A 3,000-year-old, basal S. enterica lineage from Bronze Age Xinjiang suggests spread along the Proto-Silk Road.

Salmonella enterica (S. enterica) has infected humans for a long time, but its evolutionary history and geographic spread across Eurasia is still poorly understood. Here, we screened for pathogen DNA in 14 ancient individuals from the Bronze Age Quanergou cemetery (XBQ), Xinjiang, China. In 6 individuals we detected S. enterica. We reconstructed S. enterica genomes from those individuals, which form a previously undetected phylogenetic branch basal to Paratyphi C, Typhisuis and Choleraesuis-the so-called Para C lineage. Based on pseudogene frequency, our analysis suggests that the ancient S. enterica strains were not host adapted. One genome, however, harbors the Salmonella pathogenicity island 7 (SPI-7), which is thought to be involved in (para)typhoid disease in humans. This offers first evidence that SPI-7 was acquired prior to the emergence of human-adapted Paratyphi C around 1,000 years ago. Altogether, our results show that Salmonella enterica infected humans in Eastern Eurasia at least 3,000 years ago, and provide the first ancient DNA evidence for the spread of a pathogen along the Proto-Silk Road.

Phylogenetic and population structural inference from genomic ancestry maintained in present-day common wheat Chinese landraces.

Hexaploid common wheat is one of the most important food crops worldwide. Common wheat domestication began in the Fertile Crescent of the Near East approximately 10 000 years ago and then spread west into Europe and eastward into East Asia and China. However, the possible spreading route into and within China is still unclear. In this study, we successfully extracted DNA from single ancient wheat seeds and sequenced the whole genome of seven ancient samples from Xiaohe and Gumugou cemeteries in Xinjiang, China. Genomic inference and morphological observation confirmed their identity as hexaploid common wheat grown in prehistoric China at least 3200 years before present (BP). Phylogenetic and admixture analyses with RNA-seq data of modern hexaploid wheat cultivars from both China and Western countries demonstrated a close kinship of the ancient wheat to extant common wheat landraces in southwestern China. The highly similar allelic frequencies in modern landraces of the Qinghai-Tibetan plateau with the ancient wheat support the previously suggested southwestern spreading route into highland China. A subsequent dispersal route from the Qinghai-Tibetan plateau margins to the Yangtze valley was proposed in this study. Furthermore, the common wheat populations grown in the Middle and Lower Yangtze valley wheat zones were also proposed to be established by population admixture with the wheat grown in the Upper Yangtze valley. Our study reports ancient common wheat sequences at a genome-wide scale, providing important information on the origin, dispersal, and genetic improvement under cultivation of present-day wheat landraces grown in China.

Mitochondrial Genome of an 8,400-Year-Old Individual from Northern China Reveals a Novel Subclade Under C5d.

Ancient DNA studies have always refreshed our understanding of the human past that cannot be tracked by modern DNA alone. Until recently, ancient mitochondrial genomic studies in East Asia were still very limited. Here, we retrieved the whole mitochondrial genome of an 8,400-year-old individual from Inner Mongolia, China. Phylogenetic analyses show that the individual belongs to a previously undescribed clade under haplogroup C5d that most probably originated in northern Asia and may have a very low frequency in extant populations that have not yet been sampled. We further characterized the demographic history of mitochondrial haplogroups C5 and C5d and found that C5 experienced a sharp increase in population size starting around 4,000 years before present, the time when intensive millet farming was developed by populations who are associated with the Lower Xiajiadian culture and was widely adopted in northern China. We caution that people related to haplogroup C5 may have added this farming technology to their original way of life and that the various forms of subsistence may have provided abundant food sources and further contributed to the increase in population size.

The Y-chromosome haplogroup C3*-F3918, likely attributed to the Mongol Empire, can be traced to a 2500-year-old nomadic group.

