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Objective To investigate the impact of COVID-19 social distancing on medical research from the perspective of postgraduate students. Methods A cross-sectional study using an online survey was conducted from October 31 to November 1, 2021. A questionnaire was used to assess the impact of COVID-19 social distancing on medical research among postgraduate students. The questionnaire included basic information, medical research information, and information about social distancing measures. Participants also completed the self-made Research Work Affected Scale of Postgraduates (RWAS-P; qualitative evaluation: very mildly 0–10; mildly 11–20; moderately 21–30; severely 31–40; very severely 41–50). Logistic regression was used to identify factors related to the impact of COVID-19 social distancing. Results A total of 468 participants were analyzed; 95.2% of the participants adhered to social distancing measures. The median total RWAS-P score was 22. The median RWAS-P scores for earlier research data, current research projects, future research plans, paper publication, and graduation schedule were 2, 6, 6, 6, and 4, respectively (score range 0–10). The higher grade of students, experimental research, and existence of inappetence or sleeplessness were related to negative attitude towards COVID-19 social distancing (odd ratio = 6.35, 9.80, 2.31, 2.15, 1.95, respectively). Conclusions Participants reported that social distancing had a moderate overall impact on their medical research. Social distancing had the greatest impact on current research projects, future research plans, and paper publications among postgraduate students. Higher grade level, experimental research type, inappetence, and sleeplessness were related to the impact of social distancing on their medical research.

BackgroundSkin expansion by mechanical stretch is an essential and widely used treatment for tissue defects in plastic and reconstructive surgery; however, the regenerative capacity of mechanically stretched skin limits clinical treatment results. Here, we propose a strategy to enhance the regenerative ability of mechanically stretched skin by topical application of metformin.MethodsWe established a mechanically stretched scalp model in male rats (n = 20), followed by their random division into two groups: metformin-treated (n = 10) and control (n = 10) groups. We measured skin thickness, collagen volume fraction, cell proliferation, and angiogenesis to analyze the effects of topical metformin on mechanically stretched skin, and immunofluorescence staining was performed to determine the contents of epidermal stem cells and hair follicle bulge stem cells in mechanically stretched skin. Western blot was performed to detect the protein expression of skin-derived stem cell markers.ResultsCompared with the control group, metformin treatment was beneficial to mechanical stretch-induced skin regeneration by increasing the thicknesses of epidermis (57.27 ± 10.24 vs. 31.07 ± 9.06 μm, p < 0.01) and dermis (620.2 ± 86.17 vs. 402.1 ± 22.46 μm, p < 0.01), number of blood vessels (38.30 ± 6.90 vs. 17.00 ± 3.10, p < 0.01), dermal collagen volume fraction (60.48 ± 4.47% vs. 41.28 ± 4.14%, p < 0.01), and number of PCNA+, Aurora B+, and pH3+ cells. Additionally, we observed significant elevations in the number of proliferating hair follicle bulge stem cells [cytokeratin (CK)15+/proliferating cell nuclear antigen (PCNA)+] (193.40 ± 35.31 vs. 98.25 ± 23.47, p < 0.01) and epidermal stem cells (CK14+/PCNA+) (83.00 ± 2.38 vs. 36.38 ± 8.96, p < 0.01) in the metformin-treated group, and western blot results confirmed significant increases in CK14 and CK15 expression following metformin treatment.ConclusionTopical application of metformin enhanced the regenerative capacity of mechanically stretched skin, with the underlying mechanism possibly attributed to improvements in the proliferative activity of skin-derived stem cells.

ABSTRACT The long-term exposure to enclosed environments may lead to chronic stress in crewmembers and affect their physical and mental state. Salivary microbiome and biomarkers of immune function are increasingly used in human health research. The “Lunar Palace 365” project, which was a 370-day, multicrew, enclosed experiment carried out in a ground-based bioregenerative life support system platform named Lunar Palace 1 (LP1). We investigated the temporal dynamics of the salivary microbiota and cytokines in the third phase of the “Lunar Palace 365” experiment, including 1 month before entering LP1 and 1 month after leaving Lp1. Results reveal no regular temporal change pattern in these parameters (highly abundant phyla and genera) during the experiment. Although the crewmembers’ oral microbiota temporally changed, it recovered quickly after the study subjects left the enclosed environment. The levels of IL-6, IL-10, and TNF-α in crewmembers’ saliva decreased after leaving the normal environment for the enclosed environment, indicating that their oral inflammatory response level was reduced. There were significant individual differences in crewmembers’ salivary microbiota, however, the shared living space reduced these differences. Moreover, air microbiota might have also played a significant role in reducing the individual differences. In summary, the enclosed environment did not result in persistent changes in human salivary microbiota and oral immunity. This study provides some insights for studying the effect of enclosed controlled environments on human immunity and microbiome. IMPORTANCE Long-term exposure to space environments may influence the human microbiome, the human immune system, and the intricate balance between the two, causing impaired immunity and increased disease susceptibility. It was previously believed that the main potential factors of long-term spaceflight on human health were microgravity and radiation. However, the effects of long-term enclosed environments on human health were unclear. Bioregenerative life support systems (BLSS) is a good experimental model for studying the effects of enclosed environments on human systemic microbiota and immune disorders. We monitored the microbiota and cytokines in the saliva of crewmembers before they entered BLSS, during their stay in BLSS, and after leaving BLSS. The results indicated long-term closed environment will not cause persistent changes in human salivary microbiota and immunity.

