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To determine the effects of microwave radiation at the molecular level as well as on the germination, growth and morphology of dry spores at the single-cell level. Dry Bacillus aryabhattai MCCC 1K02966 spores were microwave-treated at different powers and characterized using single-cell optical technology. As determined by laser tweezers Raman spectroscopy, the Ca[Formula: see text]-dipicolinic acid content increased and nucleic acid denaturation occurred in response to microwave treatment. Live-cell microscopy revealed that the germination and growth rates decreased as the microwave power increased. With respect to morphology, atomic force microscopy (AFM) demonstrated that spores became wrinkled and rough after microwave treatment. Furthermore, spores became smaller as the microwave power increased. Microwave treatment can damage DNA, and high-power microwaves can inhibit the germination of spores and reduce spore volumes. These results provide a new perspective on the responses of living single cells to microwave radiation and demonstrate the application of various new techniques for analyses of microorganisms at the single-cell level.

The aim of this study was to explore the microecological distribution and differences in the uterus and vaginal microbiome in women with early embryonic arrest and those with normal pregnancy by high-throughput sequencing. We systematically sampled the vaginal and uterine microbiomes of 56 pregnant women, namely, 38 patients with early embryonic arrest and 18 pregnant women with normal pregnancy-induced abortion. We obtained colonization data by 16S rRNA gene amplicon sequencing. In the vagina, Lactobacillus, Bacteroidetes and Helicobacter exhibited significant differences between the groups. We further found that Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri and Lactobacillus jensenii were the most dominant Lactobacillus species and that L. iners was significantly different between the groups. Receiver operating characteristic (ROC) curve analysis confirmed that Ensifer had the highest predictive value for early embryonic arrest. In the uterine cavity, we determined that Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria were the dominant bacteria at the phylum level and that Bacteroides, Pseudarthrobacter, Lactobacillus and Ralstonia were the dominant genera. Further classification of Lactobacillus revealed that L. iners, L. crispatus, L. gasseri, and L. jensenii were the main species. There was a significant difference in L. jensenii between the normal pregnancy group and early embryonic arrest group. Random forest analysis revealed 18 different genera in the uterus, and ROC curve analysis indicated that Candidatus Symbiobacter, Odoribacter, Blautia, Nocardioides and Ileibacterium had a certain predictive value.

It has long been disputed whether Tetranychus cinnabarinus and Tetranychus urticae belong to the same genus, with T. cinnabarinus regarded as a red form of T. urticae. However, it is unclear why T. urticae and T. cinnabarinus have different body colors. Since carotenoids are responsible for the color of many organisms, the carotenoid profiles of T. cinnabarinus and T. urticae were compared by HPLC. There was no difference in carotenoid type, but T. cinnabarinus contained significantly more neoxanthin, astaxanthin, α-carotene, β-carotene, and γ-carotene, which may contribute to the deep red color. The transcriptome sequencing of both species identified 4079 differentially expressed genes (DEGs), of which 12 were related to carotenoid metabolism. RNA interference (RNAi) experiments demonstrated that silencing seven of these DEGs resulted in the different accumulation of carotenoid compounds in T. cinnabarinus and T. urticae. In addition, the body of T. urticae turned yellow after two days of feeding with UGT double-stranded RNAs and β-UGT small interfering RNAs. In conclusion, differences in the carotenoid profiles of T. urticae and T. cinnabarinus may be responsible for the different body colors.

Chlamydia pecorum is a zoonotic pathogen. Here, we report the first case of human infection with C. pecorum. A man aged 51 years with high fever and dry cough was diagnosed with severe community-acquired pneumonia and respiratory failure. C. pecorum was found responsible for the infection, which was detected from bronchoalveolar lavage fluid through metagenomic next-generation sequencing. C. pecorum infection was further identified by quantitative polymerase chain reaction and complement fixation test. The patient's condition improved rapidly after targeted treatment. He was a farmer with diabetes mellitus and had a history of close contact with sheep, which might result in C. pecorum infection. Our report could provide a direction for the diagnosis and treatment of human C. pecorum pneumonia.

Abstract Risperidone is routinely used in the clinical management of schizophrenia, but the treatment response is highly variable among different patients. The genetic underpinnings of the treatment response are not well understood. We performed a pharmacogenomic study of the treatment response to risperidone in patients with schizophrenia by using a SNP microarray -based genome-wide association study (GWAS) and whole exome sequencing (WES)-based GWAS. DNA samples were collected from 189 patients for the GWAS and from 222 patients for the WES after quality control in multiple centers of China. Antipsychotic response phenotypes of patients who received eight weeks of risperidone treatment were quantified with percentage change on the Positive and Negative Syndrome Scale (PANSS). The GWAS revealed a significant association between several SNPs and treatment response, such as three GRM7 SNPs (rs141134664, rs57521140, and rs73809055). Gene-based analysis in WES revealed 13 genes that were associated with antipsychotic response, such as GPR12 and MAP2K3. We did not identify shared loci or genes between GWAS and WES, but association signals tended to cluster into the GPCR gene family and GPCR signaling pathway, which may play an important role in the treatment response etiology. This study may provide a research paradigm for pharmacogenomic research, and these data provide a promising illustration of our potential to identify genetic variants underlying antipsychotic responses and may ultimately facilitate precision medicine in schizophrenia.

A T/C variant in miR-27a is associated with bipolar disorder, potentially by reducing the ability of this microRNA to target important neurodevelopmental genes like NCAM1.

The whispering-gallery mode and the atomic collapse state are two distinct resonances in condensed matter associated with relativistic massless charge carriers. Now, it is shown that these states can coexist in graphene/WSe2 heterostructure quantum dots.

Background: Cytokines play a role in the progression of idiopathic-nephrotic syndrome (INS). Objectives: To investigate the association of different cytokine genes polymorphisms with INS incidence and response to steroid therapy in Chinese children. Methods: 182 children with INS and 100 healthy controls were enrolled in this study. Blood genomic DNAs were used to analyze20 single nucleotide polymorphisms (SNPs) in 8 cytokine genes includingIL-21, IL-18, IL-6, IFN-γ, IL-4, IL-10, IL-17F, IL-17A d by multi-PCR with next-generation sequencing. Results: Among 182 children with INS, 89 (48.6%) were steroid-sensitive (SS), 73 (39.9%) were steroid-dependent (SD) and 21 (11.5%) were steroid-resistant (SR). In 20 SNPs, IL-4-rs2243283 exhibited a significantly different genotype distribution between INS and the healthy controls (CC is a risk genotype: 66.5% of INS VS 51% of the control; OR=1.91, p=0.012). Patients carrying AG genotype (rs2275913, IL-17A) had a significantly higher risk of steroid-dependent response (69.1% of SD VS 46.4% of SS; OR=2.58, p=0.014). Similarly, patients carrying A allele of IL-10-rs1800872 (39.0% of SD VS 26.7% of SS; OR=1.76, p=0.018) and C allele of IL-10-rs1800896 (12.3% of SD VS 3.9% of SS; OR=3.44, p=0.004) had a higher risk of steroid-dependent response. However, none of these 20 SNPs showed a significant difference between SS group and SR group. Conclusion: Among the 20 cytokine gene SNPs, IL-4-rs2243283 might increase the susceptibility to INS in Chinese children; rs2275913 of IL-17A, rs1180972, and rs1800896 of IL-10 show association with the steroid -response in Chinese INS children.

