bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Printed Bioreactor Enabling the Pulsatile Culture of Native and Angioplastied Large Arteries
Authors: Matos Rolando S. , Maselli Davide , McVey John H. , Heiss Christian , Campagnolo Paola
Published: June 2022

Routine interventions such as balloon angioplasty, result in vascular activation and remodeling, often requiring re-intervention. 2D in vitro models and small animal experiments have enabled the discovery of important mechanisms involved in this process, however the clinical translation is often underwhelming. There is a critical need for an ex vivo model representative of the human vascular physiology and encompassing the complexity of the vascular wall and the physical forces regulating its function. Vascular bioreactors for ex vivo culture of large vessels are viable alternatives, but their custom-made design and insufficient characterization often hinders the reproducibility of the experiments. The objective of the study was to design and validate a novel 3D printed cost-efficient and versatile perfusion system, capable of sustaining the viability and functionality of large porcine arteries for 7 days and enabling early post-injury evaluations. MultiJet Fusion 3D printing was used to engineer the EasyFlow insert, converting a conventional 50 ml centrifuge tube into a mini bioreactor. Porcine carotid arteries either left untreated or injured with an angioplasty balloon, were cultured under pulsatile flow for up to 7 days. Pressure, heart rate, medium viscosity and shear conditions were adjusted to resemble arterial in vivo hemodynamics. Tissue viability, cell activation and matrix remodeling were analyzed by immunohistochemistry, and vascular function was monitored by duplex ultrasound. Culture conditions in the EasyFlow bioreactor preserved endothelial coverage and smooth muscle organization and extracellular matrix structure in the vessel wall, as compared to static culture. Injured arteries presented hallmarks of early remodeling, such as intimal denudation, smooth muscle cell disarray and media/adventitia activation in flow culture. Duplex ultrasound confirmed continuous pulsatile blood flow conditions, dose-dependent vasodilator response to nitroglycerin in untreated vessels and impaired dilator response in angioplastied vessels. The scope of this work is to validate a low-cost, robust and reproducible system to explore the culture of native and injured large arteries under pulsatile flow. While the study of vascular pathology is beyond the scope of the present paper, our system enables future investigations and provides a platform to test novel therapies and devices ex vivo, in a patient relevant system.
Brain-Derived Neurotrophic Factor Reduces Long-Term Mortality in Patients With Coronary Artery Disease and Chronic Kidney Disease
Authors: Hsu Cheng-Yueh , Sheu Wayne Huey-Herng , Lee I-Te
Published: June 2022

Objectives

Chronic kidney disease (CKD) is a risk factor for coronary artery disease (CAD). We examined the effects of circulating brain-derived neurotrophic factor (BDNF) on long-term mortality in patients with CAD and CKD.

Materials and Methods

We enrolled patients with established CAD in the present study. Serum BDNF and estimated glomerular filtration rate (eGFR) were assessed after overnight fasting. All-cause mortality served as the primary endpoint.

Results

All 348 enrolled patients were divided into four groups according to their median BDNF level and CKD status, defined according to eGFR <60 mL/min/1.73 m2. Forty-five patients reached the primary endpoint during the median follow-up time of 6.0 years. Kaplan-Meier survival analysis indicated that the group with low BDNF and CKD had a significantly higher mortality rate than the other three groups (log-rank test p < 0.001). Compared to the high BDNF without CKD group, the low BDNF with CKD group had a hazard ratio (HR) of 3.186 [95% confidence interval (CI): 1.482–6.846] for all-cause mortality according to the multivariable Cox proportional hazard regression analysis after adjusting for age and urine albumin-creatinine ratio (p = 0.003). Furthermore, there was a significantly interactive effect between BDNF and CKD status on the risk of the primary endpoint (odds ratio = 6.413, 95% CI: 1.497–27.47 in the multivariable logistic regression model and HR = 3.640, 95% CI: 1.006–13.173 in the Cox regression model).

Conclusion

We observed a synergistic effect between low serum BDNF levels and CKD on the prediction of all-cause mortality in patients with CAD.
A Fractional Order Creep Damage Model for Microbially Improved Expansive Soils
Authors: Xuwen Tian , Hongbin Xiao , Zhenyu Li , Hunayu Su , Qianwen Ouyang , Shenping Luo , Xinpei Yu
Published: June 2022

Microbial Induced Calcite Precipitation method was used to improve the expansive soils of Nanning, Guangxi. The nonlinear shear creep behavior of microbially improved expansive soil was studied by triaxial consolidation drainage shear test. The results show that when the expansive soil was applied a small partial stress, the creep curve of soil exhibits transient deformation and decay creep. When the partial stress reaches a certain value, there is decay creep, steady-state creep and accelerated creep successively showed on the creep curve. The stress-strain isochronous curves reflect there are obvious nonlinear characteristics in the creep process of improved expansive soils. The degree of this nonlinearity is related to the creep time and stress level. The longer the creep time as well as the higher the stress level, the higher the degree of nonlinearity. Based on the fractional calculus theory and statistical damage theory, the probability density function of Weibull distribution was introduced, and the damage degradation of soft component viscosity coefficient was considered. As a result, a fractional-order damage creep model which can describe the shear creep evolution of microbially improved expansive soils is established. Compared with the Kelvin creep model of integer order and the Burgers creep model of fractional order, the fractional order damage creep model has not only better comparative evaluation results but also more higher computational accuracy. It indicates that the fractional-order damage creep model can better describe the whole process of shear creep in microbially improved expansive soils. The above findings provide a theoretical basis for the study of deformation analysis of microbially improved expansive soils under long-term loading.
Second Language Teaching With STEM
Authors: Crum Sibel
Published: June 2022

