bluuebunny/crossref_metadata_2025 huggingface dataset:
Venous Leg Compression for Tissue Decongestion in Patients With Worsening Congestive Heart Failure
Authors: Civera Jose , Miñana Gema , de la Espriella Rafael , Santas Enrique , Sastre Clara , Mollar Anna , Conesa Adriana , Martínez Ana , Núñez Eduardo , Bayés-Genís Antoni , Núñez Julio
Published: July 2022

Aims

Venous leg compression (VLC) with elastic bandages has been proposed as a potentially useful strategy for decreasing tissue congestion. We aimed to evaluate the effect of VLC on short-term changes on intravascular refill, assessed by inferior vena cava (IVC) diameter in patients with worsening heart failure (WHF) requiring parenteral furosemide. Additionally, we sought to evaluate whether early changes in IVC were related to short-term decongestion.

Methods

This is a prospective study in which we included 20 consecutive ambulatory patients with WHF treated with subcutaneous furosemide and VLC for at least 72 h. The endpoints were (a) short-term changes in IVC, (b) the association between decongestion and 3-h IVC changes following VLC. Changes in continuous endpoints and their longitudinal trajectories were estimated with linear mixed regression models. All analyses were adjusted for multiple comparisons.

Results

Following administration of subcutaneous furosemide and VLC, we found a significant increase in 3-h IVC diameter (ΔIVC = 1.6 mm, CI 95%: 0.7–2.5; p < 0.001), with a greater increase in those with baseline IVC≤21 mm (2.4 vs. 0.8 mm; p < 0.001). 3-h intravascular refill (increase in IVC≥2 mm) was associated with greater decongestion (natriuresis, weight, peripheral edemas, and dyspnea) in those with baseline IVC≤21 mm but not when IVC>21 mm (p < 0.05 for all comparisons).

Conclusions

In this cohort of patients with congestive WHF treated with subcutaneous furosemide and VLC, we found a greater increase in short-term IVC in those with IVC ≤21 mm at baseline. In this subset of patients, a 3-h increase in IVC≥2 mm was associated with greater short-term decongestion.
Blood Cells and Venous Thromboembolism Risk: A Two-Sample Mendelian Randomization Study
Authors: He Jiahao , Jiang Qian , Yao Yiting , Shen Yi , Li Juan , Yang Jianuo , Ma Ran , Zhang Nuofu , Liu Chunli
Published: July 2022

Background

Previous studies have shown that various cell indices are associated with a higher risk of venous thromboembolism (VTE), however, whether these findings reflect a causal relationship remains unclear. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to assess the causal association of various blood cells with VTE risk.

Study Design and Methods

Summary statistics of genetic instruments representing cell indices for erythrocytes, leukocytes, and platelets were extracted from genome-wide association studies of European ancestry, by Two-Sample Mendelian Randomization. Inverse variance weighting (IVW) was used as the primary analytical method for MR. Sensitivity analyses were performed to detect horizontal pleiotropy and heterogeneity.

Results

Genetically predicted red blood cell distribution width, mean reticulocyte volume, and mean red blood cell volume were positively associated with VTE, with odds ratio (OR) of 1.002 [CI 1.000–1.003, P = 0.022), 1.003 (CI 1.001–1.004, P = 0.001, respectively)] and 1.001 (CI 1.000–1.002, P = 0.005). Genetically predicted monocyte count was negatively correlated with VTE, with OR = 0.998 (CI 0.996–0.999, P = 0.041).

Conclusion

Genetically liability to high- red blood cell distribution width, mean reticulocyte volume, mean red blood cell volume, and low monocyte count are associated with the higher risk of VTE. Targeting these factors might be a potential strategy to prevent VTE.
Chronology of Glacial Advances and Deglaciation in the Encierro River Valley (29° Lat. S), Southern Atacama Desert, Based on Geomorphological Mapping and Cosmogenic 10Be Exposure Ages
Authors: Aguilar G. , Riquelme R. , Lohse P. , Cabré A. , García J.-L.
Published: July 2022

The high mountain segments of the valleys of the southernmost Atacama Desert of Chile present Late Quaternary glacial landforms that developed in already incised valleys. Glacier advances and deglaciation have left a geomorphic imprint in the southernmost Atacama Desert. In this work, the glacial landforms of the Encierro River Valley (29.1°S–69.9°W) have been revisited and new detailed geomorphological mapping is provided. This work also includes new 10Be exposure ages from moraine boulders and one age from an ice-molded bedrock surface. The former glacier of the El Encierro valley extended 16 km down the valley during the last local glacial maximum recorded by a terminal moraine (ENC 1a) with an exposure age of ∼40 ka. Four inboard moraine arcs were deposited upstream in telescopic patterns (ENC 1b–d), whose exposure ages range between ∼25 and ∼33 ka (ENC 1d). Exposure ages between ∼17–24 ka on lateral moraines (ENC 1L) developed during the later ice recession of the ENC 1 drift. Thus, the ice mostly disappeared in the main valley before ∼18 ka, as is also supported by the exposure age obtained from an ice-molded bedrock surface. Seven kilometers up the valley from the ENC 1, the ENC 2a–d moraine arcs correspond to a small ice advance by ∼17–20 ka. The last glacial advance (ENC 2), which occurred after deglaciation of the last local glacial maximum (ENC 1), coincides with the start of the Heinrich Stadial Event 1 (HS1; 18–14.5 ka), which is thought to play a direct role in the last glacial termination in the Andes.
Identification of Degradation Areas of Ecological Environment and Degradation Intensity Assessment in the Yellow River Basin
Authors: Li Tiantian , Zhang Qiang , Singh Vijay P. , Zhao Jiaqi , Song Jinbo , Sun Shuai , Wang Gang , Shen Zexi , Wu Wenhuan
Published: July 2022

