bluuebunny/crossref_metadata_2025 huggingface dataset:
Traditional Chinese medicine method of tonifying kidney for hypertension: Clinical evidence and molecular mechanisms
Authors: Wang Qingqing , Lin Jianguo , Li Cheng , Lin Mingshan , Zhang Qing , Zhang Xiaoxiao , Yao Kuiwu
Published: November 2022

Hypertension is the most common chronic disease. A large amount of evidence showed that traditional Chinese medicine (TCM) method of tonifying kidney (TK) combined with routine treatment is more effective and safer in the treatment of hypertension. This study integrated meta-analysis, data mining, and network pharmacology to explore the efficacy and potential mechanisms of TK in the treatment of hypertension. Meta-analysis was performed to explore the efficacy and safety of TK combined with routine treatment in the treatment of hypertension. Data mining was used to screen the core herbs of the TK. Network pharmacology was used to predict the antihypertensive mechanism of TK core herbs. A total of 18 studies with 2,024 patients were included in this study. Meta-analysis showed that TK combined with routine treatment was superior to routine treatment alone in lowering blood pressure (systolic and diastolic blood pressures), lowering blood lipids (total cholesterol, triglyceride, low-density lipoprotein cholesterol), improving vascular endothelial functions (nitric oxide, endothelin) and TCM symptoms (headache dizziness, soreness, and weakness of waist and knees). In addition, TK was safe and has no obvious adverse reactions. Data mining showed that the core herbs of TK were Eucommia ulmoides Oliv. (Duzhong), Vitex negundo L. (Huangjing), Taxillus chinensis (DC.) Danser (Sangjisheng), Ligustrum lucidum W.T.Aiton (Nuzhenzi), Astragalus mongholicus Bunge (Huangqi), Rehmannia glutinosa (Gaertn.) DC. (Shudihuang). Network pharmacology predicted that core herbs antihypertensive components were oleanolic acid, ursolic acid, and civetone, and the antihypertensive targets were NOS3, NOS2, MMP9, TNF, PTGS2, HMOX1. In addition, the antihypertensive targets were enriched in cGMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption, HIF-1 signaling pathway. In conclusion, TK combined with routine treatment for hypertension is effective and safe. The mechanism of TK may be related to GMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption. On the premise of syndrome differentiation and treatment, it is promising to treat hypertension with TK.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022358276].
Chick early amniotic fluid component improves heart function and protects against inflammation after myocardial infarction in mice
Authors: Wang Juan , Chen Xiejiu , Zhang Lihong , Zheng Yufan , Qian Jin , Sun Ning , Ding Xiaolei , Cui Baiping
Published: November 2022

Myocardial infarction (MI) is the major cause of mortality around the world. We recently demonstrated that chick early amniotic fluid (ceAF) can effectively rescue ischemic heart injury, indicating that it has a therapeutic function in MI. However, its functional components and the underlying mechanisms remain to be clarified. Here, we demonstrated that a fraction of ceAF, peak 8 (P8), had a protective effect on acute MI. P8 significantly decreased cardiomyocyte cross-sectional areas and cardiomyocyte apoptosis in MI mice. Using a human embryonic stem cell-derived cardiomyocyte model, which was subjected to hypoxia and reoxygenation, mimicking MI state, we found that P8 treatment reduced apoptosis and reversed myocardial contractility. Mechanistically, P8 improved cardiac function by inhibiting NF-κB signaling and downregulating inflammatory cytokine expression. Using mass spectrometry, we identified that guanosine and deoxynucleoside were the main functional components of P8 that suppressed the inflammatory response in human embryonic stem cell-derived cardiomyocytes. Collectively, our data suggest that specific components from ceAF are promising therapeutic agents for ischemic heart injury and could be a potential supplement to current medications for MI.
Under the sword of Damocles: Exploring the well-being of university academics during a crisis
Authors: Subban Pearl , Laletas Stella , Creely Edwin , Southcott Jane , Fernandes Venesser
Published: November 2022

Prompted by the wide-spread impact of the global pandemic on the higher education sector in Australia, this study explores the wellbeing and mental health of university academics who were caught in this altering landscape. This mixed-methods study has three objectives. Firstly, the study involved the design and development of an instrument to measure the wellbeing of university teachers. Secondly, the new instrument was administered to a randomly drawn sample of university academics, in order to validate its use. Thirdly, the study sought to identify possible strategies utilized by participants during times of high pressure, conflict and stress. As an initial validation study, the project involved scale design, generating a tool which measures the wellbeing of university academics, especially during times of crisis. The measurement tool was constructed in four parts drawing on the established formula of academic workload: Teaching, Research, Service/Engagement, with Part 4 seeking out demographic variables for analysis. Findings suggested that most academics were concerned about the maintenance of their research output and teaching workloads. Maintaining responsibilities as care-givers and parents of school-going children proved challenging. Many conceded that maintaining equilibrium was complex. It is anticipated that the scale will be an effective means of quantifying academic wellbeing especially during a crisis, thereby offering a valid instrument to university leaders, when considering staff security and comfort, in the contemporary context.
“Do you just have to know that?” Novice and experts’ procedure when solving science problem tasks
Authors: Tóthová Martina , Rusek Martin
Published: November 2022

