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Abstract The liver plays a vital role in lipid synthesis and metabolism in poultry. To study the functional genes more effectively, it is essential to screen of reliable reference genes in the chicken liver, including females, males, embryos, as well as the Leghorn Male Hepatoma (LMH) cell line. Traditional reference gene screening involves selecting commonly used housekeeping genes (HKGs) for RT-qPCR experiments and using different algorithms to identify the most stable ones. However, this approach is limited in selecting the best reference gene from a small pool of HKGs. High-throughput sequencing technology may offer a solution to this limitation. This study aimed to identify the most consistently expressed genes by utilizing multiple published RNA-seq data of chicken liver and LMH cells. Subsequently, the stability of the newly identified reference genes was assessed in comparison to previously validated stable poultry liver expressed reference genes and the commonly employed HKGs using RT-qPCR. The findings indicated that there is a higher degree of similarity in stable expression genes between female and male liver (such as LSM14A and CDC40). In embryonic liver, the optimal new reference genes were SUDS3, TRIM33, and ERAL1. For LMH cells, the optimal new reference genes were ALDH9A1, UGGT1, and C21H1orf174. However, it is noteworthy that most HKGs did not exhibit stable expression across multiple samples, indicating potential instability under diverse conditions. Furthermore, RT-qPCR experiments proved that the stable expression genes identified from RNA-seq data outperformed commonly used HKGs and certain validated reference genes specific to poultry liver. Over all, this study successfully identified new stable reference genes in chicken liver and LMH cells using RNA-seq data, offering researchers a wider range of reference gene options for RT-qPCR in diverse situations.

This study investigated the characteristics of dissolved organic matter (DOM) in two distinct water bodies, through the utilization of three-dimensional fluorescence spectroscopy coupled with self-organizing map (SOM) methodology. Specifically, this analysis concentrated on neurons 3, 14, and 17 within the SOM model, identifying notable differences in the DOM compositions of a coal subsidence water body (TX) and the MaChang Reservoir (MC). The humic substance content of DOM TX exceeded that of MC. The origin of DOM in TX was primarily linked to agricultural inputs and rainfall runoff, whereas the DOM in MC was associated with human activities, displaying distinctive autochthonous features and heightened biological activity. Principal component analysis revealed that humic substances dominated the DOM in TX, while the natural DOM in MC was primarily autochthonous. Furthermore, a multiple linear regression model (MLR) determined that external pollution was responsible for 99.11% of variation in the humification index (HIX) of water bodies. HIGHLIGHTS Study of the variation in DOM spectral characteristics of different waterbodies.; Neural networks were applied to spectral resolution.; Source analysis was performed to identify the origin of water pollution.;

ABSTRACT: Utilizing publicly available RNA-seq data to screen for ideal reference genes is more efficient and accurate than traditional methods. Previous studies have identified optimal reference genes in various chicken tissues, but none have specifically focused on the oviduct (including the infundibulum, magnum, isthmus, uterus, and vagina), which is crucial for egg production. Identifying stable reference genes in the oviduct is essential for improving research on gene expression levels. This study investigated genes with consistent expression patterns in the chicken oviduct, encompassing both individual oviduct tract tissues and the entire oviduct, by utilizing multiple RNA-seq datasets. The screening results revealed the discovery of 100 novel reference genes in each segment of oviduct tissues, primarily associated with cell cycle regulation and RNA binding. Moreover, the majority of housekeeping genes (HKGs) showed inconsistent expression levels across distinct samples, suggesting their lack of stability under varying conditions. The stability of the newly identified reference genes was assessed in comparison to previously validated stable reference genes in chicken oviduct and commonly utilized HKGs, employing traditional reference gene screening methods. HERPUD2, CSDE1, VPS35, PBRM1, LSM14A, and YWHAB were identified to be suitable novel reference gene for different parts of the oviduct. HERPUD2 and YWHAB were reliable for gene expression normalization throughout the oviduct tract. Furthermore, overexpression and interference assays in DF1 cells showed LSM14A and YWHAB play a crucial role in cell proliferation, highlighting the importance of these newly reference genes for further research. Overall, this study has expanded the options for reference genes in RT-qPCR experiments in different segments of the chicken oviduct and the entire oviduct.

Background: Microglia-mediated inflammation is a critical factor in the progression of ischemic stroke. Consequently, mitigating excessive microglial activation represents a potential therapeutic strategy for ischemic injury. Thymol, a monophenol derived from plant essential oils, exhibits diverse beneficial biological activities, including anti-inflammatory and antioxidant properties, with demonstrated protective effects in various disease models. However, its specific effects on ischemic stroke and microglial inflammation remain unexplored. Methods: Rodent transient middle cerebral artery occlusion (tMCAO) model was established to simulate ischemic stroke. TTC staining, modified neurological function score (mNSS), and behavioral tests were used to assess the severity of neurological damage. Then immunofluorescence staining and cytoskeleton analysis were used to determine activation of microglia. Lipopolysaccharide (LPS) was utilized to induce the inflammatory response of primary microglia in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to exam the expression of inflammatory cytokines. And western blot was used to investigate the mechanism of the anti-inflammatory effect of thymol. Results: In this study, we found that thymol treatment could ameliorate post-stroke neurological impairment and reduce infarct volume by mitigating microglial activation and pro-inflammatory response (IL-1β, IL-6, and TNF-α). Mechanically, thymol could inhibit the phosphorylation of phosphatidylinositol-3-kinase (PI3K), sink serine/threonine kinase (Akt), and mammalian target of rapamycin (mTOR), thereby suppressing the activation of nuclear factor-κB (NF-κB). Conclusions: Our study demonstrated that thymol could reduce the microglial inflammation by targeting PI3K/Akt/mTOR/NF-κB signaling pathway, ultimately alleviating ischemic brain injury. These findings suggest that thymol is a promising candidate as a neuroprotective agent against ischemic stroke.

BackgroundApoptosis has been recognized as a critical pathophysiological process during cerebral ischemia. The neuroprotective effect of CART on ischemic brain injury is determined. However, there is little research on the protective effect of CART on neural stem cells (NSCs).MethodsPrimary cultured rat NSCs were utilized as the research subject. In vitro oxygen glucose deprivation (OGD) treatment was employed, and NSCs were extracted from SD pregnant rats following previous experimental protocols and identified through cell immunofluorescence staining. The appropriate concentration of CART affecting OGD NSCs was initially screened using Cell Counting Kit-8 (CCK-8) and Lactate Dehydrogenase (LDH) assays. EdU staining and Western blotting (WB) techniques were employed to assess the impact of the suitable CART concentration on the proliferation and apoptosis of OGD NSCs. Finally, Western blot analysis was conducted to investigate the cAMP-response element binding protein (CREB) pathway and expression levels of related proteins after KG-501 treatment in order to elucidate the mechanism underlying apoptosis and proliferation regulation in OGD NSCs.ResultsCCK-8 and LDH assays indicated that a concentration of 0.8 nM CART may be the optimal concentration for modulating the proliferation of OGD NSCs. Subsequently, cellular immunofluorescence and EdU detection experiments further confirmed the findings obtained from CCK-8 analysis. Western blot analysis of apoptosis-related protein expression also demonstrated that an appropriate concentration of CART could suppress the apoptosis of OGD NSCs. Finally, Western blotting was conducted to examine the CREB pathway and related protein expression after treatment with KG-501, revealing that an appropriate concentration of CART regulated both apoptosis and proliferation in OGD NSCs through CREB signaling.ConclusionThe concentration of CART at 0.8 nM may be deemed appropriate for inhibiting apoptosis and promoting proliferation in OGD NSCs in vitro. The mechanism maybe through activating the CREB pathway.

Abstract Humanoid robots have attracted much attention by virtue of their compatibility with human environments. However, biped humanoids with immense promise still cannot function steadily and reliably in real‐world settings in the current state. Hence, rationally combining a humanoid robot with different stable mobile platforms is a favoured solution for diverse scenarios. Here, a new versatile humanoid robot platform, aiming to provide a generic solution that can be flexibly deployed in diverse scenarios, for example, indoors and fields is presented. Versatile humanoid robot platform incorporates multimodal perception, and extensible interfaces on hardware and software, allowing it to be rapidly integrated with different mobile platforms and end‐effectors, only through easy‐to‐assemble interfaces. Additionally, the platform has achieved impressive integration, lightness, dexterity, and strength in its class, with human‐like size and rich perception, targeted to have human‐intelligent manipulation skills for human‐engineered environments. Overall, this article elaborates on the reasoning behind the design choices, and outlines each subsystem. Lastly, the essential performance of the platform is successfully demonstrated in a set of experiments with precise and dexterous manipulation, and human–robot collaboration requirements.

