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Purpose To evaluate the diagnostic performance of the delayed-phase difference between tumor and pancreas for differentiating solid pseudopapillary tumors (SPTs) from non-functional neuroendocrine tumors (NF-NETs) of the pancreas. Methods This retrospective review included 148 consecutive patients with SPT and 98 consecutive patients with NF-NET confirmed by pathology. Patients with SPT and NF-NET were matched via propensity score matching (PSM). All patients underwent multidetector computed tomography (MDCT). For each patient, the delayed-phase difference between the tumor and pancreas was measured, and the performance of this variable was assessed based on its discriminative ability and clinical utility. Results After PSM, 27 patients with SPT and 27 patients with NF-NET were included in the matched analysis. There were no statistically significant differences in clinical and CT characteristics between the resulting two groups (p > 0.05). The delayed-phase difference values between the tumor and pancreas were significantly lower in patients with SPT (median: -0.45; range: -2.05 to 0.73) than in patients with NF-NET (median: 0.71; range: -1.39 to 2.38). The delayed-phase difference between tumor and pancreas had a high diagnostic accuracy (area under the curve=0.88). The best cutoff point based on maximizing the sum of the sensitivity and specificity was -0.23 (sensitivity = 88.89%; specificity = 88.89%; accuracy = 0.89). Conclusions The delayed-phase difference between tumor and pancreas can accurately and noninvasively differentiate SPT from NF-NET.

Botryosphaeria dothidea causes white rot, which is among the most devastating diseases affecting apple crops globally. In this study, we assessed B. dothidea resistance to carbendazim by collecting samples from warts on the infected branches of apple trees or from fruits exhibiting evidence of white rot. All samples were collected from different orchards in nine provinces of China in 2018 and 2019. In total, 440 B. dothidea isolates were evaluated, of which 19 isolates from three provinces were found to exhibit carbendazim resistance. We additionally explored the fitness and resistance stability of these isolates, revealing that they were no less fit than carbendazim-sensitive isolates in terms of pathogenicity, sporulation, and mycelial growth and that the observed carbendazim resistance was stable. Sequencing of the β-tubulin gene in carbendazim-resistant isolates showed the presence of a substitution at codon 198 (GAG to GCG) that results in an alanine substitution in place of glutamic acid (E198A) in all 19 resistant isolates. A loop-mediated isothermal amplification (LAMP) method was then developed to rapidly and specifically identify this E198A mutation. This LAMP method offers value as a tool for rapidly detecting carbendazim-resistant isolates bearing this E198A mutation and can thus be used for the widespread monitoring of apple crops to detect and control the development of such resistance.

Germline heterozygous gain-of-function (GOF) mutation of NFKBIA, encoding IκBα, would affect the activation of NF-κB pathway and cause an autosomal dominant (AD) form of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Here we reported a Chinese patient with a heterozygous N-terminal truncation mutation of NFKBIA/IκBα, she presented recurrent fever, infectious pneumonia and chronic diarrhea with EDA-ID. Impaired NF-κB translocation and IL1R and TLR4 pathway activation were revealed in this patient. The findings suggested that the truncation mutation of IκBα caused medium impaired of activation of NF-κB but the early death. Furthermore, we reviewed all the reported patients with NFKBIA mutation to learn more about this disease.

Bovine viral diarrhea virus (BVDV) is the causative agent of bovine viral diarrhea-mucosal disease, which significantly affects the production performance of cattle, causing serious economic losses to the cattle industries worldwide. Up to now, some mechanisms involved in host–BVDV interaction are still not fully understood. The discovery of long non-coding RNAs (lncRNAs) has provided a new perspective on gene regulation in diverse biological contexts, particularly in viral infection and host immune responses. However, little is known about the profiles and functions of lncRNAs in host cells in response to BVDV infection. Here, we utilized Illumina sequencing to explore lncRNAs profiles in cytopathic (CP) biotype BVDV-infected MDBK cells to further reveal the potential roles of lncRNAs in BVDV infection and host–BVDV interaction with integrated analysis of lncRNAs and mRNA expression profiles. A total of 1747 significantly differentially expressed genes, DEGs (156 lncRNAs and 1591 mRNAs) were obtained via RNA-seq in BVDV-infected MDBK cells compared to mock-infected cells. Next, these DE lncRNAs and mRNAs were subjected to construct lncRNAs-mRNAs co-expression network followed by the prediction of potential functions of the DE lncRNAs. Co-expression network analysis elucidated that DE lncRNAs were significant enrichment in NOD-like receptor, TNF, NF-ĸB, ErbB, Ras, apoptosis, and fatty acid biosynthesis pathways, indicating that DE lncRNAs play important roles in host–BVDV interactions. Our data give an overview of changes in transcriptome and potential roles of lncRNAs, providing molecular biology basis for further exploring the mechanisms of host–BVDV interaction.

The epicardium plays an important role in cardiomyogenesis during development, while it becomes quiescent in adult heart during homeostasis. This study investigates the efficiency of thymosin β4 (Tβ4) release with RPRHQGVM conjugated to the C-terminus of RADA16-I (RADA-RPR), the functionalized self-assembling peptide (SAP), to activate the epicardium and repairing the infarcted myocardium. Methods: The functionalized SAP was constituted with self-assembling motif, Tβ4-binding site, and cell adhesive ligand. Myocardial infarction (MI) models of the transgenic mice were established by ligation of the left anterior descending coronary artery. At one week after intramyocardial injection of Tβ4-conjugated SAP, the activation of the epicardium was assessed. At four weeks after implantation, the migration and differentiation of epicardium-derived cells (EPDCs) as well as angiogenesis, lymphangiogenesis and myocardial regeneration were examined. Results: We found that the designer RADA-RPR bound Tβ4 and adhered to EPDCs and that Tβ4 released from the functionalized SAP could effectively activate the epicardium and induce EPDCs to differentiate towards cardiovascular cells as well as lymphatic endothelial cells. Moreover, SAP-released Tβ4 (SAP-Tβ4) promoted proliferation of cardiomyocytes. Furthermore, angiogenesis, lymphangiogenesis and myocardial regeneration were enhanced in the MI models at 4 weeks after delivery of SAP-Tβ4 along with attenuation of adverse myocardial remodeling and significantly improved cardiac function. Conclusions: These results demonstrate that sustained release of Tβ4 from the functionalized SAP can activate the epicardium and effectively enhance the repair of infarcted myocardium. We believe the delivery of SAP-Tβ4 may be a promising strategy for MI therapy.

The objective of this study was to investigate the single- and multiple-dose pharmacokinetics of chelerythrine (CHE) and its metabolite, dihydrochelerythrine (DHCHE), after oral and IM administrations in pigs.Six crossbreed (Landrace × Large White) female pigs (7-8 weeks old; 24.1 ± 2.6 kg bw) administered oral and IM CHE at a dose of 0.1 mg/kg orally and intramuscularly in a cross-over design. Multiple oral administration was performed at 0.1 mg/kg a time, three times a day at 8-h intervals for three consecutive days. Blood samples were collected from the anterior vena cava and placed into heparinized centrifuge tubes before dosing (time 0 h) and at different times after oral and IM administrations. Pre-treatment plasma was analysed by high-performance liquid chromatography-tandem mass spectrometry.After IM administration, CHE and DHCHE rapidly reached peak concentrations (