Only teachers who possess problem-solving skills can develop them in their students. These skills therefore need to be accentuated during teachers’ pre-service training. In this study, attention was given to pre-service chemistry teachers’ (students) problem-solving skills measured with the use of two sets of problem tasks–chemistry and general science tasks. Based on a pre-test consisting of both types of tasks, one successful, one partially successful and one unsuccessful solver was selected from a group of first-year bachelor chemistry teacher students. To compare, the tasks were also given to three experts (post-docs in the field of chemistry education). All the participants solved two tasks on a computer with their eye movements recorded. After the procedure, retrospective think-aloud and interviews were conducted to provide data about the problem-solving process. The results showed several trends. (1) Students–novices considered the chemistry task more difficult than the science task, which correlated with their task results. (2) Experts considered the science task more complex, therefore more difficult, however scored better than the students. (3) Even the successful student only solved the chemistry task using memorized facts without the support provided. (4) Experts’ direct focus on relevant parts was confirmed, whereas unsuccessful (novice) students distributed their focus toward other task parts too. (5) When students faced a problem during task solving, they used limiting strategies. This behavior was not identified in the expert group. The results thus showed a need to support students’ problem-solving strategies in several areas, especially careful reading, and identifying the main problem and supporting information. Moreover, the results showed a need to present chemistry tasks to students with more variability and explain their reasoning rather than testing field-specific, separated, memorized information.
Professional training improves early education teachers’ knowledge, skills, motivation, and self-efficacy
Authors: Hyseni Duraku Zamira , Blakaj Vigan , Shllaku Likaj Eglantina , Boci Loreta , Shtylla Hysnie
Published: November 2022

This study aimed to evaluate the impact of a training program for professional development on early education teachers’ knowledge and skills, work motivation, and self-efficacy. A one-group pre–post-test design was used to assess the effect of the training program on 75 teachers working in public early education institutions in the Tirana municipality in Albania. The results indicated that completing training was associated with a significant increase in early education teachers’ knowledge and skills, work motivation, and self-efficacy. These findings demonstrate the multiple benefits of professional training as a mechanism for supporting teachers’ personal and professional development and improving teaching practice, the quality of early education settings, and children’s early learning and growth experiences. Implications for practice, study limitations, and future research directions are also discussed.
Epworth sleepiness scale is associated with hypothyroidism in male patients with obstructive sleep apnea
Authors: Wang Le , Fang Xiaoyan , Xu Chong , Pan Na , Wang Yan , Xue Tuai , Zhang Mingchu , Cao Jie , Zhang Jing
Published: November 2022

Background

Hypothyroidism could cause obstructive sleep apnea (OSA), however, the specific association of them remained unclear. This cross-sectional study aimed to determine the prevalence of hypothyroidism among patients with OSA, and the characteristics and predictors of hypothyroidism associated with OSA.

Methods

A total of 573 patients with OSA were included in the study. Serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were measured in all participants. Univariate and binary logistic regression analysis were performed to assess the association of OSA with hypothyroidism while controlling for potential confounders. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the OSA effect in the distinction between euthyroid and hypothyroidism.

Results

The prevalence of hypothyroidism was 6.75%、5.12%、10.38% in the total, men, and women cohort, respectively, and the prevalence rate in women OSA patients was significantly higher than that in men OSA patients (P=0.018). The men OSA patients with hypothyroidism had a higher Epworth sleepiness scale (ESS) than women OSA patients with hypothyroidism (P=0.022). Additionally, the ESS was significantly higher in men OSA patients with hypothyroidism than those with euthyroid (P=0.042), while women OSA patients had no such difference (P=0.822). In men patients with OSA, ROC curve analyses revealed that the risk of hypothyroidism increased in accordance with increasing ESS after adjustment for potential confounders, and the optimal cutoff value was 10 score. Higher ESS category was significantly associated with a higher risk of prevalent hypothyroidism in men patients with OSA [odds ratio (OR) = 4.898 for ESS≥10 relative to ESS <10, 95% confidence interval (CI) 1.628-14.731, P = 0.005].

Conclusions

The prevalence of hypothyroidism in OSA patients was relatively higher, especially in women OSA patients. ESS was significantly and positively associated with hypothyroidism in men patients with OSA, suggesting that ESS may have a potential role in identification and diagnosis of men OSA patients complicated with hypothyroidism.
Machine learning models to predict in-hospital mortality in septic patients with diabetes
Authors: Qi Jing , Lei Jingchao , Li Nanyi , Huang Dan , Liu Huaizheng , Zhou Kefu , Dai Zheren , Sun Chuanzheng
Published: November 2022

Background

Sepsis is a leading cause of morbidity and mortality in hospitalized patients. Up to now, there are no well-established longitudinal networks from molecular mechanisms to clinical phenotypes in sepsis. Adding to the problem, about one of the five patients presented with diabetes. For this subgroup, management is difficult, and prognosis is difficult to evaluate.

Methods

From the three databases, a total of 7,001 patients were enrolled on the basis of sepsis-3 standard and diabetes diagnosis. Input variable selection is based on the result of correlation analysis in a handpicking way, and 53 variables were left. A total of 5,727 records were collected from Medical Information Mart for Intensive Care database and randomly split into a training set and an internal validation set at a ratio of 7:3. Then, logistic regression with lasso regularization, Bayes logistic regression, decision tree, random forest, and XGBoost were conducted to build the predictive model by using training set. Then, the models were tested by the internal validation set. The data from eICU Collaborative Research Database (n = 815) and dtChina critical care database (n = 459) were used to test the model performance as the external validation set.