BackgroundMechanical stretch is vital for soft tissue regeneration and development and is utilized by plastic surgeons for tissue expansion. Identifying the common hub genes in human dermal fibroblasts (HDFs) stimulated by mechanical stretch at different stages will help elucidate the mechanisms involved and improve the efficiency of tissue expansion.MethodsA gene expression dataset (GSE58389) was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in HDFs between cyclic mechanical stretching and static samples were identified at 5 and 24 h. Common DEGs overlapped in both the 5 h and 24 h groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the functions of the DEGs. Protein-protein interaction networks were constructed using the STRING database. The top 10 hub genes were selected using the plug-in Cytohubba within Cytoscape. The regulatory network of hub genes was predicted using NetworkAnalyst.ResultsA total of 669 and 249 DEGs were identified at the early (5 h) and late stages (24 h), respectively. Of these, 152 were present at both stages and were designated as common DEGs. The top enriched GO terms were “regulation of autophagy” at the early stage, and “sterol biosynthetic processes” at the late stage. The top KEGG terms were “pyrimidine metabolism” and “synaptic vesicle cycle” at the early and late stages, respectively. Seven common DEGs [DEAD-box helicase 17 (DDX17), exocyst complex component 7 (EXOC7), CASK interacting protein 1 (CASKIN1), ribonucleoprotein PTB-binding 1 (RAVER1), late cornified envelope 1D (LCE1D), LCE1C, and polycystin 1, transient receptor potential channel interacting (PKD1)] and three common DEGs [5′-3′ exoribonuclease 2 (XRN2), T-complex protein 1 (TCP1), and syntaxin 3 (STX3)] were shown to be downregulated and upregulated hub genes, respectively. The GO terms of the common hub genes were “skin development” and “mRNA processing.” After constructing the regulatory network, hsa-mir-92a-3p, hsa-mir-193b-3p, RNA polymerase II subunit A (POLR2A), SMAD family member 5 (SMAD5), and MYC-associated zinc finger protein (MAZ) were predicted as potential targets in both stages.ConclusionAt the early stage, there were clear changes in gene expression related to DNA and chromatin alterations; at late stages, gene expression associated with cholesterol metabolism was increased. Common DEGs related to skin development, transcriptional regulation, and cytoskeleton rearrangement identified in both stages were found to be potential targets for promoting HDF growth and alignment under mechanical stretch.

There are many potential immunotherapeutic targets for cancer immunotherapy, which should be assessed for efficacy before they enter clinical trials. Here we established an ex vivo cultured patient-derived tumor tissue model to evaluate antitumor effectiveness of one VISTA inhibitor, given that our previous study showed that VISTA was selectively highly expressed in human clear cell renal cell carcinoma (ccRCC) tumors. We observed that all the tested patients responded to the anti-VISTA monoclonal antibody as manifested by TNF-α production, but only a small fraction were responders to the anti-PD-1 antibody. Co-blockade of VISTA and PD-1 resulted in a synergistic effect in 20% of RCC patients. Taken together, these findings indicate that this ex vivo tumor slice culture model represents a viable tool to evaluate antitumor efficacies for the inhibitors of immune checkpoints and further supports that VISTA could serve as a promising target for immunotherapy in ccRCC.

Abstract Background Carotenoids play important roles in photosynthesis, hormone signaling, and secondary metabolism. Phytoene synthase (PSY) catalyzes the first step of the carotenoid biosynthetic pathway. In this study, we aimed to characterize the PSY genes in tobacco and analyze their function. Results In this study, we identified three groups of PSY genes, namely PSY1, PSY2, and PSY3, in four Nicotiana species; phylogenetic analysis indicated that these genes shared a high similarity with those in tomato but not with those in monocots such as rice and maize. The expression levels of PSY1 and PSY2 were observed to be highest in leaves compared to other tissues, and they could be elevated by treatment with certain phytohormones and exposure to strong light. No PSY3 expression was detected under these conditions. We constructed virus-induced PSY1 and PSY2 silencing in tobacco and found that the newly emerged leaves in these plants were characterized by severe bleaching and markedly decreased carotenoid and chlorophyll content. Thylakoid membrane protein complex levels in the gene-silenced plants were also less than those in the control plants. The chlorophyll fluorescence parameters such as Fv/Fm, ΦPSII, qP, and NPQ, which reflect photosynthetic system activities, of the gene-silenced plants were also significantly decreased. We further performed RNA-Seq and metabonomics analysis between gene-silenced tobacco and control plants. RNA-Seq results showed that abiotic stress, isoprenoid compounds, and amino acid catabolic processes were upregulated, whereas the biosynthesis of cell wall components was downregulated. Metabolic analysis results were consistent with the RNA-Seq. We also found the downstream genes in carotenoid biosynthesis pathways were upregulated, and putative transcription factors that regulate carotenoid biosynthesis were identified. Conclusions Our results suggest that PSY can regulate carotenoid contents not only by controlling the first biosynthesis step but also by exerting effects on the expression of downstream genes, which would thereby affect photosynthetic activity. Meanwhile, PSY may affect other processes such as amino acid catabolism and cell wall organization. The information we report here may aid further research on PSY genes and carotenoid biosynthesis.