The Mongol Empire had a significant role in shaping the landscape of modern populations. Many populations living in Eurasia may have been the product of population mixture between ancient Mongolians and natives following the expansion of Mongol Empire. Geneticists have found that most of these populations carried the Y-haplogroup C3* (C-M217). To trace the history of haplogroup (Hg) C3* and to further understand the origin and development of Mongolians, ancient human remains from the Jinggouzi, Chenwugou and Gangga archaeological sites, which belonged to the Donghu, Xianbei and Shiwei, respectively, were analysed. Our results show that nine of the eleven males of the Gangga site, two of the eight males of Chengwugou site and all of the twelve males of Jinggouzi site were found to have mutations at M130 (Hg C), M217 (Hg C3), L1373 (C2b, ISOGG2015), with the absence of mutations at M93 (Hg C3a), P39 (Hg C3b), M48 (Hg C3c), M407 (Hg C3d) and P62 (Hg C3f). These samples were attributed to the Y-chromosome Hg C3* (Hg C2b, ISOGG2015), and most of them were further typed as Hg C2b1a based on the mutation at F3918. Finally, we inferred that the Y-chromosome Hg C3*-F3918 can trace its origins to the Donghu ancient nomadic group.

Genetic diversity of two Neolithic populations provides evidence of farming expansions in North China.

The West Liao River Valley and the Yellow River Valley are recognized Neolithic farming centers in North China. The population dynamics between these two centers have significantly contributed to the present-day genetic patterns and the agricultural advances of North China. To understand the Neolithic farming expansions between the West Liao River Valley and the Yellow River Valley, we analyzed mitochondrial DNA (mtDNA) and the Y chromosome of 48 individuals from two archeological sites, Jiangjialiang (>3000 BC) and Sanguan (~1500 BC). These two sites are situated between the two farming centers and experienced a subsistence shift from hunting to farming. We did not find a significant difference in the mtDNA, but their genetic variations in the Y chromosome were different. Individuals from the Jiangjialiang belonged to two Y haplogroups, N1 (not N1a or N1c) and N1c. The individuals from the Sanguan are Y haplogroup O3. Two stages of migration are supported. Populations from the West Liao River Valley spread south at about 3000 BC, and a second northward expansion from the Yellow River Valley occurred later (3000-1500 BC).

Bufadienolides and polyhydroxycholestane derivatives from Bufo bufo gargarizans.

A new polyhydroxycholestane sulfate ester, 3α,12ß,25,26-tetrahydroxy-7-oxo-5ß-cholestane 26-O-sulfate (1), was isolated from dried skin of Bufo bufo gargarizans Cantor and its structure was elucidated on the basis of extensive 1D and 2D NMR as well as HR-ESI-MS analysis. A comparison of steroidal metabolite profiles, based on HPLC and LC-MS analyses, indicates that the chemical compositions of the various parts of toads, such as venom, skin and stratum corneum, are significantly different.

Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload.

Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 µM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca(2+)) extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP) expression and cell branching. Ca(2+) response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca(2+) concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.

[Optimization of sperm alkaline single-cell gel electrophoresis].

OBJECTIVE: To investigate the main factors that influence the results of sperm alkaline single-cell gel electrophoresis (SCGE), optimize the conditions, and standardize its procedures. METHODS: Using alkaline SCGE, we detected the DNA fragments of sperm treated with different concentrations of H2O2 and determined the influences of the number of agarose gel layers, pH during DNA unwinding and electrophoresis, the time of DNA unwinding and electrophoresis, and cumulative sperm number on the results of sperm alkaline SCGE. Then we optimized the procedures, analyzed the repeatability of the optimized method, and examined 40 semen samples using the method. RESULTS: Three agarose gel layers could reduce the background. The optimal pH during DNA unwinding and electrophoresis was 10, and the best times for DNA unwinding and electrophoresis were 40 min and 30 min, respectively. Fifty sperm were adequate to ensure the reliability of the results. Based on the percentage of tail DNA, the intra- and inter-assay repeatabilities of the optimized sperm alkaline SCGE were 3.12% and 7.13%, and by the DNA damage score, they were 2.38% and 6.09%, respectively. Sperm DNA fragments were significantly increased in the infertile patients with oligoasthenoteratozoospermia as compared with healthy fertile males (P <0.05). CONCLUSION: The optimized sperm alkaline SCGE, highly repeatable and easy to be standardized, can be applied to the clinical detection of sperm DNA fragmentation in infertile men.

STCA-SNN: self-attention-based temporal-channel joint attention for spiking neural networks.