ABSTRACT: The in ovo feeding (IOF) of L-arginine (L-Arg) to chick embryos is a viable method for improving early intestinal development, subsequently leading to an acceleration in growth rate during the posthatch stage. However, the liver, being the pivotal organ for energy metabolism in poultry, the precise effects and mechanisms of L-Arg on the liver development and metabolism remain unclear. To elucidate these, the present study injected 2 doses of L-Arg (10 mg/egg and 15 mg/egg) into the embryos of Hongyao chickens at 17.5 d of incubation, subsequently incubating them until d 19 for further analysis. IOF of 15 mg L-Arg/egg significantly increased the organ indices of liver and small intestine, as well as the duodenal villus height/crypt depth. RNA-Seq analysis of liver tissues showed that the metabolism of xenobiotics, amino acid metabolism, and the fatty acid metabolism were significantly enriched in L-Arg injection group. The core differentially expressed genes (DEGs) were primarily involved in cell proliferation and fatty acid metabolism. The CCK8 assays revealed that supplemental L-Arg significantly enhanced the proliferation of primary embryo hepatocytes and leghorn male hepatoma (LMH) cells. Upregulation of core DEGs, including HBEGF, HES4, NEK3, EGR1, and USP2, significantly promoted the proliferation of liver cells. Additionally, analysis of triglyceride and total cholesterol content, as well as oil red O staining, indicated that supplemental L-Arg effectively reduced lipid accumulation. Overall, L-Arg supplementation in late chick embryos may promote early liver and small intestine development by reducing liver lipid deposition and enhancing energy efficiency, necessitating further experimental validation. This study provides profound insights into the molecular regulatory network of L-Arg in promoting the development of chicken embryos. The identified DEGs that promote cell proliferation and lipid metabolism can serve as novel targets for further developing methods to enhance early development of chicken embryos.

Special planar structure endows two-dimensional (2D) materials with unique physical and chemical properties and the application of 2D materials to cement-based materials ensures the mechanical properties of buildings and infrastructures. Herein, a novel 2D nanoplate is synthesized through hydrothermal method with controlled sizes and morphologies. TEM and SEM measurements are used to characterize the nanostructures, confirming the morphologies, the distribution of elements among the structures and the crystal structure. The as-prepared nanoplates are able to enhance the mechanical strength of the cement mortar by its specific morphology and pozzolanic activity. The flexural strength was improved by 45.73 % after 1 d curing due to the acceleration of cement hydration. From the analysis of XRD and TG-DTG patterns, the nanoplates have strong interaction with the cement paste and the amount of the hydration products varied by the addition of the nanoplates. This approach helps promote the development of cement-based materials with high performance.

IntroductionConduct problems in children are related to callous-unemotional (CU) behaviors. However, results of the relationships between CU behaviors and conduct problems among preschoolers mainly focused on Western countries, no studies have examined whether CU behaviors predict conduct problem in Chinese preschoolers. The primary objective of the current study therefore was to examine the associations between CU behaviors and conduct problems as well as the moderating effects of surgency and child gender in Chinese preschool children.MethodsThe present study randomly selected 2,154 children (1,043 boys, Mage = 56 months, SD = 10.47) from six kindergartens in Shanghai, People’s Republic of China. Mothers rated children’s surgency and teachers reported children’s CU behaviors and conduct problems.ResultsResults demonstrated that CU behaviors were positively associated with conduct problems. Surgency and child gender significantly moderated these associations. Specifically, CU behaviors were positively associated with conduct problems, with a stronger effect found for high levels of surgency. CU behaviors had a positive association with conduct problems, with a stronger effect found for boys.DiscussionThis study indicate that temperament and gender characteristics influence conduct problems in preschoolers who exhibit high levels of CU behaviors. As well, the findings emphasize the significance of considering the meaning and implication of CU behaviors in Chinese culture.

Deep learning-based computer vision technology has been extensively utilized to assist medical microscopic smear diagnoses, such as complete blood count, detecting mycobacterium tuberculosis in sputum samples, and identifying plasmodium in blood smears. Effective medical microscopic smear detection necessitates balancing both detection accuracy and model parameters, facilitating the application of the model on low-resource computing platforms and ensuring real-time detection capabilities. Furthermore, the model should demonstrate superior generalization capabilities on microscopic smears to meet various detection tasks. In this study, we propose YOLO-FMS, a lightweight and efficient model based on YOLOv5 for medical microscopic smear detection with a compact weight of 15.06M, which can resolve the challenge of the balance between detection accuracy and model parameters. Firstly, YOLO-FMS improves the performance of small-scale platelet and mycobacterium tuberculosis detection by adding a small target detection head. Secondly, A lightweight convolutional technique, GSConv, was introduced to make the symbolic ability of the lightweight convolutional as close to the vanilla convolutional as possible and to reduce the computational cost. Thirdly, the feature extraction ability of YOLO-FMS is enhanced by C3-B-CBAM and Tiny-SPPCSPC modules constructed by our proposed method. Comprehensive experiments prove that YOLO-FMS shows high detection accuracy, with 92.5% mAP on the BCCD dataset and 87.6% mAP on the Tuberculosis-Phonecamera dataset. Additionally, numerous verification experiments are conducted on the BCDD and BBBC041 datasets, and the results confirm the effectiveness and generalization capability of YOLO-FMS in the medical microscopic smear detection field. The codes of YOLO-FMS are available at https://github.com/GefionP/YOLO-FMS.

Synthetic Aperture Radar (SAR) imaging technology is crucial for maritime vessel monitoring. However, the inherent characteristics of SAR images, such as limited feature resolution and speckle noise, pose a series of challenges for ship detection. Although existing research has made great progress in improving the model detection accuracy, it often comes at the cost of reduced efficiency and increased computational complexity. To address this issue, we propose a lightweight SAR ship detection model based on YOLOv5s, named GS-YOLO. Firstly, we adopt C3GhostV2 modules as the lightweight backbone to enhance the computational efficiency which is based on GhostNetV2 and GConv. In the neck, Squeeze and Excitation (SE) attention is employed to strengthen the feature extraction ability for small targets and improve the SAR ship detection precision. Furthermore, we develop a novel XIoU loss function to reinforce the accuracy and robustness of our model. Comparative experiment results on the HRSID dataset show that the proposed GS-YOLO achieves a significant increase in detection precision from 88.2% to 92.7% and the mean Average Precision (mAP) from 90.5% to 94.3%. In addition, the parameters are effectively reduced, achieving a good balance between detection speed and accuracy.

Recent inter-sample self-distillation methods that spread knowledge across samples further improve the performance of deep models on multiple tasks. However, their existing implementations introduce additional sampling and computational overhead. Therefore, in this work, we propose a simple improved algorithm, the center self-distillation, which achieves a better effect with almost no additional computational cost. The design process for it has two steps. First, we show using a simple visualization design that the inter-sample self-distillation results in a denser distribution of samples with identical labels in the feature space. And, the key to its effectiveness is that it reduces the intra-class variance of features through mutual learning between samples. This brings us to the idea of providing a soft target for each class as the center for all samples within that class to learn from. Then, we propose to learn class centers and consequently compute class predictions for constructing these soft targets. In particular, to prevent over-fitting arising from eliminating intra-class variation, the specific soft target for each sample is customized by fusing the corresponding class prediction with that sample’s prediction. This is helpful in mitigating overconfident predictions and can drive the network to produce more meaningful and consistent predictions. The experimental results of various image classification tasks show that this simple yet powerful approach can not only reduce intra-class variance but also greatly improve the generalization ability of modern convolutional neural networks.

