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The reconstruction of neural function and recovery of chronic damage following traumatic brain injury (TBI) remain significant clinical challenges. Exosomes derived from neural stem cells (NSCs) offer various benefits in TBI treatment. Numerous studies confirmed that appropriate preconditioning methods enhanced the targeted efficacy of exosome therapy. Interferon-gamma (IFN-γ) possesses immunomodulatory capabilities and is widely involved in neurological disorders. In this study, IFN-γ was employed for preconditioning NSCs to enhance the efficacy of exosome (IFN-Exo, IE) for TBI. miRNA sequencing revealed the potential of IFN-Exo in promoting neural differentiation and modulating inflammatory responses. Through low-temperature 3D printing, IFN-Exo was combined with collagen/chitosan (3D-CC-IE) to preserve the biological activity of the exosome. The delivery of exosomes via biomaterial scaffolds benefited the retention and therapeutic potential of exosomes, ensuring that they could exert long-term effects at the injury site. The 3D-CC-IE scaffold exhibited excellent biocompatibility and mechanical properties. Subsequently, 3D-CC-IE scaffold significantly improved impaired motor and cognitive functions after TBI in rat. Histological results showed that 3D-CC-IE scaffold markedly facilitated the reconstruction of damaged neural tissue and promoted endogenous neurogenesis. Further mechanistic validation suggested that IFN-Exo alleviated neuroinflammation by modulating the MAPK/mTOR signaling pathway. In summary, the results of this study indicated that 3D-CC-IE scaffold engaged in long-term pathophysiological processes, fostering neural function recovery after TBI, offering a promising regenerative therapy avenue.

MicroRNAs (miRNAs) are small noncoding RNAs of 18–25 bases. miRNAs are also important new biomarkers that can be used for disease diagnosis in the future. Studies have shown that miR-124 levels are significantly elevated during acute myocardial infarction (AMI) and play a key role in the cardiovascular system. A variety of methods have been established to detect myocardial infarction-related miRNAs. However, most require complex miRNA extraction and isolation, and these methods are virtually undetectable when RNA levels are low in the sample. It may lead to biased results. Thus, it is necessary to develop a technique that can detect miRNA without extracting it, which means that intracellular detection is of great significance. Here, we improved the traditional silicon spheres and obtained a biosensor that could effectively capture and detect specific noncoding nucleic acids through the layer-by-layer assembly method. The sensor is protected by hyaluronic acid so it can successfully escape the lysosome into the cell and achieve detection. With the help of a full-featured microplate reader, we determined that the detection limit of the biosensor could reach 1 fM, meeting the needs of intracellular detection. At the same time, we prepared an oxidative stress cardiomyocyte infarction model and successfully captured the overexpressed miR-124 in the infarcted cells to achieve in situ detection. This study could provide a new potential tool to develop miRNAs for sensitive diagnosis in AMI, and the proposed strategy implies its potential for biomedical research.

ABSTRACT The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) system widely occurs in prokaryotic organisms to recognize and destruct genetic invaders. Systematic collation and characterization of endogenous CRISPR-Cas systems are conducive to our understanding and potential utilization of this natural genetic machinery. In this study, we screened 39 complete and 692 incomplete genomes of myxobacteria using a combined strategy to dispose of the abridged genome information and revealed at least 19 CRISPR-Cas subtypes, which were distributed with a taxonomic difference and often lost stochastically in intraspecies strains. The cas genes in each subtype were evolutionarily clustered but deeply separated, while most of the CRISPRs were divided into four types based on the motif characteristics of repeat sequences. The spacers recorded in myxobacterial CRISPRs were in high G+C content, matching lots of phages, tiny amounts of plasmids, and, surprisingly, massive organismic genomes. We experimentally demonstrated the immune and self-target immune activities of three endogenous systems in Myxococcus xanthus DK1622 against artificial genetic invaders and revealed the microhomology-mediated end-joining mechanism for the immunity-induced DNA repair but not homology-directed repair. The panoramic view and immune activities imply potential omnipotent immune functions and applications of the endogenous CRISPR-Cas machinery.IMPORTANCEServing as an adaptive immune system, clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) empower prokaryotes to fend off the intrusion of external genetic materials. Myxobacteria are a collective of swarming Gram-stain-negative predatory bacteria distinguished by intricate multicellular social behavior. An in-depth analysis of their intrinsic CRISPR-Cas systems is beneficial for our understanding of the survival strategies employed by host cells within their environmental niches. Moreover, the experimental findings presented in this study not only suggest the robust immune functions of CRISPR-Cas in myxobacteria but also their potential applications.

The demand for crayfish surimi products has grown recently due to its high protein content. This study examined the effects of varying κ-carrageenan (CAR) and crayfish surimi (CSM) concentrations on the gelling properties of CAR-CSM composite gel and its intrinsic formation process. Our findings demonstrated that with the increasing concentration of carrageenan, the quality of CAR-CSM exhibited rising trend followed by subsequently fall. Based on the textural qualities, the highest quality CAR-CSM was achieved at 0.3% carrageenan addition. With the exception of chewiness, and the cooking loss of the gel system was 1.62%, whiteness was 82.35%, and the percentage of β-sheets increased to 57.18%. Further increase in CAR (0.4–0.5%) addition resulted in internal build-up of LCAR-CSM, conversion of intermolecular forces into disulfide bonds and gel breakage. This study exudes timely recommendations for extending the CAR application for the continuous development of crayfish surimi and its derivatives and its overall economic worth.

BackgroundMania has caused incalculable economic losses for patients, their families, and even society, but there is currently no effective treatment plan for this disease without side effects.MethodsUsing bioinformatics and Mendelian randomization methods, potential drug target genes and key substances associated with mania were explored at the mRNA level. We used the chip expression profile from the GEO database to screen differential genes and used the eQTL and mania GWAS data from the IEU database for two-sample Mendelian randomization (MR) to determine core genes by colocalization. Next, we utilized bioinformatics analysis to identify key substances involved in the mechanism of action and determined related gene targets as drug targets.ResultsAfter differential expression analysis and MR, a causal relationship between the expression of 46 genes and mania was found. Colocalization analysis yielded six core genes. Five key substances were identified via enrichment analysis, immune-related analysis, and single-gene GSVA analysis of the core genes. MR revealed phenylalanine to be the only key substance that has a unidirectional causal relationship with mania. In the end, SBNO2, PBX2, RAMP3, and QPCT, which are significantly associated with the phenylalanine metabolism pathway, were identified as drug target genes.ConclusionSBNO2, PBX2, RAMP3, and QPCT could serve as potential target genes for mania treatment and deserve further basic and clinical research. Medicinal target genes regulate the phenylalanine metabolism pathway to achieve the treatment of mania. Phenylalanine is an important intermediate substance in the treatment of mania that is regulated by drug target genes.

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin lymphoma associated with HIV infection and immunodeficiency. However, PBL can also be seen immunocompetent individuals in recent studies. PBL was characterized by distinct clinical and pathological features, such as plasmablastic morphology and universal expression of plasma cell markers. The clinicopathologic features were different between HIV-negative and HIV-positive patients. Gene expression analysis identified the unique molecular feature in PBL, including frequent c-MYC rearrangement and downregulation of BCR signaling pathway. Despite the recent advances in the treatment of PBL, the prognosis of PBL patients remains dismal. The objectives of this review are to summarize the current knowledge on the epidemiology, molecular profiles, clinical and pathological features, differential diagnosis, treatment strategies, prognostic factors, and potential novel therapeutic approaches in PBL patients.