Ecological conservation and high-quality development of the YRB (Yellow River Basin) has been adopted as a national strategy. However, the ecological environment of the YRB is fragile and it has degraded in recent years. Here we proposed an ecological degradation index system based on the Pressure-State-Response (PSR) model and evaluated trends in ecological degradation of the YRB using the Mann-Kendall trend test. We found an upward-downward-upward trend in the ecological degradation index (EDI) during the period of 2000–2019. We also observed an intensifying degradation of eco-environment from the upper to the lower YRB. Meanwhile, 69.9% of the YRB is under degraded eco-environment, while 29.5% of the YRB is dominated by improved eco-environment. Specifically, the ecological degradation intensity of Henan and Shandong Province with dense population and rapid economic development is the highest. Due to active and effective improvement measures taken by the government, the degradation intensity has been having a decreasing tendency. However, higher degradation intensity of eco-environment of the YRB should arouse human concerns. As to the driving factors, human activities can be regarded as the major driving factors for degraded eco-environment, and water stress and economic development exert increasing impacts on the eco-environment of the YRB. Our finding can provide a decision-making basis for the ecological management and high-quality development of the YRB.
Exotic Food, Food Environment, and Geographical Patterns: Big Data Analytics From Japanese Cuisine in China
Authors: Tian Chuang , Luan Weixin , Wang Hui
Published: July 2022

As urban amenity welfare, exotic food is related to consumers’ equal access to diversified food and a healthy diet. This study uses big data provided by an online catering platform to explore Japanese cuisine in China. The field intensity model and spatial econometric model are used to analyze the place effect and its relationship with local socioeconomic factors. The results illustrate that 1) the spatial distribution of Japanese cuisine shows the characteristics of an unbalanced agglomeration distribution, with the coastal economically developed cities as the key layout area and gradually extending to inland cities. 2) Price characteristics indicate that the service target of Japanese cuisine is mainly the middle class. In addition, the spatial inequality of field intensity value indicates that wealthy Eastern cities have more opportunities to enjoy more kinds of and higher quality exotic food. 3) In the local socioeconomic environment, urbanization level, population size, and economic scale are significantly related to inequal access to Japanese cuisine. The essential mechanism of these circumstances is the internal needs of pricing characteristics and the negative externalities caused by unequal urban infrastructure.
The m6A Methyltransferase METTL3 Ameliorates Methylglyoxal-Induced Impairment of Insulin Secretion in Pancreatic β Cells by Regulating MafA Expression
Authors: Cheng Yi , Yao Xin-Ming , Zhou Si-Min , Sun Yue , Meng Xiang-Jian , Wang Yong , Xing Yu-Jie , Wan Shu-Jun , Hua Qiang
Published: July 2022

Methylglyoxal, a major precursor of advanced glycation end products, is elevated in the plasma of patients with type 2 diabetes mellitus. Islet β-cell function was recently shown to be regulated by N6-methyladenosine (m6A), an RNA modification consisting of methylation at the N6 position of adenosine. However, the role of m6A methylation modification in methylglyoxal-induced impairment of insulin secretion in pancreatic β cells has not been clarified. In this study, we showed that treatment of two β-cell lines, NIT-1 and β-TC-6, with methylglyoxal reduced m6A RNA content and methyltransferase-like 3 (METTL3) expression levels. We also showed that silencing of METTL3 inhibited glucose-stimulated insulin secretion (GSIS) from NIT-1 cells, whereas upregulation of METTL3 significantly reversed the methylglyoxal-induced decrease in GSIS. The methylglyoxal-induced decreases in m6A RNA levels and METTL3 expression were not altered by knockdown of the receptor for the advanced glycation end product but were further decreased by silencing of glyoxalase 1. Mechanistic investigations revealed that silencing of METTL3 reduced m6A levels, mRNA stability, and the mRNA and protein expression levels of musculoaponeurotic fibrosarcoma oncogene family A (MafA). Overexpression of MafA greatly improved the decrease in GSIS induced by METTL3 silencing; silencing of MafA blocked the reversal of the MG-induced decrease in GSIS caused by METTL3 overexpression. The current study demonstrated that METTL3 ameliorates MG-induced impairment of insulin secretion in pancreatic β cells by regulating MafA.
Visualization Analysis on the Current Status and Development Trend of Geothermal Research: Insights Into the Database of Web of Science
Authors: Wan Xiao-fan , Zhang Hao , Shen Chuan-bo
Published: July 2022