Abstract Background Angiotensin-converting enzyme (ACE) plays a major role in blood pressure regulation and cardiovascular homeostasis. The wide distribution and multifunctional properties of ACE suggest it’s involvement in various pathophysiological conditions. Results In this study, a novel visual detection method for ACE I/D polymorphisms was designed by integrating direct PCR without the need for DNA extraction using gold magnetic nanoparticles (GMNPs)-based lateral flow assay (LFA) biosensor. The entire detection procedure could enable the genotyping of clinical samples in about 80 min. The detection limit was 0.75 ng and results could be obtained in 5 min using the LFA device. Three hundred peripheral blood samples were analyzed using the direct PCR-LFA system and then verified by sequencing to determine accuracy and repeatability. A clinical preliminary study was then performed to analyze a total of 633 clinical samples. Conclusions After grouping based on age, we found a significant difference between the genotypes and the age of patients in the CHD group. The introduction of this method into clinical practice may be helpful for the diagnosis of diseases caused by large fragment gene insertions/deletions.

[Background] Metal exposure is suspected to be correlated to kidney function. However, the combined effects of co-exposing to multiple metals, especially both toxic and protective metals, have not been completely evaluated. [Method] A prospective cohort study was conducted with the “135” cohort for the evaluation of how plasma metal levels are correlated to kidney function in a midlife and elderly community in southern China. An amount of 1368 subjects without kidney disease at baseline were enrolled in the final analysis. By using linear regression and logistic regression models, the correlation of individual metal values with renal function parameters was assessed. Measuring of the multiple metal exposure level was performed by principal component analysis (PCA). [Results] Diminished renal function, as evaluated based on fast kidney function decline, or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, was positively associated with the plasma concentrations of chromium and potassium, but it was negatively associated with selenium and iron (p < 0.05). In multiple-metal analyses, linear and logistic regression models showed that the iron and chromium exposure pattern had a protective effect on renal function, whereas the sodium and potassium exposure pattern and the cadmium and lead exposure pattern increased the risk for fast kidney function decline, and eGFR < 60 mL/min/1.73 m2. [Conclusions] Certain metals, including chromium, potassium, selenium, and iron, were correlated with kidney function in a midlife and elderly community in China. In addition, the potential combined influences of co-exposing to multiple metals were observed.

Zero and partial gravities (ZPG) increase cardiovascular risk, while the corresponding theoretical foundation remains uncertain. In the article, the ZPG were generated through a rotating frame with two degrees of freedom in combination with the random walk algorithm. A precise 3D geometric configuration of the cardiovascular system was developed, and the Navier-Stokes laminar flow and solid mechanics were used as governing equations for blood flow and the surrounding tissue in the cardiovascular system. The ZPG were designed into governing equations through the volume force term. The computational fluid dynamics’ (CFD) simulations in combination with proper boundary conditions were carried out to investigate the influences of ZPG on the distribution of blood flow velocity, pressure, and shear stress in the cardiovascular system. The findings show that as simulated gravity gradually decreases from 0.7 g to 0.5 g to 0.3 g to 0 g, as opposed to normal gravity of 1 g, the maximum values of blood flow velocity, pressure, and shear stress on the walls of the aorta and its ramification significantly increase, which would lead to cardiovascular diseases. The research will lay a theoretical foundation for the comprehension of the ZPG effect on cardiovascular risk and the development of effective prevention and control measures under the circumstance of ZPG.

Based on the 2019 satellite remote sensing data, the survey was conducted on the open-pit stopes of the building sand mines in Shigatse, Tibet, and the relationship between the number of stopes and the area, population and population density of the district/county, as well as the distribution characteristics between the main built-up areas, administrative villages and traffic roads at the county level were analyzed. This study tentatively links the open pit of building sand mine with human aggregation and human activity space, analyzes the possible correlation, distribution rules and change characteristics between it and the typical elements of social economy, and provides a research basis for improving the efficiency of mining administration in western China.

The goal of the space-based quantum network is to form the backbone of the quantum internet for long-distance secure data transfer, networked distributed quantum information processing, and other applications. Consider that the quantum network evolved from a recent form where a satellite performs a sequence of satellite-to-ground quantum key distribution (SatQKD) missions that allow any two ground nodes to have the symmetric encryption keys, we here develop a framework for the SatQKD downlink modelling and scheduling analysis. Incorporated with the orbital calculation and the meteorological data to downlink SatQKD modelling, the dynamic characteristics of the satellite-to-ground optical transmission could be simulated. Our work shows that the satellite downlink scheduling allows for the possibility to consider different strategies for SatQKD missions such as extending connection for distant ground nodes, prioritized delivery and promoting keys utilization, which may guide design and analysis of future missions for future satellite application.

As one of the most imperative antioxidants in higher plants, carotenoids serve as accessory pigments to harvest light for photosynthesis and photoprotectors for plants to adapt to high light stress. Here, we report a small subunit (SSU) of geranylgeranyl diphosphate synthase (GGPPS) in Nicotiana tabacum, NtSSU II, which takes part in the regulation carotenoid biosynthesis by forming multiple enzymatic components with NtGGPPS1 and downstream phytoene synthase (NtPSY1). NtSSU II transcript is widely distributed in various tissues and stimulated by low light and high light treatments. The confocal image revealed that NtSSU II was localized in the chloroplast. Bimolecular fluorescence complementation (BiFC) indicated that NtSSU II and NtGGPPS1 formed heterodimers, which were able to interact with phytoene synthase (NtPSY1) to channel GGPP into the carotenoid production. CRISPR/Cas9-induced ntssu II mutant exhibited decreased leaf area and biomass, along with a decline in carotenoid and chlorophyll accumulation. Moreover, the genes involved in carotenoid biosynthesis were also downregulated in transgenic plants of ntssu II mutant. Taken together, the newly identified NtSSU II could form multiple enzymatic components with NtGGPPS1 and NtPSY1 to regulate carotenoid biosynthesis in N. tabacum, in addition to the co-expression of genes in carotenoids biosynthetic pathways.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world, which is also the main death cause of cancer patients. Surgery, radiotherapy and chemotherapy can improve the prognosis of CRC patients. However, late recurrence and distant metastatic diseases cannot be cured, which will result in poor prognosis. With the cross penetration of molecular biology, oncology and immunology, the immunotherapy has made a huge breakthrough and has become an important means of tumor therapy. This article summarizes the immunotherapy of metastatic CRC at home and abroad in recent years.