Abstract Background SRPK1 is a splicing‐related protein that plays an important role in the development and function of the human brain. This article presents evidence that SRPK1 has distinct spatiotemporal expression patterns enriched in processes related to neurodevelopmental disorders across development. Material and method We used the BrainSpan growing mammalian brain transcriptome to evaluate the distribution of SRPK1 throughout the entire brain. RNA‐sequencing data were gathered from 524 tissue samples recovered from 41 postmortem brains of physiologically normal individuals spanning early developing fetus (8 postconception weeks, PCW) to later life (40 years of age). Using the Allen Human Brain Atlas (AHBA) dataset, we analyzed the spatial gene expression of 15 adult human brains. Using Toppgene, we identified genes that exhibit significant coexpression with SRPK1. Results We found evidence that analyzing the spatiotemporal gene expression profile and identifying coexpressed genes reveals that SRPK1 expression is involved in various neurodevelopmental and somatic events throughout the lifetime. Conclusion Our findings highlight the importance of detailed maps of gene expression in the human brain for improved human‐to‐human translation and illustrate differences in SRPK1 expression across anatomical areas and developmental stages in healthy human brain tissue.

Abstract Background Ischemic stroke is a disease in which cerebral blood flow is blocked due to various reasons, leading to ischemia, hypoxia, softening, and even necrosis of brain tissues. The level of cortisol is related to the occurrence and progression of ischemic stroke. However, the mechanism governing their interrelationship is still unclear. The main objective of this study was to identify and understand the molecular mechanism between cortisol and IS. Methods The common cortisol‐related biological processes were screened by mutual verification of two data sets and the cortisol‐related hub biomarkers were identified. Modular analysis of protein interaction networks was performed, and the differential pathway analysis of individual genes was conducted by GSVA and GSEA. Drug and transcription factor regulatory networks of hub genes were excavated, and the diagnostic potential of hub genes was analyzed followed by the construction of a diagnostic model. Results By screening the two data sets by GSVA, three biological processes with common differences were obtained. After variation analysis, four cortisol‐related hub biomarkers (CYP1B1, CDKN2B, MEN1, and USP8) were selected. Through the modular analysis of the protein‐protein interaction network and double verification of GSVA and GSEA, a series of potential molecular mechanisms of hub genes were discovered followed by a series of drug regulatory networks and transcription factor regulatory networks. The hub biomarkers were found to have a high diagnostic value by ROC; thus, a diagnostic model with high diagnostic efficiency was constructed. The diagnostic value was mutually confirmed in the two data sets. Conclusion Four cortisol‐related hub biomarkers are identified in this study, which provides new ideas for the key changes of cortisol during the occurrence of IS.

The increasing severity of ground subsidence, ground fissure and other disasters caused by the excessive exploitation of deep underground resources has highlighted the pressing need for effective management. A significant contributing factor to the challenges faced is the inadequacy of existing soil mechanics experimental instruments in providing effective indicators, creating a bottleneck in comprehensively understanding the mechanisms of land subsidence. It is urgent to develop a multi-field and multi-functional soil mechanics experimental system to address this issue. Based soil mechanics theories, the existing manufacturing capabilities of triaxial apparatus and the practical demands of the test system, a set of multi-field coupled high-pressure triaxial system is developed tailored for testing deep soils (at depths of approximately 3 000 m) and soft rock. This system incorporates specialized design elements such as high-pressure chamber and horizontal deformation testing devices. In addition to the conventional triaxial tester functions, its distinctive feature encompass a horizontal deformation tracking measuring device, a water release testing device and temperature control device for the sample. This ensemble facilitates testing of horizontal and vertical deformation water release and other parameters of samples under a specified stress conditions, at constant or varying temperature ranging from −40°C–90°C. The accuracy of the tested parameters meets the requirements of relevant current specifications. The test system not only provides scientifically robust data for revealing the deformation and failure mechanism of soil subjected to extreme temperature, but also offers critical data support for major engineering projects, deep exploration and mitigation efforts related to soil deformation-induced disaster.

Abstract Background Information available to date regarding the pregnancy outcomes of intrauterine insemination (IUI) without ovarian stimulation (OS) in infertile patients with unilateral tubal occlusion remains scarce. The objectives of this study were to investigate for couples affected by unilateral tubal occlusion (diagnosed via hysterosalpingography (HSG)/transvaginal real-time three-dimensional hysterosalpingo-contrast sonography (TVS RT-3D-HyCoSy)) and male infertility: (1) whether significant differences exist in pregnancy outcomes between IUI with or without OS cycles, and (2) whether the pregnancy outcomes of IUI without OS in women with unilateral tubal occlusion were similar to those of women with bilateral patent tubes. Methods 258 couples affected by male infertility completed 399 IUI cycles. The cycles were divided into three groups: group A, IUI without OS in women with unilateral tubal occlusion; group B, IUI with OS in women with unilateral tubal occlusion; and group C, IUI without OS in women with bilateral patent tubes. The main outcome measures, including clinical pregnancy rate (CPR), live birth rate (LBR), and first trimester miscarriage rate, were compared between either groups A and B or groups A and C. Results Although the number of dominant follicles > 16 mm were significantly higher in group B than that in group A (group B vs. group A: 1.6 ± 0.6 vs. 1.0 ± 0.2, P

The therapeutic benefits of available FLT3 inhibitors for AML are limited by drug resistance, which is related to mutations, as well toxicity caused by off-target effects. In this study, we introduce a new small molecule FLT3 inhibitor called danatinib, which was designed to overcome the limitations of currently approved agents. Danatinib demonstrated greater potency and selectivity, resulting in cytotoxic activity specific to FLT3-ITD and/or FLT3-TKD mutated models. It also showed a superior kinome inhibition profile compared to several currently approved FLT3 inhibitors. In diverse FLT3-TKD models, danatinib exhibited substantially improved activity at clinically relevant doses, outperforming approved FLT3 inhibitors. In vivo safety evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models proved danatinib to have an acceptable safety profile. Danatinib holds promise as a new and improved FLT3 inhibitor for the treatment of AML, offering long-lasting remissions and improved overall survival rates.

Abstract Objective Gestational diabetes mellitus (GDM) is a serious complication in pregnancy. Despite controlling the plasma glucose levels with dietary intervention (GDM-D) or insulin therapy (GDM-I), children born of diabetic mothers suffer more long-term complications from childhood to early adulthood. Placental circulation and nutrient exchange play a vital role in fetal development. Additionally, placental endothelial function is an indicator of vascular health, and plays an important role in maintaining placental circulation for nutrient exchange. This study was conducted to assess changes in fetal endothelial dysfunction in GDM under different interventions during pregnancy. Methods The primary human umbilical vein endothelial cells (HUVECs) were obtained from normal pregnant women (n = 11), GDM-D (n = 14), and GDM-I (n = 12) patients. LC-MS/MS was used to identify differentially expressed proteins in primary HUVECs among the three groups, after which Bioinformatics analysis was performed. Glucose uptake, ATP level, apoptosis, and differentially expressed proteins were assessed to investigate changes in energy metabolism. Results A total of 8174 quantifiable proteins were detected, and 142 differentially expressed proteins were identified after comparing patients with GDM-D/GDM-I and healthy controls. Of the 142, 64 proteins were upregulated while 77 were downregulated. Bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes and signaling pathways related to cellular processes, biological regulation, and metabolic processes. According to the results from KEGG analysis, there were changes in the PI3K/AKT signaling pathway after comparing the three groups. In addition, there was a decrease in glucose uptake in the GDM-I (P

Abstract Objective The aim of this study was to investigate the clinical efficacy of exercise intervention in the treatment of patients with Alzheimer's disease (AD) by meta‐analysis. Methods From January 2000 to January 2022, PubMed, Web of Science, Embase, CNKI, and WanFang databases were searched for all studies on the clinical efficacy of exercise intervention in the treatment of AD patients. Stata 17.0 statistical software was used for meta‐analysis. Results Specifically, data of 983 patients were subjected to meta‐analysis, including 463 patients in the control group (conventional drug therapy) and 520 patients in the treatment group (physical exercise on the basis of conventional therapy). The results of meta‐analysis showed that Mini‐Mental State Examination (MMSE) score and Activities of Daily Living Scale (ADL) score in the treatment group were significantly higher than those in the control group. Further subgroup analysis of exercise intervention >16 weeks found that MMSE and ADL scores in the treatment group were significantly higher than those in the control group. Subgroup analysis of exercise intervention ≤16 weeks demonstrated that MMSE and ADL in the treatment group were higher than those in the control group. In addition, the treatment group had a significant lower Neuropsychiatric Inventory (NPI) score compared with the control group (SMD = –0.76, 95% CI (–1.37, –0.16), p = .013); subgroup analysis showed that the NPI score in the treatment group were lower than that in the control group when exercise intervention was >16 weeks [SMD = –1.01, 95% CI (–1.99, –0.04), p = .042] and ≤16 weeks [SMD = 0.43, 95% CI (–0.82, –0.03), p = .034]. Conclusion Exercise intervention can improve the neuropsychiatric symptoms, activities of daily living and cognitive function of AD patients, but the improvement is not significant in case of exercise intervention ≤16 weeks.

