic profiles of 57 autosomal InDels through multiplex amplification and genotyping. Population genetic analyses were performed between Chinese Yunnan Hani group and 30 global reference populations. RESULTS: The forensic parameters, especially cumulative power of discrimination and combined probability of exclusion values, which were 0.9999999999999999999999968 and 0.999958, separately, illustrated that this novel InDel multiplex amplification system could be utilized as a powerful tool for personal identification and paternity testing in Chinese Yunnan Hani group. The results of population genetic analyses indicated that Chinese Yunnan Hani group showed relatively smaller genetic distances and similar genetic structures with the reference East Asian populations. CONCLUSIONS: The genetic polymorphisms and results of intercontinental population architecture differentiation analyses demonstrated the high efficiency of this novel InDel multiplex amplification system. The genomic data and findings of this research will contribute to the ongoing genetic exploration of Chinese Yunnan Hani group and increase our insights into the genetic architecture of worldwide populations.

Effects of Silicon Dioxide/Graphene Oxide Hybrid Modification on Curing Kinetics of Epoxy Resin.

In this study, SiO2-grafted graphene oxide (GO-SiO2) was prepared using the oxygen-containing group on the GO surface as the active site of the reaction. The chemical structure, morphology, and particle size of GO and GO-SiO2 were carefully investigated by Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Raman spectroscopy, thermogravimetry, transmission electron microscopy, scanning electron microscopy, and atomic force microscopy, and the results proved that the grafting modification was successful. Furthermore, epoxy (EP)/GO composites were prepared, and the effects of unmodified GO and GO-SiO2 on the curing kinetics of EP were comparatively studied by differential scanning calorimetry (DSC). The results showed that, compared with neat EP and EP/GO, GO-SiO2 significantly reduces the curing temperature of the composites, indicating that GO-SiO2 has a more significant catalytic effect on the curing process of EP. The calculation results of the Kissinger method showed that the curing activation energy of EP/GO-SiO2 is obviously lower than that of EP/GO and neat EP. Results of the Ozawa method showed that the introduction of GO-SiO2 reduces the curing activation energy during the whole curing process, and in the middle and late stages of curing (α = 0.5-1) can significantly reduce the curing activation energy. The related mechanism has been proposed.

Polyvinyl chloride microplastics induced gut barrier dysfunction, microbiota dysbiosis and metabolism disorder in adult mice.

Microplastics (MPs) are a new kind of environmental pollutant that has attracted extensive attention in recent years. MPs can be ingested by multiple organisms and mainly accumulate in the intestine. However, there is still little known about the toxic effects of MPs on humans. Here, we chose the male adult mice as the research model, which were exposed to 2 µm polyvinyl chloride (PVC) MPs at a concentration of 100 mg/kg for consecutive 60 days, to study the toxicity of PVC-MPs. The changes in gut histology, enzymatic biomarkers, the intestinal microbiome, and metabolomic responses were monitored in mice. The results displayed that the PVC-MPs reduced intestinal mucus secretion and increased intestinal permeability. Moreover, PVC-MPs exposure decreased mRNA expression levels of colonic mucus secretion-related genes, indicating dysfunction of intestinal mucus secretion after exposure to PVC-MPs. With regard to the gut microbiota, high throughput sequencing of the full-length 16S rRNA gene sequencing indicated 15 and 17 kinds of gut microbes changed markedly after PVC-MPs exposure at the genus and species level, respectively. Furthermore, marked alterations in the gut microbiome and fecal metabolic profiles were observed, most of which were related to intestinal injury and barrier dysfunction. These results show that exposure to PVC-MPs leads to intestinal injury and changes gut microbiome composition and metabolome profiles, thus the health risk of PVC-MPs to animals needs more concern. This study helps to provide a new idea about the health risk of PVC-MPs to humans.