Geothermal energy is considered a renewable, clean, and environmentally friendly energy source. In addition, it is efficient and relatively cost effective. Therefore, the demand for the development and utilization of geothermal resources is increasing annually. To understand the current status and developments within the context of geothermal research, quantitative and qualitative analyses were carried out by combining two visualization software applications, namely, VOSviewer and CiteSpace; this analysis also entailed the secondary development of R language. The results showed that the USA, China, and Germany are the main contributors to geothermal research. We also found that geothermal research hot spots encompass five geothermal research clusters, such as renewable energy utilization, heat flow, numerical simulation, geochemistry, and groundwater. In addition, the strategic diagram and thematic structure revealed how geothermal research has evolved over time. Finally, the timeline view and burst term highlight the possible frontiers of geothermal power generation, enhanced geothermal systems, and ecological environment protection. These insights will provide scholars and policymakers with a systematic understanding of the current research and directions for future studies.
Ultra-Short-Term Power Prediction of a Photovoltaic Power Station Based on the VMD-CEEMDAN-LSTM Model
Authors: Wang Shuaijie , Liu Shu , Guan Xin
Published: July 2022

The prediction of photovoltaic power generation is helpful to the overall allocation of power planning departments and improves the utilization rate of photovoltaic power generation. Therefore, this study puts forward an ultra-short-term power forecasting model of a photovoltaic power station based on modal decomposition and deep learning. The methodology involved taking the data of a 50 MW photovoltaic power generation system in the Inner Mongolia Autonomous Region as a sample. Furthermore, the weather conditions were classified, and the historical power data were decomposed into multiple VMF subcomponents and residual terms by the VMD method. Then, the residual term was decomposed twice by the CEEMDAN method. All subcomponents were sent to the LSTM network for prediction, and the predicted value of the photovoltaic power station was obtained by superimposing the subcomponent prediction results. ARIMA, SVM, LSTM, and VMD-LSTM models were built to compare the accuracy with the proposed models. The results revealed that the prediction accuracy of a non-combination forecasting model was limited when the weather suddenly changed. The VMD method was used to decompose the residual term twice, which could fully extract the complex data information in the residual term, and when compared with the VMD-LSTM model, the eRMSE, eMAPE, and eTIC of the VMD-CEEMDAN-LSTM model were reduced by 0.104, 16.596, and 0.038, respectively. The second decomposition technology has obvious prediction advantages. The proposed quadratic modal decomposition model effectively improves the precision of ultra-short-term prediction of photovoltaic power plants.
Insights Into the Role of Epigenetic Factors Determining the Estrogen Response in Estrogen-Positive Ovarian Cancer and Prospects of Combining Epi-Drugs With Endocrine Therapy
Authors: Sarwar Sadia , Alamro Abir , Huq Fazlul , Alghamdi Amani
Published: July 2022

Ovarian cancer is one of the most lethal malignancies. The population at the risk is continually on the rise due to the acquired drug resistance, high relapse rate, incomplete knowledge of the etiology, cross-talk with other gynecological malignancies, and diagnosis at an advanced stage. Most ovarian tumors are thought to arise in surface epithelium somehow in response to changes in the hormonal environment. Prolonged treatment with hormone replacement therapy (HRT) is also considered a contributing factor. Estrogens influence the etiology and progression of the endocrine/hormone-responsive cancers in a patient-specific manner. The concept of hormonal manipulations got attention during the last half of the 20th century when tamoxifen was approved by the FDA as the first selective estrogen receptor modulator (SERM). Endocrine therapy that has been found to be effective against breast cancer can be an option for ovarian cancer. It is now established that global changes in the epigenetic landscape are not only the hallmark of tumor development but also contribute to the development of resistance to hormone therapy. A set of functionally related genes involved in epigenetic reprogramming are controlled by specific transcription factors (TFs). Thus, the activities of TFs mediate important mechanisms through which epigenetic enzymes and co-factors modify chromatin for the worst outcome in a site-specific manner. Furthermore, the role of epigenetic aberrations involving histone modifications is established in ovarian cancer pathogenesis. This review aims to provide insights on the role of key epigenetic determinants of response as well as resistance to the hormone therapy, the current status of research along with its limitations, and future prospects of epigenetic agents as biomarkers in early diagnosis, prognosis, and personalized treatment strategies. Finally, the possibility of small phytoestrogenic molecules in combination with immunotherapy and epi-drugs targeting ovarian cancer has been discussed.
A Fatty Acid Metabolism Signature Associated With Clinical Therapy in Clear Cell Renal Cell Carcinoma
Authors: Wei Zhihao , Cheng Gong , Ye Yuzhong , Le Changjie , Miao Qi , Chen Jiawei , Yang Hongmei , Zhang Xiaoping
Published: July 2022

