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Abstract Background Ancient Chang’an in the Tang Dynasty (618–907 AD) was one of the world’s largest and most populated cities and acted as the eastern end of the world-famous Silk Road. However, little is known about the genetics of Chang’an people and whether the Western Regions-related gene flows have been prevalent in this cosmopolitan city. Results Here, we present seven genomes from Xingfulindai (XFLD) sites dating to the Tang Dynasty in Chang’an. We observed that four of seven XFLD individuals (XFLD_1) were genetically homogenous with the Late Neolithic Wadian, Pingliangtai, and Haojiatai populations from the middle reaches of the Yellow River Basin (YR_LN), with no genetic influence from the Western Eurasian or other non-Yellow River-related lineages. The remaining three XFLD individuals were a mixture of YR_LN-related ancestry and ~ 3–15% Western Eurasian-related ancestry. Mixtures of XFLD_1 and Western Eurasian-related ancestry drove the main gradient of genetic variation in northern and central Shaanxi Province today. Conclusions Our study underlined the widespread distribution of the YR_LN-related ancestry alongside the Silk Road within the territory of China during the historical era and provided direct evidence of trans-Eurasian communication in Chang’an from a genetic perspective.

Abstract Background Observational epidemiological studies suggested that immunological dysregulation and inflammation play a significant role in the placental and renal dysfunction that leads to maternal hypertension. The immunophenotypes' possible causalities with hypertensive disease of pregnancy remain ambiguous. We performed two-sample Mendelian randomization (MR) analyses to comprehensively investigate the causal effect of immunophenotypes on hypertensive disorder of pregnancy (HDP). Methods The large-scale genome-wide association studies (GWASs) data on immunological traits was taken from public catalog for 731 immunophenotypes. The summarized GWAS data in 4 types of HDP were retrieved from FinnGen database, including 811,605 Finnish individuals. The primary analysis was the inverse variance weighted (IVW) method, supplemented by conducting sensitivity analysis. To confirm whether cardiovascular proteins mediated the causal effect of immune cells on HDP, we additionally executed a mediation MR study. Results After looking into genetically predicted immunophenotype biomarkers, we discovered 14 highly correlative immunophenotypes and 104 suggestive possible factors. The IVW analysis indicated that HLA DR on myeloid DC, HLA DR on plasmacytoid DC, and HLA DR on DC had a significant association with pre-eclampsia/eclampsia (PE), whereas CD4+ CD8dim AC and CD4+ CD8dim % leukocyte were protective against gestational hypertension (GH). All of HDP in our study had no statistically significant impact on immune cells, according to reverse MR analysis. The mediating role of LOX-1between HLA DR on plasmacytoid DC and chronic hypertension prior to pregnancy was validated. Conclusion This study showed that many immunophenotypes are implicated in HDP. Furthermore, the level of LOX-1 mediated the pathophysiology relationship between HLA DR on plasmacytoid dendritic cells and chronic hypertension prior to pregnancy.

ObjectiveTo investigate potential causative associations between immunophenotype traits and cervical cancer by using two-sample Mendelian randomization (MR) analysis. MethodsThe genetic instrumental variables (IVs) of 731 immunophenotypes of peripheral blood were obtained from the GWAS Catalog database. The GWAS summary data of cervical cancer were obtained from FinnGen database. The inverse-variance weighted (IVW), weighted mode, weighted median, and MR Egger methods were used for evaluations. The sensitivity analysis and reverse Mendelian randomization analysis were conducted to eliminate bias and reverse causality. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and cervical cancer. ResultsA total of 71 immune cell subtypes associated with cervical cancer were identified, of which 31 had a strong association. The majority of the B cell panel was protective factors for cervical cancer. B-cell activating factor receptor (BAFF-R) was the most frequently expressed molecule in this analysis. It is expressed on several B cell subtypes. The CD20 on IgD+ CD38+ B cell (OR=1.887, 95%CI: 1.078-3.306, P=0.026) is the risk factor for cervical cancer. In cDC panels, the CD123 expression on plasmacytoid dendritic cell (OR=2.48, 95%CI: 1.229-5.003, P=0.011), CD123 expression on CD62L+ plasmacytoid dendritic cell (OR=2.5, 95%CI: 1.231-5.077, P=0.011), CD80 expression on plasmacytoid dendritic cell (OR=2.62,95%CI:1.244-5.515, P=0.011), and CD80 expression on CD62L+ plasmacytoid dendritic cell (OR=2.641, 95%CI: 1.246-5.596, P=0.011) were positively associated with the incidence of cervical cancer. All gynecological cancers in this study have no statistically significant effect on immune cells, according to reverse MR analysis. ConclusionThis study emphasized the genetically predicted causality between immune cells and cervical cancer. In clinical practice, it is important to pay attention to the screening of peripheral blood immune cells for patients with cervical cancer.

