bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the Temporal and Spatial Patterns of Ecosystem Services and Exploring the Spatial Differentiation of Driving Factors: a Case Study of Sichuan Basin, China
Authors: Hu Chunguang , Wang Ziyi , Li Jiaming , Liu Huan , Sun Dongqi
Published: July 2022

Exploring the factors that drive the change of ecosystem services (ES) is very important for maintaining ES function and zoning ecological management, especially in the Sichuan Basin area with high spatial heterogeneity such as natural and socio-economic characteristics. Taking the Sichuan Basin in China as an example, the PCA-MGWR model was constructed to explore the temporal and spatial patterns of ES in the Sichuan Basin from 2000 to 2015. The potential driving factors including anthropogenic factors, geomorphological factors, climate factors, and vegetation factors would be analyzed by principal component analysis (PCA). To illustrate the impact of spatial dependence in the data, the multi-scale geographically weighted regression (MGWR) technology was selected to explore the spatial differentiation of the impact of these four dimensions on ES to reflect the local differences of ecosystem service driving mechanisms in more detail. The results showed that 1) from the perspective of time series evolution, carbon storage (CS) and soil conservation (SC) in ES in the Sichuan Basin showed an upward trend, while water yield (WY) showed a downward trend; from the perspective of spatial patterns, except the main urban areas of Chengdu and Chongqing, the CS service level of other regions was high; The spatial distribution characteristics of SC services were “low in the middle and high in the periphery”; the high value area of WY service was located in Northeast Sichuan. 2) Among natural factors, elevation (DEM), slope (SLO), NDVI, annual average temperature (TEM), and annual average precipitation (PRE) had a higher contribution rate to ES, while among socio-economic factors, GDP density (GDP), night light (LIG), and population density (POP) had a higher contribution rate to ES, while other factors had a lower contribution rate. 3) Combined with the PCA-MGWR model, we analyzed the comprehensive response and spatial differentiation of driving factors to ES in the Sichuan Basin and explained in detail the influence of anthropogenic factors, geomorphological factors, climatic factors, and vegetation factors and their spatial heterogeneity in ES. It is expected that the spatial differences in the impact degree of different indicators can be considered when formulating the countermeasures of ES in the Sichuan Basin, to provide theoretical support for the implementation of regional ecological management and control.
Impacts of Water Bodies on Microclimates and Outdoor Thermal Comfort: Implications for Sustainable Rural Revitalization
Authors: Cheng Yanyan , Liu Xiao , Zeng Zhi , Liu Shengshuai , Wang Zhaoyu , Tang Xu , He Bao-Jie
Published: July 2022

Water is the source of life and the fundamental element of ecology, and climate is inseparable from water. To evaluate the influence of water-adaptive space in a traditional Weizi (polder village) settlement on its microclimate, the authors analyzed the morphological characteristics of such a polder village and applied the ENVI-met model to simulate the impact of water bodies and village morphological elements on human thermal comfort. This paper demonstrates the positive impact of water bodies on improving the thermal environment of a village and regulating its microclimate by quantifying the impact of morphological elements of the settlement on microclimate. The results indicate that: 1) The simulation model fits the actual measurements well, and the simulation accurately reflects experimental results; 2) In summer, the cooling effect of water bodies is better in the afternoon than in the morning, especially from 12:00 to 15:00. The cooling effect is significantly correlated with the distance to water bodies, i.e., the closer, the better; 3) Building density and man-made underlying surface are negatively correlated with temperature, humidity, and Physiological Equivalent Temperature value, while greening rate and water body rate are positively correlated with microclimate. Overall, water bodies can improve outdoor comfort in summer and thus should be protected and developed in rural planning and design. Villages can be built around water bodies for a maximized cooling effect, and microclimate comfort can be effectively improved by increasing green plants near the village center, and reducing man-made underlying surface and building density. The results of this study will guide the improvement of the habitat environment in the process of rural revitalization, as well as the protection and re-development of traditional villages.
Tropospheric Nitrogen Dioxide Increases Past Pre-Pandemic Levels Due to Economic Reopening in India
Authors: Liu Qian , Srirenganathanmalarvizhi Anusha , Howell Katherine , Yang Chaowei
Published: July 2022

This paper analyzes the spatiotemporal patterns of nitrogen dioxide (NO2) tropospheric vertical column densities (TVCDs) before and during the second wave of COVID-19 in India. The results indicate that the NO2 columns increase significantly in the reopening period before the second wave (Mar. 1 ∼ Apr. 20) in 2021, which exceed the levels of the same period in 2019. The relative difference from the mean of 2010–2019 is 18.76% higher in 2021 than that of 2019, during the reopening. The paper identifies Odisha, Madhya Pradesh, Chhattisgarh, Jharkhand and West Bengal as the five states with the largest increases in relative difference from 2019 to 2021, which are 33.81%, 29.83%, 23.86%, 30.01%, and 25.48% respectively. As illustrated by trends in the indices of industrial production (IIP), these unexpected increases in tropospheric NO2 can be attributed to reopening as well as elevated production across various sectors including electricity, manufacturing and mining. Analysis of NO2 TVCD levels alongside IIPs indicate a marked increase in industrial activity during the reopening period in 2021 than in the same time period in 2019. After the beginning of the second wave of COVID-19 (Apr. 21 ∼ Jun. 21), India re-implemented lockdown policies to mitigate the spread of the pandemic. During this period, the relative difference of total NO2 columns declined in India as well as in most individual study regions, when compared to 2019, due to the pandemic mitigation policies. The relative declines are as follows: 6.43% for the whole country and 14.25%, 22.88%, 4.57% and 7.89% for Odisha, Madhya Pradesh, Chhattisgarh and Jharkhan, respectively, which contain large industrial clusters. The change in relative difference in West Bengal from 2019 to 2021 is not significant during the re-lockdown period with a 0.04% increase. As with the first wave, these decreases in NO2 TVCD mainly due to the mitigation policies during the second wave.
Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma
Authors: Wang Suyu , Chen Aona , Zhu Wanli , Feng Di , Wei Juan , Li Quanfu , Shi Xuan , Lv Xin , Liu Meiyun
Published: July 2022