With the continuous development of nuclear technology, the radiation exposure caused by radiation therapy is a serious health hazard. It is of great significance to further develop effective radiation countermeasures. B cells easily succumb to irradiation exposure along with immunosuppressive response. The approach to ameliorate radiation-induced B cell damage is rarely studied, implying that the underlying mechanisms of B cell damage after exposure are eager to be revealed. Recent studies suggest that Notch signaling plays an important role in B cell-mediated immune response. Notch signaling is a critical regulator for B cells to maintain immune function. Although accumulating studies reported that Notch signaling contributes to the functionality of hematopoietic stem cells and T cells, its role in B cells is scarcely appreciated. Presently, we discussed the regulation of Notch signaling on B cells under radiation exposure to provide a scientific basis to prevent radiation-induced B cell damage.

Research on hepatic steatosis in animal husbandry has been a prominent area of study. Developing an appropriate in vitro cellular steatosis model is crucial for comprehensively investigating the mechanisms involved in liver lipid deposition in poultry and for identifying potential interventions to address abnormalities in lipid metabolism. The research on the methods of in vitro liver steatosis in chickens, particularly the effects of different fat mixtures, is still lacking. In this study, LMH cells were utilized to investigate the effects of OA, SO, PA, SP, and their pairwise combinations on steatosis development, with the aim of identifying the optimal conditions for inducing steatosis. Analysis of triglyceride (TG) content in LMH cells revealed that OA and SP had limited efficacy in increasing TG content, while a combination of SO and PA in a 1:2 ratio exhibited the highest TG content. Moreover, Oil Red O staining results in LMH cells demonstrated that the combination treatment had a more pronounced induction effect compared to 0.375 mM SO. Additionally, RNA-seq analysis showed that 0.375 mM SO significantly influenced the expression of genes associated with fatty acid metabolism compared to the control group, whereas the combination of SO and PA led to an enrichment of key GO terms associated with programmed cell death. These findings suggest that varying conditions of cellular steatosis could lead to distinct disruptions in gene expression. The optimal conditions for inducing steatosis in LMH cells were also tested on chicken embryonic liver cells and embryos. TG detection and Oil Red O staining assays showed that the combination of SO and PA successfully induced steatosis. However, the gene expression pattern differed from that of LMH cells. This study lays the foundations for further investigations into avian hepatic steatosis.

Objective: To explore the characteristics of plasma metabolites, feces gut microbiota and the crosstalk between gut microbiota and host metabolism in patients with acute ischemic stroke and phlegm-heat pattern (AIS-PHP). Methods: The metabolic and microbiome profiles of 20 AIS-PHP patients and 20 healthy controls (HCs) were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics and 16s rDNA sequencing, respectively. The covariation between LC-MS/MS-based metabolite data and 16s rDNA sequence data was presented. Results: Distinct alterations in the plasma metabolic phenotype of AIS-PHP patients were found, in which 16 metabolites differed significantly between the AIS-PHP patients and the HCs. These metabolites represented 17 different metabolic pathways, including amino acid metabolism, lipid metabolism, and nucleotide metabolism. Additionally, significant alterations of gut microbiota composition and taxon were revealed at the phylum level between the AIS-PHP patients and the HCs. In AIS-PHP, Bacteroidetes, Firmicutes, and Proteobacteria dominated. Moreover, some microbes that differed between the 2 groups manifested a sole association with certain metabolites, such as the connection between Bacteroides and inosine and between Lachnospiraceae_unclassified and hypoxanthine. Conclusion: The present study preliminarily investigated the metabolomic and gut microbiome characteristics of AIS-PHP patient indicators. The link between metabolic and microbial dysbiosis in AIS-PHP sheds new light on the function of gut microbiota and associated metabolomics in the pathogenesis of the disease.

Abstract Background Mesenchymal stem cells (MSCs) therapies are emerging as a promising approach to therapeutic regeneration. Therapeutic persistence and reduced functional stem cells following cell delivery remain critical hurdles for clinical investigation due to the senescence of freshly isolated cells and extensive in-vitro passage. Methods Cultured adipose-derived stem cells (ASCs) were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, real-time PCR, and Westernblot to evaluate the levels related to cellular senescence markers. Results The mRNA expression levels of senescence markers were significantly increased in the later passage of ASCs. We show that light activation reduced the expression of senescent genes, and SA-β-Gal in all cells at passages. Moreover, the light-activated ASCs-derived exosomes decrease the expression of senescence, and SA-β-Gal in the later passage cells. We further investigated the photoreceptive effect of Opsin3 (Opn3) in light-activated ASCs. Deletion of Opn3 abolished the differences of light activation in reduced expression of senescent genes, increased Ca 2+ influx, and cAMP levels. Conclusions ASCs can undergo cellular senescence in-vitro passage. Photomodulation might be better preserved over senescence and Opn3-dependent activation in aged ASCs. Light-activated ASCs-derived exosomes could be served as e a new protective paradigm for cellular senescence in-vitro passage. Video Abstract

Effects of microwave irradiation on bamboo cell wall structures were studied. Microwave treatment resulted in samples exhibiting smoother surfaces, deformed parenchyma cells, and increased porosity. Microwave treatment altered microfibril orientation through the formation of hydrogen bonds. The peak at 3440 cm-1, assigned to O-H stretching, decreased. Meanwhile, intermolecular and intramolecular bonds were formed, increasing the uniformity of microfibrils. Condensation reactions in surface hydroxyl groups and the formation of intramolecular hydroxyl groups in the amorphous region under microwave irradiation also improved the fiber arrangement uniformity. After treatment, the HCH and HOC bonds were reduced and the ester bonds were broken down. The methoxy and aromatic ring hydroxyl groups were oxidized, as indicated by the increase in the absorption peak at 148 ppm. The hydroxyl groups in the amorphous region near the fiber surface decreased, as did hemicellulose content, but there was an increase in secondary crystalline fibers.

The polar regions of Mars, including the South and North Poles, are crucial for studying Martian climate and geological history, as they contain the largest reservoir of subsurface water ice. This study introduces a new approach for reflector detection, which includes radargram denoising to effectively enhance the signal of underground reflectors, peak detection to extract the positions of subsurface stratification from the radar echoes, and peak points connection to form continuous layers. The mapped enhancement denoising process involves a linear brightness adjustment and a fourth-order diffusion equation to enhance the signal of the subsurface layers for effective detection. The subsurface detection extracts the surface and subsurface peak points based on a peak detection algorithm, while using locally window-enhanced peak filtering and Kullback–Leibler (KL) divergence mapping to filter out non-stratified peak points. Finally, the layered connection process uses the proximity parameter to connect peak points in the same layer. Applied to multiple SHARAD (Shallow Radar) images at the Martian poles, this algorithm demonstrated a false detection rate below 5%. Compared to other methods, this method has a missed detection rate of less than 5% and, additionally, exhibits fewer discontinuities in layer connectivity. Therefore, this algorithm shows exceptional proficiency and applicability in analyzing the complex subsurface structures of the Martian polar regions.

ObjectiveNon-invasive methods for hemoglobin (Hb) monitoring can provide additional and relatively precise information between invasive measurements of Hb to help doctors' decision-making. We aimed to develop a new method for Hb monitoring based on mask R-CNN and MobileNetV3 with eye images as input.MethodsSurgical patients from our center were enrolled. After image acquisition and pre-processing, the eye images, the manually selected palpebral conjunctiva, and features extracted, respectively, from the two kinds of images were used as inputs. A combination of feature engineering and regression, solely MobileNetV3, and a combination of mask R-CNN and MobileNetV3 were applied for model development. The model's performance was evaluated using metrics such as R2, explained variance score (EVS), and mean absolute error (MAE).ResultsA total of 1,065 original images were analyzed. The model's performance based on the combination of mask R-CNN and MobileNetV3 using the eye images achieved an R2, EVS, and MAE of 0.503 (95% CI, 0.499–0.507), 0.518 (95% CI, 0.515–0.522) and 1.6 g/dL (95% CI, 1.6–1.6 g/dL), which was similar to that based on MobileNetV3 using the manually selected palpebral conjunctiva images (R2: 0.509, EVS:0.516, MAE:1.6 g/dL).ConclusionWe developed a new and automatic method for Hb monitoring to help medical staffs' decision-making with high efficiency, especially in cases of disaster rescue, casualty transport, and so on.