Abstract The transportation of natural gas through pipelines offers numerous advantages. However, physical explosions in high‐pressure natural gas pipelines can cause casualties and property loss. There is currently no method for accurately predicting the damage range of physical explosions in pipelines, and a safer site selection plan cannot be determined during the pipeline construction design stage. This study proposes a method for determining the range of pipeline physical explosion damage by comprehensively considering two factors: the size range of the physical explosion craters, and the attenuation distance of the shock waves. A high‐pressure natural gas pipeline physical explosion crater model was constructed using HyperMesh software, and the accuracy of the model was verified using the PRCI calculation model. Based on the Sadovsky formula, a program was developed to simulate the spatiotemporal changes in shock wave diffusion, demonstrating the law of shock wave diffusion. The results show that the distance from the overpressure peak attenuation of the physical explosion shock wave in air to 0.02 MPa is calculated to be 33 m, and the maximum damage range of the crater is 9.27 m. Finally, the safe protection distance for personnel and buildings was determined to be 33 m.

In the Central Plains of China during the Zhou Dynasty (1046-256 BCE), the social hierarchy gradually solidified, accompanied by frequent wars and the phenomena of multicultural and multi-ethnic integration. These social phenomena collectively influenced the population’s genetic structure at that time. However, our understanding of the genetic history of this period remains largely unknown owing to limited ancient DNA studies. In this study, we successfully obtained 11 ancient genomes from the Guanzhuang site during the Zhou Dynasty on the central plain of China. Our findings revealed remarkable genetic continuity with the Neolithic populations of the Yellow River Basin and emphasized genetic diversity through the analysis of uniparental genetic markers. Population structure analysis further confirmed the genetic similarity between the Guanzhuang population and ancient populations of the Yellow River Basin and indicated genetic exchanges with ancient populations from surrounding regions. Intriguingly, signs of inbreeding within the Guanzhuang community cast doubt on the stringent enforcement of the contemporary marital regulations against consanguineous marriages within the same surname or clan. These revelations significantly enhance our insight into the complex interplay of ancient demography and societal organization, concurrently presenting a genetic perspective to view the complex evolution of Chinese civilization’s multiethnic.

BackgroundStudies using observational epidemiology have indicated that inflammation and immunological dysregulation are important contributors to placental and renal failure, which ultimately results in maternal hypertension. The potential causal relationships between the immunophenotypes and hypertensive disorder of pregnancy (HDP) are yet unclear.MethodsWe conducted two-sample Mendelian randomization (MR) analyses to thoroughly examine the relationship between immunophenotypes and HDP. The GWAS data on immunological traits was taken from public catalog for 731 immunophenotypes and the summarized GWAS data in 4 types of HDP were retrieved from FinnGen database. The link between immune cell traits and HDP was examined through our study methodology, taking into account both direct relationships and mediation effects of apolipoprotein A (apoA). The inverse variance weighted (IVW) method served as the main analysis, while sensitivity analysis was carried out as a supplement.ResultsWe identified 14 highly correlative immunophenotypes and 104 suggestive possible factors after investigating genetically predicted immunophenotype biomarkers. According to the IVW analysis, there was a strong correlation between HDP and HLA DR on DC and plasmacytoid DC. Reverse MR analysis showed that there was no statistically significant effect of HDP on immune cells in our investigation. Mediation analysis confirmed that apoA mediates the interaction between HLA DR on DC and HDP.ConclusionOur results highlight the complex interplay of immunophenotypes, apoA, and HDP. Moreover, the pathophysiological link between HLA DR on DC and HDP was mediated by the level of apoA.

Abstract Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.

BackgroundEvidence from observational studies suggested a connection between immune cells and gynecologic malignancies. To investigate potential causative associations between immunophenotype traits and gynecologic malignancies, we used a two-sample Mendelian randomization analysis.MethodsThe genetic instrumental variables of 731 immunophenotypes of peripheral blood were obtained by the GWAS database; the GWAS data of common gynecologic cancers were obtained from FinnGen study. The main statistic method was the inverse-variance weighted method. We also used the weighted mode, weighted median, and MR Egger for evaluations. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and gynecologic cancers.ResultsWe identified 50 highly probable immunophenotypes and 65 possible ones associated with gynecologic malignancies. The majority of the B cell panel was protective factors in cervical cancer. However, there was a correlation found in the B cells panel with a probable factor associated with an elevated risk of endometrial cancer. Immunophenotypes in the monocyte panel were linked to a lower probability of ovarian cancer and vulvar cancer. All of the gynecologic cancers in our study had no statistically significant impact on immune cells, according to reverse MR analysis.ConclusionOur study firstly emphasized the genetically predicted causality between immune cells and gynecologic malignancies. This knowledge will be critical to formulating the measures to prevent malignancies in female at risk in future clinical practice.