Abstract. Objective:. Rubicon is an inhibitory interacting protein of the autophagy-related protein Uvrag. We previously showed that Rubicon deficiency promotes autophagic flux in vivo and that autophagy can degrade lipid droplets. This study aimed to investigate the effects of Rubicon deficiency on fasting-induced hepatic steatosis. Methods:. Two-month-old wild-type (WT) and Rubicon-deficient mice were subjected to feeding or fasting for 24 hours to induce hepatic steatosis. The distribution of liver lipid droplets was revealed by oil red O staining. Hepatic and plasma triglyceride, non-esterified fatty acid (NEFA), and cholesterol levels were detected using commercially available kits. Real-time reverse transcriptase-polymerase chain reaction was performed to analyze the mRNA expression of genes related to lipid metabolism in the liver. Western blot was conducted to assess autophagy-related protein levels in the liver. The animal experiments were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University, China. Results:. We showed that under fasting conditions, Rubicon-deficient mice had more lipid droplets in the liver than WT controls. Consistent with these results, the hepatic triglyceride, NEFA, and cholesterol levels in fasted Rubicon-deficient mice were significantly higher than those of fasted WT controls. The levels of SREBP-1, a key regulator of lipid synthesis, were significantly lower in livers from fasted WT mice than those of fed WT mice. However, the decrease in SREBP-1 in fasted mice was attenuated by Rubicon deficiency. Western blot analysis demonstrated that the fasting-induced increase in autophagic flux was amplified by Rubicon deficiency. Finally, we showed that Rubicon deficiency in mice led to elevated plasma triglyceride and NEFA acid levels under fasting conditions. Conclusion:. Rubicon deficiency exacerbates fasting-induced hepatic steatosis in mice.

BackgroundSince the discovery of rehabilitation as an intervention for rotator cuff injury, its impact on the recovery of rotator cuff injury has attracted crucial attention, and the number of related studies is increasing worldwide. There were no bibliometric and visualized analysis studies in this field. This study aimed to investigate the research hotpots and trends in the rehabilitation of rotator cuff injury via bibliometric and visualized analysis and to identify the future development of clinical practice.MethodThe publications regarding rehabilitation of rotator cuff injury from inception to December 2021 were obtained from the Web of Science Core Collection database. The trends of publications, co-authorship and co-occurrence analysis and visualized analysis were carried out using Citespace, VOSviewer, Scimago Graphica software, and R Project.ResultsA total of 795 publications were included in this study. The number of publications significantly increased yearly. The United States published the highest number of related papers and the papers published by the United States had the highest citations. The University of Laval, the University of Montreal and Keele University were the top 3 most contributive institutions. Additionally, the Journal of Shoulder and Elbow Surgery was the journal with the highest number of publications. The most common keywords were “rotator cuff”, “rehabilitation”, “physical therapy”, “management”, and “telerehabilitation”.ConclusionThe total number of publications has shown a steady upward trend. The cooperation between countries globally was still relatively lacking, and therefore it is necessary to strengthen cooperation between different countries and regions to provide conditions for multi-center, large sample, and high-quality research. In addition to the relatively mature rehabilitation of rotator cuff injury such as passive motion or exercise therapy, telerehabilitation has also attracted much attention with the progress of science.

The demountable and modular light-gauge steel framed (DMLSF) wallboard is presented and used as non-load bearing exterior walls in medium and high-rise steel construction or temporary structure. Firstly, the bending tests were conducted on five wall modules to explore the flexural behavior of the wall. The numerical model was also established and verified by experimental results, and the simplified calculation method of the flexural capacity of the wall was proposed based on 68 numerical models. In addition, the reliability test of the seam between modules was finished to ensure the airtightness of the wall. Furthermore, the demountable behavior of the wall was studied by secondary loading tests and life cycle assessment (LCA) methodology. Results suggested that the wallboard could be used repeatedly after disassembled under the serviceability limit state. Raw materials, especially the insulation material, accounted for a large proportion of the environmental impact of the wallboard. The wallboard’s carbon dioxide emission and energy consumption could be significantly reduced when the wallboard was reused. This study can promote the application of the demountable concept in wall components and provide some guidance for the life cycle design of demountable structures.

Abstract Clustering enzymes in the same metabolic pathway is a natural strategy to enhance productivity. Synthetic protein, RNA and DNA scaffolds have been designed to artificially cluster multiple enzymes in the cell, which require complex construction processes and possess limited slots for target enzymes. We utilized the Escherichia coli inner cell membrane as a native scaffold to cluster four fatty acid synthases (FAS) and achieved to improve the efficiency of fatty acid synthesis in vivo. The construction strategy is as simple as fusing target enzymes to the N‐terminus or C‐terminus of the membrane anchor protein (Lgt), and the number of anchored enzymes is not restricted. This novel device not only presents a similar efficiency in clustering multiple enzymes to that of other artificial scaffolds but also promotes the product secretion, driving the entire metabolic flux forward and further increasing the gross yield compared with that in a cytoplasmic scaffold system.

Preimplantation embryo arrest (PREMBA) is a common cause of female infertility and recurrent failure of assisted reproductive technology. However, the genetic basis of PREMBA is largely unrevealed. Here, using whole-exome sequencing data from 606 women experiencing PREMBA compared with 2,813 controls, we performed a population and gene–based burden test and identified a candidate gene, karyopherin subunit α7 (KPNA7). In vitro studies showed that identified sequence variants reduced KPNA7 protein levels, impaired KPNA7 capacity for binding to its substrate ribosomal L1 domain-containing protein 1 (RSL1D1), and affected KPNA7 nuclear transport activity. Comparison between humans and mice suggested that mouse KPNA2, rather than mouse KPNA7, acts as an essential karyopherin in embryonic development. Kpna2–/– female mice showed embryo arrest due to zygotic genome activation defects, recapitulating the phenotype of human PREMBA. In addition, female mice with an oocyte-specific knockout of Rsl1d1 recapitulated the phenotype of Kpna2–/– mice, demonstrating the vital role of substrate RSL1D1. Finally, complementary RNA (cRNA) microinjection of human KPNA7, but not mouse Kpna7, was able to rescue the embryo arrest phenotype in Kpna2–/– mice, suggesting mouse KPNA2 might be a homologue of human KPNA7. Our findings uncovered a mechanistic understanding for the pathogenesis of PREMBA, which acts by impairing nuclear protein transport, and provide a diagnostic marker for PREMBA patients.