The American Council on the Teaching of Foreign Languages World-Readiness Standards for Learning Languages, also known as ACTFL 5 Cs, aims to guide pre-kindergarten through higher education second language (L2) educators in what L2 learners at every level should do to progress in each standard. The ACTFL’s 5Cs includes five goal areas: Communication, Cultures, Connections, Comparisons, and Communities. Empirical research has shown that of these standards, Connections, where the languages are connected to academic disciplines for strengthening the learning, is one of the least utilized standards in L2 classrooms. Incorporating Science, Technology, Engineering, and Mathematics (STEM) as the connection discipline can help post-secondary language learners in STEM and non-STEM fields develop the ability to effectively communicate technical and scientific STEM content within global STEM markets. This paper discusses the rationale for and the need to utilize the ACTFL’s Connections standards through STEM to grow and sustain L2 learners’ advanced language proficiency, as well as their employability and effectiveness in a highly competitive global work environment.
Effects of Anticoagulants and Immune Agents on Pregnancy Outcomes and Offspring Safety in Frozen-Thawed Embryo Transfer Cycles—A Retrospective Cohort Study
Authors: Fan Yanli , Wang Yizhuo , Luo Zhuoye , Xu Yueming , Zhang Jie , Wang Wei , Cui Na , Hao Guimin
Published: June 2022

The application of anticoagulants and immune agents in assisted reproduction technology has been in a chaotic state, and no clear conclusion has been reached regarding the effectiveness and safety of this treatment. We aimed to explore the potential association between adjuvant medication and pregnancy outcomes and offspring safety in a retrospective cohort study including 8,873 frozen-thawed embryo transfer cycles. The included cycles were divided into three groups according to the drugs used, namely, the routine treatment group (without anticoagulant agents and immune agents), the anticoagulant agent group, and the immunotherapy group. Among normal ovulatory patients, those who used immune agents had a 1.4-fold increased risk of miscarriage (≤13 weeks), but a 0.8-fold decreased chance of birth (≥28 weeks) compared with the routine treatment group. Among patients with more than 1 embryo transferred, those who used anticoagulant agents showed a 1.2-fold higher risk of multiple birth than those undergoing routine treatment. Among patients without pregnancy complications, anticoagulant treatment was associated with a 2.1-fold increased risk of congenital anomalies. Among young patients (<26 years) with a singleton pregnancy, the neonatal birth weight of the immunotherapy group and the anticoagulant treatment group was 305.4 g and 175.9 g heavier than the routine treatment group, respectively. In conclusion, adjuvant anticoagulants or immune agent treatment in assisted reproductive technology should be used under strict supervision, and the principle of individualized treatment should be followed.
Research on the Internal Flow Characteristics of Pump Turbines for Smoothing the Output Fluctuation of the Wind–Photovoltaic Complementary System
Authors: Ren Yan , Qiao Ruoyu , Wei Daohong , Hou Shangchen
Published: June 2022

Wind and photovoltaic (PV) power generation and other distributed energy sources are developing rapidly. But due to the influence of the environment and climate, the output is very unstable, which affects the power quality and power system stability. Pumped hydroelectric energy storage (PHES) systems are suitable as peaking power sources for wind and photovoltaic (Wind–PV) complementary systems because of their fast start–stop and long life. The mathematical models and operational characteristics of the three subsystems in the wind–PV–PHES complementary system are analyzed to improve the generation efficiency and access capacity of wind and PV power. The peaking characteristics of the PHES system are used to balance the maximum benefit and minimum output fluctuation of the wind–PV complementary system. The stable operation of the pump turbine is an important guarantee for the smooth output of the wind–PV complementary system. Three operating points are selected from the net load curve and converted to the pump turbine model parameters. The internal flow characteristics and laws of the pump turbine under different guide vane opening conditions are summarized through the analysis of the computational fluid dynamics (CFD) numerical simulation post-processing results. The study shows that the output of wind and PV power generation varies with the changes in wind speed and solar radiation, respectively. The output of the wind–PV complementary system still has large fluctuations, and the PHES system can effectively suppress the power fluctuation of the wind–PV complementary system and reduce the abandoned wind and light rate. CFD technology can accurately and efficiently characterize the internal flow characteristics of the pump turbine, which provides a basis for the design, optimization, and transformation of the pump turbine.
Dynamic Effects of CO2 Emissions on Anticipated Financial Development of European Countries
Authors: Liu Xiaojun , Zhang Kun , Tu Hong , Liu Cheng , Sun Yunpeng
Published: June 2022

This study investigates the motives behind the degrees of molecular pollution during the COVID-19 pandemic, which persisted from first walk 1 January 2020 to 31 December 2020. A spatial Durbin file model is used linked to an edge backslide model in this article to find the widely inclusive and nearby consequences of present-day plan and urbanization on nonrenewable energy source by things. The outcomes are discussed next: both were available in modern-day plan and urbanization from a generally inclusive standpoint. The geological consequences of CO2 emissions were concentrated on utilizing information from 22 European countries somewhere in the range of 1990–2020, and all through the examination cycle, the Durbin spatial model was discovered. Although factors such as gross domestic product per capita, urbanization, and energy power impact CO2 emissions, exchange receptivity stays unaltered. The findings will fill in as critical repercussions for state-run administrations, wellbeing experts, and regulators in the war against the return of COVID-19 in Europe. The great number of suggestions were worthless since the concept integrated six money-connected creation assessments into a coordinated arrangement. There is information to indicate that CO2 emissions are associated with money-related events in neighboring nations.
Empirical Decomposition and Forecast of Carbon Neutrality for High-End Equipment Manufacturing Industries
Authors: Lu Hang , Elahi Ehsan , Sun Zhenya
Published: June 2022

