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Background. Bone mineral density is widely used by clinicians for screening osteoporosis and assessing bone strength. However, its effectiveness has been reported unsatisfactory. In this study, it is demonstrated that bone organic-inorganic phase ratio is a fundamental determinant of bone material quality measured by stiffness, strength, and toughness. Methods and Results. Two-hundred standard bone specimens were fabricated from bovine legs, with a specialized manufacturing method that was designed to reduce the effect of bone anisotropy. Bone mechanical properties of the specimens, including Young’s modulus, yield stress, peak stress, and energy-to-failure, were measured by mechanical testing. Organic and inorganic mass contents of the specimens were then determined by bone ashing. Bone density and organic-inorganic phase ratio in the specimens were calculated. Statistical methods were applied to study relationships between the measured mechanical properties and the organic-inorganic phase ratios. Statistical characteristics of organic-inorganic phase ratios in the specimens with top material quality were investigated. Bone organic-inorganic phase ratio had strong Spearman correlation with bone material properties. Bone specimens that had the highest material quality had a very narrow scope of organic-inorganic phase ratio, which could be considered as the “optimal” ratio among the tested specimens. Conclusion. Bone organic-inorganic phase ratio is a fundamental determinant of bone material quality. There may exist an “optimal” ratio for the bone to achieve top material quality. Deviation from the “optimal” ratio is probably the fundamental cause of various bone diseases. This study suggests that bone organic-inorganic phase ratio should be considered in clinical assessment of fracture risk.

Tuberculosis (TB) is the world's most prevalently infectious disease. Molecular mechanisms behind tuberculosis remain unknown. microRNA (miRNA) is involved in a wide variety of diseases. To validate the significant genes and miRNAs in the current sample, two messenger RNA (mRNA) expression profile datasets and three miRNA expression profile datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed (DE) genes (DEGs) and miRNAs (DE miRNAs) between healthy and TB patients were filtered out. Enrichment analysis was executed, and a protein-protein interaction (PPI) network was developed to understand the enrich pathways and hub genes of TB. Additionally, the target genes of miRNA were predicted and overlapping target genes were identified. We studied a total of 181 DEGs (135 downregulated and 46 upregulated genes) and two DE miRNAs (2 downregulated miRNAs) from two gene profile datasets and three miRNA profile datasets, respectively. 10 hub genes were defined based on high degree of connectivity. A PPI network's top module was constructed. The 23 DEGs identified have a significant relationship with miRNAs. 25 critically significant Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were discovered. The detailed study revealed that, in tuberculosis, the DE miRNA and DEGs form an interaction network. The identification of novel target genes and main pathways would aid with our understanding of miRNA's function in tuberculosis progression.

Clostridium perfringens (CP) is the principal pathogenic bacterium of chicken necrotic enteritis (NE), which causes substantial economic losses in poultry worldwide. Although probiotics are known to provide multiple benefits, little is known about the potential effects of Bacillus subtilis (B. subtilis) application in preventing CP-induced necrotic enteritis. In this study, 450 male Arbor Acres broilers were divided into 5 experimental treatments: A: basal diet (control group); B: basal diet and CP challenge (model group); C: CP challenge+10 mg/kg enramycin (positive control group); D: CP challenge+ 4 × 10 7 CFU / kg of feed B. subtilis PB6 (PB6 low-dosage group); and E: CP challenge+ 6 × 10 7 CFU / kg of feed B. subtilis PB6 (PB6 high-dosage group). There were 6 replicate pens per treatment with 15 broilers per pen. The present research examined the effect of Bacillus subtilis PB6 (B. subtilis PB6) on growth performance, mRNA expression of intestinal cytokines and tight junctions, and gut flora composition in broilers challenged with CP. The entire experiment was divided into two phases: the non-CP challenge phase (d0–18) and the CP challenge phase (d18–26). PB6 did not increase the growth performance during the first stage, but the PB6 high-dosage group was found to have larger body weight gain and ADFI during the CP challenge stage. Feed supplementation with PB6 reduced the lesion score of challenged chicks, with increased tight junction-related gene expression (occludin and ZO-1) and decreased TNF-α expression compared with CP-infected birds. A decrease in the abundance of Clostridium XI, Streptococcus, and Staphylococcus was observed after CP infection ( P < 0.05 ), while supplementation with PB6 restored the ileal microbial composition. In conclusion, administration of B. subtilis PB6 improved growth performance, enhanced intestinal barrier function, and mitigated intestinal inflammation/lesions, which might be due to its restoring effects on the ileal microbial composition in CP-challenged broilers.

Naming is a commonly impaired language domain in various types of aphasia. Emerging evidence supports the cortico‐subcortical circuitry subserving naming processing, although neurovascular regulation of the non‐dominant thalamic and basal ganglia subregions underlying post‐stroke naming difficulty remains unclear. Data from 25 subacute stroke patients and 26 age‐, sex‐, and education‐matched healthy volunteers were analyzed. Region‐of‐interest‐wise functional connectivity (FC) was calculated to measure the strength of cortico‐subcortical connections. Cerebral blood flow (CBF) was determined to reflect perfusion levels. Correlation and mediation analyses were performed to identify the relationship between cortico‐subcortical connectivity, regional cerebral perfusion, and naming performance. We observed increased right‐hemispheric subcortical connectivity in patients. FC between the right posterior superior temporal sulcus (pSTS) and lateral/medial prefrontal thalamus (lPFtha/mPFtha) exhibited significantly negative correlations with total naming score. Trend‐level increased CBF in subcortical nuclei, including that in the right lPFtha, and significant negative correlations between naming and regional perfusion of the right lPFtha were observed. The relationship between CBF in the right lPFtha and naming was fully mediated by the lPFtha‐pSTS connectivity in the non‐dominant hemisphere. Our findings suggest that perfusion changes in the right thalamic subregions affect naming performance through thalamo‐cortical circuits in post‐stroke aphasia. This study highlights the neurovascular pathophysiology of the non‐dominant hemisphere and demonstrates thalamic involvement in naming after stroke., We demonstrated that cerebral perfusion changes in the non‐dominant thalamic subregions affect naming performance through the thalamo‐cortical connectivity between the right lPFtha/mPFtha and pSTS in post‐stroke aphasia. Our findings highlight the pathophysiology of non‐dominant hemisphere recruitment, and that the right thalamic involvement of the lPFtha, from functional and vascular aspects, may underlie network reorganization for naming processing after stroke.

Objective. To study the effect of a care bundle combined with continuous positive airway pressure (CPAP) in the postanesthesia care unit (PACU) on rapid recovery after pulmonary tumor resection. Methods. A total of 135 patients requiring anesthesia resuscitation after pulmonary tumor resection in our hospital from June 2020 to February 2021 were selected. They were randomly divided into three groups: the PACU experimental group, PACU control group, and operating room resuscitation (OR) group. Subsequently, their intraoperative clinical symptoms, parameters in monitoring postoperative respiratory status, and follow-up results were compared among the three groups. Results. The PACU experimental group had the highest number of right lesions, while the OR group had the highest intraoperative blood transfusion volume, urine volume, intraoperative colloid volume, intrapulmonary shunt, and intraoperative physician handover rate ( P < 0.05 ). Before surgery, serum potassium (K) in the PACU experimental group was significantly higher than that in the OR group but lower than that in the PACU control group ( P < 0.01 ). During the time in the PACU, blood partial pressure of oxygen (PO2) and oxygen index (OI) levels in the PACU experimental group were significantly higher than those in the other groups ( P < 0.01 ). After surgery, total PACU stay time, time from PACU to extubation, and stay after extubation were markedly reduced in the PACU experimental group ( P < 0.05 ). The highest number of patients with drainage was found in the PACU experimental group, while the highest number of patients without drainage was found in the PACU control group. Conclusion. A care bundle combined with CPAP in the PACU can improve the monitoring time of respiratory status and improve blood gas parameters, thus accelerating the postoperative rehabilitation process of patients undergoing pulmonary tumor resection.

