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Inflammation-resident cells within arthritic sites undergo a metabolic shift towards glycolysis, which greatly aggravates rheumatoid arthritis (RA). Reprogramming glucose metabolism can suppress abnormal proliferation and activation of inflammation-related cells without affecting normal cells, holding potential for RA therapy. Single 2-deoxy-d-glucose (2-DG, glycolysis inhibitor) treatment often cause elevated ROS, which is detrimental to RA remission. The rational combination of glycolysis inhibition with anti-inflammatory intervention might cooperatively achieve favorable RA therapy. To improve drug bioavailability and exert synergetic effect, stable co-encapsulation of drugs in long circulation and timely drug release in inflamed milieu is highly desirable. Herein, we designed a stimulus-responsive hyaluronic acid-triglycerol monostearate polymersomes (HTDD) co-delivering 2-DG and dexamethasone (Dex) to arthritic sites. After intravenous injection, HTDD polymersomes facilitated prolonged circulation and preferential distribution in inflamed sites, where overexpressed matrix metalloproteinases and acidic pH triggered drug release. Results indicated 2-DG can inhibit the excessive cell proliferation and activation, and improve Dex bioavailability by reducing Dex efflux. Dex can suppress inflammatory signaling and prevent 2-DG-induced oxidative stress. Thus, the combinational strategy ultimately mitigated RA by inhibiting glycolysis and hindering inflammatory signaling. Our study demonstrated the great potential in RA therapy by reprogramming glucose metabolism in arthritic sites.

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A trypsin affinity material was prepared by covalently immobilizing buckwheat trypsin inhibitor (BTI) on epichlorohydrin-activated cross-linked agarose gel (Selfinose CL 6 B). The optimal conditions for activating Selfinose CL 6 B were 15 % epichlorohydrin and 0.8 M NaOH at 40 °C for 2 h. The optimal pH for immobilizing BTI was 9.5. BTI-Sefinose CL 6 B showed a maximum adsorption capacity of 2.25 mg trypsin/(g support). The material also displayed good reusability, retaining over 90 % of its initial adsorption capacity after 30 cycles. High-purity trypsin was obtained from locust homogenate using BTI-Selfinose CL 6 B through one-step affinity chromatography. The molecular mass and Km value of locust trypsin were determined as 27 kDa and 0.241 mM using N-benzoyl-DL-arginine-nitroanilide as substrate. The optimal temperature and pH of trypsin activity were 55 °C and 9.0, respectively. The enzyme exhibited good stability in the temperature range of 30-50 °C and pH range of 4.0-10.0. BTI-Selfinose CL 6 B demonstrates potential application in the preparation of high-purity trypsin and the discovery of more novel trypsin from various species.

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INTRODUCTION: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. METHODS: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. RESULTS: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. CONCLUSION: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI.

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This systematic review aims to highlight the molecular mechanisms by which whole cigarette smoke affects oral carcinogenesis and its progression in human oral cells, based on evidence from original research articles published in the literature. A literature search was conducted using three databases: Web of Science, Scopus, and PubMed from May to June 2024. The articles were screened, and the data were extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (2020). The included studies were subsequently evaluated using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool for bias factors. From the 14 included studies, two types of cell lines were frequently utilized: human oral mucosal epithelial cells or oral squamous cell carcinoma cells. In these cell lines, one of three forms of exposure was applied: cigarette smoke, its extract, or condensate. The mechanism of oral carcinogenesis and tumor progression includes aberrations in the heme metabolic pathway, modulation of miRNA-145, NOD1 and BiP expression, MMP-2, MMP-9, and cathepsin modulation, abnormal TSPO binding, RIP2-mediated NF-κB activation, MZF1-mediated VEGF binding, and activation of the RAGE signaling pathway. In conclusion, cigarette smoke significantly influences the development and progression of oral squamous cell carcinoma, based on the evidence highlighted in human oral cells. While previous studies have focused on specific carcinogens and pathways, this review added to our understanding of the overall impact of whole cigarette smoke on oral carcinogenesis at the molecular and cellular levels.

