Publications by authors named "Bo Yang"

3,706 Publications

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Disrupted dynamic network reconfiguration of the brain functional networks of individuals with autism spectrum disorder.

Brain Commun 2022 1;4(4):fcac177. Epub 2022 Aug 1.

Center for Cognition and Brain Disorders, School of Clinical Medicine and the Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province 311121, PR China.

Human and animal studies on brain functions in subjects with autism spectrum disorder have confirmed the aberrant organization of functional networks. However, little is known about the neural features underlying these impairments. Using community structure analyses (recruitment and integration), the current study explored the functional network features of individuals with autism spectrum disorder from one database (101 individuals with autism spectrum disorder and 120 healthy controls) and tested the replicability in an independent database (50 individuals with autism spectrum disorder and 74 healthy controls). Additionally, the study divided subjects into different age groups and tested the features in different subgroups. As for recruitment, subjects with autism spectrum disorder had lower coefficients in the default mode network and basal ganglia network than healthy controls. The integration results showed that subjects with autism spectrum disorder had a lower coefficient than healthy controls in the default mode network-medial frontal network and basal ganglia network-limbic networks. The results for the default mode network were mostly replicated in the independent database, but the results for the basal ganglia network were not. The results for different age groups were also analysed, and the replicability was tested in different databases. The lower recruitment in subjects with autism spectrum disorder suggests that they are less efficient at engaging these networks when performing relevant tasks. The lower integration results suggest impaired flexibility in cognitive functions in individuals with autism spectrum disorder. All these findings might explain why subjects with autism spectrum disorder show impaired brain networks and have important therapeutic implications for developing potentially effective interventions.
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http://dx.doi.org/10.1093/braincomms/fcac177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356733PMC
August 2022

Comparison of polidocanol foam versus bleomycin polidocanol foam for treatment of venous malformations.

J Vasc Surg Venous Lymphat Disord 2022 Aug 5. Epub 2022 Aug 5.

Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China. Electronic address:

Objective: The objective of this research was to retrospectively investigate the difference of safety and efficacy between polidocanol foam and bleomycin polidocanol foam (BPF) in the treatment of venous malformations (VMs), and provide clinical evidence for the application of BPF for VMs.

Methods: Patients with VMs treated with polidocanol foam and BPF were included between July 2018 to July 2020. The VM tissue involvements and symptoms were collected. The treatment outcomes were evaluated by the clinical improvement of symptoms and the degree of devascularization at ultrasound or MRI. Patients were followed up for 1, 3, and 6 months after the sclerotherapy. The immediate or delayed complications were closely looked for and recorded.

Results: A total of fifty-one patients were included, including 34 females and 17 males with a mean age of 26.8 years (range, 5-65 years). The most commonly involved sites were lower extremities (31/60, 51.7%), and the most common symptom was pain (33/51, 64.7%). Fifty-four sclerotherapies were performed with a mean of 1.06±0.24 sessions (range 1-2 sessions) per patient. The reduction percentage of lesion volume in the BPF group was significantly higher than the POL group (79.4±1.6% versus 55.7±6.1%, P<0.001). Meantime, the patients' satisfaction scores in the BPF group were significantly higher than the POL group (7.2±1.1 versus 5.7±0.8, P<0.001). No major complication was observed in both groups. CIRSE grade 1 complications occurred in 5/21 patients in the BPF group and 7/30 patients in the POL group, CIRSE grade 2 complications occurred in 5/21 patients in the BPF group and 4/30 patients in the POL group, and there were no significant differences between the two groups.

Conclusions: Bleomycin polidocanol foam is a safe and effective sclerosant for VMs, showing better efficacy and similar safety than commonly used mild sclerosant. It could be a promising agent to treat VMs or other slow-flow vascular malformations.
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http://dx.doi.org/10.1016/j.jvsv.2022.06.005DOI Listing
August 2022

Visible Light-Induced Highly Regioselective and Stereoselective Oxysulfonylation of Alkynes for the Synthesis of ()-β-Phenoxy Vinylsulfones.

Org Lett 2022 Aug 8. Epub 2022 Aug 8.

International Joint Research Center for Molecular Science, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China.

A highly efficient visible light-induced regioselective and stereoselective oxysulfonylation of alkynes with arylsulfonate phenol esters has been developed. This photocatalyst- and metal-free method proceeds smoothly under very mild conditions and exhibits a broad substrate scope, providing ()-β-phenoxy vinylsulfones in moderate to excellent yields. Mechanistic studies indicated the involvement of an electron donor-acceptor complex-mediated radical process.
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http://dx.doi.org/10.1021/acs.orglett.2c02512DOI Listing
August 2022

Adaptive control of time delay teleoperation system with uncertain dynamics.

Front Neurorobot 2022 22;16:928863. Epub 2022 Jul 22.

School of Automation, University of Electronic Science and Technology of China, Chengdu, China.

A bilateral adaptive control method based on PEB control structure is designed for a class of time-delay force feedback teleoperation system without external interference and internal friction to study the uncertainty of dynamic parameters and time delay. The stability and tracking performances of the closed-loop constant time delay teleoperation system are analyzed by Lyapunov stability theory. Finally, the controller designed in this paper is successfully applied to the teleoperation system composed of a two-degree of freedom rotating manipulator as the master robot and the slave robot. The simulation is carried out in no operator and environment force or with operator and environment force. The adaptive bilateral control method's control performance is compared with that of the traditional time-delay teleoperation system. Finally, it is verified that the method has good control performance.
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http://dx.doi.org/10.3389/fnbot.2022.928863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354696PMC
July 2022

Interaction of Dietary Sodium-to-Potassium Ratio and Dinner Energy Ratio on Prevalence of Hypertension in Inner Mongolia, China.

J Epidemiol 2022 Aug 6. Epub 2022 Aug 6.

Center for Data Science in Health and Medicine, School of Public Health, Inner Mongolia Medical University.