Consistent condom use with casual partners is critical for preventing the transmission of human immunodeficiency virus (HIV) among male university students. This study aimed to determine the level of consistent condom use and explore the correlates of condom use consistency in male university students in eastern China. A descriptive cross-sectional survey was conducted in 13 universities in Zhejiang Province, which involved the recruitment of 31,674 students by stratified random sampling. Among them, 545 male students who engaged in casual sex in the year prior to this study were included. Adjusted and unadjusted logistic regression models were used to examine the correlates associated with consistent condom use. Among the 545 male university students, only 205 (37.6%) consistently used condoms in the previous year. The following correlates were associated with higher rates of consistent condom use: 1) Knowledge, specifically, the number of correct answers to "HIV infection can be determined by appearance" (AOR: 2.06, 95% CI: 1.21-3.49); 2) never finding casual partners on the internet during the past over the prior year (AOR: 0.63; 95% CI: 0.40-0.99); 3) never drinking alcohol before casual sex during the last over the prior year (AOR: 0.30; 95% CI: 0.20-0.46); 4) never engaging in commercial sex (AOR: 0.57; 95% CI: 0.34-0.96); and 5) high condom self-efficacy score (AOR: 2.55; 95% CI: 1.44-4.49). The study found a low level of consistent condom use among male university students. Promoting condom self-efficacy, reducing web-based casual sex, drinking before sex, and commercial sex are essential to improving the level of consistent condom use among male university students to reduce the transmission of HIV.

Objective: Leonurine is a bioactive alkaloid compound extracted from Leonurus japonicus Houtt, which potentially has immunomodulatory effects. The immunomodulatory effect and mechanism of leonurine on monocyte derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients were investigated for the first time.Methods: Peripheral blood from HDs and MM patients was isolated for peripheral blood mononuclear cells (PBMCs). The generation of moDCs was conducted by the incubation of monocytes from PBMCs in the medium consisting of RPMI 1640 medium, 2 mmol/L L-glutamine, 5% human serum, 800 U/mL GM-CSF, 500 U/mL IL-4, 100 U/mL penicillin and 0.1 mg/mL streptomycin. During the incubation of 7 days, the cells were administrated with 1 μM leonurine or 1 × PBS as the control group. On the 8th day, cells were harvested. The expression of maturation associated surface markers CD40, CD83, and HLA-DR on moDCs was analyzed by flow cytometry. Moreover, moDCs with or without 1 μM leonurine administration were evaluated by LC-MS/MS for metabolomics which was further analyzed for the potential mechanism of leonurine on moDCs.Results: The proportion of moDCs in the harvested cells was significantly higher in the HD group (n = 14) than in the MM patient group (n = 11) (p = 0.000). Leonurine significantly enhanced the median fluorescence intensity of CD83, HLA-DR and CD40 expression on HD-moDCs (n = 14; p = 0.042, p = 0.013, p = 0.084) as well as MM paitent-moDCs (n = 11; p = 0.020, p = 0.006, p = 0.025). The metabolomics data showed that in moDCs (HD, n = 15), 18 metabolites in the pathway of arachidonic acid metabolism showed significant differences between the leonurine group and the control group (VIP all >1 and P all

The gut microbiome and host genetics are both associated with major depressive disorder (MDD); however, the molecular mechanisms among the associations are poorly understood, especially in the Asian, Chinese group. Our study applied linear discriminant analysis (LDA) effect size (LEfSe) and genome-wide association analysis in the cohort with both gut sequencing data and genomics data. We reported the different gut microbiota characteristics between MDD and control groups in the Chinese group and further constructed the association between host genetics and the gut microbiome. Actinobacteria and Pseudomonades were found more in the MDD group. We found significant differences in the ACE and Chao indexes of alpha diversity while no discrepancy in beta diversity. We found three associations between host genetics with microbiome features: beta diversity and rs6108 (p = 8.65 × 10–9), Actinobacteria and rs77379751 (p = 8.56 × 10–9), and PWY-5913 and rs1775633082 (p = 4.54 × 10–8). A species of the Romboutsia genus was co-associated with the species of Ruminococcus gnavus in an internetwork through four genes: METTL8, ITGB2, OTULIN, and PROSER3, with a strict threshold (p < 5 × 10–4). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced SERPINA5 and other spatially close genes afterward. These findings suggest new linkages between depression and gut microbiome in Asian, Chinese people, which might be mediated by genes and microRNA regulation in space distance.

Background: Accumulating evidence shows that DNA methylation plays a role in antipsychotic response. However, the mechanisms by which DNA methylation changes are associated with antipsychotic responses remain largely unknown.Methods: We performed a methylome-wide association study (MWAS) to evaluate the association between DNA methylation and the response to risperidone in schizophrenia. Genomic DNA methylation patterns were assessed using the Agilent Human DNA Methylation Microarray.Results: We identified numerous differentially methylated positions (DMPs) and regions (DMRs) associated with antipsychotic response. CYP46A1, SPATS2, and ATP6V1E1 had the most significant DMPs, with p values of 2.50 × 10–6, 3.53 × 10–6, and 5.71 × 10–6, respectively. The top-ranked DMR was located on chromosome 7, corresponding to the PTPRN2 gene with a Šidák-corrected p-value of 9.04 × 10–13. Additionally, a significant enrichment of synaptic function and neurotransmitters was found in the differentially methylated genes after gene ontology and pathway analysis.Conclusion: The identified DMP- and DMR-overlapping genes associated with antipsychotic response are related to synaptic function and neurotransmitters. These findings may improve understanding of the mechanisms underlying antipsychotic response and guide the choice of antipsychotic in schizophrenia.