Results

In the internal validation set, the accuracy values of logistic regression with lasso regularization, Bayes logistic regression, decision tree, random forest, and XGBoost were 0.878, 0.883, 0.865, 0.883, and 0.882, respectively. Likewise, in the external validation set 1, lasso regularization = 0.879, Bayes logistic regression = 0.877, decision tree = 0.865, random forest = 0.886, and XGBoost = 0.875. In the external validation set 2, lasso regularization = 0.715, Bayes logistic regression = 0.745, decision tree = 0.763, random forest = 0.760, and XGBoost = 0.699.

Conclusion

The top three models for internal validation set were Bayes logistic regression, random forest, and XGBoost, whereas the top three models for external validation set 1 were random forest, logistic regression, and Bayes logistic regression. In addition, the top three models for the external validation set 2 were decision tree, random forest, and Bayes logistic regression. Random forest model performed well with the training and three validation sets. The most important features are age, albumin, and lactate.
A precise inversion method of cable joint core temperature with non-embedded detection based on UMAP and ISSA-BPNN
Authors: Tian Wu , Hesheng Zhu , Qinghua Zhan , Nanji Wang
Published: November 2022

Obtaining the core temperature of the cable joint is vital to ensure the safe operation of the modern power system with integration. To improve the speed and accuracy of core temperature inversion, this study proposed a non-embedded cable joint temperature inversion method named uniform manifold approximation and projection (UMAP) and the improved sparrow search algorithm (ISSA) optimized the back propagation neural network (BPNN). Firstly, UMAP is used to reduce the feature dimension of sample data input and enhance the data visualization effect. After dimension reduction, the model input features are consistent with the international ampacity calculation standard, and the calculation speed and accuracy of the model are improved. To improve the optimization ability of SSA, the Tent chaotic operator is introduced, and then the ISSA is used to optimize BPNN to address the issue of unstable output and easy falling into a local minimum. At last, the optimization ability and temperature inversion effect of the improved model were compared with other competing algorithms based on the 10 kV cable joint temperature-rise test and CEC2017 benchmark function. The experimental results show that the proposed method shortens the calculation time of the model, and the mean absolute error of temperature inversion is about 0.1°C. The overall performance is the most outstanding, the training data set is unbiased, and the interpretability of the model improves, which can provide a reliable reference for line operation and maintenance personnel.
Response of the natural grassland vegetation change to meteorological drought in Xinjiang from 1982 to 2015
Authors: Zhao Weikang , Jing Changqing
Published: November 2022

In recent years, drought frequency has gradually increased, which has reduced vegetation growth and development. The response of grassland to meteorological drought is more sensitive than other vegetation types and can differ substantially among grassland types. In this study, the response of vegetation change to meteorological drought at different time scales was evaluated using data from the normalized difference vegetation index (NDVI) and the standardized precipitation evapotranspiration index (SPEI) to analyze the spatial and temporal variation trends and correlations of the NDVI and SPEI of three grassland types in Xinjiang from 1982 to 2015. Over this 34-year period, the NDVI of meadow, steppe, and desert grassland in Xinjiang increased, with growth rates of 0.002, 0.002, and 0.0003 per decade, respectively, although the increase was insignificant (p > 0.05). The most obvious vegetation improvement areas of the three grassland types were mainly distributed in the Tianshan Mountains. The SPEI-12 of meadow, steppe, and desert grassland in Xinjiang indicated an extremely significant drying trend (p < 0.01), with change rates of −0.31, −0.38, and −0.34 per decade, respectively. The overall pattern was the gradual drying from the northwest to southeast, and the degree of aridification was the largest in eastern Xinjiang. On the annual scale, the correlation between the NDVI and SPEI-12 of the three grassland types was significantly different between northern and southern Xinjiang. The degree to which the vegetation of the three grassland types responded to drought was higher in northern Xinjiang than in southern Xinjiang, and most responses were significant. On the monthly scale, the response of meadow to the SPEI-12 was the highest in autumn (September) (r = 0.53; p < 0.05), the response of steppe to the SPEI-3 was the highest in summer (August) (r = 0.49; p < 0.05), and the response of desert grassland to the SPEI-12 was the highest in summer (June) (r = 0.44; p < 0.05). The results can provide a scientific basis for natural grassland drought response, ecological environmental improvement, and disaster prevention and mitigation.
Spatial-temporal evolution and driving factors of coupling between urban spatial functional division and green economic development: Evidence from the Yangtze River Economic Belt
Authors: Guo Siliang , Diao Yanhua
Published: November 2022