The Chinese government focuses on the high-end equipment manufacturing industry to achieve a target of carbon neutrality. This study takes China’s Bohai Rim as a case study. First, the Tapio decoupling model was used to analyze the carbon emission status of the high-end equipment manufacturing industry in the Bohai Rim. Second, LMDI was used to determine the main factors of carbon emission. Similarly, the Monte Carlo simulation predicted the time of carbon neutrality. The results found that the relationship between carbon emission and the development of the high-end equipment manufacturing industry is that of strong decoupling, but there is still a risk of “recoupling.” The scale effect is the primary driving force for carbon emission reduction in the equipment manufacturing industry, followed by a structural effect and a carbon emission intensity effect. In the baseline scenario, low-carbon scenario, and technological breakthrough scenario, carbon neutrality will be achieved before 2060. The results of the study suggest that China should improve energy utilization efficiency and encourage green innovation.
LncRNA-mRNA Expression Profiles of Osteoclast After Conditional Knockout HIF-1α
Authors: Tian Yuanye , Shao Qi , Gu Jiahong , Tang Yi , Bie Miaomiao , Zhou Yangyifan , Cheng Chunan , Liang Yi , Zhang Qian , Kang Feiwu
Published: June 2022

Background: Osteoclasts, which are multinucleated cells formed by monocyte fusion, play a key role in bone resorption. Hypoxia-inducible factor (HIF)-1α is vital for the development of osteoclasts in hypoxic environments and during bone resorption. However, additional research is required to further study the HIF-1α-dependent regulation of osteoclast differentiation at the genetic level.

Methods: In our study, RNA sequencing (RNA-seq) was used to identify the expression profiles of long noncoding RNAs (lncRNAs) and mRNAs in conditional HIF-1α-knockout osteoclasts.

Results: A total of 1,320 mRNAs and 95 lncRNAs were differentially expressed. The expression of lncRNAs MSTRG.7566.12 and MSTRG.31769.2 were strongly negatively correlated with that of Mmp9, Ctsk, etc.

Conclusion: Our research provides a basis for further understanding the role of mRNAs and lncRNAs in conditional HIF-1α-knockout osteoclasts, and many of these molecules may be potential targets for treating bone diseases related to HIF-1α.
Characterization of Different Subtypes of Immune Cell Infiltration in Glioblastoma to Aid Immunotherapy
Authors: Feng Peng , Li Zhenqing , Li Yuchen , Zhang Yuelin , Miao Xingyu
Published: June 2022

Glioblastoma multiforme (GBM) has been identified as a frequently occurring adult primary brain cancer that is highly aggressive. Currently, the prognostic outcome for GBM patients is dismal, even with intensive treatment, and the median overall survival (OS) is 14.6 months. Immunotherapy, which is specific at the cellular level and can generate persistent immunosurveillance, is now becoming a promising tool to treat diverse cancers. However, the complicated nature of the tumor microenvironment (TME) makes it challenging to develop anti-GBM immunotherapy because several cell types, cytokines, and signaling pathways are involved in generating the immunosuppressive environment. Novel immunotherapies can illustrate novel tumor-induced immunosuppressive mechanisms. Here, we used unsupervised clustering analysis to identify different subtypes of immune cell infiltration that actuated different prognoses, biological actions, and immunotherapy responses. Gene cluster A, with a hot immune cell infiltration phenotype, had high levels of immune-related genes (IRGs), which were associated with immune pathways including the interferon-gamma response and interferon-alpha response, and had low IDH1 and ATRX mutation frequencies. Gene cluster B, a cold immune cell infiltration subtype, exhibited a high expression of the KCNIP2, SCRT1, CPLX2, JPH3, UNC13A, GABRB3, ARPP21, DLGAP1, NRXN1, DLL3, CA10, MAP2, SEZ6L, GRIA2, and GRIA4 genes and a low expression of immune-related genes, i.e., low levels of immune reactivity. Our study highlighted the complex interplay between immune cell infiltration and genetic mutation in the establishment of the tumor immune phenotype. Gene cluster A was identified as an important subtype with a better prognosis and improved immunotherapy response.
Immunoinformatics Aided Design and In-Vivo Validation of a Cross-Reactive Peptide Based Multi-Epitope Vaccine Targeting Multiple Serotypes of Dengue Virus
Authors: Kaushik Vikas , G Sunil Krishnan , Gupta Lovi Raj , Kalra Utkarsh , Shaikh Abdul Rajjak , Cavallo Luigi , Chawla Mohit
Published: June 2022