In order to solve the problems that orders are widely distributed, scheduling of distribution vehicle needs a lot of manpower,and high cost of chicken distribution in large-scale poultry enterprise, in this research, combined with the idea of solving vehicle routing optimization problem, a chicken distribution vehicle scheduling optimization model based on order location clustering was proposed. By introducing the K-means clustering algorithm, a distribution unit division method based on order location was implemented, an automated order location clustering process based on the elbow rule and contour coefficient method to realize the autonomous division of order distribution units was designed. On the basis of the divided groups of orders, the optimal delivery cost was taken as the objective function to establish a chicken delivery vehicle scheduling optimization model, and the model was solved with an improved genetic algorithm.The actual order data of a poultry company in Beijing was used to compare the results of the overall scheduling optimization in the case of orders without clustering and the scheduling optimization in the case of with clustering grouping. The results showed that the model in the case of orders with clustering could reduce the average daily mileage of delivery vehicles by 69% compared with orders without clustering, it could be seen that the optimization of order grouping with clustering algorithm was more suitable for vehicle scheduling scenarios with a large actual order position span and a large number of orders. Based on the above research, a vehicle scheduling optimization service system was developed, functions such as automatic order clustering, delivery vehicle scheduling optimization were realized, and model service application programming interface was customized.The practical application results of the model showed that, the average total mileage per day decreased by 5.04% compared with manual routing, the manual routing time took 20 to 30 minutes per day, and the average time for the model to complete the routing was 14.49 s. The goal of providing intelligent delivery vehicle scheduling optimization services for poultry industry enterprises has been achieved, which could effectively improve the operation efficiency and reduce the distribution cost of the poultry enterprise.

Down syndrome (DS), or trisomy 21, is one of the critical risk factors for early-onset Alzheimer’s disease (AD), implicating key roles for chromosome 21–encoded genes in the pathogenesis of AD. We previously identified a role for the deubiquitinase USP25, encoded on chromosome 21, in regulating microglial homeostasis in the AD brain; however, whether USP25 affects amyloid pathology remains unknown. Here, by crossing 5×FAD AD and Dp16 DS mice, we observed that trisomy 21 exacerbated amyloid pathology in the 5×FAD brain. Moreover, bacterial artificial chromosome (BAC) transgene–mediated USP25 overexpression increased amyloid deposition in the 5×FAD mouse brain, whereas genetic deletion of Usp25 reduced amyloid deposition. Furthermore, our results demonstrate that USP25 promoted β cleavage of APP and Aβ generation by reducing the ubiquitination and lysosomal degradation of both APP and BACE1. Importantly, pharmacological inhibition of USP25 ameliorated amyloid pathology in the 5×FAD mouse brain. In summary, we identified the DS-related gene USP25 as a critical regulator of AD pathology, and our data suggest that USP25 serves as a potential pharmacological target for AD drug development.

Summary: Background: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). Methods: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Findings: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p

Background: Silicone implants are widely used in the field of plastic surgery for wound repair and cosmetic augmentation. However, molecular mechanisms and signaling pathways underlying the foreign body reaction (FBR) of a host tissue to the silicone require further elucidation. The purpose of this study was to identify key FBR-related transcription factors (TFs) and genes through transcriptome analysis.Methods: We used a rat model with a subcutaneous silicone implant in the scalp and performed high throughput sequencing to determine the transcriptional profiles involved in the FBR. The function was analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. A protein-protein interaction (PPI) network of differentially expressed mRNAs (DEmRNAs) was constructed to identify the hub genes and key modules and to determine the regulatory TF-mRNA relationships. In addition, the hub gene and transcript expression levels were determined by Quantitative Reverse Transcription polymerase Chain Reaction (qRT-PCR). Myofibroblasts differentiation and macrophage recruitment were identified by immunofluorescence. The protein expression of MMP9 was detected by immunohistochemistry and Western blot.Results: We identified ten hub genes (Fos, Spp1, Fn1, Ctgf, Tlr2, Itgb2, Itgax, Ccl2, Mmp9, and Serpine1) and 3 TFs (FOS, IRF4, and SPI1) that may be crucial (particularly FOS) for the FBR. Furthermore, we identified multiple differentially expressed genes involved in several important biological processes, including leukocyte migration, cytokine‒ cytokine receptor interaction, phagocytosis, extracellular matrix (ECM) organization, and angiogenesis. We also identified potentially significant signaling pathways, including cytokine‒cytokine receptor interaction, phagosome, ECM‒receptor interaction, complement and coagulation cascades, the IL-17 signaling pathway, and the PI3K‒Akt signaling pathway. In addition, qRT-PCR confirmed the expression patterns of the TFs and hub genes, Western blot and immunohistochemistry validated the expression patterns of MMP9.Conclusion: We generated a comprehensive overview of the gene networks underlying the FBR evoked by silicone implants. Moreover, we identified specific molecular and signaling pathways that may perform key functions in the silicone implant-induced FBR. Our results provide significant insights into the molecular mechanisms underlying silicone-induced FBR and determine novel therapeutic targets to reduce complications related to silicone implantation.

