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Abstract Background Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder, and its incidence of comorbid with major depressive disorder (MDD) is significantly higher than the general population. However, many patients lack proper recognition and necessary psychological health treatments. We aimed to identify potential biomarkers and mechanisms involved in the development of IBD comorbid with MDD (IBD-MDD). Methods We utilized IBD and MDD-related datasets from the GEO database for differential gene expression analysis, protein-protein interaction (PPI) and pathway enrichment analysis, random forest algorithm, LASSO regression analysis, and construction of a disease prediction model. We assessed the accuracy of the model using ROC curve, explored potential mechanisms through immune infiltration analysis, and validated candidate biomarkers using peripheral blood samples from patients in our center’s cohort. Results We identified 484 IBD-related secreted proteins and 142 key module genes associated with MDD. PPI analysis revealed two crucial modules primarily involved in inflammation and immune regulation. We identified four diagnostic genes (HGF, SPARC, ADAM12, and MMP8) from the 21 shared genes between IBD-related secreted proteins and MDD key module genes, constructed a nomogram model and confirmed its accuracy using ROC curve from an external independent dataset. Immune infiltration analysis revealed significant associations between the four diagnostic genes, and cellular immune dysregulation in MDD. Finally, we validated the expression patterns of the four diagnostic genes in our cohort. Conclusions Our study discovered four candidate biomarkers for IBD-MDD, providing new insights for the diagnosis and therapeutic intervention of serum-based IBD comorbid with MDD.

Background: Endogenous sulfur dioxide (SO2) plays a crucial role in protecting heart from myocardial fibrosis by inhibiting the excessive growth of cardiac fibroblasts. This study aimed to investigate potential mechanisms by which SO2 suppressed myocardial fibrosis. Methods and results: Mouse model of angiotensin II (Ang II)-induced cardiac fibrosis and cell model of Ang II-stimulated cardiac fibroblast proliferation were employed. Our findings discovered that SO2 mitigated the aberrant phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) induced by Ang II, leading to a reduction of fibroblast proliferation. Mechanistically, for the first time, we found that SO2 sulfenylated ERK1/2, and inhibited ERK1/2 phosphorylation and cardiac fibroblast proliferation, while a sulfhydryl reducing agent dithiothreitol (DTT) reversed the above effects of SO2. Furthermore, mutant ERK1C183S (cysteine 183 to serine) abolished the sulfenylation of ERK by SO2, thereby preventing the inhibitory effects of SO2 on ERK1 phosphorylation and cardiac fibroblast proliferation. Conclusion: Our study suggested that SO2 inhibited cardiac fibroblast proliferation by sulfenylating ERK1/2 and subsequently suppressing ERK1/2 phosphorylation. These new findings might enhance the understanding of the mechanisms underlying myocardial fibrosis and emphasize the potential of SO2 as a novel therapeutic target for myocardial fibrosis.

Traditional expression quantitative trait locus (eQTL) mapping associates single nucleotide polymorphisms (SNPs) with gene expression, where the SNPs are derived from large-scale whole-genome sequencing (WGS) data or transcriptome data. While WGS provides a high SNP density, it also incurs substantial sequencing costs. In contrast, RNA-seq data, which are more accessible and less expensive, can simultaneously yield gene expressions and SNPs. Thus, eQTL analysis based on RNA-seq offers significant potential applications. Two primary strategies were employed for eQTL in this study. The first involved analyzing expression levels in relation to variant sites detected between populations from RNA-seq data. The second approach utilized kmers, which are sequences of length k derived from RNA-seq reads, to represent variant sites and associated these kmer genotypes with gene expression. We discovered 87 significant association signals involving eGene on the basis of the SNP-based eQTL analysis. These genes include DYNLT1, NMNAT1, and MRLC2, which are closely related to neurological functions such as motor coordination and homeostasis, play a role in cellular energy metabolism, and function in regulating calcium-dependent signaling in muscle contraction, respectively. This study compared the results obtained from eQTL mapping using RNA-seq identified SNPs and gene expression with those derived from kmers. We found that the vast majority (23/30) of the association signals overlapping the two methods could be verified by haplotype block analysis. This comparison elucidates the strengths and limitations of each method, providing insights into their relative efficacy for eQTL identification.

