The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations ...because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.
With the improvement of Chinese economic status, Chinese A‐share market has attracted more and more attention from international investors. Sub‐new stock is a general name for the companies which ...list less than a year, most companies of this category come from the China Growth Enterprise Market (GEM) and are high‐tech companies with high growth. To study the influence of major asset restructuring on the stock prices of different companies, this paper adopts the event study method to calculate the samples' abnormal return in a 20‐day window period, compares related party transactions and unrelated party transactions, as well as different payment methods for the restructuring. The analysis shows that the listed companies of Growth Enterprise Market can get higher excess returns, the sample of unrelated transaction obtains more abnormal income than the sample of related transaction. The research can provide a reference for local and international investors.
To improve the properties of high pressure die cast Al9Si3Cu alloy, melt treatment via high shear was employed to form fine in-situ MgAl2O4 particles which act as potential nuclei to refine α-Al ...grains whilst providing reinforcement to enhance the tensile strengths of the alloy. Experimental results showed that the naturally formed MgAl2O4 particles in the alloy melt were approximately 1 μm in diameter and are very limited in number as observed in the concentrated samples obtained via filtration. With the implementation of the high shear technology on the alloy melt, it is possible to synthesize a large number of fine MgAl2O4 particles which were approximately 80 nm–300 nm in diameter. The yield strength of the alloy containing such in-situ sub-nano-sized particles was found to increase from 147 MPa to 169 MPa in the as-cast state. Following treatment with direct ageing at 155 °C only, the yield strength of the alloy treated with high melt shear was found to increase by 128 MPa, ultimately achieving a yield strength and ultimate tensile strength of 297 MPa and 423 MPa respectively. The improvement of the mechanical properties of the alloy is attributed to the fine and uniform microstructure achieved by the enhanced heterogeneous nucleation of both α-Al grains and α-AlFeMnSi intermetallic compound via the in-situ MgAl2O4 particles, and also to the enhanced precipitation strengthening trigged by the increased dislocation density caused by the in-situ MgAl2O4 particles.
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•The high shear melt conditioning can improve the tensile strength of LM24 alloy.•With ageing, the YS and UTS of LM24-M alloy achieve 297 MPa and 423 MPa respectively.•High shear can result in grain refinement of α-Al and of α-AlFeMnSi phase.•The dislocation enhanced precipitates result in the strength improvement of LM24.
The role of the loss-gain context in human social decision-making remains heavily debated, with mixed evidence showing that losses (vs. gains) boost both selfish and prosocial motivations. Herein, we ...propose that the loss context, compared to the gain context, exacerbates intuitive reactions in response to the conflict between self-interest and prosocial preferences, regardless of whether those dominant responses are selfish or altruistic. We then synthesize evidence from three lines of research to support the account, which indicates that losses may either enhance or inhibit altruistic behaviors depending on the dominant responses in the employed interactive economic games, prosocial/proself traits, and the explicit engagement of deliberative processes. The current perspective contributes to the ongoing debate on the association between loss-gain context and human prosociality by putting forward a theoretical framework to integrate previous conflicting perspectives.
Cancer-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) can promote tumor progression by delivering microRNA (miRNA). Whether EVs could transfer miR-1228-3p into hepatocellular ...carcinoma (HCC) cells to affect chemoresistance was discussed in this study. Normal fibroblasts (NFs) and CAFs were isolated from tissue samples of HCC patients. We assessed the functions of HCC cells after co-culturing with NFs and CAFs. miR-1228-3p gain-of-function experiments were conducted. Next, functional assays were carried out to determine the binding of miR-1228-3p to placenta associated 8 (PLAC8). In vivo models were constructed for validation. CAFs-derived EVs exerted promoting effect on proliferative, migrating, invading potential of HCC cells and their resistance to sorafenib. PLAC8 was demonstrated as a direct target of miR-1228-3p. By targeting PLAC8, miR-1228-3p activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. In addition, the transfer of miR-1228-3p from CAFs-derived EVs into HCC cells boosted chemoresistance of HCC cells, which was reversed by restoring PLAC8. All in all, CAF-EV-carried miR-1228-3p strengthens the chemoresistance of HCC through activating PLAC8-mediated PI3K/AKT pathway. This finding contributes to the development of EV-based therapies overcoming the chemoresistance of HCC.