Background Hypertension is one of the most common chronic diseases, and dietary factors play an important role in hypertension. We examined the interaction of dietary sodium-to-potassium (Na/K) ratio and dinner energy ratio on hypertension. Methods We conducted this study using data from cross-section, the National Survey for Nutrition and Adult Chronic Disease in 2015 in Inner Mongolia (China). Dietary data were collected by using 24-hour diet records with food weights across three consecutive days. Logistic regression was used to determine the interaction of dinner energy ratio and dietary Na/K ratio on hypertension. Results A total of 1,861 participants were included in this study, of those 914 individuals were hypertensive (49.1%). Dinner energy ratio and high dietary Na/K ratio were independently related to high prevalence of hypertension. A formal test showed that dinner energy ratio interacted significantly with dietary Na/K ratio on hypertension (P<0.001), with the adjusted OR (95%CI) of 1.119 (1.040-1.203). Participants whose dinner energy ratio greater than 39.1% and dietary Na/K ratio within 3.625 and 6.053 had the highest odds ratio of hypertension prevalence, with the adjusted OR (95%CI) of 2.984 (1.758-5.066), comparing with participants those dinner energy ratio within 30.2% and 39.1%, and dietary Na/K ratio less than 2.348. Conclusions Our study highlighted the interactive effect of dinner energy ratio and dietary Na/K ratio on hypertension among adults in Inner Mongolia. We advocated a balanced diet (dinner energy ratio not small or large) and a low dietary Na/K ratio for reducing the prevalence of hypertension.
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http://dx.doi.org/10.2188/jea.JE20220045DOI Listing
August 2022

The role of AMPK-Sirt1-autophagy pathway in the intestinal protection process by propofol against regional ischemia/reperfusion injury in rats.

Int Immunopharmacol 2022 Aug 4;111:109114. Epub 2022 Aug 4.

Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, PR China; Laboratory of Anesthesiology, Southwest Medical University, Luzhou, PR China. Electronic address:

Intestinal ischemia/reperfusion (II/R) is a clinical event associated with high morbidity and mortality. AMP-activated protein kinase (AMPK), a central cellular energy sensor, is associated with oxidative stress and inflammation. However, whether the AMPK is involved in the II/R-induced intestinal injury and the underlying mechanism is yet to be elucidated. Propofol has a protective effect on organs; yet, its specific mechanism of action remains unclear. This study explored the role of the AMPK-Sirt1-autophagy pathway in intestinal injury, and whether propofol could reduce intestinal injury and investigated the mechanisms in a rat model of II/R injury as well as a cell model (IEC-6 cells) of hypoxia/reoxygenation (H/R). Propofol, AMPK agonist (AICAR) and AMPK inhibitor (Compound C) were then administered, respectively. The histopathological changes, cell viability and apoptosis were detected. Furthermore, the levels of proinflammatory factors, the activities of oxidative stress, diamine oxidase, and signaling pathway were also analyzed. The results demonstrated that the AMPK-Sirt1-autophagy pathway of intestine was activated after II/R or H/R. Propofol could further activate the pathway, which reduced intestinal injury, inhibited apoptosis, reversed inflammation and oxidative stress, and improved the 24-hour survival rate in II/R rats in vivo, and attenuated H/R-induced IEC-6 cell injury, oxidative stress, and apoptosis in vitro, as fine as changes in AICAR treatment. Compound C abrogated the protective effect of propofol on II/R and H/R-induced injury. These results suggested a crucial effect of AMPK on the mechanism of intestinal injury and might provide a new insight into the mechanism of propofol reducing II/R injury.
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http://dx.doi.org/10.1016/j.intimp.2022.109114DOI Listing
August 2022

Understanding gilteritinib resistance to FLT3-F691L mutation through an integrated computational strategy.

J Mol Model 2022 Aug 6;28(9):247. Epub 2022 Aug 6.

Department of Radiology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, 210009, Jiangsu, China.

FMS-like tyrosine kinase 3 (FLT3) serves as an important drug target for acute myeloid leukemia (AML), and gene mutations of FLT3 have been closely associated with AML patients with an incidence rate of ~ 30%. However, the mechanism of the clinically relevant F691L gatekeeper mutation conferred resistance to the drug gilteritinib remained poorly understood. In this study, multiple microsecond molecular dynamics (MD) simulations, end-point free energy calculations, and dynamic correlated and network analyses were performed to investigate the molecular basis of gilteritinib resistance to the FLT3-F691L mutation. The simulations revealed that the resistant mutation largely induced the conformational changes of the activation loop (A-loop), the phosphate-binding loop, and the helix αC of the FLT3 protein. The binding abilities of the gilteritinib to the wild-type and the F691L mutant were different through the binding free energy prediction. The simulation results further indicated that the driving force to determine the binding affinity of gilteritinib was derived from the differences in the energy terms of electrostatic and van der Waals interactions. Moreover, the per-residue free energy decomposition suggested that the four residues (Phe803, Gly831, Leu832, and Ala833) located at the A-loop of FLT3 had a significant impact on the binding affinity of gilteritinib to the F691L mutant. This study may provide useful information for the design of novel FLT3 inhibitors specially targeting the F691L gatekeeper mutant.
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http://dx.doi.org/10.1007/s00894-022-05254-0DOI Listing
August 2022

Microbiota-assisted therapy for systemic inflammatory arthritis: advances and mechanistic insights.

Cell Mol Life Sci 2022 Aug 6;79(9):470. Epub 2022 Aug 6.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.

Research on the influence of gut microbiota on systemic inflammatory arthritis has exploded in the past decade. Gut microbiota changes may be a crucial regulatory component in systemic inflammatory arthritis. As a result of advancements in the field, microbiota-assisted therapy has evolved, but this discipline is still in its infancy. Consequently, we review the limitations of current systemic inflammatory arthritis treatment, analyze the connection between the microbiota and arthritis, and summarize the research progress of microbiota regulating systemic inflammatory arthritis and the further development aspects of microbiota-assisted therapy. Finally, the partial mechanisms of microbiota-assisted therapy of systemic inflammatory arthritis are being discussed. In general, this review summarizes the current progress, challenges, and prospects of microbiota-assisted therapy for systemic inflammatory arthritis and points out the direction for the development of microbiota-assisted therapy in the future.
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http://dx.doi.org/10.1007/s00018-022-04498-6DOI Listing
August 2022

Activation of STING Based on Its Structural Features.

Front Immunol 2022 19;13:808607. Epub 2022 Jul 19.

Shanxi Provincial Key Laboratory of Protein Structure Determination, Shanxi Academy of Advanced Research and Innovation, Taiyuan, China.