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During the fermentation of ripened pu-erh tea (RPT), the composition of lipids and other compounds changes significantly. In this study, we conducted industrial fermentation of RPT and observed that the levels of water extract, tea polyphenols, free amino acids, catechins, caffeine, rutin, theophylline, luteolin, and myricetin decreased, while the level of soluble sugar increased. Additionally, the levels of gallic acid, quercetin, ellagic acid, and kaempferol first increased and then decreased during fermentation. We identified a total of 731 lipids, which were classified into seven categories using a lipomics method. Among these lipids, 85 with relatively high contents decreased, while 201 lipids with low contents increased after fermentation. This led to an overall decrease in the sum contents of lipids and dominant lipids, including glycerophospholipids and saccharolipids. We also detected 33 medium- and long-chain fatty acids, with α-linolenic acid (881.202 ± 12.13-1322.263 ± 19.78 µg/g), palmitic acid (797.275 ± 19.56-955.180 ± 30.49 µg/g), and linoleic acid (539.634 ± 15.551-706.869 ± 12.14 µg/g) being the predominant ones. Coenzymes Q9 (62.76-63.57 µg/g) and Q10 (50.82-59.33 µg/g) were also identified in the fermentation process. Our findings shed light on the changes in lipids during the fermentation of RPT and highlight the potential bio-active compounds, such as α-linolenic acid, linoleic acid, Coenzymes Q9, and Q10, in ripened pu-erh tea. This contributes to a better understanding of the fermentation mechanism for RPT.

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Purpose: This study aimed to explore the impact of HSPA13 on epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells and proliferative vitreoretinopathy (PVR) development, along with its associated molecular mechanisms. Methods: HSPA13 expression was evaluated in epiretinal membranes (ERMs) from patients with PVR using immunohistochemistry. The effects of HSPA13 knockdown on TGFß1-induced EMT in hESC-RPE cells were studied through quantitative PCR (qPCR), Western blot, and wound healing assays. Intracellular Ca2+ levels were measured using Fluo-8/AM incubation. A rat PVR model was induced by the intravitreal injection of RPE cells combined with platelet-rich plasma (PRP). RNA-seq was applied to study the molecular mechanism of HSPA13 knockdown-mediated EMT inhibition. Results: HSPA13 was found in human ERMs and its expression increased with TGFß1 treatment in hESC-RPE cells. Knockdown of HSPA13 inhibited TGFß1-induced EMT and migration. In the PVR rat model, HSPA13 was expressed in the ERMs and its knockdown in RPE cells reduced the development of PVR. Consistent with these observations, RNA-seq showed a global suppression of TGFß1-induced EMT and migration by shHSPA13 in RPE cells. Mechanistically, TGFß1 treatment increased intracellular Ca2+ levels, leading to an upregulation of HSPA13 expression. Downregulation of HSPA13 hindered the phosphorylation of PI3K/Akt in TGFß1-induced RPE cells. Conclusions: Our study revealed the involvement of HSPA13 in PVR development, as well as in TGFß1-induced EMT of RPE through the PI3K/Akt signaling pathway. Targeting HSPA13-related pathways involved in regulating EMT in RPE cells could serve as a novel therapeutic approach for patients with PVR.

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The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms of the vaginal epithelium after a bacterial infection remain incompletely understood. This study showed that bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na+-H+ exchanger 1 (NHE1) without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacologic inhibition or genetic knockdown of Toll-like receptor-4 and the extracellular signal-regulated protein kinase signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited an impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicate the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis.