Objective: To explore the effect of pomalidomide on the maturation of monocyte-derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients.Methods: MoDCs were generated by the incubation of monocytes from peripheral blood mononuclear cells (PBMCs) for 7 days in a medium consisting of 800 U/ml granulocyte-macrophage colony stimulating factor (GM-CSF), 500 U/ml interleukin-4 (IL-4), RPMI 1,640 medium, 5% human serum, 100 U/ml penicillin and 0.1 mg/ml streptomycin. Meanwhile, the incubation system was administrated with 10 µM pomalidomide or 1 × PBS as the control group. On the eighth day, cells were harvested and analyzed by flow cytometry. The CD80+CD86+ cell population in total cells was gated as moDCs in the FACS analyzing system. After that, the expression of CD40 and HLA-DR on moDCs was analyzed. Meanwhile, the supernatant from the incubation system was evaluated for the secretion of cytokines interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein 1α (MIP-1α) by enzyme-linked immunosorbent assay (ELISA).Results: When analyzing all the HD-moDCs together (n = 15), pomalidomide significantly increased the mean fluorescence intensity (MFI) of CD40 expression and HLA-DR expression on moDCs compared with the control group (p = 0.003, p = 0.040). Meanwhile, the proportion of CD40+ moDCs and HLA-DR+ moDCs in total moDCs was significantly higher in the pomalidomide group than in the control group (p = 0.008, p = 0.032). When analyzing all MM patient-moDCs together (n = 11), pomalidomide significantly increased the MFI of CD40 expression and HLA-DR expression on moDCs compared with the control group (p = 0.047, p = 0.006). Meanwhile, the proportion of HLA-DR+ moDCs in total DCs was significantly higher in the pomalidomide group than in the control group (p < 0.001). Moreover, HD-moDCs (n = 8) treated with pomalidomide secreted 192% IL-12, 110% TNF-α, and 112% MIP-1α of the untreated moDCs (p = 0.020, p = 0.006, p = 0.055). However, when analyzing MM patient-moDCs (n = 10) together, the secretion of IL-12, TNF-α and MIP-1α from moDCs showed no significant difference between the pomalidomide group and the control group (p = 0.458, p = 0.377, p = 0.248).Conclusion:In vitro, 10 µM pomalidomide enhances the maturation of moDCs derived from both HDs and MM patients. Pomalidomide shows potential to be applied as a DC adjuvant for DC-based immunotherapy, such as the DC vaccine and DC cell therapy in MM.

Due to the popularity of 5G connectivity and The Internet of Things sensors, deep learning algorithms are being extended to edge devices. Compared with AI(Artificial Intelligence) cloud platforms, the deployment of deep neural networks on edge devices must focus on low power consumption, low latency, stability and reliability. In recent years, the development of lightweight deep neural network architecture has provided a basis for the deployment of deep neural networks on edge devices. However, the shortcomings of deep neural networks, such as overconfidence, vulnerability to adversarial attack, and easy over fitting when samples are insufficient, still limit their applications in many fields. One of the ways to compensate for these defects is to use deep ensemble. An ordered aggregation-based ensemble selection algorithm is proposed, which uses soft-margin as the importance assessment metric to take full advantage of the diversity and complementarity of lightweight deep neural networks obtained from different initialization training, so as to improve the overall performance of multiple edge devices. The experimental results show that this algorithm has a significant improvement in generalization performance compared with random ensemble and ordered aggregation algorithms based on accuracy or diversity, and provides a new complementary idea for the deployment of lightweight deep neural networks on edge devices.

Many patients with genetic syndromes have special facial features, which boast significant potential value for clinical diagnosis. Deep learning and computer vision technology can be employed to diagnose genetic diseases by analyzing facial features of patients. As a matter of fact, the application of deep learning technology in the area of genetic diseases is confined owing to the difficulties of patient data acquisition. This study develops BioFace, a deep learning framework that can recognize multiple genetic diseases facial attributes based on limited datasets. BioFace is a deep neural network architecture designed premised on Resnet. To increase the weight of effective features and weaken the weight of invalid or unobvious features during extraction of facial features, we add Squeeze-and-Excitation (SE) blocks in the network. In combination with this network architecture, we designed a cross-loss training method based on transfer learning. This method can transfer the ability learned from the task of face identification to the task of recognition of genetic diseases facial attribute, and improve the inter-class distance of different genetic diseases and the intra-class distance of similar genetic diseases simultaneously. These render it possible for deep learning to be applied to recognition of multiple genetic diseases facial attribute with very small amount of data. In this research, we tested 10 syndromes with our framework and the Top-1 accuracy was 93.5%, which is the state-of-the-art in multiple genetic syndromes recognition research. In practical clinical applications, our framework and methods can be extended to the disease identification of more small datasets, potentially offering valuable assistance for the auxiliary clinical application of genetic diagnosis and other related genetic research.

Abstract Background During male meiosis, the Y chromosome can form perfect pairing with the X chromosome. However, it is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs). Results We found that spermatogenesis was restarted by transplanting FGSCs into Kit w/wv mutant testes. Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kit w/wv mutant mice, cytokines and retinoic acid. Healthy offspring were produced by sperm and SLCs derived from the in vivo and in vitro transdifferentiation of FGSCs, respectively. Furthermore, high-throughput chromosome conformation capture sequencing(Hi-C-seq) and “bivalent” (H3K4me3-H3K27me3) micro chromatin immunoprecipitation sequencing (μChIP-seq) experiments showed that stimulated by retinoic acid gene 8 (STRA8)/protamine 1 (PRM1)-positive transdifferentiated germ cells (tGCs) and male germ cells (mGCs) display similar chromatin dynamics and chromatin condensation during in vitro spermatogenesis. Conclusion This study demonstrates that sperm can be produced from FGSCs without a Y chromosome. This suggests a strategy for dairy cattle breeding to produce only female offspring with a high-quality genetic background.

Abstract Background In recent years, studies that used routinely collected data (RCD), such as electronic medical records and administrative claims, for exploring drug treatment effects, including effectiveness and safety, have been increasingly published. Abstracts of such studies represent a highly attended source for busy clinicians or policy-makers, and are important for indexing by literature database. If less clearly presented, they may mislead decisions or indexing. We thus conducted a cross-sectional survey to systematically examine how the abstracts of such studies were reported. Methods We searched PubMed to identify all observational studies published in 2018 that used RCD for assessing drug treatment effects. Teams of methods-trained collected data from eligible studies using pilot-tested, standardized forms that were developed and expanded from “The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology” (RECORD-PE) statement. We used descriptive analyses to examine how authors reported data source, study design, data analysis, and interpretation of findings. Results A total of 222 studies were included, of which 118 (53.2%) reported type of database used, 17 (7.7%) clearly reported database linkage, and 140 (63.1%) reported coverage of data source. Only 44 (19.8%) studies stated a predefined hypothesis, 127 (57.2%) reported study design, 140 (63.1%) reported statistical models used, 142 (77.6%) reported adjusted estimates, 33 (14.9%) mentioned sensitivity analyses, and 39 (17.6%) made a strong claim about treatment effect. Studies published in top 5 general medicine journals were more likely to report the name of data source (94.7% vs. 67.0%) and study design (100% vs. 53.2%) than those in other journals. Conclusions The under-reporting of key methodological features in abstracts of RCD studies was common, which would substantially compromise the indexing of this type of literature and prevent the effective use of study findings. Substantial efforts to improve the reporting of abstracts in these studies are highly warranted.