It is of great significance to analyze coupling coordination feature between urban spatial functional division (USFD) and green economic development for the realization of regional high-quality sustainable development. However, few studies have investigated the coupling between USFD and green economic development. Therefore, based on the analysis of the coupling and coordination mechanism between USFD and green development, this paper innovatively calculates the indicators of USFD and green economic development of 108 cities in the Yangtze River Economic Belt (YREB) from 2009 to 2019. Moreover, we explore the spatiotemporal patterns, evolution characteristics of the coupling degree between the USFD and green economic development using the improved entropy method, coupling model, kernel density estimation and spatial autocorrelation method, and further analyzes the influence factors with the Tobit regression method. The study found that: 1) During the study period, the development level of USFD and green economy in the YREB showed a fluctuating upward trend, but the development level was still low and there was a large space for improvement. 2) During the study period, the coupling coordination degree of USFD and green economy development in the YREB shows a favorable development trend of fluctuating growth, but it is still in the stage of moderate coupling and coordination development. The coupling degree shows a trend of polarization and the phenomenon of “high-value difference and low-value convergence” over time. 3) The spatial distribution of coupling coordination degree in each region is obviously different, and the middle and lower reaches are significantly higher than the upper reaches, and there are “club convergence” phenomenon and obvious H-H and L-L spatial agglomeration characteristics. 4) Technological innovation, industrial structure and physical capital have a significant positive impact on the coupling degree of the two systems, while human capital has a restraining effect on the growth of the coupling degree. There is heterogeneity in the extent and direction of the influence of each factor on the degree of coupling between the three agglomerations. These findings have significant policy implications for the region to facilitate rational division of labor and coordinated development of the green economy.
Bacteria common to rhizosphere communities of Asiatic bittersweet across a post-glacial landscape
Authors: Nakatsu Cindy H. , Pavlovic Noel B. , Byappanahalli Muruleedhara N.
Published: November 2022

Invasive plants such as Asiatic bittersweet (Celastrus orbiculatus Thunb.) are a significant problem for land managers as they impact plant species composition, disrupt nutrient dynamics and structure of native ecosystems, and are difficult to eradicate. As a result of the increasing abundance of Asiatic bittersweet across the eastern U.S., we have been investigating underlying factors potentially contributing to the success of this plant. Recently, ecologists have been investigating the role of plant-soil-microbe interactions contributing to plant invasion. This work has led to question: are there certain microbes (e.g., bacteria, fungi) contributing to the success of some invasive plants? We hypothesize that despite differences in geologic age of soils where Asiatic bittersweet has established in the Indiana Dunes National Park there are sufficient common factors that led to common bacterial taxa in their rhizosphere. The objectives were to determine differences and commonalities in the soil chemistry, plant community and bacterial communities of Asiatic bittersweet plants. To achieve these objectives, bittersweet plants were collected at thirteen locations in the national park from soils ranging in geologic age from 150 to over 14,500 years. Surrounding soil chemistry, plant cover and the 16S rRNA gene amplicon sequences of rhizosphere soil bacterial communities of these Asiatic bittersweet were compared. Asiatic bittersweet coverage of sampling sites ranged from 2 to 77% averaging 52 ± 2%. There were statistically significant differences (p < 0.05) in alpha diversity (Shannon, Faith’s PD and Pielou’s evenness) and beta diversity (Bray Curtis, Jaccard, unweighted Unifrac, weighted Unifrac) among the samples when grouped by soil age or habitat. Despite these differences in the bacterial communities from different soil ages and habitats, some bacterial taxa (e.g., Bacillus, Streptomyces, Sphingomonas and Rhizobiales) previously found in other studies to be beneficial to plant growth were found in every rhizosphere community sampled. These microbes provide insight into a possible contributing factor to the success of this invasive plant at the Indiana Dunes National Park, and a strategy for future work to reduce the impact of Asiatic bittersweet establishment and offer some new strategies to manage this nuisance species.
Testing of human reactions during braking manoeuvres combining a physical test bed with virtual reality
Authors: Rajinovic Stefan , Safikhani Saeed , Schachner Martin , Gstrein Gregor , Kofler Desiree , Schneider Bernd , Erlinger Nico , Pirker Johanna , Klug Corina
Published: November 2022

For the development of restraint systems, the initial posture and kinematics of the occupants immediately before the crash are essential. To predict the behaviour of vehicle occupants in pre-crash manoeuvres, volunteer tests under controlled boundary conditions to calibrate and validate active human body models are needed. The challenge in such experiments is to evoke a natural behaviour of the volunteers. The aim of this study was to investigate the potential of distractions via virtual reality (VR) in volunteer tests to study pre-crash kinematics. For this purpose, it was investigated if the volunteers are able to get immersed into the virtual reality using head-mounted displays to an extent in which they forget the laboratory environment and feel as if they are really sitting in an autonomous vehicle. A total of 27 volunteers took part in the study, and 10 different trials were carried out with each of them. In the baseline trial, no VR was displayed and the volunteers were made aware that the sled is going to start moving by a countdown. In trials 3–10, the volunteers were instructed to perform various tasks in virtual reality, which we have developed for this specific purpose. The physical platform on which they were sitting on began to move mimicking a braking maneuver as they performed a task. The peak forward head excursions resulting from the different trials were compared and showed significant differences between the baseline trial and the trials where they were distracted with VR. In contrast to our expectations, peak forward head excursions were overall significantly lower for the volunteers distracted by VR compared to the baseline trial. However, volunteers, who had significantly lower peak forward head excursions in the baseline trials showed higher peak forward head excursions in the VR trials comparable in magnitude to the other volunteers. All the volunteers answered in the questionnaire that their experience had been good and they were willing to participate in the study again. Further research is needed to understand the effect of the performed activities on the volunteer muscle activation and head excursions.
Exploring the causality between ankylosing spondylitis and atrial fibrillation: A two-sample Mendelian randomization study
Authors: Chen Shuhong , Luo Xiqing , Zhao Jiaoshi , Liang Zhenguo , Gu Jieruo
Published: November 2022

Objective: To study whether ankylosing spondylitis (AS) has a causal effect on the risk of atrial fibrillation (AF) using two-sample Mendelian randomization (MR) analysis.