Intraocular lens (IOL) power calculations are less accurate in eyes that have undergone corneal refractive surgery. A wide range of methods have been proposed. We reviewed the methods and outcomes of IOL power calculations in eyes with previous LASIK, excimer laser photorefractive keratectomy (PRK), or radial keratotomy (RK). The PubMed database was searched for articles that (1) discuss methods and outcomes of IOL power calculation in eyes with previous corneal refractive surgery and (2) evaluate the outcomes of toric, multifocal, or extended depth-of-focus (EDOF) IOLs in these eyes. We excluded review articles, case reports or case studies, and non-English reports. Seventy full-text articles were included in this review. Three categories of methods exist based on whether and how they use historical data acquired before the corneal refractive surgery. The American Society of Cataract and Refractive Surgery (ASCRS) postrefractive IOL calculator incorporates many commonly used methods. In eyes with previous myopic LASIK or PRK, hyperopic LASIK or PRK, and RK, 0% to 85%, 38.1% to 71.9%, and 29% to 87.5% of eyes, respectively, showed refractive prediction errors within ±0.5 diopter (D); in eyes with toric IOL implantation that met certain inclusion criteria, 80%, 84%, and 69% of eyes, respectively, achieved postoperative astigmatism of 0.50 D or less. Intraocular lenses with negative spherical aberration (SA) will reduce the positive corneal spherical aberration induced in eyes by myopic LASIK or PRK or by RK. Intraocular lenses with 0 SA on average best match corneal SA in eyes with prior hyperopic LASIK or PRK. Studies have reported excellent outcomes of postrefractive eyes implanted with multifocal or EDOF IOLs; however, corneal topographic enrollment criteria were not specified. Despite availability of new measurement technologies and development of new IOL calculation formulas, further advances are needed to improve outcomes of cataract surgery in eyes that have undergone corneal refractive surgery. Tools like the ASCRS postrefractive IOL calculator are useful for the clinician by incorporating a variety of formulas. Toric, EDOF, and multifocal IOLs may provide excellent outcomes in selected cases that meet certain corneal topographic criteria.

Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population.

Graphical abstract The schematic diagram. Schematic illustration of the signaling cascades by which progesterone coordinates with FSH to regulate the proliferation of granular cells to slow down follicle growth during ovarian stimulation by PI3K/AKT and MAPK pathways., Highlights • Progesterone reduced oocyte yields in clinic. Yields were rescued by the higher dose of hMG. • Progesterone downregulated follicle growth and consequently reduced oocyte yields. • Progesterone inhibited granular cell proliferation via MAPK and PI3K/AKT pathways. • Progesterone and FSH coordinated follicle growth via signalling crosstalk in granular cells., Introduction As an effective inhibitor of premature ovulation, progestin was introduced to a novel ovarian stimulation regimen for infertility treatment. However, the local action of progestin on the ovary and its effect on clinical outcomes have not been described. Objectives The influence of progesterone administration on clinical oocyte outcomes and the mechanisms involved in the coordination of progesterone and follicle stimulating hormone (FSH) on follicle growth and oocyte yields were investigated. Methods Clinical outcomes of patients undergoing ovarian stimulation for in vitro fertilization were analyzed. The murine ovarian stimulation model and follicle culture system were used to evaluate the effects of progesterone on oocyte yield, follicle development, granular cell proliferation, and hormone secretion. Phospho-specific protein microarrays were used to explore involved signaling pathways. Results Progesterone decreased clinical oocyte yields, and yields were rescued with an increased dose of human menopausal gonadotropin. Administration of progesterone inhibited murine granular cell proliferation and reduced the growth rate of follicles; both of which were rescued by FSH. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) were identified as pivotal signaling pathways to integrate progesterone into the FSH signaling network in granular cells. Conclusion Progesterone inhibited granular cell proliferation and antral follicle growth during ovarian stimulation, and subsequently influenced oocyte outcomes in the clinical setting. Progesterone coordinated with FSH to regulate follicle growth through PI3K/AKT and MAPK signaling pathways. These findings advance our knowledge regarding the ovarian response to gonadotropins during progestin-primed ovarian stimulation and create an opportunity to manipulate individual oocyte yields.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example, Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals, and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion. Furthermore, many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers. Therefore, it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs. In this review, we focus on research progress in the field of immune checkpoints based on three topics: (1) immune checkpoint targets and pathways, (2) development of novel immune checkpoint-based drugs, and (3) application of immune checkpoints in the development of TCMs., Graphical abstract In this review, we provide a discussion of the applications of immune checkpoints in the development of novel drugs and TCMs.Image 1

The aim of this study was to optimize the preparation method of polymethyl methacrylate (PMMA) denture base loaded with nano silver (NAg), to more effectively and safely impart sustainable antibacterial functions. NAg solution was synthetized and mixed with acrylic acid and methyl methyacrylate (MMA) monomer in order to prepare a new type of NAg solution (NS)/polymer methyl methacrylate denture base specimens (NS/PMMA). The surface morphology, mechanical strength, antimicrobial activity, anti-aging performance, cytotoxicity and biocompatibility of NS/PMMA denture base were evaluated in comparison with specimens fabricated using traditional NAg adding methods and NAg-free denture base. The aesthetic characteristics and mechanical strength of NS/PMMA denture base met the clinical application requirements. Meanwhile, NS/PMMA denture base showed better antibacterial activity, anti-aging properties, no cytotoxicity and displayed exceptional biocompatibility. NS/PMMA denture base thus has great potential for clinical application.

Background Rapid population aging in developed countries has resulted in the working-age population increasingly being tasked with the provision of informal care. Methods An educational intervention was delivered to 21 carer-employees employed at a Canadian University. Work role function, job security, schedule control, work–family conflict, familywork conflict, and supervisor and coworker support were measured as part of an aggregated workplace experience score. This score was used to measure changes pre/post intervention and at a follow-up period approximately 12 months post intervention. Three random intercept models were created via linear mixed modeling to illustrate changes in participants' workplace experience across time. Results All three models reported statistically significant random and fixed effects intercepts, with a positive coefficient of change. Conclusion This suggests that the intervention demonstrated an improvement of the workplace experience score for participants over time, with the association particularly strong immediately after intervention.

Glucose metabolism reprogramming is one of the hallmarks of cancer cells, although functional and regulatory mechanisms of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remain incompletely understood. The aim of this study was to uncover the role of GAS6-AS1 in the regulation of progression and glucose metabolism in LUAD. We discovered that overexpression of GAS6-AS1 suppressed tumor progression of LUAD both in vitro and in vivo. Metabolism-related assays revealed that GAS6-AS1 inhibited glucose metabolism reprogramming. Mechanically, GAS6-AS1 was found to repress the expression of glucose transporter GLUT1, a key regulator of glucose metabolism. Ectopic expression of GLUT1 restored the inhibition effect of GAS6-AS1 on cancer progression and glucose metabolism reprogramming. Further investigation identified that GAS6-AS1 directly interacted with transcription factor E2F1 and suppressed E2F1-mediated transcription of GLUT1, and GAS6-AS1 was downregulated in LUAD tissues and correlated with clinicopathological characteristics and survival of patients. Taken together, our results identified GAS6-AS1 as a novel tumor suppressor in LUAD and unraveled its underlying molecular mechanism in reprogramming glucose metabolism. GAS6-AS1 potentially may serve as a prognostic marker and therapeutic target in LUAD., Graphical abstract, In this study, we identified lncRNA GAS6-AS1 as a suppressor in tumor progression and glucose metabolism reprogramming of LUAD. GAS6-AS1 exerted its biological role through binding with E2F1 and suppressing E2F1-mediated transcription of glucose transporter GLUT1.

Strangles, which is caused by Streptococcus equi subspecies equi, is one of the most prevalent equine infectious diseases and poses heavy economic losses worldwide. Although various vaccines have been used for decades, they seemed to be sub-optimal to demonstrate effective protection, and the antigen component of vaccines against S. equi remains to be optimized. In the present study, three target antigens (M-like protein, α2-macroglobulin and IgG-binding protein, and glyceraldehyde-3-phosphate dehydrogenase) were selected and expressed. Mice were immunized and challenged, and their immune response and efficacy were evaluated. The results revealed that this optimized multi-antigen treatment elicited a high expression level of T-cell receptor, major histocompatibility complex I, toll-like receptor TLR-4, and increased specific antibody. In addition, the challenge experiment showed an evidently improved protection efficacy. The present work demonstrated that these three proteins might be used as a promising multicomponent subunit vaccine candidate against S. equi infection.

