DIRMC: a database of immunotherapy-related molecular characteristics.

Cancer immunotherapy has brought about a revolutionary breakthrough in the field of cancer treatment. Immunotherapy has changed the treatment landscape for a variety of solid and hematologic malignancies. To assist researchers in efficiently uncovering valuable information related to cancer immunotherapy, we have presented a manually curated comprehensive database called DIRMC, which focuses on molecular features involved in cancer immunotherapy. All the content was collected manually from published literature, authoritative clinical trial data submitted by clinicians, some databases for drug target prediction such as DrugBank, and some experimentally confirmed high-throughput data sets for the characterization of immune-related molecular interactions in cancer, such as a curated database of T-cell receptor sequences with known antigen specificity (VDJdb), a pathology-associated TCR database (McPAS-TCR) et al. By constructing a fully connected functional network, ranging from cancer-related gene mutations to target genes to translated target proteins to protein regions or sites that may specifically affect protein function, we aim to comprehensively characterize molecular features related to cancer immunotherapy. We have developed the scoring criteria to assess the reliability of each MHC-peptide-T-cell receptor (TCR) interaction item to provide a reference for users. The database provides a user-friendly interface to browse and retrieve data by genes, target proteins, diseases and more. DIRMC also provides a download and submission page for researchers to access data of interest for further investigation or submit new interactions related to cancer immunotherapy targets. Furthermore, DIRMC provides a graphical interface to help users predict the binding affinity between their own peptide of interest and MHC or TCR. This database will provide researchers with a one-stop resource to understand cancer immunotherapy-related targets as well as data on MHC-peptide-TCR interactions. It aims to offer reliable molecular characteristics support for both the analysis of the current status of cancer immunotherapy and the development of new immunotherapy. DIRMC is available at http://www.dirmc.tech/. Database URL: http://www.dirmc.tech/.

Personalized Hydration Strategy to Improve Fluid Balance and Intermittent Exercise Performance in the Heat.

Sweat rate and electrolyte losses have a large inter-individual variability. A personalized approach to hydration can overcome this issue to meet an individual's needs. This study aimed to investigate the effects of a personalized hydration strategy (PHS) on fluid balance and intermittent exercise performance. Twelve participants conducted 11 laboratory visits including a VO2max test and two 5-day trial arms under normothermic (NOR) or hyperthermic (HYP) environmental conditions. Each arm began with three days of familiarization exercise followed by two random exercise trials with either a PHS or a control (CON). Then, participants crossed over to the second arm for: NOR+PHS, NOR+CON, HYP+PHS, or HYP+CON. The PHS was prescribed according to the participants' fluid and sweat sodium losses. CON drank ad libitum of commercially-available electrolyte solution. Exercise trials consisted of two phases: (1) 45 min constant workload; (2) high-intensity intermittent exercise (HIIT) until exhaustion. Fluids were only provided in phase 1. PHS had a significantly greater fluid intake (HYP+PHS: 831.7 ± 166.4 g; NOR+PHS: 734.2 ± 144.9 g) compared to CON (HYP+CON: 369.8 ± 221.7 g; NOR+CON: 272.3 ± 143.0 g), regardless of environmental conditions (p < 0.001). HYP+CON produced the lowest sweat sodium concentration (56.2 ± 9.0 mmol/L) compared to other trials (p < 0.001). HYP+PHS had a slower elevated thirst perception and a longer HIIT (765 ± 452 s) compared to HYP+CON (548 ± 283 s, p = 0.04). Thus, PHS reinforces fluid intake and successfully optimizes hydration status, regardless of environmental conditions. PHS may be or is an important factor in preventing negative physiological consequences during high-intensity exercise in the heat.

A transcriptome based molecular classification scheme for cholangiocarcinoma and subtype-derived prognostic biomarker.

Previous studies on the molecular classification of cholangiocarcinoma (CCA) focused on certain anatomical sites, and disregarded tissue contamination biases in transcriptomic profiles. We aim to provide universal molecular classification scheme and prognostic biomarker of CCAs across anatomical locations. Comprehensive bioinformatics analysis is performed on transcriptomic data from 438 CCA cases across various anatomical locations. After excluding CCA tumors showing normal tissue expression patterns, we identify two universal molecular subtypes across anatomical subtypes, explore the molecular, clinical, and microenvironmental features of each class. Subsequently, a 30-gene classifier and a biomarker (called "CORE-37") are developed to predict the molecular subtype of CCA and prognosis, respectively. Two subtypes display distinct molecular characteristics and survival outcomes. Key findings are validated in external cohorts regardless of the stage and anatomical location. Our study provides a CCA classification scheme that complements the conventional anatomy-based classification and presents a promising prognostic biomarker for clinical application.