Renal cell carcinoma is one of the most common tumors in the urinary system, among which clear cell renal cell carcinoma is the most common subtype with poor prognosis. As one of the tumors closely related to lipid metabolism, the role of fatty acid metabolism in ccRCC was investigated to predict the prognosis and guide treatment strategies. RNA-seq and clinical information of patients with ccRCC and expression microarray of human renal cell carcinoma cell lines were obtained from TCGA and GEO databases. Fatty acid metabolism–related risk signature was established by the univariate Cox regression and LASSO analysis to predict patient prognosis and response to different treatment modalities. Using the fatty acid metabolism risk signature, the risk score for each sample in the TCGA cohort was calculated and divided into high-risk and low-risk groups, with the cutoff point being the median. Patients with higher risk scores had a poorer prognosis than those with lower risk scores. The response of each sample to immunotherapy was predicted from the “TIDE” algorithm, while the sensitivity of each sample to sunitinib was obtained using the “pRRophetic” R package. Patients with lower risk scores had higher expression of PD-L1 and better efficacy for sunitinib than those in the high-risk group and were less likely to develop drug resistance, while patients with high-risk scores had a strong response to the anti-CTLA4 antibody therapy. A nomogram was constructed by independent prognostic factors to predict the 1-, 3-, and 5-year survival. According to the calibration curves, the nomogram had an excellent ability to predict survival for patients with ccRCC. Therefore, the fatty acid metabolism risk signature we established can not only predict the survival of patients with ccRCC but also predict patient response to targeted therapy and immunotherapy to provide optimal treatment strategies for patients.
A Predictive Model for the 10-year Overall Survival Status of Patients With Distant Metastases From Differentiated Thyroid Cancer Using XGBoost Algorithm-A Population-Based Analysis
Authors: Jin Shuai , Yang Xing , Zhong Quliang , Liu Xiangmei , Zheng Tao , Zhu Lingyan , Yang Jingyuan
Published: July 2022

Purpose: To explore clinical and non-clinical characteristics affecting the prognosis of patients with differentiated thyroid cancer with distant metastasis (DTCDM) and establish an accurate overall survival (OS) prognostic model.

Patients and methods: Study subjects and related information were obtained from the National Cancer Institute’s surveillance, epidemiology, and results database (SEER). Kaplan‐Meier analysis, log-rank test, and univariate and multivariate Cox analysis were used to screen for factors influencing the OS of patients with DTCDM. Nine variables were introduced to build a machine learning (ML) model, receiver operating characteristic (ROC) was used to evaluate the recognition ability of the model, calibration plots were used to obtain prediction accuracy, and decision curve analysis (DCA) was used to estimate clinical benefit.

Results: After applying the inclusion and exclusion criteria, a total of 3,060 patients with DTCDM were included in the survival analysis from 2004 to 2017. A machine learning prediction model was developed with nine variables: age at diagnosis, gender, race, tumor size, histology, regional lymph node metastasis, primary site surgery, radiotherapy, and chemotherapy. After excluding patients who survived <120 months, variables were sub-coded and machine learning was used to model OS prognosis in patients with DTCDM. Patients 6–50 years of age had the highest scores in the model. Other variables with high scores included small tumor size, male sex, and age 51–76. The AUC and calibration curves confirm that the XGBoost model has good performance. DCA shows that our model can be used to support clinical decision-making in a 10-years overall survival model.

Conclusion: An artificial intelligence model was constructed using the XGBoost algorithms to predict the 10-years overall survival rate of patients with DTCDM. After model validation and evaluation, the model had good discriminative ability and high clinical value. This model could serve as a clinical tool to help inform treatment decisions for patients with DTCDM.
Construction of High-Density Genetic Map and Identification of a Bruchid Resistance Locus in Mung Bean (Vigna radiata L.)
Authors: Chen Tianxiao , Hu Liangliang , Wang Suhua , Wang Lixia , Cheng Xuzhen , Chen Honglin
Published: July 2022

Mung bean (Vigna radiata L.) is an economically important grain legume cultivated in Asian countries. High-density genetic linkage is a valuable and effective tool for mapping quantitative trait loci (QTL). In the current study, a high-resolution genetic map containing 4,180 single-nucleotide polymorphisms (SNPs) was assigned to 11 linkage groups (LGs) and spanning 1,751.39 cM in length was constructed for mung bean, and the average distance between adjacent markers was 0.42 cM. Bruchids (Callosobruchus spp.) cause significant damage to and loss of legume seeds. A locus for bruchid resistance was detected. The gene Vradi05g03810, encoding a probable resistance-specific protein, was found to be the most likely key candidate gene in mung beans. A 69-bp sequence deletion was identified in the coding region by comparing the cDNA sequences of bruchid-resistant and bruchid-susceptible lines. This SNP-based high-density linkage map is one of the first to be constructed across the mung bean genome. This map will not only facilitate the genetic mapping of genes or complex loci that control important agronomic traits but also offer a tool for promoting future genetics and comparative genomic studies in Vigna.
Attitudes Toward the Copper IUD in Sweden: A Survey Study
Authors: Wemrell Maria , Gunnarsson Lena
Published: July 2022

Background

While the efficacy and safety of the contraceptive copper intrauterine device (IUD) have been affirmed, alongside its importance for the prevention of unintended pregnancies, some studies have pointed to negative attitudes toward the device. In recent years, social media communication about it has included claims about systemic side effects, unsubstantiated by medical authorities. Research from the Swedish context is sparse. This study investigates attitudes toward the copper IUD and any correlations between negative attitudes toward or experiences of the device, and (1) sociodemographic characteristics, (2) the evaluation of the reliability of different sources of information, and (3) trust in healthcare and other societal institutions.