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For BixSb2- xTe3 (BST) in thermoelectric field, the element ratio is easily influenced by the chemical environment, deviating from the stoichiometric ratio and giving rise to various intrinsic defects. In P-type polycrystalline BST, SbTe and BiTe are the primary forms of defects. Defect engineering is a crucial strategy for optimizing the electrical transport performance of Bi2Te3-based materials, but achieving synchronous improvement of thermal performance is challenging. In this study, mesoporous SiO2 is utilized to successfully mitigate the adverse impacts of vacancy defects, resulting in an enhancement of the electrical transport performance and a pronounced reduction in thermal conductivity. Crystal and the microstructure of the continuous modulation contribute to the effective phonon-electronic decoupling. Ultimately, the peak zT of Bi0.4Sb1.6Te3/0.8 wt% SiO2 (with a pore size of 4 nm) nanocomposites reaches as high as 1.5 at 348 K, and a thermoelectric conversion efficiency of 6.6% is achieved at ΔT = 222.7 K. These results present exciting possibilities for the realization of defect regulation in porous materials and hold reference significance for other material systems.

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BACKGROUND: Studying and discovering the molecular mechanism of Plasmodium sexual development is crucial for the development of transmission blocking drugs and malaria eradication. The aim of this study was to investigate the feasibility of using phosphatase inhibitors as a tool for screening proteins essential for Plasmodium sexual development and to discover proteins affecting the sexual development of malaria parasites. METHODS: Differences in protein phosphorylation among Plasmodium gametocytes incubated with BVT-948 under in vitro ookinete culture conditions were evaluated using phosphoproteomic methods. Gene Ontology (GO) analysis was performed to predict the mechanism by which BVT-948 affected gametocyte-ookinete conversion. The functions of 8 putative proteins involved in Plasmodium berghei sexual development were evaluated. Bioinformatic analysis was used to evaluate the possible mechanism of PBANKA_0100800 in gametogenesis and subsequent sexual development. RESULTS: The phosphorylation levels of 265 proteins decreased while those of 67 increased after treatment with BVT-948. Seven of the 8 genes selected for phenotype screening play roles in P. berghei sexual development, and 4 of these were associated with gametocytogenesis. PBANKA_0100800 plays essential roles in gametocyte-ookinete conversion and transmission to mosquitoes. CONCLUSIONS: Seven proteins identified by screening affect P. berghei sexual development, suggesting that phosphatase inhibitors can be used for functional protein screening.

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To study the effect of polycrystalline 3C-SiC rough friction surface on the mechanism of subsurface brittleness during nanocrystalline grinding. Initial grinding models of polycrystalline 3C-SiC and diamond abrasive grains on rough friction surfaces are developed using molecular dynamics methods and the Voronoi method for constructing polycrystalline abrasive grains. The processing mechanism of 3C-SiC is analyzed by post-processing methods such as dislocation defect analysis, atomic arrangement analysis and stress analysis. At 2.6 nm, "stress concentration" occurs between the abrasive particles and the workpiece, forming irregular force shapes. The larger the grain size, the smaller the crystal hardness, the greater the possibility of crystal fracture, and it is obvious in the crystal of larger grains. At 8 nm, the crystal breaks and creates vacancies. The roughness of the polycrystalline 3C-SiC friction surface and the cross-cutting mechanism between grains with grain boundaries are found to be effective in ameliorating the damage in the subsurface layer.

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Helicobacter pylori has been recognized not only as a causative agent of a spectrum of gastroduodenal diseases including chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, but also as the culprit in several extra-gastric diseases. However, the association of H. pylori infection with extra-gastric diseases remains elusive, prompting a reevaluation of the role of H. pylori-derived outer membrane vesicles (OMVs). Like other gram-negative bacteria, H. pylori constitutively sheds biologically active OMVs for long-distance delivery of bacterial virulence factors in a concentrated and protected form, averting the need of direct bacterial contact with distant host cells to induce extra-gastric diseases associated with this gastric pathogen. Additionally, H. pylori-derived OMVs contribute to bacterial survival and chronic gastric pathogenesis. Moreover, the immunogenic activity, non-replicable nature, and anti-bacterial adhesion effect of H. pylori OMVs make them a desirable vaccine candidate against infection. The immunogenic potency and safety concerns of the OMV contents are challenges in the development of H. pylori OMV-based vaccines. In this review, we discuss recent advances regarding H. pylori OMVs, focusing on new insights into their biogenesis mechanisms and biological functions.