The optical properties of Al nanograting deep ultraviolet LEDs with a rough surface of sapphire are investigated by the finite-difference time-domain simulation. The rough surface of sapphire is characterized by rms amplitude and correlation length. The calculation results indicate that the rough sapphire surface is easier to extract s-polarized light than p-polarized light, which leads to an increase in the polarization degree. When the rms and correlation length are around 150 nm, the light extraction efficiency (LEE) of LED devices can reach a maximum. Compared to the smooth surface condition, the LEE of Al nanograting LEDs with a period of 300 nm is improved by 65.47% at rms = 150 nm and correlation length = 100 nm. This can be attributed to the critical angle of light extraction increasing from ∼23° on a smooth surface to ∼46° on a rough surface. In addition, due to surface plasmon coupling, when the period of Al nanograting is 100–800 nm, the peak intensity of the TE or TM polarized radiation recombination rate is basically 37%–50% higher than that of the control structure with an Al plane.

Abstract Van der Waals (vdW) heterostructures composed of different two-dimensional (2D) materials offer an easily accessible way to combine properties of individual materials for applications. Owing to the discovery of a set of unanticipated physical phenomena, the twisted 2D vdW heterostructures have gained considerable attention recently. Here, we report enhanced valley splitting in twisted 2D vdW WSe2/CrI3 heterostructures. In particular, the splitting can be 1200% (or 5.18 meV) of the value for a non-twisted heterostructure. According to the k·p model, this value is equivalent to a ~20 T external magnetic field applied perpendicular to the 2D sheet. The thermodynamic stability of 2D vdW WSe2/CrI3 heterostructures, on the other hand, depends linearly on the interlayer twisting angle.

Amycolatopsis is an important source of diverse valuable bioactive natural products. The CRISPR/Cas-mediated gene editing tool has been established in some Amycolatopsis species and has accomplished the deletion of single gene or two genes. The goal of this study was to develop a high-efficient CRISPR/Cas9-mediated genome editing system in vancomycin-producing strain A. keratiniphila HCCB10007 and enhance the production of vancomycin by deleting the large fragments of ECO-0501 BGC. By adopting the promoters of gapdhp and ermE*p which drove the expressions of scocas9 and sgRNA, respectively, the all-in-one editing plasmid by homology-directed repair (HDR) precisely deleted the single gene gtfD and inserted the gene eGFP with the efficiency of 100%. Furthermore, The CRISPR/Cas9-mediated editing system successfully deleted the large fragments of cds13-17 (7.7 kb), cds23 (12.7 kb) and cds22-23 (21.2 kb) in ECO-0501 biosynthetic gene cluster (BGC) with high efficiencies of 81%–97% by selecting the sgRNAs with a suitable PAM sequence. Finally, a larger fragment of cds4-27 (87.5 kb) in ECO-0501 BGC was deleted by a dual-sgRNA strategy. The deletion of the ECO-0501 BGCs revealed a noticeable improvement of vancomycin production, and the mutants, which were deleted the ECO-0501 BGCs of cds13-17, cds22-23 and cds4-27, all achieved a 30%–40% increase in vancomycin yield. Therefore, the successful construction of the CRISPR/Cas9-mediated genome editing system and its application in large fragment deletion in A. keratiniphila HCCB10007 might provide a powerful tool for other Amycolatopsis species.

Summary: The commensal microbiota regulates the self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) in bone marrow. Whether and how the microbiota influences HSPC development during embryogenesis is unclear. Using gnotobiotic zebrafish, we show that the microbiota is necessary for HSPC development and differentiation. Individual bacterial strains differentially affect HSPC formation, independent of their effects on myeloid cells. Early-life dysbiosis in chd8−/− zebrafish impairs HSPC development. Wild-type microbiota promote HSPC development by controlling basal inflammatory cytokine expression in kidney niche, and chd8−/− commensals elicit elevated inflammatory cytokines that reduce HSPCs and enhance myeloid differentiation. We identify an Aeromonas veronii strain with immuno-modulatory activities that fails to induce HSPC development in wild-type fish but selectively inhibits kidney cytokine expression and rebalances HSPC development in chd8−/− zebrafish. Our studies highlight the important roles of a balanced microbiome during early HSPC development that ensure proper establishment of lineal precursor for adult hematopoietic system.

