Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis.

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3'UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases.

Quercetin regulates dendritic cell activation by targeting STAT4 in the treatment of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a class of autoimmune diseases mainly caused by the immune system attacking the myelin sheath of the axons in the nervous system. Although the pathogenesis of MS is complex, studies have shown that dendritic cells (DCs) play a vital role in the pathogenesis of MS. Quercetin (QU) has a unique advantage in clinical application, especially for treating autoimmune diseases. However, the mechanism of QU in the treatment of experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we explore the potential role of QU in EAE. Finally, we find that QU has anti-inflammatory activities and neural protective effects in EAE. The experimental results suggest that the cellular basis for QU's function is to inhibit the activation of DCs while modulating the Th17 cell differentiation in the co-culture system. Further, QU may target STAT4 to inhibit its activation in DCs. This work will be of great significance for the future development and utilization of QU.

Different machine learning methods based on maxillary sinus in sex estimation for northwestern Chinese Han population.

BACKGROUND & OBJECTIVE: Sex estimation is a critical aspect of forensic expertise. Some special anatomical structures, such as the maxillary sinus, can still maintain integrity in harsh environmental conditions and may be served as a basis for sex estimation. Due to the complex nature of sex estimation, several studies have been conducted using different machine learning algorithms to improve the accuracy of sex prediction from anatomical measurements. MATERIAL & METHODS: In this study, linear data of the maxillary sinus in the population of northwest China by using Cone-Beam Computed Tomography (CBCT) were collected and utilized to develop logistic, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) and random forest (RF) models for sex estimation with R 4.3.1. CBCT images from 477 samples of Han population (75 males and 81 females, aged 5-17 years; 162 males and 159 females, aged 18-72) were used to establish and verify the model. Length (MSL), width (MSW), height (MSH) of both the left and right maxillary sinuses and distance of lateral wall between two maxillary sinuses (distance) were measured. 80% of the data were randomly picked as the training set and others were testing set. Besides, these samples were grouped by age bracket and fitted models as an attempt. RESULTS: Overall, the accuracy of the sex estimation for individuals over 18 years old on the testing set was 77.78%, with a slightly higher accuracy rate for males at 78.12% compared to females at 77.42%. However, accuracy of sex estimation for individuals under 18 was challenging. In comparison to logistic, KNN and SVM, RF exhibited higher accuracy rates. Moreover, incorporating age as a variable improved the accuracy of sex estimation, particularly in the 18-27 age group, where the accuracy rate increased to 88.46%. Meanwhile, all variables showed a linear correlation with age. CONCLUSION: The linear measurements of the maxillary sinus could be a valuable tool for sex estimation in individuals aged 18 and over. A robust RF model has been developed for sex estimation within the Han population residing in the northwestern region of China. The accuracy of sex estimation could be higher when age is used as a predictive variable.

Enantioselective formal total synthesis of dihydrospirotryprostatin B.

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

Sex estimation using maxillary sinus volume for Chinese subjects based on cone-beam computed tomography.

BACKGROUND: Sex estimate is a key stage in forensic science for identifying individuals. Some anatomical structures may be useful for sex estimation since they retain their integrity even after highly severe events. However, few studies are focusing on the Chinese population. Some researchers used teeth for sex estimation, but comparison with maxillary sinus were lack. As a result, the objective of this research is to develop a sex estimation formula for the northwestern Chinese population by the volume of the maxillary sinus and compare with the accuracy of sex estimation based on teeth through cone-beam computed tomography (CBCT). METHODS: CBCT images from 349 samples were used to establish and verify the formula. The volume of both the left and right maxillary sinuses was measured and examined for appropriate formula coefficients. To create the formula, we randomly picked 80% of the data as the training set and 20% of the samples as the testing set. Another set of samples, including 20 males and 20 females, were used to compare the accuracy of maxillary sinuses and teeth. RESULTS: Overall, sex estimation accuracy by volume of the left maxillary sinus can reach 78.57%, while by the volume of the right maxillary sinus can reach 74.29%. The accuracy for females, which can reach 91.43% using the left maxillary sinus, was significantly higher than that for males, which was 65.71%. The result also shows that maxillary sinus volume was higher in males. The comparison with the available results using measurements of teeth for sex estimation performed by our group showed that the accuracy of sex estimation using canines volume was higher than the one using maxillary sinus volume, the accuracies based on mesiodistal diameter of canine and first molar were the same or lower than the volume of maxillary sinus. CONCLUSIONS: The study demonstrates that measurement of maxillary sinus volume based on CBCT scans was an available and alternative method for sex estimation. And we established a method to accurately assess the sex of the northwest Chinese population. The comparison with the results of teeth measurements made the conclusion more reliable.

