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Background: Environmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear. Methods: All eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS). Results: Blood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861 L decline in FVC, 0.648 L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively. Conclusion: Blood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.

A statistical shape model (SSM) based analysis was conducted in our study. We indicated the morphological differences of the first trapezoid-metacarpal (TMC) bone between the region-based statistical shape model (rSSM) and the nonregion-based statistical shape model (nrSSM). We aimed to characterize more specific and accurate variation results to detect and prevent osteoarthritis in an early way. CT image data of TMC from 31 healthy volunteers were simulated with 3D models. A training set of models was analyzed with principal component analysis, with both then- rSSM and rSSM. The region was identified automatically with Gaussian curvature analysis. We found four dominant shape variations from both nrSSM and rSSM. The rSSM showed more variations with fewer components compared with nrSSM. The first principal component revealed the size variation as the biggest component. A significant difference was presented in the second and the fourth principal component from rSSM, showing the torsion of the distal head of the first metacarpal which may increase the risk of osteoarthritis.

BackgroundA few studies found that the complement system may be involved in the onset and progression of community-acquired pneumonia (CAP). However, the role of the complement system in CAP was obscure. The goal of this study was to analyze the association of serum complement C3a with CAP severity scores based on a cross-sectional study.MethodsAll 190 CAP patients and 95 control subjects were enrolled. Demographic information and clinical data were extracted. Peripheral blood samples were collected on admission.ResultsSerum complement C3a on admission was elevated in CAP patients compared with healthy subjects. The level of complement C3a was gradually elevated in parallel with CAP severity scores (CURB-65, CRB-65, PSI, SMART-COP, and CURXO). Complement C3a was positively correlated with blood routine parameters, renal function markers, and inflammatory cytokines in CAP patients. Furthermore, multivariate linear and logistic regression models found that serum complement C3a on admission was positively associated with CAP severity scores. Mechanistic research suggested that complement system inhibition alleviated Streptococcus pneumoniae-induced upregulation of IL-1β, TNF-α, IL-6, and CRP in MLE-12 cells.ConclusionsSerum complement C3a on admission is positively associated with the severity of CAP patients. Inhibiting complement system attenuates S. pneumoniae-elevated secretion of inflammatory cytokines in pulmonary epithelial cells, indicating that complement C3a is involved in the pathophysiology of CAP. Serum complement C3a may serve as an earlier diagnostic biomarker for CAP.

Materials for the selective transport of K+ have application in a variety of fields including water desalination and separation processes. Here the authors report charged porous subnanometer cages that are inspired in biological KcsA channels; high K+ transport rates and high K+/Li+ and K+/Na+ selectivity ratios are obtained, showing great potential in advanced sieving processes and efficient water treatments.

Abstract A Li/KNO3 composite (LKNO), with KNO3 uniformly implanted in bulk metallic Li, is fabricated for battery anode via a facile mechanical kneading approach, which exhibits high Coulombic efficiency and prolonged cycle life. The mechanism behind the enhanced electrochemical performance of the “salt‐in‐metal” composite is investigated, where KNO3 in metallic Li composite electrode would be sustainably released into the electrolyte. The presence of NO3– stabilizes the solid electrolyte interphase by producing functional Li3N, LiNxOy, and Li2O species. K+ from KNO3 also helps to form an electrostatic shield after its adsorption on the electrode protrusions, which suppresses the dendritic growth of metallic Li. With the above advantages, uniform Li plating with dense and planar structure is realized for the LKNO electrode. These findings reveal a deep understanding of the effect of the “salt‐in‐metal” anode and provide new insights into the use of nitrate additives for high‐energy‐density Li metal batteries.

Abstract Background Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study. Methods All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II. Results Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively. Conclusions Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.

Given few reports on the interaction of miRNA-665/target gene pair, we aimed to construct a dual luciferase reporter gene vector for 3"-untranslated region (3"-UTR) of the haematopoietic prostaglandin D synthase (HPGDS) gene and elucidate the underlying molecular mechanism of miR-665 regulation of HPGDS. Bioinformatics software was used to predict miR-665 targeting of 3"-UTR region of HPGDS gene. The reliability of the synthetic psiCHECK-HPGDS-w/m-3"-UTR was determined using double luciferase digestion method. Then, miR-665 mimic/negative control was separately co-transfected with sheep luteal cells, and then, luciferase activity and HPGDS expression were detected. Results showed that 3"-UTR wild-type (psiCHECK2-HPGDS-w-3"UTR) and mutant (psiCHECK2-HPGDS-m-3"UTR) expression vectors for HPGDS were successfully constructed, and dual luciferase reporter gene assay showed that the expression of relative luciferase activity was inhibited in the w-3"-UTR group, with 52% decrease compared to the blank/negative control group, and the difference was statistically significant (P

With the increasing awareness of the risks and impacts of climate change, scholars tend to pay more attention to the applications of indicators, which access the effectiveness of climate change adaptation. This study aims to evaluate the overall progress of climate change adaptation in China during 2010–2018 in a quantitative manner. The Index for Climate Change Adaptation in China (ICCAC) has been thus developed by adopting the analytic hierarchy process weighting and expert scoring method. Namely, ICCAC is composed of national climate change impacts, adaptation actions in key sectors, adaptation progress in key sectors, and the national adaptation policy framework. Overall, the ICCAC and its four sub-indexes increased significantly from 2010 to 2018, on a yearly-basis. Each sub-index implied that the socio-economic impacts caused by climate change in China have been alleviated gradually; specifically, the mainstream endeavor of key sectors has witnessed remarkable progress, however, it is worth noting that the gap between individual adaptation actions and policies still exists; the implementation effect of policies in key sectors is not as affluent as that of actions; the current adaptation endeavor in key areas is still closely related to the mainstream business of corresponding competent ministries rather than adaptation-aimed actions; the national adaptation policy framework has been primarily formed, but there are still some deficiencies. As a result, the gap in China's adaptation process could be mainly manifested in the following five aspects: i) adaptation effectiveness assessment in forestry and urban infrastructure is urgently needed; ii) policies in marine and water resources sectors need structural reforms; iii) evaluation criteria for national adaptation are not necessarily sufficient; iv) the improvement of adaptive management efficiency has stagnated recently; and v) the adaptation works of relevant Ministries should be coordinated and put forward the corresponding strategies. Finally, this study presents four proposals: conducting an evaluation of adaptation actions in all key sectors, integrating climate change impacts into sectoral planning decisions, launching concrete action plans for adaptation, establishing a complete policy framework on adaptation.