Increasing evidences indicate that gut microbiota composition is associated with multiple inflammatory diseases. However, little is known about how gut microbiota changes with age and correlations with gut inflammation at sexual maturity stage of healthy individuals. Elucidating the dynamic changes of gut microbiota in healthy individuals at the sexual maturity stage and correlations with gut inflammation can provide clues for early risk assessment of gut diseases at the sexual maturity stage. Here, the shift in gut bacteria and its relationship with gut inflammation at the sexual maturity stage were explored. Sprague–Dawley rats at the sexual maturity stage were used in this study. 16S rRNA gene sequencing was performed to decipher gut bacteria shifts from the 7th week to the 9th week, and enzyme-linked immunosorbent assay (ELISA) was used to measure gut inflammation and gut barrier permeability. We found an increase in bacterial richness with age and a decrease in bacterial diversity with age. The gut bacteria were primarily dominated by the phyla Firmicutes and Bacteroides and the genus Prevotella. The relative abundance of Firmicutes increased with age, and the relative abundance of Bacteroides decreased with age. There was a positive correlation between body weight and the Firmicutes:Bacteroides ratio. More and more gut microbiota participated in the host gut inflammation and barrier permeability regulation with age. Ruminococcus was the only gut bacteria participated in gut inflammation and barrier permeability regulation both in the 7th week and the 15th week. These results provide a better understanding of the relationship between gut bacteria and gut inflammation in sexually mature rats and show that Ruminococcus may be a potential indicator for early risk assessment of gut inflammation.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising marker for the diagnosis of diabetic kidney disease (DKD), but its utility is currently debated. This meta-analysis aims to evaluate the diagnostic value of NGAL for DKD. Method: MEDLINE, Embase, ­Cochrane Library, CNKI, and CBM databases were searched up to April 13, 2019. In bivariate random-effect models, the diagnostic performance of NGAL for DKD was assessed using pooled estimates of sensitivity, specificity, likelihood ratio, diagnostic odds ratio, and hierarchical summary receiver-operating characteristic analysis. Results: Nineteen studies were eligible for the meta-analysis. Serum NGAL had a pooled sensitivity and specificity of 0.79 (95% confidence intervals [CI] 0.60–0.91) and 0.87 (0.75–0.93) (7 studies, 1,238 patients). The pooled positive likelihood ratio (LR+) and negative likelihood ratio (LR–) were 5.97 (3.03–11.76) and 0.24 (0.11–0.51). For urine NGAL, the pooled sensitivity, specificity, LR+, and LR– were 0.85 (0.74–0.91), 0.74 (0.57–0.86), 3.26 (1.87–5.67), and 0.21 (0.12–0.35), respectively (10 studies, 1,369 patients). The pooled sensitivity and specificity for kidney disease in normoalbuminuric patients with diabetes was 0.90 (0.82–0.95) and 0.97 (0.90–0.99) for both serum NGAL and 0.94 (0.87–0.98) and 0.90 (0.81–0.96) for urine NGAL (4 studies, 221 patients). NGAL appeared to perform similarly in subgroup analysis. Conclusion: The meta-analysis has shown that NGAL may be useful for DKD classification and also has a potential diagnostic value for normoalbuminuric kidney disease. Large-scale prospective studies are required to clarify its role in the diagnosis and risk stratification of patients with DKD.

Neuroblastoma is one of the most common malignancies in infants and children. MicroRNAs (miRNAs) have been reported as significant regulators that play important roles in neuroblastoma development. This research aimed to analyze the functional mechanism of miR-542-3p in neuroblastoma. Here, we found that miR-542-3p was downregulated and KDM1A as well as ZNF346 were upregulated in neuroblastoma tissues and cells. Both overexpression of miR-542-3p and the knockdown of KDM1A suppressed cell proliferation and invasion in neuroblastomas. Moreover, miR-542-3p reduced the levels of KDM1A and ZNF346 through interaction. Both KDM1A overexpression and ZNF346 upregulation weakened the effect of miR-542-3p on neuroblastoma cells. Besides, miR-542-3p negatively regulated tumor growth in vivo. Our results suggested that miR-542-3p suppressed cell proliferation and invasion by targeting KDM1A and ZNF346 in neuroblastomas, providing a theoretical basis for the treatment of neuroblastoma.

The use of CRISPRa in bacteria lacks predictive rules for identifying effective gRNA target sites. Here the authors define features of bacterial promoters that impose stringent requirements on effective sites.