Methods: Single nucleotide polymorphisms (SNPs) were selected as independent instrumental variables (IVs) from a GWAS study of AS. Summary data from a large-scale GWAS meta-analysis of AF was utilized as the outcome dataset. Inverse-variance weighted (IVW) model was used for the primary analysis. Multiple sensitivity and heterogeneity tests were conducted to confirm the robustness of the results.

Results: In total, 18 SNPs were identified as IVs for MR analysis. Five MR methods consistently found that ankylosing spondylitis was not causally associated with atrial fibrillation (IVW: OR = 0.983 (0.894, 1.080), p = 0.718; MR-Egger: OR = 1.190 (0.973, 1.456), p = 0.109; Simple mode: OR = 0.888 (0.718, 1.098), p = 0.287; Weighted mode: OR = 0.989 (0.854, 1.147), p = 0.890; Weight median: OR = 0.963 (0.852, 1.088), p = 0.545). Leave-one-out analysis supported the stability of MR results. Both the MR-Egger intercept and MR-PRESSO method revealed the absence of horizontal pleiotropy.

Conclusion: The two-sample MR analysis did not support a causal relationship between AS and the risk of AF.
An intranasal vaccine targeting the receptor binding domain of SARS-CoV-2 elicits a protective immune response
Authors: Chen Li , Zhang Haiwei , Li Moxuan , Wu Bihao , Zhang Zhe , Gong Rui
Published: November 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for COVID-19, has caused an ongoing worldwide pandemic. Due to the rapid emergence of variants of concern (VOCs), novel vaccines and vaccination strategies are urgently needed. We developed an intranasal vaccine consisting of the SARS-CoV-2 receptor binding domain (RBD) fused to the antibody Fc fragment (RBD-Fc). RBD-Fc could induce strong humoral immune responsesviaintranasal vaccination. Notably, this immunogen could efficiently induce IgG and IgA and establish mucosal immunity in the respiratory tract. The induced antibodies could efficiently neutralize wild-type SARS-CoV-2 and currently identified SARS-CoV-2 VOCs, including the Omicron variant. In a mouse model, intranasal immunization could provide complete protection against a lethal SARS-CoV-2 challenge. Unfortunately, the limitation of our study is the small number of animals used in the immune response analysis. Our results suggest that recombinant RBD-Fc deliveredviaintranasal vaccination has considerable potential as a mucosal vaccine that may reduce the risk of SARS-CoV-2 infection.
Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer
Authors: Zhang Xin , Zhang Yanlong , Zhao Li , Wang Jiayu , Li Jiaxing , Wang Xi , Zhang Min , Hu Xiaopeng
Published: November 2022

Background

Bladder cancer (BLCA) is one of the most prevalent urinary system malignancies, with high mortality and recurrence. The present study aimed to identify potential tumor antigens for mRNA vaccines in BLCA and patient subtypes suitable for different immunotherapy.

Methods

Gene expression profiles, mutation data, methylation data, and corresponding clinical information were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress databases. Immunohistochemical staining of microarrays was performed to assess protein expression levels of IGF2BP2 and MMP9. Differential gene analysis, survival analysis, correlation analysis, consensus clustering analysis, and immune cell infiltration analysis were conducted using R software. Finally, the R package “immcluster” was used based on Combat and eXtreme Gradient Boosting algorithms to predict immune clusters of BLCA samples.

Results

Two mutated, amplified, and over-expressed tumor antigens, IGF2BP2 and MMP9, were found to be associated with clinical outcomes and the abundance of antigen-presenting cells (APCs). Subsequently, three immune subtypes (BIS1, BIS2, and BIS3) were defined in the BLCA cohort. BIS3 subtype exhibited an “active” immune phenotype, while BIS1 and BIS2 subtypes have a “suppressive” immune phenotype. Patients in BIS1 and BIS2 had a poor prognosis compared to BIS3. BIS3 had a higher score in checkpoints or immunomodulators (CP) and immunophenoscore (IPS), while BIS1 and BIS2 scored higher in major histocompatibility complex-related molecules (MHC molecules). Meanwhile, BIS2 and BIS3 had a significantly higher tumor mutational burden (TMB) compared to patients with BIS1. Finally, the “immcluster” package was applied to the dataset, which has been shown to accurately predict the immune subtypes of BLCA samples in many cohorts.

Conclusions

IGF2BP2 and MMP9 were potential antigens for developing mRNA vaccines against BLCA. The results in the present study suggested that immunotherapy targeting these two antigens would be suitable for patients falling under the BIS2 subtype. R package “immcluster” could assist in screening suitable BLCA patients for antitumor therapy.
Efficacy of Pgp3 vaccination for Chlamydia urogenital tract infection depends on its native conformation
Authors: Peng Bo , Zhong Shufang , Hua Yaoqin , Luo Qizheng , Dong Weilei , Wang Chuan , Li Zhongyu , Yang Chunfen , Lei Aihua , Lu Chunxue
Published: November 2022