The cGAS-cGAMP-STING pathway is an important innate immune signaling cascade responsible for the sensing of abnormal cytosolic double-stranded DNA (dsDNA), which is a hallmark of infection or cancers. Recently, tremendous progress has been made in the understanding of the STING activation mechanism from various aspects. In this review, the molecular mechanism of activation of STING protein based on its structural features is briefly discussed. The underlying molecular mechanism of STING activation will enable us to develop novel therapeutics to treat STING-associated diseases and understand how STING has evolved to eliminate infection and maintain immune homeostasis in innate immunity.
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http://dx.doi.org/10.3389/fimmu.2022.808607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343627PMC
August 2022

Development and Verification of Prognostic Prediction Models for Patients with Brain Trauma Based on Coagulation Function Indexes.

J Immunol Res 2022 26;2022:3876805. Epub 2022 Jul 26.

Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 450052.

Objective: To assess the effect of adding coagulation indices to the currently existing prognostic prediction models of traumatic brain injury (TBI) in the prediction of outcome.

Methods: A total of 210 TBI patients from 2017 to 2019 and 131 TBI patients in 2020 were selected for development and internal verification of the new model. The primary outcomes include death at 14 days and Glasgow Outcome Score (GOS) at 6 months. The performance of each model is evaluated by means of discrimination (area under the curve (AUC)), calibration (Hosmer-Lemeshow (H-L) goodness-of-fit test), and precision (Brier score).

Results: The IMPACT Core model showed better prediction ability than the CRASH Basic model. Adding one coagulation index at a time to the IMPACT Core model, the new combined models IMPACT Core+FIB and IMPACT Core+APTT are optimal for the 6-month unfavorable outcome and 6-month mortality, respectively (AUC, 0.830 and 0.878). The new models were built based on the regression coefficients of the models. Internal verification indicated that for the prediction of 6-month unfavorable outcome and 6-month mortality, both the IMPACT Core+FIB model and the IMPACT Core+APTT model show better discrimination (AUC, 0.823 vs. 0.818 and 0.853 vs. 0.837), better calibration (HL, = 0.114 and = 0.317) and higher precision (Brier score, 0.148 vs. 0.141 and 0.147 vs. 0.164), respectively, than the original models.

Conclusion: Our research shows that the combination of the traumatic brain injury prognostic models and coagulation indices can improve the 6-month outcome prediction of patients with TBI.
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http://dx.doi.org/10.1155/2022/3876805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345690PMC
August 2022

Tumor Suppressor DAPK1 Catalyzes Adhesion Assembly on Rigid but Anoikis on Soft Matrices.

Front Cell Dev Biol 2022 19;10:959521. Epub 2022 Jul 19.

Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Cancer cells normally grow on soft surfaces due to impaired mechanosensing of the extracellular matrix rigidity. Upon restoration of proper mechanosensing, cancer cells undergo apoptosis on soft surfaces (anoikis) like most normal cells. However, the link between mechanosensing and activation of anoikis is not clear. Here we show that death associated protein kinase 1 (DAPK1), a tumor suppressor that activates cell death, is directly linked to anoikis activation through rigidity sensing. We find that when rigidity sensing is decreased through inhibition of DAPK1 activity, cells are transformed for growth on soft matrices. Further, DAPK1 catalyzes matrix adhesion assembly and is part of adhesions on rigid surfaces. This pathway involves DAPK1 phosphorylation of tropomyosin1.1, the talin1 head domain, and tyrosine phosphorylation of DAPK1 by Src. On soft surfaces, DAPK1 rapidly dissociates from the adhesion complexes and activates apoptosis as catalyzed by PTPN12 activity and talin1 head. Thus, DAPK1 is important for adhesion assembly on rigid surfaces and the activation of anoikis on soft surfaces through its binding to rigidity-sensing modules.
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http://dx.doi.org/10.3389/fcell.2022.959521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343699PMC
July 2022

Activation of the sigma-1 receptor exerts cardioprotection in a rodent model of chronic heart failure by stimulation of angiogenesis.

Mol Med 2022 Aug 3;28(1):87. Epub 2022 Aug 3.

Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, People's Republic of China.

Background: Angiogenesis plays a critical role on post-infarction heart failure (PIHF), the presence of which facilitates additional blood supply to maintain the survival of residual cardiomyocytes. The sigma-1 receptor (S1R) has been substantiated to stimulate angiogenesis, with the effect on a model of PIHF remaining unknown.

Aims: This study aims to investigate the effects of S1R on PIHF and the underlying mechanisms involved.

Methods: Rats were implemented left anterior descending artery ligation followed by rearing for 6 weeks to induce a phenotype of heart failure. Daily intraperitoneal injection of S1R agonist or antagonist for 5 weeks was applied from 2nd week after surgery. The effects exerted by S1R were detected by echocardiography, hemodynamic testing, western blot, Sirius red dyeing, ELISA, immunohistochemistry and fluorescence. We also cultured HUVECs to verify the mechanisms in vitro.

Results: Stimulation of S1R significantly ameliorated the cardiac function resulted from PIHF, in addition to the observation of reduced fibrosis in the peri-infarct region and the apoptosis of residual cardiomyocytes, which were associated with augmentation of microvascular density in peri-infarct region through activation of the JAK2/STAT3 pathway. We also indicated that suppression of JAK2/STAT3 pathway by specific inhibitor in vitro reversed the pro-angiogenic effects of S1R on HUVECs, which further confirmed that angiogenesis, responsible for PIHF amelioration, by S1R stimulation was in a JAK2/STAT3 pathway-dependent manner.

Conclusion: S1R stimulation improved PIHF-induced cardiac dysfunction and ventricular remodeling through promoting angiogenesis by activating the JAK2/STAT3 pathway.
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http://dx.doi.org/10.1186/s10020-022-00517-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347174PMC
August 2022

Neoadjuvant Chemotherapy Improves the Immunosuppressive Microenvironment of Bladder Cancer and Increases the Sensitivity to Immune Checkpoint Blockade.

J Immunol Res 2022 21;2022:9962397. Epub 2022 Jul 21.

Department of Oncology, Army Medical Center, Chongqing 400042, China.

