Search

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.

Abstract 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.

Abstract 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.

Abstract 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.

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.

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.

Background Insertion/deletion polymorphism (InDel), as the third genetic marker, has been given a lot of attention by forensic geneticists since it has the advantages of extensive distributions in the human genome, small amplicon, and low mutation rate. However, the extant InDel panels were only viewed as supplemental tools for kinship analyses. In addition, these panels were not conductive to mixture deconvolution because InDels in these panels mainly displayed two alleles. Aims The purpose of this study is to investigate genetic distributions of a novel panel of InDels and STRs in the Guizhou Han population; assess the forensic application value of the panel; and conduct population genetic analyses of the Guizhou Han and other reference populations based on the overlapping loci. Subjects and methods The bloodstain samples of 209 Guizhou Han were gathered and genotyped by the novel panel. Allelic frequencies and forensic parameters of two miniSTRs and 59 InDels in the panel were estimated. In addition, we assessed phylogenetic relationships among the Guizhou Han and other reference populations by principal component analysis, DA genetic distance, and neighbor-joining tree. Results A total of 139 alleles of 61 loci could be observed in the Guizhou Han population. Polymorphic information content values of 59 InDels were greater than 0.3 in the Guizhou Han population. The cumulative power of discrimination and probability of exclusion of two miniSTRs and 59 InDels in the Guizhou Han population were 0.999999999999999999999999997984 and 0.9999986, respectively. Principal component analysis of 14 populations showed that the Guizhou Han population located closer to Hunan Han and Southern Han Chinese (CHS) populations. Similar results were also discerned from DA genetic distances and the neighbor-joining tree. Conclusion To sum up, the novel panel could be employed for forensic personal identification and paternity testing in the Guizhou Han population as a promising independent tool. Besides, the principal component analysis and phylogenetic tree of the Guizhou Han and other compared populations revealed that the Guizhou Han population possesses close genetic affinities with Hunan Han, CHS, and Han Chinese in Beijing (CHB) populations.

Objective Patients undergoing spinal surgery in the prone position may experience venous stasis, often resulting in edema in dependent areas of the body, including the head, and increased postoperative cognitive dysfunction (POCD). Not only does POCD present challenges for post‐operative care and recovery, it can also cause permanent damage to the patient's brain and increase mortality and social costs. We aimed to clarify the incidence of POCD in patients with hypertension after prone spine surgery and to further determine the association between intraoperative somatic tissue oxygen saturation (SstO2)/cerebral tissue oxygen saturation (SctO2) and POCD. Methods Patients with hypertension scheduled for open prone spine surgery from January 2020 to April 2021 were included in this single‐center, prospective, observational study. SctO2 and SstO2 were monitored by near‐infrared spectroscopy continuously throughout the surgery. The primary outcome was POCD assessed using the Mini‐Mental Status Examination (MMSE). The association of SstO2 and SctO2 with POCD was evaluated with unadjusted analyses and multivariable logistic regression. Results One hundred and one of 112 identified patients were included, 28 (27.8%) of whom developed POCD. None of the investigated SctO2 indices were predictive of POCD. However, the patients with POCD had greater decreases in intraoperative absolute SstO2 and relative SstO2 than the patients without POCD (P = 0.037, P = 0.036). Moreover, three SstO2 indices were associated with POCD, including a greater absolute SstO2 decrease (P = 0.021), a greater relative SstO2 decrease (P = 0.032), and a drop below 90% of the baseline SstO2 (P = 0.002), independent of ASA III status, preoperative platelets and postoperative sepsis. In addition, there was no correlation between intraoperative SctO2 and intraoperative SstO2 or between their respective absolute declines. Conclusion Twenty‐eight (27.7%) of 101 patients developed POCD in patients with hypertension undergoing prone spine surgery, and intraoperative SstO2 is associated with POCD, whereas SctO2 shows no association with POCD. This study may initially provide a valuable new approach to the prevention of POCD in this population.

The tremendous development of peptide-based cancer vaccine has attracted incremental interest as a powerful approach in cancer management, prevention and treatment. As successful as tumor vaccine has been, major challenges associated with achieving efficient immune response against cancer are (1) drainage to and retention in lymph nodes; (2) uptake by dendritic cells (DCs); (3) activation of DCs. In order to overcome these barriers, here we construct PBE-modified TRP2 nanovaccine, which comprises TRP2 peptide tumor antigen and diblock copolymer PEG-b-PAsp grafted with phenylboronic ester (PBE). We confirmed that this TRP2 nanovaccine can be effectively trapped into lymph node, uptake by dendritic cells and induce DC maturation, relying on increased negative charge, ROS response and pH response. Consistently, this vehicle loaded with TRP2 peptide could boost the strongest T cell immune response against melanoma in vivo and potentiate antitumor efficacy both in tumor prevention and tumor treatment without any exogenous adjuvant. Furthermore, the TRP2 nanovaccine can suppress the tumor growth and prolong animal survival time, which may result from its synergistic effect of inhibiting tumor immunosuppression and increasing cytotoxic lymphocyte (CTL) response. Hence this type of PBE-modified nanovaccine would be widely used as a simple, safe and robust platform to deliver other antigen in cancer immunotherapy.

Background Dong people in Southwest China are officially recognised as an ethnic group, but there has been a lack of population genetic research on this group, especially based on mitochondrial DNA data. Aim To study the sequences and haplogroups of the mitochondrial DNA control region in a typical Dong population, and to provide help for the construction of a forensic mitochondrial DNA analysis reference database in East Asia. Subjects and methods The sequences of the mitochondrial DNA control region were analysed in 200 individuals of Dong in Guizhou. The haplotype frequencies, haplogroup distribution and paired Fst values of Guizhou Dong and 51 other populations in the world were calculated and explained to explore the genetic polymorphism and population relationships. Results A total of 180 haplotypes were detected, with frequencies of 0.005–0.02. All haplotypes were assigned to 97 different haplogroups. The haplotype diversity and random matching probability were 0.998643 and 0.00635, respectively. The paired Fst values and correlation p values of 52 populations showed that the Guizhou Dong had the closest genetic relationship with the Henan Han and the Guizhou Miao in China, and were closest to the Punjab population in Pakistan and the Kashmiri population when compared with the world populations. Conclusions Our study was based on the matrilineal genetic structure of Guizhou Dong to study mitochondrial DNA, which was helpful to promote the establishment of the forensic DNA reference database in East Asia and provide reference for anthropological research.

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.