Urogenital tract infections with Chlamydia trachomatis have frequently been detected among patients diagnosed with sexually transmitted infections, and such infections lead to inflammatory complications. Currently, no licensed chlamydial vaccine is available in clinical practice. We previously reported that immunization with recombinant C. trachomatis plasmid-encoded virulence factor Pgp3 provided cross-serovar protection against C. muridarum genital tract infection. Because Pgp3 is a homotrimer and human antisera only recognize the trimeric form of Pgp3, we compared the effects of the native conformation of Pgp3 (trimer) and heat-denatured Pgp3 (monomer) to determine whether the native conformation is dispensable for the induction of protective immunity against chlamydial vaginal challenge. Both Pgp3 trimer and monomer immunization induced corresponding specific antibody production, but only trimer-induced antibody recognized endogenous Pgp3, and trimer-immunized mouse splenocytes showed the highest IFN-γ production upon restimulation with the chlamydial elementary body or native Pgp3 in vitro. Importantly, only Pgp3 trimer-immunized mice showed shortened lower genital tract chlamydial shedding and decreased upper genital tract pathology. Thus, Pgp3-induced protective immunity against Chlamydia urogenital tract infection is highly dependent on the native conformation, which will guide the design of Pgp3-based polypeptides and multi-subunit chlamydial vaccines.
Indirubin combined with umbilical cord mesenchymal stem cells to relieve psoriasis-like skin lesions in BALB/c mice
Authors: Lu XiaoJuan , Wang Hao , Wang Hongwei , Xie Fan , Jiang Cuibao , Shen Danpeng , Zhang Hongpeng , Yang Jie , Lin Youshu
Published: November 2022

Objective

To investigate the efficacy of indirubin combined with human umbilical cord mesenchymal stem cells (hUC-MSCs) in the treatment of psoriatic lesions in BALB/c mice and to explore the related mechanism of indirubin in the treatment of psoriasis.

Methods

A BALB/c mouse psoriasis model induced by imiquimod was established and randomly divided into the control group, model group, indirubin group, hUC-MSCs group, and indirubin combined with hUC-MSCs group. Psoriasis area and severity index (PASI) score was used to observe skin lesion changes in the psoriasis-like mouse model. The epidermal scale, the degree of keratinization, and the infiltration of inflammatory cells were observed by hematoxylin eosin (HE) staining. The concentrations of TNF-α, IFN-γ, IL-17A, and IL-23 in serum of mice were measured using enzyme-linked immunosorbent assay (ELISA).

Results

The PASI integral trend chart indicates that hUC-MSCs and indirubin and the combination of drugs could relieve the appearance of skin lesions and accelerate the recovery of skin lesions. The indirubin group had the best effect in improving the scale of skin lesions. HE staining showed that the number of parakeratosis cells in the three treatment groups was significantly reduced, the degree of erythrocyte extravasation dermis hyperplasia and inflammatory cell infiltration was significantly lower than that in the model group, and the skin thickness and spleen index of the combined treatment group exhibited the most noticeable improvement. ELISA showed that the concentrations of TNF-α, IFN-γ, IL-17A, and IL-23 in serum of mice in the hUC-MSCs treatment group, indirubin group, and combined administration group were all decreased compared with those in the model group, and the concentrations of IFN-γ, IL-17A, and IL-23 could be decreased significantly in the indirubin group.

Conclusions

Both hUC-MSCs and indirubin can effectively reduce psoriasis-like lesions in BALB/c mice, and the combined administration of these drugs has the best effect.
Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: Potential for a novel biomarker of disease
Authors: Pan Sheng-Wei , Syed Rehan R. , Catanzaro Donald G. , Ho Mei-Lin , Shu Chin-Chung , Tsai Tsung-Yeh , Tseng Yen-Han , Feng Jia-Yih , Chen Yuh-Min , Su Wei-Juin , Catanzaro Antonino , Rodwell Timothy C.
Published: November 2022

Objectives

Human mitochondrial cell-free DNA (Mt-cfDNA) may serve as a useful biomarker for infectious processes. We investigated Mt-cfDNA dynamics in patients with pulmonary mycobacterial infections to determine if this novel biomarker could be used to differentiate disease states and severity.

Methods

Patients with pulmonary tuberculosis (PTB), latent tuberculosis infection (LTBI), and nontuberculous mycobacterial-lung disease (NTM-LD) were enrolled at a tertiary care hospital in Taiwan between June 2018 and August 2021. Human Mt-cfDNA and nuclear-cfDNA (Nu-cfDNA) copy numbers were estimated by quantitative polymerase chain reaction. Variables associated with PTB and 2-month sputum culture-positivity, indicating poor treatment response, were assessed using logistic regression.

Results

Among 97 patients with PTB, 64 with LTBI, and 51 with NTM-LD, Mt-cfDNA levels were higher in patients with PTB than in LTBI (p=0.001) or NTM-LD (p=0.006). In the Mycobacterium tuberculosis-infected population, Mt-cfDNA levels were highest in smear-positive PTB patients, followed by smear-negative PTB (p<0.001), and were lowest in LTBI persons (p=0.009). A Mt-cfDNA, but not Nu-cfDNA, level higher than the median helped differentiate culture-positive PTB from culture-negative PTB and LTBI (adjusted OR 2.430 [95% CI 1.139–5.186], p=0.022) and differentiate PTB from NTM-LD (adjusted OR 4.007 [1.382–12.031], p=0.011). Mt-cfDNA levels decreased after 2 months of treatment in PTB patients (p=0.010). A cutoff Mt-cfDNA level greater than 62.62 x 106 copies/μL-plasma was associated with a 10-fold risk of 2-month culture-positivity (adjusted OR 9.691 [1.046–89.813], p=0.046).