Left ventricular noncompaction (LVNC) is a heterogeneous disorder with unclear genetic causes and an unknown mechanism. eIF3a, an important member of the Eukaryotic translation initiation factor 3 (eIF3) family, is involved in multiple biological processes, including cell proliferation and migration during myocardial development, suggesting it could play a role in LVNC development. To investigate the association between a novel variant (c.1145 A- > G) in eIF3a and LVNC, and explore potential mechanisms that could lead to the development of LVNC. A novel eIF3a variant, c.1145 A- > G, was identified by whole-exome sequencing in a familial pedigree with LVNC. Adenovirus vectors containing wild-type eIF3a and the mutated version were constructed and co-infected into H9C2 cells. Cell proliferation, apoptosis, cell migration, and differentiation, as well as phosphorylation of ERK1/2 were studied and were measured by proliferation assays, flow cytometry, real-time PCR and Western blot, respectively. The eIF3a mutation inhibited the proliferation of H9C2 cells, induced apoptosis, promoted cell migration, and inhibited the differentiation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The effect of the eIF3a mutation may be attributed to a decrease in expression of p-ERK1/2. A novel eIF3a gene mutation disrupted the p-ERK1/2 pathway and caused decreased myocardium proliferation, differentiation, accelerated migration.This finding may provide some insight into the mechanism involved in LVNC development.

Abstract Background CRISPR/Cas9 systems have been repurposed as canonical genome editing tools in a variety of species, but no application for the model strain Rhodobacter sphaeroides 2.4.1 was unveiled. Results Here we showed two kinds of programmable base editing systems, cytosine base editors (CBEs) and adenine base editors (ABEs), generated by fusing endonuclease Cas9 variant to cytosine deaminase PmCDA1 or heterodimer adenine deaminase TadA–TadA*, respectively. Using CBEs, we were able to obtain C-to-T mutation of single and double targets following the first induction step, with the efficiency of up to 97% and 43%; while the second induction step was needed in the case of triple target, with the screening rate of 47%. Using ABEs, we were only able to gain A-to-G mutation of single target after the second induction step, with the screening rate of 30%. Additionally, we performed a knockout analysis to identify the genes responsible for coenzyme Q10 biosynthesis and found that ubiF, ubiA, ubiG, and ubiX to be the most crucial ones. Conclusions Together, CBEs and ABEs serve as alternative methods for genetic manipulation in Rhodobacter sphaeroides and will shed light on the fundamental research of other bacteria that are hard to be directly edited by Cas9-sgRNA.

Objectives: The study was designed to explore the role of endogenous gaseous signaling molecule sulfur dioxide (SO2) in the control of cardiomyocyte apoptosis and its molecular mechanisms.Methods: Neonatal mouse cardiac myocytes (NMCMs) and H9c2 cells were used in the cell experiments. The endogenous SO2 pathway including SO2 level and the expression of SO2-generating enzyme aspartate aminotransferase 1/2 (AAT1/2) were detected in NMCMs. The apoptosis of cardiomyocytes was examined by a TUNEL assay. The cleavage and the activity of apoptotic proteins caspase9 and caspase3 were measured. The content of ATP, the opening of mitochondrial permeability transition pore (mPTP), and the cytochrome c (cytc) leakage were detected by immunofluorescence. The sulphenylation of cyclophilin-D (CypD) was detected by biotin switch analysis. The four CypD mutant plasmids in which cysteine sites were mutated to serine were constructed to identify the SO2-affected site in vitro.Results: ISO down-regulated the endogenous SO2/AAT pathway of cardiomyocytes in association with a significant increase in cardiomyocyte apoptosis, demonstrated by the increases in apoptosis, cleaved-caspase3/caspase3 ratio, and caspase3 activity. Furthermore, ISO significantly reduced ATP production in H9c2 cells, but the supplement of SO2 significantly restored the content of ATP. ISO stimulated mPTP opening, resulting in an increase in the release of cytc, which further increased the ratio of cleaved caspase9/caspase9 and enhanced the protein activity of caspase9. While, the supplementation of SO2 reversed the above effects. Mechanistically, SO2 did not affect CypD protein expression, but sulphenylated CypD and inhibited mPTP opening, resulting in an inhibition of cardiomyocyte apoptosis. The C104S mutation in CypD abolished SO2-induced sulphenylation of CypD, and thereby blocked the inhibitory effect of SO2 on the mPTP opening and cardiomyocyte apoptosis.Conclusion: Endogenous SO2 sulphenylated CypD at Cys104 to inhibit mPTP opening, and thus protected against cardiomyocyte apoptosis.