Insertion/deletion polymorphisms (InDels) show great application values in forensic research because they own superiorities of short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs). Whereas, InDels commonly display low genetic diversities in comparison to STRs. Therefore, they may provide limited genetic information in forensic kinship testing. Here, we evaluated forensic application efficiency of a novel multiplex amplification system including two STRs, 59 InDels, and three sex-determination loci in the Guizhou Dong group. In addition, we explored the genetic background of the Guizhou Dong group in comparison to other reported populations based on 59 InDels. We found that 59 InDels displayed relatively high genetic diversities in the Guizhou Dong group. Moreover, the cumulative forensic efficiency of two STRs and 59 InDels could meet the requirement of individual identification and paternity testing in the Guizhou Dong group. For these 59 InDels, we observed that some loci exhibited relatively high genetic differentiations among different continental populations, especially for African and Non-African populations, which could be viewed as candidate ancestry informative markers in the future. Genetic structure results indicated that the Dong group had close genetic relationships with East Asian and some Southern Chinese Han populations. To sum up, we stated that the 64-plex panel could be performed for forensic application of the Guizhou Dong group.

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-β 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.

Background X-chromosomes show a specific genetic mode, which makes genetic markers on the X-chromosome play crucial roles in forensic research and human evolution. Dong group, one of 55 minority groups in China, live in Guizhou, Guangxi, and Hunan provinces. Even though some genetic data of Y chromosomal short tandem repeats (STRs) and autosomal insertion/deletion polymorphism (InDels) in Dong groups have been reported, there is little research about X-STRs in the Dong group. Aim Purposes of this study are to investigate allelic distributions and forensic statistical parameters of 19 X-STRs in the Guizhou Dong group, and explore the genetic composition of the Guizhou Dong group and its phylogenetic relationships with other reference populations. Subjects and methods Five hundred and seven Dongs (272 males and 235 females) living in Guizhou province were typed using the AGCU X19 STR kit. Allelic frequencies and forensic parameters of 19 X-STRs in the Guizhou Dong group were calculated. Population genetic analyses of Guizhou Dong and another 17 reference populations were conducted using DA genetic distances, phylogenetic tree, principal component analysis, and multidimensional scaling. Results A total of 230 alleles of 19 X-STRs were identified in all Dongs. The frequencies of 19 loci ranged from 0.0013 to 0.6838. The values for cumulative power of discrimination in males (PDM), cumulative power of discrimination in females (PDF), and four different kinds of mean exclusion chance (MEC_Kruger, MEC_Kishida, MEC_Desmarais, and MEC_Desmarais_du) for the 19 X-STRs in all individuals were 0.999999999999761, 0.9999999999999999999993951, 0.999999964841617, 0.999999999997261, 0.999999999997297, and 0.999999993623172, respectively. Besides, genetic polymorphisms of seven linkage clusters ranged from 0.9381 to 0.9963. In addition, these seven groups showed high polymorphism information content (PIC), PDM, PDF, MEC_Kruger, MEC_Kishida, MEC_Desmarais, and MEC_Desmarais_duo. Population genetic analyses of Guizhou Dong and another 17 reference populations showed that the Guizhou Dong group had close genetic relationships with surrounding Tai–Kadai-speaking, Hmong-Mien-speaking, and Han groups. Conclusion Nineteen X-STRs displayed high genetic diversities and could be employed for forensic personal identification and paternity analysis in the Guizhou Dong group. Close genetic affinities between Guizhou Dong and surrounding populations were observed based on the 19 X-STRs in 17 reference populations.

Background Sui people are officially recognised people living in southwest China, but there has been a lack of genetic research, especially based on mitochondrial DNA data. Aim To study the sequences and haplogroups of the mitochondrial DNA control region in a typical Sui population, with the aim of helping to promote the establishment of a forensic DNA analysis reference database in East Asia. Subjects and methods We analysed 201 Sui individuals and observed the sequences of the mitochondrial DNA control region. We calculated and explained the haplotype frequencies, haplogroup distribution and pairwise Fst values between the Sui and 47 other populations in the world, in order to explore genetic polymorphisms and population relationships. Results 161 haplotypes were found in the Sui population, with frequencies of 0.0049–0.0199. All samples were assigned to 80 different haplogroups. The haplotype diversity and random matching probability were 0.999938 and 0.024729, respectively. The pairwise Fst values and correlation p-values of 48 populations showed that the Sui population was most closely related to the Miao population in Guizhou and the Han population in Henan, and closer to the Punjab population and Pukhtunkhwa population in Pakistan, and was significantly different from the other 43 groups. Compared with the other 43 groups, it is relatively isolated. Conclusion Our results show that the study of mitochondrial DNA based on the analysis of matrilineal genetic structure of the Sui population can help to promote the establishment of a forensic DNA reference database in East Asia and provide reference for future anthropological research.

Psychostimulants, such as methamphetamine (METH) can induce structural remodeling of synapses by remodeling presynaptic and postsynaptic morphology. Escalating or long-lasting high dose METH accounts for neurodegeneration by targeting multiple neurotransmitters. However, the effects of low dose METH on synaptic structure and the modulation mechanism remain elusive. This study aims to assess the effects of low dose (2 mg/kg) and high dose (10 mg/kg) of METH on synaptic structure alternation in hippocampus and prefrontal cortex (PFC) and to reveal the underlying mechanism involved in the process. Low dose METH promoted spine formation, synaptic number increase, post-synaptic density length elongation, and memory function. High dose of METH induced synaptic degeneration, neuronal number loss and memory impairment. Moreover, high dose, but not low dose, of METH caused gliosis in PFC and hippocampus. Mechanism-wise, low dose METH inactivated ras-related C3 botulinum toxin substrate 1 (Rac1) and activated cell division control protein 42 homolog (Cdc42); whereas high dose METH inactivated Cdc42 and activated Rac1. We provided evidence that low and high doses of METH differentially regulate synaptic plasticity in cortex and hippocampus.

Multi-InDel, as the novel genetic markers, showed great potential in forensic research. Whereas, most scholars mainly focused on autosomal Multi-InDels, which might provide limited genetic information in some complex kinship cases. In this study, we selected 17 Multi-InDels on the X chromosome and developed a multiplex amplification panel based on the next-generation sequencing (NGS) technology. Genetic distributions of these 17 loci in Beijing Han, Chinese Southern Han, and the studied Guizhou Han populations revealed that most loci showed relatively high forensic application values in these Han populations. In addition, more allelic variations of some loci were observed in the Guizhou Han than those in Beijing Han and Southern Han populations. Pairwise FST values, multi-dimensional analysis, and phylogenetic tree of different continental populations showed that selected 17 loci generally could differentiate African, European, East Asian, and South Asian populations. To sum up, the developed panel in this study is not only viewed as the high-efficient supplementary tool for forensic individual identification and paternity analysis, but it is also beneficial for inferring biogeographical origins of different continental populations.