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Fatty acid metabolism takes part in malignancy progression. However, the roles fatty acid metabolism plays in LUAD are still unclear.

Methods: The transcriptomic and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were extracted. ssGSEA, WGCNA, univariable Cox regression, and LASSO Cox regression analyses were performed to identify the fatty acid metabolism-related genes which influenced the overall survival (OS) and build a fatty acid-related risk score (FARS) model. A nomogram was established based on the FARS and other clinicopathological features, and ROC and calibration plots were used to validate the prediction accuracy. The tumor microenvironment (TME) of patients with high and low FARS was compared.

Results: A total of 38 genes were identified to be independently related to the survival outcome and put into a FARS model. High FARS patients exhibited significantly worse OS. The nomogram included the FARS and pathological stage, and the AUC of the nomogram predicting 1-, 2-, 3-, 4-, and 5-year OS was 0.789, 0.807, 0.798, 0.809, and 0.753, respectively. Calibration plots also indicated good accuracy. Moreover, the samples of the high FARS had higher expression of PDL1.

Conclusion: We constructed a FARS model which could accurately predict the survival outcome of the LUAD patients. The genes of the FARS are related to the tumor microenvironment and patients with high FARS can potentially benefit more from anti-PD1/PDL1 immunotherapy. In addition, the mechanisms of the genes in the FARS affecting prognosis are worthy of further research to develop new gene-targeted drugs.
Integrated Bioinformatics Analysis Identifies Robust Biomarkers and Its Correlation With Immune Microenvironment in Nonalcoholic Fatty Liver Disease
Authors: Zhang Feng , Zhang Zhengwei , Li Yapeng , Sun Yi , Zhou Xinliang , Chen Xiaoning , Sun Shibo
Published: July 2022

Objective: Nonalcoholic fatty liver disease (NAFLD) is a serious threat to human health worldwide. In this study, the aim is to analyze diagnosis biomarkers in NAFLD and its relationship with the immune microenvironment based on bioinformatics analysis.

Methods: We downloaded microarray datasets (GSE48452 and GSE63067) from the Gene Expression Omnibus (GEO) database for screening differentially expressed genes (DEGs). The hub genes were screened by a series of machine learning analyses, such as support vector machine (SVM), least absolute shrinkage and selection operator (LASSO), and weighted gene co-expression network analysis (WGCNA). It is worth mentioning that we used the gene enrichment analysis to explore the driver pathways of NAFLD occurrence. Subsequently, the aforementioned genes were validated by external datasets (GSE66676). Moreover, the CIBERSORT algorithm was used to estimate the proportion of different types of immune cells. Finally, the Spearman analysis was used to verify the relationship between hub genes and immune cells.

Results: Hub genes (CAMK1D, CENPV, and TRHDE) were identified. In addition, we found that the pathogenesis of NAFLD is mainly related to nutrient metabolism and the immune system. In correlation analysis, CENPV expression had a strong negative correlation with resting memory CD4 T cells, and TRHDE expression had a strong positive correlation with naive B cells.

Conclusion: CAMK1D, CENPV, and TRHDE play regulatory roles in NAFLD. In particular, CENPV and TRHDE may regulate the immune microenvironment by mediating resting memory CD4 T cells and naive B cells, respectively, and thus influence disease progression.
Smoking patients with laryngeal cancer screened with a novel immunogenomics-based prognostic signature
Authors: Shen Yujie , Zhou Han , Dong Shikun , Dong Weida , Zhang Liqing
Published: July 2022

The immune system greatly affects the prognosis of various malignancies. Studies on differentially expressed immune-related genes (IRGs) in the immune microenvironment of laryngeal squamous cell carcinoma (LSCC) have rarely been reported. In this paper, the prognostic potentials of IRGs were explored in LSCC patients with smoking use. The RNA-seq data containing IRGs and corresponding clinical information of smoking LSCC patients was obtained from The Cancer Genome Atlas (TCGA). Differentially expressed IRGs were identified and functional enrichment analysis was used to reveal the pathway of IRGs. Then, IRGs with prognostic potentials in smoking LSCC patients were screened out by univariate Cox regression analysis. Finally, multivariate Cox regression analysis was conducted to assess the prognostic signature of 5 IRGs after adjustment of clinical factors and patients were classified into two subgroups based on different IRGs expression. The prognostic capacity of the model was verified by another independent cohort from Gene Expression Omnibus (GEO) database. Nomogram including the prognostic signature was established and shown some clinical net benefit. These findings may contribute to the development of potential therapeutic targets and biomarkers for the new-immunotherapy of LSCC patients with smoking use.
Myeloid-Derived Suppressor Cells in Patients With Acute Pancreatitis With Increased Inhibitory Function
Authors: Ding Lili , Wan Minjie , Wang Dong , Cao Huiru , Wang Haijiao , Gao Pujun
Published: July 2022