Although tumor immune microenvironment plays an important role in antitumor therapy, few studies explored the gene signatures associated with the tumor immune microenvironment of bladder cancer after neoadjuvant chemotherapy. We examined and analyzed differentially expressed genes from 9 patients with stage I-III bladder cancer by RNA immune-oncology profiling platform. After neoadjuvant chemotherapy, the expressions of 43 genes in 19 pathways and 10 genes in 5 pathways were upregulated and downregulated, respectively. Neoadjuvant chemotherapy also promoted the expression of genes related to the activation of antitumor immune responses and decreased the expression of genes related to tumor proliferation pathways. In addition, neoadjuvant chemotherapy improved tumor response to immune checkpoint blockade. Furthermore, this study also identified several genes that can be used to predict the efficacy of neoadjuvant chemotherapy and their possible molecular mechanisms. In conclusion, neoadjuvant chemotherapy may promote the activation of antitumor effects, improve the suppressive tumor immune microenvironment, and increase the sensitivity of bladder cancer to immune checkpoint blockade.
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http://dx.doi.org/10.1155/2022/9962397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338739PMC
August 2022

An Intelligent Animation Interaction Design Algorithm Based on Example and Parameterization.

Comput Intell Neurosci 2022 21;2022:6017254. Epub 2022 Jul 21.

Department of Secrecy Archive and Screen Culture, Logistics University of PAPF, Tianjin 300300, China.

Intelligent design for the animation interaction is very challenging and needs to be resolved on priority basis. If this design is based on smart learning based mechanism, then it will be more appropriate and effective. Therefore, based on the idea of process modeling, the concrete method is based on example modeling and parameterization, and the VC programming environment is the tool. Animated interactions are not counted. The animation parameterization in the sample animation software and its attribute information are calculated, and the principle and realization process of the new animation interaction design are given, as well as the calculation method and steps of each area of animation elements. The same interaction design pattern can be filled in different areas by using parametric methods. In practice, we have increased the diversity of animation interaction design. The method proposed in this paper can quickly and automatically generate a virtual animation design network according to the user's design ideas and can be controlled by the user in real time interactively, providing a good interface and a new way for the user to design animation environment modeling.
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http://dx.doi.org/10.1155/2022/6017254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334100PMC
August 2022

Clinical manifestations of COVID-19: An overview of 102 systematic reviews with evidence mapping.

J Evid Based Med 2022 Jul 31. Epub 2022 Jul 31.

School of Public Health, Lanzhou University, Lanzhou, China.

Objective: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, but there is so far no comprehensive analysis of all known symptoms of the disease. Our study aimed to present a comprehensive picture of the clinical symptoms of COVID-19 using an evidence map.

Methods: We systematically searched MEDLINE via PubMed, Web of Science, Embase, and Cochrane library from their inception to March 16, 2021. We included systematic reviews reporting the clinical manifestations of COVID-19 patients. We followed the PRISMA guidelines, and the study selection, data extraction, and quality assessment were done by two individuals independently. We assessed the methodological quality of the studies using AMSTAR. We visually presented the clinical symptoms of COVID-19 and their prevalence.

Results: A total of 102 systematic reviews were included, of which, 68 studies (66.7%) were of high quality, 19 studies (18.6%) of medium quality, and 15 studies (14.7%) of low quality. We identified a total of 74 symptoms including 17 symptoms of the respiratory system, 21 symptoms of the neurological system, 10 symptoms of the gastrointestinal system, 16 cutaneous symptoms, and 10 ocular symptoms. The most common symptoms were fever (67 studies, ranging 16.3%-91.0%, pooled prevalence: 64.6%, 95%CI, 61.3%-67.9%), cough (68 studies, ranging 30.0%-72.2%, pooled prevalence: 53.6%, 95%CI, 52.1%-55.1%), muscle soreness (56 studies, ranging 3.0%-44.0%, pooled prevalence: 18.7%, 95%CI, 16.3%-21.3%), and fatigue (52 studies, ranging 3.3%-58.5%, pooled prevalence: 29.4%, 95%CI, 27.5%-31.3%). The prevalence estimates for COVID-19 symptoms were generally lower in neonates, children and adolescents, and pregnant women than in the general populations.

Conclusion: At least 74 different clinical manifestations are associated with COVID-19. Fever, cough, muscle soreness, and fatigue are the most common, but attention should also be paid to the rare symptoms that can help in the early diagnosis of the disease.
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http://dx.doi.org/10.1111/jebm.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353366PMC
July 2022

Ferroptosis-Related lncRNA Signature Correlates with the Prognosis, Tumor Microenvironment, and Therapeutic Sensitivity of Esophageal Squamous Cell Carcinoma.

Oxid Med Cell Longev 2022 16;2022:7465880. Epub 2022 Jul 16.

Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214000, China.

Esophageal squamous cell carcinoma (ESCC) is the most prevalent form of esophageal cancer in China and is closely associated with malignant biological characteristics and poor survival. Ferroptosis is a newly discovered iron-dependent mode of cell death that plays an important role in the biological behavior of ESCC cells. The clinical significance of ferroptosis-related long noncoding RNAs (FRLs) in ESCC remains unknown and warrants further research. The current study obtained RNA sequencing profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and FRLs were obtained through coexpression analysis. Consensus clustering was employed to divide the subjects into clusters, and immune-associated pathways were identified by functional analysis. The current study observed significant differences in the enrichment scores of immune cells among different clusters. Patients from TCGA-ESCC database were designated as the training cohort. A ten-FRL prediction signature was established using the least absolute shrinkage and selection operator Cox regression model and validated using the GEO cohort and our own independent validation database. Real-time quantitative polymerase chain reaction was used to verify the expression of the ten FRLs, and the ssGSEA analysis was employed to evaluate their function. In addition, the IMvigor database was used to assess the predictive value of the signature in terms of immunotherapeutic responses. Multivariate Cox and stratification analyses revealed that the ten-FRL signature was an independent predictor of the overall survival (OS). Patients with ESCC in the high-risk group displayed worse survival, a characteristic tumor immune microenvironment, and low immunotherapeutic benefits compared to those in the low-risk group. Collectively, the risk model established in this study could serve as a promising predictor of prognosis and immunotherapeutic response in patients with ESCC.
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http://dx.doi.org/10.1155/2022/7465880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315452PMC
August 2022

Prognostic Value of HPV E6 and APOBEC3B in Upper Urinary Tract Urothelial Carcinoma.

Dis Markers 2022 19;2022:2147494. Epub 2022 Jul 19.