Abstract Background Lotus (Nelumbo nucifera) is an aquatic plant with important agronomic, horticulture, art and religion values. It was the basal eudicot species occupying a critical phylogenetic position in flowering plants. After the domestication for thousands of years, lotus has differentiated into three cultivated types -flower lotus, seed lotus and rhizome lotus. Although the phenotypic and genetic differentiations based on molecular markers have been reported, the variation on whole-genome level among the different lotus types is still ambiguous. Results In order to reveal the evolution and domestication characteristics of lotus, a total of 69 lotus accessions were selected, including 45 cultivated accessions, 22 wild sacred lotus accessions, and 2 wild American lotus accessions. With Illumina technology, the genomes of these lotus accessions were resequenced to > 13× raw data coverage. On the basis of these genomic data, 25 million single-nucleotide polymorphisms (SNPs) were identified in lotus. Population analysis showed that the rhizome and seed lotus were monophyletic and genetically homogeneous, whereas the flower lotus was biphyletic and genetically heterogeneous. Using population SNP data, we identified 1214 selected regions in seed lotus, 95 in rhizome lotus, and 37 in flower lotus. Some of the genes in these regions contributed to the essential domestication traits of lotus. The selected genes of seed lotus mainly affected lotus seed weight, size and nutritional quality. While the selected genes were responsible for insect resistance, antibacterial immunity and freezing and heat stress resistance in flower lotus, and improved the size of rhizome in rhizome lotus, respectively. Conclusions The genome differentiation and a set of domestication genes were identified from three types of cultivated lotus- flower lotus, seed lotus and rhizome lotus, respectively. Among cultivated lotus, flower lotus showed the greatest variation. The domestication genes may show agronomic importance via enhancing insect resistance, improving seed weight and size, or regulating lotus rhizome size. The domestication history of lotus enhances our knowledge of perennial aquatic crop evolution, and the obtained dataset provides a basis for future genomics-enabled breeding.

With the booming development of the cyber-physical system, human society is much more dependent on information technology. Unfortunately, like software, hardware is not trusted at all, due to so many third parties involved in the separated integrated circuit's (IC) design and manufacturing stages for the high profit. The malicious circuits (named Hardware Trojans) can be implanted during any stage of the ICs' design and manufacturing process. However, the existing pre-silicon approaches based on machine learning theory have good performance, they all belong to supervised learning methods, which have a key prerequisite that is numerous already known information. Meanwhile, hardware Trojans are even more unimaginable because today's ICs are becoming more complicated. The known information is even harder to gain. Furthermore, the training process for supervised learning methods tends to be time-consuming and generally requires a huge amount of balanced training data. Therefore, this paper proposes an unsupervised hardware Trojans detection approach by combined the principal component analysis (PCA) and local outlier factor (LOF) algorithm, called PL-HTD. We firstly visualize the distribution features of normal nets and Trojan nets, and then reveal the differences between the two types of nets to reduce the dimension of the feature set. According to the outliers of each net, the abnormal nets are selected and verified by professionals later to confirm whether it is a true Trojan relative to the host circuit to realize the detection. The experiments show that the proposed method can detect hardware Trojans effectively and reduce the cost of manual secondary detection. For the Trust-HUB benchmarks, the PL-HTD achieves up to 73.08% TPR and 97.52% average TNR, moreover, it achieves average 96.00% accuracy, which shows the feasibility and efficiency of hardware Trojans detecting by employing a method without the guidance of class label information.

Anxiety is frequently observed in patients with systemic lupus erythematosus (SLE) and the immune system could act as a trigger for anxiety. To recognize abnormal T-cell and B-cell subsets for SLE patients with anxiety, in this study, patient disease phenotypes data from electronic lupus symptom records were extracted by using natural language processing. The Hospital Anxiety and Depression Scale (HADS) was used to distinguish patients, and 107 patients were selected to meet research requirements. Then, peripheral blood was collected from two patient groups for multicolor flow cytometry experiments. The characteristics of 75 T-cell and 15 B-cell subsets were investigated between SLE patients with- (n = 23) and without-anxiety (n = 84) groups by four machine learning methods. The findings showed 13 T-cell subsets were significantly different between the two groups. Furthermore, BMI, fatigue, depression, unstable emotions, CD27+CD28+ Th/Treg, CD27−CD28− Th/Treg, CD45RA−CD27− Th, and CD45RA+HLADR+ Th cells may be important characteristics between SLE patients with- and without-anxiety groups. The findings not only point out the difference of T-cell subsets in SLE patients with or without anxiety, but also imply that T cells might play the important role in patients with anxiety disorder.

In order to study the effect of water and CH4 concentration on gas explosion, a 20L spherical explosive device was used to carry out a water-containing gas explosion experiment, and the explosion simulation was carried out with CHEMKIN-PRO, the mechanism of water on gas explosion was analyzed from the perspective of free radicals and energy. The results showed that the upper limit of gas explosion, maximum explosion pressure and temperature decreased significantly with the increase of water content. The higher the concentration of CH4, the more obvious the inhibitory effect of water on gas explosion pressure, and the optimal explosion concentration of CH4 decreased with the increase of water content. As the water content and CH4 concentration increase, the residual CH4 content increases after the explosion, the O2 content decreases, and the CO content produced increases. When the CH4 concentration is lower than the optimal concentration, water promotes the formation of CO2 to a certain extent; when the CH4 concentration is higher than the optimal explosive concentration, the CO2 content decreases with the increase of water content. Overall, water inhibits methane explosion, the addition of water on the one hand reduces the concentration of active free radicals H, O, OH, on the other hand, it interferes with the generation of gas explosion energy and consumes the kinetic energy of the gas explosion flame shock wave through heat absorption, thus inhibiting the intensity of gas explosion.