AIM: To investigate the safety and efficacy of phacoemulsification with capsular-tension-ring implantation and posterior chamber intraocular lens implantation combined with ophthalmic endoscope-controlled goniosynechialysis (Phaco-CTR-IOL-OE-GSL) for treating secondary angle-closure glaucoma induced by traumatic lens subluxation. METHODS: A retrospective and descriptive study was performed on patients with lens subluxation, angle closure, goniosynechia, and evaluated intraocular pressure (IOP) that cannot be controlled with medication, who underwent Phaco-CTR-IOL-OE-GSL. The postoperative best-corrected visual acuity (BCVA), IOP, range of goniosynechia and complications were retrospectively observed. RESULTS: Nine patients with secondary angle-closure glaucoma induced by traumatic lens subluxation were included. The follow-up period was 51.1±8.6mo. The preoperative range of zonule rupture was 158.2°±33.0°, and the range of goniosynechia was 220.0°±92.5°. The baseline BCVA was 0.9±1.0 logMAR, IOP was 30.7±17.3 mm Hg, and number of anti-glaucoma medication was 3.2±1.1. Mild intraoperative hyphaemia with 8 eyes (88.8%) in the anterior chamber, and was absorbed two days postoperatively. One eye (11.1%) had postoperative ciliary body detachment and was recovered after five days of topical drug treatment. BCVA was 0.2±0.2 logMAR at 3mo postoperatively. The average IOP at the last follow-up was 16.7±2.0 mm Hg, and no anti-glaucoma medications were used. The average range of recurrent goniosynechia was 54.9°±33° at the final postoperative gonioscopic examination. CONCLUSION: Phaco-CTR-IOL-OE-GSL is safe and effective in the treatment of secondary angle-closure glaucoma induced by traumatic lens subluxation. The use of an endoscope provides a more direct and clear examination for GSL, and 360° dissection is easily achieved.

The development of coagulation factor VIII (FVIII) inhibitory antibodies is a serious complication in hemophilia A (HA) patients after FVIII replacement therapy. Inhibitors render regular prophylaxis ineffective and increase the risk of morbidity and mortality. Immune tolerance induction (ITI) regimens have become the only clinically proven therapy for eradicating these inhibitors. However, this is a lengthy and costly strategy. For HA patients with high titer inhibitors, bypassing or new hemostatic agents must be used in clinical prophylaxis due to the ineffective ITI regimens. Since multiple genetic and environmental factors are involved in the pathogenesis of inhibitor generation, understanding the mechanisms by which inhibitors develop could help identify critical targets that can be exploited to prevent or eradicate inhibitors. In this review, we provide a comprehensive overview of the recent advances related to mechanistic insights into anti-FVIII antibody development and discuss novel therapeutic approaches for HA patients with inhibitors.

In order to study the effect of the symmetry error generated by processing on the herringbone character gear meshing transmission， improve the stability of the transmission， according to the structural characteristics of herringbone gear and gear geometry contact model， consider the tooth surface gap， force equilibrium conditions and axial displacement， the herringbone gear bearing contact analysis model of symmetry error is established. The influence of different symmetry error on the gear contact and axial vibration of a pair of herringbone gear is analyzed， and then a compensation method that uses coupling effect of axial assembling error and symmetry error is put forward. The research result shows that symmetry error seriously reduces the stability and reliability of herringbone gear transmission. The error coupling compensation can lower partial loaded and axial vibration caused by symmetry error which provides new methods for the optimization of transmission process and is of greatly significant to improve the dynamic characteristics of herringbone gear system.

Abstract Lightning strike is one of the natural disasters to the roof components of ancient buildings. To investigate the causes and damage effects of lightning strikes on the roofing glazed tiles of ancient buildings, artificial lightning strike tests were carried out on glazed tiles. Based on the experiment results, a coupled electrical–thermal finite element model of mortar-containing glazed tiles was established and the Joule heat effect of lightning current was further investigated. The results show that when the lightning channel is attached to the surface of the enamel and body with a low electrical conductivity, the lightning current is mainly released in the form of surface flashover, and a minor damage is induced along the flashover path; when the lightning channel is attached to the mortar with a high electrical conductivity, the lightning current is injected into the mortar, resulting in significant tile damage. The spatial distributions of the temperature present clear gradient characteristics. The high-temperature area appears in the mortar while the high–thermal–stress area appears in the body connected to the grounding rail. As the peak of the lightning current increases, both the high-temperature and high–thermal–stress areas of the glazed tiles expand. The combination of the experiments and the numerical analysis results demonstrate that the damage mechanism of lightning Joule heat effect to glazed tiles may include two aspects. One is the internal explosive force generated from the sharp vaporization and expansion of the moisture inside the tiles due to rapid temperature increase, and the other is the thermal stress caused by the uneven temperature distribution.