Dengue virus (DENV) is an arboviral disease affecting more than 400 million people annually. Only a single vaccine formulation is available commercially and many others are still under clinical trials. Despite all the efforts in vaccine designing, the improvement in vaccine formulation against DENV is very much needed. In this study, we used a roboust immunoinformatics approach, targeting all the four serotypes of DENV to design a multi-epitope vaccine. A total of 13501 MHC II binding CD4+ epitope peptides were predicted from polyprotein sequences of four dengue virus serotypes. Among them, ten conserved epitope peptides that were interferon-inducing were selected and found to be conserved among all the four dengue serotypes. The vaccine was formulated using antigenic, non-toxic and conserved multi epitopes discovered in the in-silico study. Further, the molecular docking and molecular dynamics predicted stable interactions between predicted vaccine and immune receptor, TLR-5. Finally, one of the mapped epitope peptides was synthesized for the validation of antigenicity and antibody production ability where the in-vivo tests on rabbit model was conducted. Our in-vivo analysis clearly indicate that the imunogen designed in this study could stimulate the production of antibodies which further suggest that the vaccine designed possesses good immunogenicity.
Cellular Mechanisms Underlying B Cell Abnormalities in Patients With Gain-of-Function Mutations in the PIK3CD Gene
Authors: Wang Wenjie , Min Qing , Lai Nannan , Csomos Krisztian , Wang Ying , Liu Luyao , Meng Xin , Sun Jinqiao , Hou Jia , Ying Wenjing , Zhou Qinhua , Sun Bijun , Hui Xiaoying , Ujhazi Boglarka , Gordon Sumai , Buchbinder David , Schuetz Catharina , Butte Manish , Walter Jolan E. , Wang Xiaochuan , Wang Ji-Yang
Published: June 2022

Background

Activated phosphoinositide 3 kinase (PI3K) -delta syndrome (APDS) is an inborn error of immunity with variable clinical phenotype of immunodeficiency and immune dysregulation and caused by gain-of-function mutations in PIK3CD. The hallmark of immune phenotype is increased proportions of transitional B cells and plasmablasts (PB), progressive B cell loss, and elevated levels of serum IgM.

Objective

To explore unique B cell subsets and the pathomechanisms driving B cell dysregulation beyond the transitional B cell stage in APDS.

Methods

Clinical and immunological data was collected from 24 patients with APDS. In five cases, we performed an in-depth analysis of B cell phenotypes and cultured purified naïve B cells to evaluate their survival, activation, Ig gene class switch recombination (CSR), PB differentiation and antibody secretion. We also analyzed PB differentiation capacity of sorted CD27-IgD- double-negative B (DNB) cells.

Results

The patients had increased B cell sizes and higher proportions of IgM+ DNB cells than healthy controls (HC). Their naïve B cells exhibited increased death, impaired CSR but relatively normal PB differentiation. Upon stimulation, patient’s DNB cells secreted a similar level of IgG but a higher level of IgM than DNB cells from HC. Targeted therapy of PI3K inhibition partially restored B cell phenotypes.

Conclusions

The present study suggests additional mechanistic insight into B cell pathology of APDS: (1) decreased peripheral B cell numbers may be due to the increased death of naïve B cells; (2) larger B cell sizes and expanded DNB population suggest enhanced activation and differentiation of naïve B cells into DNB cells; (3) the impaired CSR yet normal PB differentiation can predominantly generate IgM-secreting cells, resulting in elevated IgM levels.
Individual and Synergistic Anti-Coronavirus Activities of SOCS1/3 Antagonist and Interferon α1 Peptides
Authors: Ahmed Chulbul M. , Grams Tristan R. , Bloom David C. , Johnson Howard M. , Lewin Alfred S.
Published: June 2022

Suppressors of Cytokine Signaling (SOCS) are intracellular proteins that negatively regulate the induction of cytokines. Amongst these, SOCS1 and SOCS3 are particularly involved in inhibition of various interferons. Several viruses have hijacked this regulatory pathway: by inducing SOCS1and 3 early in infection, they suppress the host immune response. Within the cell, SOCS1/3 binds and inhibits tyrosine kinases, such as JAK2 and TYK2. We have developed a cell penetrating peptide from the activation loop of the tyrosine kinase, JAK2 (residues 1001-1013), denoted as pJAK2 that acts as a decoy and suppresses SOCS1 and 3 activity. This peptide thereby protects against several viruses in cell culture and mouse models. Herein, we show that treatment with pJAK2 inhibited the replication and release of the beta coronavirus HuCoV-OC43 and reduced production of the viral RNA, as measured by RT-qPCR, Western blot and by immunohistochemistry. We confirmed induction of SOCS1 and 3 in rhabdomyosarcoma (RD) cells, and this induction was suppressed by pJAK2 peptide. A peptide derived from the C-terminus of IFNα (IFNα-C) also inhibited replication of OC43. Furthermore, IFNα-C plus pJAK2 provided more potent inhibition than either peptide alone. To extend this study to a pandemic beta-coronavirus, we determined that treatment of cells with pJAK2 inhibited replication and release of SARS-CoV-2 in Calu-3 cells. We propose that these peptides offer a new approach to therapy against the rapidly evolving strains of beta-coronaviruses.
Proteomic Analyses Reveal Higher Levels of Neutrophil Activation in Men Than in Women With Systemic Lupus Erythematosus
Authors: Cai Ming-long , Gui Lan , Huang He , Zhang Yu-kun , Zhang Li , Chen Zhu , Sheng Yu-jun
Published: June 2022

Objective

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays a significant gender difference in terms of incidence and severity. However, the underlying mechanisms accounting for sexual dimorphism remain unclear. The aim of this work was to reveal the heterogeneity in the pathogenesis of SLE between male and female patients.

Methods

PBMC were collected from 15 patients with SLE (7 males, 8 females) and 15 age-matched healthy controls (7 males, 8 females) for proteomic analysis. The proteins of interest were validated in independent samples (6 male SLE, 6 female SLE). Biomarkers for neutrophil activation (calprotectin), neutrophil extracellular traps (cell-free DNA and elastase), and reactive oxygen species (glutathione) were measured, using enzyme-linked immunosorbent assay, in plasma obtained from 52 individuals.