The genome-wide characteristics and admixture history of the Tai-Kadai-speaking populations are essential for understanding the population genetic diversity in southern China. We genotyped about 700,000 single nucleotide polymorphisms (SNPs) of 239 individuals from six Tai-Kadai-speaking populations residing in the mountainous Guizhou Province of southwestern China. We merged the genome-wide data with available populations and ancients in East and Southeast Asia to infer Tai-Kadai-speaking populations’ admixture history and genetic structure. We observed a genetic substructure within the studied six populations in the PCA, ADMIXTURE, ChromoPainter, GLOBETROTTER, f-statistics, and qpWave analysis. The Dong, Zhuang, and Bouyei people had a strong genetic affinity with other Tai-Kadai-speaking and Austronesian groups in the surrounding area. However, Gelao showed an affinity to Sino-Tibetan groups, and Mulao people were genetically close to Hmong-Mien populations. qpAdm further illuminated that Gelao and Dong_Tongren composited more Han-related ancestry than Dong, Zhuang, Bouyei, and Mulao people. Meanwhile, we observed high frequencies of Y-chromosome haplogroup O in studied Tai-Kadai-speaking groups except for Gelao people with a high haplogroup N frequency. From the maternal side, haplogroup M7 was frequent in studied populations except for Tongren Dong, who had a high frequency of haplogroup B5. Our newly reported data are helpful for further exploring population dynamics in southern China.

As a single matrilineal gene, human mitochondrial DNA plays a very important role in the study of population genetics. The whole mitogenome sequences of 287 individuals of the Tai-Kadai-speaking population in Guizhou were obtained. It was discovered that there were 82, 104, and 94 haplotypes in 83 Bouyei individuals, 107 Dong individuals, and 97 Sui individuals, respectively; and the haplotype diversity in Bouyei, Dong, and Sui groups was 1.000 ± 0.02, 0.9993 ± 0.0015, and 0.999 ± 0.002, respectively. The result of neutrality tests of the Tai-Kadai-speaking population in Guizhou showed significant negative values, and the analysis of mismatch distribution showed an obvious unimodal distribution. The results implied that Guizhou Tai-Kadai-speaking populations had high genetic diversities and may have experienced recent population expansion. In addition, the primary haplogroups of studied populations were M*, F, B, D, and R*, implying that they may origin from Southern China. The matrilineal genetic structure of the Tai-Kadai-speaking populations in Guizhou was analyzed by merging the mitogenome data of 79 worldwide populations as reference data. The results showed that there were close relationships between studied populations and other Tai-Kadai as well as some Austronesian populations in East and Southeast Asia. Overall, the mitogenome data generated in this study will provide important data for the study of genetic structure of Tai-Kadai speaking populations.

Mitophagy plays a vital role in the selective elimination of dysfunctional and unwanted mitochondria. As a receptor of mitophagy, FUN14 domain containing 1 (FUNDC1) is attracting considerably critical attention. FUNDC1 is involved in the mitochondria fission, the clearance of unfolded protein, iron metabolism in mitochondria, and the crosstalk between mitochondria and endoplasmic reticulum besides mitophagy. Studies have demonstrated that FUNDC1 is associated with the progression of ischemic disease, cancer, and metabolic disease. In this review, we systematically examine the recent advancements in FUNDC1 and the implications of this protein in health and disease.

Aging is usually accompanied by the decline of physiological function and dysfunction of cellular processes. Genetic markers related to aging not only reveal the biological mechanism of aging but also provide age information in forensic research. In this study, we aimed to screen age-associated mRNAs based on the previously reported genome-wide expression data. In addition, predicted models for age estimations were built by three machine learning methods. We identified 283 differentially expressed mRNAs between two groups with different age ranges. Nine mRNAs out of 283 mRNAs showed different expression patterns between smokers and non-smokers and were eliminated from the following analysis. Age-associated mRNAs were further screened from the remaining mRNAs by the cross-validation error analysis of random forest. Finally, 14 mRNAs were chosen to build the model for age predictions. These 14 mRNAs showed relatively high correlations with age. Furthermore, we found that random forest showed the optimal performance for age prediction in comparison to the generalized linear model and support vector machine. To sum up, the 14 age-associated mRNAs identified in this study could be viewed as valuable markers for age estimations and studying the aging process.

Southern China was the original center of multiple ancestral populations related to modern Hmong-Mien, Tai-Kadai, Austroasiatic, and Austronesian people. More recent genetic surveys have focused on the fine-scale genetic structure and admixture history of southern Chinese populations, but the genetic formation and diversification of Hmong-Mien speakers are far from clear due to the sparse genetic sampling. Here, we reported nearly 700,000 single-nucleotide polymorphisms (SNPs) data from 130 Guizhou Miao and Yao individuals. We used principal component analysis, ADMIXTURE, f-statistics, qpAdm, phylogenetic tree, fineSTRUCTURE, and ALDER to explore the fine-scale population genetic structure and admixture pattern of Hmong-Mien people. The sharing allele patterns showed that our studied populations had a strong genetic affinity with ancient and modern groups from southern and southeastern East Asia. We identified one unique ancestry component maximized in Yao people, which widely existed in other Hmong-Mien-speaking populations in southern China and Southeast Asia and ancient samples of Guangxi. Guizhou Hmong-Mien speakers harbored the dominant proportions of ancestry related to southern indigenous East Asians and minor proportions of northern ancestry related to Yellow River farmers, suggesting the possibility of genetic admixture between Hmong-Mien people and recent southward Sino-Tibetan-related populations. Furthermore, we found a genetic substructure among geographically different Miao and Yao people in Leishan and Songtao. The Yao and Miao people in Leishan harbored more southern East Asian ancestry, but Miao in Songtao received more northern East Asian genetic influence. We observed high mtDNA but low Y-chromosome diversity in studied Hmong-Mien groups, supporting the role of sex-specific residence in influencing human genetic variation. Our data provide valuable clues for further exploring population dynamics in southern China.

Leisure time is crucial for personal development and leisure consumption. Accurate prediction of leisure time and analysis of its influencing factors creates a benefit by increasing personal leisure time. We predict leisure time and analyze its key influencing factors according to survey data of Beijing residents’ time allocation in 2011, 2016, and 2021, with an effective sample size of 3356. A Light Gradient Boosting Machine (LightGBM) model is utilized to classify and predict leisure time, and the SHapley Additive exPlanation (SHAP) approach is utilized to conduct feature importance analysis and influence mechanism analysis of influencing factors from four perspectives: time allocation, demographics, occupation, and family characteristics. The results verify that LightGBM effectively predicts personal leisure time, with the test set’s accuracy, recall, and F1 values being 0.85 and the AUC value reaching 0.91. The results of SHAP highlight that work/study time within the system is the main constraint on leisure time. Demographic factors, such as gender and age, are also of great significance for leisure time. Occupational and family heterogeneity exist in leisure time as well. The results contribute to the government improving the public holiday system, companies designing personalized leisure products for users with different leisure characteristics, and residents understanding and independently increasing their leisure time.