Liver fibrosis is a pathological variation caused by almost all chronic liver injuries. As an edible and medicinal natural resource, Phyllanthus emblica (PE) has been reported to possess hepatoprotective, antioxidant, and anti-inflammatory activities and may have an ameliorating effect on hepatic fibrosis. To investigate the protective effect of the aqueous extract of PE (AEPE) against liver fibrosis and to uncover its related mechanisms, the chemical profile of AEPE was characterized by high performance liquid chromatography (HPLC) and sulfuric acid-phenol method. Ameliorative effects of different doses of AEPE were investigated in carbon-tetrachloride- (CCl4-) induced liver fibrosis rats by analyzing biochemical markers, morphologic pathology, and related proteins expression in liver tissue. The results indicated that AEPE (1.8, 3.6 g/kg) could significantly reduce levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), collagen IV (Col IV), type III precollagen (PCIII), hyaluronic acid (HA), laminin (LN), malondialdehyde (MDA), nitric oxide (NO), protein carbonyl (PC), tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and hydroxyproline (Hyp) and increase the levels of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Hematoxylin-eosin (H&E), Sirius red, and Masson staining showed AEPE-treated improved fibrotic lesions and inflammatory cell infiltration. Meanwhile, AEPE treatment also significantly downregulates the expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in the liver tissue and serum, respectively. In conclusion, AEPE possesses curative efficacy against liver fibrosis through its antioxidant, anti-inflammatory, and antifibrotic effects.

Computer-aided diagnosis (CAD) has nearly fifty years of history and has assisted many clinicians in the diagnosis. With the development of technology, recently, researches use the deep learning method to get high accuracy results in the CAD system. With CAD, the computer output can be used as a second choice for radiologists and contribute to doctors doing the final right decisions. Chest abnormality detection is a classic detection and classification problem; researchers need to classify common thoracic lung diseases and localize critical findings. For the detection problem, there are two deep learning methods: one-stage method and two-stage method. In our paper, we introduce and analyze some representative model, such as RCNN, SSD, and YOLO series. In order to better solve the problem of chest abnormality detection, we proposed a new model based on YOLOv5 and ResNet50. YOLOv5 is the latest YOLO series, which is more flexible than the one-stage detection algorithms before. The function of YOLOv5 in our paper is to localize the abnormality region. On the other hand, we use ResNet, avoiding gradient explosion problems in deep learning for classification. And we filter the result we got from YOLOv5 and ResNet. If ResNet recognizes that the image is not abnormal, the YOLOv5 detection result is discarded. The dataset is collected via VinBigData’s web-based platform, VinLab. We train our model on the dataset using Pytorch frame and use the mAP, precision, and F1-score as the metrics to evaluate our model’s performance. In the progress of experiments, our method achieves superior performance over the other classical approaches on the same dataset. The experiments show that YOLOv5’s mAP is 0.010, 0.020, 0.023 higher than those of YOLOv5, Fast RCNN, and EfficientDet. In addition, in the dimension of precision, our model also performs better than other models. The precision of our model is 0.512, which is 0.018, 0.027, 0.033 higher than YOLOv5, Fast RCNN, and EfficientDet.

X-ray detection is of great significance in biomedical, nondestructive, and scientific research. Lead halide perovskites have recently emerged as one of the most promising materials for direct X-ray detection. However, the lead toxicity remains a worrisome concern for further commercial application. Great efforts have been made to search for lead-free perovskites with similar optoelectronic properties. Here, we present a lead-free oxide double perovskite material Ba(2)AgIO(6) for X-ray detection. The lead-free, all-inorganic nature, as well as the high density of Ba(2)AgIO(6), promises excellent prospects in X-ray applications. By employing the hydrothermal method, we successfully synthesized highly crystalline Ba(2)AgIO(6) powder with pure phase. Furthermore, we prepared Ba(2)AgIO(6) wafers through isostatic pressure and built X-ray detectors with Au/Ba(2)AgIO(6) wafer/Au photo-conductive structure. The as-prepared X-ray detectors showed a sensitivity of 18.9 µC/(Gy(air)·cm(2)) at 5 V/mm, similar to commercial α-Se detectors showcasing their advantages for X-ray detection. [Image: see text]

Deer velvet antlers are the young horns of male deer that are not ossified and densely overgrown. Velvet antler and its preparations have been widely used in the treatment of postmenopausal osteoporosis (PMOP) in recent years, although its mechanism of action in the human body remains unclear. To screen the effective ingredients and targets of velvet antler in the treatment of PMOP using network pharmacology and to explore the potential mechanisms of velvet antler action in such treatments, we screened the active ingredients and targets of velvet antler in the BATMAN-TCM database. We also screened the relevant targets of PMOP in the GeneCards and OMIM databases and then compared the targets at the intersection of both velvet antler and PMOP. We used Cytoscape 3.7.2 software to construct a network diagram of “disease-drug-components-targets” and a protein-protein interaction (PPI) network through the STRING database and screened out the core targets; the R language was then used to analyze the shared targets between antler and PMOP for GO-enrichment analysis and KEGG pathway-annotation analysis. Furthermore, we used the professional software Maestro 11.1 to verify the predictive analysis based on network pharmacology. Hematoxylin-eosin (H&E) staining and micro-CT were used to observe the changes in trabecular bone tissue, further confirming the results of network pharmacological analysis. The potentially effective components of velvet antler principally include 17β-E2, adenosine triphosphate, and oestrone. These components act on key target genes such as AKT1, IL6, MAPK3, TP53, EGFR, SRC, and TNF and regulate the PI3K/Akt-signaling and MAPK-signaling pathways. These molecules participate in a series of processes such as cellular differentiation, apoptosis, metabolism, and inflammation and can ultimately be used to treat PMOP; they reflect the overall regulation, network regulation, and protein interactions.

Objective To determine whether the metabolites of Kynurenine pathway (KP) could serve as biomarkers for distinguishing between viral CNS infections and autoimmune neuroinflammatory diseases, especially anti‐N‐methyl‐D‐aspartate receptor encephalitis (NMDARE) and herpes virus encephalitis (HSE). Methods This study enrolled CSF samples from 76 patients with viral CNS infections, autoimmune neuroinflammatory, and non‐inflammatory neurological diseases. We measured cerebrospinal fluid (CSF) concentrations of tryptophan (Trp) and kynurenine (Kyn) by ELISA. Results Kyn concentrations and Kyn/Trp ratios were highly increased (p

Objective. The purpose of this study is to identify novel biomarkers for the prognosis of Ewing’s sarcoma based on bioinformatics analysis. Methods. The GSE63157 and GSE17679 datasets contain patient and healthy control microarray data that were downloaded from the Gene Expression Omnibus (GEO) database and analyzed through R language software to obtain differentially expressed genes (DEGs). Firstly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, protein-protein interaction (PPI) networks, and Cytoscape Molecular Complex Detection (MCODE) plug-in were then used to compute the highest scores of the module. After survival analysis, the hub genes were lastly obtained from the two module genes. Results. A total of 1181 DEGs were identified from the two GSEs. Through MCODE and survival analysis, we obtain 53 DEGs from the module and 29 overall survival- (OS-) related genes. ZBTB16 was the only downregulated gene after Venn diagrams. Survival analysis indicates that there was a significant correlation between the high expression of ZBTB16 and the OS of Ewing’s sarcoma (ES), and the low expression group had an unfavorable OS when compared to the high expression group. Conclusions. High expression of ZBTB16 may serve as a predictor biomarker of poor prognosis in ES patients.

Aim The aim of this paper was to translate the English version of the Inpatient Dignity Scale into Mandarin and to test the psychometric properties of the Mandarin version of the Inpatient Dignity Scale. Design This research is a cross‐sectional survey, using convenience sampling. Methods The English version of the Inpatient Dignity Scale was translated into Mandarin Chinese. From June–August 2020, 736 inpatients from 50 tertiary hospitals in Guangzhou were recruited to assess the psychometric attributes of the Inpatient Dignity Scale. Results The Mandarin version of the Inpatient Dignity Scale consists of expectation and satisfaction subscales. It differs from the English language version, as the expectation subscale includes three dimensions and the satisfaction subscale includes two dimensions. The total Cronbach alpha coefficient of the expectation subscale and the satisfaction subscale were .820 and .965, respectively, and the split‐half reliability of the expectation subscale and the satisfaction subscale were 0.740 and 0.928, respectively, indicating good internal consistency and effectiveness. Known‐groups validity was established, as 70% of the hypotheses were supported.