Methods

A survey was distributed online to adult women in Sweden (n = 2,000). Aside from descriptive statistics, associations between negative attitudes toward or experiences of the copper IUD and sociodemographic and other variables were calculated using logistic regressions and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). Open survey responses (n = 650) were analyzed thematically.

Results

While many reported positive attitudes toward and experiences of the IUD, 34.7% of all respondents reported negative attitudes and 45.4% of users reported negative experiences. Negative attitudes were strongly correlated with negative experiences. Negative attitudes and experiences were associated with low income, but no conclusive associations were identified with other socioeconomic variables. Negative attitudes and experiences were associated with lower levels of confidence in and satisfaction with healthcare, as well as lower self-assessed access and ability to assess the origin and reliability of information about the IUD. In open responses, negative comments were prevalent and included references to both common and unestablished perceived side-effects. Respondents pointed to problematic aspects of information and knowledge about the copper IUD and called for improved healthcare communication and updated research.

Conclusion

Healthcare provider communication about the copper IUD should promote reproductive autonomy and trust by providing clear information about potential side effects and being open to discuss women's experiences and concerns. Further research on copper IUD dissatisfaction and ways in which health professionals do and may best respond to it is needed.
Inflammation in Preeclampsia: Genetic Biomarkers, Mechanisms, and Therapeutic Strategies
Authors: Wang Yue , Li Baoxuan , Zhao Yan
Published: July 2022

Objective

Preeclampsia is a common and serious complication of pregnancy, posing a threat to maternal and fetal safety due to the lack of effective biomarkers and treatment strategies. This study aimed to identify potential biomarkers that can be used to predict preeclampsia and identify the molecular mechanisms of preeclampsia pathogenesis and drug prediction at the transcriptome level.

Methods

We analyzed differential expression genes (DEGs) in preeclampsia and non-preeclampsia groups in the GSE75010 dataset, cross-linking with extracted inflammatory response-related genes to obtain differentially expressed inflammation-related genes (DINRGs). Enrichment analysis and protein-protein interaction (PPI) networks were constructed to understand the functions and enrichment pathways. Machine learning models were used to identify key genes associated with preeclampsia and build a nomogram in the training set, which was validated in the validation set. The R package RcisTarget was used to predict transcription factors, and Cytoscape was used to construct miRNA-mRNA pathways, which could identify the molecular mechanisms. Then, we conducted molecular docking of the obtained key genes INHBA (inhibin subunit beta A), OPRK1 (opioid receptor kappa 1), and TPBG (trophoblast glycoprotein), as well as predicted transcription factors with drug molecules. Additionally, the CIBERSORT method explored the differences in immune cell infiltration between preeclampsia and non-preeclampsia samples based on the GSE75010 dataset.

Results

A total of 69 DINRGs associated with preeclampsia patients were screened. INHBA, OPRK1, and TPBG were the key genes based on machine learning models. A nomogram for prediction was further constructed, and the receiver operating curves (ROCs) showed good performance. Based on the transcriptome level of key genes, we proposed that RELA-miR-548K/miR-1206-TPBG may be a potential RNA regulatory pathway regulating the progression of early preeclampsia. Molecular docking suggested the effectiveness of curcumin in the treatment of preeclampsia. Additionally, regulatory T cells (Tregs) and resting mast cells were significantly different between the two groups.

Conclusion

In summary, we identified three key inflammation-associated genes, namely INHBA, OPRK1, and TPBG, which can be used as potential genetic biomarkers for preeclampsia prediction and treatment, and established a nomogram as a predictive model. Additionally, we provided insights into the mechanisms of preeclampsia development at the transcriptome level and performed corresponding drug predictions.
Mesalamine-Mediated Amelioration of Experimental Colitis in Piglets Involves Gut Microbiota Modulation and Intestinal Immune Cell Infiltration
Authors: Huang Yonggang , Wu Miaomiao , Xiao Hao , Liu Hongnan , Yang Guan
Published: July 2022