Dental Age Estimation in Northern Chinese Han Children and Adolescents Using Demirjian's Method Combined with Machine Learning Algorithms.

OBJECTIVES: To investigate the application value of combining the Demirjian's method with machine learning algorithms for dental age estimation in northern Chinese Han children and adolescents. METHODS: Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected. The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method. Various machine learning algorithms, including support vector regression (SVR), gradient boosting regression (GBR), linear regression (LR), random forest regression (RFR), and decision tree regression (DTR) were employed. Age estimation models were constructed based on total, female, and male samples respectively using these algorithms. The fitting performance of different machine learning algorithms in these three groups was evaluated. RESULTS: SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples, while GBR showed the best performance in male samples. The mean absolute error (MAE) of the optimal age estimation model was 1.246 3, 1.281 8 and 1.153 8 years in the total, female and male samples, respectively. The optimal age estimation model exhibited varying levels of accuracy across different age ranges, which provided relatively accurate age estimations in individuals under 18 years old. CONCLUSIONS: The machine learning model developed in this study exhibits good age estimation efficiency in northern Chinese Han children and adolescents. However, its performance is not ideal when applied to adult population. To improve the accuracy in age estimation, the other variables can be considered.

Engineering Rich Active Sites and Efficient Water Dissociation for Ni-Doped MoS2/CoS2 Hierarchical Structures toward Excellent Alkaline Hydrogen Evolution.

Besides improving charge transfer, there are two key factors, such as increasing active sites and promoting water dissociation, to be deeply investigated to realize high-performance MoS2-based electrocatalysts in alkaline hydrogen evolution reaction (HER). Herein, we have demonstrated the synergistic engineering to realize rich unsaturated sulfur atoms and activated O-H bonds toward the water for Ni-doped MoS2/CoS2 hierarchical structures by an approach to Ni doping coupled with in situ sulfurizing for excellent alkaline HER. In this work, the Ni-doped atoms are evolved into Ni(OH)2 during alkaline HER. Interestingly, the extra unsaturated sulfur atoms will be modulated into MoS2 nanosheets by breaking Ni-S bonds during the formation of Ni(OH)2. On the other hand, the higher the mass of the Ni precursor (mNi) for the fabrication of our samples, the more Ni(OH)2 is evolved, indicating a stronger ability for water dissociation of our samples during alkaline HER. Our results further reveal that regulating mNi is crucial to the HER activity of the as-synthesized samples. By regulating mNi to 0.300 g, a balance between increasing active sites and promoting water dissociation is achieved for the Ni-doped MoS2/CoS2 samples to boost alkaline HER. Consequently, the optimal samples present the highest HER activity among all counterparts, accompanied by reliable long-term stability. This work will promise important applications in the field of electrocatalytic hydrogen evolution in alkaline environments.

Nutritional qualities and antioxidant activity of Pleurotus floridanus grown on composted peach sawdust substrate with different composting time.

Recently, composting cultivation method is widely used in oyster mushroom production. In this study, we focused on the effects of composting processes on nutritional qualities and antioxidant activity of Pleurotus floridanus mushroom fruiting bodies. Three treatments of different composting time (2, 4, and 5 days) were performed with an atmospheric sterilization treatment as the control. The results showed that the pH value, total carbon content, and total nitrogen content of substrate were critical parameters which would significantly affect mushroom qualities and bioactivities. Fruiting bodies of the control demonstrated significantly higher crude protein content, total amino acid content, and essential amino acid content than that of composting treatments. Moreover, fruiting bodies of treatment D4 and D5 manifested significantly higher crude polysaccharide contents. Crude polysaccharide of treatment D4 represented the highest scavenging ability toward both radical 3-ethylbenzthiazoline-6-sulfonic acid (ABTS·+ ) and Hydroxyl radical (OH·). It suggests that composting processes is suitable for oyster mushroom cultivation based on nutritional and antioxidant qualities of fruiting bodies.

ChecMatE: A workflow package to automatically generate machine learning potentials and phase diagrams for semiconductor alloys.