Abstract Background Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. Aim The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. Methods Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. Results The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. Conclusions Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.

Abstract Background The effects of traumatic brain injury (TBI) can include physical disability and even death. The development of effective therapies to promote neurological recovery is still a challenging problem. 3D-printed biomaterials are considered to have a promising future in TBI repair. The injury-preconditioned secretome derived from human umbilical cord blood mesenchymal stem cells showed better stability in neurological recovery after TBI. Therefore, it is reasonable to assume that a biological scaffold loaded with an injury-preconditioned secretome could facilitate neural network reconstruction after TBI. Methods In this study, we fabricated injury-preconditioned secretome/collagen/heparan sulfate scaffolds by 3D printing. The scaffold structure and porosity were examined by scanning electron microscopy and HE staining. The cytocompatibility of the scaffolds was characterized by MTT analysis, HE staining and electron microscopy. The modified Neurological Severity Score (mNSS), Morris water maze (MWM), and motor evoked potential (MEP) were used to examine the recovery of cognitive and locomotor function after TBI in rats. HE staining, silver staining, Nissl staining, immunofluorescence, and transmission electron microscopy were used to detect the reconstruction of neural structures and pathophysiological processes. The biocompatibility of the scaffolds in vivo was characterized by tolerance exposure and liver/kidney function assays. Results The excellent mechanical and porosity characteristics of the composite scaffold allowed it to efficiently regulate the secretome release rate. MTT and cell adhesion assays demonstrated that the scaffold loaded with the injury-preconditioned secretome (3D-CH-IB-ST) had better cytocompatibility than that loaded with the normal secretome (3D-CH-ST). In the rat TBI model, cognitive and locomotor function including mNSS, MWM, and MEP clearly improved when the scaffold was transplanted into the damage site. There is a significant improvement in nerve tissue at the site of lesion. More abundant endogenous neurons with nerve fibers, synaptic structures, and myelin sheaths were observed in the 3D-CH-IB-ST group. Furthermore, the apoptotic response and neuroinflammation were significantly reduced and functional vessels were observed at the injury site. Good exposure tolerance in vivo demonstrated favorable biocompatibility of the scaffold. Conclusions Our results demonstrated that injury-preconditioned secretome/collagen/heparan sulfate scaffolds fabricated by 3D printing promoted neurological recovery after TBI by reconstructing neural networks, suggesting that the implantation of the scaffolds could be a novel way to alleviate brain damage following TBI. Graphical abstract

Oxadiazole is a five-membered heterocyclic compound containing two nitrogen atoms and one oxygen atom. The 1,3,4-oxadiazole and 1,2,4-oxadiazole have favourable physical, chemical, and pharmacokinetic properties, which significantly increase their pharmacological activity via hydrogen bond interactions with biomacromolecules. In recent years, oxadiazole has been demonstrated to be the biologically active unit in a number of compounds. Oxadiazole derivatives exhibit antibacterial, anti-inflammatory, anti-tuberculous, anti-fungal, anti-diabetic and anticancer activities. In this paper, we report a series of compounds containing oxadiazole rings that have been published in the last three years only (2020–2022) as there was no report or their activities described in any article in 2019, which will be useful to scientists in research fields of organic synthesis, medicinal chemistry, and pharmacology.

Abstract Background Stroke is the leading cause of disability worldwide, resulting in severe damage to the central nervous system and disrupting neurological functions. There is no effective therapy for promoting neurological recovery. Growing evidence suggests that the composition of exosomes from different microenvironments may benefit stroke. Therefore, it is reasonable to assume that exosomes secreted in response to infarction microenvironment could have further therapeutic effects. Methods In our study, cerebral infarct tissue extracts were used to pretreat umbilical cord mesenchymal stem cells (UCMSC). Infarct-preconditioned exosomes were injected into rats via tail vein after middle cerebral artery occlusion (MCAO). The effect of infarct-preconditioned exosomes on the neurological recovery of rats was examined using Tunel assay, 2,3,5-triphenyltetrazolium chloride (TTC) assay, magnetic resonance imaging (MRI) analyses, modified Neurological Severity Score (mNSS), Morris water maze (MWM), and vascular remodeling analysis. Mi-RNA sequencing and functional enrichment analysis were used to validate the signal pathway involved in the effect of infarct-preconditioned exosomes. Human umbilical vein endothelial cells (HUVECs) were co-cultured with the isolated exosomes. Cell Counting Kit-8 (CCK-8) assay, scratch healing, and Western blot analysis were used to detect the biological behavior of HUVECs. Results The results showed that compared with normal exosomes, infarct-preconditioned exosomes further promoted vascular remodeling and recovery of neurological function after stroke. The function of upregulated miRNAs and their target genes which is beneficial to vascular smooth muscle cells verified the importance of vascular remodeling in improving stroke. Better resistance to oxygen–glucose deprivation/reoxygenation (OGD/R), reduced apoptosis, and enhanced migration were observed in infarct-preconditioned exosomes-treated umbilical vein endothelial cells. Conclusions Our results demonstrated that infarct-preconditioned exosomes promoted neurological recovery after stroke by enhancing vascular endothelial remodeling, suggested that infarct-preconditioned exosomes could be a novel way to alleviate brain damage following a stroke.

BackgroundMuscle strength is closely related to chronic noncommunicable diseases; specifically, a decline in handgrip strength (HS) is predominant globally. Exposure to green space—built environment components used for health intervention—reportedly decreases the risk of certain diseases and all-cause mortality. However, evidence in this area is limited.ObjectiveWe aimed to explore the association between green space exposure and muscle strength and ascertain the combined effect of physical activity and green space exposure on muscle strength.MethodData from 128,759 participants (aged 20–79 years) were obtained using a complex stratified multistage probability cluster sampling design. The green space was assessed as normalized difference vegetation index (NDVI) data for a 500-m buffer zone based on the geolocation information of sampling sites. We used a questionnaire to investigate transportation, occupation, physical activity, leisure-time exercise behaviors, and sedentary time within a usual week of the preceding year. The outcome was low relative HS, defined as HS-to-body weight ratio, and the percentage of men and women with relative HS in the lower third. We defined adequate physical activity as 150 min of moderate-intensity or 75 min of vigorous physical activity per week and calculated the weighted proportion of participants with insufficient physical activity. Categorical variables of NDVI and physical activity were used as exposure variables and their interrelationship was evaluated in a generalized linear mixed model (GLMM) to estimate the odds ratios (ORs) and 95% confidence intervals (95% CI). We measured interaction on an additive or multiplicative scale using a GLMM to test the interaction between green space exposure and physical activity. All analyses were performed for the total sample and subgroups (urban and rural).ResultThe high NDVI group had a lower risk of low relative HS than the low NDVI group (OR [95% CI]: 0.92 [0.88–0.95]). The sufficient physical activity group had a lower risk of low relative HS than the insufficient physical activity group (OR [95% CI]: 0.85 [0.81–0.88]). There was an interactive effect on the additive scale (relative excess risk owing to interaction: 0.29, 95% CI 0.22–0.36, p < 0.001) between green space exposure and physical activity.ConclusionHigh NDVI and adequate physical activity were protective factors against low relative HS in Chinese adults. Increasing green space exposure and physical activity together may have a greater potentiating effect on muscle strength improvement than these two protective factors individually. Green spaces should be incorporated into city design or built environments.