Abstract Objectives This study aimed to evaluate the comorbidities among severe and non‐severe COVID‐19 patients in Asian versus non‐Asian populations. Design Systemic review and Meta‐analysis. Methods A systematic literature search was conducted using PubMed, Embase, Scopus and the web of science Database up to 24 March 2021. Odds ratios were calculated using a random‐effects model. Results We identified 66 studies including 39 Asian and 27 non‐Asian studies. This study demonstrated that the proportion of hypertension was significantly higher in severe group than in non‐severe group for Asian (OR = 2.46) and non‐Asian (OR = 1.60, 95% CI: 1.37–1.86, I2 = 84%; p

Finite element simulation is able to predict cutting force, temperature, stress distribution and chip formation. Constructing a constitutive model suitable for cutting simulation can accurately describe the state of the cutting process, which plays an important role in improving surface quality as well as optimizing cutting parameters and tool geometric design. Nickel-based superalloys are widely used in aerospace due to their excellent physical and mechanical properties at high temperatures. In this study, J-C parameters reverse identification of Inconel 718 alloy was carried out in both the solution annealed state and precipitation hardened state. The average cutting force and chip thickness were obtained by conducting orthogonal cutting experiments, after which the shear angle was calculated. Through quasi-static compression experiments, the yield strength, strain hardening modulus and hardening index of the material were then obtained. Considering the influence of the cutting-edge radius on cutting force during the cutting process, the Waldorf model was introduced into the analytical model in order to describe the deformation characteristics (strain, temperature, strain rate and stress) of the primary shear zone, after which the shear force was modified. The J-C constitutive parameters of the solution annealed state and precipitation hardened state were inversely identified by the intelligent optimization algorithm. According to the given range of cutting conditions, the accuracy of the method was verified through comparison with the cutting force and chip morphology of the finite element simulation. The differences in quasi-static and cutting dynamic mechanical responses of the two states were subsequently expounded. The effects of tool wear types and cutting parameters on the material flow characteristics at the tool tip as well as the thermal-mechanical load on the machined surface of precipitation hardened state Inconel 718 alloy were analyzed via numerical simulation. Accordingly, this study may provide insight into the identification of constitutive parameters of superalloys as well as the control of machined surface quality.

Medium spatial resolution surface reflectance image series from the combination of Landsat-8 Operational Land Imager and Sentinel-2 Multispectral Imager observations have great importance to the land surface monitoring tasks, for which great efforts have been paid for blending the two data. However, most of the efforts focus on the image series with spatial resolution of 30 m, which cannot meet the data demand of some applications. Therefore, it is necessary to fuse Landsat-8 and Sentinel-2 images to provide 10-m image series. Currently, there are three means to achieve that, including the area-to-point regression kriging fusion approach (ATPRK), spatiotemporal fusion methods, and deep-learning-based fusion models. However, the ATPRK and spatiotemporal fusion methods suffer from the limited fusion performance, while the deep-learning-based fusion models are hardware dependent, i.e., requiring the graphics processing units, which may not be satisfied sometimes. To address these issues, in this article, we develop a new pixel-wise local normalization-based fusion method (LN-FM) for fusing Sentinel-2 and Landsat-8 images. The newly proposed LN-FM is compared to the ATPRK and three representative spatiotemporal fusion methods in experiments, which use imagery collected from both a rural area and an urban area. The experimental results demonstrate that the newly developed LN-FM exhibits excellent qualitative and quantitative performance, as well as remarkable spatial, spectral, and pixel distribution fidelity. Furthermore, this approach is fast, which may improve its applicability

Abstract Background Indian Hedgehog (IHH), an important cell signaling protein, plays a key regulatory role in development of cartilage and chondrogenesis. Earlier studies have shown that heterozygous missense mutations in IHH gene may cause brachydactyly type A1 (BDA1), an autosomal dominant inheritance disease characterized by apparent shortness or absence of the middle phalanges of all digits. MicroRNAs (miRNAs) have been found to be significant post-transcriptional regulators of gene expression and significantly influence the process of bone-development. Therefore, it is possible that miRNAs are involved in the mechanism underlying the development of BDA1. However, the relationship between miRNAs and the pathogenesis of BDA1 remains unclear. Methods In this study, we used microarray-based miRNA profiling to investigate the role of miRNAs in BDA1 by characterization of differentially expressed miRNAs in C3H10T1/2 cell line induced by wild type (WT) and p.E95K mutant (MT) IHH signaling. Results Our results identified 6 differentially expressed miRNAs between WT and control (CT) group and 5 differentially expressed miRNAs between MT and CT groups. In particular, miR-135a-1-3p was found to be a significantly differentially expressed miRNA between WT and CT group. Results of dual-luciferase reporter gene experiment successfully discovered Hoxd10 was one of the target gene of miR-135a-1-3p. Additionally, our pathway analysis revealed that the targets of these miRNAs of interest were highly involved with Runx1/2, Notch and collagen-related pathways. Conclusions Taken together, our findings provided important clue for future study of the process of miRNA-regulation in IHH signaling and novel insights into the regulatory role of miRNA in pathogenesis of BDA1.

We introduce an approach for the direct measurement of the gravitational potential (GP) along the trajectory of a satellite, with a specific focus on Low-Earth Orbit (LEO) satellites. A LEO satellite communicates with several Geosynchronous Equatorial Orbit (GEO) satellites via frequency signal links. The GP difference can be measured in real-time using the gravitational frequency shift approach by equipping both LEO and GEO satellites with precise atomic clocks. Since the GP at the high orbits of the GEO satellites can be precisely determined by the present gravitational field model EGM2008, the GP along the LEO satellite’s trajectory can be determined. In this study, simulation experiments were conducted, featuring a GRACE-type satellite as the LEO satellite in communication with three equidistant GEO satellites. The results indicated that the accuracy of the GP measurements along the LEO satellite’s trajectory primarily depends on the precision of the onboard atomic clocks. Supposing optical atomic clocks attain an instability level of 1×10−17τ−1/2 (τ in seconds), we determined the GP distribution covered by the LEO satellite’s trajectories with 30-day observations. Then, we determined a gravitational field at the centimeter level based on the GP distribution. The GP data derived from the trajectory of a LEO satellite can be utilized to establish temporal gravitational fields, which have broad applications in different disciplines.

High-entropy alloys (HEAs) with excellent mechanical properties have broad application scope and application prospects. However, it is difficult to obtain the optimized element composition, based on the traditional equiatomic or near-equiatomic statistical analysis of the phase selection rules. The non-equiatomic HEAs have abundant constituents combination by optimizing the type and content of elements. In this study, Ni10Cr6WFe9TiAlx (x = 0, 1.0 and 1.5, at.%) HEAs were prepared by vacuum arc melting. The effect of Al content x on microstructure and mechanical properties of HEAs was systematically studied. The results show that the HEAs are composed mainly of face-centered cubic (FCC) with hexagonal Al2W phase. The increase of Al content promotes the formation of the hexagonal Al2W phase. When the Al mole content is 1.0, the Ni10Cr6WFe9TiAl HEA material has achieved superior mechanical properties. The alloy exhibited a high ultimate tensile strength of 741 MPa and a large total elongation of 46%. The improvement in the mechanical properties of the Ni10Cr6WFe9TiAl HEA is mainly attributed to the precipitation strengthening of the high-density Al2W phase. This work provides a reference for the future design of Al2W precipitation-strengthened non-equiatomic HEAs with ideal properties.