Spiking Neural Networks (SNNs) have shown great promise in processing spatio-temporal information compared to Artificial Neural Networks (ANNs). However, there remains a performance gap between SNNs and ANNs, which impedes the practical application of SNNs. With intrinsic event-triggered property and temporal dynamics, SNNs have the potential to effectively extract spatio-temporal features from event streams. To leverage the temporal potential of SNNs, we propose a self-attention-based temporal-channel joint attention SNN (STCA-SNN) with end-to-end training, which infers attention weights along both temporal and channel dimensions concurrently. It models global temporal and channel information correlations with self-attention, enabling the network to learn 'what' and 'when' to attend simultaneously. Our experimental results show that STCA-SNNs achieve better performance on N-MNIST (99.67%), CIFAR10-DVS (81.6%), and N-Caltech 101 (80.88%) compared with the state-of-the-art SNNs. Meanwhile, our ablation study demonstrates that STCA-SNNs improve the accuracy of event stream classification tasks.

Acquired aplastic anaemia after SARS-CoV-2 infection in China: a case report.

Since the coronavirus disease 2019 (COVID-19) pandemic began, several research groups in different countries have described cases of aplastic anaemia (AA) after COVID-19 or COVID-19 vaccination. Here, we present the case of a patient with new-onset AA in Changsha, China, that was presumably associated with preceding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted an epidemiological assessment of the incidence rate of blood system diseases from July 1, 2022, to May 31, 2023, in the haematology department of the Second Xiangya Hospital of Central South University and Hunan Children's Hospital. The detection rates of AA and leukaemia in the first two months after the epidemic outbreak were higher than those before and during the outbreak. However, only the difference in the detection rate of leukaemia was statistically significant.

[Chemical constituents from Bufonis periostracum and their antitumor activity in vitro].

Eight compounds were isolated from Bufonis periostracum by repeated column chromatography on silica gel, ODS and Sephadex LH-20 and their structures were characterized as palmitatic acid cholesteryl ester (1), cholesterol (2), 5alpha, 8alpha-epidioxycholesta-6-en-3beta-ol (3), cholest-5-en-3beta, 7beta-diol (4), cholest-7-en-3beta, 5alpha, 6beta-triol (5), 3-octaddecyloxy-1, 2-propanediol (6), isisamide (7) and bufothionine (8) on the base of spectral analysis. Compounds 1-8 were isolated from Bufonis periostracum for the first time and compounds 3, 5, 6, 7 were obtained from Bufo bufo gargarizans and Bufo genus for the first time. The bioassays showed all tested samples displayed no antitumor activity against the cell lines such as A549, BeL 7402, HGC-27 and HL-60, except the control compound bufalin.

Ancient genomes from northern China suggest links between subsistence changes and human migration.

Northern China harbored the world's earliest complex societies based on millet farming, in two major centers in the Yellow (YR) and West Liao (WLR) River basins. Until now, their genetic histories have remained largely unknown. Here we present 55 ancient genomes dating to 7500-1700 BP from the YR, WLR, and Amur River (AR) regions. Contrary to the genetic stability in the AR, the YR and WLR genetic profiles substantially changed over time. The YR populations show a monotonic increase over time in their genetic affinity with present-day southern Chinese and Southeast Asians. In the WLR, intensification of farming in the Late Neolithic is correlated with increased YR affinity while the inclusion of a pastoral economy in the Bronze Age was correlated with increased AR affinity. Our results suggest a link between changes in subsistence strategy and human migration, and fuel the debate about archaeolinguistic signatures of past human migration.

Ancient Genomes Reveal Yamnaya-Related Ancestry and a Potential Source of Indo-European Speakers in Iron Age Tianshan.

Recent studies of early Bronze Age human genomes revealed a massive population expansion by individuals-related to the Yamnaya culture, from the Pontic Caspian steppe into Western and Eastern Eurasia, likely accompanied by the spread of Indo-European languages [1-5]. The south eastern extent of this migration is currently not known. Modern-day human populations from the Xinjiang region in northwestern China show a complex population history, with genetic links to both Eastern and Western Eurasia [6-10]. However, due to the lack of ancient genomic data, it remains unclear which source populations contributed to the Xinjiang population and what was the timing and the number of admixture events. Here, we report the first genome-wide data of 10 ancient individuals from northeastern Xinjiang. They are dated to around 2,200 years ago and were found at the Iron Age Shirenzigou site. We find them to be already genetically admixed between Eastern and Western Eurasians. We also find that the majority of the East Eurasian ancestry in the Shirenzigou individuals is-related to northeastern Asian populations, while the West Eurasian ancestry is best presented by ∼20% to 80% Yamnaya-like ancestry. Our data thus suggest a Western Eurasian steppe origin for at least part of the ancient Xinjiang population. Our findings furthermore support a Yamnaya-related origin for the now extinct Tocharian languages in the Tarim Basin, in southern Xinjiang.

Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway.

Aspirin, one of the most commonly used anti-inflammatory drugs, has been recently reported to display multiple effects in the central nervous system (CNS), including neuroprotection and upregulation of ciliary neurotrophic factor (CNTF) expression in astrocytes. Although it was most recently reported that aspirin could promote the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) after white matter lesion, the underlying mechanisms remain unclear. To dissect the effects of aspirin on oligodendroglial development and explore possible mechanisms, we here demonstrated the following: (i) in vitro treatment of aspirin on OPC cultures significantly increased the number of differentiated oligodendrocytes (OLs) but had no effect on the number of proliferative OPCs, indicating that aspirin can promote OPC differentiation but not proliferation; (ii) in vivo treatment of aspirin on neonatal (P3) rats for 4 days led to a nearly twofold increase in the expression of myelin basic protein (MBP), devoid of change in OPC proliferaion, in the corpus callosum (CC); (iii) finally, aspirin treatment increased the phosphorylation level of ß-catenin and counteracted Wnt signaling pathway synergist QS11-induced suppression on OPC differentiation. Together, our data show that aspirin can directly target oligodendroglial lineage cells and promote their differentiation through inhibition of Wnt/ß-catenin signaling pathway. These findings suggest that aspirin may be a novel candidate for the treatment of demyelinating diseases.

Optimized volume models of earthquake-triggered landslides.

In this study, we proposed three optimized models for calculating the total volume of landslides triggered by the 2008 Wenchuan, China Mw 7.9 earthquake. First, we calculated the volume of each deposit of 1,415 landslides triggered by the quake based on pre- and post-quake DEMs in 20 m resolution. The samples were used to fit the conventional landslide "volume-area" power law relationship and the 3 optimized models we proposed, respectively. Two data fitting methods, i.e. log-transformed-based linear and original data-based nonlinear least square, were employed to the 4 models. Results show that original data-based nonlinear least square combining with an optimized model considering length, width, height, lithology, slope, peak ground acceleration, and slope aspect shows the best performance. This model was subsequently applied to the database of landslides triggered by the quake except for two largest ones with known volumes. It indicates that the total volume of the 196,007 landslides is about 1.2 × 10(10) m(3) in deposit materials and 1 × 10(10) m(3) in source areas, respectively. The result from the relationship of quake magnitude and entire landslide volume related to individual earthquake is much less than that from this study, which reminds us the necessity to update the power-law relationship.

[Screening for congenital hypothyroidism in 106 224 neonates in Hunan Province].

OBJECTIVE: Diagnosing congenital hypothyroidism (CH) early was studied in this paper through neonatal screening to prevent children's mental retardation. METHODS: The first step is mensurating the concentration of thyroid stimulating hormone (TSH) with the method of time-distinguished fluorometry immunoassay. If the result is positive, then it is necessary to mensurate the serum TSH, free triiodothyronine (FT3),free thyroxin (FT4) with chemiluminescence immunoassay (CLIA) and execute clinical diagnosis. RESULTS: There were 68 confirmed congenital hypothyroidism patients among the 106,224 samples from Apr.1997 to Dec.2003 in Hunan province. The positive rate was 1/1,562, which was obviously higher than the national average value (1/3,009). CONCLUSION: First, neonatal screening is the key to prevent mental retardation through early diagnosing and treating CH. Second, the probability of suffering CH is high in Hunan province. Third, the positive rate is relative to the development of science and technology, while the accumulated rate is better to reflect the real incidence of the disease. Fourth, selecting proper critical value will help to prevent missing screening.

Quetiapine Inhibits Microglial Activation by Neutralizing Abnormal STIM1-Mediated Intercellular Calcium Homeostasis and Promotes Myelin Repair in a Cuprizone-Induced Mouse Model of Demyelination.