Systemic Type 2 Inflammation-Associated Atopic Dermatitis Exacerbates Periodontitis.

INTRODUCTION: Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin disease characterized by Th2 cell-mediated type 2 inflammation. Emerging evidence indicated that AD patients exhibit an increased incidence of oral disorders. In the present study, we sought mechanistic insights into how AD affects periodontitis. METHODS: Onset of AD was induced by 2,4-dinitrochlorobenzene (DNCB). Furthermore, we induced periodontitis (P) in AD mice. The effect of AD in promoting inflammation and bone resorption in gingiva was evaluated. Hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, immunofluorescence assay, and flow cytometry were used to investigate histomorphology and cytology analysis, respectively. RNA sequencing of oral mucosa is used tissues to further understand the dynamic transcriptome changes. 16S rRNA microbial analysis is used to profile oral microbial composition. RESULTS: Compared to control group, mice in AD group showed inflammatory signatures and infiltration of a proallergic Th2 (Th2A)-like subset in oral mucosa but not periodontitis, as identified by not substantial changes in mucosa swelling, alveolar bone loss, and TRAP+ osteoclasts infiltration. Similarly, more Th2A-like cell infiltration and interleukin-4 levels were significantly elevated in the oral mucosa of DNCB-P mice compared to P mice. More importantly, AD exacerbates periodontitis when periodontitis has occurred and the severity of periodontitis increased with aggravation of dermatitis. Transcriptional analysis revealed that aggravated periodontitis was positively correlated with more macrophage infiltration and abundant CCL3 secreted. AD also altered oral microbiota, indicating the re-organization of extracellular matrix. CONCLUSIONS: These data provide solid evidence about exacerbation of periodontitis caused by type 2 dermatitis, advancing our understanding in cellular and microbial changes during AD-periodontitis progression.

Soluble epoxide hydrolase deficiency attenuates airway inflammation in COPD via IRE1α/JNK/AP-1 signaling pathway.

BACKGROUND: Soluble Epoxide Hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids and critically affects airway inflammation in chronic obstructive pulmonary disease (COPD). Considering the excessive endoplasmic reticulum stress is associated with the earlier onset of COPD. The role of sEH and endoplasmic reticulum stress in the pathogenesis of COPD remains unknown. METHOD: 16 weeks of cigarette-exposed mice were used to detect the relationship between sEH and endoplasmic reticulum stress in COPD. Human epithelial cells were used in vitro to determine the regulation mechanism of sEH in endoplasmic reticulum stress induced by cigarette smoke. RESULTS: sEH deficiency helps reduce emphysema formation after smoke exposure by alleviating endoplasmic reticulum stress response. sEH deficiency effectively reverses the upregulation of phosphorylation IRE1α and JNK and the nuclear expression of AP-1, alleviating the secretion of inflammatory factors induced by cigarette smoke extract. Furthermore, the treatment with endoplasmic reticulum stress and IRE1α inhibitor downregulated cigarette smoke extract-induced sEH expression and the secretion of inflammatory factors. CONCLUSION: sEH probably alleviates airway inflammatory response and endoplasmic reticulum stress via the IRE1α/JNK/AP-1 pathway, which might attenuate lung injury caused by long-term smoking and provide a new pharmacological target for preventing and treating COPD.

Integration of multiple-omics data to reveal the shared genetic architecture of educational attainment, intelligence, cognitive performance, and Alzheimer's disease.

Growing evidence suggests the effect of educational attainment (EA) on Alzheimer's disease (AD), but less is known about the shared genetic architecture between them. Here, leveraging genome-wide association studies (GWAS) for AD (N = 21,982/41,944), EA (N = 1,131,881), cognitive performance (N = 257,828), and intelligence (N = 78,308), we investigated their causal association with the linkage disequilibrium score (LDSC) and Mendelian randomization and their shared loci with the conjunctional false discovery rate (conjFDR), transcriptome-wide association studies (TWAS), and colocalization. We observed significant genetic correlations of EA (rg = -0.22, p = 5.07E-05), cognitive performance (rg = -0.27, p = 2.44E-05), and intelligence (rg = -0.30, p = 3.00E-04) with AD, and a causal relationship between EA and AD (OR = 0.74, 95% CI: 0.58-0.94, p = 0.013). We identified 13 shared loci at conjFDR <0.01, of which five were novel, and prioritized three causal genes. These findings inform early prevention strategies for AD.

Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study.

Background: Escin is the main active component in Aesculus hippocastanum. It has been demonstrated that escin has anti-inflammatory properties. This study combined the methods of network pharmacology, molecular docking, and molecular dynamics to explore the molecular mechanism of escin against neuropathic pain (NP). Methods: The Swiss Target Prediction and the Pharm Mapper database were employed for predicting the targets of escin. Also, the candidate targets of NP were gathered via the databases including Therapeutic Targets, DisGeNet, GeneCards, DrugBank, and OMIM. Subsequently, the network of protein-protein interaction was screened for the key targets by the software Cytoscape 3.8.0. Then, the intersection of these targets was analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Additionally, we further investigated the ligand-target interactions by molecular docking and molecular dynamics simulations. Results: In total, 94 escin targets were predicted by network pharmacology. Among them, SRC, MMP9, PTGS2, and MAPK1 were the core candidate targets. Subsequently, the analysis of GO and KEGG enrichment revealed that escin affected NP by regulating protein kinase C, MAP kinase, TRP channels, the T-cell receptors signaling pathway, and the TNF signaling pathway. The results of molecular docking and molecular dynamics simulation confirmed that escin not only had a strong binding activity with the four core target proteins but also stably combined in 50 ns. Conclusions: Our study revealed that escin acts on the core targets SRC, MMP9, PTGS2, MAPK1, and associated enrichment pathways to alleviate neuronal inflammation and regulate the immune response, thus exerting anti-NP efficacy. This study provided innovative ideas and methods for the promising treatment of escin in relieving NP.

Evolution analysis of research on disaster-causing mechanism and prevention technology of mine goaf disaster.

The goaf is an important factor that induces major accidents. Based on the quantitative analysis of the existing research results, summarize and sort out the research and prevention technology of the goaf disaster with the experience of experts. Temporally, the research on goaf disasters was divided into two stages: the embryonic stage and the rapid development stage. Spatially, a collaborative network with the United States, China, Germany, France, Turkey, and the United Kingdom as the core, including India, Japan, Belgium, Italy, South Korea, and Canada, was analyzed. By constructing a co-occurrence and clustering network of keywords and co-cited literature to explore the focus and hotspots of goaf disaster research, the hotspots of goaf disaster research are summarized into four main aspects, such as goaf detection technology, goaf disaster analysis, goaf risk assessment and goaf treatment technology, which grasp the content of goaf research from a macro perspective. The burst detection analysis of keywords and co-cited literature was conducted to obtain the research frontiers of goaf disaster research in different periods. At the current stage, the microstructural characteristics of surrounding rocks in the context of deep mining and complex goaf group effect and the mining technology of the integration of excavation, anchoring and supporting are the current frontier research directions. This combined qualitative and quantitative method is more helpful to grasp the development context of goaf disaster research and provides a new reference perspective for sorting out the process of goaf disaster research.

Seasonal changes in physiological and psychological parameters of stress in collegiate swimmers.

To investigate the seasonal changes in physiological and psychological parameters of stress in collegiate swimmers. Fifteen NCAA Division I swimmers (8 men) participated in a tethered anaerobic swim test to determine physiological responses in an ecologically-relevant, graded exercise test. Wisconsin Upper Respiratory Symptom Survey (WURSS-21), Activation-Deactivation Adjective Check List (AD-ACL), Daily Analysis of Life Demands of Athletes (DALDA), and Pittsburgh Sleep Quality Index were assessed at post-season in April (V1), the end of off-season in June (V2), and pre-season in October (V3). The percent change was determined from V2-V1 (off-season phase), V3-V2 (pre-season phase), V1-V3 (in-season phase). Spearman's rho correlation was used to examine associations between change in physiological and psychological outcomes. All data results showed a better swim performance occurred at V2. Men tended to have faster speed (p = 0.07) in fewer strokes (p = 0.10) and greater work per stroke (p = 0.10) at V2 than V1. Women were faster during V2 compared to V1 (p = 0.02) and V3 (p = 0.05). Women had fewer strokes (p = 0.02) and greater work per stroke (p = 0.01) at V2 compared to V3. Women had the lowest HR and lactate concentration at V3 compared to other visits (p < 0.05). During the in-season phase, swim speed decreased the greatest extent and stress sources and symptoms assessed by DALDA had greatest elevation (p < 0.05). An increased in stress sources and symptoms assessed by DALDA was associated with an increase in upper respiratory illness from WURSS-21 (rho = 0.44, p = 0.009), being less energetic (rho = - 0.35, p = 0.04) and greater tension state (rho = 0.49, p = 0.003; AD-ACL), and a decrease in swim speed (rho =- 0.38, p = 0.03). Swim performance peaked at off-season when psychological stress was at its lowest. The relationship between DALDA scores with psychological parameters and swim performance suggested physiological and psychological parameters of stress is an important aspect to avoid overtraining when approaching high swim performance.