Cancer Center, Daping Hospital & Army Medical Center of PLA, Third Military Medical University (Army Medical University), Chongqing, China.

Background: APOBEC mutation signature is common in upper urinary tract urothelial carcinoma (UTUC). When virus infection occurs, upregulated APOBEC plays an antiviral role by deoxycytidine deaminase activity. However, the carcinogenic roles of HPV E6 protein and APOBEC mutation signature in UTUC have not been investigated.

Aims: This study explored the relationship among HPV E6, APOBEC, and clinicopathological characteristics in patients with UTUC and impacts of their expression on the prognosis.

Methods: The expression of HPV E6 and APOBEC3B of 78 patients with UTUC was detected by immunohistochemistry. Correlation of HPV E6 and APOBEC3B expression levels with clinicopathological characteristics was statistically analyzed. Univariate and multivariate Cox regression analyses were used to evaluate the prognosis of HPV E6 and APOBEC3B for disease-free survival (DFS); survival analysis was performed using Kaplan-Meier methods.

Results: The expression of APOBEC3B was positively correlated with the expression of HPV E6 ( = 0.383, = 0.001). HPV E6 was significantly increased in patients with stage I ( = 4.938, = 0.026) and low-grade urothelial carcinoma ( = 3.939, = 0.047), as well as in patients without LVI ( = 4.064, = 0.044). Meanwhile, APOBEC3B was highly expressed in patients with stage I ( = 4.057, = 0.044) and low-grade urothelial carcinoma ( = 7.153, = 0.007). Multivariate Cox regression analysis revealed the APOBEC3B expression was the independent prognostic factor for DFS, Kaplan-Meier survival analysis showed that low expression of APOBEC3B and HPV E6 was significantly associated with the poor prognosis of UTUC patients.

Conclusion: HPV E6 expression is positively associated with APOBEC3B expression, and the high expression of HPV E6 and APOBEC3B is associated with favorable prognosis of patients with UTUC.
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http://dx.doi.org/10.1155/2022/2147494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325345PMC
August 2022

Functional supramolecular micelles driven by the amphiphilic complex of biotin-acyclic cucurbituril and cannabidiol for cell-targeted drug delivery.

Int J Pharm 2022 Jul 25;625:122048. Epub 2022 Jul 25.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, PR China. Electronic address:

Precise delivery of hydrophobic drugs has always been a great challenge for drug delivery systems. To overcome this problem, we designed and synthesized a novel supramolecular host biotin-acyclic cucurbituril (ACBB) at the first time, and we have developed a host-guest amphiphilic complex based on ACBB and amantadine-conjugated cannabinoids (AD-CBD) that self-assembles to form functionalized supramolecular micelles (FSMs) for cell-targeted drug delivery. The 1:1 stoichiometric ratio of the amphiphilic complex and its possible host-guest inclusion behaviors are obtained by fluorescence titration, nuclear magnetic resonance (NMR), Fourier transform-infrared spectroscopy (FT-IR) and thermal analysis (TGA and DSC). Using transmission electron microscope (TEM) and dynamic light scattering (DLS), we have observed that the shape of FSMs was spherical and size was 137-192 nm. In addition, MTT test results show that FSMs have good antitumor activity, taking MCF-7 as an example, the in vitro half-maximal inhibitory concentration (IC) values of FSMs were 1.53 μM and 5.02 μM, which were better than 30.83 μM of cisplatin. Confocal laser scanning microscopy (CLSM) results showed that FSMs loaded with Rhodamine B can specifically aggregate on the surface of tumor cells and the targeting ability has been directly verified. Flow cytometry results showed that FSMs could promote tumor cell apoptosis. All results indicated that FSMs had high bioavailability, stability, accurate targeting and excellent delivery efficiency, which had great application potential in the field of drug delivery.
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http://dx.doi.org/10.1016/j.ijpharm.2022.122048DOI Listing
July 2022

Effect of three-dimensional interstitial high-dose-rate brachytherapy with regional metastatic lymph node intensity-modulated radiation therapy in locally advanced peripheral non-small cell lung cancer: 5-year follow-up of a phase II clinical trial.

Int J Radiat Oncol Biol Phys 2022 Jul 25. Epub 2022 Jul 25.

Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, China. Electronic address:

Purpose: We aimed to reveal the 5-year clinical outcomes of three-dimensional (3D) interstitial high-dose-rate (HDR) brachytherapy with regional metastatic lymph node intensity-modulated radiation therapy (IMRT) for locally advanced peripheral non-small cell lung cancer (NSCLC), which has been shown to have low toxicity and improved 2-year survival rates in patients with this disease.

Methods: In this phase II, single-arm, open-label clinical trial, 83 patients with locally advanced peripheral NSCLC were enrolled (median follow-up [range], 53.7 [4.3-120.4] months). All eligible patients received 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT. The primary endpoint was overall survival (OS). Secondary endpoints were local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), progression-free survival (PFS), distant metastasis-free survival (DMFS), toxicities, and quality of life.

Results: The final analysis included 75 patients (19 [25.3%] females, 56 [74.7%] males; median [range] age, 64 [44-80] years; stage IIIA, 34 [45.3%]; stage IIIB, 41 [54.7%]). At the latest follow-up, 32 (42.7%) patients had survived. The median OS was 38.0 months (5-year OS, 44.5%; 95% confidence interval [CI], 33.8%-58.6%). The LRFS, RRFS, and DMFS at 5 years were 79.2% (95% CI, 68.5%-91.5%), 73.6% (95% CI, 61.5%-88.1%), and 50.3% (95% CI, 38.3%-66.1%), respectively. The dominant failure pattern was distant disease, corresponding to 40% (30/75) of patients and 65.2% (30/46) of all failures. Two (2.7%) patients developed grade 1 acute pneumonitis. Grade 2 and 3 acute esophagitis occurred in 11 (14.7%) and 4 (5.3%) patients, respectively. No late radiation-related grade ≥2 late adverse events were observed.

Conclusions: 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT for locally advanced peripheral NSCLC shows significant OS and has a low toxicity rate. Additional evaluation in a phase III trial is recommended to substantiate these findings.
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http://dx.doi.org/10.1016/j.ijrobp.2022.07.028DOI Listing
July 2022

Repurposing of the antihistamine mebhydrolin napadisylate for treatment of Zika virus infection.