Magnetic clusters have attracted great attention and interest due to their novel electronic properties, and they have potential applications in nanoscale information storage devices and spintronics. The interaction between magnetic clusters and substrates is still one of the challenging research focuses. Here, by using the density functional theory (DFT), we study the structural stability and magnetic properties of iridium clusters (Irn, n = 3–5) adsorbed on two-dimensional (2D) substrates, such as graphene and hexagonal boron nitride (hBN). We find that the most favorable configurations of free Irn clusters change when adsorbed on 2D substrates. In the meantime, the magnetic moments of the most stable Irn reduce to 53% (graphene) and 23.6% (hBN) compared with those of the free−standing ones. Interestingly, about 12-times enlargement on the magnetic anisotropy energy can be found on hBN substrates. These theoretical results indicate that the cluster–substrate interaction has vital effects on the properties of Irn clusters.

The recent pandemic caused by SARS-CoV-2 has spread to over 100 countries, infected more than 47 million people and resulted in more than 1.2 million deaths worldwide until October. It is well known that, the SARS-CoV-2 starts an infection by binding its Receptor Binding Domain (RBD) of spike protein to human Angiotensin converting enzyme 2 (ACE2) receptor, and strenuous efforts had been made to prevent the infection. However, no successful drugs or vaccines have appeared. Herein, molecular docking and molecular simulations were carried out to study the interaction between RBD and two glycopeptide antibiotics (Vancomycin and Teicoplanin). Key residues in binding pocket were highlighted and the binding free energies were calculated. Our results suggested that Vancomycin and Teicoplanin, as natural and accepted antibiotics, could block the interaction between RBD of spike protein and human ACE2 receptor, which might be developed to potential drugs against the SARS-CoV-2.

BackgroundOur previous study showed that the ribosomal protein L21 (RPL21) may play an important role in the development and survival of pancreatic cancer. In this article, RNA interference (RNAi) experiments were performed with RPL21-specific small interfering RNA (siRNA) to elucidate the mechanism by which RPL21 controls PC PANC-1 and BxPC-3 cell proliferation.MethodsIn the present study, PANC-1, BxPC-3 cells, and BALB/c nude mice were used to investigate antitumor effect and mechanism by which RPL21 controls cell proliferation and apoptosis in vitro and in vivo. The effects of RPL21 knockdown on PANC-1 and BxPC-3 cell proliferation, cell cycle and cell apoptosis in vitro were determined using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assays and flow cytometry assay. The mechanism of RPL21 regulating cell proliferation was investigated using transcriptome sequencing analysis and luciferase reporter assay. The effects of RPL21 knockdown on PANC-1 and BxPC-3 cell proliferation in vivo were determined using BALB/c nude mice tumor model.ResultsIn PANC-1 and BxPC-3 cells, the knockdown of RPL21 expression with corresponding siRNA suppressed cell proliferation in vitro and in vivo, inhibited DNA replication, and induced arrests in the G1 phase of the cell cycle. Further results showed that the mini-chromosome maintenance (MCM) protein family (MCM2-7), CCND1 and CCNE1 were down-regulated significantly in PANC-1 and BxPC-3 cells after transfected with RPL21 siRNA, which suggests that the suppression of DNA replication is due to the reduced expression of MCM2-7 family, and the induction of G1 arrest is correlated with the inhibition of CCND1 and CCNE1. Luciferase reporter assay showed that RPL21 controls the DNA replication and G1-S phase progression possibly through the regulation of E2F1 transcription factor in PC cells. Moreover, RPL21 siRNA showed an apoptosis-inducing effect only in BxPC-3 and PANC-1 cells but not in normal HPDE6-C7 cells. The increase of caspase-8 activities and the loss of mitochondrial membrane potential after RPL21 silencing indicates that the RPL21 gene may be involved in caspase-8-related mitochondrial apoptosis.ConclusionOur findings suggest that siRNA against the RPL21 gene possesses a potential anti-cancer activity for PC cells by inhibiting their proliferation and DNA replication, as well as inducing cell cycle G1 arrest and cell apoptosis.