Impact of maximal exercise on immune cell mobilization and bioenergetics.

Acute aerobic exercise increases the number and proportions of circulating peripheral blood mononuclear cells (PMBC) and can alter PBMC mitochondrial bioenergetics. In this study, we aimed to examine the impact of a maximal exercise bout on immune cell metabolism in collegiate swimmers. Eleven (7 M/4F) collegiate swimmers completed a maximal exercise test to measure anaerobic power and capacity. Pre- and postexercise PBMCs were isolated to measure the immune cell phenotypes and mitochondrial bioenergetics using flow cytometry and high-resolution respirometry. The maximal exercise bout increased circulating levels of PBMCs, particularly in central memory (KLRG1+/CD57-) and senescent (KLRG1+/CD57+) CD8+ T cells, whether measured as a % of PMBCs or as absolute concentrations (all p < 0.05). At the cellularlevel, the routine oxygen flow (IO2 [pmol·s-1 ·106 PBMCs-1 ]) increased following maximal exercise (p = 0.042); however, there were no effects of exercise on the IO2 measured under the LEAK, oxidative phosphorylation (OXPHOS), or electron transfer (ET) capacities. There were exercise-induced increases in the tissue-level oxygen flow (IO2-tissue [pmol·s-1 ·mL blood-1 ]) for all respiratory states (all p < 0.01), except for the LEAK state, after accounting for the mobilization of PBMCs. Future subtype-specific studies are needed to characterize further maximal exercise's true impact on immune cell bioenergetics.

Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022.

Background: Idiopathic pulmonary fibrosis (IPF) is a disease with significant morbidity, progressive deterioration of lung function till death, and lack of effective treatment options. This study aims to explore the global research trends in IPF and immune response to predict the research hotspot in the future. Materials and methods. All related publications on IPF and immune response since the establishment of diagnostic criteria for IPF were retrieved using the Web of Science (WOS) database. VOSviewer, GraphPad Prism 6, CiteSpace version 5.6. R5 64-bit, and a bibliometrics online platform were used to extract and analyze the trends in relevant fields. Results: From March 1, 2000, to September 30, 2022, a total of 658 articles with 25,126 citations met the inclusion criteria. The United States ranked first in number of publications (n = 217), number of citations (n = 14,745), and H-index (62). China ranked second in publications (n = 124) and seventh and fifth for citation frequency and H-index, respectively. The American Journal of Respiratory and Critical Care Medicine (impact factor = 30.528) published the most articles in the field. The author Kaminski N. from the United States was the most influential author with 26 publications and an H-index of 24. Among the 52 keywords that co-occurred at least 20 times, the main keywords were concentrated in "Inflammation related" and "Biomarker related" clusters. "biomarker" (AAY 2018.64, 25 times) was a newly emerged keyword. Conclusions: The United States has an unequivocal advantage in IPF and immunization, but China shows a faster developing trend. The American Journal of Respiratory and Critical Care Medicine should be prioritized for leading articles. This study indicates that exploration of ideal immune-related biomarkers to provide evidence for the clinical work of IPF might be a hotspot in the near future.

High Red Blood Cell Distribution Width to Platelet Ratio is an Independent Poor Prognostic Factor in Patients with Newly Diagnosed Multiple Myeloma.