Semiconductor alloy materials are highly versatile due to their adjustable properties; however, exploring their structural space is a challenging task that affects the control of their properties. Traditional methods rely on ad hoc design based on the understanding of known chemistry and crystallography, which have limitations in computational efficiency and search space. In this work, we present ChecMatE (Chemical Material Explorer), a software package that automatically generates machine learning potentials (MLPs) and uses global search algorithms to screen semiconductor alloy materials. Taking advantage of MLPs, ChecMatE enables a more efficient and cost-effective exploration of the structural space of materials and predicts their energy and relative stability with ab initio accuracy. We demonstrate the efficacy of ChecMatE through a case study of the InxGa1-xN system, where it accelerates structural exploration at reduced costs. Our automatic framework offers a promising solution to the challenging task of exploring the structural space of semiconductor alloy materials.

A targeted extracellular vesicles loaded with montelukast in the treatment of demyelinating diseases.

The main pathological characteristics of demyelinating diseases are central nervous system (CNS) myelin damage, and the differentiation of oligodendrocyte precursor cells is the therapeutic target of myelin repair. Previous studies have found that a large number of platelet-derived growth factor receptor α(PDGFRα) positive oligodendrocyte progenitor cells (OPCs) accumulate in the lesion area of myelin injury, and differentiation is blocked. However, the therapeutic effects of drugs currently used clinically on OPCs differentiation and myelin repair are limited. The main reason is that it is difficult to reach the effective concentration of the drug in the lesion area. Therefore, efficiently delivering into the CNS lesion area is of great significance for the treatment of MS. Natural exosomes have good biocompatibility and are ideal drug carriers. The delivery of drugs to lesion areas can be achieved by giving the exosomes armed targeting ligand. Therefore, in this study, combining exosomes with PDGFA helps them accumulate in OPCs in vitro and in vivo. Further, load montelukast into exosomes to achieve targeted therapy for cuprizone-induced demyelination animal model. The implementation of this research will help provide effective treatments for demyelinating diseases and lay a theoretical foundation for its application in the clinical treatment of different demyelinating diseases.

Treatment with anacardic acid modulates dendritic cell activation and alleviates the disease development of autoimmune neuroinflammation in mice.

Anacardic acid (AA) is a phenolic acid extract found in a number of plants, crops, and fruits. It exhibits a wide range of biological activities. This study displayed that AA effectively alleviated EAE, a classical mouse model of multiple sclerosis. AA administered to the EAE greatly decreased inflammatory cell infiltration to the CNS and protected the myelin integrity in the white matter of the spinal cord. AA could block lipopolysaccharide-induced DC activation. inhibited the polarization of 2D2 mice-derived T cells by inhibiting the DCs activity. Immunoblot results indicated that the phosphorylation of NF-κB is significantly suppressed in AA-treated DCs. This work displayed that AA possessed a potential anti-inflammatory therapeutic effect for the treatment of autoimmune disease.

Hormone-response transcriptional landscapes of wheat seedlings and the development of a JA fluorescent reporter.

Wheat is an essential energy and protein source for humans. Climate change brings daunting challenges to wheat yield through environmental stresses, in which phytohormones play critical roles. Nevertheless, the comprehensive understanding of wheat phytohormone responses remains elusive. Here, we investigated the transcriptome response of wheat seedlings to five phytohormones, cytokinin (6-BA), abscisic acid (ABA), gibberellic acid (GA), jasmonate (JA) and salicylic acid (SA). We further selected two JA marker genes and cloned their promoters to drive the expression of 3XEGFP (tandem trimeric enhanced green fluorescent protein) in transgenic lines. The JA fluorescent reporter displayed a fast and stable response to JA treatment as an ideal tool to follow JA dynamics during fungal and cold stresses at a cellular resolution. Overall, this study provided a transcriptional landscape and facilitated generating fluorescent reporters to monitor the dynamics of phytohormones in food crops.

[Polymorphisms of 35 Insertion/deletion Loci and Genetic Structure of the Han Population in Shaanxi Province].