ObjectiveIncreasing evidence suggests that gut microbiota is involved in the occurrence and progression of urinary system diseases such as clear cell renal cell carcinoma (ccRCC). However, the mechanism of how alteration of gut metagenome promotes ccRCC remains unclear. Here we aim to elucidate the association of specific gut bacteria and their metabolites with ccRCC.MethodsIn a pilot case-control study among 30 ccRCC patients (RCC group) and 30 healthy controls (Control group), 16S ribosomal RNA (rRNA) gene sequencing were analyzed from fecal samples collected prior to surgery or hospitalization. Alpha diversity and beta diversity analysis of the gut microbiota were performed, and differential taxa were identified by multivariate statistics. Meanwhile, serum metabolism was measured by UHPLC-MS, and differential genes were identified based on the TCGA database.ResultsAlpha diversity found there were no significant microbial diversity differences of gut microbiota between the RCC group and the Control group. However, beta diversity analysis showed that the overall structures of the two groups were significantly separated (p = 0.008). Random Forests revealed the relative abundances of 20 species differed significantly between the RCC group and the Control group, among which nine species were enriched in the RCC group such as Desulfovibrionaceae, and 11 species were less abundant such as four kinds of Lactobacillus. Concomitantly, serum level of taurine, which was considered to be consumed by Desulfovibrionaceae and released by Lactobacillus, has decreased in the RCC group. In addition, macrophage-related genes such as Gabbr1 was upregulated in ccRCC patients.ConclusionReduction of protective bacteria, proliferation of sulfide-degrading bacteria Desulfovibrionaceae, reduction of taurine, and enrichment of macrophage related genes might be the risk predictors of ccRCC.

Chiral emitters with high photoluminescence quantum yield are desirable for use in circularly polarized LEDs. The authors demonstrate the transfer of chirality from nanoscale copper iodide clusters to microscale chiral luminescent polycrystals by non-classical crystallization.

Abstract Background Atopic dermatitis (AD) is a chronic relapsing skin disease that has long-term physical and mental health impacts on children with this condition. Current treatments mainly include anti-inflammatory, antibacterial, and anti-allergic interventions, systemic therapy, and recently emerging target-focused agents. However, these treatments have limited effectiveness and unwanted side effects. The use of traditional Chinese medicine (TCM) in the treatment of AD has a long history, with promising efficacies, low toxicity, and improvements in the quality of life of patients with AD. Longmu Tang granule, a TCM, has been used to effectively treat AD since 2008 through doctors’ prescriptions. To scientifically evaluate the clinical efficacy and safety of Longmu Tang granule, we proposed to launch a single-centred, double-blinded, randomised, placebo-controlled trial. Methods In this single-centred, double-blinded, randomised, placebo-controlled clinical trial conducted at Xiyuan Hospital of China Academy of Chinese Medical Sciences, a total of 60 participants will be randomly assigned (1:1) to receive the Longmu Tang granule or placebo granule for 8 weeks. The primary outcome will be evaluated using the index of Scoring Atopic Dermatitis. The secondary outcomes will be evaluated using the Children’s Dermatology Life Quality Index and the number cancellation test. The mechanistic evidence will be the serum levels of inflammatory cytokines, including immunoglobulin E, tumour necrosis factor-α, interleukin-1, and interleukin-6. Discussion The results of this trial will provide evidence of the efficacy and safety of the Longmu Tang granule and prove its anti-inflammatory action in patients with AD. Trial registration Chinese Clinical Trial Registry Chictr.org ID: ChiCTR2100041591 . Registered on 1 January 2021

Abstract Background Microwave ablation (MWA) is a popular therapy for liver malignant tumor in recent years. Few studies have been conducted on its use in the treatment of hepatic alveolar echinococcosis (HAE). The study aims to evaluate the efficacy and safety of MWA in the treatment of HAE. Methods This study analyzed the data of 45 patients (mean age, 38 ± 2 years; 24 males) diagnosed with HAE and underwent MWA treatment between June 2014 to December 2019. The patients after MWA were examined by CT or MRI [follow-up: 32 months (IQR 23–48.5)] to determine whether the lesions were relapsed and to evaluate the therapeutic effect of MWA. The safety of MWA was evaluated by monitoring postoperative complications. Clinical data, such as patient demographics, imaging features of the lesions, relevant findings of laboratory tests before and after ablation, and information related to ablation, were collected and analyzed. Paired-sample t tests and paired-sample Wilcoxon signed-rank tests were used to compare relevant laboratory indicators before and after MWA. Results MWA was applied to 57 HAE lesions in 45 patients. The median size of lesions was 3.42 cm (IQR2.85–4.41). The rate of complete ablation was 100% (57/57). The median follow-up time was 32 months (IQR 23–48.5). The recurrence rate was 13% (6/45), and the median time of recurrence was 22 months. The rate of minor complications was 11.1% (5/45), and there were no major complications and deaths. Compared to preoperative, ALB, RBC, HBG, and PLT were decreased (p 0.05). Conclusions MWA might be a safe and effective way to cure HAE. Meanwhile, it provides a new option and a new way of thinking about treatment for patients with HAE.

Abstract Background This study aims to validate the diagnostic accuracy of the International Ovarian Tumor Analysis (IOTA) the Assessment of Different NEoplasias in the adneXa (ADNEX) model in the preoperative diagnosis of adnexal masses in the hands of nonexpert ultrasonographers in a gynaecological oncology centre in China. Methods This was a single oncology centre, retrospective diagnostic accuracy study of 620 patients. All patients underwent surgery, and the histopathological diagnosis was used as a reference standard. The masses were divided into five types according to the ADNEX model: benign ovarian tumours, borderline ovarian tumours (BOTs), stage I ovarian cancer (OC), stage II-IV OC and ovarian metastasis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of the ADNEX model to classify tumours into different histological types with and without cancer antigen 125 (CA 125) results. Results Of the 620 women, 402 (64.8%) had a benign ovarian tumour and 218 (35.2%) had a malignant ovarian tumour, including 86 (13.9%) with BOT, 75 (12.1%) with stage I OC, 53 (8.5%) with stage II-IV OC and 4 (0.6%) with ovarian metastasis. The AUC of the model to differentiate benign and malignant adnexal masses was 0.97 (95% CI, 0.96–0.98). Performance was excellent for the discrimination between benign and stage II-IV OC and between benign and ovarian metastasis, with AUCs of 0.99 (95% CI, 0.99–1.00) and 0.99 (95% CI, 0.98–1.00), respectively. The model was less effective at distinguishing between BOT and stage I OC and between BOT and ovarian metastasis, with AUCs of 0.54 (95% CI, 0.45–0.64) and 0.66 (95% CI, 0.56–0.77), respectively. When including CA125 in the model, the performance in discriminating between stage II–IV OC and stage I OC and between stage II–IV OC ovarian metastasis was improved (AUC increased from 0.88 to 0.94, P = 0.01, and from 0.86 to 0.97, p = 0.01). Conclusions The IOTA ADNEX model has excellent performance in differentiating benign and malignant adnexal masses in the hands of nonexpert ultrasonographers with limited experience in China. In classifying different subtypes of ovarian cancers, the model has difficulty differentiating BOTs from stage I OC and BOTs from ovarian metastases.

Background: We present the first case report of the treatment of congenital vaginal atresia by 3D-printed patient-specific vaginal scaffold from China. Case presentation: A 17-year-old female patient was referred to our department for treatment of congenital vaginal atresia and complications arising from previous failed operations. Pelvic examination was conducted to understand the morphological characteristics and severity of stenosis, and based on which we designed our prototypes of vaginal scaffold using software UG NX10.0. We finally obtained our patient-specific mold, which was 50 mm in length, 28 mm in diameter, 2 mm of thickness with a whole weight of 7.6 g, and it was made of polycaprolactone. After removing scar tissues caused by vaginal stenosis, an 8 cm long artificial tunnel was created, and then the polycaprolactone (PCL) vaginal mold was placed and sutured. The patient had no discomfort after surgery and was discharged 3 days after the surgery. Follow-up for 1 year after surgery, through hysteroscopy and colposcopy, it was found that the cervix was smooth, the vaginal wall was covered with stratified squamous epithelium, and the vaginal wall was soft and lubricated, which was close to a normal vagina. The incompletely absorbed mold was taken out one year after the operation. Hysteroscopy and colposcopy were performed one year and two years after the mold was taken out. The vagina was unobstructed and the length was about 12 cm. The appearance of the vaginal wrinkles was normal. The patient's quality of sexual life was good. Conclusion: Our team tried to treat congenital vaginal atresia by 3D-printed patient-specific vaginal scaffold, which can effectively reduce patient complications and reduce patient pain. Through long-term follow-up, we found that this technique has achieved favorable results and improved the patient's quality of sexual life.