BACKGROUND: The red blood cell distribution width to platelet ratio (RPR) is an inflammatory marker that is a convenient and reliable prognostic indicator for several solid malignancies. However, the correlation between RPR and myeloma prognosis has not been reported. Therefore, this study aims to explore the correlation between RPR level and the prognosis of multiple myeloma (MM) patients. METHODS: We retrospectively analyzed 145 newly diagnosed patients with MM. The receiver operating characteristic curve (ROC) method was used to determine the RPR cut-off value. In addition, we studied the correlation between pre-treatment RPR levels and clinical characteristics, immunophenotype, cytogenetics, and its impact on the disease prognosis. RESULTS: The optimal cut-off value for RPR was 0.12 and was divided into high RPR and low RPR groups. Patients in the high RPR group are more likely to have anemia, thrombocytopenia, high ß2-macroglobulinemia, a high percentage of bone marrow plasma cells, late-stage status by Dury-Salmon (DS) and international staging system (ISS) (p < 0.05). More notably, between the high RPR and low RPR groups, the incidence rates of CD56-positive, D13S319-positive, RB1-positive, and 1q21 amplification were statistically significant (p < 0.05). Additionally, survival analysis revealed that compared with patients in the low RPR group, the median progression-free survival (PFS) and overall survival (OS) of patients in the high RPR group were substantially shortened (p < 0.05). Multivariate analysis confirmed that RPR ≥0.12, D13S319-positive, and 1q21 amplification were independent risk factors for poor PFS and OS. CONCLUSIONS: RPR is a practical and effective prognostic marker in newly diagnosed patients with MM, and a high RPR is an independent poor prognostic factor.

MARVELD3 inhibits the epithelial-mesenchymal transition and cell migration by suppressing the Wnt/ß-catenin signaling pathway in non-small cell lung cancer cells.

BACKGROUND: The epithelial-mesenchymal transition (EMT), featured by abatement of cell-cell contact, is related to exacerbating non-small cell lung cancer (NSCLC) by inducing metastasis. MAL and relevant proteins for vesicle trafficking and membrane link domain 3 (MARVELD3) is a novel tight junction protein participated in the EMT. There is limited information available about the mechanism of MARVELD3 in NSCLC. In this trial, the inhibition effect of MARVELD3 on human NSCLC cells will be discussed. METHODS: MARVELD3 expression was measured in NSCLC tissues and para-carcinoma tissues. The expression of MARVELD3 and EMT-related genes were examined in transforming growth factor (TGF)-ß1-induced NSCLC cells. NSCLC cells with MARVELD3-knockdown and overexpressed were established to analyze the relationship between MARVELD3 and EMT and cell migration. The Wnt/ß-catenin pathway expression was also analyzed in NSCLC cell models and clinic species. RESULTS: Lower protein levels of MARVELD3 were observed in NSCLC samples than para-carcinoma specimens, and the decreased expression of MARVELD3 in NSCLC specimens was associated with tumor metastasis. E-Cadherin and MARVELD3 expression was reduced in TGF-ß1 treated NSCLC cells, whereas increased Vimentin expression was detected. MARVELD3 changed the EMT-related genes and induced cell migration. In addition, Wnt/ß-catenin pathway and target genes, MYC and CCND1, expressions were inhibited in MARVELD3 overexpressed NSCLC cells. CONCLUSIONS: TGF-ß1 induced EMT in human NSCLC cells can be suppressed by MARVELD3 through Wnt/ß-catenin signaling pathway. These results indicate that MARVELD3 might be a potential therapeutic modality useful in the treatment of NSCLC.

Differential effects of recombinant human thrombopoietin on clinical outcomes in CD7-positive and CD7-negative acute myeloid leukaemia.

To investigate the effect of recombinant human thrombopoietin (rhTPO) application on the clinical outcomes of CD7-positive acute myeloid leukaemia (CD7 + AML) patients following chemotherapy, we retrospectively studied 159 newly diagnosed non-M3 AML patients. Patients were divided into the following four groups according to the expression of CD7 in AML blasts and the use of rhTPO after chemotherapy: the CD7 + rhTPO group (n = 41), the CD7 + non-rhTPO group (n = 42), the CD7 negative (CD7-) rhTPO group (n = 37), and the CD7- non-rhTPO group (n = 39). The complete remission rate was higher in the CD7 + rhTPO group than in the CD7 + non-rhTPO group. Importantly, patients in the CD7 + rhTPO group had significantly higher 3-year overall survival (OS) rates and event-free survival (EFS) rates than those in the CD7 + non-rhTPO group, whereas they did not differ statistically between the CD7- rhTPO and CD7- non-rhTPO groups. In addition, multivariate analysis showed that rhTPO was an independent prognostic factor for OS and EFS in CD7 + AML. In conclusion, rhTPO led to better clinical outcomes for patients with CD7 + AML, while it had no significant effect on those with CD7- AML.