BackgroundThis study aimed to assess the prevalence and causes of vision loss in sub-Saharan Africa (SSA) in 2015, compared with prior years, and to estimate expected values for 2020.MethodsA systematic review and meta-analysis assessed the prevalence of blindness (presenting distance visual acuity In SSA, age-standardised prevalence of blindness, MSVI and MVI in 2015 were 1.03% (80% uncertainty interval (UI) 0.39–1.81), 3.64% (80% UI 1.71–5.94) and 2.94% (80% UI 1.05–5.34), respectively, for male and 1.08% (80% UI 0.40–1.93), 3.84% (80% UI 1.72–6.37) and 3.06% (80% UI 1.07–5.61) for females, constituting a significant decrease since 2010 for both genders. There were an estimated 4.28 million blind individuals and 17.36 million individuals with MSVI; 101.08 million individuals were estimated to have near vision loss due to presbyopia. Cataract was the most common cause of blindness (40.1%), whereas undercorrected refractive error (URE) (48.5%) was the most common cause of MSVI. Sub-Saharan West Africa had the highest proportion of blindness compared with the other SSA subregions.ConclusionsCataract and URE, two of the major causes of blindness and vision impairment, are reversible with treatment and thus promising targets to alleviate vision impairment in SSA.

Cortical surface registration is an essential step and prerequisite for surface-based neuroimaging analysis. It aligns cortical surfaces across individuals and time points to establish cross-sectional and longitudinal cortical correspondences to facilitate neuroimaging studies. Though achieving good performance, available methods are either time consuming or not flexible to extend to multiple or high dimensional features. Considering the explosive availability of large-scale and multimodal brain MRI data, fast surface registration methods that can flexibly handle multimodal features are desired. In this study, we develop a Superfast Spherical Surface Registration (S3Reg) framework for the cerebral cortex. Leveraging an end-to-end unsupervised learning strategy, S3Reg offers great flexibility in the choice of input feature sets and output similarity measures for registration, and meanwhile reduces the registration time significantly. Specifically, we exploit the powerful learning capability of spherical Convolutional Neural Network (CNN) to directly learn the deformation fields in spherical space and implement diffeomorphic design with “scaling and squaring” layers to guarantee topology-preserving deformations. To handle the polar-distortion issue, we construct a novel spherical CNN model using three orthogonal Spherical U-Nets. Experiments are performed on two different datasets to align both adult and infant multimodal cortical features. Results demonstrate that our S3Reg shows superior or comparable performance with state-of-the-art methods, while improving the registration time from 1 min to 10 sec.

Anhedonia is common in individuals with traumatic experience. Anhedonia symptoms play an important role in posttraumatic psychopathology, and are related to various adverse outcomes. The current study is a preliminary neuroimaging study of the neural correlates of posttraumatic anhedonia symptoms. Resting-state fMRI data were acquired from 88 Chinese earthquake survivors. Whole brain analyses and exploratory ROI-to-ROI analyses were performed to examine the relationship between posttraumatic anhedonia symptoms and resting-state functional connectivity (rsFC) of reward-related subcortical nucleus including nucleus accumbens and ventral pallidum. The rsFC between left ventral pallidum and areas of bilateral posterior cingulate cortex (PCC) and precuneus cortex were found lower in the high posttraumatic anhedonia group, after controlling for sex, age and other posttraumatic stress symptoms. The rsFC between left ventral pallidum and PCC and the rsFC between left ventral pallidum and lateral parietal cortex were significantly lower in the high anhedonia group. Our findings suggest that decreased functional connectivity between the ventral pallidum and the brain default mode network (DMN) regions could be the neural correlates of posttraumatic anhedonia symptoms.

Background It is indicated that Low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C ratio) has greater predictive value for thickened carotid intima-media thickness (CIMT) comparing with classic lipid parameters. However, there have been few reports about their association in general Chinese population. Method We included a total of 1220 CIMT participants and 2440 matched controls, who had ultrasonography of carotid artery during 2009 and 2016. Univariate and multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for thickened CIMT risk associated with LDL-C/HDL-C ratio. Result In the univariate logistic regression model, there was significant association between LDL-C/HDL-C ratio and thickened CIMT (Q4 vs. Q1, OR = 1.94, 95% CI: 1.60–2.36; ptrend < 0.05). After adjusting for potential covariates, LDL-C/HDL-C ratio remained significantly associated with thickened CIMT (Q4 vs. Q1, OR = 1.81, 95% CI: 1.41–2.34, ptrend < 0.001; ≥3.05 v.s. trend 2) (OR = 2.22; 95% CI = 1.63-3.03; Ptrend < 0.05) and BMI ≥25 (kg/m2) (OR = 2.50, 95% CI: 1.76–3.54; Ptrend < 0.05), dyslipidemia (OR = 3.28, 95% CI: 1.83–5,85; Ptrend < 0.001), and without periodontitis (OR = 2.08, 95% CI: 1.54–2.81 ; Ptrend < 0.05) comparing Q4 to Q1. Similar results were observed in the subgroup analyses for LDL-C/HDL-C ratio ≥3.05 v.s. Conclusion High LDL-C/HDL-C ratio could significantly increase the risk of thickened CIMT independent of gender, IFG, hypertension, and fatty liver disease in general Chinese population.

Plant growth and development is usually characterized by chronological age over the plants’ lifetimes. Age-related changes actually originate with meristems because they control if, where, when, and how new tissues are formed along the axis of the shoot. The “time-keeping” of plant meristem development is a complex process. To uncover the post-transcriptional regulation underlying the chronological development of Larix kaempferi (Japanese larch) meristems, we investigated the miRNA-mediated regulatory network in the defoliated, uppermost main stems of 1-, 2-, 5-, 10-, 25-, and 50-year-old L. kaempferi using RNA-seq methods. We identified 29 high-confidence miRNAs, three of which were defined, age-related miRNAs whose expression changed depending on L. kaempferi age, and 17 showed coordinated expression patterns with three age-related miRNAs based on hierarchical correlations. All hierarchically coordinated miRNAs and their targets constituted a miRNA-mediated regulatory network. The developmental timing pathway lka-miR-1-5p-156-SBP/SPL (Squamosa Promoter Binding Protein-Like), the lignin biosynthesis pathway lka-miR-7,13-5p-397-LAC (Laccase), and an unknown pathway lka-miR-3-5p-CMSS1 (Cms1 Ribosomal Small Subunit Homolog) were age-driven, and information from auxin and light could be integrated by the lka-miR-9-5p-390-TAS/ARF (Trans-Acting siRNA3/Auxin Response Factor) and lka-miR-8-5p-IRL4 (Plant Intracellular Ras-Group-Related LRR Protein 4) pathways, respectively. Age-driven regulatory network will lead the way to understand which and how genes mutually cross-regulate their activity orchestrating development of meristems of L. kaempferi with age. We also discussed and contributed to miRNA annotation and nomenclature.

BACKGROUND: Primary school students are to grow experience and interact with others and environment, gradually developing personal views on their characteristics and abilities and establishing self-concepts. However, the existing primary education causes increased mental pressure on students. OBJECTIVE: Primary school students’ mental health and risk assessment are analyzed from physical and mental health to understand their response to math learning pressure. METHODS: Taken students in grades 4–6 as research objects, differences and relationships among students with different genders in math learning anxiety, mathematics self-efficacy, and sleep quality are investigated based on quantitative questionnaire data. RESULTS: The correlation coefficients between math anxiety and mathematics self-efficacy, between math anxiety and sleep quality, and between mathematics self-efficacy and sleep quality are –0.563, –0.673, and 0.403 in turn, with a marked correlation at the level of 0.01. Thus, the higher the math anxiety is, the lower the mathematics self-efficacy and sleep quality are; the higher the mathematics self-efficacy is, the better the sleep quality is. CONCLUSION: This study can provide data support to establish self-identity and develop good habits, reduce mental health risks, and provide strong support for mathematics education reform.