Tissue expansion is widely used to obtain new skin tissue for repairing defects in the clinical practice of plastic surgery. One major complication can be dermal thinning during expansion, which usually leads to skin rupture. Collagen synthesis can determine dermal thickness and can be influenced by macrophage polarization during expansion. The aim of the study was to test whether pigment epithelium-derived factor (PEDF) could be a modulator of collagen synthesis in fibroblasts by regulating macrophage polarization during skin expansion. Our results showed that PEDF mRNA expression was increased in expanded human and mouse epidermis. PEDF protein levels were elevated in the subcutaneous exudates of a rat skin expansion model. Increased PEDF mRNA expression was accompanied by dermal thinning during a three-week expansion protocol. Subcutaneous injection of PEDF in vivo further resulted in dermal thinning and cell number increase of M1 macrophage in the expanded skin. PEDF also promoted macrophage polarization in vitro to the M1 subtype under hypoxic conditions. PEDF did not influence collagen gene expression in fibroblasts directly, but attenuated collagen synthesis in a macrophage-mediated manner. Additionally, blockage of PEDF receptors on macrophages with inhibitors rescued collagen synthesis in fibroblasts. Our research demonstrated PEDF elevation in expanded skin leads to dermal thinning through M1 macrophage-mediated collagen synthesis inhibition in fibroblasts. Our results could form a basis for the development of novel strategies to improve skin integrity in expanded skin by using PEDF.

C23H15ClCuN4O3, monoclinic, P21/c (no. 14), a = 10.63346(14) Å, b = 17.99387(15) Å, c = 11.60320(16) Å, β = 116.2165(17)°, V = 1991.74(5) Å3, Z = 4, Rgt(F) = 0.0315, wRref(F2) = 0.0898, T = 293(2) K.

A simple method for the synthesis of the title compounds by an efficient in-situ reduction and cyclization reactions of aromatic aldehydes, tert-butyl 2,4-dioxopiperidine-1-carboxylate and 5-nitro-1H-indazole or 6-nitro-1H-indazole was developed.

Summary: Inflammatory bowel disease (IBD) is multi-factorial chronic intestinal inflammation driven by pathogenic T cells, among which a large portion of patients are resistant to current anti-inflammatory regimes. The mechanisms underlying colitis pathogenicity and drug resistance are not fully understood. Here, we demonstrate that RORα is highly expressed in active UC patients, particularly in those non-responsive to anti-TNF treatment. Rorα deficiency in CD4+ T cells greatly reduced colitis development. Mechanistically, RORα regulated T cell infiltration in colon and inhibited T cell apoptosis. Meanwhile, genome-wide occupancy and transcriptome analysis revealed that RORα promoted mTORC1 activation. mTORC1 signaling, also hyperactivated in active UC patients, is necessary for T cell-mediated colitis. Our results thus demonstrate a crucial role of the RORα-mTORC1 axis in CD4+ T cells in promoting IBD, which may be targeted in human patients.

Background: Mechanical stretch is utilized to promote skin regeneration during tissue expansion for reconstructive surgery. Although mechanical stretch induces characteristic morphological changes in the skin, the biological processes and molecular mechanisms involved in mechanically induced skin regeneration are not well elucidated.Methods: A male rat scalp expansion model was established and the important biological processes related to mechanical stretch-induced skin regeneration were identified using Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA). Analysis was also conducted by constructing a protein–protein interaction (PPI) network, identifying key modules and hub genes, determining transcription factor (TF)-mRNA regulatory relationships, and confirming the expression pattern of the TFs and hub genes.Results: We identified nine robust hub genes (CXCL1, NEB, ACTN3, MYOZ1, ACTA1, TNNT3, PYGM, AMPD1, and CKM) that may serve as key molecules in skin growth. These genes were determined to be involved in several important biological processes, including keratinocyte differentiation, cytoskeleton reorganization, chemokine signaling pathway, glycogen metabolism, and voltage-gated ion channel activity. The potentially significant pathways, including the glucagon signaling pathway, the Wnt signaling pathway, and cytokine–cytokine receptor interaction, were distinguished. In addition, we identified six TFs (LEF1, TCF7, HMGA1, TFAP2C, FOSL1, and ELF5) and constructed regulatory TF–mRNA interaction networks.Conclusion: This study generated a comprehensive overview of the gene networks underlying mechanically induced skin regeneration. The functions of these key genes and the pathways in which they participate may reveal new aspects of skin regeneration under mechanical strain. Furthermore, the identified TF regulators can be used as potential candidates for clinical therapeutics for skin pretreatment before reconstructive surgery.

Meiosis initiation and progression are regulated by both germ cells and gonadal somatic cells. However, little is known about what genes or proteins connecting somatic and germ cells are required for this regulation. Our results show that deficiency for adhesion molecule IGSF11, which is expressed in both Sertoli cells and germ cells, leads to male infertility in mice. Combining a new meiotic fluorescent reporter system with testicular cell transplantation, we demonstrated that IGSF11 is required in both somatic cells and spermatogenic cells for primary spermatocyte development. In the absence of IGSF11, spermatocytes proceed through pachytene, but the pericentric heterochromatin of nonhomologous chromosomes remains inappropriately clustered from late pachytene onward, resulting in undissolved interchromosomal interactions. Hi-C analysis reveals elevated levels of interchromosomal interactions occurring mostly at the chromosome ends. Collectively, our data elucidates that IGSF11 in somatic cells and germ cells is required for pericentric heterochromatin dissociation during diplotene in mouse primary spermatocytes.