Endoplasmic Reticulum Stress in Chronic Obstructive Pulmonary Disease: Mechanisms and Future Perspectives.

The endoplasmic reticulum (ER) is an integral organelle for maintaining protein homeostasis. Multiple factors can disrupt protein folding in the lumen of the ER, triggering ER stress and activating the unfolded protein response (UPR), which interrelates with various damage mechanisms, such as inflammation, apoptosis, and autophagy. Numerous studies have linked ER stress and UPR to the progression of chronic obstructive pulmonary disease (COPD). This review focuses on the mechanisms of other cellular processes triggered by UPR and summarizes drug intervention strategies targeting the UPR pathway in COPD to explore new therapeutic approaches and preventive measures for COPD.

Removal behavior and key drivers of antibiotic resistance genes in two full-scale leachate treatment plants.

Leachate is a critical reservoir of antibiotic resistance genes (ARGs) and its proper treatment is closely related to human health and ecosystem safety. Here, we used high-throughput qPCR to explore the removal behavior of ARGs in two full-scale leachate treatment plants (LTPs) where biological treatment and membrane filtration processes were integrated. A total of 286 ARGs and 55 mobile genetic elements (MGEs) were detected, with aminoglycoside, multidrug and MLSB resistance genes being the most prevalent and abundant. Anaerobic digestion was found to be an important pretreatment process for leachate, while anoxic/aerobic tanks in membrane bioreactor (MBR) acted as incubators for ARGs due to their significant proliferation effect on ARGs. Integrated membrane filtration (UF-NF-RO) excelled in ARGs removal with absolute abundances reduced by 3 to 6 orders of magnitude, from about 109 copies/mL in raw leachate to 103-105 copies/mL in effluents. Our results also showed that leachate treatment processes significantly altered the composition of ARGs and bacterial communities. Procrustes analysis and network analysis revealed strong associations between microbes and ARGs, with several hub genes and bacterial genera identified. Structural equation models (SEMs) indicated that bacterial composition, MGEs and basic water properties were the key drivers shaping ARGs dynamics in the raw leachate, biological system and filtration system, respectively. Notably, several pathogens (e.g., Klebsiella, Vibrio, Aeromonas) were closely correlated with ARGs in raw leachate and may amplify the dissemination risks of ARGs. Moreover, insertion sequences in biological systems would accelerate the horizontal gene transfer of ARGs. In short, this study provides new insights into the mechanisms of ARGs removal and dissemination behavior in industrial-scale LTPs.

Analysis of Influencing Factors for Exercise Ventilation Efficiency of COPD Patients.

Dynamic pulmonary hyperinflation and abnormal air exchange are the primary causes of the exercise limitation of chronic obstructive pulmonary disease (COPD) patients. During exercise, COPD sufferers' lungs are dynamically hyperinflated. Increased inefficient ventilation reduces ventilation efficiency and causes a mismatch between ventilation volume and blood flow. The ventilatory equivalent for CO2 (VeqCO2) is a physiological parameter that can be measured using cardiopulmonary exercise testing. Therefore, the aim of this exploratory study was to perform cardiopulmonary exercise testing on people with COPD, investigate the impact of static pulmonary function on ventilation efficiency under the exercise state, and screen the predictive indicators of ventilation efficiency. Subject. The aim of this study was to look at the factors that influence the exercise ventilation efficiency of people with COPD. Method. A total of 76 people with COPD were recruited during the stable period. Age, gender, body height, body mass, and other basic information were recorded. The body mass index (BMI) was determined, and forced vital capacity (FVC), forced expiratory volume in one second (FEV1), residual volume/total lung capacity (RV/TLC), diffusing capacity of the lung for carbon monoxide (DLCO), and DLCO divided by the alveolar volume (DLCO/VA) were measured. The ventilatory equivalent for carbon dioxide (VE/VCO2) under the rest state (EqCO2rest), anaerobic threshold (EqCO2at), and maximum exercise state (EqCO2 max) were calculated to investigate the influencing factors for ventilation efficiency of people with COPD. Results. FEV1% was negatively correlated with EqCO2rest (r = -0.277, P value <0.05); FEV1/FVC % was negatively correlated with EqCO2rest and EqCO2at (r = -0.311, -0.287, P value <0.05); DLCO% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = -0.408, -0.462, and -0.285, P value <0.05); DLCO/VA% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = -0.390, -0.392, and -0.245, P value <0.05); RV/TLC was positively correlated with EqCO2rest and EqCO2at (r = 0.289, 0.258, P-value <0.05). The prediction equation from the multivariable regression analysis equation was Y = 40.04-0.075X (Y = EqCO2, X = DLCO/VA%). Conclusions. As the degree of ventilatory obstruction increased, the ventilation efficiency of the stable people with COPD under the exercise state showed a progressive decrease; the ventilation efficiency of the people with COPD decreased significantly under the maximum exercise state, and the ventilation capacity and diffusion capacity were the significant factors that affected the exercise ventilation efficiency. The diffusion function may predict the maximum ventilation efficiency and enable primary hospitals without exercise test equipment in developing countries to predict and screen patients at risk for current exercise based on limited information.