Acute pancreatitis (AP) is pancreatic or systemic inflammation without or with motion organ dysfunction. Severe acute pancreatitis (SAP) is the main cause of death for patients with AP. A pro-/anti-inflammatory imbalance is considered the key regulation of disease severity. However, the real mechanism of SAP remains unclear. This study aimed to identify the frequency and specific roll of myeloid-derived suppressor cell (MDSC) in AP. We evaluated MDSC frequency and disease severity by analyzing MDSCs in the peripheral blood of healthy controls (HCs) and patients with mild acute pancreatitis (MAP) and SAP by flow cytometry. We also compared the frequency and inhibitory ability of MDSCs from HCs and SAP, and finally detected the reason for the difference in inhibitory ability. AP was marked by expansion of MDSCs as well as its subsets, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). The proportion of MDSC in the peripheral blood mononuclear cells of patients with AP was increased and positively correlated with AP severity. The frequency of MDSC was decreased after treatment compared with pre-treatment. CD3+ T cells were remarkably inhibited by MDSC derived from the patients with SAP. In the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), the MDSCs from patients with SAP increased. These findings demonstrated that MDSCs expanded in the peripheral blood in patients with AP, especially in those with SAP. Moreover, the inhibitory ability of MDSCs was increased in the patients with SAP compared with that in the HCs. The enhanced suppressive function was possibly caused by an overexpression of Arg-1 and ROS.
The Protective Effect of the Soluble Egg Antigen of Schistosoma japonicum in A Mouse Skin Transplantation Model
Authors: Jiang Jie , Li Junhui , Zhang Yu , Zhou Chen , Guo Chen , Zhou Zhaoqin , Ming Yingzi
Published: July 2022

Background

Organ transplantation is currently an effective method for treating organ failure. Long-term use of immunosuppressive drugs has huge side effects, which severely restricts the long-term survival of patients.Schistosomacan affect the host’s immune system by synthesizing, secreting, or excreting a variety of immunomodulatory molecules, but its role in transplantation was not well defined. In order to explore whetherSchistosoma-related products can suppress rejection and induce long-term survival of the transplant, we used soluble egg antigen (SEA) ofSchistosoma japonicumin mouse skin transplantation models.

Materials and methods

Each mouse was intraperitoneally injected with 100 μg of SEA three times a week for four consecutive weeks before allogenic skin transplant. Skin transplants were performed on day 0 to observe graft survival. Pathological examination of skin grafts was conducted 7 days post transplantation. The skin grafts were subjected to mRNA sequencing. Bioinformatics analysis was conducted and the expression of hub genes was verified by qPCR. Flow cytometry analysis was performed to evaluate the immune status and validate the results from bioinformatic analysis.

Results

The mean survival time (MST) of mouse skin grafts in the SEA-treated group was 11.67 ± 0.69 days, while that of the control group was 8.00 ± 0.36 days. Pathological analysis showed thatSjSEA treatment led to reduced inflammatory infiltration within skin grafts 7 days after allogenic skin transplantation. Bioinformatics analysis identified 86 DEGs between theSjSEA treatment group and the control group, including 39 upregulated genes and 47 downregulated genes. Further analysis revealed thatSjSEA mediated regulation on cellular response to interferon-γ, activation of IL-17 signaling and chemokine signaling pathways, as well as cytokine–cytokine receptor interaction. Flow cytometry analysis showed that SEA treatment led to higher percentages of CD4+IL-4+T cells and CD4+Foxp3+T cells and decreased CD4+IFN-γ+T cells in skin transplantation.

Conclusion

SjSEA treatment suppressed rejection and prolonged skin graft survival by regulating immune responses.SjSEA treatment might be a potential new therapeutic strategy to facilitate anti-rejection therapy and even to induce tolerance.
Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain
Authors: Zou Yu , Bai Xue-Hui , Kong Ling-Chi , Xu Fei-Fei , Ding Ting-Yu , Zhang Peng-Fei , Dong Fu-Lu , Ling Yue-Juan , Jiang Bao-Chun
Published: July 2022

Histone lysine crotonylation (KCR), a novel epigenetic modification, is important in regulating a broad spectrum of biological processes and various diseases. However, whether KCR is involved in neuropathic pain remains to be elucidated. We found KCR occurs in macrophages, sensory neurons, and satellite glial cells of trigeminal ganglia (TG), neurons, astrocytes, and microglia of the medulla oblongata. KCR in TG was detected mainly in small and medium sensory neurons, to a lesser extent in large neurons. Peripheral nerve injury elevated KCR levels in macrophages in the trigeminal and dorsal root ganglia and microglia in the medulla oblongata but reduced KCR levels in sensory neurons. Inhibition of histone crotonyltransferases (p300) by intra-TG or intrathecal administration of C646 significantly alleviated partial infraorbital nerve transection (pIONT)- or spinal nerve ligation (SNL)-induced mechanical allodynia and thermal hyperalgesia. Intra-TG or intrathecal administration of Crotonyl coenzyme A trilithium salt to upregulate KCR dose-dependently induced mechanical allodynia and thermal hyperalgesia in mice. Mechanismly, inhibition of p300 alleviated pIONT-induced macrophage activation and reduced the expression of pain-related inflammatory cytokines Tnfα, Il1β and chemokines Ccl2 and Cxcl10. Correspondingly, exogenous crotonyl-CoA induced macrophage activation and the expression of Tnfα, Il1β, Il6, Ccl2 and Ccl7 in TG, which C646 can repress. These findings suggest that histone crotonylation might be functionally involved in neuropathic pain and neuroinflammation regulation.
Combining Immune-Related Genes For Delineating the Extracellular Matrix and Predicting Hormone Therapy and Neoadjuvant Chemotherapy Benefits In Breast Cancer
Authors: Liu Jianyu , Lei Bo , Yu Xin , Li Yingpu , Deng Yuhan , Yang Guang , Li Zhigao , Liu Tong , Ye Leiguang
Published: July 2022