Mesalamine (MES), also known as 5-aminosalicylic acid, is effective in treating mild to moderate ulcerative colitis (UC). The mechanisms of its actions are not fully elucidated. The aim of this study was to investigate the effects of MES treatment on intestinal microbiota and immune system in an dextran sulfate sodium (DSS)-induced UC model in postweaning piglets. Eighteen weaned piglets were assigned randomly to the following treatments: control group (CON, distilled water), DSS group (DSS, 3% DSS), and MES group (MES, 3% DSS + 2 g/day MES). Our results showed that MES treatment alleviates DSS-induced colitis in piglets, as evidenced by a reduced diarrhea index score and increased average daily gain (P < 0.05). This is accompanied by decreased diamine oxidase activity, D-lactate level (P < 0.05), and attenuated mucosal damage. MES treatment also decreased the abundance of Methanogens and reduced colon CD11b+ macrophage and CD3+ T-cell infiltrations in piglets with DSS-induced colitis (P < 0.05). Collectively, these data indicate that MES treatment-mediated colitis protection may involve microbiota and immune cell alterations.
Phenotypic Changes of Peripheral γδ T Cell and Its Subsets in Patients With Coronary Artery Disease
Authors: Li Yan , Jiang Silin , Li Jiawei , Yin Mengzhuo , Yan Fuxin , Chen Yuyuan , Chen Yan , Wu Tongwei , Cheng Mengliang , He Yihua , Liang Hongbin , Yu Hang , Qiao Qingqing , Guo Zhigang , Xu Yan , Zhang Yanan , Xiang Zheng , Yin Zhinan
Published: July 2022

Coronary atherosclerotic heart disease (CAD) is a chronic inflammatory cardiovascular disease with high morbidity and mortality. Growing data indicate that many immune cells are involved in the development of atherosclerosis. However, the immunological roles of γδ T cells in the initiation and progression of CAD are not fully understood. Here, we used flow cytometry to determine phenotypical changes of γδ T cells and their subpopulations in peripheral blood samples collected from 37 CAD patients. The Pearson correlation coefficient was used to analyze the relationship between the clinical parameter (serum LDL-C level) and the changes of immunophenotypes of γδ T cells. Our results demonstrated that the frequencies and absolute numbers of total γδ T cells and Vδ2+ T cells were significantly decreased in CAD patients when compared to healthy individuals. However, the proportion of Vδ1+ T cells was much lower in CAD patients than that of healthy individuals. Most importantly, a significant alteration of the Vδ1/Vδ2 ratio was found in CAD patients. In addition, a series of surface markers that are associated with costimulatory signals (CD28, CD40L, CD80, CD86), activation levels (CD69, CD25, HLA-DR), activating NK cell receptors (NKp30, NKp46, NKG2D) and inhibitory receptors (PD-1, CTLA-4, PD-1, Tim-3) were determined and then analyzed in the total γδ T cells, Vδ2+T cells and Vδ2-T cells of CAD patients and healthy individuals. The data demonstrated that immunological activities of total γδ T cells, Vδ2+T cells, and Vδ2-T cells of CAD patients were much lower than those in healthy individuals. Moreover, we found that there were positive correlations between the serum LDL-C levels and frequencies of CD3+γδ+ T cells, CD69+Vδ2+T cells, NKG2D+Vδ2+T cells, and NKp46+Vδ2+T cells. By contrast, there was an inverse correlation between the levels of serum LDL-C and the frequencies of CD69+Vδ2-T cells and NKp46+Vδ2-T cells. Accordingly, these findings could help us to better understand the roles of γδ T cells in the CAD, and shed light on the development of novel diagnostic techniques and therapeutic strategies by targeting γδ T cells for CAD patients.
Colorectal Cancer-Infiltrating Regulatory T Cells: Functional Heterogeneity, Metabolic Adaptation, and Therapeutic Targeting
Authors: Aristin Revilla Sonia , Kranenburg Onno , Coffer Paul J.
Published: July 2022

Colorectal cancer (CRC) is a heterogeneous disease with one of the highest rates of incidence and mortality among cancers worldwide. Understanding the CRC tumor microenvironment (TME) is essential to improve diagnosis and treatment. Within the CRC TME, tumor-infiltrating lymphocytes (TILs) consist of a heterogeneous mixture of adaptive immune cells composed of mainly anti-tumor effector T cells (CD4+ and CD8+ subpopulations), and suppressive regulatory CD4+ T (Treg) cells. The balance between these two populations is critical in anti-tumor immunity. In general, while tumor antigen-specific T cell responses are observed, tumor clearance frequently does not occur. Treg cells are considered to play an important role in tumor immune escape by hampering effective anti-tumor immune responses. Therefore, CRC-tumors with increased numbers of Treg cells have been associated with promoting tumor development, immunotherapy failure, and a poorer prognosis. Enrichment of Treg cells in CRC can have multiple causes including their differentiation, recruitment, and preferential transcriptional and metabolic adaptation to the TME. Targeting tumor-associated Treg cell may be an effective addition to current immunotherapy approaches. Strategies for depleting Treg cells, such as low-dose cyclophosphamide treatment, or targeting one or more checkpoint receptors such as CTLA-4 with PD-1 with monoclonal antibodies, have been explored. These have resulted in activation of anti-tumor immune responses in CRC-patients. Overall, it seems likely that CRC-associated Treg cells play an important role in determining the success of such therapeutic approaches. Here, we review our understanding of the role of Treg cells in CRC, the possible mechanisms that support their homeostasis in the tumor microenvironment, and current approaches for manipulating Treg cells function in cancer.
The Cholesterol-Binding Sequence in Monomeric C-Reactive Protein Binds to the SARS-CoV-2 Spike Receptor-Binding Domain and Blocks Interaction With Angiotensin-Converting Enzyme 2
Authors: Li Hai-yun , Gao Ning , Liu Cheng-yang , Liu Xiao-ling , Wu Feng , Dai Nini , Han Jing , Li Qiu-yu
Published: July 2022

The receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is a prerequisite for the virus to enter the cell. C-reactive protein (CRP) is an important marker of inflammation and is a putative soluble pattern recognition receptor. Clinical elevation of CRP levels in patients with COVID-19 is one of the characteristics of the disease; however, whether CRP is involved in COVID-19 pathogenesis is unknown. Here, we report that monomeric CRP (mCRP) can bind to the SARS-CoV-2 spike RBD and competitively inhibit its binding to ACE2. Furthermore, truncated mutant peptide competition assays and surface plasmon resonance binding experiments showed that the cholesterol-binding sequence (CBS, amino acids 35-47) in mCRP was critical for mediating the binding of mCRP to spike RBD. In a cell model of spike RBD and ACE2 interaction, the CBS motif effectively reduced the binding of spike RBD to ACE2 overexpressed on the cell surface. Thus, this study highlights the pattern recognition function of mCRP in innate immunity and provides a preliminary theoretical basis for the development of the CBS motif in mCRP into a functional peptide with both diagnostic significance and potential therapeutic capabilities.
Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy
Authors: Peng Peng , Lou Yue , Wang Junjun , Wang Shicheng , Liu Ping , Xu Lisa X.
Published: July 2022

Recent studies suggest that highly activated, polyfunctional CD4+ T cells are incredibly effective in strengthening and sustaining overall host antitumor immunity, promoting tumor-specific CD4+ T-cell responses and effectively enhancing antitumor immunity by immunotherapy. Previously, we developed a novel cryo-thermal therapy for local tumor ablation and achieved long-term survival rates in several tumor models. It was discovered that cryo-thermal therapy remodeled the tumor microenvironment and induced an antigen-specific CD4+ T-cell response, which mediated stronger antitumor immunity in vivo. In this study, the phenotype of bulk T cells in spleen was analyzed by flow cytometry after cryo-thermal therapy and both CD4+ Th1 and CD8+ CTL were activated. In addition, by using T-cell depletion, isolation, and adoptive T-cell therapy, it was found that cryo-thermal therapy induced Th1-dominant CD4+ T cells that directly inhibited the growth of tumor cells, promoted the maturation of MDSCs via CD4+ T-cell-derived IFN-γ and enhanced the cytotoxic effector function of NK cells and CD8+ T cells, and promoted the maturation of APCs via cell-cell contact and CD4+ T-cell-derived IFN-γ. Considering the multiple roles of cryo-thermal-induced Th1-dominant CD4+ T cells in augmenting antitumor immune memory, we suggest that local cryo-thermal therapy is an attractive thermo-immunotherapy strategy to harness host antitumor immunity and has great potential for clinical application.
Ang2-Targeted Combination Therapy for Cancer Treatment
Authors: Liu Na , Liu Mengfang , Fu Shengqiao , Wang Jinglei , Tang Haowen , Isah Adamu Danbala , Chen Deyu , Wang Xu
Published: July 2022

Angiopoietin-2 (Ang2), a member of the angiopoietin family, is widely involved in the process of vascular physiology, bone physiology, adipose tissue physiology and the occurrence and development of inflammation, cardiac hypertrophy, rheumatoid, tumor and other diseases under pathological conditions. Proliferation and metastasis of cancer largely depend on angiogenesis. Therefore, anti-angiogenesis has become the target of tumor therapy. Due to the Ang2 plays a key role in promoting angiogenesis and stability in vascular physiology, the imbalance of its expression is an important condition for the occurrence and development of cancer. It has been proved that blocking Ang2 can inhibit the growth, invasion and metastasis of cancer cells. In recent years, research has been constantly supplemented. We focus on the mechanisms that regulate the expression of Ang2 mRNA and protein levels in different cancers, contributing to a better understanding of how Ang2 exerts different effects in different cancers and stages, as well as facilitating more specific targeting of relevant molecules in cancer therapy. At the same time, the importance of Ang2 in cancer growth, metastasis, prognosis and combination therapy is pointed out. And finally, we will discuss the current investigations and future challenges of combining Ang2 inhibition with chemotherapy, immunotherapy, and radiotherapy to increase its efficacy in cancer patients. This review provides a theoretical reference for the development of new targets and effective combination therapy strategies for cancer treatment in the future.
Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer
Authors: Feng Songwei , Xu Yi , Dai Zhu , Yin Han , Zhang Ke , Shen Yang
Published: July 2022

Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression.
Sargassum horneri as a Prebiotic Dietary Supplement for Immunity Development in Streptococcus parauberis Infected Zebrafish Model
Authors: Liyanage Nisansala Madushani , Kim Young-Sang , Nagahawatta Dineth Pramuditha , Jin Hwang , Yang Hye-Won , Jayawardhana Henarath Hetti Arachchilage Chathuri Kanchana , Jayawardena Thilina U. , Jeon You-Jin
Published: July 2022