Objective To evaluate the genetic polymorphisms and forensic efficiencies of 35 deletion/insertion polymorphism(DIP)loci and explore the genetic structure of the Han population in Shaanxi province.Methods Blood samples of 305 unrelated healthy individuals of the Han population in Shaanxi province were collected.And the allelic frequencies and forensic parameters of 35 DIP loci were calculated and analyzed based on their genotyping results by a self-developed amplification system.The genetic relationship of the Han population in Shaanxi province with the reference populations was explored by molecular variance analyses,phylogenetic tree reconstruction,multidimensional scale analyses,principal component analyses,and STRUCTURE analyses.Results The combined power of discrimination and probability of exclusion of the 35 DIP loci in the Han population in Shaanxi province were 0.999 999 999 999 991 119 and 0.9991,respectively.Population genetic analyses indicated that the Han population in Shaanxi province shared relatively closer genetic relationships with those in other regions of China.Conclusions The 35 DIP loci possessed high polymorphisms and could be used as an effective tool for forensic identification of individuals of the Han population in Shaanxi province.Furthermore,the 35 DIP loci could provide basic data for the genetic analysis of the Han population in Shaanxi province.

Research in forensic medicine under the view of biosafety.

In recent years, biotechnology is gradually getting popular and is playing a significant role in human productivity and life. The consequent biosafety problems are becoming increasingly prominent. Based on the connotation and extension of biosafety, this article sorts out the biosafety contents involved in traditional and modern forensic medicine research and analyzes the risks and challenges facing forensic medicine research from the perspective of biosafety. Based on the protection of legal medical experts, the establishment of working standards, and the promotion and support of research in forensic medicine on biosafety field and other aspects, this article discusses the prospectives of forensic medicine research from a biosafety point of view, and provides the insights and references for a smooth implementation of forensic medicine practice in the future.

A small NGS-SNP panel of ancestry inference designed to distinguish African, European, East, and South Asian populations.

In this study, a small set of ancestry informative SNPs was selected to differentiate African, European, East and South Asian samples, which was detected by the next-generation sequencing technology. A total of 127 Chinese Shaanxi Han individuals were collected as test samples. No statistically significant linkage disequilibrium of any pair of loci or departure from Hardy-Weinberg equilibrium of each locus was observed in the test population. To evaluate the performance of ancestry assignment using this panel, admixture analysis, principal component analysis, and likelihood ratio calculations were conducted based on the 1000 genome data and test samples. All populations were clustered into four groups, African, European, South and East Asian populations, which were consistent with their geographical origins. The pairwise fixation index (FST ) between populations from different continental groups ranged from 0.140 to 0.621 with average 0.415, and the pairwise FST between populations from the same continent ranged from 0.000 to 0.056 with average 0.012. The likelihood ratio results of 125 test individuals indicated that their ancestry components were highly possible from East Asia. In conclusion, this small set of ancestry informative SNPs can be used as a reliable tool to identify and quantify ancestry components of unknown samples.

Developing and population analysis of a new multiplex panel of 18 microhaplotypes and compound markers using next generation sequencing and its application in the Shaanxi Han population.

Compound marker consists of two different types of genetic markers, like deletion/insertion polymorphism and single nucleotide polymorphism in the genomic region of 200 bp, and microhaplotype consists of a series of closely linked single nucleotide polymorphisms in a small DNA segment (<300 bp), which show great potential for human identifications and mixture analyses. In this study, we initially selected 23 novel genetic markers comprising 10 microhaplotypes and 13 compound markers according to previously reported single nucleotide polymorphism or deletion/insertion polymorphism loci. Genetic distributions of these 23 loci in different continental populations showed that they could be used as valuable loci for forensic human identification purpose. Besides, high informativeness values (>0.1) were observed in six loci which could be further employed for forensic ancestry analyses. Finally, 18 loci were successfully developed into a multiplex panel and detected by the next generation sequencing (NGS) technology. Further analyses of these 18 loci in the studied Shaanxi Han population showed that 15 loci exhibited relatively high expected heterozygosities (>0.5). Cumulative power of discrimination (0.999 999 999 99 4835) of these 18 loci revealed that the multiplex panel could also be utilized for human identifications in the studied Shaanxi Han population.

Biogeographic origin prediction of three continental populations through 42 ancestry informative SNPs.