An InAlN/GaN heterostructure has been successfully grown on GaN/sapphire and AlN/sapphire substrate by metal organic chemical vapor deposition. The whole epitaxial quality has been confirmed through X-ray diffraction, while some corresponding micro-structural propagation defects have been characterized by means of transmission electron microscopy. It can be concluded that these defects have been originating from the extended threading dislocation in GaN layer. In addition, with the increasing of acceleration voltage, a series of the cathodoluminescence peak shifting can be clearly observed, and the interesting phenomenon has been attributed to the several complex factors, such as inhomogeneous composition, internal absorption, and so on. Nevertheless, with further optimization of the structural parameters of the epilayers, it can be expected that these experimental results would promote a better epitaxy quality and the optoelectronic device design.

The light extraction behavior of an AlGaN-based deep-ultraviolet LED covered with Al nanoparticles (NPs) is investigated by three-dimensional finite-difference time-domain simulation. For the transmission spectra of s- and p-polarizations in different emission directions, the position of maximum transmittance can be changed from (θ = 0°, λ = 273 nm) to (θ = 0°, λ = 286 nm) by increasing the diameter of Al NPs from 40 nm to 80 nm. In the direction that is greater than the critical angle, the transmittance of s-polarization is very small due to the strong absorption of Al NPs, while the transmittance spectrum of p-polarization can be observed obviously for the 80 nm Al NPs structure. For a ~284 nm AlGaN-based LED with surface plasmon (SP) coupling, although the luminous efficiency is significantly improved due to the improvement of the radiation recombination rate as compared with the conventional LED, the light extraction efficiency (LEE) is lower than 2.61% of the conventional LED without considering the lateral surface extraction and bottom reflection. The LEE is not greater than ~0.98% (~2.12%) for an SP coupling LED with 40 nm (80 nm) Al NPs. The lower LEE can be attributed to the strong absorption of Al NPs.

Abstract Background Cordyceps sinensis has been used for centuries in China as one of the most valued herbal medicine and tonic food. Paecilomyces hepiali, a fungal strain isolated from natural C. sinensis, has been used widely as a substitute of C. sinensis in medicine and health food. P. hepiali has been reported to have various pharmaceutical benefits, including triglyceride-lowing activity. However, its effects on triglyceride metabolism in adipocytes remain unknown. The purpose of the present study was to evaluate the effect of P. hepiali mycelia on adipocyte lipolysis and to clarify the underlying mechanisms. Methods The fully differentiated 3T3-L1 adipocytes were treated with methanol extract of Paecilomyces hepiali mycelia (PHME). Contents of glycerol released into the culture medium and intracellular triglyceride were measured as indices of lipolysis using glycerol assay kit and Oil red O staining, respectively. Then, effects of PHME on the main lipases or kinases involved in lipolysis regulation were investigated. Protein expression of adipose triglyceride lipase (ATGL) and perilipin, as well as phosphorylation of hormone-sensitive lipase (HSL), AMP-activated protein kinase (AMPK), and mitogen-activated protein kinases (MAPKs) were determined by western blotting. Moreover, nucleosides, important constituents of PHME, were analyzed using high performance liquid chromatography (HPLC). Results Treatment with PHME led to a significant increase in glycerol release thereby reduced intracellular triglyceride accumulation in fully differentiated adipocytes. PHME upregulated protein kinase (PK) A-mediated phosphorylation of HSL at serine residues of 563 and 660. Meanwhile, PHME treatment also upregulated phosphorylation of extracellular signal-regulated kinase (ERK), and downregulated the protein level of perilipin. Pretreatment with the PKA inhibitor, H89, blunted the PHME-induced lipolysis and the phosphorylation of HSL (Ser 563 and 660). Moreover, pretreatment with ERK inhibitor, PD98059, weakened the PHME-caused glycerol release and downregulation of perilipin expression. HPLC analysis indicated there were adenosine, cordycepin, uridine and vernine in PHME. Conclusions Our results showed that PHME significantly induced lipolysis in 3T3-L1 adipocytes, which is mainly mediated by activation of HSL through PKA pathway and by downregulation of perilipin through activation of ERK pathway.