A djurleite crystal was discovered from a natural sample originally labelled as chalcocite. The djurleite crystal under investigation has a refined composition of Cu61.39S32, thus revealing a Cu deficiency compared to the originally reported Cu62S32 phase [Evans (1979). Z. Kristallogr. 150, 299–320], where all atomic sites are reported to be fully occupied. In addition, the current refinement revealed a splitting of eight of the Cu sites into pairs.

Northern China contains some of the world’s earliest farming societies. Here, authors use 55 ancient genomes to trace the genetic history of human migrations across northern China for the last 7500 years, and document genetic changes mirroring shifts in subsistence strategy.

Abstract Background Bluetongue virus (BTV), an emerging insect vector mediated pathogen affecting both wild ruminants and livestock, has a genome consisting of 10 linear double-stranded RNA genome segments. BTV has a severe economic impact on agriculture in many parts of the world. Current reverse genetics (RG) strategy to rescue BTV mainly rely on in vitro synthesis of RNA transcripts from cloned complimentary DNA (cDNA) corresponding to viral genome segments with the aid of helper plasmids. RNA synthesis is a laborious job which is further complicated with a need for expensive reagents and a meticulous operational procedure. Additionally, the target genes must be cloned into a specific vector to prepare templates for RNA transcription. Result In this study, we have developed a PCR based BTV RG system with easy two-step transfection. Viable viruses were recovered following a first transfection with the seven helper plasmids and a second transfection with the 10 PCR products on the BSR cells. Further, recovered viruses were characterized with indirect immunofluorescence assays (IFA) and gene sequencing. And the proliferation properties of these viruses were also compared with wild type BTV. Interestingly, we have identified that viruses containing the segment 2 of the genome from reassortant BTV, grew slightly slower than the others. Conclusion In this study, a convenient PCR based RG platform for BTV is established, and this strategy could be an effective alternative to the original available BTV rescue methods. Furthermore, this RG strategy is likely applicable for other Orbiviruses.

The data presented in this article describe an effect of N-acetylneuraminic acid and/or quercetin on the inflammatory proteins expressions (TNF-α, ICAM-1, VCAM-1 and MOMA-2) and the N-acetylneuraminic acid (NANA) levels of apolipoprotein E-deficient mice that are given a high-fat diet. Protein expression was performed by immunohistochemical imaging and NANA was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or semi-quantified using Image-Pro Plus software after ligation with fluorescein-5-thiosemicarbazide (FTSC). Further interpretation and discussion could be found at our research article entitled “Exogenous supplement of N-acetylneuraminic acid ameliorates atherosclerosis in apolipoprotein E-deficient mice” (Guo et al., 2016) [1]. Keywords: Immunohistochemistry, LC-MS/MS, Sialic acid, Fluorescent labeling, Imaging

Hydrocephalus is widely known as “hydrocephaly” or “water in the brain,” a building up of abnormal cerebrospinal fluid in the brain ventricles. Due to this abnormality, the size of the head becomes larger and increases the pressure in the skull. This pressure compresses the brain and causes damage to the brain. Identification by imaging techniques on the hydrocephalus is mandatory to treat the disease. Various methods and equipment have been used to image the hydrocephalus. Among them, computerized tomography (CT) scan and nuclear magnetic resonance (NMR) are the most considered methods and gives accurate result of imaging. Apart from imaging, cerebrospinal fluid-based biomarkers are also used to identify the condition of hydrocephalus. This review is discussed on “hydrocephalus” and its imaging captured by CT scan and NMR to support the biomarker analysis.