Breast cancer (BC) is the most prevalent cancer in women worldwide. A systematic approach to BC treatment, comprising adjuvant and neoadjuvant chemotherapy (NAC), as well as hormone therapy, forms the foundation of the disease’s therapeutic strategy. The extracellular matrix (ECM) is a dynamic network that exerts a robust biological effect on the tumor microenvironment (TME), and it is highly regulated by several immunological components, such as chemokines and cytokines. It has been established that the ECM promotes the development of an immunosuppressive TME. Therefore, while analyzing the ECM of BC, immune-related genes must be considered. In this study, we used bioinformatic approaches to identify the most valuable ECM-related immune genes. We used weighted gene co-expression network analysis to identify the immune-related genes that potentially regulate the ECM and then combined them with the original ECM-related gene set for further analysis. Least absolute shrinkage and selection operator (LASSO) regression and SurvivalRandomForest were used to narrow our ECM-related gene list and establish an ECM index (ECMI) to better delineate the ECM signature. We stratified BC patients into ECMI high and low groups and evaluated their clinical, biological, and genomic characteristics. We found that the ECMI is highly correlated with long-term BC survival. In terms of the biological process, this index is positively associated with the cell cycle, DNA damage repair, and homologous recombination but negatively with processes involved in angiogenesis and epithelial–mesenchymal transition. Furthermore, the tumor mutational burden, copy number variation, and DNA methylation levels were found to be related to the ECMI. In the Metabric cohort, we demonstrated that hormone therapy is more effective in patients with a low ECMI. Additionally, differentially expressed genes from the ECM-related gene list were extracted from patients with a pathologic complete response (pCR) to NAC and with residual disease (RD) to construct a neural network model for predicting the chance of achieving pCR individually. Finally, we performed qRT-PCR to validate our findings and demonstrate the important role of the gene OGN in predicting the pCR rate. In conclusion, delineation of the ECM signature with immune-related genes is anticipated to aid in the prediction of the prognosis of patients with BC and the benefits of hormone therapy and NAC in BC patients.
A Glimpse Into the Microbiome of Sjögren’s Syndrome
Authors: Deng Chuiwen , Xiao Qiufeng , Fei Yunyun
Published: July 2022

Sjögren’s syndrome (SS) is a common chronic systemic autoimmune disease and its main characteristic is lymphoid infiltration of the exocrine glands, particularly the salivary and lacrimal glands, leading to sicca symptoms of the mouth and eyes. Growing evidence has shown that SS is also characterized by microbial perturbations like other autoimmune diseases. Significant alterations in diversity, composition, and function of the microbiota were observed in SS. The dysbiosis of the microbiome correlates with worse symptoms and higher disease severity, suggesting that dysbiosis may be of great importance in the pathogenesis of SS. In this review, we provide a general view of recent studies describing the microbiota alterations of SS, the possible pathways that may cause microbiota dysbiosis to trigger SS, and the existence of the gut-ocular/gut-oral axis in SS.
GDF-15: A Potential Biomarker and Therapeutic Target in Systemic Lupus Erythematosus
Authors: Xu Wang-Dong , Huang Qi , Yang Chan , Li Rong , Huang An-Fang
Published: July 2022

Systemic lupus erythematosus (SLE) is a rheumatic disease. Growth differentiation factor 15 (GDF-15) is a member of transforming growth factor-β superfamily. To date, association of GDF-15 with SLE pathogenesis is not clarified. This study discussed GDF-15 serum levels and gene polymorphisms in SLE patients and lupus mouse model further demonstrated the role of GDF-15 in lupus development. We conducted two independent case-control studies for SLE patients. One is to evaluate serum levels of GDF-15 in 54 SLE patients and 90 healthy controls, and the other one is to analyze gene polymorphisms of GDF-15 in 289 SLE patients and 525 healthy controls. Serum levels of GDF-15 were detected by ELISA. GDF-15 gene polymorphisms (rs1055150, rs1058587, rs1059519, rs1059369, rs1227731, rs4808793, and rs16982345) were genotyped by the Kompetitive Allele-Specific PCR (KASP) method. Addition of recombinant GDF-15 into pristane-induced lupus mice evaluated histological and serological changes. Results showed that serum levels of GDF-15 were overexpressed in SLE patients and associated with disease activity. Polymorphisms rs1055150, rs1059369, rs1059519, and rs4808793 of GDF-15 gene were related to SLE risk. Lupus mice showed splenomegaly, severe histological scores, and high levels of autoantibodies [antinuclear antibodies (ANA) and total immunoglobulin G (IgG)], whereas administration of GDF-15 into lupus mice reduced the histological changes. Percentages of CD8+, CD11b+, CD19+, CD11C+ cells, TH2 cells, and pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-21, and IL-22) were reduced after GDF-15 treatment in lupus mice. In conclusion, GDF-15 was related to lupus pathogenesis and inhibited lupus development.
A Feedback Regulatory Loop Involving dTrbd/dTak1 in Controlling IMD Signaling in Drosophila Melanogaster
Authors: Hua Yongzhi , Zhu Yangyang , Hu Yixuan , Kong Fanrui , Duan Renjie , Zhang Chao , Zhang Chuchu , Zhang Shikun , Jin Yiheng , Ye Yizhu , Cai Qingshuang , Ji Shanming
Published: July 2022