Results

Enrichment analysis of proteomic data revealed that type I interferon signaling and neutrophil activation networks mapped to both male and female SLE, while male SLE has a higher level of neutrophil activation compared with female SLE. Western blot validated that PGAM1, BST2, and SERPINB10 involved in neutrophil activation are more abundant in male SLE than in female SLE. Moreover, biomarkers of neutrophil activation and reactive oxygen species were increased in male SLE compared with female SLE.

Conclusion

Type I interferon activation is a common signature in both male and female SLE, while neutrophil activation is more prominent in male SLE compared with female SLE. Our findings define gender heterogeneity in the pathogenesis of SLE and may facilitate the development of gender-specific treatments.
An Emerging Role for Neutrophil Extracellular Traps in IgA Vasculitis: A Mini-Review
Authors: Chen Xiu-Qi , Tu Li , Tang Qing , Huang Li , Qin Yuan-Han
Published: June 2022

Immunoglobulin A vasculitis (IgAV) is the most common systemic small vessel vasculitis in childhood. Its clinical manifestations are non-thrombocytopenic purpura, accompanied by gastrointestinal tract, joint, kidney and other organ system involvement. The pathogenesis of IgAV has not been fully elucidated. It may be related to many factors including genetics, infection, environmental factors, and drugs. The most commonly accepted view is that galactose-deficient IgA1 and the deposition of IgA and complement C3 in small blood vessel walls are key contributors to the IgAV pathogenesis. Extensive neutrophil extracellular traps (NETs) in the peripheral circulation and skin, kidney, and gastrointestinal tissue of patients with IgAV has been identified in the past two years and is associated with disease activity. This mini-review provides a possible mechanism for NETs involvement in the pathogenesis of IgAV.
Is the Number of Missing Teeth Associated With Mortality? A Longitudinal Study Using a National Health Screening Cohort
Authors: Kim So Young , Lee Chang Ho , Yoo Dae Myoung , Kwon Mi Jung , Kim Ji Hee , Kim Joo-Hee , Byun Soo-Hwan , Park Bumjung , Lee Hyo-Jeong , Choi Hyo Geun
Published: June 2022

This study aimed to estimate the risk of mortality related to the number of missing teeth in a South Korean population. The ≥ 40-year-old population of the Korean National Health Insurance Service-Health Screening Cohort 2002–2003 was analyzed. Participants were selected from a total of 220,189 participants and included in groups of 0 teeth lost, 1–2 teeth lost, and ≥ 3 teeth lost. Among the total population, 17,211 participants were included in no missing teeth, 1–2 missing teeth, and ≥ 3 missing teeth and were randomly matched 1:1:1 for age and sex. Mortality from specific causes and all-cause mortality were compared among the groups. The hazard ratio (HR) of the number of missing teeth for all-cause mortality or each cause of mortality was analyzed using Cox proportional hazard models. According to the cause of death, the HRs for metabolic disease, digestive disease, and trauma were greater in the group with ≥ 3 missing teeth than in the no missing teeth group. The group with ≥ 3 missing teeth indicated a 1.19-fold higher HR for all-cause mortality than the no missing teeth group [95% confidence intervals (95% CIs) = 1.12–1.27, P < 0.001]. The group with 1- 2 missing teeth did not show a higher HR for all-cause mortality. In the group with 1–2 missing teeth, the HRs for mortality from mental disease and digestive disease were higher than those in the no missing teeth group. The group with 1–2 missing teeth did not show a higher HR for all-cause mortality. The number of missing teeth was linked with a higher risk of mortality. For specific causes of mortality, mortality from metabolic disease, digestive disease, and trauma was higher in the participants with the number of missing teeth.
In-center Nocturnal Hemodialysis Reduced the Circulating FGF23, Left Ventricular Hypertrophy, and All-Cause Mortality: A Retrospective Cohort Study
Authors: Kang Meizi , Chen Jing , Liu Lingling , Xue Cheng , Tang Xiaojing , Lv Jiayi , Fu Lili , Mei Changlin , Mao Zhiguo , Liu Yawei , Dai Bing
Published: June 2022

Fibroblast growth factor 23(FGF23) is the most important biomarker and pathogenic factor in Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD). In the moderate and severe stages of chronic renal failure, abnormally elevated circulating FGF23 can lead to some complications, including myocardial hypertrophy, which is positively correlated with all-cause mortality. However, the circulating FGF23 level of different hemodialysis modalities, the underlying essential regulatory factors, and potential clinical benefits remain to be elucidated. In this retrospective cohort study, 90 in-center nocturnal hemodialysis (INHD) and 90 matched conventional hemodialysis (CHD) patients were enrolled. The complete blood count, intact FGF23(iFGF23), calcium, phosphorus, PTH, and other biochemical and echocardiographic parameters of INHD and CHD patients were collected and analyzed at 1-year follow-up. The all-cause mortality was recorded during the 7-year follow-up. Furthermore, the regulatory factors of iFGF23 and its association with echocardiographic parameters and mortality were investigated by multivariate regression. The levels of iFGF23 and serum phosphate in patients undergoing INHD were significantly lower than those in patients undergoing CHD. The left ventricular volume index (LVMI) in patients with INHD was significantly attenuated and positively correlated with the drop of serum iFGF23. The INHD group had reduced all-cause mortality compared to the CHD group. Multivariate analysis showed that iFGF23 was positively correlated with serum calcium, serum phosphorus, and calcium-phosphate product. The calcium-phosphate product is an independent determining factor of serum iFGF23. Compared with the CHD group, the INHD group presented with a significantly reduced circulating iFGF23 level, which was closely associated with attenuation of left ventricular hypertrophy, but INHD reduced all-cause mortality in an FGF23 independent manner.
Mitochondrial DNA as a Biomarker for Acute Central Serous Chorioretinopathy: A Case-Control Study
Authors: Hashida Noriyasu , Asao Kazunobu , Hara Chikako , Quantock Andrew J. , Saita Ryotaro , Kurakami Hiroyuki , Maruyama Kazuichi , Nishida Kohji
Published: June 2022