The use of insect-specific odorants to control the behavior of insects has always been a hot spot in research on “green” control strategies of insects. However, it is generally time-consuming and laborious to explore insect-specific odorants with traditional reverse chemical ecology methods. Here, an insect odorant receptor (OR) and ligand database website (iORandLigandDB) was developed for the specific exploration of insect-specific odorants by using deep learning algorithms. The website provides a range of specific odorants before molecular biology experiments as well as the properties of ORs in closely related insects. At present, the existing three-dimensional structures of ORs in insects and the docking data with related odorants can be retrieved from the database and further analyzed.

The International Association of Geodesy (IAG) aims to establish the International Height Reference System (IHRS) as one of its primary scientific objectives. Central to the realization of the IHRS is global vertical datum unification, which requires the connection of existing local vertical height reference systems (VHS) robustly and consistently. However, conventional methods are not suitable for estimating the offsets between two distant local height systems. In this paper, we propose a framework for connecting two local VHSs using ultraprecise clock frequency signal links between satellites and ground stations, referred to as the satellite frequency signal transmission (SFST) approach. The SFST approach allows for the direct determination of the geopotential and height differences between two ground datum stations without any location restrictions between the two VHSs. The simulation results show that the VHSs of China and the US can be unified with an accuracy of several centimeters, provided that the stability of atomic clocks used on-board the satellite and at on-ground datum locations reaches 4.8×10−17τ−1/2 for an averaging time τ (in seconds). We conclude that the SFST approach shows promise for achieving centimeter-level accuracy in unifying the global vertical height datum and represents a new paradigm for the realization of the IHRS.

Abstract The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.

Abstract Schizophrenia is a debilitating mental disorder and often has a prodromal period, referred to as clinical high risk (CHR) for psychosis, prior to the first episode. The etiology and pathogenesis of schizophrenia remain unclear. Despite the human gut microbiome being associated with schizophrenia, the role of the oral microbiome, which is a vital player in the mouth–body connection, is not well understood. To address this, we performed 16S rRNA gene sequencing to investigate the salivary microbiome in 85 patients with drug-naïve first-episode schizophrenia (FES), 43 individuals at CHR, and 80 healthy controls (HCs). The salivary microbiome of FES patients was characterized by higher α-diversity and lower β-diversity heterogeneity than those of CHR subjects and HCs. Proteobacteria, the predominant phylum, was depleted, while Firmicutes and the Firmicutes/Proteobacteria ratio was enriched, in a stepwise manner from HC to CHR to FES. H2S-producing bacteria exhibited disease-stage-specific enrichment and could be potential diagnostic biomarkers for FES and CHR. Certain salivary microbiota exhibited disease-specific correlation patterns with symptomatic severities, peripheral pro-inflammatory cytokines, thioredoxin, and S100B in FES. Furthermore, the metabolic functions from inferred metagenomes of the salivary microbiome were disrupted in FES, especially amino acid metabolism, carbohydrate metabolism, and xenobiotic degradation. This study has established a link between salivary microbiome alterations and disease initiation and provided the hypothesis of how the oral microbiota could influence schizophrenia.

The microstructure of machined superficial layer significantly affects the mechanical properties and service life of mechanical components. Herein, to obtain a machined surface with excellent properties, a comprehensive application of theoretical calculations and test analysis research methods was conducted to investigate the influence mechanism of machining on performance and quality of machined superficial layer of high-strength alloy steel during machining, and reveal the intrinsic correlation between microstructure evolution, quality and performance of machined superficial layer. The results indicate that the machining can achieve gradient microstructure on the machined surface, which can improve the performance of machined surface greatly. From the surface to the inside region, the layers are respectively the recrystallized layer where compact nano-sized equiaxed grains are located, the rheological layer with clusters of high-density sub-grain structures, and the distorted layer with residual distorted grains. The maximum strain of superficial layer in the machined state is 2.81 times that of the original state. The grains are evidently refined and the grain size is reduced by 49.03%. The dislocation density is enhanced by 100.69%, while the number of small-angle grain boundaries (SAGB) and other substructures increase sharply, being 5.26 times that in the original state. By performance testing, the machining substantially enhances the hardness of the superficial layer of high-strength alloy steel with certain rise in toughness simultaneously, which is exactly the result of the combined effect of fine-grain strengthening and dislocation strengthening caused by the machining process above.

Abstract Background Restenosis after angioplasty is a major challenge for the treatment of coronary artery diseases. Facilitation of vascular smooth muscle cell (VSMC) apoptosis may be an attractive approach to decrease the incidence of restenosis. We synthesized a 16-amino acid mitofusin-2 (Mfn-2) gene related peptide (MRSP) based on the sequence of the p21ras signature motif, the smallest functional sequence of the Mfn-2 gene with proapoptotic properties in VSMC. We investigated whether MRSP enhanced apoptotic activities to inhibit VSMC accumulation and neointimal hyperplasia in rats with carotid balloon injury. Methods VSMCs were treated with different concentrations of MRSP, the PI3K agonist 740 Y-P and the inhibitor LY294002. Cell apoptosis and related pathway molecules were assessed. MRSP was also given to rats with carotid artery balloon injury. Neointimal hyperplasia and cell apoptotic pathways were detected. Results In vitro experiments revealed that MRSP treatment significantly increased VSMC apoptosis and induced increases in procaspase-9 cleavage, caspase-3 activation, cytochrome c release from mitochondria to the cytoplasm and the Bax/Bcl-2 ratio but not caspase-8 expression, indicating that the mitochondrial apoptotic cascade was activated by MRSP, which might be attributed to suppression of the PI3K/Akt signaling pathway. We further found that the PI3K agonist 740 Y-P prevented and that the inhibitor LY294002 strengthened the proapoptotic effects of MRSP. MRSP strongly inhibited neointimal hyperplasia and VSMC accumulation, but increased VSMC apoptosis in the vascular wall after balloon injury. Moreover, MRSP substantially enhanced Bax and cleaved caspase-3 expression and decreased Bcl-2 levels in intima, accompanied by decreased levels of phosphorylated Akt and PI3K in vivo. Conclusions Taken together, the present study showed that MRSP treatment results in a strong proapoptotic effect by activating the mitochondrial apoptotic cascade through suppression of the PI3K/Akt pathway.

Enantiomeric bridged [2,2,1] bicyclic lactone skeletons and their ring-opening products are important scaffolds widely occurring in both pharmaceutics and biology active compounds. Here the authors show an efficient method for enantioselective construction of these compounds bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/ pyridinium chlorochromate oxidation.