Aim To investigate the relationship between research ability and research motivation of postgraduate nursing students in traditional Chinese medicine colleges and identify other factors that may have an impact on the research ability of postgraduate nursing students. Design A cross‐sectional electronic survey was used to collect data from 191 postgraduate nursing students. Methods A total of 191 postgraduate nursing students from seven traditional Chinese medicine colleges were investigated from October to November 2020 using self‐rated scales for research ability and research motivation. The relationship between the variables affecting the research ability of postgraduate nursing students in traditional Chinese medicine colleges was determined. Results There was a positive correlation between the score of self‐rated research ability and research motivation among 191 postgraduate nursing students in traditional Chinese medicine colleges. Multiple stepwise regression analysis showed that grade, research motivation, age and active participation in class discussions were the main factors affecting the self‐rated research ability. Conclusion The self‐rated research ability of postgraduate nursing students in traditional Chinese medicine colleges is positively correlated with research motivation. According to the research motivation orientation, adopting targeted training methods and establishing correct professional understanding may improve the research ability of postgraduate nursing students.

Background Direct associations of tobacco exposure during pregnancy with pregnancy complications and adverse birth outcomes have been proven. Previous studies suggest that expecting a child provides a valuable opportunity to promote behavioural changes, such as smoking cessation, among the male partners of pregnant women. Thorough understandings of Chinese expectant fathers’ smoking behaviour during the transition to fatherhood is a prerequisite to the development of appropriate interventions to facilitate smoking cessation. This study aimed to explore the perceptions, behaviours and attitudes related to smoking among male partners of pregnant women in China. Methods A descriptive phenomenological approach was adopted. A purposive sample of expectant fathers aged 18 years or older who had a tobacco use history within the past year were recruited at obstetrics and gynaecology clinics and invited to participate in one-to-one, 20–30-min semi-structured interviews. The data analysis followed Colaizzi’s descriptive phenomenological method. Results Twenty-five expectant fathers were interviewed. Four themes were generated: 1) the benefits of smoking and respondents’ misperceptions of the impact of smoking and SHS and neglectful attitude of the impact of smoking, which were given as the major reasons for continuing to smoke; 2) factors contributing to smoking cessation, including concern for the potential health impact of continued smoking on the pregnant partner and baby, the role of being father, and the encouragement to quit from family members; and 3) perceived barriers to smoking cessation, including withdrawal symptoms or cigarette cravings, absence of smoking cessation support, and increasing stress. Conclusion This study provides a comprehensive understanding of the perception, behaviours, and attitudes related to smoking among Chinese expectant fathers. The findings of this study can guide healthcare professionals and policymakers in combining the distribution of educational information about the hazards of SHS for maternal and neonatal health with smoking cessation assistance for expectant fathers through policy initiatives and other types of incentives and programmes targeted to enhance smoking cessation among this population. Trial registration Prospectively registered at clinicaltrial.org (NCT03401021) on 8 Jan 2018.

Graphical abstract, Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus that causes severe infection in humans characterized by an acute febrile illness with thrombocytopenia and hemorrhagic complications, and a mortality rate of up to 30%. Understanding on virus-host protein interactions may facilitate the identification of druggable antiviral targets. Herein, we utilized liquid chromatography-tandem mass spectrometry to characterize the SFTSV interactome in human embryonic kidney-derived permanent culture (HEK-293T) cells. We identified 445 host proteins that co-precipitated with the viral glycoprotein N, glycoprotein C, nucleoprotein, or nonstructural protein. A network of SFTSV-host protein interactions based on reduced viral fitness affected upon host factor down-regulation was then generated. Screening of the DrugBank database revealed numerous drug compounds that inhibited the prioritized host factors in this SFTSV interactome. Among these drug compounds, the clinically approved artenimol (an antimalarial) and omacetaxine mepesuccinate (a cephalotaxine) were found to exhibit anti-SFTSV activity in vitro. The higher selectivity of artenimol (71.83) than omacetaxine mepesuccinate (8.00) highlights artenimol’s potential for further antiviral development. Mechanistic evaluation showed that artenimol interfered with the interaction between the SFTSV nucleoprotein and the host glucose-6-phosphate isomerase (GPI), and that omacetaxine mepesuccinate interfered with the interaction between the viral nucleoprotein with the host ribosomal protein L3 (RPL3). In summary, the novel interactomic data in this study revealed the virus-host protein interactions in SFTSV infection and facilitated the discovery of potential anti-SFTSV treatments.

Rhus chinensis Mill. (RCM) is the host plant of Galla chinensis, which is valued in traditional medicine. Environmental temperature directly determines the probability of gallnut formation and RCM growth. At present, there is no experiment to systematically analyse the stability of internal reference gene (RG) expression in RCM. In this experiment, leaves that did not form gallnuts were used as the control group, while leaves that formed gallnuts were used as the experimental group. First, we conducted transcriptome experiments on RCM leaves to obtain 45 103 differential genes and functional enrichment annotations between the two groups. On this basis, this experiment established a transcriptional gene change model of leaves in the process of gallnut formation after being bitten by aphids, and RCM reference candidate genes were screened from RNA sequencing (RNA‐seq) data. This study is based on RCM transcriptome data and evaluates the stability of 11 potential reference genes under cold stress (4 °C) and heat stress (34 °C), using three statistical algorithms (geNorm, NormFinder, and BestKeeper). The results show that GAPDH1 + PP2A2/UBQ are stable reference genes under heat stress, while GAPDH1 + ACT are the most stable under cold stress. This study is the first to screen candidate reference genes in RCM and could help guide future molecular studies in this genus., Appropriate and stable reference genes are important for normalization of gene expression. This study is based on Rhus chinensis Mill. transcriptome data and evaluates the stability of 11 potential reference genes under cold stress (4 °C) and heat stress (34 °C), using three statistical algorithms (geNorm, NormFinder, and BestKeeper). This study is the first to screen candidate reference genes in Rhus chinensis Mill. and could help guide future molecular studies in this genus.

Context Qingluoyin (QLY) is a traditional Chinese medicine (TCM) formula which has been used in treating human rheumatoid arthritis (RA) for years in China. Objective This study investigates the effect of QLY granules on adjuvant arthritis (AA) and the possible mechanism. Materials and methods Sprague-Dawley (SD) rats were injected with Complete Freund’s adjuvant (CFA) to induce the AA model. After the onset of arthritis, rats received intragastric administrations of the QLY granules (1.35, 2.70, and 5.40 g/kg) or Tripterygium glycosides (TG) tablets (positive drug, 10 mg/kg) for 14 d. After 28 d immunization, the symptoms, inflammatory parameters and molecular mechanisms were investigated. Results In the QLY granule (1.35, 2.70, and 5.40 g/kg) therapy groups, the arthritis index decreased to 6.30 ± 2.06, 5.80 ± 1.55, 5.30 ± 1.16 compared with the model (9.00 ± 3.01), paw swelling decreased to 1.56 ± 0.40, 1.28 ± 0.38, 1.12 ± 0.41 mL compared with the model (2.22 ± 0.73 mL). QLY granules (1.35, 2.70 and 5.40 g/kg) significantly reduced the thymus and the spleen indexes, inhibited the production of pro-inflammatory cytokines, and alleviated the pathological changes of joints compared with the model group. Furthermore, the treatment of QLY granules (2.70 and 5.40 g/kg) markedly inhibited CXCL12, CXCR4 (in spleen and synovium) and p-NF-κB p65 (in synovium) protein expression of AA rats. Conclusions QLY granules have obvious therapeutic effects on AA rats, which may be associated with downregulating the CXCL12/CXCR4-NF-κB signalling pathway. QLY granules can be used as a candidate for the treatment of RA, which deserves further study.

Our aim was to explore the effects of dietary and behavior interventions on lipometabolism caused by an unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks and then intervened for another 4 weeks. Eight of them were classified into high-fat control group, and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet in swimming group, and 7 were just for refeeding normal diet group. Then, the data of body weight was recorded and analyzed. Indexes of serum samples were tested by kits. AMPKα, HNF1α, and CTRP6 in pancreas, liver, cardiac, and epididymis adipose tissues were detected by western blot. According to our experiments, swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by upregulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T-CHO ( P < 0.001 ) and LDL-C ( P < 0.05 ), but higher weight gain ( P < 0.001 ), insulin level ( P < 0.01 ), and pancreas AMPKα ( P < 0.01 ) than high-fat control rats. Compared with rats intervened by swimming or rice vinegar, they showed higher weight gain ( P < 0.001 ), insulin level ( P < 0.01 ), and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.