Bioorg Chem 2022 Jul 22;128:106024. Epub 2022 Jul 22.

CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tiantanxili, Beijing 100050 China. Electronic address:

Zika virus (ZIKV) infection can lead to severe neurological disorders and fetal defects, which has become a public health problem worldwide. However, effective clinical treatment for ZIKV infection was still arduous. Antihistamines are attractive candidates for drug repurposing due to their low price and widespread availability. Here we screened FDA-approved antihistamine drugs to obtain anti-ZIKV candidate compounds and identified mebhydrolin napadisylate (MHL) that exhibits the potent inhibition of ZIKV infection in various cell lines in a histamine H1 receptor-independent manner. Mechanistic studies suggest that MHL acts as a ZIKV NS5 RNA-dependent RNA polymerase (RdRp) inhibitor, supported by a structure-activity relationship (SAR) analysis showing the correlation between the inhibitory effect upon viral RNA synthesis and ZIKV infectivity. Furthermore, MHL was shown to bind ZIKV NS5 RdRp in vitro and predicted to interact with key residues at the active site of ZIKV NS5 RdRp by molecular docking analysis. Our data together suggest that MHL suppresses ZIKV infection through the inhibition of ZIKV NS5 RdRp activity. This study highlights that MHL might be a promising clinical anti-ZIKV therapeutic.
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http://dx.doi.org/10.1016/j.bioorg.2022.106024DOI Listing
July 2022

Development of the Nurses' Willingness to Engage in Palliative Care Scale.

J Hosp Palliat Nurs 2022 Jul 28. Epub 2022 Jul 28.

Nurses play an important role in palliative care, and their willingness to engage in such work is thus crucial. The purpose of this study was to develop, and test the reliability and validity of, the Nurses' Willingness to Engage in Palliative Care Scale. The sample consisted of 224 Chinese nurses with a mean age of 32.36 (SD, 5.986) years. The critical ratio method was used for item analysis. Reliability was assessed by calculating Cronbach α. Content validity was assessed by calculating a content validity index based on ratings from 5 nursing experts. Structural validity was calculated by exploratory factor analysis. The developed scale consists of 20 items over 4 dimensions (attitude toward the behavior, subjective norms, perceived behavioral control, and behavioral intention) and has high content validity (0.97). The reliability of the scale was found to be sufficient (Cronbach α = .896). Four common factors were extracted from exploratory factor analysis, and the cumulative variance explained was 68.938%. The Nurses' Willingness to Engage in Palliative Care Scale has good reliability and validity and can be used to assess nurses' willingness to work in palliative care units.
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http://dx.doi.org/10.1097/NJH.0000000000000898DOI Listing
July 2022

Efficacy and Safety of Apatinib plus Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cancer: A Phase II Trial.

Biomed Res Int 2022 18;2022:4727407. Epub 2022 Jul 18.

Department of Thoracic Oncology, Anyang Tumor Hospital, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Henan Medical Key Laboratory of Precise Prevention and Treatment of Esophageal Cancer, Anyang, 455000, China.

Evidence for neoadjuvant chemotherapy combined with targeted therapy for locally advanced esophageal squamous cancer (ESCC) is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of apatinib combined with taxol and cisplatin (ATP) for locally advanced ESCC. All patients were cT3-4aN0-3 M0 (IIIb-IVa) stage, which were confirmed by histopathology. Apatinib was taken orally (425 mg/d) for two cycles, followed by one cycle of rest. Taxol was administered at 135 mg/m intravenously on day 1, and cisplatin was administered at 20 mg/m intravenously on day 1 to day 3. Radical ESCC resection was performed 4 weeks after ATP. The primary endpoint was pathological response rate (pCR). Secondary endpoints were pathologic response rate (MPR), disease-free survival (DFS), overall survival (OS), R0 resection rate, and safety profile. This trial was registered. We evaluated 41 patients for screening from Oct 2018 to July 2020, of whom 39 were enrolled in the study, with a median age of 65 years (range 49-75 years), and 29 (74.4%) were male. Among the 39 patients, 1 was considered unresectable by the multidisciplinary team due to tumor progression, and 38 patients underwent surgery eventually. The median follow-up was 22 months (range 5-29 months), and the follow-up rate was 100%. The 1-year and 2-year OS was 95% and 95%, and the 1-year and 2-year DFS was 85% and 82%, respectively. Thirty-eight (97.3%) successfully underwent R0 resection. Of the 38 evaluable patients, 9 (23.6%) were pCR, and 15 (39.5%) were MPR. The most common ATP-related AEs were nausea (76.9%), leucopenia (53.8%), neutropenia (51.2%) and vomit (51.2%), anemia (41.0%), and hypertension (25.6%). The most frequent grade 3-4 events included leucopenia (15.3%), neutropenia (15.3%), nausea (12.8%), vomit (12.8%), and hypertension (10.2%). No treatment-related death occurred. Neoadjuvant apatinib combined with taxol and cisplatin for locally advanced ESCC showed favorable activity and manageable safety.
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http://dx.doi.org/10.1155/2022/4727407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313985PMC
July 2022

Study on Influencing Factors Analysis of Gastric Tube Insertion Length and Construction of Estimation Method.

Front Surg 2022 11;9:942881. Epub 2022 Jul 11.

Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Influenced by individual differences, the depth of gastric tube placement is often different. Clinically, it is necessary to seek a simple and accurate gastric tube insertion scheme to improve the clinical efficacy of indwelling gastric tube.

Materials And Methods: A total of 100 adult patients undergoing transesophageal manometry nose were included in the study. The length (NCL) of apex-cardia was measured. At the same time, we entered our institutional database, summarized the clinical data of 100 patients, and analyzed the risk factors affecting NCL using stepwise regression analysis.

Results: The NCL length scores of patients with different gender, age, marital status, height, weight, BMI, sitting height, sternum length, hairline-xiphoid process, nose tip-earlobe-xiphoid process and earlobe-xiphoid process were statistically significant ( < 0.05). Height, sitting height, gender, BMI and earlobe-xiphoid process were the factors that affected the NCL length score ( < 0.05). The prediction equation of the estimation method of gastric tube insertion length was as follows: NCL length score = 39.907 + 2.909× height +0.865× sitting height. Adjust to 0.506. NCL was positively correlated with height and sitting height. Among them, the correlation with height (= 0.711, < 0.001) and sitting height (= 0.397, < 0.001).