Weed control tries to suppress competitors for a crop and often relies on differential intoxication, making use of differences in uptake, development, or metabolism. We explored the possibility of using natural signals to shift competition in favour of the crop. Using the competitive horsemint (Mentha longifolia) as a paradigm, we showed that essential oils from certain mint species suppress the seedling development of different target species in a specific and efficient manner. The specificity concerned both the donor and the receptor. We demonstrated further that the effect of horsemint oil was specific for actin filaments, and not for microtubules. Since the elimination of actin will impair auxin transport, which is essential for root regeneration in vegetatively propagating weeds, we tested the efficacy of horsemint essential oil in combination with a slow-release carrier against field bindweed (Convolvulus arvensis), a pertinent weed in organic cereal production. We observed that the development of this weed can be specifically blocked, especially if the carrier is worked into the soil. We propose that allelopathic interactions, often relying on manipulative chemical signalling, harbour significant potential for organic weed control.

Abstract Background According to data estimated by the WHO, primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of death around the world. Hepatocellular carcinoma (HCC) is one of the most common primary liver malignancies, so effective therapy is highly desired for HCC. Results In this study, the use of poly(l-Aspartic acid)-poly(ethylene glycol)/combretastatin A4 (CA4-NPs) was aimed to significantly disrupt new blood vessels in tumor tissues for targeted hepatic tumor therapy. Here, PEG-b-PAsp-g-CA4 showed significantly prolonged retention in plasma and tumor tissue. Most importantly, CA4-NPs were mainly distributed at the tumor site because of the triple target effects—enhanced permeability and retention (EPR) effect, acid-sensitive (pH = 5.5) effect to the tumor microenvironment (TME), and good selectivity of CA4 for central tumor blood vessel. Considering that CA4-NPs might induce severe hypoxic conditions resulting in high expression of HIF-1α in tumor tissues, which could induce the overexpression of PD-L1, herein we also used a programmed death-ligand 1 antibody (aPD-L1) to prevent immunosuppression. This way of complementary combination is able to achieve an ideal treatment effect in tumor site where CA4-NPs and aPD-L1 could respond to the inner area and peripheral area, respectively. As a result, a significant decrease in tumor volume and weight was observed in the combination group of CA4-NPs plus aPD-L1 compared with CA4-NPs or aPD-L1 monotherapy in subcutaneous Hepa1-6 hepatic tumor models. Conclusions We presented a new idea that co-administration of CA4-NPs and aPD-L1 possessed notable anti-tumor efficacy for HCC treatment. Graphic abstract

Adding flame retardant into leather is an effective way to improve the flame resistance of leather products. In this paper, a Nitrogen-Phosphorus Intumescent (NPI) flame retardant was synthesized and then added to the fatliquoring process to modify leather. The effect of NPI flame retardant on the flame-retardant properties of leather was investigated using Limiting Oxygen Index (LOI), smoke density, vertical combustion, cone calorimeter tests, and SEM. The results revealed that LOI of leather modified with NPI flame retardant increased with the increase of flame retardant. The flame and flameless combustion time of the modified leather was effectively reduced. Compared with unmodified leather, HRR of the modified leather with 6% NPI flame retardant decreased from 80.32 MJ/m2 to 63.45 MJ/m2; the peak HRR dropped from 108.71 MJ/m2 to 77.23 MJ/m2. Moreover, the fire growth index of the modified leather with 6% NPI flame retardant is close to half of that of the unmodified sample. The results certified the enhancing effect of NPI flame retardant added in the fatliquoring process on flame retardancy of leather samples.

Short tandem repeats (STRs) are the most frequently used genetic markers in forensic genetics due to their high genetic diversities and abundant distributions in the human genome. Currently, the combined DNA index system is commonly incorporated into various commercial kits for forensic research. Some novel STRs that are different from the combined DNA index system were not only used to assess complex paternity cases but also could provide more genetic information and higher forensic efficiency in combination with those commonly used STRs. In this study, we validated forensic performance of a novel multiplex amplification STR panel to evaluate its sensitivity, species specificity, forensic application values, and so on. Obtained results revealed that the kit showed high sensitivity, and the complete allelic profile could be observed at 0.125 ng DNA sample. In addition, the kit possessed high species specificity, good tolerance to common inhibitors, and accurate genotyping ability. More importantly, STRs out of the kit displayed high discrimination power and probability of exclusion. To sum up, the novel kit presented in this study can be viewed as a promising tool for forensic human identification and complex paternity analysis.

Glioblastoma multiforme (GBM) is a common intracranial malignancy characterized by abundant and aberrant vasculature. The efficiency of existing antivascular treatments remains unsatisfactory. The transition of glioblastoma stem-like cells (GSCs) into tumor endothelioid cells (ECs) has been thought to cause glioma neovascularization and anti-angiogenesis tolerance, but the mechanisms regulating glioma transdifferentiation remains unclear. Our previous study found that P4HA1 regulates GSCs vascular mimicry in a hypoxic microenvironment, but the detailed molecular mechanism has not been determined. In this study, candidate protein COL6A1 was screened by mass spectrometry. In vitro experiments show that P4HA1 regulates the expression of CD31 via COL6A1, with the levels of expression of P4HA1, COL6A1 and the vascular endothelial molecular markers CD31 showing positive correlations in vivo assay. Altering the expression of P4HA1 in GSCs altered the expression of COL6A1 and CD31, thereby inducing glioma angiogenesis. In conclusion, this study revealed that the P4HA1/COL6A1 axis modulates the transdifferentiation process of GSCs into ECs. Interrupting this signaling axis can inhibit glioma angiogenesis, suggesting that this axis may be a novel target for antivascular therapy in patients with glioma.

The male-specific region of the human Y chromosome is a useful genetic marker for genealogical searching, male inheritance testing, and male DNA mixture deconvolution in forensic studies. However, the Y chromosomal short tandem repeats (Y-STRs) are difficult to distinguish among related males due to their low/medium mutation rate. In contrast, rapidly mutating (RM) Y-STRs exhibit unusually high mutation rates and possess great potential for differentiating male lineages. In this study, we developed a novel Y-STRs multiplex amplification assay of 32 RM Y-STRs by fragment analysis using six dye-labeled technologies (FAM, HEX, TAMRA, ROX, VIG, and SIZ). The development and the validation of the kit were carried out in accordance with the Scientific Working Group guidelines on DNA Analysis Methods. Identical allelic profiles of the 32 RM Y-STRs using a DNA 9948 sample as the positive control could be observed at different concentrations of PCR reagents. Further, the RM Y-STRs did not show cross-reactions with other common animal species, and the developed assay could tolerate interferences from common PCR inhibitors and mixed DNA samples. More importantly, the kit showed relatively high sensitivity and could detect trace DNA samples. Genetic distributions of 32 RM Y-STRs in the Guizhou Han population revealed that these RM Y-STRs showed relatively high genetic diversities. In conclusion, the RM Y-STR assay developed here showed good species specificity, high sensitivity, tolerance to inhibitors, and sample compatibility, which can be viewed as a highly efficient tool with high discrimination capacity for forensic male differentiation.

Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5′monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway.Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining.Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor.Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.

Previous research shows that ginsenoside Rb3 (G-Rb3) exhibit significant protective effects on cardiomyocytes and is considered a promising treatment for myocardial infraction (MI). However, how to improve its oral bioavailability and reduce its dosage remains to be studied. Previous studies suggest that Ferruginol (FGL) may have synergistic effects with G-Rb3. However, the underlying mechanisms remain to be explored. In this study, left anterior descending branch (LAD) coronary artery ligation or oxygen-glucose deprivation-reperfusion (OGD/R) were used to establish MI models in vivo and in vitro. Subsequently, the pharmacological effects and mechanisms of G-Rb3-FGL were explored by in vitro studies. The results showed that the G-Rb3-FGL co-treatment improved heart functions better than the G-Rb3 treatment alone in MI mice models. Meanwhile, the G-Rb3-FGL co-treatment can upregulate fatty acids oxidation (FAO) and suppress oxidative stress in the heart tissues of MI mice. In vitro studies demonstrated that the synergistic effect of G-Rb3-FGL on FAO, oxidation and inflammation was abolished by RXRα inhibitor HX531 in the H9C2 cell model. In summary, we revealed that G-Rb3 and FGL have a synergistic effect against MI. They protected cardiomyocytes by promoting FAO, inhibiting oxidative stress, and suppressing inflammation through the RXRα-Nrf2 signaling pathway.

Guizhou Province harbors extensive ethnolinguistic and cultural diversity with Sino-Tibetan-, Hmong–Mien-, and Tai–Kadai-speaking populations. However, previous genetic analyses mainly focused on the genetic admixture history of the former two linguistic groups. The admixture history of Tai–Kadai-speaking populations in Guizhou needed to be characterized further. Thus, we genotyped genome-wide SNP data from 41 Tai–Kadai-speaking Maonan people and made a comprehensive population genetic analysis to explore their genetic origin and admixture history based on the pattern of the sharing alleles and haplotypes. We found a genetic affinity among geographically different Tai–Kadai-speaking populations, especially for Guizhou Maonan people and reference Maonan from Guangxi. Furthermore, formal tests based on the f3/f4-statistics further identified an adjacent connection between Maonan and geographically adjacent Hmong–Mien and Sino-Tibetan people, which was consistent with their historically documented shared material culture (Zhang et al., iScience, 2020, 23, 101032). Fitted qpAdm-based two-way admixture models with ancestral sources from northern and southern East Asians demonstrated that Maonan people were an admixed population with primary ancestry related to Guangxi historical people and a minor proportion of ancestry from Northeast Asians, consistent with their linguistically supported southern China origin. Here, we presented the landscape of genetic structure and diversity of Maonan people and a simple demographic model for their evolutionary process. Further whole-genome-sequence–based projects can be presented with more detailed information about the population history and adaptative history of the Guizhou Maonan people.

Background. Oral iron supplement is commonly prescribed to heart failure patients with iron deficiency. However, the effects of oral iron for heart failure remain controversial. This study included randomized controlled trials (RCTs) for meta-analysis to evaluate the effects of oral iron for heart failure patients. Methods. Nine databases (The Cochrane Library, Embase, PubMed, CINAHL, Web of science, CNKI, SinoMed, VIP, and Wanfang) were searched for RCTs of oral iron for heart failure from inception to October 2021. The effects were assessed with a meta-analysis using Revman 5.3 software. The trial sequential analysis was performed by TSA 0.9.5.10 beta software. The risk of bias of trials was evaluated via Risk of Bias tool. The evidence quality was assessed through GRADE tool. Results. Four studies including 582 patients with heart failure and iron deficiency were enrolled. The results indicated that oral iron treatment could improve left ventricular ejection fraction (LVEF, MD=1.52%, 95% CI: 0.69 to 2.36, P=0.0003) and serum ferritin (MD=1.64, 95% CI: 0.26 to 3.02, P=0.02). However, there was no between-group difference in the 6-minute walk distances (6MWT), N terminal pro B type natriuretic peptide (NT-proBNP) or hemoglobin level when compared with control group. Subgroup analyses revealed that the effects of oral iron on 6 MWT and serum ferritin could not be affected by duration and frequency of oral iron uptakes. In trial sequential analysis of LVEF and serum ferritin, the Z-curves crossed the traditional boundary and trail sequential monitoring boundary but did not reach the required information size. Conclusion. This analysis showed that oral iron could improve cardiac function measured by LVEF, and iron stores measured serum ferritin, but lack of effect on exercise capacity measured by 6 MWT, and iron stores measured by hemoglobin. Given the overall poor methodological quality and evidence quality, these findings should be treated cautiously.

Background Y-chromosomal short tandem repeats (Y-STRs) are widely used in paternity identification, pedigree investigation, and human population genetic history. Aim To investigate the Y-STR polymorphisms in a typical Miao population, and explore the genetic differentiation between the Miao population and reference groups. Subjects and methods We detected 36 Y-STRs genotyping in 455 unrelated Miao individuals from Guizhou province, and analysed genetic differentiation between the Miao population and 76 reference groups. Results A total of 369 alleles were obtained, and the allele frequencies ranged from 0.0022 to 0.9802. In addition, the haplotype diversity, random match probability, and discrimination capacity values were 0.99997, 0.0022, and 0.9934, respectively. Moreover, the genetic relationships between Guizhou Miao and 76 ethnic populations showed that the population stratification was almost consistent with geographic distribution and language-family. Conclusions The 36 Y-STR loci in this study have good polymorphism distributions in the Guizhou Miao population, and therefore would be a useful tool in forensic identification and male parentage testing and even pedigree investigation.