Background

The literature suggests that stress may play a pivotal role in the precipitation of acute central serous chorioretinopathy (CSC) because chorioretinal integrity can be affected by the psychosocial state of the patient, indicating the need for a biomarker. Not only physical stress but also psychological stress causes many types of physical disorders. However, little is known about the pathophysiology of stress-induced disease. The objective of this study was to investigate whether serum factors might be involved in the development of stress-induced ocular diseases.

Methods

This observational case series included 33 eyes of 33 consecutive patients with treatment-naïve acute CSC. Fifty eyes of 50 age-matched healthy volunteers were included in this study as non-CSC controls. Serum samples were collected from all participants, and the levels of mitochondrial DNA (mtDNA) were measured by quantitative real-time (RT)-PCR. Serum levels of high-mobility group box (HMGB) 1 and 8-hydroxy-2′-deoxyguanosine (8-OHdG), biological markers of acute/chronic inflammation and oxidative stress, were also measured. The relationships between serum mtDNA, 8-OHdG, and HMGB1 concentrations were investigated by multivariate regression analysis, alongside an assessment of clinical data.

Results

In the treatment-naïve acute CSC group, the serum mtDNA levels (36.5 ± 32.4 ng/mL) were significantly higher than the levels in the control group (7.4 ± 5.9 ng/mL; p < 0.001). Serum levels of 8-OHdG and HMGB1 in treatment-naïve acute CSC patients measured 0.12 ± 0.08 ng/mL and 18.1 ± 35.0 ng/mL, respectively, indicating that HMGB1 levels were elevated in CSC compared with the control group. Multivariable regression analysis demonstrated that increased serum mtDNA levels were significantly associated with the height of serous retinal detachment.

Conclusion

We showed serum mtDNA and HMGB1 level elevation and its relation to the clinical activities of CSC, indicating that serum mtDNA and HMGB1 could serve as biomarkers for the acute phase of the disease. The use of these biomarkers makes it possible to predict disease onset and determine disease severity.
The Distinguishing Bacterial Features From Active and Remission Stages of Ulcerative Colitis Revealed by Paired Fecal Metagenomes
Authors: Zhu Ran , Tang Junrui , Xing Chengfeng , Nan Qiong , Liang Guili , Luo Juan , Zhou Jiao , Miao Yinglei , Cao Yu , Dai Shaoxing , Lan Danfeng
Published: June 2022

Ulcerative colitis (UC) is a serious chronic intestinal inflammatory disease, with an increased incidence in recent years. The intestinal microbiota plays a key role in the pathogenesis of UC. However, there is no unified conclusion on how the intestinal microbiota changes. Most studies focus on the change between UC patients and healthy individuals, rather than the active and remission stage of the same patient. To minimize the influences of genetic differences, environmental and dietary factors, we studied the intestinal microbiota of paired fecal samples from 42 UC patients at the active and remission stages. We identified 175 species of microbes from 11 phyla and found no difference of the alpha and beta diversities between the active and remission stages. Paired t-test analysis revealed differential microbiota at levels of the phyla, class, order, family, genus, and species, including 13 species with differential abundance. For example, CAG-269 sp001916005, Eubacterium F sp003491505, Lachnospira sp000436475, et al. were downregulated in the remission, while the species of Parabacteroides distasonis, Prevotellamassilia sp900540885, CAG-495 sp001917125, et al. were upregulated in the remission. The 13 species can effectively distinguish the active and remission stages. Functional analysis showed that the sporulation and biosynthesis were downregulated, and the hydrogen peroxide catabolic process was upregulated in remission of UC. Our study suggests that the 13 species together may serve as a biomarker panel contributing to identify the active and remission stages of UC, which provides a valuable reference for the treatment of UC patients by FMT or other therapeutic methods.
Diverse Aquatic Animal Matrices Play a Key Role in Survival and Potential Virulence of Non-O1/O139 Vibrio cholerae Isolates
Authors: Yan Lili , Jin Yinzhe , Zhang Beiyu , Xu Yingwei , Peng Xu , Qin Si , Chen Lanming
Published: June 2022