Abstract Background The high degree of heterogeneity brought great challenges to the diagnosis and treatment of acute myeloid leukemia (AML). Although several different AML prognostic scoring models have been proposed to assess the prognosis of patients, the accuracy still needs to be improved. As important components of the tumor microenvironment, immune cells played important roles in the physiological functions of tumors and had certain research value. Therefore, whether the tumor immune microenvironment (TIME) can be used to assess the prognosis of AML aroused our great interest. Methods The patients’ gene expression profile from 7 GEO databases was normalized after removing the batch effect. TIME cell components were explored through Xcell tools and then hierarchically clustered to establish TIME classification. Subsequently, a prognostic model was established by Lasso-Cox. Multiple GEO databases and the Cancer Genome Atlas dataset were employed to validate the prognostic performance of the model. Receiver operating characteristic (ROC) and the concordance index (C-index) were utilized to assess the prognostic efficacy. Results After analyzing the composition of TIME cells in AML, we found infiltration of ten types of cells with prognostic significance. Then using hierarchical clustering methods, we established a TIME classification system, which clustered all patients into three groups with distinct prognostic characteristics. Using the differential genes between the first and third groups in the TIME classification, we constructed a 121-gene prognostic model. The model successfully divided 1229 patients into the low and high groups which had obvious differences in prognosis. The high group with shorter overall survival had more patients older than 60 years and more poor-risk patients (both P

The visualization of flood disasters in virtual reality (VR) scenes is useful for the representation and sharing of disaster knowledge and can effectively improve users’ cognitive efficiency in comprehending disaster information. However, the existing VR methods of visualizing flood disaster scenes have some shortcomings, such as low rendering efficiency and poor user experience. In this paper, a tunnel vision optimization method for VR flood scenes based on Gaussian blur is proposed. The key techniques are studied, such as region of interest (ROI) calculation and tunnel vision optimization considering the characteristics of the human visual system. A prototype system has been developed and used to carry out an experimental case analysis. The experimental results show that the number of triangles drawn in a flood VR scene is reduced by approximately 30%–40% using this method and that the average frame rate is stable at approximately 90 frames per second (fps), significantly improving the efficiency of scene rendering and reducing motion sickness.

Clinical infections arise from multidrug-resistant bacteria and pose a serious threat to human and global public health. Moreover, due to very few antibiotics being discovered, there is an urgent need to develop new antibacterial agents to combat antimicrobial resistance challenges. In this study, a series of new chalcone derivatives bearing a 3′-hydroxyisoprenyl moiety were prepared to employ Claisen–Schmidt condensation as a key step by combinatorial chemistry, and overall yields of these novel derivatives are in the range of 28–68% in the two-step reaction. Sanjuanolide and the synthesized derivatives have been investigated for their expected antibacterial activities against Gram-positive bacteria (Staphylococcus aureus CMCC 26003) and Gram-negative bacteria (Escherichia coli CMCC 44102). Among these compounds, only 4c (MIC = 12.5 μg/ml) and 4d (MIC = 25 μg/ml) exhibited antibacterial activity comparable to sanjuanolide (MIC = 12.5 μg/ml, against S. aureus CMCC 26003), and the results of subsequent in vivo experiments on sanjuanolide suggest that sanjuanolide exhibits bacteriostatic and bactericidal effects by altering the cellular structure, disrupting the integrity of cell membranes, and reducing the outer membrane potential.

BackgroundCysteine-rich 61 (CYR61) is implicated in many pulmonary diseases. However, the relationship between CYR61 and community-acquired pneumonia (CAP) patients was unknown. This research aimed to estimate the correlations of serum CYR61 with severity and prognosis in CAP patients through a prospective cohort study.MethodsAll 541 CAP patients were enrolled in this study. Fasting venous blood was collected. Clinical characteristics and demographic information were obtained. CYR61 and inflammatory cytokines were detected in serum using ELISA.ResultsSerum CYR61 was gradually increased in parallel with severity scores in CAP patients. Correlative analysis indicated that serum CYR61 was strongly associated with many clinical parameters in CAP patients. Moreover, mixed logistic and linear regression models found that there were positive correlations between serum CYR61 and CAP severity scores after adjusted for age, BMI, and respiratory rate. Stratified analyses suggested that age affected the associations between serum CYR61 and severity scores. On admission, higher serum CYR61 levels elevated the risks of mechanical ventilation, vasoactive agent, ICU admission, death, and longer hospital stays during hospitalization. Moreover, serum CYR61 in combination with severity scores upregulated the predictive capacities for severity and death than single serum CYR61 or severity scores in CAP patients.ConclusionThere are significantly positive dose-response associations of serum CYR61 on admission with the severity and adverse prognostic outcomes, demonstrating that CYR61 is involved in the pathophysiology of CAP. Serum CYR61 may be used as a potential biomarker for the diagnosis and prognosis in CAP patients.

Apple fruits are susceptible to infection by postharvest fungal pathogens, which may cause fruit decay and severe economic losses. This study investigated the antifungal spectrum of vanillin against common decay pathogens of apple and explored the antifungal mechanisms of vanillin in vitro. In vivo experiments were carried out to evaluate the effects of vanillin on apple postharvest disease control and fruit quality. Moreover, the induced resistance mechanism of vanillin on apple fruit was preliminarily explored. The results showed that vanillin has broad-spectrum antifungal effects, especially on Alternaria alternata. Vanillin could significantly inhibit the growth rate, mycelium biomass, and spore germination of pathogenic fungi by increasing the cell membrane permeability and lipid peroxidation. Importantly, vanillin treatment reduced the incidence of apple decay caused by A. alternata and Penicillium expansum, and contributed to improve fruit quality. Further studies indicated that vanillin could induce elevation in the activities of defense-related enzymes in apple fruit, such as phenylalanine ammonia-lyase (PAL), chitinase (CHI) and β-1,3-glucanase (β-1,3-GA), and increase total phenols and flavonoids contents. Generally, these results suggest that vanillin may contribute to the induced resistance of apple fruits to pathogenic fungi. To conclude, the results of this research provide theoretical foundations for the application of vanillin in the control of apple postharvest decay caused by fungal pathogens.