BackgroundDespite accumulating evidence revealing that Glucose-6-phosphate dehydrogenase (G6PD) is highly expressed in many tumor tissues and plays a remarkable role in cancer tumorigenesis and progression, there is still a lack of G6PD pan-cancer analysis. This study was designed to analyze the expression status and prognostic significance of G6PD in pan-cancer.MethodsG6PD expression data were obtained from multiple data resources including the Genotype-Tissue Expression, the Cancer Genome Atlas, and the Tumor Immunity Estimation Resource. These data were used to assess the G6PD expression, prognostic value, and clinical characteristics. The ESTIMATE algorithms were used to analyze the association between G6PD expression and immune-infiltrating cells and the tumor microenvironment. The functional enrichment analysis was also performed across pan-cancer. In addition, the GDSC1 database containing 403 drugs was utilized to explore the relationship between drug sensitivity and G6PD expression levels. Furthermore, we also performed clinical validation and in vitro experiments to further validate the role of G6PD in hepatocellular carcinoma (HCC) cells and its correlation with prognosis. The R software was used for statistical analysis and data visualization.ResultsG6PD expression was upregulated in most cancers compared to their normal counterparts. The study also revealed that G6PD expression was a prognostic indicator and high levels of G6PD expression were correlated with worse clinical prognosis including overall survival, disease-specific survival, and progression-free interval in multiple cancers. Furthermore, the G6PD level was also related to cancer immunity infiltration in most of the cancers, especially in KIRC, LGG, and LIHC. In addition to this, G6PD expression was positively related to pathological stages of KIRP, BRCA, KIRC, and LIHC. Functional analysis and protein-protein interactions network results revealed that G6PD was involved in metabolism-related activities, immune responses, proliferation, and apoptosis. Drug sensitivity analysis showed that IC50 values of most identified anti-cancer drugs were positively correlated with the G6PD expression. Notably, in vitro functional validation showed that G6PD knockdown attenuated the phenotypes of proliferation in HCC.ConclusionG6PD may serve as a potential prognostic biomarker for cancers and may be a potential therapeutic target gene for tumor therapy.

Background Given the reported effects of nuclear paraspeckle assembly transcript 1 (NEAT1) on kidney injury, a study is worth formulating to investigate whether and how NEAT1 impacts podocytes.Materials and methods A mouse podocyte injury model was established using the adriamycin (ADR)-induced mouse podocyte cell line (MPC5). The target relationships between NEAT1 and microRNA (miR)-23b-3p and between miR-23b-3p and Bcl-2 interacting protein 3 like (BNIP3L) were verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. After ADR-induced MPC5 cells were transfected with NEAT1 overexpression plasmid (oe-NEAT1) or shNEAT1, the viability and apoptosis of MPC5 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The expressions of MPC5, miR-23b-3p, BNIP3L and the factors related to podocyte injury, apoptosis and epithelial-mesenchymal transition were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot.Results NEAT1 was high-expressed in ADR-induced cell model. After transfection with oe-NEAT1, the expression of NEAT1, the levels of marker (Desmin) and apoptosis were promoted, while the viability and the levels of podocyte injury markers (WT1, Nephrin) were inhibited in ADR-induced cells. However, shNEAT1 generated the effects opposite to oe-NEAT1. Besides, miR-23b-3p competitively bound to NEAT1 and targeted BNIP3L. MiR-23b-3p inhibitor reversed the effect of shNEAT1, while its effect could be further offset by shBNIP3L. Furthermore, miR-23b-3p inhibitor affected mouse podocyte injury through downregulating Bcl-2 and E-cadherin levels and upregulating Cleaved-caspase-3, Bax, N-cadherin, Vimentin and Snail levels, but shBNIP3L did oppositely.Conclusion NEAT1 promotes the podocyte injury via targeting miR-23b-3p/BNIP3L axis.

Highlights Female RAGE−/− mice showed significantly improved glucose and insulin tolerance compared to male RAGE−/− mice. Female RAGE deficiency promotes M2 macrophage polarization in adipose tissues. Female RAGE deficiency prevents oxidative stress in adipose tissues. Female RAGE deficiency protects insulin-AKT signaling in adipose tissues.

Tea aroma plays an important role in its quality and preference. A fully analysis of tea aroma characteristics will help guide tea processing and further improve its quality. Extracting and identifying volatile compounds in different types of tea are critical steps to analyze its aroma characteristics. To this end, this paper mainly introduce the commonly used extraction methods for tea volatile compounds, the analytical methods of key aroma substances are summarized, and the aroma characteristics of six major tea categories are also overviewed based on research progress domestic and abroad, aiming to provide a theoretical basis for the in-depth study of tea aroma.

BackgroundThe chronic injury of the hematopoietic system caused by ionizing radiation (IR) is often ignored. The essential cause of this injury is the damage of hematopoietic stem and progenitor cells (HSPCs).ObjectiveTo explore the long-term effects of IR at different radiation doses and at different radiation fractions of the same radiation dose on HSPCs in the bone marrow of mice, and to provide a scientific basis for reducing the chronic damage to the hematopoietic system caused by IR.MethodsA total of 16 male C57BL/6 mice aged 8-10 weeks were randomly divided into four groups that received different doses or fractions of total body X-ray irradiation, including 1.5 Gy×4 irradiation group (n=5), 3 Gy irradiation group (n=4), 6 Gy irradiation group (n=4), and non-irradiation group (n=3). Two months after irradiation, bone marrow cells from each mouse were collected and counted. The clone forming ability of bone marrow cells was analyzed by cobblestone area-forming cell (CAFC) assay. The proportion of HSPCs was measured by flow cytometry. The cell cycle of HSPCs was assessed by antigen identified by monoclonal antibody Ki 67 (Ki-67) and 7-amino-actinomycin D (7-AAD) double staining. The reactive oxygen species (ROS) levels of HSPCs were estimated with a 2,7-dichlorodihydrofluorescein diacetate (DCFDA) probe. The cellular senescence of HSPCs was evaluated with a 5-dodecanoylaminofluorescein di-β-D-galactopyranoside (C12FDG) probe. The expression of senescence related genes such as P16, P19, P21, and P27 was measured by real-time fluorescence quantitative PCR.ResultsThere was no significant change in the numbers of bone marrow cells 2 months after different doses and fractions of radiation (P>0.05). The clone forming ability of bone marrow cells was significantly decreased after 3 Gy and 6 Gy irradiation when compared to non-irradiated mice (P0.05), the proportions of hematopoietic progenitor cells (HPCs), hematopoietic stem cells (HSCs), short-term hematopoietic stem cells (ST-HSCs), and multipotent progenitors 2 (MPP2) increased after irradiation (P0.05). The cellular senescent proportion of HPCs, LSK, and HSCs increased after irradiation (P

Measurement(s) Neighborhood context Technology Type(s) Naturally-occurring data Sample Characteristic - Environment City neighborhoods Sample Characteristic - Location Boston, MA, USA

Background: Hepatitis C virus (HCV) infection is a global health threat to the public, and vaccines against it are not yet available. The HCV envelope glycoprotein E2 is a key target for anti-HCV vaccines. The majority of previous studies have focused on the hypervariable region and the glycosylation sites of the_HCV structural protein. This study aims to investigate a conserved domain of HCV E2 glycoprotein and explore its potential to induce an immune response against HCV. Methods: HCV E2 conserved domain (encompassing amino acids 505–702) was prepared in Escherichia coli (E. coli). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with HCV or healthy controls. Interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot assay was conducted to examine the HCV E2-specific immune response as reflected by IFN-γ-secreting cells/106 PBMCs. Results: HCV E2 conserved domain was highly conserved among 25 HCV subtypes, and its recombinant soluble production in E. coli was recognized by anti-HCV E2 monoclonal antibodies. This study characterized in vitro direct interaction between bacterially expressed HCV E2 conserved domain and human CD81 (hCD81). Furthermore, the recombinant HCV E2_conserved domain markedly induced the production of IFN-γ by PBMCs from patients with HCV. Its stimulated specific immune response was significantly different from non-specific peptide controls or PBMCs isolated from healthy controls. Conclusions: HCV E2 conserved domain directly binds hCD81 and activates the production of IFN-γ in the PBMCs of patients with HCV. Therefore, the conserved domain of HCV E2 glycoprotein may be a new candidate for developing an HCV vaccine.