Negative regulators of the inflammatory responses are essential for the maintenance of immune homeostasis and organismal fitness. In Drosophila, the deubiquitinase (Dub) dTrbd selectively restricts the K63-linked ubiquitination modification of dTak1, a pivotal kinase of the IMD signaling pathway, to regulate the IMD innate immune response. However, which domain and how it functions to enable dTrbd’s activity remain unexplored. Here, we provide compelling evidence showing that the NZF domain of dTrbd is essential for its association with dTak1. Meanwhile, the Linker region of dTrbd is involved in modulating its condensation, a functional state representing the Dub enzymatical activity of dTrbd. Of interest, the activated IMD signals following bacterial stimuli enhance the dTrbd/dTak1 interaction, as well as the condensate assembly and Dub enzymatical activity of dTrbd. Collectively, our studies shed light on the dual mechanisms by which the IMD signaling-mediated feedback loop of dTrbd/dTak1 precisely regulates the innate immune response in Drosophila.
Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement
Authors: Saldi Simonetta , Perriello Vincenzo Maria , Falini Lorenza , Ruggeri Loredana , Fulcheri Christian , Ciardelli Sara , Innocente Alessandra , Ballanti Stelvio , Baffa Nicodemo , Flenghi Leonardo , Pierini Antonio , Aristei Cynthia , Falini Brunangelo
Published: July 2022

CAR T cell therapy has transformed the salvage approach for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Maintaining disease control before CAR T cell infusion during product manufacturing (so-called bridging therapy) is an important step to optimizing outcome. Among possible bridging therapies, radiation therapy (RT) represents a valuable option, particularly when the disease is limited. Here, we report for the first time on a patient with chemorefractory-transformed DLBCL showing nodal, extranodal, and massive bone marrow (BM) lymphoma infiltration associated with leukemic involvement, a successful bridge therapy to CD19-directed CAR T cell therapy by subtotal lymphoid/total marrow irradiation plus thiothepa followed by reinfusion of CD34+ autologous hematopoietic stem cells. Such a novel bridging regimen allowed a significant reduction of nodal and BM tumor volume while improving blood cell count before CAR T cell infusion. The PET-CT scan and BM evaluation performed at 1, 3, and 6 months after treatment showed complete remission of the disease. A relapse occurred at almost 1 year in lymph nodes because of CD19 antigen escape while the BM remained free of disease. This extended radiotherapy approach may be an effective bridging therapy for chemorefractory DLBCL patients eligible for CAR T cells who present with a high tumor burden, including massive BM involvement associated with leukemic involvement. This preliminary evidence is worth confirming in additional patients.
Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis
Authors: Huang Yun-Ju , Lin Chiung-Hung , Yang Huang-Yu , Luo Shue-Fen , Kuo Chang-Fu
Published: July 2022

Introduction

Urine-soluble CD163 (usCD163) is released from alternatively activated macrophages involved in the resolution of inflammation in glomeruli and plays an important role in glomerulonephritis. This study explored the role of usCD163 in patients with systemic lupus erythematosus (SLE).

Materials and Methods

usCD163 concentrations were measured cross-sectionally in 261 SLE patients in Taiwan. Clinical and laboratory data were collected, and SLE disease activity scores were calculated to assess the correlation with usCD163.

Results

SLE patients with high usCD163 levels tended to be younger, with a higher hospital admission rate, higher prednisolone dose, lower estimated glomerular filtration rate, higher urine protein creatinine ratio (UPCR), more pyuria and hematuria, higher levels of inflammatory markers, higher rates of anemia, neutropenia, and lymphopenia, lower complement 3 (C3) levels, higher anti-double-stranded DNA antibody (anti-dsDNA Ab) levels, and higher disease activity scores (p < 0.05). usCD163 levels were significantly higher in patients with active lupus nephritis (LN) than in those with extrarenal or inactive SLE and correlated with UPCR, disease activity, and anti-dsDNA Ab levels. SLE patients with high usCD163 levels tended to have a higher chronic kidney disease stage.