The rapid spread of capitalism in rural areas has facilitated rural land commodification (RLC). While some scholars have studied RLC, few have analyzed its spatial characteristics. Taking Shijiazhuang city as a study area, this paper applies Moran’s I method and spatial regression models to analyze township-scale RLC patterns and driving factors. The study investigates four common pathways of RLC: production-oriented farmland, tourism-oriented farmland, rural homesteads, and construction land commodification which are predominantly found in urban fringe areas. The distribution of RLC demonstrates positive spatial autocorrelation, characterized by spatial aggregation and polarization. Population, economic level, agriculture, and location conditions are identified as key drivers, and their specific mechanisms vary across development pathways. Future efforts should focus on ensuring balanced and coordinated RLC development in accordance with regional conditions and capacity, while also addressing the implications arising from the coexistence of RLC with rural aging and poverty.

OTUD5 (OTU Deubiquitinase 5) is a functional cysteine protease with deubiquitinase activity and is a member of the ovarian tumor protease (OTU) family. OTUD5 is involved in the deubiquitination of many key proteins in various cellular signaling pathways and plays an important role in maintaining normal human development and physiological functions. Its dysfunction can affect physiological processes, such as immunity and DNA damage repair, and it can even lead to tumors, inflammatory diseases and genetic disorders. Therefore, the regulation of OTUD5 activity and expression has become a hot topic of research. A comprehensive understanding of the regulatory mechanisms of OTUD5 and its use as a therapeutic target for diseases is of great value. Herein, we review the physiological processes and molecular mechanisms of OTUD5 regulation, outline the specific regulatory processes of OTUD5 activity and expression, and link OTUD5 to diseases from the perspective of studies on signaling pathways, molecular interactions, DNA damage repair and immune regulation, thus providing a theoretical basis for future studies.

Perovskites with nano-flexible texture structures and excellent catalytic properties have attracted considerable attention for persulfate activation in addressing the organic pollutants in water. In this study, highly crystalline nano-sized LaFeO3 was synthesized by a non-aqueous benzyl alcohol (BA) route. Under optimal conditions, an 83.9% tetracycline (TC) degradation and 54.3% mineralization were achieved at 120 min by using a coupled persulfate/photocatalytic process. Especially compared to LaFeO3-CA (synthesized by a citric acid complexation route), the pseudo-first-order reaction rate constant increased by 1.8 times. We attribute this good degradation performance to the highly specific surface area and small crystallite size of the obtained materials. In this study, we also investigated the effects of some key reaction parameters. Then, the catalyst stability and toxicity tests were also discussed. The surface sulfate radicals were identified as the major reactive species during the oxidation process. This study provided a new insight into nano-constructing a novel perovskite catalyst for the removal of tetracycline in water.

Abstract Background Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis. Methods The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily. Results BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA. Conclusions These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.

Preventing phosphorylation of BAD (3SA) in mouse models and human cells inhibits mammary gland development, acting by disrupting 4E-BP1- mediated translation and affecting focal adhesion/protrusion stability, cell migration and ductal tubulogenesis.

Abstract Background The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML). Methods We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients. Results FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT 3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 109/L vs. 24.2 × 109/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3 wtAML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup. Conclusions Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.

Abstract Background Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study. Methods A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured. Results Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients. Conclusion Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.

BackgroundFour-hydroxynonenal (4-HNE) exerts a central role in the pathophysiological process of pulmonary diseases. The aim of this project was to evaluate the correlations between serum 4-HNE with severity and prognosis in patients with community-acquired pneumonia (CAP) by a prospective cohort study.Materials and MethodsA total of 239 patients with CAP and healthy volunteers were recruited. Fasting blood was collected. Serum 4-HNE was measured with ELISA. Clinical characteristics and demographic information were obtained. The relationships between serum 4-HNE and clinical characteristics were evaluated through the Spearman or Pearson correlation coefficient. The associations of serum 4-HNE with severity and prognosis were estimated through logistic regression analysis.ResultsOn admission, serum 4-HNE was upregulated in patients with CAP compared with healthy volunteers. Serum 4-HNE was gradually increased in line with CAP scores. Additionally, elderly patients with CAP were more prone to suffer from 4-HNE elevation. Moreover, serum 4-HNE was positively correlated with CAP severity scores. Meanwhile, the poor prognostic outcomes were tracked among patients with CAP. Higher serum 4-HNE on admission increased the risks of mechanical ventilation, vasoactive agent usage, and death in patients with CAP during hospitalization. The predictive powers for severity and death were increased in serum 4-HNE compared with CAP severity scores and inflammatory cytokines.ConclusionSerum 4-HNE on admission is positively correlated with the severity and poor prognosis among patients with CAP, indicating that 4-HNE participates in the pathophysiology of CAP. Serum 4-HNE may be used as an earlier biomarker for diagnosis and prognosis in patients with CAP.

The goal of this study was to analyze whether mitochondria-associated endoplasmic reticulum membrane (MAMs) dysfunction mediated arsenic (As)-evoked pulmonary ferroptosis and acute lung injury (ALI). As exposure led to alveolar structure damage, inflammatory cell infiltration and pulmonary function decline in mice. Ferritin, the marker of iron overload, was increased, GPX4, the index of lipid peroxidation, was decreased in As-exposed lungs and pulmonary epithelial cells (MLE-12). Pretreatment with ferrostatin-1 (Fer-1), the inhibitor of ferroptosis, alleviated As-evoked ALI. In addition, As-induced non-heme iron deposition was inhibited in Fer-1 pretreated-mice. Moreover, As-triggered mitochondria damage and ferroptosis were mitigated in Fer-1 pretreated-MLE-12 cells. Mechanistically, PERK phosphorylation and mitofusin-2 (Mfn-2) reduction was observed in As-exposed MLE-12 cells and mice lungs. Additionally, the interaction between PERK and Mfn-2 was downregulated and MAMs dysfunction was observed in As-exposed MLE-12 cells. Intriguingly, PERK inhibitor and Mfn-2-overexpression all mitigated As-induced ferroptosis in MLE-12 cells. Additionally, CLPP and mtHSP70, the markers of mitochondrial stress, were upregulated, mitochondrial ROS (mtROS) was elevated, mitochondrial membrane potential (MMP) and ATP were decreased in As-exposed MLE-12 cells. Mitoquinone mesylate (MitoQ), a novel mitochondrial-targeted antioxidant, alleviated As-induced excess mtROS, mitochondrial stress, MAMs dysfunction in pulmonary epithelial cells. Similarly, in vivo experiments indicated that MitoQ pretreatment countered As-induced pulmonary ferroptosis and ALI. These data indicated that mtROS-initiated MAMs dysfunction is, at least partially, implicated in As-evoked ferroptosis and ALI.