Vibrio cholerae can cause pandemic cholera in humans. The waterborne bacterium is frequently isolated from aquatic products worldwide. However, current literature on the impact of aquatic product matrices on the survival and pathogenicity of cholerae is rare. In this study, the growth of eleven non-O1/0O139 V. cholerae isolates recovered from eight species of commonly consumed fish and shellfish was for the first time determined in the eight aquatic animal matrices, most of which highly increased the bacterial biomass when compared with routine trypsin soybean broth (TSB) medium. Secretomes of the V. cholerae isolates (draft genome size: 3,852,021–4,144,013 bp) were determined using two-dimensional gel electrophoresis (2DE-GE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques. Comparative secretomic analyses revealed 74 differential extracellular proteins, including several virulence- and resistance-associated proteins secreted by the V. cholerae isolates when grown in the eight matrices. Meanwhile, a total of 8,119 intracellular proteins were identified, including 83 virulence- and 8 resistance-associated proteins, of which 61 virulence-associated proteins were absent from proteomes of these isolates when grown in the TSB medium. Additionally, comparative genomic and proteomic analyses also revealed several strain-specific proteins with unknown functions in the V. cholerae isolates. Taken, the results in this study demonstrate that distinct secretomes and proteomes induced by the aquatic animal matrices facilitate V. cholerae resistance in the edible aquatic animals and enhance the pathogenicity of the leading waterborne pathogen worldwide.
Early Weaning and Milk Substitutes Affect the Gut Microbiome, Metabolomics, and Antibody Profile in Goat Kids Suffering From Diarrhea
Authors: Zhong Tao , Wang Cheng , Wang Xinlu , Freitas-de-Melo Aline , Zeng Bo , Zhao Qianjun , Zhan Siyuan , Wang Linjie , Cao Jiaxue , Dai Dinghui , Guo Jiazhong , Li Li , Zhang Hongping , Niu Lili
Published: June 2022

Early weaning and milk substitutes increase the incidence of diarrhea in young ruminants, which may modify their gut microbiota, metabolism, immunity, and health. The aim of the study was to determine if early weaning and milk substitutes affect the gut microbiota, metabolism, and immunological status of goat kids suffering from diarrhea. The 16S rRNA gene and metagenomic sequencing in feces and serum metabolomics of early-weaned and artificially reared goat kids suffering from diarrhea (DK group) and healthy goat kids reared by their mothers (HK group) were analyzed. The serum biochemistry and immunoglobulin concentration were also determined. Several probiotics, such as Streptococcus and Lactobacillus, were higher in the feces of the DK group than in feces of the HK group. Ruminococcus sp. was elevated in the feces of HKs, likely being a biomarker for goat health. Taking all the carbohydrate-active enzyme (CAZyme) families into consideration, 20 CAZyme families were different between the groups. Compared with the DK group, the relative quantity of glycoside hydrolases (GH) and glycosyltransferase (GT) families in the HK group decreased. GT70 was only identified in HK kids participating in the activity of β-glucuronosyltransferase during the carbohydrate metabolism. Overall, 24 metabolites were different between the groups, which were mainly involved in protein digestion and absorption, cyanoamino acid metabolism, and cholesterol metabolism. The concentrations of immunoglobulins G and M were significantly lower in the DK than in the HK group. In conclusion, our study characterized the fecal microbiota, metabolism, and immunological status of early-weaned and artificially reared goat kids suffering from diarrhea.
A Distinct Tobamovirus Associated With Trichosanthes kirilowii Mottle Mosaic Disease
Authors: Chen Cheng , Du Min , Peng Deliang , Li Wulun , Xu Jingfeng , Yang Xiuling , Zhou Xueping
Published: June 2022

Trichosanthes kirilowii is one of the most important perennial herbaceous vines that have been used in traditional Chinese medicine. In this study, a novel RNA virus was discovered in T. kirilowii plants showing leaf mottling and mosaic symptoms. The complete genome of this virus is 6,524 nucleotides long and encodes four open reading frames which are arranged in a manner typical of tobamoviruses. Phylogenetic analysis based on the complete genome sequence revealed that the virus was clustered into a branch with the tobamoviruses whose natural host are plants belonging to the family Cucurbitaceae. A full-length infectious cDNA clone was then constructed and demonstrated to establish a systemic infection with typical symptoms in Nicotiana benthamiana, T. kirilowii, and five other cucurbitaceous crops including Cucumis melo, C. lanatus, C. sativus, Luffa aegyptiaca, and Cucurbita pepo via agrobacterium-mediated infectivity assays. Further experiments provided evidence that the rod-shaped viral particles derived from the infectious clone could be mechanically transmitted and reproduce indistinguishable symptoms in the tested plants. Taken together, the mottle mosaic disease of T. kirilowii is caused by a distinct tobamovirus, for which the name Trichosanthes mottle mosaic virus (TrMMV) is proposed. As the infectious cDNA clone of TrMMV could also infect five other cucurbit crops, this distinct tobamovirus could be a potential threat to other cucurbitaceous crops.
New Kid on the Block: The Efficacy of Phytomedicine Extracts Urox® in Reducing Overactive Bladder Symptoms in Rats
Authors: Zapała Łukasz , Juszczak Kajetan , Adamczyk Przemysław , Adamowicz Jan , Ślusarczyk Aleksander , Kluz Tomasz , Misiek Marcin , Rogowski Artur , Grzybowska Magdalena Emilia , Stangel-Wójcikiewicz Klaudia , Zaborowski Mikołaj Piotr , Poleszak Ewa , Radziszewski Piotr , Wróbel Andrzej
Published: June 2022