Background: In addition to intrahepatic angiogenesis, patients with cholestasis cirrhosis develop extrahepatic vasculature disorders and functional disturbances of multiple organ systems. Without effective intervention, these vascular disorders will eventually turn into multiple organs vascular syndromes, including the brain, lung and other organ systems. However, studies on the pathogenesis of vascular alterations among extrahepatic organ disturbances are still carried out separately, which hampered the successful translation of preclinical studies to the human setting and required further mechanistic insight into these complications. This study aims to investigate the relationship between extrahepatic angiogenesis and multiple organ impairment, and whether the vascular endothelial growth factor (VEGF) family members and their receptors are involved in this process. Methods: Pathological changes of the multiple organs were determined by histopathological and immunohistochemical staining in the established common bile duct ligation (CBDL) rats, and angiogenesis was estimated by microvessel density (MVD). Levels of the VEGF family members and their receptors in the serum and organ tissues were also measured by using enzyme-linked immunosorbent assays. Results: The MVD and VEGF family members and their receptors were significantly increased in CBDL rats with multiple organ injury, especially in the liver, lung and cerebral cortex. Meanwhile, we noticed moderate elevation of soluble receptor of the vascular endothelial growth factor-1 (sFlt-1) in the liver, lung, and cerebral cortex, whereas the levels of placental growth factor (PLGF) increased significantly. Conclusions: Extrahepatic angiogenesis may represent a common pathophysiological basis for multiple organ dysfunction and the sFlt-1/PLGF ratio could offer an avenue for further studies to target extrahepatic angiogenesis in cholestatic cirrhosis.

Our study aimed to explore the effects of postbiotics on protecting against Salmonella infection in mice and clarify the underlying mechanisms. Eighty 5-week-old C57BL/6 mice were gavaged daily with Lactiplantibacillus plantarum (LP)-derived postbiotics (heat-killed bacteria, LPBinactive; culture supernatant, LPC) or the active bacteria (LPBactive), and gavaged with Salmonella enterica Typhimurium (ST). The Turbidimetry test and agar diffusion assay indicated that LPC directly inhibited Salmonella growth. Real-time PCR and biofilm inhibition assay showed that LPC had a strong ability in suppressing Salmonella pathogenicity by reducing virulence genes (SopE, SopB, InvA, InvF, SipB, HilA, SipA and SopD2), pili genes (FilF, SefA, LpfA, FimF), flagellum genes (FlhD, FliC, FliD) and biofilm formation. LP postbiotics were more effective than LP on attenuating ST-induced intestinal damage in mice, as indicated by increasing villus/crypt ratio and increasing the expression levels of tight junction proteins (Occludin and Claudin-1). Elisa assay showed that LP postbiotics significantly reduced ST-induced inflammation by regulating the levels of inflammatory cytokines (the increased IL-4 and IL-10 and the decreased TNF-α) in serum and ileum (p < 0.05). Furthermore, LP postbiotics inhibited the activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome by decreasing the protein expression of NLRP3 and Caspase-1, and the gene expression of Caspase-1, IL-1β and IL-18. Meanwhile, both LPC and LPB observably activated autophagy under ST infection, as indicated by the up-regulated expression of LC3 and Beclin1 and the downregulated p62 level (p < 0.05). Finally, we found that LP postbiotics could trigger an AMP-activated protein kinase (AMPK) signaling pathway to induce autophagy. In summary, Lactiplantibacillus plantarum-derived postbiotics alleviated Salmonella infection via modulating bacterial pathogenicity, autophagy and NLRP3 inflammasome in mice. Our results confirmed the effectiveness of postbiotics agents in the control of Salmonella infection.

Background and aims: Effective hepatic blood flow (EHBF) decreases with liver disease progression, and identifying liver pathology is critical for patients with liver disease. This study was designed to elucidate the correlation between EHBF and liver pathology and explore the potential of EHBF for predicting the degree of liver pathology. Methods: In this study, 207 patients with hepatitis B virus (HBV) who underwent liver biopsy and indocyanine green (ICG) clearance tests were enrolled. EHBF was measured using the ICG clearance test, and liver tissue was histologically analyzed to determine the pathological stage according to the Scheuer scoring system. Demographic data, biochemical indexes, and FibroScan data were collected for statistical analysis. Results: EHBF levels decreased as the liver histological stages of inflammation and fibrosis increased (P

Abstract Objective The aim of this systematic review was to critically evaluate the Patient-Reported Outcome Measures (PROMs) for masticatory function in adults. Methods Five electronic databases (Medline, Embase, Web of Science Core Collection, CINAHL Plus and APA PsycINFO) were searched up to March 2021. Studies reporting development or validation of PROMs for masticatory function on adults were identified. Methodological quality of the included studies was evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist. Psychometric properties of the PROM in each included study were rated against the criteria for good measurement properties based on the COSMIN guideline. Results Twenty-three studies investigating 19 PROMs were included. Methodological qualities of these studies were diverse. Four types of PROMs were identified: questions using food items to assess masticatory function (13 PROMs), questions on chewing problems (3 PROMs), questions using both food items and chewing problems (2 PROMs) and a global question (1 PROM). Only a few of these PROMs, namely chewing function questionnaire-Chinese, Croatian or Albanian, food intake questionnaire-Japanese, new food intake questionnaire-Japanese, screening for masticatory disorders in older adults and perceived difficulty of chewing-Tanzania demonstrated high or moderate level of evidence in several psychometric properties. Conclusions Currently, there is no PROM for masticatory function in adults with high-level evidence for all psychometric properties. There are variations in the psychometric properties among the different reported PROMs. Trial Registration PROSPERO (CRD42020171591).

Social avoidance has been found to be related to negative social adjustment, yet evidence of the relationship between social avoidance and social adjustment is very limited in suburban preschoolers in China. Moreover, the underlying mechanisms that help to explain the associations between social avoidance and socio-emotional adjustment remain poorly considered. The goal of the present study was to examine the moderating effect of marital conflict in the link between social avoidance and indices of socio-emotional functioning among young children in mainland China. Participants were N = 256 children aged from 49 to 72 months (125 boys, 131 girls, Mage = 59.06 months, SD = 6.58) attending preschools/kindergartens in suburban areas of Shanghai, People’s Republic of China. Multi-source assessments were employed, with mothers reporting marital conflict as well as rating their children’s social withdrawal (i.e., social avoidance, shyness, unsociability), and teachers assessing indices of children’s socio-emotional functioning at school (i.e., anxious-fearful behavior, peer exclusion, and loneliness). Children were asked about their loneliness. Among the results, social avoidance was positively associated with anxious-fearful behavior, peer exclusion, and loneliness (marginal significance). Moreover, as hypothesized, marital conflict was found to exacerbate the relations between social avoidance and peer exclusion, and loneliness. Results are discussed in terms of the etiology and implications of social avoidance among young children in mainland China.

Abatract Obesity is known to be associated with adipose tissue inflammation and insulin resistance. Importantly, in obesity, the accumulation of proinflammatory macrophages in adipose tissue correlates with insulin resistance. We hypothesized that the receptor for advanced glycation end products (RAGE) and associated ligands are involved in adipose tissue insulin resistance, and that the activation of the AGE–RAGE axis plays an important role in obesity-associated inflammation. C57BL/6J mice (WT) and RAGE deficient (RAGE−/−) mice were fed a high fat diet (HFD) and subjected to glucose and insulin tolerance tests. Epdidymal adipose tissue (eAT) was collected and adipose stromal vascular cells isolated using flow cytometry. Visceral adipose tissue macrophage polarization was assessed by quantitative real time PCR. Immunoblotting was performed to evaluate the insulin signaling in adipose tissues. In additional studies, cell trafficking was assessed by injecting labeled blood monocytes into recipient mice. RAGE−/− mice displayed improved insulin sensitivity and glucose tolerance, accompanied by decreased body weight and eAT mass. Exogenous methylglyoxal (MGO) impaired insulin-stimulated AKT signaling in adipose tissues from WT mice fed a normal chow diet, but not in RAGE−/− mice. In contrast, in obese mice, treatment with MGO did not reduce insulin-induced phosphorylation of AKT in WT-HFD mice. Moreover, insulin-induced AKT phosphorylation was found to be impaired in adipose tissue from RAGE−/−-HFD mice. RAGE−/− mice displayed improved inflammatory profiles and evidence for increased adipose tissue browning. This observation is consistent with the finding of reduced plasma levels of FFA, glycerol, IL-6, and leptin in RAGE−/− mice compared to WT mice. Collectively the data demonstrate that RAGE-mediated adipose tissue inflammation and insulin-signaling are potentially important mechanisms that contribute to the development of obesity-associated insulin resistance.