BackgroundFlowering plants (angiosperms) are dominant components of global terrestrial ecosystems, but phylogenetic relationships at the familial level and above remain only partially resolved, greatly impeding our full understanding of their evolution and early diversification. The plastome, typically mapped as a circular genome, has been the most important molecular data source for plant phylogeny reconstruction for decades.ResultsHere, we assembled by far the largest plastid dataset of angiosperms, composed of 80 genes from 4792 plastomes of 4660 species in 2024 genera representing all currently recognized families. Our phylogenetic tree (PPA II) is essentially congruent with those of previous plastid phylogenomic analyses but generally provides greater clade support. In the PPA II tree, 75% of nodes at or above the ordinal level and 78% at or above the familial level were resolved with high bootstrap support (BP ≥ 90). We obtained strong support for many interordinal and interfamilial relationships that were poorly resolved previously within the core eudicots, such as Dilleniales, Saxifragales, and Vitales being resolved as successive sisters to the remaining rosids, and Santalales, Berberidopsidales, and Caryophyllales as successive sisters to the asterids. However, the placement of magnoliids, although resolved as sister to all otherMesangiospermae, is not well supported and disagrees with topologies inferred from nuclear data. Relationships among the five major clades ofMesangiospermaeremain intractable despite increased sampling, probably due to an ancient rapid radiation.ConclusionsWe provide the most comprehensive dataset of plastomes to date and a well-resolved phylogenetic tree, which together provide a strong foundation for future evolutionary studies of flowering plants.

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest. Supplementary Information The online version contains supplementary material available at 10.1007/s13238-021-00885-0.

Aim To investigate the extent of post‐traumatic growth, and the correlation between post‐traumatic growth and self‐perceived stress, post‐traumatic growth and self‐perceived burden among CAPD patients. Design A cross‐sectional study. Methods This was a multi‐centre study including 752 patients from 44 hospitals. Self‐perceived stress, self‐perceived burden and post‐traumatic growth were measured using the post‐traumatic growth inventory (PTGI), the Chinese version of the perceived stress questionnaire (CPSQ) and the self‐perceived burden scale (SPBS). A multiple stepwise regression analysis was fit with the total PTGI score as the outcome of interest. Results Patients concurrently experienced post‐traumatic growth and stress following peritoneal dialysis. The initiation of patients’ education level, employment status and self‐perceived stress were all found to relate to growth among Chinese CAPD patients. There was not sufficient evidence to suggest that self‐perceived burden was related to experiencing growth.

Introduction: COVID-19, a continuously emerging human-to-human infectious disease, has exerted a significant impact on the mental health of college students. However, little is known regarding the variations in the mental health issues experienced by college students during the peak versus reopening stages of the COVID-19 epidemic in China. Methods: To assess these issues, an online longitudinal survey was conducted via a WeChat applet. Undergraduates (n = 300) were recruited from 26 universities throughout Jinan in February 2020 (T1 – the epidemic peak stage) and in January 2021 (T2 – the society reopening stage). Their mental status was determined using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 item, and the Insomnia Severity Index. Results: Of the original 300 college students recruited for this survey, 294 responses at T1 and 285 at T2 were analyzed. Compared with responses obtained at T1, college students at T2 showed a greater prevalence of depression (65.3 vs. 51.0%; p = 0.001) and anxiety (47.7 vs. 38.1%, p = 0.019), and experienced more severe depression (p < 0.001) and anxiety (p < 0.001). Both males (p = 0.03) and females (p < 0.01) showed higher levels of depression at T2 versus T1, while no differences were obtained with regard to anxiety and insomnia. At T1, Grade 4 students showed greater levels of depression (p = 0.005) and anxiety (p = 0.008) than that of Grade 1 students. While at T2, only greater levels of depression (p = 0.004) were present when compared with that of Grade 1 students. Additionally, Grade 4 college students demonstrated a greater prevalence of depression at T2 versus T1 (p = 0.03), but no statistically differences were present for anxiety and insomnia. No statistically significant differences were obtained among the 4 grades of college students for insomnia at either the T1 or T2. Conclusion: With progression of the COVID-19 epidemic, college students showed increasing levels of depression and anxiety, with Grade 4 college students being most seriously affected. It is imperative that intervention strategies be implemented to mitigate against these mental health issues resulting from the COVID-19 epidemic.

Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis in endemic regions of Asia. The neurotropism of JEV and its high-efficiency replication in neurons are the key events for pathogenesis. Revealing the interplay between virus and host cells in metabolic facet is of great importance both for unraveling the pathogenesis mechanisms and providing novel antiviral targets. This study took advantage of the integration analysis of metabolomics and transcriptomics to depict the metabolic profiles of neurons during the early stage of JEV infection. Increased glycolysis and its branched pentose phosphate pathway (PPP) flux and impaired oxidative phosphorylation (OXPHOS) in glucose utilization, and the catabolic patterns of lipid metabolism were created to facilitate the biosynthesis of precursors needed for JEV replication in neurons. Pharmacological inhibitions of both glycolysis pathway and PPP in neurons suggested its indispensable role in maintaining the optimal propagation of JEV. In addition, analysis of metabolomic-transcriptomic regulatory network showed the pivotal biological function of lipid metabolism during JEV infection. Several pro-inflammatory lipid metabolites were significantly up-regulated and might partially be responsible for the progression of encephalitis. These unique metabolic reprogramming features might give deeper insight into JEV infected neurons and provide promising antiviral approaches targeting metabolism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12250-021-00445-0.

Ginsenoside Rh2 is considered as a new direction for future cancer treatment because of its excellent anticancer effect. However, due to its low bioavailability, it cannot exert its significant anticancer effect when applied directly to the human body. Chitosan (CS), a nanomaterial, has been verified to be able to enhance drug efficacy via its coating for drugs. Thus, we designed this study to investigate the impact of CS-coated ginsenoside Rh2 on the metastasis and growth of colon cancer (CC). First, ginsenoside Rh2 chitosan tripolyphosphate (CS-Rh2-TPP) nanoparticles (NPs) were constructed, and MTT, transwell, scratch adhesion, and flow cytometry assays were carried out for determining the impact of CS-Rh2-TPP at various concentrations on growth, metastasis, and apoptosis of colon cancer cells (CCCs). qRT-PCR was used to detect the expression of mircoRNA-491 (miR-491) in CCCs. According to TEM-based image analysis, CS-Rh2-TPP NPs were spherical or spheroidal in even distribution, with a particle size of about 220 mm and a zeta potential of −44.58 ± 2.84 mV. Additionally, CCCs presented lower miR-491 than normal colon cells, and its relative expression in CCCs showed a stronger increase after intervention of CS-Rh2-TPP than that after intervention of ginsenoside Rh2. Moreover, CS-Rh2-TPP suppressed the activity, invasion, as well as migration of CCCs and accelerated their apoptosis more significantly than ginsenoside Rh2. According to these results, CS-Rh2-TPP is able to upregulate miR-491 in CCCs, thus suppressing the metastasis and growth of CC.

The longevity and reusability of N95‐grade filtering facepiece respirators (N95 FFRs) are limited by consecutive donning and disinfection treatments. Herein, we developed stable N97 nanofibrous respirators based on chemically modified surface to enable remarkable filtration characteristics via polarity driven interaction. This was achieved by a thin‐film coated polyacrylonitrile nanofibrous membrane (TFPNM), giving an overall long‐lasting filtration performance with high quality factor at 0.42 Pa−1 (filtration efficiency: over 97 %; pressure drop: around 10 Pa), which is higher than that of the commercial N95 FFRs (0.10–0.41 Pa−1) tested with a flow rate of 5 L min−1 and the 0.26 μm NaCl aerosol. A coxsackie B4 virus filtration test demonstrated that TFPNM also had strong virus capture capacity of 97.67 %. As compared with N95 FFRs, the TFPNM was more resistant to a wider variety of disinfection protocols, and the overall filtration characteristics remained N97 standard., A polarity‐driven air filtration approach is achieved based on the thin‐film coated PAN nanofibrous membranes (TFPNMs), possessing a superior filtration efficiency reaching to N97 grade with outstanding longevity and reusability compared with the N95 FFRs. The TFPNMs can be reused upon various disinfection treatments, giving great potential for personal health care.