Abstract. Background:. High-frequency irreversible electroporation (H-FIRE) is a novel, next-generation nanoknife technology with the advantage of relieving irreversible electroporation (IRE)-induced muscle contractions. However, the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined. This study aimed to compare the efficacy of the two treatments in vivo. Methods:. Ten Bama miniature swine were divided into two group: five in the 1-day group and five in the 7-day group. The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant (Krans), rate constant (Kep) and extravascular extracellular volume fraction (Ve) value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), size of the ablation zone, and histologic analysis. Each animal underwent the IRE and H-FIRE. Temperatures of the electrodes were measured during ablation. DCE-MRI images were obtained 1, 4, and 7 days after ablation in the 7-day group. All animals in the two groups were euthanized 1 day or 7 days after ablation, and subsequently, IRE and H-FIRE treated liver tissues were collected for histological examination. Student's t test or Mann-Whitney U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch's ANOVA test followed by Holm-Sidak's multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis H test followed by Dunn's multiple comparison test was used for multiple group comparisons and post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables. Results:. Higher Ve was seen in IRE zone than in H-FIRE zone (0.14 ± 0.02 vs. 0.08 ± 0.05, t = 2.408, P = 0.043) on day 4, but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points (all P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 (P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cm2vs. 3.20 ± 0.77 cm2, t = 3.241, P = 0.009) and 4 days (2.22 ± 0.83 cm2vs. 1.30 ± 0.50 cm2, t = 2.343, P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 vs. 0.73 ± 0.06 vs. 0.68 ± 0.07, F = 241.300, P 0.05). Electrode temperature variations were not significantly different between the two zones (18.00 ± 3.77°C vs. 16.20 ± 7.45°C, t = 0.682, P = 0.504). The Ktrans value (r = 0.940, P = 0.017) and the Kep value (r = 0.895, P = 0.040) of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone. Conclusions:. H-FIRE showed a comparable ablation effect to IRE. DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.

Abstract. Background:. Prenatal evaluation of fetal lung maturity (FLM) is a challenge, and an effective non-invasive method for prenatal assessment of FLM is needed. The study aimed to establish a normal fetal lung gestational age (GA) grading model based on deep learning (DL) algorithms, validate the effectiveness of the model, and explore the potential value of DL algorithms in assessing FLM. Methods:. A total of 7013 ultrasound images obtained from 1023 normal pregnancies between 20 and 41 + 6 weeks were analyzed in this study. There were no pregnancy-related complications that affected fetal lung development, and all infants were born without neonatal respiratory diseases. The images were divided into three classes based on the gestational week: class I: 20 to 29 + 6 weeks, class II: 30 to 36 + 6 weeks, and class III: 37 to 41 + 6 weeks. There were 3323, 2142, and 1548 images in each class, respectively. First, we performed a pre-processing algorithm to remove irrelevant information from each image. Then, a convolutional neural network was designed to identify different categories of fetal lung ultrasound images. Finally, we used ten-fold cross-validation to validate the performance of our model. This new machine learning algorithm automatically extracted and classified lung ultrasound image information related to GA. This was used to establish a grading model. The performance of the grading model was assessed using accuracy, sensitivity, specificity, and receiver operating characteristic curves. Results:. A normal fetal lung GA grading model was established and validated. The sensitivity of each class in the independent test set was 91.7%, 69.8%, and 86.4%, respectively. The specificity of each class in the independent test set was 76.8%, 90.0%, and 83.1%, respectively. The total accuracy was 83.8%. The area under the curve (AUC) of each class was 0.982, 0.907, and 0.960, respectively. The micro-average AUC was 0.957, and the macro-average AUC was 0.949. Conclusions:. The normal fetal lung GA grading model could accurately identify ultrasound images of the fetal lung at different GAs, which can be used to identify cases of abnormal lung development due to gestational diseases and evaluate lung maturity after antenatal corticosteroid therapy. The results indicate that DL algorithms can be used as a non-invasive method to predict FLM.

BackgroundSleep quality has been always an important problem for patients after hepatectomy. The main purpose of the study is to investigate the effects of early ambulation on sleep quality in patients after liver resection via a quantitative study.MethodsPatients undergoing liver tumor resection were randomly divided into two groups, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess the postoperative activities and sleep quality.ResultsPatients who started early ambulation after liver resection had significantly better sleep quality, faster recovery of gastrointestinal function and shorter lengths of postoperative hospital stay compared with the control group. And there was no significant difference in the incidence of postoperative complications between the two groups.ConclusionEarly standardized physical activities are feasible for patients after liver resection, which can significantly improve patient's sleep quality, reduce patient's pain and the nursing workload, and achieve rapid recovery.

To study the effect and mechanism of selenium sources on the selenium content and quality of fresh tea leaves, tea seedlings (Camellia sinensis (L.) O. Kuntze) were the research object. A solution of 100 mg/L sodium selenate (Na2SeO4), sodium selenite (Na2SeO3), and selenium yeast (selenium yeast) were applied on the leaves surface of 5-week-old tea plants, and the selenium levels in the leaves, roots, and stems were determined at 20 weeks of age. The effects of different selenium sources on the mineral nutrient content, antioxidant enzyme activity, and quality parameters content in leaves were analyzed. The mechanism was analyzed by detecting the expression levels of related genes. The results showed that the three selenium sources can increase the growth of tea seedlings and the selenium content in leaves and stems, and the selenium yeast treatment had the most significant effect. Selenium spraying promoted the absorption of mineral nutrients such as nitrogen, phosphorus, and potassium, but had no significant impact on the absorption of calcium and magnesium. Spraying the three selenium sources dramatically increased the activities of APX, POD, and SOD antioxidant enzymes, among which the selenium yeast treatment had the most significant effect. However, there was no significant impact on the MDA level in this study. Selenium sources markedly increased leaves total amino acid levels, accompanied by up-regulation the genes of amino acid synthetic enzymes (CsGS, CsGOGAT, and CsGDH). Leaves glucose, tea polyphenol, total soluble protein, catechin, flavonoid contents, and sucrose were higher in selenium sources treatments than in control treatment seedlings. Moreover, selenium sources up-regulated expression of CsHMGR, CsAPX, and CsTCS1 genes. selenium yeast had the best comprehensive effect of the three selenium sources. These results confirmed that selenium sources play a positive role on the selenium content and quality of tea by increasing the antioxidant capacity of leaves, the absorption rate of mineral nutrients, and regulating expression of related genes in Camellia sinensis.

Drought stress limits plant development and reproduction. Multiple mechanisms in plants are activated to respond to stress. The MYC2 transcription factor is a core regulator of the jasmonate (JA) pathway and plays a vital role in the crosstalk between abscisic acid (ABA) and JA. In this study, we found that SlMYC2 responded to drought stress and regulated stomatal aperture in tomato (Solanum lycopersicum). Overexpression of SlMYC2 repressed SlCHS1 expression and decreased the flavonol content, increased the reactive oxygen species (ROS) content in guard cells and promoted the accumulation of JA and ABA in leaves. Additionally, silencing the SlCHS1 gene produced a phenotype that was similar to that of the MYC2-overexpressing (MYC2-OE) strain, especially in terms of stomatal dynamics and ROS levels. Finally, we confirmed that SlMYC2 directly repressed the expression of SlCHS1. Our study revealed that SlMYC2 drove stomatal closure by modulating the accumulation of flavonol and the JA and ABA contents, helping us decipher the mechanism of stomatal movement under drought stress.