Abstract Background The results of a previous study verified that umbilical cord mesenchymal stem cells (UCMSCs) have good therapeutic effects for the treatment of HBV-related acute-on-chronic liver failure (ACLF) and liver cirrhosis (LC). Nevertheless, it is still unknown whether the effects of UCMSCs are affected by recipient age. Methods Patients treated with UCMSCs who met the criteria of HBV-related ACLF and liver cirrhosis were identified in this retrospective observational study. Patients were divided into subgroups according to the World Health Organization (WHO) age criteria (

Enhanced recovery after surgery (ERAS) can accelerate patient recovery. However, little research has been done on optimizing the ERAS-related measures and how the measures interact with each other. The Bayesian network (BN) is a graphical model that describes the dependencies between variables and is also a model for uncertainty reasoning. In this study, we aimed to develop a method for optimizing anesthetic decisions in ERAS and then investigate the relationship between anesthetic decisions and outcomes. First, assuming that the indicators used were independent, the effects of combinations of single indicators were analyzed based on BN. Additionally, the impact indicators for outcomes were selected with statistical tests. Then, based on the previously selected indicators, the Bayesian network was constructed using the proposed structure learning method based on Strongly Connected Components (SCC) Local Structure determination by Hill Climbing Twice (LSHCT) and adjusted according to the expert’s knowledge. Finally, the relationship is analyzed. The proposed method is validated by the real clinical data of patients with benign gynecological tumors from 3 hospitals in China. Postoperative length of stay (LOS) and total cost (TC) were chosen as the outcomes. Experimental results show that the ERAS protocol has some pivotal indicators influencing LOS and TC. Identifying the relationship between these indicators can help anesthesiologists optimize the ERAS protocol and make individualized decisions.

Currently, interferon add-on therapy brings hope for clinical cure of chronic hepatitis B patients with low HBsAg. However, in clinical practice patients with poor responses to their first interferon therapy were often switched to nucleos(t)ide analog therapy and then labeled as unsuitable patients for interferon therapy. Even if their HBsAg levels dropped to a low level, they were reluctant or not recommended to take interferon again, which caused them to miss out on interferon add-on therapy and clinical cure. Therefore, it is urgent to elucidate the effectiveness of interferon add-on therapy to get clinical cure for these interferon-experienced patients with low HBsAg. The purpose of this study was to investigate whether interferon-experienced patients could achieve the same HBsAg clearance and HBsAg seroconversion rates as interferon-naive patients. Also, the associated factor of HBsAg clearance and seroconversion were aimed to be clarified. 292 patients, including 85 interferon-experienced patients, were enrolled with HBsAg< 1500 IU/ml, HBeAg negative and HBV-DNA negative. And then, peg-interferon α-2b add-on therapy was performed. The results showed that the week 48 HBsAg clearance and seroconversion rates of all patients were 29.8% and 22.0%. There was no statistically significant difference between interferon-experienced and interferon-naive patients in week 48 HBsAg clearance and seroconversion rates, suggesting satisfactory clinical cure of the interferon add-on therapy for interferon-experienced patients. The age, baseline HBsAg, and week 12 HBsAg were negative correlated factors for week 48 HBsAg clearance and seroconversion. Furthermore, the age, baseline HBsAg and week 12 HBsAg for predicting the week 48 HBsAg clearance were cut off at 40.5 years, at 152.0 IU/ml and at 34.99 IU/ml, and for predicting seroconversion were cut off at 40.5 years, at 181.9 IU/ml and at 34.99 IU/ml, correspondingly. Significantly, interferon-experienced patients with low HBsAg were suggested with interferon add-on therapy to achieve clinical cure as soon as possible. This research provided evidences and cut-offs for the interferon add-on therapy against chronic hepatitis B.

Drought is one of the most significant limiting factors affecting plant growth and development on the Qinghai–Tibet Plateau (QTP). Mining the drought-tolerant genes of the endemic perennial grass of the QTP, Siberian wildrye (Elymus sibiricus), is of great significance to creating new drought-resistant varieties which can be used in the development of grassland livestock and restoring natural grassland projects in the QTP. To investigate the transcriptomic responsiveness of E. sibiricus to drought stress, PEG-induced short- and long-term drought stress was applied to two Siberian wildrye genotypes (drought-tolerant and drought-sensitive accessions), followed by third- and second-generation transcriptome sequencing analysis. A total of 40,708 isoforms were detected, of which 10,659 differentially expressed genes (DEGs) were common to both genotypes. There were 2107 and 2498 unique DEGs in the drought-tolerant and drought-sensitive genotypes, respectively. Additionally, 2798 and 1850 DEGs were identified in the drought-tolerant genotype only under short- and long-term conditions, respectively. DEGs numbering 1641 and 1330 were identified in the drought-sensitive genotype only under short- and long-term conditions, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that all the DEGs responding to drought stress in E. sibiricus were mainly associated with the mitogen-activated protein kinase (MAKP) signaling pathway, plant hormone signal transduction, the linoleic acid metabolism pathway, the ribosome pathway, and plant circadian rhythms. In addition, Nitrate transporter 1/Peptide transporter family protein 3.1 (NPF3.1) and Auxin/Indole-3-Acetic Acid (Aux/IAA) family protein 31(IAA31) also played an important role in helping E. sibiricus resist drought. This study used transcriptomics to investigate how E. sibiricus responds to drought stress, and may provide genetic resources and references for research into the molecular mechanisms of drought resistance in native perennial grasses and for breeding drought-tolerant varieties.

Coronavirus disease 2019 (COVID-19) threatens public health all over the world. It is well-accepted that the immune cells in peripheral blood are widely involved in the pathological process of COVID-19. However, hematopoietic stem and progenitor cells (HSPCs), as the main source of peripheral immune cells, have not been well studied during COVID-19 infection. We comprehensively revealed the transcriptome changes of peripheral blood HSPCs after COVID-19 infection and vaccination by single-cell RNA-seq. Compared with healthy individuals, the proportion of HSPCs in COVID-19 patients significantly increased. The increase in the proportion of HSPCs might be partly attributed to the enhancement of the HSPCs proliferation upon COVID-19 infection. However, the stemness damage of HSPCs is reflected by the decrease of differentiation signal, which can be used as a potential specific indicator of the severity and duration of COVID-19 infection. Type I interferon (IFN-I) and translation signals in HSPCs were mostly activated and inhibited after COVID-19 infection, respectively. In addition, the response of COVID-19 vaccination to the body is mild, while the secondary vaccination strengthens the immune response of primary vaccination. In conclusion, our study provides new insights into understanding the immune mechanism of COVID-19 infection.

Abstract Background Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. Methods We demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Results In diet-induced obesity, implantation of light-treated ASCs improved glucose tolerance and ameliorated systemic insulin resistance. Intriguingly, compared with non-light-treated ASCs, light-treated ASCs reduced monocyte infiltration and the levels of ATMs in EAT. Moreover, implantation of light-treated ASCs exerts more anti-inflammatory effects by suppressing M1 polarization and enhancing macrophage M2 polarization in EAT. Mass spectrometry revealed that light-treated human obese ASCs conditioned medium retained a more complete secretome with significant downregulation of pro-inflammatory cytokines and chemokines. Conclusions These data suggest that the combined application of photoactivation and ASCs using transplantation into dysfunctional adipose tissue contribute to selective suppression of inflammatory responses and protection from insulin resistance in obesity and type 2 diabetes.