Conclusion: Height, sitting height, gender, BMI and earlobe-xiphoid process were the factors that affected the score of NCL length. There was a significant positive correlation between height, sitting height and NCL length. On this basis, the length of nasogastric tube insertion could be estimated.
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http://dx.doi.org/10.3389/fsurg.2022.942881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309469PMC
July 2022

Stromal Interaction Molecule 1 Promotes the Replication of vvIBDV by Mobilizing Ca in the ER.

Viruses 2022 07 13;14(7). Epub 2022 Jul 13.

State Key Laboratory of Veterinary Biotechnology, Avian Immunosuppressive Diseases Division, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

Infectious bursal disease virus (IBDV) is one of the main threats to the poultry industry worldwide. Very virulent IBDV (vvIBDV) is a fatal virus strain that causes heavy mortality in young chicken flocks. Ca is one of the most universal and versatile signalling molecules and is involved in almost every aspect of cellular processes. Clinical examination showed that one of the characteristics of vvIBDV-infected chickens was severe metabolic disorders, and the chemical examination showed that their serum Ca level decreased significantly. However, there are limited studies on how vvIBDV infection modulates the cellular Ca level and the effect of Ca level changes on vvIBDV replication. In our study, we found Ca levels in the endoplasmic reticulum (ER) of vvIBDV-infected B cells were higher than that of mock-infected cells, and the expression level of stromal interaction molecule 1 (STIM1), an ER Ca sensor, was significantly upregulated due to vvIBDV infection. The knock-down expression of STIM1 led to decreased Ca level in the ER and suppressed vvIBDV replication, while the over-expressed STIM1 led to ER Ca upregulation and promoted vvIBDV replication. We also showed that the inhibition of Ca-release-activated-Ca (CRAC) channels could reduce vvIBDV infection by blocking Ca from entering the ER. This study suggests a new mechanism that STIM1 promotes the replication of vvIBDV by mobilizing Ca in the ER.
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http://dx.doi.org/10.3390/v14071524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320076PMC
July 2022

Inosine Pretreatment Attenuates LPS-Induced Lung Injury through Regulating the TLR4/MyD88/NF-κB Signaling Pathway In Vivo.

Nutrients 2022 Jul 9;14(14). Epub 2022 Jul 9.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Inosine is a type of purine nucleoside, which is considered to a physiological energy source, and exerts a widely range of anti-inflammatory efficacy. The TLR4/MyD88/NF-κB signaling pathway is essential for preventing host oxidative stresses and inflammation, and represents a promising target for host-directed strategies to improve some forms of disease-related inflammation. In the present study, the results showed that inosine pre-intervention significantly suppressed the pulmonary elevation of pro-inflammatory cytokines (including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)), malondialdehyde (MDA), nitric oxide (NO), and reactive oxygen species (ROS) levels, and restored the pulmonary catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities ( < 0.05) in lipopolysaccharide (LPS)-treated mice. Simultaneously, inosine pre-intervention shifted the composition of the intestinal microbiota by decreasing the ratio of Firmicutes/Bacteroidetes, elevating the relative abundance of Tenericutes and Deferribacteres. Moreover, inosine pretreatment affected the TLR4/MyD88/NF-κB signaling pathway in the pulmonary inflammatory response, and then regulated the expression of pulmonary iNOS, COX2, Nrf2, HO-1, TNF-α, IL-1β, and IL-6 levels. These findings suggest that oral administration of inosine pretreatment attenuates LPS-induced pulmonary inflammatory response by regulating the TLR4/MyD88/NF-κB signaling pathway, and ameliorates intestinal microbiota disorder.
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http://dx.doi.org/10.3390/nu14142830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318366PMC
July 2022

Precision Layered Stealth Dicing of SiC Wafers by Ultrafast Lasers.

Micromachines (Basel) 2022 Jun 27;13(7). Epub 2022 Jun 27.

The Institute of Technological Sciences, Wuhan University, Wuhan 430072, China.

With the intrinsic material advantages, silicon carbide (SiC) power devices can operate at high voltage, high switching frequency, and high temperature. However, for SiC wafers with high hardness (Mohs hardness of 9.5), the diamond blade dicing suffers from problems such as debris contaminants and unnecessary thermal damage. In this work, a precision layered stealth dicing (PLSD) method by ultrafast lasers is proposed to separate the semi-insulated 4H-SiC wafer with a thickness of 508 μm. The laser power attenuates linearly from 100% to 62% in a gradient of 2% layer by layer from the bottom to the top of the wafer. A cross section with a roughness of about 1 μm was successfully achieved. We have analyzed the effects of laser pulse energy, pulse width, and crystal orientation of the SiC wafer. The anisotropy of the SiC wafer results in various qualities of PLSD cross sections, with the roughness of the crystal plane {10-10} being 20% lower than that of the crystal plane {11-20}.
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http://dx.doi.org/10.3390/mi13071011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315561PMC
June 2022

MORC3 restricts human cytomegalovirus infection by suppressing the major immediate-early promoter activity.

J Med Virol 2022 Jul 25. Epub 2022 Jul 25.

Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou, China.

During the long coevolution of human cytomegalovirus (HCMV) and humans, the host has formed a defense system of multiple layers to eradicate the invader, and the virus has developed various strategies to evade host surveillance programs. The intrinsic immunity primarily orchestrated by promyelocytic leukemia (PML) nuclear bodies (PML-NBs) represents the first line of defense against HCMV infection. Here, we demonstrate that microrchidia family CW-type zinc finger 3 (MORC3), a PML-NBs component, is a restriction factor targeting HCMV infection. We show that depletion of MORC3 through knockdown by RNA interference or knockout by CRISPR-Cas9 augmented immediate-early protein 1 (IE1) gene expression and subsequent viral replication, and overexpressing MORC3 inhibited HCMV replication by suppressing IE1 gene expression. To relief the restriction, HCMV induces transient reduction of MORC3 protein level via the ubiquitin-proteasome pathway during the immediate-early to early stage. However, MORC3 transcription is upregulated, and the protein level recovers in the late stages. Further analyses with temporal-controlled MORC3 expression and the major immediate-early promoter (MIEP)-based reporters show that MORC3 suppresses MIEP activity and consequent IE1 expression with the assistance of PML. Taken together, our data reveal that HCMV enforces temporary loss of MORC3 to evade its repression against the initiation of immediate-early gene expression.
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http://dx.doi.org/10.1002/jmv.28025DOI Listing
July 2022

A Novel mechanisms of the signaling cascade associated with the SAPK10-bZIP20-NHX1 synergistic interaction to enhance tolerance of plant to abiotic stress in rice (Oryza sativa L.).