Human SETD2 is the unique histone methyltransferase that generates H3K36 trimethylation (H3K36me3), an epigenetic mark that plays a key role in normal hematopoiesis. Interestingly, recurrent inactivating mutations of SETD2 and aberrant H3K36me3 are increasingly reported to be involved in hematopoietic malignancies. Benzene (BZ) is a ubiquitous environmental pollutant and carcinogen that causes leukemia. The leukemogenic properties of BZ depend on its biotransformation in the bone marrow into oxidative metabolites, in particular 1,4-benzoquinone (BQ). This hematotoxic metabolite can form DNA and protein adducts that result in the damage and the alteration of cellular processes. Recent studies suggest that BZ-dependent leukemogenesis could depend on epigenetic perturbations, notably aberrant histone methylation. We investigated whether H3K36 trimethylation by SETD2 could be impacted by BZ and its hematotoxic metabolites. Herein, we show that BQ, the major leukemogenic metabolite of BZ, inhibits irreversibly the human histone methyltransferase SETD2, resulting in decreased H3K36me3. Our mechanistic studies further indicate that the BQ-dependent inactivation of SETD2 is due to covalent binding of BQ to reactive Zn-finger cysteines within the catalytic domain of the enzyme. The formation of these quinoprotein adducts results in loss of enzyme activity and protein crosslinks/oligomers. Experiments conducted in hematopoietic cells confirm that exposure to BQ results in the formation of SETD2 crosslinks/oligomers and concomitant loss of H3K36me3 in cells. Taken together, our data indicate that BQ, a major hematotoxic metabolite of BZ, could contribute to BZ-dependent leukemogenesis by perturbing the functions of SETD2, a histone lysine methyltransferase of hematopoietic relevance. SIGNIFICANCE STATEMENT: Benzoquinone is a major leukemogenic metabolite of benzene. Dysregulation of histone methyltransferase is involved in hematopoietic malignancies. This study found that benzoquinone irreversibly impairs SET domain containing 2, a histone H3K36 methyltransferase that plays a key role in hematopoiesis. Benzoquinone forms covalent adducts on Zn-finger cysteines within the catalytic site, leading to loss of activity, protein crosslinks/oligomers, and concomitant decrease of H3K36me3 histone mark. These data provide evidence that a leukemogenic metabolite of benzene can impair a key epigenetic enzyme.

Mathematics and science are highly integrated disciplines, but the brain association between mathematics and science remains unclear. The current study used functional magnetic resonance imaging (fMRI) scans of 34 undergraduates (17 males, mean age = 20.3±1.64 years old) while they completed mathematical, physical and chemical principles, arithmetic computation, and sentence comprehension. We examined neural activation level, neural activation pattern, and neural connectivity to investigate the neural associations between mathematics and science (including physics and chemistry). The results showed that mathematical, physical, and chemical principles elicited similar neural activation level and neural activation pattern in the visuospatial network (mainly in the middle frontal gyrus and inferior parietal lobule), which were different from those elicited by sentence comprehension; those three principles also elicited similar neural activation level and neural activation pattern in the semantic network (mainly in the middle temporal gyrus, angular gyrus, inferior frontal gyrus, and dorsomedial prefrontal cortex), in contrast to that elicited by arithmetic computation. Effective connectivity analyses showed stronger connectivity between the middle temporal gyrus and inferior parietal lobule for mathematical, physical, and chemical principles than for sentence comprehension. The results suggest that visuospatial and semantic networks were critical for processing both mathematics and science.

Propylea japonica has been regarded as one of the most remarkable natural enemies against aphid in China. However, the mechanism of juvenile hormone (JH) regulation of reproduction in P. japonica is still unclear. In this study, we investigated the JH titers of P. japonica and the development of the ovaries. We selected the six different developmental stages of ladybeetle females for transcriptome sequencing. We identified 583 genes involved in insect reproduction regulation, including 107 insect hormone synthesis signaling pathway-related genes and 476 nutrition-sensing signaling pathway-related genes. Transcriptome analysis indicated that a large number JH synthesis- and metabolism-related enzyme genes and some potential nutrient signal sensing- and transduction-related genes were significantly differentially expressed during P. japonica development. We investigated the effects of Met gene silencing on the reproduction of female adults and found that the ovarian maturation, vitellogenesis, and follicular epithelium development in the dsMet treatment group were significantly inhibited.

Background: Adipogenesis and fibrogenesis can be considered as a competitive process in muscle, which may affect the intramuscular fat deposition. The CCAAT/enhancer-binding protein beta (C/EBPβ) plays an important role in adipogenesis, which is well-characterized in mice, but little known in bovine so far. Results: In this study, real-time qPCR revealed that the level of C/EBPβ was increased during the developmental stages of bovine and adipogenesis process of preadipocytes. Overexpression of C/EBPβ promoted bovine fibroblast proliferation through mitotic clonal expansion (MCE), a necessary process for initiating adipogenesis, by significantly downregulating levels of p21 and p27 (p

Several immune checkpoint blockades (ICBs) capable of overcoming the immunosuppressive roles of the tumor immune microenvironment have been approved by the US Food and Drug Administration as front-line treatments of various tumor types. However, due to the considerable heterogeneity of solid tumor cells, inhibiting one target will only influence a portion of the tumor cells. One way to enhance the tumor-killing efficiency is to develop a multiagent therapeutic strategy targeting different aspects of tumor biology and the microenvironment to provide the maximal clinical benefit for patients with late-stage disease. One such strategy is the administration of anti-PD1, an ICB, in combination with the humanized monoclonal antibody bevacizumab, an anti-angiogenic therapy, to patients with recurrent/metastatic malignancies, including hepatocellular carcinoma, metastatic renal cell carcinoma, non-small cell lung cancer, and uterine cancer. Radiotherapy (RT), a critical component of solid cancer management, has the capacity to prime the immune system for an adaptive antitumor response. Here, we present an overview of the most recent published data in preclinical and clinical studies elucidating that RT could further potentiate the antitumor effects of immune checkpoint and angiogenesis dual blockade. In addition, we explore opportunities of triple combinational treatment, as well as discuss the challenges of validating biomarkers and the management of associated toxicity.

Purpose Evidence suggests that the oxytocin receptor (OXTR) gene may be involved in the psychopathology of posttraumatic stress disorder (PTSD). This study aimed to investigate the effects of OXTR rs53576 genotype on PTSD symptoms introduced in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5). Methods This study was a cross-sectional study conducted among 1140 adults who had personally experienced the Wenchuan earthquake. PTSD symptoms were measured with the PTSD checklist for DSM-5. A custom-by-design 2 × 48-Plex SNPscanTM Kit were used to determine the OXTR rs53576. Multiple regression models were used to analyze the independent and interactive effects of OXTR rs53576 genotype and earthquake exposure on the severity of total PTSD symptoms and different dimensions of PTSD symptoms. Results The results revealed that the rs53576 genotype could significantly predict PTSD symptoms (β = 0.055, p = 0.045). Further analysis showed that the rs53576 genotype was only significantly associated with dysphoric arousal symptoms of PTSD (β = 0.080, p = 0.005). The rs53576 genotype × earthquake exposure interaction had no significant effect on different symptom clusters (p > 0.05). Conclusion This study showed that the rs53576 genotype was only associated with the dysphoric arousal symptoms but not with other symptom clusters of PTSD. These findings support the role of the OXTR on the psychopathology of PTSD and help us to understand the genetic basis of PTSD.