A biogeographic estimate of a certain population can not only discern population substructure in the whole genome association study, but also provide informative clues for forensic investigations when obtained DNA genotypes do not find a match in the available forensic DNA database. In this study, 100 ancestry informative single nucleotide polymorphisms (AISNPs) were first presented to differentiate three continental ancestries (African, East Asian and European). Ultimately, forty-two AISNPs were chosen from the 100 AISNPs. Distinguishing power of the 100 and 42 AISNPs for differentiating continental populations was further evaluated with population cluster analyses. Results indicated both of AISNP sets could efficiently differentiate 11 training populations from the three continents. Further validation of 42 AISNPs in testing population set indicated these 42 AISNPs performed well for ancestry inferences of these testing individuals. Ancestry components of Uyghur group were assessed by comparing with different continental populations based on these 42 AISNPs. Results revealed that East Asian populations contributed more ancestry components to the studied Uyghur group than European populations. In conclusion, our study is expected to provide more AISNP markers and enrich extant reference database.

Ancestry informative DIP loci for dissecting genetic structure and ancestry proportions of Qinghai Tibetan and Tibet Tibetan groups.

Tibetans living in the Qing-Tibet plateau show unique genetic features since they are exposed to the high altitude environment. Accordingly, it is necessary for us to analyze genetic components of the Tibetan groups. Here, genetic structure and ancestry proportions of Tibet Tibetan and Qinghai Tibetan groups are dissected by using a previously published ancestral deletion/insertion polymorphisms (DIPs) panel. Genetic distributions of the analyzed DIPs in both Tibetan groups reveal that some DIPs show relatively balanced frequency distributions with the values ranging from 0.4 to 0.6, implying that these DIPs could be used as individual identification loci for forensic applications in both groups. Besides, the cumulative power of discrimination of the panel also reflects that the panel could serve as a valuable tool for forensic individual identifications in Tibet Tibetan and Qinghai Tibetan groups. Population genetic analyses including principal component analysis, DA genetic distances, phylogenetic tree, and genetic structure reveal that two studied Tibetan groups have closer genetic affiliations with East Asian populations. Genetic differentiation analyses of two Han populations, Xinjiang Uyghur and two Tibetan groups reveal that some DIP loci might be informative for differentiating Uyghurs from the other populations.

Haplogroup Structure and Genetic Variation Analyses of 60 Mitochondrial DNA Markers in Southern Shaanxi Han Population.

Mitochondrial DNA (mtDNA) has been widely employed as one tool for the studies of human migration and phylogenetic evolution owing to the characteristics of its lack of recombination and matrilineal inheritance. In this study, we analyze genetic distributions of 60 mtDNA markers in 126 unrelated individuals of Southern Shaanxi Han population and classify their haplogroups. Genetic distribution comparisons between Southern Shaanxi Han and other populations from different continents are conducted based on the same mtDNA markers. The majority of 60 mtDNA markers are polymorphic in Southern Shaanxi Han population. The most common haplogroups observed in Southern Shaanxi Han population are B5, followed by D5, A, D4e, and N9a1'3. Obtained matching probability for these 60 mtDNA markers indicates that the panel could be used as a valuable tool in forensic caseworks. Results of genetic distances (Fst) and multidimensional scaling analysis show that Southern Shaanxi Han population has relatively close genetic relationships with other Han populations in different regions. In conclusion, the panel comprising 60 mtDNA markers could be utilized for forensic applications in Southern Shaanxi Han population.

Genetic distribution analyses and population background explorations of Gansu Yugur and Guizhou Miao groups via InDel markers.

Insertion and deletion markers (InDels) have gained considerable attentions in population genetics and forensic research. In this study, we investigated genetic distributions of 30 InDels in Gansu Yugur and Guizhou Miao groups and evaluated their forensic application values. Genetic relationship analyses between Gansu Yugur, Guizhou Miao groups and other published populations were conducted based on these 30 InDels. Power of discrimination and power of exclusion in trio and duo cases of 30 InDels ranged from 0.3528 to 0.6247, 0.0937 to 0.1873, and 0.0219 to 0.1247 in Gansu Yugur group; and they ranged from 0.2579 to 0.6247, 0.0671 to 0.1874, and 0.0105 to 0.1247 in Guizhou Miao group. Obtained cumulative power of discrimination values indicated these InDels could be used for forensic individual identifications in both ethnic groups. Principal component analysis and phylogenetic reconstruction revealed that Gansu Yugur and Guizhou Miao groups had close affinities with their neighboring populations. Genetic structure analyses among these populations also indicated that studied Gansu Yugur and Guizhou Miao groups showed similar genetic structure with their neighboring populations. Further analyses of Y-STR, mtDNA, and ancestry informative markers should be conducted to better understand genetic backgrounds of Gansu Yugur and Guizhou Miao groups in the future.