Discussion and conclusion

The usCD163 level correlates with the severity of LN and disease activity in renal SLE.
Cold Plasma Irradiation Attenuates Atopic Dermatitis via Enhancing HIF-1α-Induced MANF Transcription Expression
Authors: Sun Tao , Zhang Xinru , Hou Chao , Yu Shujun , Zhang Yujing , Yu Zhuo , Kong Ling , Liu Changqing , Feng Lijie , Wang Dong , Ni Guohua
Published: July 2022

Cold atmospheric plasma has been widely applied in medical treatment clinically, especially skin diseases. However, the mechanism of cold atmospheric plasma on the treatment of skin diseases is still undefined. In this study, dinitrofluorobenzene-induced atopic dermatitis mice model was constructed. Cold atmospheric plasma was able to decrease skin cells apoptosis, relieve skin inflammation, ER stress and oxidative stress caused by dinitrofluorobenzene stimulation, which was mediated by cold atmospheric plasma-induced MANF expression. In terms of mechanism, hypoxia-inducible factor-1α expression was increased intracellularly after cold atmospheric plasma treatment, which further bound to the promoter region of manf gene and enhanced MANF transcriptional expression. This study reveals that cold atmospheric plasma has a positive effect on atopic dermatitis treatment, also demonstrates the regulatory mechanism of cold atmospheric plasma on MANF expression via HIF-1α, which indicates the potential medical application of cold atmospheric plasma for atopic dermatitis treatment.
Potential Gut Microbiota Features for Non-Invasive Detection of Schistosomiasis
Authors: Lin Datao , Song Qiuyue , Liu Jiahua , Chen Fang , Zhang Yishu , Wu Zhongdao , Sun Xi , Wu Xiaoying
Published: July 2022

The gut microbiota has been identified as a predictive biomarker for various diseases. However, few studies focused on the diagnostic accuracy of gut microbiota derived-signature for predicting hepatic injuries in schistosomiasis. Here, we characterized the gut microbiomes from 94 human and mouse stool samples using 16S rRNA gene sequencing. The diversity and composition of gut microbiomes in Schistosoma japonicum infection-induced disease changed significantly. Gut microbes, such as Bacteroides, Blautia, Enterococcus, Alloprevotella, Parabacteroides and Mucispirillum, showed a significant correlation with the level of hepatic granuloma, fibrosis, hydroxyproline, ALT or AST in S. japonicum infection-induced disease. We identified a range of gut bacterial features to distinguish schistosomiasis from hepatic injuries using the random forest classifier model, LEfSe and STAMP analysis. Significant features Bacteroides, Blautia, and Enterococcus and their combinations have a robust predictive accuracy (AUC: from 0.8182 to 0.9639) for detecting liver injuries induced by S. japonicum infection in humans and mice. Our study revealed associations between gut microbiota features and physiopathology and serological shifts of schistosomiasis and provided preliminary evidence for novel gut microbiota-derived features for the non-invasive detection of schistosomiasis.
Efficacy and safety of camrelizumab in combination with neoadjuvant chemotherapy for ESCC and its impact on esophagectomy
Authors: Qiao Yujin , Zhao Cong , Li Xiangnan , Zhao Jia , Huang Qi , Ding Zheng , Zhang Yan , Jiao Jia , Zhang Guoqing , Zhao Song
Published: July 2022

Background

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. The use of neoadjuvant immunotherapy for the treatment of ESCC is gradually increasing. Camrelizumab is one such immune checkpoint inhibitor (ICI) used for treatment. In this retrospective study, we explored the efficacy, safety, and short-term perioperative prognosis of camrelizumab in combination with neoadjuvant chemotherapy for ESCC.

Materials and Methods

A total of 254 Chinese patients with ESCC were enrolled in the study; 48 received camrelizumab in combination with neoadjuvant chemotherapy (C-NC group), and 206 received neoadjuvant chemotherapy (NC group). All patients underwent surgery after the completion of 2 cycles of neoadjuvant therapy.

Results

Twenty patients (20/48, 41.7%) in the C-NC group and 22 patients (22/206, 10.7%) in the NC group achieved a pathologic complete response (pCR) (p<0.001). Twenty-nine patients (29/48, 60.4%) in the C-NC group and 56 patients (56/206, 27.2%) in the NC group achieved major pathologic remission (MPR) (p<0.001). There was a lower incidence of myelosuppression during neoadjuvant therapy in patients in the C-NC group (33/48, 68.8%) than in the NC group (174/206, 84.5%, p=0.012). The total incidence of adverse reactions during neoadjuvant therapy was also lower in the C-NC group (37/48, 77.1%) than in the NC group (189/206, 91.7%, p=0.003). Patients in the C-NC group had more lymph nodes cleared during surgery than those in the NC group (34 vs.30, p<0.001). The logistic model showed that the treatment regimen, age, and presence of lymph node metastasis were influential factors for achieving a pCR in these patients (p<0.001). Regarding other adverse events and surgery-related data, there were no significant differences observed between the two groups.

Conclusion

Camrelizumab in combination with neoadjuvant chemotherapy is an efficacious neoadjuvant regimen with an acceptable safety profile and does not increase the difficulty of surgery or the incidence of complications. A pCR is more likely to be achieved in patients treated with camrelizumab in combination with neoadjuvant chemotherapy, in younger patients, or in those without lymph node metastases.
Metabolomic Profiling Reveals Changes in Amino Acid and Energy Metabolism Pathways in Liver, Intestine and Brain of Zebrafish Exposed to Different Thermal Conditions
Authors: Aguilar Andrea , Mattos Humberto , Carnicero Beatriz , Sanhueza Nataly , Muñoz David , Teles Mariana , Tort Lluis , Boltaña Sebastian
Published: July 2022