Chromatin remodeler ALC1 (amplification in liver cancer 1) is crucial for repairing damaged DNA. It is autoinhibited and activated by nucleosomal epitopes. However, the mechanisms by which ALC1 is regulated remain unclear. Here we report the crystal structure of human ALC1 and the cryoEM structure bound to the nucleosome. The structure shows the macro domain of ALC1 binds to lobe 2 of the ATPase motor, sequestering two elements for nucleosome recognition, explaining the autoinhibition mechanism of the enzyme. The H4 tail competes with the macro domain for lobe 2-binding, explaining the requirement for this nucleosomal epitope for ALC1 activation. A dual-arginine-anchor motif of ALC1 recognizes the acidic pocket of the nucleosome, which is critical for chromatin remodeling in vitro. Together, our findings illustrate the structures of ALC1 and shed light on its regulation mechanisms, paving the way for the discovery of drugs targeting ALC1 for the treatment of cancer., The oncogenic chromatin remodeler ALC1 (amplification in liver cancer 1), also known as CHD1L is an ATP-dependent chromatin remodeler that relaxes chromatin and plays an important role in the poly(ADP-ribose) polymerase 1 -mediated DNA repair pathway. Here, the authors present the ALC1 crystal structure and a cryo-EM structure of ALC1 bound to a nucleosome, which reveal that ALC1 is autoinhibited and how it becomes activated.

Background The Spo0B-associated GTP-binding protein (Obg) GTPase, has diverse and important functions in bacteria, including morphological development, DNA replication and ribosome maturation. Homologs of the Bacillus subtilis Obg have been also found in chloroplast of Oryza sativa, but their primary roles remain unknown. Results We clarify that OsObgC1 is a functional homolog of AtObgC. The mutant obgc1-d1 exhibited hypersensitivity to the DNA replication inhibitor hydroxyurea. Quantitative PCR results showed that the ratio of chloroplast DNA to nuclear DNA in the mutants was higher than that of the wild-type plants. After DAPI staining, OsObgC1 mutants showed abnormal nucleoid architectures. The specific punctate staining pattern of OsObgC1-GFP signal suggests that this protein localizes to the chloroplast nucleoids. Furthermore, loss-of-function mutation in OsObgC1 led to a severe suppression of protein biosynthesis by affecting plastid rRNA processing. It was also demonstrated through rRNA profiling that plastid rRNA processing was decreased in obgc1-d mutants, which resulted in impaired ribosome biogenesis. The sucrose density gradient profiles revealed a defective chloroplast ribosome maturation of obgc1-d1 mutants. Conclusion Our findings here indicate that the OsObgC1 retains the evolutionarily biological conserved roles of prokaryotic Obg, which acts as a signaling hub that regulates DNA replication and ribosome biogenesis in chloroplast nucleoids.

In this study, the effect of microwave-ultrasound or/and toughening treatment on the physicochemical, structural properties, and in vitro digestibility of A- and B-type granules isolated from wheat starch were investigated. From the SEM, microwave-ultrasound and toughening treatment (MU-T) led to the appearance of irregular and disrupted structure significantly and an increment in the resistant starch content of A- and B-type granule. Furthermore, the MU-T starch possessed the lowest swelling power, light transmittance, and gelatinization temperature range (Tc -To) and the highest ΔH. After MU-T, the relative crystallinity (RC) of X-ray pattern, Fourier transform infrared ratio of 1047/1022 cm-1, and the content of double helix and single helix of 13C CP/MAS NMR had increased significantly. In particular, there was a difference in the content of RS and SDS between A-starch granules and B-starch granules as well as their changes after modification (from 69.305% to 82.93 for A-starch and form 74.97% to 88.17 for B-starch, respectively), which was a similar trend with RC and helix content. This study indicated that, for both A-type granule and B-type granule starches, microwave-ultrasound and toughening treated samples had unique properties compared to singly modified starches.

To develop and validate a machine learning classifier based on magnetic resonance imaging (MRI), for the preoperative prediction of tumor-infiltrating lymphocytes (TILs) in patients with pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, 156 patients with PDAC underwent MR scan and surgical resection. The expression of CD4, CD8 and CD20 was detected and quantified using immunohistochemistry, and TILs score was achieved by Cox regression model. All patients were divided into TILs score-low and TILs score-high groups. The least absolute shrinkage and selection operator method and the extreme gradient boosting (XGBoost) were used to select the features and to construct a prediction model. The performance of the models was assessed using the training cohort (116 patients) and the validation cohort (40 patients), and decision curve analysis (DCA) was applied for clinical use. The XGBoost prediction model showed good discrimination in the training (AUC 0.86; 95% CI 0.79–0.93) and validation sets (AUC 0.79; 95% CI 0.64–0.93). The sensitivity, specificity, and accuracy for the training set were 86.67%, 75.00%, and 0.81, respectively, whereas those for the validation set were 84.21%, 66.67%, and 0.75, respectively. Decision curve analysis indicated the clinical usefulness of the XGBoost classifier. The model constructed by XGBoost could predict PDAC TILs and may aid clinical decision making for immune therapy.

Aims Older patients with cardiovascular diseases (CVDs) are more likely to develop frailty. Few studies have investigated frailty status, and its multiple associated factors, in this population. The aim of the present study was to explore frailty status, and its multidimensional associated factors, in elderly inpatients with CVDs. Methods and results In this cross-sectional study, 1021 inpatients with CVDs aged ≥60 years old were recruited through convenience sampling from multiple hospitals in Suzhou, China. The FRAIL scale was used to assess frailty. A self-designed questionnaire gathered sociodemographic, clinical, and health-related information related to the physiological, psychological, and social dimensions of frailty. Among the 629 elderly inpatients with CVDs (73.64 ± 7.93 years old) who met inclusion criteria and completed the assessments, 176 (28.0%) were classified as frail. Univariate analyses demonstrated that the proportion of frailty was significantly associated with multiple factors. Logistic regression analysis indicated that, compared to their counterparts, the risk of frailty was higher in participants with cardiac function classes II, III, and IV [odds ratio (OR) = 1.866, 3.393, and 6.351, respectively]; average and bad mastication function (OR = 2.534 and 2.945, respectively); and often or always using walking aids (OR = 2.713). Conversely, the risk of frailty was lower in participants with good nutritional status (OR = 0.879) and regular exercise habits (OR = 0.573), as compared with their counterparts. Conclusion Frailty in elderly inpatients with CVDs is common and associated with multiple physiological factors including cardiac function, mastication function, nutritional status, use of walking aids, and regular exercise habits.

Emerging evidence indicates the early growth response 1 (Egr1) plays an important role in the pathogenesis of chronic pain. However, the regulation of Egr1 expression in the DRG and spinal cord in neuropathic pain remains unclear. In the current study, the neuropathic pain was conducted by lumber 5 spinal nerve ligation (SNL) in rats. The role of miR-124-3p in Egr1 expression was examined. Our results showed that the SNL led to a significant increase in the expression of Egr1 mRNA and protein in the DRG and dorsal horn. This increased expression of Egr1 correlated with a reduction of miR-124-3p in the same region. Prior i.t. injection of Egr1 decoy AYX1 inhibited the expression of Egr1 and attenuated the neuropathic pain-like hypersensitivity following SNL. The dual-luciferase reporter assay revealed the luciferase activity of the Egr1 3'-UTR plasmid was inhibited by the miR-124-3p agomir. But this inhibition was completely reversed in the mutant 3'-UTR Egr1 group. In vivo, the SNL-induced behavioral signs of neuropathic pain and the increases in Egr1 mRNA and protein in the DRG and dorsal horn were prevented by prior to i.t. injection of miR-124-3p agomir. While, i.t. injection of miR-124-3p antagomir in naïve rats resulted in mechanical allodynia and thermal hyperalgesia and an overexpression of Egr1 in the DRG and dorsal horn. Together, our results suggest that the miR-124-3p-regulated Egr1 expression in the DRG and dorsal horn contributes to the development of neuropathic pain. Targeting miR-124-3p might be a promising therapeutic strategy in the treatment of chronic pain.