Abstract. Introduction:. Diffuse midline glioma with H3-K27M mutation is an infiltrative high-grade glioma, with predominantly astrocytic differentiation. Patient concerns:. A 54-year-old Chinese woman presented with memory loss for a month and walking instability for 15 days. Diagnosis:. Magnetic resonance imaging showed a mass shadow of isometric T1 and slightly longer T2 with mild mixed signals in the third ventricle of the suprasellar region. Histologically, the tumor was primarily sheet-like, with many “anucleate areas” composed of long and thin fibrillary processes of the bipolar cells, which formed “whorls.” The neoplastic nuclei were ovoid and moderate in size. The tumor showed brisk mitotic activity and vascular proliferation, with no necrosis. In addition to histone H3K27M mutation, immunohistochemical staining showed that the tumor cells were positive for glial fibrillary acidic protein, oligodendrocyte transcription factor 2, alpha-thalassemia/mental retardation syndrome X, S-100 and Vimentin. The “anucleate areas” were positive for glial fibrillary acidic protein and negative for synaptophysin. The Ki-67 proliferation index was about 10%. Molecular genetic analyses detected H3F3A K27M mutation, but no mutations in IDH1 or IDH2, TERT promoter mutations, MGMT promoter methylation, KIAA1549-BRAF fusion or deletion of 1p/19q were found. Based on these findings, the patient was diagnosed as diffuse midline glioma with H3-K27M mutation in the third ventricle, corresponding to WHO grade 4. Interventions:. A craniotomy with total excision of the tumor was performed. Outcomes:. After surgery, she was routinely treated with temozolomide for chemotherapy and synchronous radiotherapy. It has been 11 months now, and the patient is living well. Conclusion:. This case report provides information on the microscopic morphological features of diffuse midline glioma with H3K27M mutation, which can help pathologists to make a definitive diagnosis of this tumor.

BackgroundThe T classification of non-small-cell lung cancer (NSCLC) was upgraded from T1 to T2 when accompanied by visceral pleural invasion (VPI). However, the association between VPI and prognostic outcomes was obscure in NSCLC patients with ≤3 cm tumor size (TS), which leaded the controversy of selection of T classification. The goal was to evaluate the effect of VPI on the prognosis of NSCLC with ≤ 3cm TS and present a modified T classification.MethodsA total of 14,934 NSCLC patients without distant metastasis were recruited through a retrospective study in the SEER database. The effect of VPI on lung cancer specific survival (LCSS) was evaluated using survival curve and COX regression analysis in NSCLC patients with ≤3 cm TS.ResultsAlthough there was no difference of the LCSS of PL0 and PL1 patients with ≤2 cm TS in patients without lymph node (LN) metastasis, the LCSS was lower in PL2 patients than those in PL0 (T1a: p

Thrombocytopenia is a multifactorial condition that frequently involves concomitant defects in platelet production and clearance. The physiopathology of low platelet count in thrombocytopenia remains unclear. Sialylation on platelet membrane glycoprotein and follicular helper T cells (TFHs) are thought to be the novel platelet clearance pathways. The aim of this study was to clarify the roles of platelet desialylation and circulating TFHs in patients with immune thrombocytopenia (ITP) and non-ITP thrombocytopenia. We enrolled 190 patients with ITP and 94 patients with non-ITP related thrombocytopenia including case of aplastic anemia (AA) and myelodysplastic syndromes (MDS). One hundred and ten healthy volunteers were included as controls. We found significantly increased desialylated platelets in patients with ITP or thrombocytopenia in the context of AA and MDS. Platelet desialylation was negatively correlated with platelet count. Meanwhile, the circulating TFH levels in patients with thrombocytopenia were significantly higher than those of normal controls, and were positively correlated with desialylated platelet levels. Moreover, TFHs-related chemokine CXCL13 and apoptotic platelet levels were abnormally high in ITP patients. The upregulation of pro-apoptotic proteins and the activation of the MAPK/mTOR pathway were observed in the same cohort. These findings suggested that platelet desialylation and circulating TFHs may become the potential biomarkers for evaluating the disease process associated with thrombocytopenia in patients with ITP and non-ITP.

Magnetic resonance imaging (MRI) studies have documented that there were structural abnormalities in acquired immune deficiency syndrome (AIDS) patients. Although the long-term survival rate of AIDS patients can be improved by the combined antiretroviral therapy (cART), little is known about the effect of cART on brain structural alterations in AIDS patients. In this study, three-dimensional high-resolution brain structure MRI and voxel-based morphometric methods were used to explore the effects of cART on brain gray matter volume in AIDS patients. The results indicate that cART may effectively mitigate the occurrence of abnormal brain structure in AIDS patients, emphasizing the importance of early initiation of cART.

Abstract Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the malignant clonal expansion of lymphoid hematopoietic precursors. It is regulated by various signaling molecules such as cytokines and adhesion molecules in its microenvironment. Chemokines are chemotactic cytokines that regulate migration, positioning and interactions of cells. Many chemokine axes such as CXCL12/CXCR4 and CCL25/CCR9 have been proved to play important roles in leukemia microenvironment and further affect ALL outcomes. In this review, we summarize the chemokines that are involved in ALL progression and elaborate on their roles and mechanisms in leukemia cell proliferation, infiltration, drug resistance and disease relapse. We also discuss the potential of targeting chemokine axes for ALL treatments, since many related inhibitors have shown promising efficacy in preclinical trials, and some of them have entered clinical trials.