Sargassum horneri (SH) is a brown macroalgal species commonly found along the coast of Japan, China, and Korea. SH possesses valuable bioactive compounds that can be developed as functional food ingredients as well as pharmaceutical agents for both humans and animals. In this study, SH was tested for its potential prebiotic effect. Several solvent-assisted extracts of SH were tested on the growth of three species of probiotics (LAB) (Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus brevis) and fish pathogen bacteria (Streptococcus iniae, Streptococcus parauberis, Edwersiella tarda) both in vitro and in vivo. According to the in vitro results, Celluclast extract (SHC) and crude polysaccharide extract (SHCPs) of SH showed outstanding growth enhancing activity in all LAB species and excellent antibacterial activity against pathogenic bacteria dose-dependently. Both SHC and SHCPs induced the production of secondary metabolites from LAB. The secondary metabolites successfully reduced pathogenic bacterial growth. Furthermore, in vivo experiments revealed that co-treatment with LAB and SHC/SHCPs diminished the mortality of Streptococcus parauberis infected zebrafish by modulating iNOS, COX-2 expressions. Similarly, SH act as an anti-inflammatory agent against S. parauberis infection by hindering NF-κB pathway activation. Conclusively, the results achieved from the study suggest that S. horneri has the potential to be used as a prebiotic dietary supplement and possesses a protective effect against S. parauberis infections in the aquaculture industry.
An Insight on the Estimation of Wave Propagation Constants in an Orthogonal Grid of a Simple Line-Supported Periodic Plate Using a Finite Element Mathematical Model
Authors: Pany Chitaranjan
Published: July 2022

This article describes the propagation of free waves in a two-dimensional periodic plate using the finite element (FE) method. The advantage of periodic structure analysis is that all the dynamic properties of a finite structure are derived from a single phase-frequency curve or surface. Infinite plates are considered as a combination of periodic plates on an orthogonal array of simple, evenly spaced line supports. A single periodic unit of the system is represented by a more accurate high-precision arbitrary triangular shallow shell FE model to find the plane wave frequency in terms of the propagation constants of the 2D periodic plate. Only the purely propagating waves with no attenuation are considered here. The natural frequency of the infinite plate was obtained for different propagation constants in the two directions of the plate. The results are compared with the literature data. The bounding frequency of the propagation surface is compared to the data published from single square and rectangular plates with different edge boundary conditions. In addition, the natural frequency of the plate supported by finite line support with spans Nx (x-direction) and Ny (y-direction) is compared with the frequency obtained from the propagation curve by the discretization principle. The comparison is seen to be very close. It is found that the current PS-FEM approach can be used to generate dispersion relations with reasonable accuracy.
Network Meta-Analysis of Perioperative Analgesic Effects of Different Interventions on Postoperative Pain After Arthroscopic Shoulder Surgery Based on Randomized Controlled Trials
Authors: Jiangping Wu , Xiaolin Quan , Han Shu , Zhou Xiaolan , Mao Nie , Zhibo Deng , Ting Gong , Shidong Hu , Xiangwei Li , Xin Yuan , Guoyin Shu
Published: July 2022

Background

Shoulder arthroscopic surgery is a common surgical method used in orthopedics. However, severe postoperative pain can significantly limit the early joint movement of patients and adversely affect the impact of the surgery. At present, there is no consistent and effective analgesic scheme for the management of postoperative pain after arthroscopic surgery of the shoulder.

Purpose

The aim of this study was to search for the most effective analgesic scheme to control pain in the perioperative period of arthroscopic surgery of the shoulder.

Study Design

Network meta-analysis.

Methods

We searched 5 different databases (i.e., Medline, PubMed, Embase, Web of Science, and the Cochrane Library) from January 2011 to January 2021 for English literature. Thereafter, we sifted out randomized controlled trials (RCTs), which compared different intervention schemes for pain management after shoulder arthroscopy and selected only 12 h, 24 h, or 48 h after the patient leaves the operating room as an optimal period for administration of analgesic intervention schemes. Only patients with shoulder disease who have undergone arthroscopic shoulder surgery were included in this study. The Cochrane “risk of bias” was used for the quality assessment. Moreover, some additional tests were performed to enhance the credibility of the results.

Results

Twenty-nine RCTs involving 1,885 patients were included in this frequentist network meta-analysis (NMA). These articles mainly were divided into two distinct groups, namely, the nerve block group and the non-nerve block group. Regarding the nerve block group, at postoperative 12 h, the intervention suprascapular nerve block + interscalene nerve block (SSNB + INB) was ranked first, whereas INB + intra-articular injection (INB + IAI) was ranked first at 24 h and 48 h postoperation. In the non-nerve block group, external application (EA) was ranked first at postoperative 12 h, but oral administration (OA) exhibited a better analgesic effect at postoperative 24 h and postoperative 48 h.

Conclusion

We conclude that the analgesic effect of SSNB+INB was the best at postoperative 12 h, and INB+IAI was the best at postoperative 24 h and 48 h in the nerve block group. For the non-nerve block group, the effect of EA was the best at postoperative 12 h, and the analgesic effect of OA at postoperative 24 h and 48 h was significantly better than any other interventions.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42021286777.