Angelica dahurica (A. dahurica) root is a famous edible medicinal herb that has been used in China for thousands of years. To date, more than 300 chemical constituents have been discovered from A. dahurica. Among these ingredients, coumarins and volatile oils are the major active compounds. Moreover, a few other compounds have also been isolated from the root of A. dahurica, such as alkaloids, phenols, sterols, benzofurans, polyacetylenes and polysaccharides. Modern pharmacological studies demonstrated that the root of A. dahurica and its active components displayed various bioactivities such as anti-inflammation, anti-tumor, anti-oxidation, analgesic activity, antiviral and anti-microbial effects, effects on the cardiovascular system, neuroprotective function, hepatoprotective activity, effects on skin diseases and so on. Based on these studies, this review focused on the research publications of A. dahurica and aimed to summarize the advances in the traditional uses, phytochemistry and pharmacology which will provide reference for the further studies and applications of A. dahurica.

Abstract Recent studies reported sex differences in patients with coronavirus disease‐2019 (COVID‐19). We aim to analyze sex differences in clinical characteristics and risk factors for disease severity of hospitalized patients with COVID‐19 in Beijing. All adults (185 cases) diagnosed with COVID‐19 and admitted to Beijing Ditan Hospital, Capital Medical University were included in samples. The median age of all patients was 41 years. The mean body mass index (BMI) of males was relatively higher compared to females (p

AIM: To evaluate the clinical effect of a limbus protection technique during epithelium-on corneal collagen cross-linking(Epi-on CXL)for keratoconus treatment.METHODS: Prospectively clinical study. A total of 15 patients(30 eyes)with diagnosed binocular progressive keratoconus were selected and treated with Epi-on CXL in my hospital from Jan. to Dec. 2019, and divided into 2 groups, Limbus-protecting Group and Control Group. The differences in corrected distance visual acuity, astigmatism, Km, thickness at the thinnest point of cornea, postoperative discomfort score, corneal epithelium healing time, and tear breakup time were compared between the two groups pre- and postoperatively.RESULTS: The corrected distance visual acuity and astigmatism were improved at 3mo postoperatively(P0.05). However, the postoperative corneal epithelium healing time in Limbus-protecting Group was shorter than in Control Group(3.20±0.56d vs 3.73±0.96d, P=0.041).CONCLUSION:This limbal protection technique can reduce the corneal epithelium healing time after Epi-on CXL surgery, which preliminarily shows the feasibility of this technique.

Abstract. Background:. Fetal weight is an important parameter to ensure maternal and child safety. The purpose of this study was to use three-dimensional (3D) limb volume ultrasound combined with fetal abdominal circumference (AC) measurement to establish a model to predict fetal weight and evaluate its efficiency. Methods:. A total of 211 participants with single pregnancy (28–42 weeks) were selected between September 2017 and December 2018 in the Beijing Obstetrics and Gynecology Hospital of Capital Medical University. The upper arm (AVol)/thigh volume (TVol) of fetuses was measured by the 3D limb volume technique. Fetal AC was measured by two-dimensional ultrasound. Nine cases were excluded due to incomplete information or the interval between examination and delivery >7 days. The enrolled 202 participants were divided into a model group (134 cases, 70%) and a verification group (68 cases, 30%) by mechanical sampling method. The linear relationship between limb volume and fetal weight was evaluated using Pearson Chi-squared test. The prediction model formula was established by multivariate regression with data from the model group. Accuracy of the model formula was evaluated with verification group data and compared with traditional formulas (Hadlock, Lee2009, and INTERGROWTH-21st) by paired t-test and residual analysis. Receiver operating characteristic curves were generated to predict macrosomia. Results:. AC, AVol, and TVol were linearly related to fetal weight. Pearson correlation coefficient was 0.866, 0.862, and 0.910, respectively. The prediction model based on AVol/TVol and AC was established as follows: Y = −481.965 + 12.194TVol + 15.358AVol + 67.998AC, R2adj = 0.868. The scatter plot showed that when birth weight fluctuated by 5% (i.e., 95% to 105%), the difference between the predicted fetal weight by the model and the actual weight was small. A paired t-test showed that there was no significant difference between the predicted fetal weight and the actual birth weight (t = −1.015, P = 0.314). Moreover, the residual analysis showed that the model formula's prediction efficiency was better than the traditional formulas with a mean residual of 35,360.170. The combined model of AVol/TVol and AC was superior to the Lee2009 and INTERGROWTH-21st formulas in the diagnosis of macrosomia. Its predictive sensitivity and specificity were 87.5% and 91.7%, respectively. Conclusion:. Fetal weight prediction model established by semi-automatic 3D limb volume combined with AC is of high accuracy, sensitivity, and specificity. The prediction model formula shows higher predictive efficiency, especially for the diagnosis of macrosomia. Trial Registration:. ClinicalTrials.gov, NCT03002246; https://clinicaltrials.gov/ct2/show/NCT03002246?recrs=e&cond=fetal&draw=8&rank=67.

A novel folded multi-pass cell consisting of three non-coaxial mirrors (spherical mirror or plane mirror) is proposed for laser spectroscopy. Three mirrors of the folded multi-pass cell can arrange in V-shape to form a stable non-coaxial multi-pass cell. Furthermore, in order to research the stability of the multi-pass cell under off-axis mirror’s astigmatism circumstance, an equivalent coaxial multi-pass cell and modified ABCD matrix model for the spot pattern of the folded multi-pass cell is proposed, by which a series of the detailed numerical calculations were implemented to analyze the optical path length of the multi-pass cell. Many spot patterns obtained with a high fill factor improve the utilization efficiency of the surface of the mirror and produce a longer total optical path length. The several typical types of folded multi-pass cells consisting of the different mirrors and base lengths were selected to demonstrate the cell’s self-consistent condition and power for a longer-optical path length. Three effective optical path lengths of 49.6, 97.6 and 173.6 m were obtained, respectively.

Abstract Background Some studies have stated that intrauterine insemination (IUI) with controlled ovarian stimulation (COS) might increase the pregnancy rate, while others suggest that IUI in the natural cycle (NC) should be the first line of treatment. It remains unclear whether it is necessary to use COS at the same time when IUI is applied to treat isolated male factor infertility. Thus, we aimed to investigate efficacy of IUI with COS for isolated male factor infertility. Methods A total of 601 IUI cycles from 307 couples who sought medical care for isolated male factor infertility between January 2010 and February 2020 were divided into two groups: NC-IUI and COS-IUI. The COS-IUI group was further divided into two subgroups according to the number of pre-ovulatory follicles on the day of HCG: cycles with monofollicular development (one follicle group) and cycles with at least two pre-ovulatory follicles (≥ 2 follicles group). The IUI outcomes, including clinical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and multiple pregnancy rates were compared. Results The clinical pregnancy, live birth, spontaneous abortion, and ectopic pregnancy rates were comparable between the NC-IUI and COS-IUI group. Similar results were also observed among the NC-IUI, one follicle, and ≥ 2 follicles groups. However, with respect to the multiple pregnancy rate, a trend toward higher multiple pregnancy rate was observed in the COS-IUI group compared to the NC-IUI group (8.7% vs. 0, P = 0.091), and a significant difference was found between the NC-IUI and ≥ 2 follicles group (0 vs. 16.7%, P = 0.033). Conclusion In COS cycles, especially in those with at least two pre-ovulatory follicles, the multiple pregnancy rate increased without a substantial gain in overall pregnancy rate; thus, COS should not be preferred in IUI for isolated male factor infertility. If COS is required, one stimulated follicle and one healthy baby should be the goal considering the safety of both mothers and foetuses.