Abstract. Objective:. Venlafaxine is a common antidepressant and its therapeutic effect varies among people with different genetic backgrounds. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the SLC17A7 gene are associated with the treatment outcome of venlafaxine in a Chinese Han population with major depressive disorder. Methods:. This prospective pharmacogenetic case-control study that involved genotyping of four SNPs of SLC17A7 was conducted on 175 major depressive disorder patients of Chinese Han origin, aged 18 to 65 years, participated in the study from April 2005 to September 2006. Comparisons of allele and genotype frequencies of all SNPs were performed between the responder/remission group and the nonresponder/nonremission group. This study was approved by the Institutional Ethics Committee of Sichuan University (approval No. 20151112-265). Results:. The allele and genotype frequencies of the four candidate SNPs in SCL17A7 showed no significant difference between responders and nonresponders. Meanwhile, no significant difference was detected in the four investigated SLC17A7 SNPs between patients who did and did not exhibit remission. Although one of the investigated SLC17A7 variants (rs1578944) demonstrated a significant association (P = 0.022) with a response to venlafaxine after 6 weeks of treatment in the survival analysis, the association was unclear after a Bonferroni multiple comparisons test was conducted. Conclusion:. No significant association exists between the four candidate SNPs (rs1043558, rs1320301, rs1578944, and rs74174284) in SLC17A7 and venlafaxine treatment in the Chinese Han population.

High-speed and low-speed streak structures in the near wall region of a turbulent boundary layer with a Mach number of 3 are experimentally examined by employing the spatiotemporally resolved nanoparticle plane laser scattering technique. The time evolution characteristics of the high-speed and low-speed streaks in the supersonic turbulent boundary layer are systematically investigated through the speed field sequence results at various time intervals. The obtained results reveal that the dynamic behavior of the bands is chiefly represented by the translation along the flow direction. The process of dissipation of the existing streaks and the formation of a new streak is also observed and analyzed. The duration values of the high-speed and low-speed streak structures are assessed by utilizing the time-resolved characteristics of the speed field, and the predicted duration of the streak structure and the maximum flow length exceed 306 µs and 23.6 times the thickness of the boundary layers, respectively. Finally, the merging phenomenon of medium and low-speed streaks in the turbulent boundary layer is carefully scrutinized. The merging of low-speed streaks observed under supersonic conditions is consistent with the vortex packet merging model proposed by Tomkins and Adrian.

Background High blood pressure is a leading cardiovascular disease risk factor and considered to be associated with psychological factors. However, the causal relationships between blood pressure and anxiety, depressive symptoms, neuroticism and subjective well-being are not clear.Aims The current study explored the genetic causal relationships between blood pressure and anxiety, depressive symptoms, neuroticism and subjective well-being.Methods Mendelian randomisation (MR) analyses were performed using the generalised summary-data-based MR analysis method with eight large-scale genome-wide association study datasets for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, anxiety, depressive symptoms, neuroticism and subjective well-being.Results A causal effect of DBP on neuroticism was found, and 1074 independent instrumental single nucleotide polymorphisms were identified by the incorporated Heterogeneity in Dependent Instruments-outlier test among the bidirectional causal relationship between blood pressure and the four psychological states.Conclusions DBP has a causal effect on neuroticism. Appropriate management of blood pressure may reduce neuroticism, neuroticism-inducing mood disorders and cardiovascular diseases.

As the world’s population ages, neurodegenerative diseases (NDs) have brought a great burden to the world. However, effective treatment measures have not been found to alleviate the occurrence and development of NDs. Abnormal accumulation of pathogenic proteins is an important cause of NDs. Therefore, effective inhibition of the accumulation of pathogenic proteins has become a priority. As the second brain of human, the gut plays an important role in regulate emotion and cognition functions. Recent studies have reported that the disturbance of gut microbiota (GM) is closely related to accumulation of pathogenic proteins in NDs. On the one hand, pathogenic proteins directly produced by GM are transmitted from the gut to the central center via vagus nerve. On the other hand, The harmful substances produced by GM enter the peripheral circulation through intestinal barrier and cause inflammation, or cross the blood–brain barrier into the central center to cause inflammation, and cytokines produced by the central center cause the production of pathogenic proteins. These pathogenic proteins can produced by the above two aspects can cause the activation of central microglia and further lead to NDs development. In addition, certain GM and metabolites have been shown to have neuroprotective effects. Therefore, modulating GM may be a potential clinical therapeutic approach for NDs. In this review, we summarized the possible mechanism of NDs caused by abnormal accumulation of pathogenic proteins mediated by GM to induce the activation of central microglia, cause central inflammation and explore the therapeutic potential of dietary therapy and fecal microbiota transplantation (FMT) in NDs.

BackgroundAs an emerging technology, virtual reality (VR) has been broadly applied in the medical field, especially in neurorehabilitation. The growing application of VR therapy promotes an increasing amount of clinical studies. In this paper, we present a bibliometric analysis of the existing studies to reveal the current research hotspots and guide future research directions.MethodsArticles and reviews on the related topic were retrieved from the Science Citation Index Expanded of Web of Science Core Collection database. VOSviewer and Citespace software were applied to systematically analyze information about publications, countries, institutions, authors, journals, citations, and keywords from the included studies.ResultsA total of 1,556 papers published between 1995 and 2021 were identified. The annual number of papers increased gradually over the past three decades, with a peak publication year in 2021 (n = 276). Countries and institutions from North America and Western European were playing leading roles in publications and total citations. Current hotspots were focused on the effectiveness of VR therapy in cognitive and upper limb motor rehabilitation. The clusters of keywords contained the four targeted neurological diseases of VR, while the burst keywords represented that the latest studies were directed toward more defined types of VR therapy and greater study design.ConclusionsOur study offers information regarding to the current hotspots and emerging trends in the VR for rehabilitation field. It could guide future research and application of VR therapy in neurorehabilitation.

This study aimed to explore the main influencing factors of suicide risk among Chinese students and establish an early warning model to provide interventions for high-risk students. We conducted surveys of students in their first and third years from a cohort study at Jining Medical College. Logistic regression models were used to screen the early warning factors, and four machine learning models were used to establish early warning models. There were 8 factors related to suicide risk that were eventually obtained through screening, including age, having a rough father, and CES-D, OHQ, ASLEC-4, BFI-Neuroticism, BFI-Openness, and MMC-AF-C scores. A random forest model with SMOTE was adopted, and it verified that these 8 early warning signs, for suicide risk can effectively predict suicide risk within 2 years with an AUC score of 0.947. Among the factors, we constructed a model that indicated that different personality traits affected suicide risk by different paths. Moreover, the factors obtained by screening can be used to identify college students in the same year with a high risk of suicide, with an AUC score that reached 0.953. Based on this study, we suggested some interventions to prevent students going high suicide risk.