Background Chuanqing is an unrecognised ethnic group in Guizhou, southwest China. The genetic history of the Chuanqing people is hotly debated due to a lack of available genetic data. Aim To infer the genetic structure and population history of the Chuanqing people and genetic relationships of the Chuanqing with other East Asians. Subjects and methods We collected samples from 14 Chuanqing individuals from Guizhou and genotyped about 690,000 genome-wide single nucleotide polymorphisms (SNPs). We used Principal Component Analysis (PCA), ADMIXTURE analysis, and f statistics to infer the population genetic structure and admixture. Results Chuanqing people show a distinct genetic profile from indigenous Tai-Kadai and Tibeto-Burman speaking populations in southwest China, but they are genetically similar to southern Han Chinese, Miao, She and Tujia populations. The Han Chinese characteristic Y chromosomal lineages reach high frequencies in the Chuanqing. Conclusions The genetic formation of the Chuanqing people has been greatly influenced by Han Chinese related populations.

Abstract Background Doxorubicin is effective in a variety of solid and hematological malignancies. Unfortunately, clinical application of doxorubicin is limited due to a cumulative dose-dependent cardiotoxicity. Dihydrotanshinone I (DHT) is a natural product from Salvia miltiorrhiza Bunge with multiple anti-tumor activity and anti-inflammation effects. However, its anti-doxorubicin-induced cardiotoxicity (DIC) effect, either in vivo or in vitro, has not been elucidated yet. This study aims to explore the anti-inflammation effects of DHT against DIC, and to elucidate the potential regulatory mechanism. Methods Effects of DHT on DIC were assessed in zebrafish, C57BL/6 mice and H9C2 cardiomyocytes. Echocardiography, histological examination, flow cytometry, immunochemistry and immunofluorescence were utilized to evaluate cardio-protective effects and anti-inflammation effects. mTOR agonist and lentivirus vector carrying GFP-TFEB were applied to explore the regulatory signaling pathway. Results DHT improved cardiac function via inhibiting the activation of M1 macrophages and the excessive release of pro-inflammatory cytokines both in vivo and in vitro. The activation and nuclear localization of NF-κB were suppressed by DHT, and the effect was abolished by mTOR agonist with concomitant reduced expression of nuclear TFEB. Furthermore, reduced expression of nuclear TFEB is accompanied by up-regulated phosphorylation of IKKα/β and NF-κB, while TFEB overexpression reversed these changes. Intriguingly, DHT could upregulate nuclear expression of TFEB and reduce expressions of p-IKKα/β and p-NF-κB. Conclusions Our results demonstrated that DHT can be applied as a novel cardioprotective compound in the anti-inflammation management of DIC via mTOR-TFEB-NF-κB signaling pathway. The current study implicates TFEB-IKK-NF-κB signaling axis as a previously undescribed, druggable pathway for DIC.

Objective: To evaluate the effect of Qishen granule (QSG) on heart failure (HF) and the potential mechanisms involved in animal models. Methods: Studies of QSG in animals with HF were identified by searches of eight databases up to August 1, 2019. Two authors independently reviewed each study and the Collaborative Approach to Meta-analysis and Review of Animal Data from Experimental Studies 10-item checklist was used for quality assessment. The primary outcomes were indicators of left ventricular ejection fraction and/or left ventricular fractional shortening. The secondary outcome measures were ventricular structure, hemodynamics, myocardial injury-related indicators, and the mechanisms whereby QSG ameliorates HF. A meta-analysis was performed and all the data were analyzed using RevMan 5.3 software. Results: Thirteen studies containing a total of 240 animals met the criteria for the meta-analysis. The quality score of the studies ranged from three to six points. The meta-analysis showed a significant effect of QSG to improve cardiac function, inhibit ventricular remodeling, improve circulation, and attenuate myocardial injury. The possible mechanisms was identified to be suppression of the renin-angiotensin-aldosterone system, which has anti-fibrotic, anti-apoptotic, anti-inflammatory, and anti-oxidative effects in the myocardium, the prevention of calcium overload, and the promotion of myocardial energy metabolism. Conclusion: Our review shows that QSG has a cardioprotective effect in animal models of CHF. However, due to the relatively poor quality of the included studies and the differences between humans and animal models, the results should be interpreted with caution.

Abstract Background Qishen granules (QSG) has been applied to treat heart failure (HF) for decades. Our previous transcriptomics study has suggested that Qishen granules (QSG) could regulate the pathways of cardiac energy metabolism in HF, but the specific regulatory mechanism has not yet been clarified. This study was to investigate the potential mechanism of QSG in regulating myocardial fatty acid (FA) and glucose metabolism in a rat model of HF. Methods The model of HF was induced by left anterior descending coronary artery ligation. Cardiac structure and function were assessed by cine magnetic resonance imaging (MRI) and echocardiography. Level of glucose metabolism was non-invasively evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Blood lipid levels were determined by enzymatic analysis. The mitochondrial ultrastructure was observed with a transmission electron microscope. The critical proteins related to FA metabolism, glucose metabolism and mitochondrial function were measured by western blotting. The ANOVA followed by a Fisher’s LSD test was used for within-group comparisons. Results QSG ameliorated cardiac functions and attenuated myocardial remodeling in HF model. The levels of serum TC, TG and LDL-C were significantly reduced by QSG. The proteins mediating FA uptake, transportation into mitochondria and β-oxidation (FAT/CD36, CPT1A, ACADL, ACADM, ACAA2 and SCP2) as well as the upstreaming transcriptional regulators of FA metabolism (PPARα, RXRα, RXRβ and RXRγ) were up-regulated by QSG. As to glucose metabolism, QSG inhibited glycolytic activity by decreasing LDHA, while stimulated glucose oxidation by decreasing PDK4. Furthermore, QSG could facilitate tricarboxylic acid cycle, promote the transportation of ATP from mitochondria to cytoplasm and restore the mitochondrial function by increasing SUCLA2, CKMT2 and PGC-1α and decreasing UCP2 simultaneously. Conclusion QSG improved myocardial energy metabolism through increasing FA metabolism,inhibiting uncoupling of glycolysis from glucose oxidation.

Background: Miao people are an officially recognised ethnic group living in southwest China, but have seldom been studied genetically, especially with respect to mtDNA data. Aim: To investigate the sequences and haplogroups of the mtDNA control region in a typical Miao population, with the aim of providing a good start for the expansion of the East Asian mtDNA reference database for forensic DNA analysis. Subjects and methods: We analysed 203 Miao individuals, looking at mtDNA control region sequences. We calculated and illustrated the haplotype frequencies, haplogroup distribution and pairwise Fst values between the Miao and six other worldwide populations to explore genetic polymorphisms and population relationships. Results: We observed 121 haplotypes with corresponding frequencies ranging from 0.0049 to 0.0690 in the Miao population. All the samples were assigned to 71 different haplogroups. The haplotype diversity and the random match probability were estimated to be 0.9844 and 0.0204, respectively. The pairwise Fst values and associated p values among seven populations suggest that the Miao population has significant differences to the other six populations, and is relatively isolated compared with them. Conclusions: Our results suggest that frequency estimates for mtDNA haplotypes in Miao ethnic groups should be determined independently rather than being pooled with other populations.