AIM: To evaluate the effect of opaque bubble layer(OBL)on the ocular cylotorsion compensation during FS-LASIK procedures. METHODS: Prospectively clinical study. From July 2019 to September 2019, two-hundred FS-LASIK patients(400 eyes)were randomly included into this study. The total OBL incidence, flap-out OBL incidence, flap-in OBL incidence, incidence of dynamic cyclotorsion component(DCC)and incidence of static cyclotorsion component(SCC)were statistically analyzed. RESULTS: OBL developed in 183 eyes of 400 FS-LASIK eyes, with a total OBL incidence of 45.8%. DCC was successfully performed on 397 eyes, with a total DCC incidence of 99.2%. SCC was successfully performed on 293 eyes, with a total SCC incidence of 73.2%. Neither flap-out OBL nor flap-in OBL could disturb the successful implementation of DCC during the operation(P>0.05). Both flap-out OBL and flap-in OBL could impact the SCC implementation and make it fail(P

Effects of three compound growth regulators formulated with hypersensitivity protein, spermidine, salicylic acid and DA-6 (diethyl aminoethanol hexanoate) were tested on Xinjiang Jun Jujube. The doses of compound growth regulators were named as A (Hypersensitivity protein + spermidine + salicylic acid at the rate of 30 mg/L, 0.1 mmol/L and 0.25 mmol/L, respectively), B (Hypersensitive protein + spermidine + DA-6 at the rate of 30 mg/L, 0.1 mmol/L and 30 mg/L, respectively) and C (Spermidine + salicylic acid + DA-6 at the rate of 0.1 mmol/L, 0.25 mmol/L and 30 mg/L, respectively) versus a control group CK (contained only water). Fruit anatomical structures were compared after spraying. The results indicated that after spraying, the thickness of the upper and lower epidermal cells and the stratum corneum were increased. However, the upper epidermal stratum corneum became significantly thicker than the lower epidermis. Spraying with A improved the thickness of upper and lower epidermal cells, stratum corneum, the central vein and mesophyll. The cumulative effects of all these changes in leaf and fruit anatomical structures provided the resistance of the experimental fruit plant to stress. While the B and C regulators had inhibitory effects. So, the results obtained after spraying A category were beneficial to improve the stress resistance of the fruits. The length and cell area of pericarp and sarcocarp cells in the treatment groups were not changed significantly. But the length, number of sarcocarp cells and number of gaps were lower than those in the CK. This study can provide new measures for improving plant resistance in jujube production.

Abstract Background AUF1 is one of the AU‐rich binding proteins, which promotes rapid ARE‐mRNA degradation. Recently, it has been reported that AUF1 is involved in regulating the antioxidant system because of its capacity to bind specifically to RNA containing oxidized bases and degrade oxidized RNA. Many antioxidant proteins have been reported to be overexpressed in colorectal cancer (CRC), however, the role of AUF1 in the progression of CRC has not been explored. Methods The expression level of AUF1 protein in human CRC cell lines and CRC tissues was detected by western blotting and immunohistochemistry (IHC. The effects of AUF1 knockdown on CRC cell proliferation, migration, invasion and changes in the signaling pathways were evaluated using a cell counting kit‐8 (CCK‐8), Transwell assays and western blotting. Subcutaneous xenograft tumor model was employed to further substantiate the role of AUF1 in CRC. Results AUF1 protein was upregulated in CRC tissues and CRC cells, and high expression of AUF1 was significantly associated with advanced AJCC stage (P = .001), lymph node metastasis (P = .007), distant metastasis (P = .038) and differentiation (P = .009) of CRC specimens. CRC patients with the high expression of AUF1 had an extremely poor prognosis. The knockdown of AUF1 suppressed CRC cell line proliferation, migration and invasion, inhibited CRC cells tumorigenesis and growth in nude mice, and reduced phosphorylated‐ERK1/2 and phosphorylated AKT in CRC cells. Conclusion Our findings demonstrate that AUF1 is probably involved in the progression of CRC via the activation of the ERK1/2 and AKT pathways. AU‐rich RNA‐binding factor 1 could be used as a novel prognostic biomarker and a potential therapeutic target for CRC.

As a versatile cruciferous species, Eruca sativa is widely cultivated, but in some areas, it has become an invasive weed. There are few studies on its seed dormancy and soil seed bank. This research examined seed dormancy, germination, and dynamics of the soil seed bank of E. sativa, with a view to provide support for its prevention and control. We tested the effects of temperature, light, storage, water, and salinity stress on seed germination and burial depth on seedling emergence of E. sativa. Dynamics of the soil seed bank were determined with a 24 month in situ seed-burial study. Seeds of E. sativa can germinate in a temperature range of 5–35°C; moreover, they exhibited non-deep physiological dormancy (NDPD) at maturity, which can be broken by dry storage or exposure to low temperature in winter. Germination of E. sativa seeds was sensitive to water and salinity stress, and most seeds did not germinate at -0.3 MPa. When buried in soil in the field, seeds exhibited an annual dormancy/non-dormancy cycle and formed at least a short-term persistent soil seed bank. Seeds buried deeper than 5 cm can hardly emerge. Seeds of E. sativa have a wide germination temperature range and exhibited dormancy cycling, which promotes the formation of a persistent soil seed bank and enables it to better adapt to the harsh low-temperature climate of the Qinghai-Tibet Plateau. No-tillage would be a good management strategy for this species.

Chicken infectious anemia (CIA) is an immunosuppressive disease caused by the chicken infectious anemia virus (CIAV) resulting in heavy economic losses once an outbreak is established. This study conducted a systematic analysis of the epidemiology and pathology of CIA in Henan province, China. A total of 437 clinical tissue samples and 120 poultry disease-related live attenuated vaccines were collected during 2017–2020; of which 45 were positive for CIAV nucleic acid, with a positive rate of 8.08%. Our results showed that genome sequence similarity among a total of 12 CIAV isolates was high, and ranged from 97.1 to 99.3%, and their similarity to the vaccine strains Cux-1 and Del-Ros ranged from 97.8 to 98.6%. However, There were mutations in the locus of the major capsid proteins VP1, VP2, and VP3 among all isolates. The subsequent sequence analysis indicated that the isolates of HN-4 and HN-8 showed genetic recombination and follow up animal experiments revealed that HN-4 might be a pathogenic strain. Our results reveal that both field infection and non-CIAV vaccines contamination promote the epidemiology of CIAV in China and some dominant epidemic viruses have undergone recombination and evolution. This study provides important information to help with the prevention and control of CIAV in the poultry industry.

All‐inorganic cesium lead halide perovskite colloidal nanocrystals (NCs) (CsPbX3, X = Cl, Br, I) have emerged as potential candidates for next‐generation light‐emitting diodes (LEDs). However, high trap states on the surface of CsPbX3 NCs caused by ionic nature and dynamic bonding of organic ligands limit the performance of CsPbX3 NCs‐based LEDs. Herein, a microemulsion (ME)‐modified strategy to decorate CsPbBr3 NC cores with inorganic PbWO4 is developed. It is demonstrated that ME‐assisted modification plays a crucial role in bridging the WO42− anion solution and the CsPbBr3 NC suspension. Compared with pristine CsPbBr3 NCs, the obtained PbWO4‐modified NCs exhibit improved photoluminescence efficiency. The corresponding NC films also show enhanced stability at elevated temperature and also in humid atmosphere. Consequently, the PbWO4‐modified NCs‐based LED exhibits a pronounced improvement of electroluminescence with an external quantum efficiency from 0.2% to 5.7% and twofold enhancement of the operational lifetime through PbWO4 passivation in comparison with that of pristine CsPbBr3 NCs‐based LED. These results show a promising pathway by ME‐induced anionic modification for high‐performance and stable LEDs based on perovskite NCs.