Microglial activation has been considered as a crucial process in the pathogenesis of neuroinflammation and psychiatric disorders. Several antipsychotic drugs (APDs) have been shown to display inhibitory effects on microglial activation in vitro, possibly through the suppression of elevated intracellular calcium (Ca(2+)) concentration. However, the exact underlying mechanisms still remain elusive. In this study, we aimed to investigate the inhibitory effects of quetiapine (Que), an atypical APD, on microglial activation. We utilized a chronic cuprizone (CPZ)-induced demyelination mouse model to determine the direct effect of Que on microglial activation. Our results showed that treatment with Que significantly reduced recruitment and activation of microglia/macrophage in the lesion of corpus callosum and promoted remyelination after CPZ withdrawal. Our in vitro studies also confirmed the direct effect of Que on lipopolysaccharide (LPS)-induced activation of microglial N9 cells, whereby Que significantly inhibited the release of nitric oxide (NO) and tumor necrosis factor α (TNF-α). Moreover, we demonstrated that pretreatment with Que, neutralized the up-regulation of STIM1 induced by LPS and declined both LPS and thapsigargin (Tg)-induced store-operated Ca(2+) entry (SOCE). Finally, we found that pretreatment with Que significantly reduced the translocation of nuclear factor kappa B (NF-κB) p65 subunit from cytoplasm to nuclei in LPS-activated primary microglial cells. Overall, our data suggested that Que may inhibit microglial activation by neutralization of the LPS-induced abnormal STIM1-mediated intercellular calcium homeostasis.

Overexpression of CDK5 in neural stem cells facilitates maturation of embryonic neurocytes derived from rats in vitro.

To further understand the effects of cyclin-dependent kinase 5 (CDK5) on the differentiation of neural stem cells, which were cultured and transfected with CDK5-EGFP recombinant overexpression vector (OV-CDK5 Group), successful transfection was confirmed by RT-PCR and Western blot. Our results showed that the CDK5 mRNA expression significantly increased in 6 h after transfection. Increase in the levels of the CDK5 protein expression was observed in 72 h, compared with Empty Vector Control Group (EV-CTL Group) (P < 0.01). Furthermore, in OV-CDK5 Group, the percentage of S-phase cells was significantly higher than in EV-CTL Group (P < 0.01). Differentiated cells were showed with short processes in 24 h and with obviously enlarged cell body, and extended cellular processes in 72 h, in comparison to those in EV-CTL Group (P < 0.01). In 72 h under treatment with 10 µmol/L all-trans retinoic acid (ATRA), in OV-CDK5 Group, processes of the GFP-positive cells were reduced slightly and little GFP-positive debris was found. However, in the EV-CTL Group, processes of the GFP-positive cells were obviously shortened and deformed and much GFP-positive debris were found. Moreover, the percentage of G0/G1-phase cells was lesser, while the percentage of S-phase cells was higher than that in EV-CTL Group (P < 0.01, P < 0.01). In conclusion, our experiment suggested that CDK5 might promote proliferation and differentiation of neural stem cells, lengthen the processes of differentiated neurocytes, and accelerate morphological maturation of such cells. Furthermore, CDK5 might antagonize ATRA-induced inhibition against proliferation and differentiation in differentiated neurocytes.

Comparison of toad venoms from different Bufo species by HPLC and LC-DAD-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Toad venom, called Chansu in China, has been widely used for the treatment of heart failure, sores, pains, and various cancers for a long time in clinic. AIM OF THE STUDY: The aim of the study is to investigate the chemical differences among a variety of toad venoms from different geographic locations and related Bufo species. MATERIALS AND METHODS: Ten batches of commercial toad venom collected from different regions in China, one batch of fresh toad venom obtained from Bufo bufo gargarizans, and six batches of related Bufo species were analyzed by HPLC and LC-DAD-MS/MS. Individual components were identified by comparison of retention times, UV spectra, and mass spectra with authentic compounds, standard addition, as well as summarized MS fragmentation rules. Based on the profile of identified constituents and the content of cinobufagin and resibufogenin, the chemical differences observed among different samples are discussed. RESULTS: Overall, 43 compounds were identified in the methanolic extracts of the different samples of toad venom. Besides of suberoyl arginine, several free bufadienolides, bufadienolide sulfates, and suberoyl esters of bufadienolides were found. The total amounts of cinobufagin and resibufogenin, which are the only two control markers according to the current Chinese Pharmacopoeia, varied widely from 0.7% to 10.9% in the commercial Chansu samples collected in the different locations in China. Low levels of resibufogenin, but no cinobufagin was observed in the samples from Bufo melanosticus and Bufo marinus, and even neither of both compounds was found in the sample from Bufo viridis. CONCLUSIONS: The chemical profiles of the different commercial and collected toad venoms from related Bufo species differed significantly, not only in the absolute and relative contents, but also in the number and type of the constituents. The main reason for this variation are species-specific differences, but additional factors, such as the harvest and post-harvest processing, and adaption to environmental factors in different geographic locations, also seem to contribute.