Nuclear magnetic resonance (NMR) is used widely to characterize petrophysical properties of siliciclastic and carbonate rocks but rarely to study those of mixed siliciclastic−carbonate rocks. In this study, 13 different core samples and eight acidified core samples selected amongst those 13 from the Paleogene Shahejie Formation in Southern Laizhouwan Sag, Bohai Bay Basin, were tested by scanning electron microscopy (SEM), micro-nano-computed tomography (CT), and NMR. SEM and CT results revealed a complex pore structure diversity, pore distribution, and pore-throat connectivity in mixed reservoirs. Sixteen groups of NMR experiments addressed changes in these properties and permeabilities of mixed siliciclastic−carbonate rocks before and after acidification to determine its effects on such reservoirs. NMR experimental results showed no “diffusion coupling” effect in mixed siliciclastic−carbonate rocks. Distributions of NMR T2 cutoff values (T2C) are closely related to the pore structure and lithologic characteristics before and after acidification. The T2C index separates irreducible and movable fluids in porous rocks and is a key factor in permeability prediction. Centrifugation experiments showed that, before acidification, the T2C of mixed siliciclastic−carbonate rocks with 60−90% siliciclastic content (MSR) ranged widely from 1.5 to 9.8 ms; the T2C of mixed siliciclastic−carbonate rocks with 60−90% carbonate content (MCR) ranged from 1.8 to 5.6 ms. After acidification, the T2C of MSR ranged widely from 2.6 to 11.6 ms, the T2C of MCR ranged from 1.5 to 5.6 ms, and no significant difference was observed between MCR reservoirs. Based on an analysis of the morphology of NMR T2 spectra, we propose a new T2 cutoff value prediction method for mixed siliciclastic−carbonate rocks based on a normal distribution function to predict various T2C values from morphological differences in NMR T2 spectra and to calculate the irreducible water saturation (Swir), i.e., the ratio of irreducible total fluid volume to effective porosity. The reliability of the proposed method is verified by comparing predicted T2C and Swir values with those from NMR experimental results. New experiments and modeling demonstrate the applicability of NMR for the petrophysical characterization of mixed siliciclastic−carbonate rock reservoirs. Our results have potential applications for identification and evaluation of mixed siliciclastic−carbonate rock reservoirs using NMR logging.

Apelin receptor(s) (APLNR) are suggested to mediate the actions of apelin and Elabela (ELA) peptides in many physiological processes, including cardiovascular development and food intake in vertebrates. However, the functionality of APLNR has not been examined in most vertebrate groups. Here, we characterized two APLNRs APLNR1, APLNR2) in chickens and red-eared sliders, and three APLNRs in zebrafish (APLNR2a, APLNR2b, APLNR3a), which are homologous to human APLNR. Using luciferase-reporter assays or Western blot, we demonstrated that in chickens, APLNR1 (not APLNR2) expressed in HEK293 cells was potently activated by chicken apelin-36 and ELA-32 and coupled to Gi-cAMP and MAPK/ERK signaling pathways, indicating a crucial role of APLNR1 in mediating apelin/ELA actions; in red-eared sliders, APLNR2 (not APLNR1) was potently activated by apelin-36/ELA-32, suggesting that APLNR2 may mediate apelin/ELA actions; in zebrafish, both APLNR2a and APLNR2b were potently activated by apelin-36/ELA-32 and coupled to Gi-cAMP signaling pathway, as previously proposed, whereas the novel APLNR3a was specifically and potently activated by apelin. Similarly, an apelin-specific receptor (APLNR3b) sharing 57% sequence identity with zebrafish APLNR3a was identified in Nile tilapia. Collectively, our data facilitates the uncovering of the roles of APLNR signaling in different vertebrate groups and suggests a key functional switch between APLNR1 and APLNR2/3 in mediating the actions of ELA and apelin during vertebrate evolution.

The hot deformation behavior and microstructure evolution of a 7.5 vol.% TiBw/near α-Ti composite with fine matrix microstructure were investigated under the deformation conditions in a temperature range of 800−950 °C and strain rate range of 0.001−1 s−1 using plane strain compression tests. The flow stress curves show different characteristics according to the various deformation conditions. At a higher strain rate (1 s−1), the flow stress of the composite continuously increases until a peak value is reached. The activation energy is 410.40 kJ/mol, much lower than the activation energy of as-sintered or as-forged composites. The decreased activation energy is ascribed to the breaking of the TiBw reinforcement during the multi-directional forging and the resultant fine matrix microstructure. Refined reinforcement and refined matrix microstructure significantly improve the hot deformation ability of the composite. The deformation conditions determine the morphology and fraction of α and β phases. At 800−900 °C and 0.01 s−1 the matrix α grains are much refined due to the continuous dynamic recrystallization (CDRX). The processing map is constructed based on the hot deformation behavior and microstructure evolution. The optimal hot processing window is determined to be 800−950 °C/0.001−0.01 s−1, which lead to CDRX of primary α grains or dynamic recovery (DRV) and dynamic recrystallization (DRX) of β phase.