The establishment of anterior–posterior (AP) regional identity is an essential step in the appropriate development of the vertebrate central nervous system. An important aspect of AP neural axis formation is the inherent plasticity that allows developing cells to respond to and recover from the various perturbations that embryos continually face during the course of development. While the mechanisms governing the regionalization of the nervous system have been extensively studied, relatively less is known about the nature and limits of early neural plasticity of the anterior–posterior neural axis. This study aims to characterize the degree of neural axis plasticity in Xenopus laevis by investigating the response of embryos to a 180-degree rotation of their AP neural axis during gastrula stages by assessing the expression of regional marker genes using in situ hybridization. Our results reveal the presence of a narrow window of time between the mid- and late gastrula stage, during which embryos are able undergo significant recovery following a 180-degree rotation of their neural axis and eventually express appropriate regional marker genes including Otx, Engrailed, and Krox. By the late gastrula stage, embryos show misregulation of regional marker genes following neural axis rotation, suggesting that this profound axial plasticity is a transient phenomenon that is lost by late gastrula stages.

Geographic and gender-specific disparity can be observed in nasopharyngeal carcinoma (NPC). While screening and more effective therapies, such as induction chemotherapy, could improve survival rates, they are costly. This study aims to explore the correlation between healthcare expenditure and the mortality-to-incidence ratio (MIR) in NPC. Data were obtained from the World Health Organization and the Global Cancer Observatory. The correlation was evaluated by Spearman’s rank correlation coefficient. Most new cases and deaths occur in Asia, and more males are affected than females. Our study shows that countries with higher MIRs have lower levels of health expenditure regardless of the NPC’s gender-specific incidence. Correspondingly, MIRs are all significantly negatively associated with current health expenditure (CHE) per capita and CHE as a percentage of gross domestic product (CHE/GDP) in both genders. CHE per capita and CHE/GDP have a significant impact on NPC outcomes. Moreover, economic status is a potential major factor in MIR differences between countries.

The site quality evaluation of plantations has consistently been the focus in matching tree species with sites. This paper studied the site quality of Chinese fir (Cunninghamia lanceolata) plantations in Lin’an District, Zhejiang Province, China. The site quality model was constructed using the algebraic difference approach (ADA) to classify the site quality grades. The rough set algorithm was used to screen out the key site factors affecting the site rank of Chinese fir plantations. Site quality classification models based on random forest were established, and the importance of key site factors was evaluated. The results are as follows. The random forest model based on the rough set algorithm had small scale and low complexity, and the training and testing accuracies of the model were 92.47% and 78.46%, respectively, which were better than the model without attribute reduction. The most important factors affecting Chinese fir growth in the study area were the slope aspect, slope grade, and canopy closure. The least important factors were the humus layer thickness, soil layer thickness, naturalness, and stand origin. The attribute reduction method proposed in this study overcame the subjectivity of traditional site factor selection, and the site quality classification model constructed improved the model accuracy and reduced the complexity of the algorithm. The methods used in this study can be extended to other tree species to provide a basis for matching tree species with sites and to improve the level of forest management in the future.

Carbon dots (CDs) have caught enormous attention owing to their distinctive properties, such as their high water solubility, tunable optical properties, and easy surface modification, which can be generally used for the detection of heavy metals and organic pollutants. Herein, nitrogen and fluorine co-doped carbon dots (NFCDs) were designed via a rapid, low-cost, and one-step microwave-assisted technique using DL-malic acid and levofloxacin. The NFCDs emitted intense green fluorescence under UV lighting, and the optical emission peak at 490 nm was observed upon a 280 nm excitation, with a high quantum yield of 21.03%. Interestingly, the spectral measurements illustrated excitation-independent and concentration-independent single-color fluorescence owing to the presence of nitrogen and fluorine elements in the surface functional groups. Additionally, the NFCDs were applied for the selective detection of Fe3+ and ascorbic acid based on the “turn-off” mode. The detection limits were determined as 1.03 and 4.22 µM, respectively. The quenching mechanisms were explored using the static quenching mechanism and the inner filter effect. Therefore, a NFCDs fluorescent probe with single color emission was successfully developed for the convenient and rapid detection of Fe3+ and ascorbic acid in environments.

As the largest group of structurally diverse metabolites, terpenoids are versatile natural compounds that act as metabolism mediators, plant volatiles, and ecological communicators. However, few terpenoid compounds have been identified in plant parts of sacred lotus (Nelumbo nucifera Gaertn.). To elucidate the molecular genetic basis of the terpene biosynthetic pathway, terpenes from different parts of the plant, including seeds (S), young leaves (YL), mature leaves (ML), white flowers (WF), yellow flowers (YF), and red flowers (RF), were identified by LC-MS/MS and the relative contents of the same terpenes in different parts were compared. The results indicate that all plant parts primarily consist of triterpenes, with only minor quantities of sesquiterpenes and diterpenes, and there were differences in the terpene content detected in different plant parts. To illustrate the biosynthesis of various terpenoids, RNA sequencing was performed to profile the transcriptomes of various plant parts, which generated a total of 126.95 GB clean data and assembled into 29,630 unigenes. Among these unigenes, 105 candidate unigenes are involved in the mevalonate (MVA) pathway, methyl-erythritol phosphate (MEP) pathway, terpenoid backbone biosynthesis pathway, and terpenoid synthases pathway. Moreover, the co-expression network between terpene synthase (TPS) and WRKY transcription factors provides new information for the terpene biosynthesis pathway.