MHCRoBERTa: pan-specific peptide-MHC class I binding prediction through transfer learning with label-agnostic protein sequences.

Predicting the binding of peptide and major histocompatibility complex (MHC) plays a vital role in immunotherapy for cancer. The success of Alphafold of applying natural language processing (NLP) algorithms in protein secondary struction prediction has inspired us to explore the possibility of NLP methods in predicting peptide-MHC class I binding. Based on the above motivations, we propose the MHCRoBERTa method, RoBERTa pre-training approach, for predicting the binding affinity between type I MHC and peptides. Analysis of the results on benchmark dataset demonstrates that MHCRoBERTa can outperform other state-of-art prediction methods with an increase of the Spearman rank correlation coefficient (SRCC) value. Notably, our model gave a significant improvement on IC50 value. Our method has achieved SRCC value and AUC value as 0.785 and 0.817, respectively. Our SRCC value is 14.3% higher than NetMHCpan3.0 (the second highest SRCC value on pan-specific) and is 3% higher than MHCflurry (the second highest SRCC value on all methods). The AUC value is also better than any other pan-specific methods. Moreover, we visualize the multi-head self-attention for the token representation across the layers and heads by this method. Through the analysis of the representation of each layer and head, we can show whether the model has learned the syntax and semantics necessary to perform the prediction task well. All these results demonstrate that our model can accurately predict the peptide-MHC class I binding affinity and that MHCRoBERTa is a powerful tool for screening potential neoantigens for cancer immunotherapy. MHCRoBERTa is available as an open source software at github (https://github.com/FuxuWang/MHCRoBERTa).

Selective Mitochondrial Protein Labeling Enabled by Biocompatible Photocatalytic Reactions inside Live Cells.

Biocompatible reactions are powerful tools to probe protein functions in their native environment. Due to the difficulty of penetrating the live-cell membrane and the complex intracellular environment, the biocompatible reactions inside live cells are challenging, especially at the subcellular level with spatial resolution. Here we report the first biocompatible photocatalytic azide conjugation reaction inside live cells to achieve the mitochondria-selective proteins labeling. The organic dyes acridine orange, fluorescein, and rhodamine 123 were developed as the biocompatible photocatalysts for the proteins labeling with aryl azides, which yielded benzazirines and ketenimines from triplet nitrenes for the protein nucleophilic residue trapping. The photocatalytic azide conjugation reaction with rhodamine 123 selectively labeled the mitochondrial proteins via the organic dye's mitochondrial localization. In response to the mitochondrial stress induced by rotenone, this photocatalytic azide-promoted labeling method mapped the dynamic mitochondrial proteome changes with high temporal-spatial precision and identified several potential mitochondrial stress-response proteins for the first time. The high temporal-spatial precision of this photocatalytic azide-promoted labeling method holds excellent potential for intracellular protein network investigations.

Role of specialized pro-resolving lipid mediators in pulmonary inflammation diseases: mechanisms and development.

Inflammation is an essential mechanism of various diseases. The development and resolution of inflammation are complex immune-modulation processes which induce the involvement of various types of immune cells. Specialized pro-resolving lipid mediators (SPMs) have been demonstrated to be signaling molecules in inflammation. SPMs are involved in the pathophysiology of different diseases, especially respiratory diseases, including asthma, pneumonia, and chronic obstructive pulmonary disease. All of these diseases are related to the inflammatory response and its persistence. Therefore, a deeper understanding of the mechanisms and development of inflammation in respiratory disease, and the roles of the SPM family in the resolution process, might be useful in the quest for novel therapies and preventive measures for pulmonary diseases.