Abstract Introduction Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure. Materials and methods All 154 patients with COVID-19 were recruited from the Second People’s Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study. Results There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge. Conclusion Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.

Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1st, 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome. Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs. Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted. Registration PROSPERO CRD42020218818.

As a member of the TRIM (tripartite motif) protein family, TRIM56 can function as an E3 ubiquitin ligase. In addition, TRIM56 has been shown to possess deubiquitinase activity and the ability to bind RNA. This adds to the complexity of the regulatory mechanism of TRIM56. TRIM56 was initially found to be able to regulate the innate immune response. In recent years, its role in direct antiviral and tumor development has also attracted the interest of researchers, but there is no systematic review on TRIM56. Here, we first summarize the structural features and expression of TRIM56. Then, we review the functions of TRIM56 in TLR and cGAS-STING pathways of innate immune response, the mechanisms and structural specificity of TRIM56 against different types of viruses, and the dual roles of TRIM56 in tumorigenesis. Finally, we discuss the future research directions regarding TRIM56.

OTU domain-containing protein 3 (OTUD3) knockout mice exhibited loss of nigral dopaminergic neurons and Parkinsonian symptoms. However, the underlying mechanisms are largely unknown. In this study, we observed that the inositol-requiring enzyme 1α (IRE1α)-induced endoplasmic reticulum (ER) stress was involved in this process. We found that the ER thickness and the expression of protein disulphide isomerase (PDI) were increased, and the apoptosis level was elevated in the dopaminergic neurons of OTUD3 knockout mice. These phenomena were ameliorated by ER stress inhibitor tauroursodeoxycholic acid (TUDCA) treatment. The ratio of p-IRE1α/IRE1α, and the expression of X-box binding protein 1-spliced (XBP1s) were remarkably increased after OTUD3 knockdown, which was inhibited by IRE1α inhibitor STF-083010 treatment. Moreover, OTUD3 regulated the ubiquitination level of Fortilin through binding with the OTU domain. OTUD3 knockdown resulted in a decrease in the interaction ability of IRE1α with Fortilin and finally enhanced the activity of IRE1α. Taken together, we revealed that OTUD3 knockout-induced injury of dopaminergic neurons might be caused by activating IRE1α signaling in ER stress. These findings demonstrated that OTUD3 played a critical role in dopaminergic neuron neurodegeneration, which provided new evidence for the multiple and tissue-dependent functions of OTUD3.

Entity and relation linking are the core tasks in knowledge base question answering (KBQA). They connect natural language questions with triples in the knowledge base. In most studies, researchers perform these two tasks independently, which ignores the interplay between the entity and relation linking. To address the above problems, some researchers have proposed a framework for joint entity and relation linking based on feature joint and multi-attention. In this paper, based on their method, we offer a candidate set generation expansion model to improve the coverage of correct candidate words and to ensure that the correct disambiguation objects exist in the candidate list as much as possible. Our framework first uses the initial relation candidate set to obtain the entity nodes in the knowledge graph related to this relation. Second, the filtering rule filters out the less-relevant entity candidates to obtain the expanded entity candidate set. Third, the relation nodes directly connected to the nodes in the expanded entity candidate set are added to the initial relation candidate set. Finally, a ranking algorithm filters out the less-relevant relation candidates to obtain the expanded relation candidate set. An empirical study shows that this model improves the recall and correctness of the entity and relation linking for KBQA. The candidate set expansion method based on entity–relation interaction proposed in this paper is highly portable and scalable. The method in this paper considers the connections between question subgraphs in knowledge graphs and provides new ideas for the candidate set expansion.

A novel virus named SARS-CoV-2 has caused a worldwide pandemic, resulting in a disastrous impact to the public health since 2019. The disease is much more lethal among patients with malignant disease. Vaccination plays an important role in the prevention of infection and subsequent severe COVID-19. However, the efficacy and safety of vaccines for cancer patients needs further investigation. Encouragingly, there have been important findings deduced from research so far. In this review, an overview of the immunogenicity, effectiveness, and safeness of COVID-19 vaccines in patients with cancer to date is to be shown. We also highlight important questions to consider and directions that could be followed in future research.

To explore the effect of exogenous application of chlorinated amino acetic acid on cadmium (Cd) transport characteristics in rice seedlings, X24 and Z35 rice were taken as the research objects to carry out hydroponics experiments, and the changes of Cd content in rice seedlings, rice mineral elements and amino acid content in rice were analyzed. The results showed that exogenous application of 1.2 mmol·L−1 chlorinated amino acetic acid inhibited cadmium in shoots and roots of rice seedlings; Cd content in shoots and roots were reduced by up to 62.19% and 45.61%, respectively. The majority of cadmium was in the cell wall of shoots and roots; this decreased with the increase of the concentration of chlorinated acetic acid. In addition, the Mn content in shoots and Ca content in roots of rice seedlings increased significantly after the application of chlorinated amino acetic acid. The results of amino acid analysis showed that the contents of aspartic acid, glutamic acid and cystine in rice seedlings were increased. These results indicate that exogenous application of chlorinated amino acetic acid is beneficial to the synthesis of aspartic acid, glutamic acid and cysteine in rice seedlings, increases the content of Mn in shoots and Ca in roots of rice seedlings, and significantly alleviates cadmium stress in seedlings. This provides a theoretical basis for the development of an environmentally friendly Cd-lowering foliar fertilizer for rice.