Conclusion

Elevated Mt-cfDNA levels were associated with PTB disease and failed sputum conversion at 2 months in PTB patients, and decreased after treatment.
Label-free quantitative proteomics and immunoblotting identifies immunoreactive and other excretory-secretory (E/S) proteins of Anoplocephala perfoliata
Authors: Hautala Katja , Pursiainen Jami , Näreaho Anu , Nyman Tuula , Varmanen Pekka , Sukura Antti , Nielsen Martin K. , Savijoki Kirsi
Published: November 2022

Anoplocephala perfoliata is a common tapeworm in horses causing colic and even mortalities. Current diagnostic tests to detect A. perfoliata infections have their limitations and an improved method is needed. Immunoreactive excretory/secretory proteins (E/S proteome) of this parasite can provide promising candidates for diagnostic tests. We compared E/S proteins produced by small (length < 20 mm, width < 5 mm) and large (length 20 to 40 mm, width 5 to 10 mm) A. perfoliata worms in vitro by label-free quantitative proteomics using a database composed of related Hymenolepis diminuta, Echinococcus multilocularis/granulosus and Taenia aseatica proteins for protein identifications. Altogether, 509 E/S proteins were identified after incubating the worms in vitro for three and eight hours. The greatest E/S proteome changes suggested both worm size- and time-dependent changes in cytoskeleton remodeling, apoptosis, and production of antigens/immunogens. The E/S proteins collected at the three-hour time point represented the natural conditions better than those collected at the eight-hour time point, and thereby contained the most relevant diagnostic targets. Immunoblotting using antibodies from horses tested positive/negative for A. perfoliata indicated strongest antigenicity/immunogenicity with 13-, 30- and 100-kDa proteins, involving a thioredoxin, heat-shock chaperone 90 (Hsp90), dynein light chain component (DYNLL), tubulin-specific chaperone A (TBCA) and signaling pathway modulators (14-3-3 and Sj-Ts4). This is among the first studies identifying new diagnostic targets and A. perfoliata antigens eliciting a IgG-response in horses.
Brain-gut axis and psychiatric disorders: A perspective from bibliometric and visual analysis
Authors: Chen Pan , Zhang Ling , Feng Yuan , Liu Yu-Fei , Si Tong Leong , Su Zhaohui , Cheung Teris , Ungvari Gabor S. , Ng Chee H. , Xiang Yu-Tao
Published: November 2022

Background

The Brain-Gut Axis, a bidirectional signaling pathway that connects the intestinal and central nervous systems, plays an important role in the development of psychiatric disorders. However, the overall research trends in this field are unclear. This study explored the patterns of research on the brain-gut axis and psychiatric disorders from a bibliometric perspective.

Methods

Relevant data were retrieved from the Web of Science Core Collection, with search terms on psychiatric disorders and the brain-gut axis. R (version 4.2.0), VOSviewer (version 1.6.17), CiteSpace software, and the online bibliometric platform were used in the data analysis.

Results

A total of 2,298 articles published between 1993 and 2022 were identified, showing an increasing trend over time. China (1,859; 20.70%) was the country that contributed the most publications. The journal Nutrients (95; 4.13%) published the most publications. Cryan JF (153; H-index=73) and University College Cork (559; 22.54%) were the most influential author and the most productive institution, respectively. The high-frequency keywords were clustered into six themes, including neurodegenerative diseases, stress-related diseases, immune, brain behavior, depression, and probiotic-related topics; of which, depression (880; 2019), anxiety (207; 2018) and autism (191; 2019) were the most studied psychiatric disorders in the past 5 years. “Depressive symptom” (2019-2020) and “probiotic treatment” (2019-2020) were the main areas addressed in recent years.

Conclusion

Research on the brain-gut axis and psychiatric disorders has attracted increasing attention in the past decade, with most publications originating from high-income level countries. This study provides a useful perspective on understanding the research trends, key hot topics, and research gaps in this expanding field.
Neutrophils inhibit γδ T cell functions in the imiquimod-induced mouse model of psoriasis
Authors: Costa Sara , Bevilacqua Dalila , Caveggion Elena , Gasperini Sara , Zenaro Elena , Pettinella Francesca , Donini Marta , Dusi Stefano , Constantin Gabriela , Lonardi Silvia , Vermi William , De Sanctis Francesco , Ugel Stefano , Cestari Tiziana , Abram Clare L. , Lowell Clifford A. , Rodegher Pamela , Tagliaro Franco , Girolomoni Giampiero , Cassatella Marco A. , Scapini Patrizia
Published: November 2022

Background

Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is a histological feature that characterizes psoriasis. However, the role of neutrophils in psoriasis onset and development remains poorly understood.

Methods

In this study, we utilized the model of psoriasiform dermatitis, caused by the repeated topical application of an imiquimod containing cream, in neutrophil-depleted mice or in mice carrying impairment in neutrophil functions, including p47phox -/- mice (lacking a cytosolic subunit of the phagocyte nicotinamide adenine dinucleotide phosphate - NADPH - oxidase) and Sykfl/fl MRP8-cre+ mice (carrying the specific deletion of the Syk kinase in neutrophils only), to elucidate the specific contribution of neutrophils to psoriasis development.