A giant deep-strata oil-gas field with complex fluid characteristics was recently discovered in the Hade-Yuke area of the east Tabei uplift (Tarim Basin, NW China). The deep fluids show a lateral ...co-existence of several gas, condensate and oil phase reservoirs characterized through the integration of complimentary geochemical (e.g., bulk composition, biomarker and stable carbon isotope) and geological data. Typical features of the gas and condensate reservoirs, which were mainly distributed in the eastern parts of the study site, included high GOR (gas-to-oil ratio), hydrocarbon gases with relatively heavy δ13C values and crude oils with high wax content. In contrast oil reservoirs, which mostly occurred in more westerly locations, had lower GOR values, lighter δ13C values and lower wax content, indicating gradual change of fluid characters. The petroleum accumulations derive from two hydrocarbon charge events: an early oil charge in the Late Hercynian and a later gas charge in the Late Himalayan which migrated from east to west, leading to a gradual variation in fluid phase and characteristics. Alteration of paleo oil reservoirs by this secondary gas charge was therefore primarily responsible for the complex fluid character and multi-phase reservoirs presently in place. Secondary condensates were formed from the retrograde condensation of paleo reservoirs. Our re-construction of the hydrocarbon accumulation process encourages future exploration endeavours to target commercially viable gas accumulations in the deep east strata and oil reservoirs in the west.
•Late gas invasion into paleo oils led to the changes of hydrocarbon phases.•The intensity of gas invasion controlled the variation of fluid features and phases.•Liquid hydrocarbon can be preserved due to steady rapid subsidence.
The increased activity of regulatory B cells (Breg) is known to be involved in immunosuppression during helminth infection, which is characterized by inducing IL-10-producing Breg cells. However, the ...current knowledge of B cell subsets differentiation and IL-10-independent immunoregulatory mechanisms of B cells in schistosomiasis is insufficient.
BALB/c mice were percutaneously infected with cercariae for investigating the profile of B cell subsets during Schistosoma japonicum infection. B cells isolated from the spleen or peritoneal cavity were analyzed for the regulatory phenotype after stimulation with soluble egg antigens (SEA) in vitro. CD4
T cells were then cocultured with B cells pretreated with or without anti-PD-L1 antibody for investigating the role of B cells from infected mice on regulating CD4
T cells. Furthermore, the in vivo administration of anti-PD-L1 antibody was conducted to investigate the role of PD-L1 in regulating host immunity during infection.
The percentages of peritoneal and splenic B-1a cells, as well as marginal zone B (MZB) cells were decreased at eight and twelve weeks after infection compared to those from uninfected mice. In splenic B cells, TGF-β expression was increased at eight weeks but declined at twelve weeks of infection, and PD-L1 expression was elevated at both eight and twelve weeks of infection. In addition, SEA stimulation in vitro significantly promoted the expression of IL-10 in peritoneal B cells and CD5 in splenic B cells, and the SEA-stimulated splenic and peritoneal B cells preferentially expressed PD-L1 and TGF-β. The splenic B cells from infected mice were able to suppress the function of Th1 and Th2 cells in vitro but to expand the expression of Tfh transcription factor Bcl6, which was further enhanced by blocking PD-L1 of B cells before co-cultivation. Moreover, Th2 response and Bcl6 expression in CD4
T cells were also increased in vivo by blocking PD-L1 after infection, although the hepatic pathology was slightly influenced.
Our findings revealed that S. japonicum infection modulates the differentiation of B cell subsets that have the capability to affect the CD4
T cell response. This study contributes to a better understanding of B cells immune response during schistosomiasis.