Periodontal disease (PD) is one of the main causes of periodontal bone resorption and tooth loss in adults. How to repair the alveolar bone effectively has always been a challenge. This study was designed to clarify the effects and the underlying molecular mechanisms of chlorogenic acid (CGA) on osteogenic differentiation of human dental pulp stem cells (hDPSCs). In this study, we used CGA to treat hDPSCs. The osteogenic experiment showed that CGA can promote hDPSCs osteogenic differentiation. RNA-Seq and quantitative real-time polymerase chain reaction showed that CGA treatment enhanced the expression of the osteogenesis genes for frizzled-related protein

In the early December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, China, followed by an outbreak that spread around the world. Numerous studies have shown that liver injury is common in patients with coronavirus disease 2019 (COVID-19), and may aggravate the severity of the disease. However, the exact cause and specific mechanism of COVID-associated liver injury needs to be elucidated further. In this review, we present an analysis of the clinical features, potential mechanisms, and treatment strategies for liver injury associated with COVID-19. We hope that this review would benefit clinicians in devising better strategies for management of such patients.

This study used two waves of data from the Canadian Longitudinal Study on Aging (CLSA) to investigate the association between social participation and depressive symptoms in carer-employees (CEs) and non-carer-employees (NCEs).Adopting Pearlin et al.'s stress model, multivariate linear regression was used to examine the relationships among carer role, social participation, and depressive symptoms in Canadian employees using the first two waves of CLSA data, while controlling for possible confounders.Higher levels of social participation were found to be associated with lower depressive symptoms in both waves. Social participation was found to moderate depressive symptoms for CEs when compared with NCEs in Wave 2 but not in Wave 1.The present study highlights the importance of social participation in reducing CEs' depressive symptoms. The findings provide support for innovative policy and intervention efforts to encourage and enhance social participation at work via carer-friendly workplace policies for CEs across Canada.RéSUMé: OBJECTIFS: Cette étude a utilisé deux vagues de données de l’Étude longitudinale canadienne sur le vieillissement (ÉLCV) pour étudier l’association entre la participation sociale et les symptômes dépressifs chez les employés soignants (ES) et les employés non soignants (ENS). MéTHODES: Adoptant le concept du modèle de stress de Pearlin et al., une régression linéaire multivariée a été utilisée pour examiner les relations entre le rôle de l’aidant, la participation sociale et les symptômes dépressifs chez les employés canadiens en utilisant les deux premières vagues de données de l’ÉLCV, tout en contrôlant leurs facteurs de confusion. RéSULTATS: Des niveaux plus élevés de participation sociale se sont avérés être associés à des symptômes dépressifs plus faibles de façon constante dans les deux vagues. Au fil du temps, la participation s’est avérée modérer les symptômes dépressifs pour les ES par rapport aux ENS dans la vague 2 mais pas dans la vague 1. CONCLUSION: La présente étude souligne l’importance de la participation sociale en ce qui concerne l’atténuation des symptômes dépressifs des ES. Les résultats appuient les efforts politiques et d’intervention visant à encourager et à améliorer la participation sociale au travail des ES partout au Canada.

Background: We describe the first studies investigating a role for opiorphin genes ( PROL1, SMR3A and SMR3B) in prostate cancer (PrCa). Materials & methods: Databases and PrCa tissue arrays were screened for opiorphin expression. Xenografted tumor growth of human PrCa cells overexpressing PROL1 was compared with controls in nude mice. Modulated gene expression by overexpression of PROL1 was determined by RNA sequencing. Results: PrCa is associated with overexpression of opiorphin genes. Xenografted androgen-sensitive PrCa cells overexpressing PROL1 developed into tumors in castrated male mice (in contrast to parental cells). PROL1 overexpression modulates expression of genes in angiogenesis, steroid and hypoxic response pathways. Conclusions: Opiorphins promote the development of androgen-insensitive PrCa and activate pathways that potentially overcome the hypoxic barrier generated during tumor growth.

Background: Previous researches had not proposed any prediction models for occult lymph node metastasis (OLNM). Considering the occurrence of OLNM and the importance of OLNM management, we aimed to develop a nomogram to predict OLNM of patients with lung adenocarcinoma ≤2 cm. Methods: Characteristics of patients with lung adenocarcinoma of ≤2 cm diameter at the Peking Union Medical College Hospital were retrospectively reviewed. Univariate and multivariate logistic regressions were performed. A nomogram model was developed. The concordance index (C-index) and calibration and decision curves were used to evaluate the predictive ability. Results: A total of 473 patients were enrolled, with an OLNM incidence of 7.4%. Four factors were selected as risk factors. The model had a C-index of 0.932. Calibration and decision curves were determined. Conclusion: Patients with pure ground-glass opacity (pGGO) or noninvasive adenocarcinoma have significantly lower risk of OLNM. SUVmax, CEA, micropapillary and solid component were identified as independent risk factors. The nomogram model was effective in predicting OLNM preoperatively.

BACKGROUND Abnormal tuftelin 1 (TUFT1) has been reported in multiple cancers and exhibits oncogenic roles in tumor progression. However, limited data are available on the relationship between TUFT1 and hepatocellular carcinoma (HCC), and the exact biological mechanism of TUFT1 is still poorly understood in HCC. AIM To investigate TUFT1 expression in HCC and how interfering TUFT1 transcription affects HCC growth. METHODS TUFT1 in HCC and non-HCC tissues based on databases of the Cancer Genome Atlas and Oncomine were analyzed, and TUFT1 in human HCC tissues on microarray were detected by immunohistochemistry for clinicopathological features, overall survival, and disease-free survival. HCC cells were transfected with constructed vectors of TUFT1 that interfere or over-express TUFT1 for analyzing the biological behaviors of HCC cells. Proliferation, invasion, migration, and apoptosis of cells were detected by cell counting kit-8, scratch assay, transwell tests, and flow cytometry and confirmed by Western blotting, respectively. RESULTS Abnormal TUFT1 levels in databases expressed in HCC at messenger RNA (mRNA) level and HCC tissues were mainly located in cytoplasm and membrane. The level of TUFT1 expression in the HCC group was significantly higher (χ2 = 18.563, P < 0.001) than that in the non-cancerous group, closely related to clinical staging, size, vascular invasion of tumor, hepatitis B e-antigen positive, and ascites (P < 0.01) of HCC patients, and negatively to HCC patients' overall survival and disease-free survival (P < 0.001). After interfering with TUFT1 transcription at mRNA level in the MHCC-97H cells by the specific TUFT1-short hairpin RNA, cell proliferation, invasion, and metastasis were significantly inhibited with increasing apoptosis rate. In contrast, proliferation, invasion, and migration were significantly enhanced after over-expression of TUFT1 mRNA in Hep3B cells in vitro. CONCLUSION Oncogenic TUFT1 was associated with the progression of HCC and could be a potential molecular-target for inhibiting HCC growth.

Head and neck squamous cell carcinomas (HNSCCs) often present as local-regionally advanced disease at diagnosis, for which a current standard of care is x-ray–based radiation therapy, with or without chemotherapy. This approach provides effective local regional tumor control, but at the cost of acute and late toxicity that can worsen quality of life and contribute to mortality. For patients with human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (SCC) in particular, for whom the prognosis is generally favorable, de-escalation of the radiation dose to surrounding normal tissues without diminishing the radiation dose to tumors is desired to mitigate radiation-related toxic effects. Proton radiation therapy (PRT) may be an excellent de-escalation strategy because of its physical properties (that eliminate unnecessary radiation to surrounding tissues) and because of its biological properties (including tumor-specific variations in relative biological effectiveness [RBE] and linear energy transfer [LET]), in combination with concurrent systemic therapy. Early clinical evidence has shown that compared with x-ray–based radiation therapy, PRT offers comparable disease control with fewer and less severe treatment-related toxicities that can worsen the quality of life for patients with HNSCC. Herein, we review aspects of the biological basis of enhanced HNSCC cell response to proton versus x-ray irradiation in terms of radiation-induced gene and protein expression, DNA damage and repair, cell death, tumor immune responses, and radiosensitization of tumors.