Plant Sci 2022 Jul 22;323:111393. Epub 2022 Jul 22.

Lianyungang Institute of Agricultural Sciences, Collaborative Innovation Center for Modern Crop Production, Lianyungang, Jiangsu province 222006, China. Electronic address:

The bzip transcription factors can modulate the transcriptional expressions of target genes by binding specifically to cis-regulatory elements in the promoter region of stress-related genes, hence regulating plant stress resistance. Here, we investigated a stress-responsive transcription factor Osbzip20 under abiotic stresses. The OsbZIP20-GFP fusion protein predominantly aggregated in the nucleus, in accordance with our subcellular localization. OsbZIP20 transcript was observed in all vegetative tissues with highest levels being detected in the seed. Transcription of Osbzip20 was induced by salinity, exsiccation, and abscisic acid. Overexpression of OsbZIP20 in transgenic rice considerably improved tolerance to salt and drought stresses, as well as increased sensitivity to ABA. Furthermore, abiotic stress responsive genes transcript were found to be remarkably elevated in transgenic rice overexpressing OsbZIP20 than in wild-type plants. SAPK10 was discovered to directly interact with and phosphorylate OsbZIP20. Yeast one-hybrid and luciferase assay revealed that OsbZIP20 acted as a transcriptional stimulator. Interestingly, gel shift assay showed that phosphorylated bZIP20 augmented its DNA-binding affinity to the ABRE element of the NHX1 promoter and induced its transcription. In sum, our findings establish a novel signaling pathway associated with the SAPK10-bZIP20-NHX1 synergistic interaction, as well as a new strategy for enhancing rice drought and salt tolerance.
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http://dx.doi.org/10.1016/j.plantsci.2022.111393DOI Listing
July 2022

Association of Dietary Intake and Biomarker of α-Linolenic Acid With Incident Colorectal Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

Front Nutr 2022 7;9:948604. Epub 2022 Jul 7.

Institute of Lipids Medicine, Wenzhou Medical University, Wenzhou, China.

Background And Objective: There is keen interest in better understanding the impacts of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, in ameliorating the development of cancer; however, results of several prospective cohorts present an inconsistent association between ALA intake and the incident colorectal cancer (CRC). We aimed to investigate the summary association of dietary intake and biomarkers of ALA with CRC risk based on the prospective cohorts.

Methods: Pertinent prospective cohorts were identified in Cochrane Library, PubMed, and EMBASE from inception to February 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) for comparing the top with the bottom quartiles of ALA levels were combined using a random-effects model. Nonlinear dose-response relationships of ALA levels in diet and blood with CRC risk were assessed using the restricted cubic spline models, respectively.

Results: Over the duration of follow-up with a median of 9.3 years ranging from 1 to 28 years, 12,239 CRC cases occurred among 861,725 participants from 15 cohorts (11 studies on diet and 5 studies on biomarkers including 4 on blood and 1 on adipose tissue). The summary RR was 1.03 (95% CI: 0.97, 1.10; I: 0.00%) for dietary intake and 0.83 (95% CI: 0.69, 0.99; I: 0.00%) for biomarker. Each 0.1% increase in the levels of ALA in blood was associated with a 10% reduction in risk of CRC (summary RR: 0.90, 95% CI: 0.80, 0.99; I: 38.60%), whereas no significant dose-response association was found between dietary intake of ALA and the incident CRC (p for non-linearity = 0.18; p for linearity = 0.24).

Conclusions: Blood levels of ALA were inversely and linearly associated with the risk of CRC, which suggested that increased intake of ALA to improve circulating levels was beneficial for CRC prevention.
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http://dx.doi.org/10.3389/fnut.2022.948604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301188PMC
July 2022

A double crosslinking adhesion mechanism for developing tough hydrogel adhesives.

Acta Biomater 2022 Jul 20. Epub 2022 Jul 20.

Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Cancer Center at Illinois (CCIL), Urbana, IL 61801, United States; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Carle College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States. Electronic address:

Tough hydrogel adhesives that consist of a robust gel network and can strongly adhere to wet tissues have shown great promise as the next generation of bioadhesives. While a variety of chemistries can be utilized to construct the tough gel network, the covalent conjugation methods for tissue adhesion are still limited. Here we report, for the first time, the use of side product-free amine-thiolactone chemistry which initiates a double crosslinking adhesion mechanism to develop tough gel adhesives. Thiolactone groups can conjugate with tissue-surface amines via a ring-opening reaction. The resultant thiol end groups can be further crosslinked into disulfide linkages, enabling the formation of a robust and stable adhesion layer. The thiolactone-bearing tough hydrogel composed of methacrylate-modified gelatin, acrylic acid, and thiolacone acrylamide exhibited good biocompatibility and mechanical properties, and strong adhesion to various types of engineering solids and tissues. We also demonstrated its ability to function as a tissue sealant and drug depot. The novel adhesion mechanism will diversify future design of bioadhesives for hemostasis, drug delivery, tissue repair, and other applications. STATEMENT OF SIGNIFICANCE: Tough hydrogel adhesives with excellent tissue-adhesive and mechanical properties have demonstrated tremendous promise for hemostasis, tissue repair, and drug delivery applications. However, the covalent chemistry for tissue adhesion has been limited, which narrows the choice of materials for the design of bioadhesives and may pose a safety concern. Here, for the first time, we report the use of side product-free amine-thiolactone chemistry, which involves a double crosslinking adhesion mechanism, for developing tough hydrogel adhesives. We demonstrate that thiolactone-bearing tough hydrogels exhibit favorable biocompatibility and mechanical properties, and superior adhesion to both engineering solids and tissues. Our new adhesion technology will greatly facilitate future development of advanced bioadhesives for numerous biomedical applications.
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http://dx.doi.org/10.1016/j.actbio.2022.07.028DOI Listing
July 2022
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