Global warming is predicted to increase prolonged thermal challenges for aquatic ectotherms, i.e. it causes metabolic performance declines, impacts food intake, and finally causes impaired growth. In this research work, we investigated whether a tropical fish, Danio rerio (zebrafish), could tolerate prolonged thermal challenges and whether the temperature increase has a significant impact on growth and metabolism. To answer our questions, we evaluate the metabolomic performance, a question that has received little attention so far, using differential chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS). Three groups of fish were exposed to various temperatures of 27.6 ± 2°C, 30.7 ± 2°C or 32.2 ± 2°C during 270 days post fecundation (dpf) to evaluate the impact of the temperature increase on the growth and metabolomic performance. The results obtained demonstrated different metabolomic changes in response to acclimation to the different temperatures. After 270 days, the fish maintained at the highest tested temperature (32°C) showed reduced growth, reduced condition factor, and elevated levels of metabolites associated with amino acid catabolism and lipid metabolism pathways in the liver and intestine compared with fish kept at lower temperatures (27.6 ± 2°C). These findings demonstrate an explicit redistribution of energy stores and protein catabolism in fish at the highest temperature, thus showing a preference for maintaining length growth during limited energy availability. Moreover, here we also screened out both the marker metabolites and the altered metabolic pathways to provide essential insights to ascertain the effects of the water temperature increase on the growth and development of tropical fish.
CGAN Based Improved ASI Retrieval Algorithm for Antarctic Sea Ice Concentration
Authors: Wang Xingdong , Zhao Yue , Yang Shuhui , Wang Yuhua , Shangguan Donghui
Published: July 2022

Sea ice change is closely related to the change of global atmosphere and ocean circulation, which plays an important role in the study of global climate change. Sea ice concentration is one of the important parameters to study the temporal and spatial change of sea ice. Accurately retrieving sea ice concentration is the innovation of this paper. At present, the high-resolution microwave-detected sea ice concentration product was provided by the University of Bremen, which was derived by the Arctic Radiation and Turbulence Interaction Study (ARTSIST) Sea Ice (ASI) algorithm based on the Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E) 89-GHz brightness temperature data. The AMSR-E/AMSR-2 89-GHz brightness temperature data has higher spatial resolution, but it is often affected by cloud and water vapor, which affects the recognition and subsequent use of ground feature. Although the weather filters can remove some errors in the edge regions of the sea water and the sea ice, the errors of the sea ice concentration in other regions cannot be removed. The generative model of Conditional Generative Adversarial Network (CGAN) increases the utilization of image feature information through skip connection, which improves the removal of the influence of cloud and water vapor. The discriminative model can retain the image feature information and realize the non-linear mapping from the image to the image. The loss function can reduce the pixel-level loss, which can remove the influence of cloud and water vapor. Therefore, this paper proposed an improved ASI algorithm based on CGAN. Firstly, the relatively stable relationship between the 89-GHz brightness temperature data which is not disturbed or less affected by the external environment and the 36-GHz brightness temperature data was determined, and the 89-GHz brightness temperature data with large interference was screened. Secondly, based on the 36-GHz brightness temperature data with high reliability, the 89-GHz brightness temperature data with large interference was corrected through CGAN. Finally, the ASI algorithm was used to retrieve sea ice concentration. Compared with sea ice concentration retrieved by the ASI algorithm, the results showed that the improved ASI algorithm based on CGAN was feasible. Compared with sea ice distribution obtained from the Landsat 8 OLI-L1T data, the improved ASI algorithm based on CGAN significantly improves the inversion accuracy of sea ice concentration. The improved ASI algorithm based on CGAN makes use of the reliable 36-GHz brightness temperature data, which greatly reduces the error caused by cloud and water vapor, and the method effectively corrects sea ice concentration of the pixels affected by the external environment. Therefore, the improved ASI algorithm based on CGAN realizes high spatial resolution and significantly improves the inversion accuracy of sea ice concentration.
Temporal Dynamics in Energy Fluxes and Trophic Structure of a Portunus trituberculatus Polyculture Ecosystem During Different Culture Periods
Authors: Feng Jie , Tian Xiang-Li , Dong Shuang-Lin , He Rui-Peng , Zhang Kai , Zhang Dong-Xu , Zhang Qing-Qi
Published: July 2022

Swimming crab (Portunus trituberculatus) are an important aquaculture species in eastern coastal areas of China. To improve the understanding of P. trituberculatus culture ecosystem functioning, the dynamics of energy flow and trophic structure of a P. trituberculatus polyculture system (co-culture with white shrimp Litopenaeus vannamei and short-necked clam Ruditapes philippinarum) were investigated in this study. Three Ecopath models representing the early, middle, and late culture periods of a P. trituberculatus polyculture ecosystem, respectively, were constructed to compare ecosystem traits at different culture periods. The results demonstrated that detritus was the main energy source in this polyculture ecosystem, and most of the total system throughput occurred at trophic levels I and II. Artificial food input and consumption by the culture organisms increased from early to middle and late periods, which produced marked impacts on biomass structure and primary production. R. philippinarum was considered to have a dominant influence on phytoplankton community dynamics which changed from nano- to pico-phytoplankton predominance, from the middle to the late period. Considering the low utilization efficiency of pico-phytoplankton production, large amounts of detritus accumulated in the sediment in the late period, which may constitute a potential risk for the ecosystem. Ecological network analyses indicated that the total energy flow and level of system organization increased from the early to the middle and late periods, whereas food web complexity and system resilience decreased from early to middle and late periods, which may indicate a trend of decreasing ecosystem stability. The system may be further optimized by increased stocking density of R. philippinarum and by introducing macro-algae at a suitable biomass to increase ecosystem stability, energy utilization efficiency, and aquaculture production.
High expression of RRM2 mediated by non-coding RNAs correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma
Authors: Mao Guochao , Li Lan , Shan Changyou , Liang Baobao , Ma Li , Zhang Shuqun
Published: July 2022