Background Ral family is a member of Ras-like GTPase superfamily, which includes RalA and RalB. RalA/B play important roles in many cell biological functions, including cytoskeleton dynamics, cell division, membrane transport, gene expression and signal transduction. However, whether RalA/B involve into the mammalian oocyte meiosis is still unclear. This study aimed to explore the roles of RalA/B during mouse oocyte maturation. Results Our results showed that RalA/B expressed at all stages of oocyte maturation, and they were enriched at the spindle periphery area after meiosis resumption. The injection of RalA/B siRNAs into the oocytes significantly disturbed the polar body extrusion, indicating the essential roles of RalA/B for oocyte maturation. We observed that in the RalA/B knockdown oocytes the actin filament fluorescence intensity was significantly increased at the both cortex and cytoplasm, and the chromosomes were failed to locate near the cortex, indicating that RalA/B regulate actin dynamics for spindle migration in mouse oocytes. Moreover, we also found that the Golgi apparatus distribution at the spindle periphery was disturbed after RalA/B depletion. Conclusions In summary, our results indicated that RalA/B affect actin dynamics for chromosome positioning and Golgi apparatus distribution in mouse oocytes.

This article studies the effects of arthroscopic imaging treatment and clinical rehabilitation of knee sports injuries. Arthroscopy was used to perform meniscus trimming and resection for 40 patients with knee sports injuries. The ages of the patients ranged from 20 to 60 years old. All patients received routine rehabilitation training such as continuous passive motion of the knee joint, biofeedback of the lower limbs, and air pressure therapy of the lower limbs. In addition, the control group was given muscle strength training, and the training began after the patients received the quadriceps muscle strength test. The removal of the joint cavity and the joint debridement has achieved satisfactory treatment results. In the experiment, the test cases were divided into two groups, and the sensor test platform was used for signal collection. Normal activities can be resumed 2 weeks after the operation. After a follow-up of 6 to 24 months, the knee joint pain disappeared, the joint was free of swelling, and the knee function was normal up to 93%. Arthroscopic reconstruction of the anterior and posterior cruciate ligament joint repair/reconstruction of the medial and posterolateral ligament knots is safe and feasible for the treatment of multiple ligament injuries of the knee joint. It has the advantages of less trauma and quick recovery. Early postoperative systemic and standardized rehabilitation exercises can obtain good knee joint function.

Background Deoxynivalenol (DON) is a widespread mycotoxin that induces intestinal inflammation and oxidative stress in humans and animals. Resveratrol (RES) effectively exerts anti-inflammatory and antioxidant effects. However, the protective effects of RES on alleviating DON toxicity in piglets and the underlying mechanism remain unclear. Therefore, this study aimed to investigate the effect of RES on growth performance, gut health and the gut microbiota in DON-challenged piglets. A total of 64 weaned piglets [Duroc × (Landrace × Yorkshire), 21-d-old, 6.97 ± 0.10 kg body weight (BW)] were randomly allocated to 4 treatment groups (8 replicate pens per treatment, each pen containing 2 males; n = 16 per treatment) for 28 d. The piglets were fed a control diet (CON) or the CON diet supplemented with 300 mg RES/kg diet (RES group), 3.8 mg DON/kg diet (DON) or both (DON+RES) in a 2 × 2 factorial design. Results DON-challenged piglets fed the RES-supplemented diet had significantly decreased D-lactate concentrations and tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) mRNA and protein expression, and increased zonula occludens-1 (ZO-1) mRNA and protein expression compared with those of DON-challenged piglets fed the unsupplemented diet (P GCLC, GCLM, HO-1, SOD1 and NQO-1) and glutamate-cysteine-ligase modulatory subunit (GCLM) protein expression (P < 0.05). Moreover, RES supplementation significantly abrogated the increase in the proportion of TUNEL-positive cells and the protein expression of caspase3 in DON-challenged piglets (P Roseburia and butyrate concentrations, while decreasing the abundances of Bacteroides and unidentified-Enterobacteriaceae in DON-challenged piglets compared with DON-challenged piglets alone (P Conclusions RES supplementation improved gut health in DON-challenged piglets by strengthening intestinal barrier function, alleviating intestinal inflammation and oxidative damage, and positively modulating the gut microbiota. The protective effects of RES on gut health may be linked to increased Roseburia and butyrate concentrations, and decreased levels of Bacteroides and unidentified-Enterobacteriaceae.

Taraxacum kok‐saghyz Rodin (TKS) is an important potential alternative source of natural inulin and rubber production, which has great significance for the production of industrial products. In this study, we sequenced 58 wild TKS individuals collected from four different geography regions worldwide to elucidate the population structure, genetic diversity, and the patterns of evolution. Also, the first flowering time, crown diameter, morphological characteristics of leaf, and scape of all TKS individuals were measured and evaluated statistically. Phylogenetic analysis based on SNPs and cluster analysis based on agronomic traits showed that all 58 TKS individuals could be roughly divided into three distinct groups: (a) Zhaosu County in Xinjiang (population AB, including a few individuals from population C and D); (b) Tekes County in Xinjiang (population C); and (c) Tuzkol lake in Kazakhstan (population D). Population D exhibited a closer genetic relationship with population C compared with population AB. Genetic diversity analysis further revealed that population expansion from C and D to AB occurred, as well as gene flow between them. Additionally, some natural selection regions were identified in AB population. Function annotation of candidate genes identified in these regions revealed that they mainly participated in biological regulation processes, such as transporter activity, structural molecule activity, and molecular function regulator. We speculated that the genes identified in selective sweep regions may contribute to TKS adaptation to the Yili River Valley of Xinjiang. In general, this study provides new insights in clarifying population structure and genetic diversity analysis of TKS using SNP molecular markers and agronomic traits.

Osteoarthritis (OA) is the most prevalent joint disease and is one of the major causes of disability in the world. There has been an increase in the incidence of OA, which is associated with an aging population, sedentary lifestyle, and reduced physical activity. Due to the complex OA pathogenesis, there are limited diagnostic tools. OA is a degenerative joint disorder with a recognized inflammatory component, usually described as abnormal expression of inflammatory factors. For instance, interleukin 6 (IL‐6) has been shown to be upregulated in serum and synovial fluid among patients with OA. Most of the inflammatory factors have been associated with the expression of long noncoding RNAs (lncRNAs). However, the role of the novel lncRNA Fer-1-like protein 4 (FER1L4) in OA is yet to be determined. Here, we interrogated the expression profile of FER1L4 in patients with OA to define its potential application as a diagnostic marker. We collected synovial fluid and blood samples from both OA cases and normal controls. Using qRT-PCR, we evaluated the expression of FER1L4 in plasma and synovial fluid. On the other hand, the expression of IL-6 in plasma and synovial fluid was assessed using ELISA. Besides, the effect of age, gender or disease stage in the expression of the FER1L4 in plasma was also estimated. Moreover, the receiver operating characteristic (ROC) curves were used to determine the impact of FER1L4 in OA cases compared with the normal controls. In addition, we analyzed the correlation between FER1L4 and IL-6 through Pearson correlation analysis. Also, IL-6 expression in overexpressed FER1L4 samples was detected in chondrocytes through western blot analysis, while FER1L4 expression following endogenous IL-6 exposure was detected by qRT-PCR. Our data showed that whereas lncRNA FER1L4 is downregulated in OA patients, IL‐6 is upregulated. The plasma FER1L4 levels among the OA cases were suppressed with disease progression and old age, and the down-regulation could efficiently discriminate OA patients from normal subjects. In addition, upregulation of FER1L4 inhibited IL‐6 expression in human chondrocyte cells, and treatment with different concentrations of exogenous IL‐6 did not affect the expression of FER1L4. Taken together, our data demonstrates that FER1L4 could efficiently identify OA cases from normal subjects, and can also modulate the expression of IL‐6 in human chondrocytes.