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The joint groundwater pollution prevention and control (GPPC) strategy has been extensively implemented to address the coastal region groundwater pollution challenges in China. However, regional groundwater pollution control and treatment efficiency cannot achieve the expected results due to the lack of regional priority control orders and accurate restoration levels. Thus, this study developed a new region demarcation framework method for delineating GPPC zones, in tandem with a comprehensive pollution index method, the DRASTIC model, source apportionment. To validate the new methodological framework, a case study of groundwater pollution in Qinhuangdao, the western of Bohai Bay, China, was implemented to calculate pollution prevention and control zoning. In total, 340 groundwater samples from shallow aquifers with 9 target pollutants (NO3-, NO2-, NH4+, As, Cd, Cr, Cu, Pb, and Ni) were selected as the dataset for GPPC regionalization. The results showed that GPPC zoning further clarified the direction of groundwater pollution protection and management in Qinhuangdao. Compared to the traditional method, the new GPPC zoning better reflects groundwater mobility characteristics and pollution transport and enrichment patterns in terms of groundwater functional integrity and delineation. This new regional demarcation framework method contributes to providing support for the fine division of groundwater pollution zoning and precise pollution control for groundwater resource management in China.

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In light of the escalating industrial and environmental pollution, there is a pressing need for the development of novel materials capable of swiftly detecting pollutants. Here, we report the synthesis of five lanthanide metal-organic frameworks sharing a common structure, prepared via a hydrothermal method and denoted as [Ln2(H2DHBDC)2(phen)(H2O)6]n (where CUST-888 corresponds to Tb, CUST-889 corresponds to Eu, CUST-890 corresponds to Gd, CUST-891 corresponds to Dy, and CUST-892 corresponds to Nd). Notably, CUST-888 and CUST-889 exhibit discernible visual alterations in response to acidic and alkaline conditions. To assess their practical utility, luminescent test strips and light-emitting diode lights based on CUST-888 and CUST-889 were devised, enabling the visual detection of luminescence color changes induced by Hg2+, Cr2O72-, tetracycline, and 2,4,6-trinitrophenol. Furthermore, highlighters derived from CUST-888 and CUST-889 were designed, showcasing robust stability, adjustable color, and substantial potential for application in the realm of anticounterfeiting.

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Plant non-structural carbohydrates (NSCs), which largely comprise starch and soluble sugars, are essential energy reserves to support plant growth and physiological functions. While it is known that increasing global deposition of nitrogen (N) affects plant concentration of NSCs, quantification of seasonal responses and drivers of woody species leaf and root NSCs to N addition at larger spatial scales remains lacking. Here, we systematically analyzed data from 53 field experiments distributed across China, comprising 1202 observations, to test for effects of N addition on woody plant leaf and root NSCs across and within growing and non-growing seasons. We found (1) no overall effects of N addition on the concentrations of leaf and root NSCs, soluble sugars or starch during the growing season or the non-growing season for leaves. However, N addition decreased root NSC and starch concentrations by 13.8 % and 39.0 %, respectively, and increased soluble sugars concentration by 15.0 % during the non-growing season. (2) Shifts in leaf NSC concentration under N addition were driven by responses by soluble sugars in both seasons, while shifts in root NSC were driven by soluble sugars in the non-growing season and starch and soluble sugars in the growing season. (3) Relationships between N, carbon, and phosphorus stoichiometry with leaf and root NSCs indicated effects of N addition on woody plant NSCs allocation through impacts on plant photosynthesis, respiration, and growth. (4) Effects of N addition on leaf and root NSCs varied with plant functional types, where effects were more pronounced in roots than in leaves during the non-growing season. Overall, our results reveal divergent responses of woody plant leaf and root NSCs to N addition within non-growing season and highlight the role of ecological stoichiometry and plant functional types in woody plant allocation patterns of NSCs in response to ongoing N deposition under global change.