Postbiotics are the inactive bacteria and/or metabolites of beneficial microbes which have been recently found to be as effective as their live probiotic. This study aimed to evaluate the benefits of Lactobacillus plantarum (LP)-derived postbiotics on ameliorating Salmonella-induced neurological dysfunctions. Mice were pretreated with LP postbiotics (heat-killed bacteria or the metabolites) or active bacteria, and then challenged with Salmonella enterica Typhimurium (ST). Results showed that LP postbiotics, particularly the metabolites, effectively prevented ST infection in mice, as evidenced by the inhibited weight loss, bacterial translocation, and tissue damages. The LP postbiotics markedly suppressed brain injuries and neuroinflammation (the decreased interleukin (IL)-1β and IL-6, and the increased IL-4 and IL-10). Behavior tests indicated that LP postbiotics, especially the metabolites, protected mice from ST-induced anxiety and depressive-like behaviors and cognitive impairment. A significant modulation of neuroactive molecules (5-hydroxytryptamine, gamma-aminobutyric acid, brain-derived neurotrophic factor, dopamine, acetylcholine, and neuropeptide Y) was also found by LP postbiotic pretreatment. Microbiome analysis revealed that LP postbiotics optimized the cecal microbial composition by increasing Helicobacter, Lactobacillus and Dubosiella, and decreasing Mucispirillum, norank_f_Oscillospiraceae, and Eubacterium_siraeum_group. Moreover, LP postbiotics inhibited the reduction of short-chain fatty acids caused by ST infection. Pearson's correlation assays further confirmed the strong relationship of LP postbiotics-mediated benefits and gut microbiota. This study highlights the effectiveness of postbiotics and provide a promising strategy for preventing infection-induced brain disorders by targeting gut–brain axis.

Background: It has been suggested that cortisol levels are abnormal in chronic urticaria and atopic dermatitis, but other steroids, such as dehydroepiandrosterone (DHEA) and testosterone, are still unknown, and whether these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. Limited data are available on steroid levels in prurigo nodularis (PN)-related research, and no study has examined the association between pruritus severity and steroid levels in PN patients.Aims: This pilot study aimed to investigate the differences in the levels of five steroids combined with their ratios in plasma between PN patients and controls and to examine the associations between the biomarkers and pruritus severity.Methods: Plasma concentrations of five steroids, including cortisol, cortisone, testosterone, progesterone, and dehydroepiandrosterone (DHEA), in 36 patients with PN were compared with concentrations in thirty-six and matched healthy controls. The concentrations of steroids were quantitated using liquid chromatography-tandem mass spectrometry. The PN symptoms, including pruritus severity, pain, and life quality, were assessed with the use of the visual analog scale, prurigo score index, numerical rating scale, and verbal rating scale and dermatology life quality index scores.Results: In comparison with controls, PN patients had lower levels of plasma cortisol and cortisone, which negatively correlated with PN symptoms. PN patients had higher levels of cortisone and testosterone to cortisol, which positively correlated with pruritus severity. Additionally, there were no significant differences in plasma concentrations of DHEA and testosterone between the two groups. We found no correlation between plasma concentrations of DHEA and testosterone and pruritus severity.Conclusion: This pilot study suggests that there may be abnormalities in peripheral blood levels of cortisol, and cortisone and the ratios of cortisone and testosterone to cortisol in patients with PN, and they are related to pruritus severity. The plasma concentrations of testosterone and DHEA may be not abnormal in PN patients and may not be associated with pruritus severity.

ObjectiveTo develop and validate a noninvasive radiomic-based machine learning (ML) model to identify P504s/P63 status and further achieve the diagnosis of prostate cancer (PCa).MethodsA retrospective dataset of patients with preoperative prostate MRI examination and P504s/P63 pathological immunohistochemical results between June 2016 and February 2021 was conducted. As indicated by P504s/P63 expression, the patients were divided into label 0 (atypical prostatic hyperplasia), label 1 (benign prostatic hyperplasia, BPH) and label 2 (PCa) groups. This study employed T2WI, DWI and ADC sequences to assess prostate diseases and manually segmented regions of interest (ROIs) with Artificial Intelligence Kit software for radiomics feature acquisition. Feature dimensionality reduction and selection were performed by using a mutual information algorithm. Based on screened features, P504s/P63 prediction models were established by random forest (RF), gradient boosting decision tree (GBDT), logistic regression (LR), adaptive boosting (AdaBoost) and k-nearest neighbor (KNN) algorithms. The performance was evaluated by the area under the ROC curve (AUC) and accuracy.ResultsA total of 315 patients were enrolled. Among the 851 radiomic features, the 32 top features were derived from T2WI, in which the gray-level run length matrix (GLRLM) and gray-level cooccurrence matrix (GLCM) features accounted for the largest proportion. Among the five models, the RF algorithm performed best in general evaluations (microaverage AUC=0.920, macroaverage AUC=0.870) and provided the most accurate result in further sublabel prediction (the accuracies of label 0, 1, and 2 were 0.831, 0.831, and 0.932, respectively). In comparative sequence analyses, T2WI was the best single-sequence candidate (microaverage AUC=0.94 and macroaverage AUC=0.78). The merged datasets of T2WI, DWI, and ADC yielded optimal AUCs (microaverage AUC=0.930 and macroaverage AUC=0.900).ConclusionsThe radiomic-based RF classifier has the potential to be used to evaluate the presurgical P504s/P63 status and further diagnose PCa noninvasively and accurately.

A detailed understanding of the distribution and degree of genetic variation within a species is important for determining their evolutionary potential, which in return facilitates the development of efficient conservation strategies aimed at preserving adaptive genetic variation. As an important perennial, cool-season grass in temperate Eurasia, increasing attention has been paid to Siberian wildrye (Elymus sibiricus) due to its excellent ecological utilization value and forage production potential in China, particularly in the Qinghai–Tibet Plateau (QTP) regions. In this study, we applied two chloroplast (cp) genes (matK and rbcL), three cp spacer regions (trnY-GUA∼trnD-GUC, atpH∼atpF, and rps4∼trnT-UGU), and six cpSSR markers to the genetic and phylogenetic analysis of 137 wild E. sibiricus accessions from 23 natural populations that represent the main distribution regions in China. The results show the highest genetic diversity (h = 0.913) and haplotype richness (10 haplotypes) for the QTP population, which indicates QTP as the probable diversity center and geographic origin of E. sibiricus in China. Population divergence was high, indicating a significant phylogeographic structure together with a significantly higher Nst value (Nst > Gst, P < 0.05) at the species level, QTP+XJ (combined populations from QTP and Xinjiang), QTP+NC (combined populations from QTP and North China), and XJ+NC (combined populations from Xinjiang and North China) group levels, respectively. An expansion was revealed in the distributional range of E. sibiricus in China from paleo times up to the recent past, while a dramatic range of contraction was predicted for the near future. The predicted main limiting factor for the further spread of E. sibiricus is an increasing global mean temperature. We recommend that the combination of Es-cpDNA1 and Es-cpDNA3+4+5 can be used as effective markers for phylogenetic analysis and phylogeographical history analysis of E. sibiricus. These findings shed new light on the historical population dynamics of cold-season herbs in the QTP region and the north of China and are of great significance for the future establishment of protection and collection strategies for wild E. sibiricus germplasm.

Inspired by the microstructures feature in the architected composites, which are consisted of a stiff phase and a soft phase, the concept of varying the struts thickness in the uniform honeycomb (UH) is proposed to enhance the toughness of UH structures through heterogeneous design. We specifically examine the effect of the choice of reinforcement phase, particularly its patterning and organization, on the toughness and deformation mechanisms of heterogeneous designed hexagonal (HDH) lattices. The HDH lattice is fabricated by using the 3D-laser cutting, and the HDH lattice composite is made by a hybrid manufacturing process on this basis. The experimental results show that the crack paths of the substrate lattice are consistent with the lattice composite. With longer crack paths, the total energy dissipation of the HDH lattice composite is significantly enhanced, and thus the toughness increases accordingly. In addition, theory and simulation studies for the substrate lattice are also carried out to explore the crack deflection mechanism. These results provide tougher lattice structures and shed new insights into the structure–property relationship which may further facilitate the design and usage of lattices in a wide range of structural engineering applications.