Virtual Landslide Disaster environments are important for multilevel simulation, analysis and decision-making about Landslide Disasters. However, in the existing related studies, complex disaster scene objects and relationships are not deeply analyzed, and the scene contents are fixed, which is not conducive to meeting multilevel visualization task requirements for diverse users. To resolve the above issues, a construction method for Personalized Virtual Landslide Disaster Environments Based on Knowledge Graphs and Deep Neural networks is proposed in this paper. The characteristics of relationships among users, scenes and data were first discussed in detail; then, a knowledge graph of virtual Landslide Disaster environments was established to clarify the complex relationships among disaster scene objects, and a Deep Neural network was introduced to mine the user history information and the relationships among object entities in the knowledge graph. Therefore, a personalized Landslide Disaster scene data recommendation mechanism was proposed. Finally, a prototype system was developed, and an experimental analysis was conducted. The experimental results show that the method can be used to recommend intelligently appropriate disaster information and scene data to diverse users. The recommendation accuracy stabilizes above 80% – a level able to effectively support The Construction of Personalized Virtual Landslide Disaster environments.

Callerya dielsiana is a Chinese endemic tropical/subtropical liana. We sequenced the complete chloroplast genome with the Illumina Hiseq X-Ten platform. The genome is obtained with 132,301 bp in length, lacking an inverted repeat (IR) region, contains 4 rRNAs, 30 tRNAs genes, and 76 protein-coding genes. The overall GC content is 33.9%. Based on the whole chloroplast genomes of 14 legume species, a phylogenetic tree is constructed and indicated that C. dielsiana belongs to the well-supported tribe Wisterieae. The tribe is sister to Glycyrrhiza and nested within the IRLC (Inverted Repeat-Lacking Clade) group of the subfamily Papilionoideae (Fabaceae).

Purpose: To investigate the changes in choroidal vascular structures after exercise in patients with glaucoma using an image binarisation algorithm with enhanced-depth imaging optical coherence tomography.Methods: Thirty-four eyes of 19 patients with primary open-angle glaucoma and 40 eyes of 20 normal subjects were included in the glaucoma and control groups, respectively. All subjects were evaluated before, immediately after, and 30 min after 20-min running at moderate speed. The subfoveal choroidal area was segmented into the luminal area (LA) and stromal area (SA), and the choroidal vascularity index (CVI) was measured by calculating the ratio of LA to the total choroidal area (TCA). The mean intraocular pressure (IOP), subfoveal choroidal thickness, CVI, SA, CA, and TCA were compared within and between both groups. The correlation between CVI, IOP, and other vascular indexes was investigated.Results: In the glaucoma group, a significantly lower CVI was found immediately after exercise and recovered 30 min after exercise. Higher TCA and LA levels were demonstrated 30 min after exercise compared to immediately after exercise. In both groups, IOP decreased immediately after exercise but was restored after a 30-min rest. In the glaucoma group, there was a higher correlation between CVI and other choroidal vascular parameters than in the control group. There was no difference in IOP or choroidal parameters between the groups at different time points.Conclusion: In patients with glaucoma, CVI decreased significantly immediately after exercise, indicating that the choroidal layer is affected by exercise and an unhealthy vascular regulatory mechanism.

This study was aimed to evaluate the effects of post-transportation vitamin E (VE) supplementation on health condition, blood biochemical parameters, blood antioxidant indices and blood metabolomics in yak. Five yaks were used in this study. After 2100 km of highway transportation from Riwoqe county to Rongchang County, Chongqing, blood was collected immediately after arrival and these samples served as the baseline (control, CON_VE). A VE injection (40 mg/kg) was then performed and blood samples were collected 10 days later. Injection of VE led to lower serum VE concentration. Relative to the CON_VE, VE injection led to greater concentrations of creatinine and lower concentrations of glutamate pyruvic transaminase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, indirect bilirubin, direct bilirubin, UREA and glucose. Compared with CON_VE, VE injection led the lower serum level of malondialdehydeand greater serum level of glutathione s-transferase, glutathione peroxidase, glutathione reductase and glutathione peroxidase 4. Based on metabolomics analysis, 119 differentially altered serum metabolites (P1.0) were identified with VE injection relative to CON_VE. VE injection resulted in changes of lysophosphatidylethanolamine, lysophosphatidylcholine, phosphocholine, choline, malate, citrate, α-Oxo-glutarate, phenylalanine, 3-Phenylpropanoic acid and 3-(3-Hydroxyphenyl) propanoic acid. These metabolites are associated with lipid metabolism, tricarboxylic acid cycle and oxidative stress. Overall, our study indicates that VE injection can alleviate transportation stress in yak partly through protecting liver and kidney, and improving antioxidant defense systems.

Introduction Several reports have noted that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced lymphopenia in coronavirus disease 2019 (COVID-19) patients. However, the clinical significance of lymphopenia remains unclear. The objective of this study was to analyze the association between lymphopenia at an early stage and the prognosis of COVID-19 patients. Material and methods All 192 hospitalized patients with COVID-19 were enrolled. Demographic data and clinical characteristics were collected and patient’s prognosis was followed up. Results On admission, 84 (43.8%) patients suffered from lymphopenia among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among patients over 70 years old than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphopenia. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphopenia. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphopenia. Moreover, total bilirubin (TBIL) and direct bilirubin (DBIL), two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphopenia. Among 84 COVID-19 patients with lymphopenia, 32.1% died. The fatality rate was obviously higher in COVID-19 patients with lymphopenia. Conclusions Older COVID-19 patients are more susceptible to lymphopenia. Multiple organ injuries were more serious in COVID-19 patients with lymphopenia. Lymphopenia at an early stage aggravates the severity and elevates the death risk of COVID-19 patients.