An invasive biopsy followed by histological staining is the benchmark for pathological diagnosis of skin tumors. The process is cumbersome and time-consuming, often leading to unnecessary biopsies ...and scars. Emerging noninvasive optical technologies such as reflectance confocal microscopy (RCM) can provide label-free, cellular-level resolution, in vivo images of skin without performing a biopsy. Although RCM is a useful diagnostic tool, it requires specialized training because the acquired images are grayscale, lack nuclear features, and are difficult to correlate with tissue pathology. Here, we present a deep learning-based framework that uses a convolutional neural network to rapidly transform in vivo RCM images of unstained skin into virtually-stained hematoxylin and eosin-like images with microscopic resolution, enabling visualization of the epidermis, dermal-epidermal junction, and superficial dermis layers. The network was trained under an adversarial learning scheme, which takes ex vivo RCM images of excised unstained/label-free tissue as inputs and uses the microscopic images of the same tissue labeled with acetic acid nuclear contrast staining as the ground truth. We show that this trained neural network can be used to rapidly perform virtual histology of in vivo, label-free RCM images of normal skin structure, basal cell carcinoma, and melanocytic nevi with pigmented melanocytes, demonstrating similar histological features to traditional histology from the same excised tissue. This application of deep learning-based virtual staining to noninvasive imaging technologies may permit more rapid diagnoses of malignant skin neoplasms and reduce invasive skin biopsies.
Abstract
Previous scientific research on reservoirs of the Deng IV Member in the Gaoshiti-Moxi area, the main production area of the Anyue gas field with reserves of tens of billions of cubic metres, ...has focused on karst palaeogeomorphology reconstruction, the facies distribution on platform margins, and their effects on creating favourable reservoirs. However, the quality of microbial carbonate reservoirs is also closely related to their original depositional environments on both inner and marginal platforms. Therefore, this paper attempts to reveal favourable microbial carbonate reservoir characteristics and the sedimentary effects on their distribution and prediction based predominantly on a synthetic analysis of the sequence stratigraphy and depositional facies. The results show that favourable reservoirs of the Deng IV Member are classified into three types according to their reservoir spaces: fracture-cavity, pore-cavity and pore reservoirs. Secondary dissolution pores and cavities are primary reservoir spaces developed mainly in nonskeletal grain dolomites with sparry cements, thrombolites, and stromatolites. The physical properties of the fracture-cavity and pore-cavity types of reservoirs are better than those of pore reservoirs and have porosities between 1 and 5% and permeabilities between 0.01 × 10
–3
and 1 × 10
–3
μm
2
. Vertically, favourable reservoirs are developed mainly in parasequence set 6 (PSS6) and PSS7 and are laterally distributed in well zone MX9-MX19-MX1 for the fracture-cavity type, MX105-MX110-GS20 for the pore-cavity type and MX17-MX107-MX41-MX102-GS102 for the pore type. Moreover, depositional effects on reservoirs in terms of depositional sequences, seismic facies, microfacies and microfacies associations indicate that to some extent, the fracture-cavity type of reservoir is constrained by the top boundaries of PSS7, PSS2, parasequence 17 (PS17) and PS14; the pore-cavity type of reservoir is constrained by the top boundaries of PSS7, PSS4, PS18 and PS12; and the pore type of reservoir is constrained by the top boundaries of PSS7, PSS6, PSS3, PSS2, PS18, PS17, PS14, and PS12. Seismic facies associated with shoals and mound-flat complexes are related to the facies distributions of pore cavities and pore reservoirs. MA1, MA3, MA7, and MA8 are predominant microfacies associations of favourable reservoirs of the Deng IV Member in the Gaoshiti-Moxi area. The above results are significant for further petroleum exploration and exploitation of ultradeep microbial carbonate reservoirs in this area.
ABSTRACT
Numerical simulation in coupled elastic and poroelastic media is important in oil and gas exploration. However, the interface between elastic and poroelastic media is a challenge to handle. ...In order to deal with the coupled model, the first‐order velocity–stress wave equations are used to unify the elastic and poroelastic wave equations. In addition, an arbitrary high‐order discontinuous Galerkin method is used to simulate the wave propagation in coupled elastic–poroelastic media, which achieves same order accuracy in time and space domain simultaneously. The interfaces between the two media are explicitly tackled by the Godunov numerical flux. The proposed forms of numerical flux can be used efficiently and conveniently to simulate the wave propagation at the interfaces of the coupled model and handle the absorbing boundary conditions properly. Numerical results on coupled elastic–poroelastic media with straight and curved interfaces are compared with those from a software that is based on finite element method and the interfaces are handled by boundary conditions, demonstrating the feasibility of the proposed scheme in dealing with coupled elastic–poroelastic media. In addition, the proposed method is used to simulate a more complex coupled model. The numerical results show that the proposed method is feasible to simulate the wave propagation in such a media and is easy to implement.
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