Background Breast cancer ( BC ), especially metastatic BC , is one of the most lethal diseases in women. CA 125 and CA 15-3 are commonly used indicators for diagnosis and prognosis of BC. Some serological indicators, such as lactate dehydrogenase (LDH) and C-reactive protein (CRP), can also be used to assess the prognosis and progression in BC. Methods Univariate Cox regression analysis and LASSO regression analysis were performed to identify prognostic factors and build prognostic models. We distributed the patients into 2 groups based on the median risk score, analyzed prognosis by Kaplan–Meier curve, and screened independent prognostic factors by multivariate Cox regression analysis. Result We identified 4 indicators-LDH, CRP, CA 15-3, and CA 125—related to the prognosis in BC and established a prognostic model. The high LDH group showed worse overall survival (OS) than low LDH group ( P = .017; hazard ratio (HR), 1.528; 95% confidence interval (CI), 1.055-2.215). The high CRP group showed worse OS than low CRP group ( P = .004; HR, 1.666; 95% CI, 1.143-2.429). The high CA153 group showed worse OS than low CA 15-3 group (P=.011; HR, 1.563; 95% CI, 1.075-2.274). The high CA 125 group showed worse OS than low CA 125 group ( P = .021; HR, 1.499; 95% CI, 1.031-2.181). The area under the curve for risk score was .824, Ki-67 was .628, age was .511, and grade was .545. Risk score was found to be an independent prognostic factor using multivariate Cox regression analysis. Conclusion We successfully established an optimization model by combining 4 prognosis-related indicators to assess the prognosis in patients with metastatic BC.

Glycolysis has been reported to be critical for cancer stem cells (CSCs), which are associated with tumor chemoresistance, metastasis and recurrence. Thus, selectively targeting glycolytic enzymes may be a potential therapy for ovarian cancer. 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3), the main source of fructose-2,6-bisphosphate, controls the first committed step in glycolysis. We investigate the clinical significance and roles of PFKFB3 in ovarian cancer using in vitro and in vivo experiments. We demonstrate that PFKFB3 is widely overexpressed in ovarian cancer and correlates with advanced stage/grade and poor outcomes. Significant up-regulation of PFKFB3 was found in ascites and metastatic foci, as well as CSC-enriched tumorspheres and ALDH+CD44+ cells. 3PO, a PFKFB3 inhibitor, reduced lactate level and sensitized A2780CP cells to cisplatin treatment, along with the modulation of inhibitors of apoptosis proteins (c-IAP1, c-IAP2 and survivin) and an immune modulator CD70. Blockade of PFKFB3 by siRNA approach in the CSC-enriched subset led to decreases in glycolysis and CSC properties, and activation of the NF-κB cascade. PFK158, another potent inhibitor of PFKFB3, impaired the stemness of ALDH+CD44+ cells in vitro and in vivo, whereas ectopic expression of PFKFB3 had the opposite results. Overall, PFKFB3 was found to mediate metabolic reprogramming, chemoresistance, metastasis and stemness in ovarian cancer, possibly via the modulation of inhibitors of apoptosis proteins and the NF-κB signaling pathway; thus, suggesting that PFKFB3 may be a potential therapeutic target for ovarian cancer.

A Higher education system is closely related to a country’s development. Governments need to make appropriate adjustments to ensure the healthy and sustainable development of higher education. To measure and evaluate the development status of the national higher education system and propose a set of policies, the following work has been done in this paper: First, this paper establishes a comprehensive evaluation index system based on the AHP-FCE model. The healthy development of education in significant countries was compared horizontally and vertically. The results of weighted scores were used to determine the Japanese higher education system as the research object. Secondly, this paper uses factor analysis and principal component analysis to evaluate the level of sustainable development of higher education, detecting development barriers that migrate from the current to the future. This paper proposes a healthy and sustainable development policy blueprint from four aspects. Finally, this article uses the ARMA time series model to predict the development trend of Japanese higher education in the next 30 years and formulates a timetable for corresponding implementation arrangements. In addition, this paper quantitatively evaluates the effectiveness of the policies we propose and their impact on reality and provides references for other countries in the world.

AIM: To investigate the differences of the choroidal vascularity index between type 2 diabetes with diabetic retinopathy and non-diabetes patients.METHODS: A retrospective cross-sectional study was performed at Beijing Friendship Hospital. Enhanced depth imaging spectral-domain optical coherence tomography(EDI-OCT)scans of 68 eyes of 68 type 2 diabetes who with diabetic retinopathy were compared with those of right eyes of 34 age- and gender-matched healthy controls. The choroidal images were binarized into luminal areas(LA)and stromal areas(SA). CVI was defined as the ratio of LA to total circumscribed subfoveal choroidal area. Mean choroidal thickness, mean retinal thickness and mean CVI between patients and controls were compared using t-test. RESULTS: There were no significant differences in total circumscribed subfoveal choroidal area(0.53±0.14mm2 vs 0.49±0.15mm2), LA(0.35±0.09mm2 vs 0.32±0.10mm2), SA(0.17±0.05mm2 vs 0.17±0.06mm2), or subfoveal choroidal thickness(347.9±76.9μm vs 325.9±92.9μm)between patients with DR and controls(P>0.05). However, there was a significantly lower CVI in patients with diabetes as compared to controls(64.33%±3.25% vs 67.04%±2.46%, PCONCLUSION: CVI is a kind of biological indicators which can directly reflect the changes of choroidal internal structure, and it is more stable and reliable than SFCT. For type 2 diabetic patients who with diabetic retinopathy, CVI is lower than that of healthy people.

Abstract Background Long-term mechanical ventilation with hyperoxia can induce lung injury. General anesthesia is associated with a very high incidence of hyperoxaemia, despite it usually lasts for a relatively short period of time. It remains unclear whether short-term mechanical ventilation with hyperoxia has an adverse impact on or cause injury to the lungs. The present study aimed to assess whether short-term mechanical ventilation with hyperoxia may cause lung injury in rats and whether deferoxamine (DFO), a ferrous ion chelator, could mitigate such injury to the lungs and explore the possible mechanism. Methods Twenty-four SD rats were randomly divided into 3 groups (n = 8/group): mechanical ventilated with normoxia group (MV group, FiO2 = 21%), with hyperoxia group (HMV group, FiO2 = 90%), or with hyperoxia + DFO group (HMV + DFO group, FiO2 = 90%). Mechanical ventilation under different oxygen concentrations was given for 4 h, and ECG was monitored. The HMV + DFO group received continuous intravenous infusion of DFO at 50 mg•kg− 1•h− 1, while the MV and HMV groups received an equal volume of normal saline. Carotid artery cannulation was carried out to monitor the blood gas parameters under mechanical ventilation for 2 and 4 h, respectively, and the PaO2/FiO2 ratio was calculated. After 4 h ventilation, the right anterior lobe of the lung and bronchoalveolar lavage fluid from the right lung was sampled for pathological and biochemical assays. Results PaO2 in the HMV and HMV + DFO groups were significantly higher, but the PaO2/FiO2 ratio were significantly lower than those of the MV group (all p

Abstract Background Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown. Methods This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild group (n = 79) and severe group(n = 26). We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined. Results 56.2% (59/105) of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% (96/105) cases the level of ALT, AST or TBil ≤3 fold of the upper limit of normal reference range (ULN). The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (P

Summary: Background: The impact of bile leakage (BL) on the long-term prognosis in patients with primary liver cancers after hepatectomy remains unclear. Methods: One thousand nine hundred and seventy-one consecutive patients with primary liver cancers who underwent curative hepatectomy were enrolled. 75 patients encountered BL, including 34 long-time BL (LTBL) and 41 short-time BL (STBL) according to 4-weeks demarcation. Variables associated with BL were identified using multiple logistic regression analysis. 75 patients without BL were enrolled into the Non-BL group using a one-to-one propensity score matched analysis before assessing the impact of BL on the long-term prognosis. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum and drain fluid were detected and compared. Results: The tumor size, type of liver cancer, operation time, blood loss and blood transfusion were independent risk factors for BL. The long-term survival showed no difference between the patients with and without BL (p > 0.05), while the LTBL was a significant predictor of poor long-term prognosis (p

Acid-sensing ion channel 1a (ASIC1a) mediates acidic neuronal necroptosis via recruiting receptor-interacting protein kinase 1 (RIPK1). Here authors show that auto-inhibition of ASICa prevents RIPK1 recruitment and demonstrate that targeting the auto-inhibition has therapeutic potential to prevent acidotoxicity.