Pristinamycin, produced by Streptomyces pristinaespiralis, which is a streptogramin-like antibiotic consisting of two chemically unrelated components: pristinamycin I (PI) and pristinamycin II (PII), shows potent activity against many antibiotic-resistant pathogens. However, so far pristinamycin production titers are still quite low, particularly those of PI. In this study, we constructed a PI single component producing strain by deleting the PII biosynthetic genes (snaE1 and snaE2). Then, two metabolic engineering approaches, including deletion of the repressor gene papR3 and chromosomal integration of an extra copy of the PI biosynthetic gene cluster (BGC), were employed to improve PI production. The final engineered strain ΔPIIΔpapR3/PI produced a maximum PI level of 132 mg/L, with an approximately 2.4-fold higher than that of the parental strain S. pristinaespiralis HCCB10218. Considering that the PI biosynthetic genes are clustered in two main regions in the 210 kb “supercluster” containing the PI and PII biosynthetic genes as well as a cryptic polyketide BGC, these two regions were cloned separately and then were successfully assembled into the PI BGC by the transformation-associated recombination (TAR) system. Collectively, the metabolic engineering approaches employed is very efficient for strain improvement in order to enhance PI titer.

To enhance the impact ionization coefficient of holes, we proposed an improved solar-blind AlGaN avalanche photodiode (APD) structure by using a low-Al-composition AlGaN multiplication layer and a filter based on periodic photonic crystal together with a composition graded interlayer between separate absorption and multiplication regions. The simulation results show that the improved APD presents a lower breakdown voltage and dark current, and a higher optical gain when compared to its conventional counterpart. Further, we found that the composition graded interlayer can modify profitably energy-band profile of heterostructure interfaces besides adjusting the electric field distribution, which is beneficial to the injection of holes from the absorption region to multiplication region. Therefore, we optimized the doping concentration and thickness of the interlayer, and analyzed the effects of these parameters on the APD performances.

Gut microbiota dysbiosis is closely associated with primary hepatocellular carcinoma (HCC). Recent studies have evaluated the early diagnosis of primary HCC through analysis of gut microbiota dysbiosis. However, the relationship between the degree of dysbiosis and the prognosis of primary HCC remains unclear. Because primary HCC is accompanied by dysbiosis and dysbiosis usually increases the circulatory concentrations of endotoxin and other harmful bacterial substances, which further increases liver damage, we hypothesized that level of dysbiosis associated with primary HCC increases with the stage of cancer progression. To test this hypothesis, we introduced a more integrated index referred to as the degree of dysbiosis (Ddys); and we investigated Ddys of the gut microbiota with the development of primary HCC through high-throughput sequencing of 16S rRNA gene amplicons. Our results showed that compared with healthy individuals, patients with primary HCC showed increased pro-inflammatory bacteria in their fecal microbiota. The Ddys increased significantly in patients with primary HCC compared with that in healthy controls. Moreover, there was a tendency for the Ddys to increase with the development of primary HCC, although no significant difference was detected between different stages of primary HCC. Our findings provide important insights into the use of gut microbiota analysis during the treatment of primary HCC.

Standardizing the storage conditions of semen samples can improve the accuracy of detection results of sperm DNA fragmentation index (DFI) and reduce variability. This study aimed to investigate how different storage conditions affect the DFI results of sperm. To do this, thirty-five leftover semen samples were selected after routine testing. These samples had a sperm concentration of at least 10 × 106/mL, normal liquefaction, and no or few round cells. Each specimen was stored at room temperature (20 °C) for 2 and 4 hours, chilled (2–8 °C) for 1, 2 and 3 days, and frozen (−20 °C) for 3, 5 and 7 days, respectively. Each sample was frozen and thawed three times repeatedly. The sperm DFI at different time points was detected by sperm chromatin structure analysis (SCSA) based on flow cytometry. The results showed no significant differences in the sperm DFI of semen samples stored at room temperature for 0, 2 and 4 hours, chilled for 1, 2 and 3 days and frozen for 3, 5 and 7 days (p > 0.05). There were also no significant differences in the sperm DFI of semen samples frozen-thawed 1, 2 and 3 times repeatedly (p > 0.05). In conclusion, storage at room temperature for less than 4 hours, chilling for less than 3 days, freezing for less than 7 days and repeated freezing-thawing for 3 times have no significant impact on the sperm DNA damage of semen samples with sperm concentration ≥10 × 106/mL, normal liquefaction, and no or few round cells found in routine semen examination.

A series of AlN/GaN heterostructures were grown on 150 mm Si substrates by metal organic chemical vapor deposition (MOCVD). Different cap layer structures, including gallium nitride (GaN) and silicon nitride (SiN _x ), were used to passivate the heterostructure surface. A 3.5 nm thick SiN _x cap is able to maintain the two dimensional electron gas (2DEG) stability in a long period. An AlN/GaN heterostructure with a 4.5 nm thick AlN barrier exhibits the best 2DEG properties, in terms of sheet resistance, carrier mobility and stability. The carrier mobility of the 2DEG can be enhanced by a combination of SiNx and GaN cap layers to over 1400 cm ^2 /Vs.