Objectives. The present study is aimed at investigating the frequency and associated factors of asymmetrical prominent veins (APV) in patients with acute ischemic stroke (AIS). Methods. Consecutive patients with AIS admitted to the Comprehensive Stroke Center of Shanghai Fourth People’s Hospital between January 2013 and December 2017 were enrolled. MRI including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and susceptibility-weighted imaging (SWI) was performed within 12 hours of symptom onset. The volume of asymmetrical prominent veins (APV) was evaluated using the Signal Processing In nuclear magnetic resonance software (SPIN, Detroit, Michigan, USA). Multivariate analysis was used to assess relationships between APV findings and medical history, clinical variables as well as cardio-metabolic indices. Results. Seventy-six patients met the inclusion criteria. The frequency of APV ≥ 10 mL was 46.05% (35/76). Multivariate analyses showed that proximal artery stenosis or occlusion (≥50%) ( P < 0.001 , adjusted odds ratio OR = 660.0 , 95 % CI = 57.28 -7604.88) and history of atrial fibrillation ( P < 0.001 , adjusted OR = 10.48 , 95 % CI = 1.78 -61.68) were independent factors associated with high APV (≥10 mL). Conclusion. Our findings suggest that the frequency of APV ≥ 10 mL is high in patients with AIS within 12 hours of symptom onset. History of atrial fibrillation and severe proximal artery stenosis or occlusion are strong predictors of high APV as calculated by SPIN on the SWI map.

KIFs have been reported to play a critical role in a variety of tumors, and KIF20B is a protein in KFIs. In this research, KIF20B was highly expressed in the GEO database and our hospital’s data, and high expression of KIF20B suggested poor prognosis. We detect the expression of KIF20B in pancreatic cancer and adjacent normal tissues using immunohistochemistry. Knockdown of KIF20B in pancreatic cancer cell lines, PANC-1 and BxPC-3 cells, inhibited cell proliferation which are detected by colony formation assays, CCK8, and western bolt of Ki-67 and PCNA. Xenograft assay showed a similar result in vivo. KIF20B is a potential therapeutic target in pancreatic cancer.

Introduction. Stage IIB cervical cancer (CC) is an advanced stage CC with poor prognosis. Inflammatory response plays a crucial role in the development of CC, and systemic inflammatory indexes were related to the prognosis in several cancers. The objective of the study was to determine the prognostic value of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and systemic inflammation response index (SIRI) as inflammatory indexes in patients with stage IIB CC. Materials and Methods. A retrospective study was performed in 260 patients with stage IIB CC. PLR, NLR, MLR, BLR, and SIRI were obtained from routine blood tests. Prognosis information of the patients was acquired from regular clinical follow-up. Recurrence and response to therapy were determined through electronic medical records (EMRs). Correlations of the inflammatory indexes with overall survival (OS), progression-free survival (PFS), recurrence, and response to therapy were analyzed using SPSS version 26.0 software. Results. Receiver operating characteristic (ROC) curve analyses suggested that NLR, MLR, and SIRI had better predictive value than PLR as well as BLR in the prognosis and recurrence risk. Both univariate and multivariate survival analyses showed that higher NLR and MLR were significantly associated with shorter OS as well as PFS, whereas SIRI was not an independent predictive factor of PFS. Chi-square test results revealed that increased NLR was significantly correlated with higher recurrence rate ( P = 0.046 ), and increased MLR showed significant correlation with elevated recurrence risk ( P = 0.002 ). Univariate and binary logistic regression analyses for response to therapy indicated that elevated NLR was associated with decreased complete remission (CR) rate ( P = 0.031 ), and the P value lost statistical significance while being adjusted by tumor size ( P = 0.108 ). Conclusions. For patients with stage IIB CC, both NLR and MLR are independent prognostic factors as well as risk factors for recurrence; NLR serves as a potential marker for therapeutic response.

Background: To investigate the intergenerational effects of grandmaternal smoking during pregnancy (GMSDP) on the DNA methylation of grandchildren. Methods: Data from the Isle of Wight birth cohort with information regarding GMSDP and DNA methylation profiling at the birth of grandchildren (n = 161) were used. Differentially methylated CpG sites related to GMSDP were identified using testing–training screening, analysis of variance and multivariate analysis of covariance. The association between identified CpG sites and expression levels of neighboring genes was tested by linear regression. Results: Twenty-three CpG sites were differentially methylated in grandchildren because of GMSDP, and eight of these were associated with expression levels of 13 neighboring genes. Conclusion: GMSDP has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy.

Yes-associated protein 1 (YAP1) is an important signaling pathway activator molecule. Studies have shown that it is involved in the occurrence of malignant tumors. This study identified a microRNA (miR/miRNA) targeting the 3′ untranslated region (3″ utr) of the YAP1 gene and evaluated its biological impact on human cervical cancer cells and related molecular mechanisms. qPCR and western blotting were used to detect the levels of miR-375 and YAP1 in HeLa cells. TargetScan software was used to identify the binding sites of YAP1 and miR-375. The MTT method was used to determine the viability of HeLa cells transfected with miR-375 mimic and YAP1 interference vector, the Transwell chamber experiment was used to detect the invasion of HeLa cells after transfection, the apoptosis of HeLa cells after transfection was detected by flow cytometry, and the western blotting was used to detect the epithelial mesenchymal transition (EMT) of HeLa cells after transfection. The expression of miR-375 in HeLa cells was significantly lower than that of normal control cervical cells, and the expression of YAP1 in HeLa cells was significantly higher than that of normal control cervical cells. TargetScan analysis showed that miR-375 was bound to the 3′ UTR of YAP1. qPCR and western blot analysis showed that transfection of miR-375 mimics inhibited YAP1 expression in HeLa cells. Transfection of miR-375 mimic and YAP1 interference vector inhibited HeLa cell invasion and EMT and promoted HeLa cell apoptosis. These findings indicate that miR-375 inhibits the malignant development of human cervical cancer cells by regulating the expression of YAP1.

There is no specific drug for coronavirus disease 2019 (COVID-19). We aimed to investigate the possible clinical efficacy of moderate-dose vitamin C infusion among inpatients with severe COVID-19. Data of 397 adult patients with severe COVID-19 admitted to a designated clinical center of Wuhan Union Hospital (China) between February 13 and February 29, 2020, were collected. Besides standard therapies, patients were treated with vitamin C (2–4 g/day) or not. The primary outcome was all-cause death. Secondary outcome was clinical improvement of 2 points on a 6-point ordinal scale. About 70 participants were treated with intravenous vitamin C, and 327 did not receive it. No significant association was found between vitamin C use and death on inverse probability treatment weighting (IPTW) analysis (weighted hazard ratio [HR], 2.69; 95% confidence interval [CI], 0.91–7.89). Clinical improvement occurred in 74.3% (52/70) of patients in the vitamin C group and 95.1% (311/327) in the no vitamin C group. No significant difference was observed between the two groups on IPTW analysis (weighted HR, 0.76; 95% CI, 0.55–1.07). Our findings revealed that in patients with severe COVID-19, treatment with moderate dose of intravenous vitamin C had no significant benefit on reducing the risk of death and obtaining clinical improvement.

Background The composition of the population of immune‐related long non‐coding ribonucleic acid (irlncRNA) generates a signature, irrespective of expression level, with potential value in predicting the survival status of patients with invasive breast carcinoma. Methods The current study uses univariate analysis to identify differentially expressed irlncRNA (DEirlncRNA) pairs from RNA‐Seq data from The Cancer Genome Atlas (TCGA). 36 pairs of DEirlncRNA pairs were identified. Using various algorithms to construct a model, we have compared the area under the curve and calculated the 5‐year curve of Akaike information criterion (AIC) values, which allows determination of the threshold indicating the maximum value for differentiation. Through cut‐off point to establish the optimal model for distinguishing high‐risk or low‐risk groups among breast cancer patients. We assigned individual patients with invasive breast cancer to either high risk or low risk groups depending on the cut‐off point, re‐evaluated the tumor immune cell infiltration, the effectiveness of chemotherapy, immunosuppressive biomarkers, and immunotherapy. Results After re‐assessing patients according to the threshold, we demonstrated an effective means of distinguish the severity of the disease, and identified patients with different clinicopathological characteristics, specific tumor immune infiltration states, high sensitivity to chemotherapy,wellpredicted response to immunotherapy and thus a more favorable survival outcome. Conclusions The current study presents novel findings regarding the use of irlncRNA without the need to predict precise expression levels in the prognosis of breast cancer patients and to indicate their suitability for anti‐tumor immunotherapy., The manuscript is an immune‐related lncRNA pairing strategy to construct a risk assessment model. We did not use precise expression levels of the target lncRNAs in the signature.