Hepatocellular carcinoma (HCC) is known to have a poor prognosis. Accumulating evidence indicates that RRM2 plays a critical role in the occurrence and progression of multiple human cancers. However, the knowledge about RRM2 in HCC is still insufficient, and further research is needed. Here, we first analyzed the expression and prognosis of RRM2 using TCGA and GTEx data, and found that RRM2 may play a potential carcinogenic role in HCC. Then, through a series of comprehensive analysis, including expression analysis, correlation analysis or survival analysis, non-coding RNAs (ncRNAs) that regulate RRM2 overexpression were identified. Finally, MIR4435-2HG/CYTOR were observed to be the most promising upstream lncRNAs for the miR-125b-5p/RRM2 axis in HCC. In addition, RRM2 expression was significantly positively related to immune cell infiltration, immune cell biomarker or immune checkpoint expression in HCC. Altogether, the upregulation of RRM2 mediated by ncRNAs correlates with poor prognosis and tumor immune infiltration of HCC.
Fresh Frozen Plasma in Cases of Acute Upper Gastrointestinal Bleeding Does Not Improve Outcomes
Authors: Liu Shuang , Zhang Xiaoming , Walline Joseph Harold , Yu Xuezhong , Zhu Huadong
Published: July 2022

Background

Blood products are commonly transfused in patients with acute upper gastrointestinal bleeding (UGIB). There exists considerable practice variation and less evidence to guide fresh frozen plasma transfusion in patients with UGIB. The aim of this study was to explore any association between fresh frozen plasma transfusion following acute UGIB and clinical outcomes.

Methods

This was a prospective, observational, multicenter study conducted at 20 tertiary hospitals in China. Patients with acute UGIB with an international normalized ratio ≤ 2.0 at emergency department admission were included. Multivariate logistic regression models were used to examine and quantify any clinical associations.

Results

A total of 976 patients (61.57 ± 15.79 years old, 73.05% male) were included, of whom 17.42% received fresh frozen plasma transfusion. The overall 90-day mortality and rebleeding rates were 10.20 and 12.19%, respectively. After adjusting for confounding factors, transfusion of fresh frozen plasma during hospitalization was associated with higher 90-day mortality [odd ratio (OR), 2.36; 95% confidence interval (CI), 1.36–4.09; p = 0.002] but not rebleeding (OR, 1.5; 95% CI; 0.94-2.54; p = 0.085). In a subgroup analysis, patients with an international normalized ratio <1.5 who were treated with fresh frozen plasma were associated with both significantly higher 90-day mortality (OR, 2.78; 95% CI, 1.49–5.21; p = 0.001) and rebleeding (OR, 2.02; 95% CI, 1.16–3.52; p = 0.013), whereas in patients with an international normalized ratio between 1.5 and 2, we did not find any significant correlation.

Conclusion

This study found an association between fresh frozen plasma transfusion following acute UGIB and elevated 90-day mortality. Both 90-day mortality and rebleeding risk were significantly higher in patients with an international normalized ratio < 1.5. Fresh frozen plasma transfusion in acute UGIB does not improve the poor outcomes (Chinese Clinical Trial registry, Number ChiCTR1900028676).
Cable Bacteria Activity Modulates Arsenic Release From Sediments in a Seasonally Hypoxic Marine Basin
Authors: van de Velde Sebastiaan J. , Burdorf Laurine D. W. , Hidalgo-Martinez Silvia , Leermakers Martine , Meysman Filip J. R.
Published: July 2022

Eutrophication and global change are increasing the occurrence of seasonal hypoxia (bottom-water oxygen concentration <63 μM) in coastal systems worldwide. In extreme cases, the bottom water can become completely anoxic, allowing sulfide to escape from the sediments and leading to the development of bottom-water euxinia. In seasonally hypoxic coastal basins, electrogenic sulfur oxidation by long, filamentous cable bacteria has been shown to stimulate the formation of an iron oxide layer near the sediment-water interface, while the bottom waters are oxygenated. Upon the development of bottom-water anoxia, this iron oxide “firewall” prevents the sedimentary release of sulfide. Iron oxides also act as an adsorption trap for elements such as arsenic. Arsenic is a toxic trace metal, and its release from sediments can have a negative impact on marine ecosystems. Yet, it is currently unknown how electrogenic sulfur oxidation impacts arsenic cycling in seasonally hypoxic basins. In this study, we presented results from a seasonal field study of an uncontaminated marine lake, complemented with a long-term sediment core incubation experiment, which reveals that cable bacteria have a strong impact on the arsenic cycle in a seasonally hypoxic system. Electrogenic sulfur oxidation significantly modulates the arsenic fluxes over a seasonal time scale by enriching arsenic in the iron oxide layer near the sediment-water interface in the oxic period and pulse-releasing arsenic during the anoxic period. Fluxes as large as 20 μmol m−2 day−1 were measured, which are comparable to As fluxes reported from highly contaminated sediments. Since cable bacteria are recognized as active components of the microbial community in seasonally hypoxic systems worldwide, this seasonal amplification of arsenic fluxes is likely a widespread phenomenon.