Background: Guizhou province is located in southwest China with abundant genetic, linguistic and cultural diversity. The Bouyei is one of the 18 officially recognised minority groups in Guizhou, accounting for about 97% of the total Bouyei population in China. However, the genetic history and forensic characterisation of the Bouyei people is largely unknown due to a lack of genetic data. Aim: We aim to investigate genetic polymorphisms and forensic characterisation of the Guizhou Bouyei population, as well as the relationships between the Bouyei and other East Asian populations. Subjects and methods: We genotyped 19 X-STRs in 188 males and 165 females of Guizhou Bouyei using the AGCU X19 STR Kit. We estimated allele frequencies, forensic parameters and genetic distances between the Bouyei and other East Asian populations. We presented the genetic distances in a phylogenetic tree, an MDS plot and a PCA plot. Results: In Guizhou Bouyei individuals, we observed 216 alleles with corresponding frequencies ranging from 0.0019 to 0.6757. All of the six combined powers of PDm, PDf, MEC Krüger, MEC Kishida, MEC Desmarais and MEC Desmarais in allele diversity and haplotype diversity are larger than 0.99999995. We found genetic affinities among the Bouyei people and their geographical neighbouring populations in Guizhou, such as the Sui, Miao and Han. Conclusions: The highly polymorphic and informative forensic parameters of the 19 X-STRs in Bouyei people show the powerful potential of those markers in forensic identification and parentage tests. The genetic relationships of the Bouyei with other East Asian populations correspond well with geographic affiliations as well as linguistic classifications.

As a major part of the modern Trans-Eurasian or Altaic language family, most of the Mongolic and Tungusic languages were mainly spoken in northern China, Mongolia, and southern Siberia, but some were also found in southern China. Previous genetic surveys only focused on the dissection of genetic structure of northern Altaic-speaking populations; however, the ancestral origin and genomic diversification of Mongolic and Tungusic–speaking populations from southwestern East Asia remain poorly understood because of the paucity of high-density sampling and genome-wide data. Here, we generated genome-wide data at nearly 700,000 single-nucleotide polymorphisms (SNPs) in 26 Mongolians and 55 Manchus collected from Guizhou province in southwestern China. We applied principal component analysis (PCA), ADMIXTURE, f statistics, qpWave/qpAdm analysis, qpGraph, TreeMix, Fst, and ALDER to infer the fine-scale population genetic structure and admixture history. We found significant genetic differentiation between northern and southern Mongolic and Tungusic speakers, as one specific genetic cline of Manchu and Mongolian was identified in Guizhou province. Further results from ADMIXTURE and f statistics showed that the studied Guizhou Mongolians and Manchus had a strong genetic affinity with southern East Asians, especially for inland southern East Asians. The qpAdm-based estimates of ancestry admixture proportion demonstrated that Guizhou Mongolians and Manchus people could be modeled as the admixtures of one northern ancestry related to northern Tungusic/Mongolic speakers or Yellow River farmers and one southern ancestry associated with Austronesian, Tai-Kadai, and Austroasiatic speakers. The qpGraph-based phylogeny and neighbor-joining tree further confirmed that Guizhou Manchus and Mongolians derived approximately half of the ancestry from their northern ancestors and the other half from southern Indigenous East Asians. The estimated admixture time ranged from 600 to 1,000 years ago, which further confirmed the admixture events were mediated via the Mongolians Empire expansion during the formation of the Yuan dynasty.

Liposome modification by targeting ligands has been used to mediate specific interactions and drug delivery to target cells. In this study, a new peptide ligand, CP7, was found to be able to effectively bind to FGFR1 through reverse molecular docking and could cooperate with VEGFR3 to achieve targeting of A549 cells. CP7 was modified on the surface of the liposome to construct a targeted and safe nanovehicle for the delivery of a therapeutic gene, Mcl-1 siRNA. Due to the specific binding between CP7 and A549 cells, siRNA-loaded liposome-PEG-CP7 showed increased cellular uptake in vitro, resulting in significant apoptosis of tumor cells through silencing of the Mcl-1 gene, which is associated with apoptosis and angiogenesis. This gene delivery system also showed significantly better antitumor activity in tumor-bearing mice in vivo. All of these suggested that siRNA-loaded liposome-PEG-CP7 could be a promising gene drug delivery system with good bioavailability and minimal side effects for treatment.

Retinoid X receptors (RXRs) are members of ligand-dependent transcription factors whose effects on a diversity of cellular processes, including cellular proliferation, the immune response, and lipid and glucose metabolism. Knock out of RXRα causes a hypoplasia of the myocardium which is lethal during fetal life. In addition, the heart maintains a well-orchestrated balances in utilizing fatty acids (FAs) and other substrates to meet the high energy requirements. As the master transcriptional regulators of lipid metabolism, RXRs become particularly important for the energy needs of the heart. Accumulating evidence suggested that RXRs may exert direct beneficial effects in the heart both through heterodimerization with other nuclear receptors (NRs) and homodimerization, thus standing as suitable targets for treating in cardiovascular diseases. Although compounds that target RXRs are promising drugs, their use is limited by toxicity. A better understanding of the structural biology of RXRs in cardiovascular disease should enable the rational design of more selective nuclear receptor modulators to overcome these problems. Here, this review summarizes a brief overview of RXRs structure and versatility of RXR action in the control of cardiovascular diseases. And we also discussed the therapeutic potential of RXR ligand.

Abstract Dendritic cells (DCs) based cancer immunotherapy is largely dependent on adequate antigen delivery and efficient induction of DCs maturation to produce sufficient antigen presentation and ultimately lead to substantial activation of tumor‐specific CD8+ T cells. Carbon nanotubes (CNTs) have attracted great attention in biomedicine because of their unique physicochemical properties. In order to effectively deliver tumor antigens to DCs and trigger a strong anti‐tumor immune response, herein, a specific DCs target delivery system was assembled by using multi‐walled carbon nanotubes modified with mannose which can specifically bind to the mannose receptor on DCs membrane. Ovalbumin (OVA) as a model antigen, could be adsorbed on the surface of mannose modified multi‐walled carbon nanotubes (Man‐MWCNTs) with a large drug loading content. This nanotube‐antigen complex showed low cytotoxicity to DCs and was efficiently engulfed by DCs to induce DCs maturation and cytokine release in vitro, indicating that it could be a potent antigen‐adjuvant nanovector of efficient antigen delivery for therapeutic purpose.