Background Mortality and complications remain high after acute type A aortic dissection (ATAAD) open surgery and are associated with coagulation dysfunction. Platelets play an important role in the process of coagulation. This study explored the relationship between postoperative platelet counts and 3-year mortality after operation in patients with ATAAD undergoing open aortic repair surgery. Methods Patients with ATAAD who underwent Total Arch Replacement and Frozen Elephant Trunk in Fuwai Hospital from 2011 to 2015 were selected for this study. The perioperative data were collected and sorted through the electronic clinical case system. Multivariate Logistic regression was used to analyze the risk factors for death within three years after surgery. Results A total of 495 patients were included in the analysis. After correction for confounding factors, decreased postoperative platelet count remained an independent factor that was associated with lower mortality (OR = 0.918, 95% CI 0.853–0.988, P = 0.023). Conclusions The study indicated that decreased postoperative platelet count may lead to increased 3-year mortality, in patients with ATAAD who underwent open aortic repair surgery.

MicroRNAs (miRNAs) have been proved to be involved in many biological processes during tumorigenesis and progression, including cell proliferation and cell cycle progression. However, the potential role of miR-26b-5p in tongue squamous cell carcinoma (TSCC) remains unclear. In the present study, we demonstrated that miR-26b-5p was decreased in TSCC tissues in both TCGA-TSCC subset and eight paired samples from TSCC patients, while Proline Rich 11 (PRR11) was obviously increased. Transfection of miR-26b-5p mimics inhibited CALL7 cell proliferation by arresting the cells at the S/G2 transition. Meanwhile, miR-26b-5p inhibitor had the opposite biological functions. The results of luciferase activity and RNA-pulldown assays indicated that miR-26b-5p directly targeted the PRR11 3ʹ -untranslated region in CAL27 cells. Furthermore, the effects of miR-26b-5p on cell cycle regulation were reversed after treatment with siRNA against PRR11. In summary, our findings indicate that miR-26b-5p induce cell cycle arrest in TSCC by targeting PRR11. Hence, targeting miR-26b-5p could be a promising therapeutic strategy for the treatment of TSCC.

Introduction Sublobar resection has been widely accepted for treating pure ground-glass opacities (GGOs). As GGOs have good prognosis, preserving postoperative pulmonary function is the major concern in surgery. No studies have yet compared the success rates of pulmonary function reservation between segmentectomy and wedge resection. Method The three-dimensional rebuild of computed tomography (CT) images was performed, the segmentectomy and wedge resection of the GGO in the target segment were simulated, and the area of cut surface was measured, which was important data for successful postoperative pulmonary recruitment maneuvers. Result With equal volumes of tissue removed, segmentectomy and wedge resection showed similar surface area loss for RS4 and RS5, followed by LS7 + 8, LS6 and LS1 + 2 segments. Compared with other segments, wedge resection performed in RS10, LS3, LS10, RS9 and RS7 may lead to a loss of lot more surface area than segmentectomy. Conclusion Wedge resection is suggested for segments RS4, RS5, LS1 + 2 and LS7 + 8, whereas segmentectomy is advised for segments RS1, LS4 + 5 and RS2. Meanwhile, deep wedge resection should be avoided for segments RS8, RS7, RS10, LS3, LS10. RS9 and LS9, in order to preserve a larger lung surface area.

Background A key issue for implementation of CRISPR-Cas9 genome editing for plant trait improvement and gene function analysis is to efficiently deliver the components, including guide RNAs (gRNAs) and Cas9, into plants. Plant virus-based gRNA delivery strategy has proven to be an important tool for genome editing. However, its application in soybean which is an important crop has not been reported yet. ALSV (apple latent spherical virus) is highly infectious virus and could be explored for delivering elements for genome editing. Results To develop a ALSV-based gRNA delivery system, the Cas9-based Csy4-processed ALSV Carry (CCAC) system was developed. In this system, we engineered the soybean-infecting ALSV to carry and deliver gRNA(s). The endoribonuclease Csy4 effectively releases gRNAs that function efficiently in Cas9-mediated genome editing. Genome editing of endogenous phytoene desaturase (PDS) loci and exogenous 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) sequence in Nicotiana. benthamiana (N. benthamiana) through CCAC was confirmed using Sanger sequencing. Furthermore, CCAC-induced mutagenesis in two soybean endogenous GW2 paralogs was detected. Conclusions With the aid of the CCAC system, the target-specific gRNA(s) can be easily manipulated and efficiently delivered into soybean plant cells by viral infection. This is the first virus-based gRNA delivery system for soybean for genome editing and can be used for gene function study and trait improvement.

Background Circular RNAs have been identified as crucial players in the initiation and progression of cancers, including colorectal cancer (CRC). The Has_circ_0000467 (circ_0000467) expression has been found to be upregulated in CRC, but its function and mechanism remain unclear. Methods The expression levels of circ_0000467, microRNA-4766-5p (miR-4766-5p), and Krueppel-like factor 12 (KLF12) were examined using reverse transcription-quantitative polymerase chain reaction. Cell proliferation was analyzed by cell counting kit-8 assay and colony formation assay. The apoptosis was measured by flow cytometry. Transwell migration and invasion assays were applied to evaluate cell metastatic ability. Angiogenesis was detected using tube formation assay. All protein expressions were quantified by western blot assay. Dual-luciferase reporter assay was used to analyze intergenic binding. Xenograft models were constructed for the experiment of circ_0000467 in vivo. Results The expression of circ_0000467 was upregulated in CRC tissues and cells. Knockdown of circ_0000467 repressed cell proliferation, metastasis, and angiogenesis, but it induced apoptosis in CRC cells. circ_0000467 targeted miR-4766-5p and inhibited the expression of miR-4766-5p. Silencing of circ_0000467 inhibited CRC progression by upregulating miR-4766-5p. miR-4766-5p suppressed the expression of target gene KLF12 and KLF12 overexpression reversed the effects of miR-4766-5p on CRC cell behaviors. circ_0000467 positively regulated the expression of KLF12 by targeting miR-4766-5p. circ_0000467 downregulation in vivo reduced CRC tumorigenesis by regulating miR-4766-5p and KLF12. Conclusion circ_0000467 acted as an oncogene in CRC through regulating KLF12 expression by sponging miR-4766-5p. Therefore, circ_0000467 can be used as an effective target in CRC diagnosis and therapy.

Aim The study aimed to investigate the current status of reproductive concerns and explore the associated factors among young female chronic kidney disease (CKD) patients. Design A multi‐center cross‐sectional study was designed. Methods The study was conducted in six representative tertiary hospitals across southwest China. A total of 295 female Chronic kidney disease patients between 18–45 years of age completed a 20 min, web‐based survey, which included demographics and disease‐related information questionnaire, Reproductive Concerns Scale, Generalized Anxiety Disorder 7 (GAD‐7) instrument and Patient Health Questionnaire 9 (PHQ‐9) instrument. Result The survey total collected 270 valid questionnaires. The mean reproductive concern score was 54.39 ± 10.90 (out of a maximum of 90), with the mean scores for sub‐scales ranging from 7.80 ± 1.69 to 10.44 ± 1.85. Multiple regression analysis showed that those with higher reproductive concerns were more likely to have pregnancy intentions, to be in Chronic kidney disease stages 1–3, and to have a higher GAD‐7 score. This study offered further evidence of the need for improved education and emotional support surrounding reproductive concerns among young Chinese women with Chronic kidney disease.