OBJECTIVES:Genetic polymorphism of viral receptors is relevant to risks of HIV-1 infection, while it is still under debated whether the polymorphism of SDF1, a unique ligand for HIV-1 coreceptor CXCR4, is associated with HIV susceptibility and AIDS disease progression. Therefore, we provided an updated quantitative assessment by meta-analysis from 16 case-control and 7 cohort studies. METHODS:Articles reporting the relationship between SDF1 polymorphism and HIV susceptibility or AIDS progression were retrieved from PubMed, Embase and Ovid electronic databases up to Apr 2017. Data were pooled by odds ratios (ORs) for HIV-1 infection with 95% confidence intervals (CIs) and summary relative hazards (RHs) for AIDS progression with 95% CIs using 1987 Center for Disease Control (CDC) case definition of AIDS (CDC87) and 1993 Center for Disease Control (CDC) case definition of AIDS (CDC93) and death as endpoints. RESULTS:As a result, 16 studies regarding susceptibility to HIV-1 infection with 2803 HIV-infected patients and 3697 healthy individuals and 7 studies regarding disease progression with 4239 subjects were included in the meta-analysis. For risks of infection, no evidences indicated SDF1 polymorphism was associated with the risk of HIV-1 infection in all genetic models (recessive model: OR = 0.94, 95% Cl: 0.75-1.17; homozygous model: OR = 0.89, 95% Cl: 0.70-1.15; heterozygous model: OR = 1.06, 95% Cl: 0.83-1.35; allele model: OR = 0.95, 95% Cl: 0.79-1.13), Furthermore, we failed to find an delayed AIDS progression except in some specific cohorts including MACS cohorts (RH = 0.38, 95% Cl: 0.17-0.59 for time to AIDS; RH = 0.27, 95% Cl: 0.07-0.46 for time to death at the study entry). CONCLUSIONS:Overall, no significant association was found between SDF1 polymorphism and HIV susceptibility. A protective effect of SDF1 on AIDS progression and death was seen especially in two studies based on the same cohorts. In conclusion, SDF1 polymorphism exerts a moderate protective effect against AIDS disease deterioration in some specific populations.

Objectives: Altitude-hypoxia induces pulmonary arterial hypertension and altered cardiac morphology and function, which is little known in healthy children at high altitude. We compared the cardiopulmonary measurements between the healthy children at 16 m and those at 3700 m in China and between the Hans and the Tibetans at 3700 m. Methods: Echocardiography was assessed in 477 children (15 day–14 years) including 220 at 16 m and 257 at 3700 m. The dimensions and wall thickness of the left- and right-sided heart, systolic and diastolic functions including cardiac output index (CI) were measured using standard methods. Mean pulmonary arterial pressure (mPAP) was estimated by the Doppler waveforms in the main pulmonary artery. Results: Compared to the 16 m-group, 3700 m-group had higher mPAP, increasing dilatation of the right heart, and slower decrease in right ventricular hypertrophy in 14 years (p 0.20). Systolic and diastolic functions of both ventricles were significantly reduced, but CI was higher (p 0.05). Conclusions: Children living at high altitude in China have significantly higher mPAP, dilated right heart and slower regression of right ventricular hypertrophy in the first 14 years of life. Systolic and diastolic functions of both ventricles were reduced with a paradoxically higher CI. There was no significant difference in these features between the Hans and the Tibetans. These values provide references for the care of healthy children and the sick ones with cardiopulmonary diseases at high altitude.

Background: We investigated the application of a predictive nursing education process on the degree of comfort and quality of life for cancer patients. Methods: A total of 168-cancer patient in Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China between June 2014 and June 2016 were enrolled and admitted for surgery or radiotherapy/chemotherapy treatment. Patients were randomly divided into control and observation groups, each containing 84 cases. Patients in the control group received routine cancer care, whereas the observation group received care incorporating a predictive nursing education process. Patients were assessed after admission and prior to discharge via the Kolcaba's comfort status scale (through a General Comfort Questionnaire (GCQ)), quality of life scale (QOL), and Barthel Index (BI) for activities of daily living (ADL). Patient mental state was also evaluated using the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). Results: GCQ, QOL, and BI scores of the observation group were all significantly higher than those of the control group (P