Background: Guizhou Sui people are an officially recognised ethnic group living in southwest China, but have seldom been studied genetically. Aim: To investigate the polymorphisms of 19 X-chromosome STR loci in a typical Sui population and enrich the East Asian X-STR reference database for forensic DNA analysis. Subjects and methods: A total of 400 Sui individuals (195 males and 205 females) were genotyped at 19 X-STR loci using the AGCU X19 STR Kit. The allele frequencies and forensic parameters were calculated and illustrated and the data of Guizhou Sui were merged with 18 other nationwide populations to explore genetic polymorphisms and population relationships. Results: A total of 215 alleles were observed with corresponding frequencies ranging from 0.0017–0.6512 in Sui using male and female pooled allele frequencies. Large values were observed, at least 0.9999999933, in combined powers of discrimination of Sui males and females, as well as the four mean paternity exclusion chances (MECs). The phylogenetic analysis among 19 populations showed that Sui have close genetic affinities with other Tai-Kadai populations, as well as the Sinitic populations living in southern China. Conclusions: The AGCU X-19 STRs are highly polymorphic and informative in Guizhou Sui people. The genetic relationships between Sui and other populations in China are generally consistent with the language classification and geographical distance.

Summary: Supported Pt catalyst has been intensively investigated for formaldehyde elimination owing to its superior reactivity at room temperature (RT). However, the high Pt content is challenging because of its high cost. Herein, we report PbO-supported Pt catalysts with only 0.1 wt % Pt, which can achieve complete conversion of formaldehyde and reliable stability at RT under demanding conditions. Both experiments and simulations demonstrate that PbO interacts strongly with the Pt species, resulting in tight Pb-O-Pt bonding at the metal/support interface and concomitant activation of the surface lattice oxygen of the support. Moreover, PbO exhibits an extremely high capacity of formaldehyde capture through methylene glycol chemisorption rather than the common hydroxyl-associated adsorption, presenting a different reaction mechanism because the active surface lattice oxygen in the vicinity of Pt species offers improved reactivity. This work provides a valuable example for the design of an efficient catalyst for formaldehyde and potentially oxidation of other carbohydrates. : Chemistry; Catalysis; Chemical Substance Subject Areas: Chemistry, Catalysis, Chemical Substance

Abstract Background Male‐specifically inherited Y‐STRs have been widely used in population genetics and forensic investigations. Methods We genotyped and analyzed Y chromosome haplotypes of 408 unrelated Tibeto‐Burman‐speaking Yi male individuals from Guizhou using Goldeneye® Y‐PLUS kit. Population comparisons between the Guizhou Yi and 67 reference groups were performed via the AMOVA, MDS, and phylogenetic relationship reconstruction. Results A total of 389 alleles and 396 haplotypes could be detected, and the allelic frequencies ranged from 0.0025 to 0.9875. The haplotype diversity, random match probability, and discrimination capacity values were 0.9999, 0.0026, and 0.9900, respectively. The gene diversity (GD) of 36 Y‐STR loci in the studied group ranged from 0.0248 (DYS645) to 0.9601 (DYS385a/b). Our newly genotyped Yi samples show a close affinity with other Tibeto‐Burman speaking groups in China and Southeast Asia. Conclusions The population stratification was almost consistent with the geographic distribution and language‐family, both among Chinese and worldwide ethnic groups. Our data may provide useful information for paternal lineage in the forensic application and population genetics, as well as evidence for archaeological and historical research.

The origin and diversification of Muslim Hui people in China via demic or simple cultural diffusion is a long-going debate. We here generated genome-wide data at nearly 700,000 single nucleotide polymorphisms (SNPs) from 45 Hui and 14 Han Chinese individuals collected from Guizhou province in southwest China. We applied principal component analysis (PCA), ADMIXTURE, f-statistics, qpWave, and qpAdm analysis to infer the population genetic structure and admixture history. Our results revealed the Guizhou Hui people have a limited amount of West Eurasian related ancestry at a proportion of 6%, but show massive genetic assimilation with indigenous southern Han Chinese and Tibetan or Tungusic/Mongolic related northern East Asians. We also detected a high frequency of North Asia or Central Asia related paternal Y-chromosome but not maternal mtDNA lineages in Guizhou Hui. Our observation supports the cultural diffusion has played a vital role in the formation of Hui people and the migration of Hui people to southwest China was probably a sex-biased male-driven process.

Guizhou province in southwest China has abundant genetic and cultural diversities, but the forensic features and genetic structure of Guizhou populations remain poorly understood due to the sparse sampling of present-day populations. Here, we present 30 insertion/deletion polymorphisms (InDels) data of 591 human individuals collected from four populations, Dong, Yi, Han, and Chuanqing residing in Guizhou. We calculated the forensic parameters of 30 InDel loci and found that this panel meets the efficiency of forensic personal identification based on the high combined power of discrimination, but it could only be used as a complementary tool in the parentage testing because of the lower combined probability of exclusion values. The studied populations are genetically closer related to geographically adjacent or linguistically related populations in southern China, such as the Tai-Kadai and Hmong-Mien speaking groups. The unrecognized ethnic Chuanqing people show an additional genetic affinity with Han Chinese, highlighting the role of possible military immigrations in their origin.

AimHeart failure (HF) post-acute myocardial infarction (AMI) leads to a large number of hospitalizations and deaths worldwide. Danqi pill (DQP) is included in the 2015 national pharmacopoeia and widely applied in the treatment of HF in clinics in China. We examined whether DQP acted on glucose metabolism to protect against HF post-AMI via hypoxia inducible factor-1 alpha (HIF-1α)/peroxisome proliferator-activated receptor α co-activator (PGC-1α) pathway.Methods and ResultsIn this study, left anterior descending (LAD) artery ligation induced HF post-AMI rats and oxygen-glucose deprivation-reperfusion (OGD/R)-induced H9C2 cell model were structured to explore the efficacy and mechanism of DQP. Here we showed that DQP protected the heart against ischemic damage as evidenced by improved cardiac functions and attenuated inflammatory infiltration. The expressions of critical proteins involved in glucose intake and transportation such as GLUT4 and PKM2 were up-regulated, while negative regulatory proteins involved in oxidative phosphorylation were attenuated in the treatment of DQP. Moreover, DQP up-regulated NRF1 and TFAM, promoted mitochondrial biogenesis and increased myocardial adenosine triphosphate (ATP) level. The protection effects of DQP were significantly compromised by HIF-1α siRNA, suggesting that HIF-1α signaling pathway was the potential target of DQP on HF post-AMI.ConclusionsDQP exhibits the efficacy to improve myocardial glucose metabolism, mitochondrial oxidative phosphorylation and biogenesis by regulating HIF-1α/PGC-1α signaling pathway in HF post-AMI rats.