BACKGROUND: Postoperative acute kidney injury (AKI) is a major complication associated with increased morbidity and mortality after surgery for acute type A aortic dissection (AAAD). To the best of our knowledge, risk prediction models for AKI following AAAD surgery have not been reported. The goal of the present study was to develop a prediction model to predict severe AKI after AAAD surgery. METHODS: A total of 485 patients who underwent AAAD surgery were enrolled and randomly divided into the training cohort (70%) and the validation cohort (30%). Severe AKI was defined as AKI stage III following the Kidney Disease: Improving Global Outcomes criteria. Preoperative variables, intraoperative variables and postoperative data were collected for analysis. Multivariable logistic regression analysis was performed to select predictors and develop a nomogram in the study cohort. The final prediction model was validated using the bootstrapping techniques and in the validation cohort. RESULTS: The incidence of severe AKI was 23.0% (n = 78), and 14.7% (n = 50) of patients needed renal replacement treatment. The hospital mortality rate was 8.3% (n = 28), while for AKI patients, the mortality rate was 13.1%, which increased to 20.5% for severe AKI patients. Univariate and multivariate analyses showed that age, cardiopulmonary bypass time, serum creatinine, and D-dimer were key predictors for severe AKI following AAAD surgery. The logistic regression model incorporated these predictors to develop a nomogram for predicting severe AKI after AAAD surgery. The nomogram showed optimal discrimination ability, with an area under the curve of 0.716 in the training cohort and 0.739 in the validation cohort. Calibration curve analysis demonstrated good correlations in both the training cohort and the validation cohort. CONCLUSIONS: We developed a prognostic model including age, cardiopulmonary bypass time, serum creatinine, and D-dimer to predict severe AKI after AAAD surgery. The prognostic model demonstrated an effective predictive capability for severe AKI, which may help improve risk stratification for poor in-hospital outcomes after AAAD surgery.

Detection of dysphonia is useful for monitoring the progression of phonatory impairment for patients with Parkinson’s disease (PD), and also helps assess the disease severity. This paper describes the statistical pattern analysis methods to study different vocal measurements of sustained phonations. The feature dimension reduction procedure was implemented by using the sequential forward selection (SFS) and kernel principal component analysis (KPCA) methods. Four selected vocal measures were projected by the KPCA onto the bivariate feature space, in which the class-conditional feature densities can be approximated with the nonparametric kernel density estimation technique. In the vocal pattern classification experiments, Fisher’s linear discriminant analysis (FLDA) was applied to perform the linear classification of voice records for healthy control subjects and PD patients, and the maximum a posteriori (MAP) decision rule and support vector machine (SVM) with radial basis function kernels were employed for the nonlinear classification tasks. Based on the KPCA-mapped feature densities, the MAP classifier successfully distinguished 91.8% voice records, with a sensitivity rate of 0.986, a specificity rate of 0.708, and an area value of 0.94 under the receiver operating characteristic (ROC) curve. The diagnostic performance provided by the MAP classifier was superior to those of the FLDA and SVM classifiers. In addition, the classification results indicated that gender is insensitive to dysphonia detection, and the sustained phonations of PD patients with minimal functional disability are more difficult to be correctly identified.

As one of the ligands of aryl hydrocarbon receptor (AhR), baicalein, isolated from Scutellaria baicalensis Georgi, has been proved to exert potential therapeutic effects on ulcerative colitis (UC), but its therapeutic mechanism remains obscure. Authentically, ulcerative colitis can be alleviated by regulating the differentiation of naïve CD4+ T cells via AhR activation. So, our study planned to prove the hypothesis that baicalein protected mice against UC by regulating the balance of Th17/Treg cells via AhR activation. Immunofluorescence and western blot results showed that baicalein could promote AhR activation and induce it to transfer to the nucleus. We further determined the effect of baicalein on naïve CD4+ T cell differentiation in vitro by magnetic cell separation and drug intervention. The results showed that baicalein could promote Treg cell differentiation by activating AhR. In vivo study, UC mice were established by free drinking of dextran sulfate sodium (DSS) for 7 days and then were orally administrated by baicalein (10, 20, and 40 mg/kg), TCDD (AhR agonist), and CH223191 (antagonist). The results demonstrated that baicalein improved the symptoms of UC mice, regulated the balance of Th17/Treg cells, and restored the balance of proinflammatory cytokines such as IL-17, IL-6, and TNF-α; anti-inflammatory cytokines such as IL-10 and TGF-β; and epithelial protective cytokine IL-22 in UC mice, and these effects were related to AhR. Taken together, our research found that baicalein might be a potential drug for UC via regulating Treg cell differentiation and maintaining immune homeostasis and attempted to shed a light on the pivotal role of AhR in these effects.

This study is aimed at exploring the expression pattern and methylation level of G0S2 in the peripheral blood mononuclear cells (PBMCs) of myasthenia gravis (MG) patients with positive acetylcholine receptor (AChR) autoantibodies and revealing the relationship between the G0S2 methylation pattern and MG. The relationship between the NFAT family members and G0S2 was explored to reveal the regulatory mechanism of G0S2 in the pathogenesis and treatment of AChR MG. Moreover, we attempted to demonstrate the potential therapeutic mechanism of tacrolimus in AChR MG. The relative G0S2 expression level in the PBMCs of healthy people was compared with that in the PBMCs of AChR MG patients with quantitative real-time PCR (qRT-PCR). The methylation frequency of the G0S2 promoter was detected by bisulfite sequencing PCR (BSP) and pyrosequencing. A dual-luciferase reporter system was used to reveal the relationship between the G0S2 promoter and nuclear factor of activated T cells 5 (NFAT5). The qRT-PCR results showed that G0S2 expression was significantly upregulated in the B cells and CD8+ T cells of AChR MG patients but not in the CD4+ T cells, and these expression differences were significantly associated with a decrease in G0S2 methylation. NFAT5, which was speculated to bind to island 1 (p1) in the G0S2 promoter, may regulate the lymphocyte balance by regulating G0S2 gene expression but failed to affect the methylation of the G0S2 promoter. Tacrolimus therapy-induced methylation and overexpression of NFAT5 could significantly reduce the expression of G0S2 in AChR MG patients. The G0S2 gene was remarkably upregulated in the PBMCs of MG patients. NFAT5 may affect transcription initiation and downregulate G0S2 expression through p1 in the promoter, thus controlling G0S2 gene expression and regulating the lymphocyte balance. Therefore, G0S2 could be an immune regulatory factor in both AChR MG occurrence and treatment with tacrolimus.

Clostridioides difficile, which causes life-threatening diarrheal disease, presents an urgent threat to health care systems. In this study, we present a retrospective genomic and epidemiological analysis of C. difficile in a large teaching hospital. First, we collected 894 nonduplicate fecal samples from patients during a whole year to elucidate the C. difficile molecular epidemiology. We then presented a detailed description of the population structure of C. difficile based on 270 isolates separated between 2015 and 2020 and clarified the genetic and phenotypic features by MIC and whole-genome sequencing. We observed a high carriage rate (19.4%, 173/894) of C. difficile among patients in this hospital. The population structure of C. difficile was diverse with a total of 36 distinct STs assigned. In total, 64.8% (175/270) of the isolates were toxigenic, including four CDT-positive (C. difficile transferase) isolates, and 50.4% (135/268) of the isolates were multidrug-resistant. Statistically, the rates of resistance to erythromycin, moxifloxacin, and rifaximin were higher for nontoxigenic isolates. Although no vancomycin-resistant isolates were detected, the MIC for vancomycin was higher for toxigenic isolates (P < 0.01). The in-hospital transmission was observed, with 43.8% (110/251) of isolates being genetically linked to a prior case. However, no strong correlation was detected between the genetic linkage and epidemiological linkage. Asymptomatic colonized patients play the same role in nosocomial transmission as infected patients, raising the issue of routine screening of C. difficile on admission. This work provides an in-depth description of C. difficile in a hospital setting and paves the way for better surveillance and effective prevention of related diseases in China. IMPORTANCE Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries. However, research on CDI remains limited in China. Here, we characterized the comprehensive spectrum of C. difficile by whole-genome sequencing (WGS) in a Chinese hospital, showing a high detection rate among patients, diverse genome characteristics, a high level of antibiotic resistance, and an unknown nosocomial transmission risk of C. difficile. During the study period, two C. difficile transferase (CDT)-positive isolates belonging to a new multilocus sequence type (ST820) were detected, which have caused serious clinical symptoms. This work describes C. difficile integrally and provides new insight into C. difficile surveillance based on WGS in China.

Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage and/or chondrocyte destruction, and although it has long been considered as a primary disease, the importance of meniscus endothelial cell modulation in the subchondral microenvironment has recently drawn attention. Previous studies have shown that apelin could potentially inhibit cellular apoptosis; however, it remains unclear whether apelin could play a protective role in protecting the endothelium in the OA meniscus. In this study, with the advantages of single-cell RNA sequencing (scRNA-seq) data, in combination with flow cytometry, we identified two endothelial subclusters in the meniscus, featured by high expression of Homeobox A13 (HOXA13) and Ras Protein-Specific Guanine Nucleotide Releasing Factor 2 (RASGRF2), respectively. Compared with control patients, both subclusters decreased in absolute cell numbers and exhibited downregulated APJ endogenous ligand (APLN, coding for apelin) and upregulated apelin receptor (APLNR, coding apelin receptor). Furthermore, we confirmed that in OA, decreased endothelial cell numbers, including both subclusters, were related to intrinsic apoptosis factors: one more relevant to caspase 3 (CASP3) and the other to BH3-Interacting Domain Death agonist (BID). In vitro culturing of meniscal endothelial cells purified from patients proved that apelin could significantly inhibit apoptosis by downregulating these two factors in endothelial cell subclusters, suggesting that apelin could potentially serve as a therapeutic target for patients with OA.

Background Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. Methods In this study, we compared the single‐cell transcriptomes of immune cells from 12 species. Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. Results Our data revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular crosstalks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM‐CD44 was highly conserved among the immune cells. Conclusions This study is the first to provide a comprehensive analysis of the cross‐species single‐cell transcriptome atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders., Our study compared the single‐cell transcriptomes of immune cells from 12 species. The results revealed the heterogeneity and compositions of circulating immune cells. We explored the conserved and divergent cellular crosstalks and genetic regulatory networks among vertebrate immune cells.

Background. Docking protein 5 (DOK5) is a member of the docking protein group of membrane proteins and is an adapter protein involved in signal transduction. Nevertheless, the role of DOK5 expression in the prognosis of gastric cancer (GC) remains unclear. Methods. In this study, clinical prognostic parameters and survival data related to DOK5, in patients with GC, were analyzed using bioinformatics analysis comprising Oncomine and TIMER, UALCAN database, Kaplan-Meier plotter, GEPIA, GSEA, DAVID, and cBioPortal websites. Results. In our study, GC contained various DOK5 expressions, which forecasted poor survival outcomes. Moreover, our research showed that high DOK5 could predict high-level infiltration of several GC immune cells, as evidenced by M1, TAM, M2, B cell, and T cell failure. Hence, DOK5 might become a new gastric cancer biomarker and therapeutic target. In the following analysis, in order to explore the prognostic value of DOK5 in GC, more clinical trials are needed to validate our results. Conclusions. Through multiple database verifications, DOK5 was found to be part of the pathogenic genes for GC. Thus, it can change the formation and progression of tumors by acting on human immunity.

Background. This study is aimed at evaluating the diagnostic efficacy of ultrasound-based risk stratification for thyroid nodules in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the American Thyroid Association (ATA) risk stratification systems. Methods. 286 patients with thyroid cancer were included in the tumor group, with 259 nontumor cases included in the nontumor group. The ACR TI-RADS and ATA risk stratification systems assessed all thyroid nodules for malignant risks. The diagnostic effect of ACR and ATA risk stratification system for thyroid nodules was evaluated by receiver operating characteristic (ROC) analysis using postoperative pathological diagnosis as the gold standard. Results. The distributions and mean scores of ACR and ATA rating risk stratification were significantly different between the tumor and nontumor groups. The lesion diameter > 1 cm subgroup had higher malignant ultrasound feature rates detected and ACR and ATA scores. A significant difference was not found in the ACR and ATA scores between patients with or without Hashimoto’s disease. The area under the receiver operating curve (AUC) for the ACR TI-RADS and the ATA systems was 0.891 and 0.896, respectively. The ACR had better specificity (0.90) while the ATA system had higher sensitivity (0.92), with both scenarios having almost the same overall diagnostic accuracy (0.84). Conclusion. Both the ACR TI-RADS and the ATA risk stratification systems provide a clinically feasible thyroid malignant risk classification, with high thyroid nodule malignant risk diagnostic efficacy.

Cutting propagation is widely used in establishing poplar plantations, and this approach requires efficient adventitious root (AR) forming capacities. Although poplar species are considered to form roots easily, interspecific variations in AR formation are still observed. To better understand the gene regulatory network underlying the conserved modified pathways that are essential for AR formation in poplar species, comparative transcriptomic approaches were applied to identify the conserved common genes that were differentially expressed during the AR formation processes in two poplar species (Populus × euramericana and P. simonii) in woody plant medium (WPM). A total of 2146 genes were identified as conserved genes that shared similar gene expression profiles in at least one comparison. These conserved genes were enriched in diverse hormone signaling pathways, as well as the mitogen-associated protein kinase (MAPK) signaling pathway, suggesting an important role for signaling transduction in coordinating external stimuli and endogenous physiological status during AR regulation in poplar. Furthermore, the co-expression network analysis of conserved genes allowed identification of several co-expressed modules (CM) that are co-expressed with distinct biological functions, for instance, CM1 was enriched in defense response and hormone signaling, CM2 and CM3 were overrepresented in defense response-related pathways and for cell cycle, respectively. These results suggest that the AR formation processes in poplar were finely tuned at the transcriptomic level by integrating multiple biological processes essential for AR formation. Our results suggest conserved machinery for AR formation in poplar and generated informative gene co-expression networks that describe the basis of AR formation in these species. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01054-7.

Background. A lack of knowledge and inadequate practices of health care providers (HCPs) are the main obstacles to effective cancer pain management (CPM). The main objective of the study was to evaluate the CPM knowledge, CPM practice, and attitudes towards pharmacists’ participation and advanced methods in CPM of physicians, nurses, and pharmacists in China. Methods. An open online survey was adopted using social media software (WeChat) as the platform to conduct a nationwide survey of HCPs involved in CPM in public medical institutions at all levels in China from March to June 2019. Results. A total of 1279 physicians, 2267 nurses, and 1466 pharmacists participated in the survey. Among the three types of professionals, nurses had the highest level of practical ability (61.63 ± 28.99) and best attitudes towards pharmacists’ participation and advanced methods in CPM (72.05 ± 33.71) and physicians had the best mastery of CPM-related knowledge (69.60 ± 28.45), while pharmacists performed the worst in these three aspects (50.04 ± 26.69, 61.49 ± 28.95, and 62.07 ± 36.46, respectively). Only 19.69% of the hospitals had a pharmacist to tumor patient ratio ≥1 : 50. Hierarchical analysis showed that passing a good pain management (GPM) ward program and participating in advanced training had positive impacts on the scores of all three parts in the three professions (ptrend

Gut microbiota (GM) dysbiosis and bile acid (BA) metabolism disorder play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Probiotics had a beneficial effect on NAFLD, but further study is needed to explore probiotics as a potential therapeutic agent to NAFLD. The aim of this study was to investigate the regulatory effect of probiotics on gut microbiota in NAFLD rats and to explore the possible mechanism of probiotics regulating the bile acid receptor farnesoid X receptor/growth factor 15 (FXR/FGF15) signaling pathway in rats. We established a rat model of NAFLD fed with a high-fat diet (HFD) for 14 weeks, which was given different interventions (312 mg/kg/day probiotics or 10 mg/kg/day atorvastatin) from the 7th week. Serum lipids and total bile acids (TBA) were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE staining. The expression levels of FXR, FGF15 mRNA, and protein in rat liver were detected. 16S rDNA was used to detect the changes of gut microbiota in rats. Compared with the HFD group, probiotics and atorvastatin significantly reduced serum lipids and TBA levels. And probiotics increased dramatically the expression of FXR, FGF15 mRNA, and protein in the liver. But there were no significant changes in the atorvastatin group. Probiotics and atorvastatin can upregulate the diversity of gut microbiota and downregulate the abundance of pathogenic bacteria in NAFLD model rats. In summary, probiotics alleviated NAFLD in HFD rats via the gut microbiota/FXR/FGF15 signaling pathway.