Purpose This study was to explore the toxicological mechanisms by which PM2.5 causes lung dysfunction. Methods The expression of circ_0038467 and miR-138-1-3p in PM2.5-induced human bronchial epithelial cell line BEAS-2B was detected by RT-qPCR. The effects of circ_0038467 and miR-138-1-3p on proliferation, apoptosis, and inflammatory cytokines (IL-6 and IL-8) in PM2.5-induced BEAS-2B were determined using cell counting kit-8, flow cytometry, western blot, and enzyme-linked immunosorbent assay, respectively. The levels of nuclear factor kappa B (NF-κB) pathway-related protein were also analyzed by western blot. The binding interaction between circ_0038467 and miR-138-1-3p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay and pull-down assay. Results circ_0038467 expression was increased by PM2.5 treatment in BEAS-2B cells in time- and dose-dependent methods, and knockdown of circ_0038467 reversed PM2.5-triggered BEAS-2B cell death and inflammatory response. miR-138-1-3p was decreased by PM2.5 treatment, and restoration of miR-138-1-3p attenuated PM2.5-induced BEAS-2B cell injury. In a mechanical study, we found circ_0038467 directly bound to miR-138-1-3p, and further rescue experiments exhibited miR-138-1-3p inhibition partially overturned the regulatory functions of circ_0038467 knockdown in PM2.5-induced BEAS-2B cells. Conclusion circ_0038467 provided a potential therapeutic strategy for future clinic intervention in air pollution-triggered lung dysfunction.

PURPOSE: We aimed to determine if balanced crystalloids compared with saline improve outcomes in critically ill adults admitted with low plasma bicarbonate. MATERIALS AND METHODS: We performed a secondary analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). We included patients who presented to the Emergency Department with a first measured plasma bicarbonate less than 20mmol/L. Among these patients, we compared the effect of balanced crystalloid versus saline on the primary outcome of major adverse kidney events within 30 days (MAKE30), defined as a composite of death, new renal-replacement therapy, or persistent renal dysfunction (final inpatient creatinine ≥ 200% baseline). Secondary outcomes included 30 day in-hospital mortality, receipt of new RRT, persistent renal dysfunction, incident AKI, and vasopressor-free days. RESULTS: Among the 2029 patients with an initial plasma bicarbonate concentration < 20 mmol/L, there was no difference in the incidence of MAKE30 between those assigned to balanced crystalloid versus saline (21.8% vs 21.3%; P = 0.93). Secondary outcomes were similar between the balanced crystalloid and saline groups. CONCLUSIONS: Among critically ill adults presenting to the Emergency Department, initial plasma bicarbonate concentration does not appear to be a useful marker to guide the selection of balanced crystalloid versus saline.

Background:. The impacts of previous cardio-cerebrovascular disease (pre-CCVD) on the outcomes of hematopoietic cell transplantation (HCT) are not well described. Patients with pre-CCVD may often be poor candidates for HCT. This study aimed to investigate the impact of pre-CCVD on transplant outcomes. Methods:. A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status. The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared. The primary endpoints were post-transplant cardio-cerebrovascular disease (post-CCVD) and non-relapse mortality (NRM). We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios (HRs). Results:. The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group. No significant differences were noted in terms of engraftment, overall survival (OS) (67.00% vs. 67.90%, P = 0.983), or relapse (29.78% vs. 28.26%, P = 0.561) between the pre-CCVD group and the control group. The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls (14.68% vs. 17.08%, P = 0.670). However, pre-CCVD was associated with an increased incidence of post-CCVD (HR: 12.50, 95% confidence interval [CI]: 3.88–40.30, P

The exploration of modified luffa sponge (LS) cellulose fiber in the field of polymer composite can contribute to the development of high-performance and lightweight composites. In this study, two chemical treatments (10%NaOH–20%CH3COOH (Method 1) and 10%NaOH–5%Na2SO3 (Method 2)) and two drying methods (air drying and freeze-drying) were used to treat LS. The microscopic characteristics and physical properties showed that Methods 1 and 2 caused shrinkage of the LS fibers and increased their fiber density by 30.6% and 15.0%. Meanwhile, freeze-drying kept the cells of modified LS fibers full and decreased their fiber density by 5.0% and 21.0%, respectively. The tensile properties test analyses indicated that freeze-drying further increased the elongation at break values of modified LS fibers by 25.3% and 17.7%, respectively. The moisture absorption analyses showed that freeze-drying could further decrease the moisture absorption ratios of modified LS fibers by 25.8% and 35.8%, respectively, which was useful for improving the dimensional stability of composite materials. Moreover, the thermogravimetric analysis reveals that freeze-drying increased onset degradation temperatures of the modified fibers by 24.0 °C and 6.7 °C, which was beneficial to improve the thermal stability of the composite material.

Presently, there have been some limitations in most of methods to determine poly (γ-glutamic acid) (γ-PGA) content because of many impurities in test specimens. It is necessary to establish a rapid and accurate method to quantify γ-PGA content. In this work, γ-PGA and some impurities commonly seen in fermented broth like glucose, glutamic acid and proteins were used to complex with copper ions. The results show that only γ-PGA can make copper ion precipitated, which content linearly correlates with the precipitate amount. From the study on the validity of the method, it is found that the accuracy and precision are 95.82% and 99.29%, much higher than the ones of method UV and weighing. Therefore, the method via the complexation of copper ion will be popularized to determine γ-PGA content in crude biological samples.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has spread rapidly around the world, with substantial mortality, since December 2019. To date, the relevant treatments to contain the disease include not only antiviral medications, antibacterial medications, steroids and human immunoglobulin, but Chinese herbal medicines (CHM) showing promise. CHM, recommended in national treatment guidelines in China, has been used to treat patients with COVID-19 effectively in clinic. Although, respiratory tract manifestations such as fever and cough are the most commonly reported symptoms in patients with COVID-19, digestive symptoms and liver injury are not uncommon in patients with COVID-19. Emerging data showed that the gastrointestinal tract and liver also represent target organs of SARS-CoV-2 on the basis of the findings that angiotensin-converting enzyme 2 (ACE2), the major receptor of SARS-CoV-2, is expressed in the gastrointestinal tract as well as liver cells.However, to the best of our knowledge, CHM as an adjuvant medicine for improving gastrointestinal symptoms and liver functions in COVID-19 has not been well studied with definitive results by the evidence assessment. Although the use of CHM shows promise, the evidence supporting its use in the treatment of COVID-19 remains limited, and thus our systematic review and meta‐analysis are necessary. We will conduct a systematic review and meta-analysis of emerging studies reporting gastrointestinal symptoms and liver function in COVID-19 patients treated with CHM plus conventional pharmacotherapy. A systematic literature search of the PubMed, ScienceDirect, Web of science, Scopus, Google Scholar, WorldCat Dissertations database and Index to Theses, PsycINFO, ProQuest, the Chinese National Knowledge Infrastructure, the VIP Information Database, and the Wanfang Database was conducted on November 8, 2020 (updated February 9, 2021) for relevant articles including accepted pre-proof publications in the last 1 year, to identify the latest information on COVID-19. The following grouped terms were used as search strategy and modified to suit each database to screen publications that might be valuable for the present review: (“coronavirus disease 2019” OR “COVID-19” OR “severe acute respiratory syndrome coronavirus 2” OR “SARS-CoV-2” OR “coronavirus” OR “novel coronavirus” OR “nCoV” OR “2019-nCoV”) AND (“Medicine, Chinese Traditional’ OR “Traditional Medicine, Chinese” OR “Chinese herbal medicine” OR “traditional Chinese medicine” OR “Chinese Traditional Medicine” OR “Chinese Medicine, Traditional” OR “Chinese medicine formulae“ OR “Chinese medicine formulations” OR “Chinese herb” OR “Chinese herb therapy” OR “herbal medicine” OR “herb remedy” OR “herb therapy” OR “Zhong Yi Xue” OR “Chung I Hsueh” OR “Hsueh, Chung I”). Given the urgency of treating COVID-19, a grey literature search was also performed. Furthermore, COVID-19 articles in the WHO database and some key journals in this field including New England Journal of Medicine, BMJ, the Lancet COVID-19 Resource Centre and JAMA were searched manually for potentially relevant publications. Additional articles were retrieved by hand based on the reference lists of relevant papers.