The combination of Unmanned Aerial Vehicle (UAV) technologies and computer vision makes UAV applications more and more popular. Computer vision tasks based on deep learning usually require a large amount of task-related data to train algorithms for specific tasks. Since the commonly used datasets are not designed for specific scenarios, in order to give UAVs stronger computer vision capabilities, large enough aerial image datasets are needed to be collected to meet the training requirements. In this paper, we take low-altitude aerial image object detection as an example to propose a framework to demonstrate how to construct datasets for specific tasks. Firstly, we introduce the existing low-altitude aerial images datasets and analyze the characteristics of low-altitude aerial images. On this basis, we put forward some suggestions on data collection of low-altitude aerial images. Then, we recommend several commonly used image annotation tools and crowdsourcing platforms for data annotation to generate labeled data for model training. In addition, in order to make up the shortage of data, we introduce data augmentation techniques, including traditional data augmentation and data augmentation based on oversampling and generative adversarial networks.

Gait generation method is one of the important contents of snake robot motion control. Different gait generation methods produce completely different forms of control functions, so snake robots need more complicated programming logic and processes to realize various gaits and their transformation. Therefore, we propose a new unified expression of gait method, The MCC (main characteristics control) method simplifies and unifies the control functions of different snake robots gaits by extracting the main features of the backbone curves of snake robots gaits. Since all periodic curves that meet the Dirichlet conditions can be formed by superposition of sinusoidal curves, taking the “lowest frequency” part that reflects the main characteristics of the curve as the target configuration can simplify the motion control function of snake robots’ gaits. Based on the MCC method, some snake robot gaits are reconstructed, including serpentine gait, rolling gait, helix rolling gait, and crawler gait. In addition, based on MCC method, an AEH-sidewinding gait control method is proposed. The backbone of the AEH-sidewinding gait is closer to the ideal elliptic helix, thus improving the accuracy of its kinematics modeling of snake robot sidewinding gait. Finally, the validity of this gait is verified by experiments. This unified gait expression of snake robots will be helpful to realize smooth gait switching between different gaits of snake robots.

This paper explores the scientific & technological innovation performance of world-class universities in China from 2014 to 2019, based on the super-efficiency DEA model and Malmquist index. Then we provide a novel five-dimensional analysis framework to research influencing factors of their S&T innovation efficiency with the Tobit-DEA model. The results show that 36.6% of the sample universities are DEA efficient, and their efficiency varies according to their type and location. Besides, the technical efficiency index of universities is relatively high and the total factor productivity is volatile, which are reflected in the ability of transforming scientific research achievements into practical productivity. From the perspective of dynamic analysis, the sample universities expand slowly in the frontier of S&T innovation efficiency. In addition, the S&T innovation performance is highly related to the input quality and matching structure of scientific research elements, government relevance, and industry-academia-research collaboration level. Among these main factors, the high proportion of full-time teachers with senior titles, reasonable resource allocation structure and government support have significant positive impact, whereas the number of participants in international academic has negative impact.

Genetically encoded non-canonical amino acids (ncAAs) with electrophilic moieties are excellent tools to investigate protein-protein interactions (PPIs) both in vitro and in vivo. These ncAAs, including a series of alkyl bromide-based ncAAs, mainly target cysteine residues to form protein-protein cross-links. Although some reactivities towards lysine and tyrosine residues have been reported, a comprehensive understanding of their reactivity towards a broad range of nucleophilic amino acids is lacking. Here we used a recently developed OpenUaa search engine to perform an in-depth analysis of mass spec data generated for Thioredoxin and its direct binding proteins cross-linked with an alkyl bromide-based ncAA, BprY. The analysis showed that, besides cysteine residues, BprY also targeted a broad range of nucleophilic amino acids. We validated this broad reactivity of BprY with Affibody/Z protein complex. We then successfully applied BprY to map a binding interface between SUMO2 and SUMO-interacting motifs (SIMs). BprY was further applied to probe SUMO2 interaction partners. We identified 264 SUMO2 binders, including several validated SUMO2 binders and many new binders. Our data demonstrated that BprY can be effectively used to probe protein-protein interaction interfaces even without cysteine residues, which will greatly expand the power of BprY in studying PPIs.

Abstract Background Umbilical cord mesenchymal stem cells (UCMSCs) have been demonstrated to have good therapeutic effects in the treatment of HBV-related liver diseases. However, the therapeutic effect of UCMSCs on HBV-related liver failure and liver cirrhosis and the variations in the efficacy of UCMSCs after different treatment courses remain poorly understood. Therefore, this study was designed to answer these two questions. Methods This was an observational study that retrospectively considered a 3-year period during which 513 patients who received stem cell infusion and met the criteria of hepatic failure and liver cirrhosis were identified from the databases of the Third Affiliated Hospital of Sun Yat-sen University. The eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the duration of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks of stem cell therapy. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and the patients in group D received less than 4 weeks of stem cell therapy. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and model for end-stage liver disease (MELD) scores were recorded and compared among different groups. Results A total of 64 patients met the criteria for liver failure, and 59 patients met the criteria for liver cirrhosis. After UCMSC treatment, the levels of alanine aminotransferase (ALT), glutamic-oxaloacetic transaminase (AST), and total bilirubin (TBIL) at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the prothrombin activity (PTA) and MELD scores gradually improved in only the liver failure group. Four weeks after UCMSC treatment, patients who received prolonged treatment with UCMSCs had a larger decrease in TBIL levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there were no statistically significant differences in the changes in ALT, AST, TBIL, and PTA values and MELD scores between patients with liver failure who received prolonged treatment with UCMSCs and patients with liver cirrhosis who received prolonged treatment with UCMSCs at any time point. However, the median decrease and cumulative decrease in the TBIL level of patients with liver failure with a standard 4-week treatment course were larger than those of patients with liver cirrhosis with a standard 4-week treatment course. Conclusion Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.

Hepatic encephalopathy (HE) is a serious complication caused by liver disease and is one of the leading causes of death in patients. Studies have shown that proper emergency care for patients after the occurrence of HE can improve their prognosis and quality of life. Therefore, this study focuses on the effect of optimizing the emergency care process on the effectiveness and prognosis of emergency care for patients with hepatic encephalopathy. In this study, we set 32 patients with HE admitted to receive routine emergency care between May 2020 and March 2021 as the control group and 34 patients with HE admitted to receive optimized emergency care processes between April 2021 and February 2022 as the observation group. The satisfaction of patients’ families with this care was assessed using a self-administered nursing satisfaction questionnaire to record the outcome of emergency care, quality of care, and prognosis of patients in the two groups of palliative care. The data collected were analyzed using SPSS17.0 software, and the results showed that the time spent on diagnosis, resuscitation, DTP, and DTT was much lower in the observation group than in the control group, and the scores related to the quality of care, such as ambulance technique, humanistic care, resuscitation efficiency, and resuscitation effect, were all higher than those of the control group, and the satisfaction of the family members in the observation group was also significantly higher than that of the control group (P0.05). It can be seen that the application of an optimized emergency nursing process in HE patients is effective, which can effectively improve the success rate of HE resuscitation, shorten the resuscitation time and condition diagnosis, improve the resuscitation effect, improve the quality of nursing care, and improve the prognosis of patients to a certain extent.

Organic rheology modifiers, especially superplasticizers and viscosity-modifying admixtures (VMAs), have become key components for the workability optimization of modern concrete. The development of these admixtures is crucial to the further performance improvement of modern concrete under different casting and service conditions. Many of the former reviews have summarized research advances in respect of these admixtures from chemical and material perspectives, focusing on the effects of structure and the performance. In this paper, from a rheological perspective, an overview is provided of the microscale behavior of polycarboxylate (PCE) superplasticizers and VMAs (e.g., adsorption, conformation, and bridging) in terms of the evolution of the microstructure of the paste, the effect of chemical structure on the yield stress, the apparent viscosity and thixotropy of cement-based materials, and the structure design of these admixtures. Most importantly, in addition to a general discussion with assumptions (monolayer adsorption of a “flat” conformation, with each molecule on a single particle; statistical polymer composition), special conditions (e.g., preferential adsorption, depletion effects, hydration modification effects, and the polydispersity of the polymer composition) are discussed. Newly developed admixtures, realized through regulation of the microscale behavior, and by the modification of adsorption, topological structure, and molecular frame, are introduced.