Harnessing disease-suppressive microbiomes constitutes a promising strategy for optimizing plant growth. However, relatively little information is available about the relationship between bulk and rhizosphere soil microbiomes. Here, the assembly of banana bulk soil and rhizosphere microbiomes was investigated in a monoculture system consisting of bio-organic (BIO) and organic management practices. Applying BIO practice in newly reclaimed fields resulted in a high-efficiency biocontrol rate, thus providing a promising strategy for pre-control of Fusarium wilt disease. The soil microbiota was further characterized by MiSeq sequencing and quantitative PCR. The results indicate that disease suppression was mediated by the structure of a suppressive rhizosphere microbiome with respect to distinct community composition, diversity and abundance. Overall microbiome suppressiveness was primarily related to a particular set of enriched bacterial taxa affiliated with Pseudomonas, Terrimonas, Cupriavidus, Gp6, Ohtaekwangia and Duganella. Finally, structural equation modeling was used to show that the changes in bulk soil bacterial community determined its induced rhizosphere bacterial community, which serves as an important and direct factor in restraining the pathogen. Collectively, this study provides an integrative approach to disentangle the biological basis of disease-suppressive microbiomes in the context of agricultural practice and soil management.

Abstract Background To investigate the long term surgical outcomes of cataract surgery in severe and end stage glaucoma patients with preoperative intraocular pressure less than 21 mmHg, and to detect the associated factors. Methods A retrospective study of primary angle closure glaucoma patients was conducted on who underwent cataract surgery or combined with goniosynechialysis from March 2015 to April 2018. Main outcome measures were visual acuity, intraocular pressure, number of glaucoma medications and complications. Results Sixteen patients (19 eyes) were included. The mean age was 64.89 ± 11.68 years and the mean followed up duration was 21.89 ± 7.85 months. The final visual acuity was significantly improved from 0.69 ± 0.55 to 0.46 ± 0.52 logMAR, within 12 (63.2%) eyes improved, 4 (21.1%) eyes kept unchanged, and 3 (15.8%) eyes reduced. Linear regression analysis indicated that higher mean deviation, higher visual field index and lower glaucoma stage associated with better final visual acuity (r = − 0.511, r = − 0.493, r = 0.537 respectively). Moreover, the final number of medications were reduced from 1.26 ± 0.99 to 0.26 ± 0.56 (p

The automatic extraction of building outlines from high-resolution images is an important and challenging task. Convolutional neural networks have shown excellent results compared with traditional building extraction methods because of their ability to extract high-level abstract features from images. However, it is difficult to fully utilize the multiple features of current building extraction methods; consequently, the resulting building boundaries are irregular. To overcome these limitations, we propose a method for extracting buildings from high-resolution images using a multifeature convolutional neural network (MFCNN) and morphological filtering. Our method consists of two steps. First, the MFCNN, which consists of residual connected unit, dilated perception unit, and pyramid aggregation unit, is used to achieve pixel-level segmentation of the buildings. Second, morphological filtering is used to optimize the building boundaries, improve the boundary regularity, and obtain refined building boundaries. The Massachusetts and Inria datasets are selected for experimental analysis. Under the same experimental conditions, the extraction results achieved with the proposed MFCNN are compared with the results of other deep learning models that have been commonly used in recent years: FCN-8s, SegNet, and U-Net. The results on both datasets reveal that the proposed model improves the F1-score by 3.31%-5.99%, increases the overall accuracy (OA) by 1.85%-3.07%, and increases the intersection over union (IOU) by 3.47%-8.82%. These findings illustrate that the proposed method is effective at extracting buildings from complex scenes.

Abstract Recent advances in endocrine therapy have improved the prospects for estrogen receptor‐positive breast cancer. Tamoxifen is an effective drug for patients with estrogen receptor‐positive breast cancer, but the development of resistance is common. Therefore, discovering ways to enhance the sensitivity of cancer cells to tamoxifen may help improve breast cancer treatment. We studied the biological role of sirtuin 4 (SIRT4) in tamoxifen‐treated MCF7 and T47D cells. The levels of the MYC proto‐oncogene (MYC) and cyclin D1 (CCND1) were detected by western blotting and quantitative reverse transcription‐polymerase chain reaction in breast cancer cells with SIRT4 overexpression or depletion. Immunofluorescence and western blotting were used to assess the phosphorylation status of signal transducer and activator of transcription 3 (STAT3). SIRT4 overexpression decreased the half maximal inhibitory concentration of tamoxifen in MCF7 and T47D cells, while its depletion increased it. Thus, SIRT4 enhances the sensitivity of breast cancer cells to tamoxifen. Moreover, western blotting revealed decreased STAT3 phosphorylation after SIRT4 transfection. The transcription and translation of MYC and CCND1, target genes of the STAT3 pathway, were also blocked. Immunofluorescence revealed that pathway activation and nuclear STAT4 translocation were suppressed when SIRT4 was overexpressed. Furthermore, the effects of SIRT4 overexpression or depletion on proliferation could be offset by STAT3 activation or inhibition. Taken together, these results demonstrate that SIRT4 enhances the tamoxifen sensitivity of breast cancer cells by inhibiting the STAT3 signaling pathway. With this knowledge, therapeutic strategies with reduced drug resistance risk may be developed.

Summary: We previously showed stabilization of NIK−induced activation of NF-κB non-canonical signaling suppresses MLL-AF9−induced AML. In the current study, we demonstrate that deletion of NF-κB non-canonical RelB prevents the inhibitory effect of NIK stabilization in MLL-AF9 AML. Mechanistically, RelB suppresses its direct target, TIFAB, which is upregulated in human AML and correlates negatively with the survival of AML patients. Forced expression of TIFAB reverses NIK−induced impaired AML development through downregulation of RelB and upregulation of HOXA9. Consistent with upregulation of HOXA9, gene set enrichment analysis shows that forced expression of TIFAB blocks myeloid cell development, upregulates leukemia stem cell signature and induces similar gene expression patterns to those of HOXA9-MEIS1 and HOXA9-NUP98, and upregulates oxidative phosphorylation. Accordingly, forced expression of HOXA9 also largely releases the inhibitory impact of NIK stabilization via downregulation of RelB and upregulation of RelA. Our data suggest that NIK/RelB suppresses MLL-AF9−induced AML mainly through downregulation of TIFAB/HOXA9.