The aim of the current study was to determine if phytomedicine (Urox®) would reverse retinyl acetate (RA)–induced changes characteristic of bladder overactivity. There were 60 rats divided into the following 4 groups: I—control, II—received RA to induce detrusor overactivity (DO), III—received Urox (840 mg daily for 14 days), and IV—received combination of RA and Urox®. The cystometry was performed 2 days after the last dose of Urox®. Next, urothelium thickness and biochemical parameter measurements were performed. In group IV, a decrease in basal pressure and detrusor overactivity index was noted when compared to group II. Furthermore, in group IV the following parameters were increased: threshold pressure, voided volume, intercontraction interval, and bladder compliance in comparison with group II. There were significant elevations in c-Fos expression in the neuronal voiding centers in group II, while the expression of c-Fos in group IV was normalized. No significant changes in the values of the analyzed biomarkers in group III were found, while in group II, an elevation in BDNF, NGF, CGRP, ATP, Rho kinase, malondialdehyde, 3-nitrotyrosine, TRPV1, OCT-3, and VAChT and then a decrease in E-cadherin and Z01 were found. A successful restoration of all the abovementioned biomarkers’ levels was observed in group IV. Phytomedicine extracts (Urox®) were found to be potent in reversing RA-induced changes in several cystometric and biochemical parameters that are determinants of overactive bladder (OAB). The actions of Urox® were proved to be dependent on several factors, such as growth factors and several OAB biomarkers but not pro-inflammatory cytokines.
Network Pharmacology-Based Strategy to Investigate the Pharmacologic Mechanisms of Coptidis Rhizoma for the Treatment of Alzheimer's Disease
Authors: Ye Xian-wen , Wang Hai-li , Cheng Shui-qing , Xia Liang-jing , Xu Xin-fang , Li Xiang-ri
Published: June 2022

Background

Alzheimer's disease (AD) is becoming a more prevalent public health issue in today's culture. The experimental study of Coptidis Rhizoma (CR) and its chemical components in AD treatment has been widely reported, but the principle of multi-level and multi-mechanism treatment of AD urgently needs to be clarified.

Objective

This study focuses on network pharmacology to clarify the mechanism of CR's multi-target impact on Alzheimer's disease.

Methods

The Phytochemical-compounds of CR have been accessed from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and Symmap database or HPLC determination. The values of Oral Bioavailability (OB) ≥ 30% and Drug Like (DL) ≥ 0.18 or blood ingredient were used to screen the active components of CR; the interactive network of targets and compounds were constructed by STRING and Cytoscape platform, and the network was analyzed by Molecular Complex Detection (MCODE); Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) and metabolic pathway enrichment of targets were carried out with Metascape, the Database for Annotation, Visualization and Integrated Discovery (DAVID) and MetaboAnalyst platform; Based on CytoHubba, the potential efficient targets were screened by Maximal Clique Centrality (MCC) and Degree, the correlation between potential efficient targets and amyloid β-protein (Aβ), Tau pathology was analyzed by Alzdata database, and the genes related to aging were analyzed by Aging Altas database, and finally, the core targets were obtained; the binding ability between ingredients and core targets evaluated by molecular docking, and the clinical significance of core targets was assessed with Gene Expression Omnibus (GEO) database.

Results

19 active components correspond to 267 therapeutic targets for AD, of which 69 is potentially effective; in module analysis, RELA, TRAF2, STAT3, and so on are the critical targets of each module; among the six core targets, RELA, MAPK8, STAT3, and TGFB1 have clinical therapeutic significance; GO function, including 3050 biological processes (BP), 257 molecular functions (MF), 184 cellular components (CC), whose functions are mainly related to antioxidation, regulation of apoptosis and cell composition; the HIF-1 signaling pathway, glutathione metabolism is the most significant result of 134 KEGG signal pathways and four metabolic pathways, respectively; most of the active components have an excellent affinity in docking with critical targets.

Conclusion

The pharmacological target prediction of CR based on molecular network pharmacology paves the way for a multi-level networking strategy. The study of CR in AD treatment shows a bright prospect for curing neurodegenerative diseases.
Are Mind-Body Exercise Beneficial for Treating Pain, Function, and Quality of Life in Middle-Aged and Old People With Chronic Pain? A Systematic Review and Meta-Analysis
Authors: Wen Yu-Rong , Shi Jian , Wang Ya-Fei , Lin Yang-Yang , Hu Zheng-Yu , Lin You-Tian , Wang Xue-Qiang , Wang Yu-Ling
Published: June 2022

Background

Aging is a significant risk factor in chronic pain development with extensive disability and greater health care costs. Mind-body exercise (MBE) has been scientifically proven to affect the pain intensity and physical health.

Objectives

To assess the effects of MBE modes (Tai Chi, yoga, and qigong) for treating chronic pain among middle-aged and old people, compared with nonactive and active treatment, as well as function, quality of life, and adverse events.

Methods

We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journals Full-Text Database (VIP) till March 2022. No restrictions were chartered within the year and language of publication. We included randomized controlled trials of MBE treatment in middle-aged and elderly people with chronic pain. The overall certainty of evidence was evaluated by using the GRADE approach.

Results

A total of 17 studies (n = 1,332) were included in this review. There was low-certainty evidence indicating that MBE had a moderate effect on reducing pain compared with the nonactive and active control group (standard mean difference (SMD): −0.64, 95% confidence interval (CI): −0.86 to −0.42, P < 0.001). Very-low-certainty evidence showed that the pooled SMD for the functional improvement was −0.75 (95% CI: −1.13 to −0.37, P < 0.001). Low-certainty evidence presented that no influence was observed in physical component summary (SMD: 0.23, 95% CI: −0.16 to 0.62, P = 0.24) and mental component summary (SMD: −0.01, 95% CI −0.39 to 0.36, P = 0.95).

Conclusion

Our results indicated that MBE was an effective treatment for reducing symptoms of middle-aged and elderly people with chronic pain compared with nonactive and active control groups. TC and qigong had obvious benefits for knee osteoarthritis in self-reported function, but the efficacy of chronic low back pain was uncertain. No significant benefit of MBE on quality of life in older adults with chronic pain was found. More high-quality RCTs should be conducted to explore the efficacy and mechanism of MBE on chronic pain in middle-aged and elderly people from various dimensions, such as affective and cognitive dimensions.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316591, identifier CRD42022316591.