Results

By analyzing disease development/progression in neutrophil-depleted mice, we now report that neutrophils act as negative modulators of disease propagation and exacerbation by inhibiting gammadelta T cell effector functions via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species (ROS) production. We also report that Syk functions as a crucial molecule in determining the outcome of neutrophil and γδ T cell interactions. Accordingly, we uncover that a selective impairment of Syk-dependent signaling in neutrophils is sufficient to reproduce the enhancement of skin inflammation and γδ T cell infiltration observed in neutrophil-depleted mice.

Conclusions

Overall, our findings add new insights into the specific contribution of neutrophils to disease progression in the IMQ-induced mouse model of psoriasis, namely as negative regulatory cells.
Elevation of circulating TNF receptor 2 in cancer: A systematic meta-analysis for its potential as a diagnostic cancer biomarker
Authors: Kartikasari Apriliana E. R. , Cassar Emily , Razqan Mohammed A. M. , Szydzik Crispin , Huertas Cesar S. , Mitchell Arnan , Plebanski Magdalena
Published: November 2022

High Tumor Necrosis Factor Receptor 2 (TNFR2) expression is characteristic of diverse malignant cells during tumorigenesis. The protein is also expressed by many immunosuppressive cells during cancer development, allowing cancer immune escape. A growing body of evidence further suggests a correlation between the circulating form of this protein and cancer development. Here we conducted a systematic meta-analysis of cancer studies published up until 1stOctober 2022, in which the circulating soluble TNFR2 (sTNFR2) concentrations in patients with cancers were recorded and their association with cancer risk was assessed. Of the 14,615 identified articles, 44 studies provided data on the correlation between cancer risk and the level of circulating sTNFR2. The pooled means comparison showed a consistently significant increase in the levels of sTNFR2 in diverse cancers when compared to healthy controls. These included colorectal cancer, ovarian cancer, breast cancer, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, lung cancer, hepatocarcinoma, and glioblastoma. In a random-effect meta-analysis, the cancer-specific odd ratios (OR) showed significant correlations between increased circulating sTNFR2 levels and the risk of colorectal cancer, non-Hodgkin’s lymphoma, and hepatocarcinoma at 1.59 (95% CI:1.20-2.11), 1.98 (95% CI:1.49-2.64) and 4.32 (95% CI:2.25-8.31) respectively. The overall result showed an association between circulating levels of sTNFR2 and the risk of developing cancer at 1.76 (95% CI:1.53-2.02). This meta-analysis supports sTNFR2 as a potential diagnostic biomarker for cancer, albeit with different predictive strengths for different cancer types. This is consistent with a potential key role for TNFR2 involvement in cancer development.
Neutralizing epitopes on Clostridioides difficile toxin A revealed by the structures of two camelid VHH antibodies
Authors: Chen Baohua , Perry Kay , Jin Rongsheng
Published: November 2022

Toxin A (TcdA) and toxin B (TcdB) are two key virulence factors secreted by Clostridioides difficile, which is listed as an urgent threat by the CDC. These two large homologous exotoxins are mainly responsible for diseases associated with C. difficile infection (CDI) with symptoms ranging from diarrhea to life threatening pseudomembranous colitis. Single-domain camelid antibodies (VHHs) AH3 and AA6 are two potent antitoxins against TcdA, which when combined with two TcdB-targeting VHHs showed effective protection against both primary and recurrent CDI in animal models. Here, we report the co-crystal structures of AH3 and AA6 when they form complexes with the glucosyltransferase domain (GTD) and a fragment of the delivery and receptor-binding domain (DRBD) of TcdA, respectively. Based on these structures, we find that AH3 binding enhances the overall stability of the GTD and interferes with its unfolding at acidic pH, and AA6 may inhibit the pH-dependent conformational changes in the DRBD that is necessary for pore formation of TcdA. These studies reveal two functionally critical epitopes on TcdA and shed new insights into neutralizing mechanisms and potential development of epitope-focused vaccines against TcdA.
Microplastic contamination and microbial colonization in coastal area of Busan City, Korea
Authors: Bae Suyeon , Yoo Keunje
Published: November 2022

This study investigated the potential role of the concentration, shape, size, and polymer type of microplastics (MP), in addition to the microbial community in six coastal areas of Busan city, South Korea. The results showed that the average MP concentration was 94 ± 41 particles·m-3, and particles sized 20 μm –300 μm accounted for 67.5 ± 9.6% of the total MP abundance throughout the study sites. Further, polyethylene (PE), polypropylene (PP), and polystyrene (PS) polymers were abundant among the collected fragment- and fiber-shaped MPs, implying that highly populated and industrialized areas are major sources of MPs contamination. Moreover, the bacterial diversity and taxa-based on 16S rRNA gene sequencing was significantly different between MPs and seawater (SW) samples. Specifically, Psychrobacter, Pseudomonas, Flavobacterium, and Winogradskyella were significantly enriched in MPs compared with SW (p <0.05). Redundancy analysis revealed that nutrient concentrations, salinity, and temperature potentially contributed to shaping the microbial communities on MPs. These results indicate the dynamic and complicated interactions of MP contamination with the physiochemical and environmental factors of the surrounding area. Our findings would help in understanding of MP contamination levels in marine environments and their characteristics, as well as bacterial colonization on plastics in urban coastal areas of Busan, South Korea.