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Xp11 translocation renal cell carcinoma (tRCC) is a rare, female-predominant cancer driven by a fusion between the transcription factor binding to IGHM enhancer 3 (TFE3) gene on chromosome Xp11.2 and a partner gene on either chromosome X (chrX) or an autosome. It remains unknown what types of rearrangements underlie TFE3 fusions, whether fusions can arise from both the active (chrXa) and inactive X (chrXi) chromosomes, and whether TFE3 fusions from chrXi translocations account for the female predominance of tRCC. To address these questions, we performed haplotype-specific analyses of chrX rearrangements in tRCC whole genomes. We show that TFE3 fusions universally arise as reciprocal translocations and that oncogenic TFE3 fusions can arise from chrXi:autosomal translocations. Female-specific chrXi:autosomal translocations result in a 2:1 female-to-male ratio of TFE3 fusions involving autosomal partner genes and account for the female predominance of tRCC. Our results highlight how X chromosome genetics constrains somatic chrX alterations and underlies cancer sex differences.

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It is challenging to attain strong near-infrared (NIR) emissive gold nanoclusters. Here we show a rod-shaped cluster with the composition of [Au28(p-MBT)14(Hdppa)3](SO3CF3)2 (1 for short, Hdppa is N,N-bis(diphenylphosphino)amine, p-MBT is 4-methylbenzenethiolate) has been synthesized. Single crystal X-ray structural analysis reveals that it has a rod-like face-centered cubic (fcc) Au22 kernel built from two interpenetrating bicapped cuboctahedral Au15 units. 1 features NIR luminescence with an emission maximum at 920 nm, and the photoluminescence quantum yield (PLQY) is 12%, which is 30-fold of [Au21(m-MBT)12(Hdppa)2]SO3CF3 (2, m-MBT is 3-methylbenzenethiolate) with a similar composition and 60-fold of Au30S(S­t­Bu)18 with a similar structure. time-dependent DFT(TDDFT)calculations reveal that the luminescence of 1 is associated with the Au22 kernel. The small Stokes shift of 1 indicates that it has a very small excited state structural distortion, leading to high radiative decay rate (kr) probability. The emission of cluster 1 is a mixture of phosphorescence and thermally activated delayed fluorescence(TADF), and the enhancement of the NIR emission is mainly due to the promotion of kr rather than the inhibition of knr. This work demonstrates that the metal kernel and the surface structure are both very important for cluster-based NIR luminescence materials.

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Biochar application is an effective strategy to address Agro-climatic challenges. However, the agro-environmental impacts of different biochar technology models are lacking of systematic summaries and reviews. Therefore, this paper comprehensively reviews recent developments derived from published literature, delving into the economic implications and environmental benefits of three distinct process namely technologies-pyrolysis, gasification, and hydrothermal carbonization. This paper specifically focuses on the agricultural life cycle assessment (LCA) methodology, and the influence of biochar preparation technologies and products on energy consumption and agricultural carbon emissions. LCA analysis shows that process and feedstock pose a predominant role on the properties and production rate of biochar, while gasification technology exhibits excellent economic attributes compared to the other two technologies. Biochar applications in agricultural has the beneficial effect of sequestering carbon and reducing emissions, especially in the area of mitigating the carbon footprint of farmland. However, the complexity of the composition of the prepared feedstock and the mismatch between the biochar properties and the application scenarios are considered as potential sources of risks. Notably, mechanism of carbon sequestration and emission reduction by soil microorganisms and agro-environmental sequestration by biochar application remains unclear, calling for in-depth studies. We review novel aspects that have not been covered by previous reviews by comparing the technical, economic, and environmental benefits of pyrolysis, gasification, and hydrothermal carbonization systematically. Overall, this study will provide a valuable framework to environmental implications of biochar preparation, application, and life cycle assessments.