Calcium phosphate bone cement (CPC) serves as an excellent scaffold material for bone tissue engineering owing to its good biocompatibility, injectability, self-setting property and three-dimensional porous structure. However, its clinical use is limited due to the cytotoxic effect of its setting reaction on cells and difficulties in degradation into bone. In this study, bone marrow mesenchymal stem cells (BMSCs) were encapsulated in alginate chitosan alginate (ACA) microcapsules and compounded with calcium phosphate bone cement. Changes in the compressive strength, porosity, injectability and collapsibility of CPC at different volume ratios of microcapsules were evaluated. At a 40% volume ratio of microcapsules, the composite scaffold displayed high porosity and injectability with good collapsibility and compressive strength. Cell live/dead double staining, Cell Counting Kit-8 (CCK-8) assays and scanning electron microscopy were used to detect the viability, proliferation and adhesion of cells after cell microcapsules were combined with CPC. The results revealed that cells protected by microcapsules proliferated and adhered better than those that were directly combined with CPC paste, and cell microcapsules could effectively form macropores in scaffold material. The composite was subsequently implanted subcutaneously on the backs of nude mice, and ectopic osteogenesis of the scaffold was detected via haematoxylin-eosin (H&E), Masson’s trichrome and Goldner’s trichrome staining. CPC clearly displayed better new bone formation function and degradability after addition of pure microcapsules and cell microcapsules. Furthermore, the cell microcapsule treatment group showed greater osteogenesis than the pure microcapsule group. Collectively, these results indicate that BMSCs encapsulated in ACA microcapsules combined with CPC composite scaffolds have good application prospects as bone tissue engineering materials.

BackgroundChildren with autism spectrum disorders (ASDs) suffer from sleep disorders to a considerable degree; however, there is no safe and effective treatment available in clinical practice. The objective of the trial is to assess the clinical effectiveness of auricular plaster therapy (APT) in treating sleep disorders in children with ASD.MethodThis is a single-center, patient-assessor blind, randomized controlled trial. A total of 44 preschool children with sleep disorders with ASD will be included in this study. Eligible participants will be randomly assigned to either the auricular plaster group or the sham auricular plaster group in a 1:1 ratio. Participants in the different groups will receive APT or sham APT, respectively, for a total of 30 sessions over 30 days. The primary outcome includes the Children's Sleep Habits Questionnaire (CSHQ), while secondary outcomes include the Autism Behavior Checklist (ABC) and polysomnography (PSG) for total sleep time, sleep latency, awakening duration, and sleep structures. The CSHQ and ABC will be assessed at baseline, 10, 20, 30, 60, 90, and 120 days after randomization, whereas PSG will be assessed at baseline and 30 days after randomization. The follow-up period will be scheduled to be 60, 90, and 120 days after randomization.DiscussionThe results of this study may provide evidence of the efficacy of APT, as well as offer new alternatives for the treatment of sleep disorders in children with ASD.Trial registrationCHiCTR.org.cn (ChiCTR2100048257). Registered on July 5, 2021.

Supercritical carbon-dioxide (SC-CO2) is a promising two-phase technology for flavor components (volatile oil and alkylamides) extract from Zanthoxylum bungeanum pericarp. However, the gastric protective effect of SC-CO2 extract from Z. bungeanum (SZB) have not been systematically investigated. In this study, response surface methodology (RSM) was employed to optimize the yield of SZB, and the average yield of 11.07 % were obtained under optimal parameters (30 MPa, 43 °C and time 75 min). Here, limonene, linalool and hydroxy-α-sanshool were identified as the main compounds of SZB by GC–MS and UPLC-Q-Extractive Orbitrap/MS analysis. When the gastric protective effect of SZB (5, 10 and 20 mg/kg, p.o.) were evaluated, significant increase in body weight and organ indexes of rat, and decreased gastric lesion were observed. Furthermore, nineteen serum metabolites were regarded as the potential biomarkers for the gastric protective effect of SZB. Collectively, this study provides a comprehensive perspective into the chemical composition analysis and gastric protective effect of Z. bungeanum SC-CO2 extract.

The mind has puzzled humans for centuries, and its disorders, such as psychoses, have caused tremendous difficulties. However, relatively recent biotechnological breakthroughs, such as DNA technology and neuroimaging, have empowered scientists to explore the more fundamental aspects of psychosis. From searching for psychosis-causing genes to imaging the depths of the brain, scientists worldwide seek novel methods to understand the mind and the causes of its disorders. This article will briefly review the history of understanding and managing psychosis and the main findings of modern genetic research and then attempt to stimulate thought for decoding the biological mechanisms of psychosis in the present era of brain science.

ObjectivesBoth right ventricular free wall longitudinal strain (RVFWLS) and right ventricular global longitudinal strain (RVGLS) using two-dimensional speckle tracking echocardiography (2D-STE) has been demonstrated to predict adverse outcomes in patients with repaired tetralogy of Fallot (r-TOF). However, RVGLS may be affected by left ventricular (LV) function owing to the fact that the interventricular septum is also a part of the left ventricle. Therefore, the aim of our study was to compare the predictive value of RVFWLS with that of RVGLS in patients with r-TOF.Materials and methodsA total of 179 patients with r-TOF were included in this study. RVFWLS, RVGLS, and left ventricle global longitudinal strain (LVGLS) were evaluated by 2D-STE. The adverse clinical events were death or r-TOF-related rehospitalization. Prognostic performance was evaluated by C-statistic and Akaike information criterion (AIC).ResultsThirty-one patients developed poor outcomes during a median follow-up period of 2.8 years. Compared with patients without end-point events, those with end-point events had higher incidence of moderate/severe pulmonary regurgitation, larger right heart sizes, and lower RV fractional area change (RVFAC), RVFWLS, RVGLS, and LVGLS than those without. Multivariate Cox regression analysis revealed that RVFAC, RVFWLS, RVGLS, and LVGLS were predictive of poor outcomes in patients with r-TOF after adjustment for transannular patch and QRS duration. A Cox model using RVFWLS (C index = 0.876, AIC = 228) was found to predict unfavorable outcomes more accurately than a model with RVGLS (C index = 0.856, AIC = 243), RVFAC (C index = 0.811, AIC = 248), and LVGLS (C index = 0.830, AIC = 248).ConclusionAlthough both RVGLS and RVFWLS are associated with adverse events, RVFWLS provides superior prognostic value than that of RVGLS in patients with r-TOF.

Purpose: We report a case with over 6 years of follow-up for well-differentiated liposarcoma or atypical lipomatous tumor (WDL/ALT). Observations: Over a 6-year time course, a patient with a recurrent right orbital mass was biopsied/debulked four times. It was not until the fourth biopsy that a diagnosis of WDL/ALT was obtained. Throughout the time course, the patient maintained good vision and there has been no evidence of dedifferentiation or metastasis thus far. Conclusions: The diagnosis of WDL/ALT sound be considered in the cases of a recurrent orbit mass when pathology continually shows nonspecific fibrofatty tissue with chronic inflammatory changes.