The rapid development of valleytronics makes the application of two-dimensional (2D) transition-metal dichalcogenides (TMDs) in valley electronics important. As a new degree of freedom, valley splitting of TMDs has been achieved and tuned by many methods. Among them, using the magnetic proximity effect (MPE) generated from the interface of 2D van der Waals (vdW) heterostructures stacked with TMDs and one magnetic substrate, valley splitting can be achieved through band edge lifting at the adjacent K/K′ valley. However, the comprehensive mechanism and strategy of valley splitting in 2D TMD heterostructures need to be explored ulteriorly. Here, we systematically investigated valley splitting of MX2 in MX2/CrI3 (M = W, Mo; X = S, Se, Te) vdW heterostructures using first-principles approaches. We demonstrated that twisting is an effective method to enhance valley splitting in MX2/CrI3 vdW heterostructures. Furthermore, we also showed a ∼10 times enhancement in valley splitting by changing the stacking patterns between WTe2 and CrI3 layers. We attribute this to the interlayer magnetic and electronic coupling between the two layers of the vdW heterostructure. The present results provide a theoretical basis and effective methods for tuning valley splitting 2D TMD heterostructures. [ABSTRACT FROM AUTHOR]

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and proapoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy. [ABSTRACT FROM AUTHOR]

The pressure drop characteristics of subcooled water were experimentally investigated in a circular cooling channel with and without a twisted tape (TT) under high heat fluxes, which was designed for the water-cooling structure of the divertor target in a tokamak device. The working medium was deionized water, and the main parameters were mass flux G = 3000–8000 kg·m−2·s−1, inlet pressure of the test section p = 3, 4.2, 5 MPa, equivalent one-side heating flux qe = 5~10 MW·m−2. The off-center circular channel is electrically heated to simulate the unilateral radiation heating on the divertor target by high-temperature plasma. The pressure drop experiment of vertical upward circular cooling channels under high and unilateral heat flux is carried out. The influences of the TT and system parameters such as qe, G, and p on the pressure drop of the test section (Δp) were discussed in detail. In the single-phase (SP) flow region, Δp is mainly affected by the TT, G, and qe. The pressure drop with a TT is significantly higher than that without a TT, a higher G and a lower qe lead to a greater Δp. In the subcooled boiling (SB) flow region, Δp is correlated with the TT, qe, G, and p: the influence of the TT and G decreases, while the influence of p increases. The higher the qe, the higher the G, and the lower the p, the larger the Δp. The results show that almost all of the SP pressure drop correlations for heated circular channels overestimate the experimental pressure drop coefficient ratio for a given viscosity ratio. According to the test results, a new correlation of SP pressure drop under high and unilateral heat fluxes has been proposed, the average error (AE) and root mean square error (RMSE) of which are 0.26% and 3.17%, respectively. [ABSTRACT FROM AUTHOR]

To study the pressure drop characteristics of hypervapotron, which was designed as a water-cooling structure in the divertor dome of the fusion reactor, the pressure drop tests of subcooled water were carried out in a vertically upward hypervapotron. To simulate the one-side radiant heating condition in the engineering application, the non-uniform heat fluxes were obtained by using the off-center electrically heating method. The system parameters were as follows: mass flux G = 2000–5000 kg·m−2·s−1, inlet pressure p = 2–4 MPa, and equivalent one-side radiating heat flux qe = 0–5 MW·m−2. The effects of the parameters on the pressure drop were discussed in detail. It was observed that in the single-phase (SP) region, the pressure drop was little influenced by the inlet fluid temperature (Tb,in). However, in the subcooled boiling region, the pressure drop increased rapidly with the increasing Tb,in. A higher G leads to a high pressure drop. In the SP region, the influence of p on the pressure drop is not obvious, and the pressure drop decreased with the increasing qe. The test data are used to evaluate the typical pressure drop correlation, and the results show that none of these correlations can predict the pressure drop well under the test conditions. Therefore, a new pressure drop correlation is proposed for subcooled water in a hypervapotron under high and non-uniform heat fluxes. The new correlation has a high prediction accuracy for the test data, and the mean relative error (MRE) and root mean square error (RMSE) are 0.72% and 4.33%, respectively. The test results have a reference value for the design of the water-cooling structure of the diverter. [ABSTRACT FROM AUTHOR]