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OBJECTIVE: To introduce a novel approach for predicting the personalized probability of success of DPC treatment in carious mature permanent teeth using explainable machine learning (ML) models. METHODS: Clinical data were obtained from our previous single-center retrospective study, comprising 393 carious mature permanent teeth from 372 patients who underwent DPC and attended 1-year follow-up between January 2015 and February 2021. Six ML models were derived based on 80 % cases of the cohort, with the remaining 20 % cases used for validation. Shapley additive explanation (SHAP) values were utilized to assess feature importance and the clinical relevance of prediction models. RESULTS: Within the cohort, 9.67 % (38 out of 393) of teeth experienced failure at the 1-year follow-up after DPC treatment. Among the six evaluated ML models, the XGBoost model exhibited the highest discriminative ability. By prioritizing features based on their importance, streamlined and interpretable XGBoost model with 11 features were developed for 1-year prognostication post-DPC. The model demonstrated predictive accuracy with area under the curve (AUC) scores of 0.86 for the 1-year prediction. The final model has been translated into a web application to facilitate clinical decision-making. CONCLUSION: By incorporating demographic and clinical examination data, the XGBoost model offered a user-friendly tool for dentists to predict personalized probability of success, thereby improving personalized dental care and patient counseling. The utilization of SHAP for model interpretation provided transparent insights into the decision-making process.

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BACKGROUND: To evaluate the efficacy and safety of nab-paclitaxel plus cisplatin as the regimen of conversional chemoradiotherapy (cCRT) in locally advanced borderline resectable or unresectable esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC (cT3­4, Nany, M0­1, M1 was limited to lymph node metastasis in the supraclavicular area) were enrolled. All the patients received the cCRT of nab-paclitaxel plus cisplatin. After the cCRT, those resectable patients received esophagectomy; those unresectable patients continued to receive the definitive chemoradiotherapy (dCRT). The locoregional control (LRC), overall survival (OS), event-free survival (EFS), distant metastasis free survival (DMFS), pathological complete response (pCR), R0 resection rate, adverse events (AEs) and postoperative complications were calculated. RESULTS: 45 patients with ESCC treated from October 2019 to May 2021 were finally included. The median follow-up time was 30.3 months. The LRC, OS, EFS, DMFS at 1 and 2 years were 81.5%, 86.6%, 64.3%, 73.2 and 72.4%, 68.8%, 44.8%, 52.7% respectively. 21 patients (46.7%) received conversional chemoradiotherapy plus surgery (cCRT+S). The pCR rate and R0 resection rate were 47.6 and 84.0%. The LRC rate at 1 and 2 years were 95.0%, 87.1% in cCRT+S patitents and 69.3%, 58.7% in dCRT patients respectively (HR, 5.14; 95%CI, 1.10-23.94; P = 0.021). The toxicities during chemoradiotherapy were tolerated, and the most common grade 3-4 toxicitiy was radiation esophagitis (15.6%). The most common postoperative complication was pleural effusion (38.1%) and no grade ≥ IIIb complications were observed. CONCLUSION: nab-paclitaxel plus cisplatin are safe as the regimen of conversional chemoradiotherapy of ESCC.

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BACKGROUND: Thermostability is a fundamental property of proteins to maintain their biological functions. Predicting protein stability changes upon mutation is important for our understanding protein structure-function relationship, and is also of great interest in protein engineering and pharmaceutical design. RESULTS: Here we present mutDDG-SSM, a deep learning-based framework that uses the geometric representations encoded in protein structure to predict the mutation-induced protein stability changes. mutDDG-SSM consists of two parts: a graph attention network-based protein structural feature extractor that is trained with a self-supervised learning scheme using large-scale high-resolution protein structures, and an eXtreme Gradient Boosting model-based stability change predictor with an advantage of alleviating overfitting problem. The performance of mutDDG-SSM was tested on several widely-used independent datasets. Then, myoglobin and p53 were used as case studies to illustrate the effectiveness of the model in predicting protein stability changes upon mutations. Our results show that mutDDG-SSM achieved high performance in estimating the effects of mutations on protein stability. In addition, mutDDG-SSM exhibited good unbiasedness, where the prediction accuracy on the inverse mutations is as well as that on the direct mutations. CONCLUSION: Meaningful features can be extracted from our pre-trained model to build downstream tasks and our model may serve as a valuable tool for protein engineering and drug design.

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