Synergistic Effect of Electron Scattering and Space Charge Transfer Enabled Unprecedented Room Temperature NO2 Sensing Response of SnO2.

Metal oxide gas sensors have long faced the challenge of low response and poor selectivity, especially at room temperature (RT). Herein, a synergistic effect of electron scattering and space charge transfer is proposed to comprehensively improve gas sensing performance of n-type metal oxides toward oxidizing NO2 (electron acceptor) at RT. To this end, the porous SnO2 nanoparticles (NPs) assembled from grains of about 4 nm with rich oxygen vacancies are developed through an acetylacetone-assisted solvent evaporation approach combined with precise N2 and air calcinations. The results show that the as-fabricated porous SnO2 NPs sensor exhibits an unprecedented NO2 -sensing performance, including outstanding response (Rg /Ra  = 772.33 @ 5 ppm), fast recovery (<2 s), an extremely low detection limit (10 ppb), and exceptional selectivity (response ratio >30) at RT. Theoretical calculation and experimental tests confirm that the excellent NO2 sensing performance is mainly attributed to the unique synergistic effect of electron scattering and space charge transfer. This work proposes a useful strategy for developing high-performance RT NO2 sensors using metal oxides, and provides an in-depth understanding for the basic characteristics of the synergistic effect on gas sensing, paving the way for efficient and low power consumption gas detection at RT.

Adsorption of CH4, CO, and H2S on a MoTe2 Monolayer Doped with Metal Atoms (Au and Ru): An Ab Initio Study.

Detecting toxic gases, such as CH4, CO, and H2S, in everyday life holds great significance. This research article focuses on investigating the adsorption characteristics of CH4, CO, and H2S on MoTe2 and MoTe2 doped with Au and Ru using the density functional theory. The study examines various aspects, including adsorption energy, charge transfer, density of states, and charge density difference of the adsorption configuration. The findings demonstrate that the adsorption properties of Ru-doped MoTe2 exhibit a significant enhancement for all three gases, with CO displaying the highest adsorption performance. Through comparative analysis, it is evident that the adsorption affinity between MoTe2-Ru and the three gases is robust, thus indicating improved gas detection capabilities.

Recent Progress in MOF-Based Electrochemical Sensors for Non-Enzymatic Glucose Detection.

In recent years, substantial advancements have been made in the development of enzyme-free glucose sensors utilizing pristine metal-organic frameworks (MOFs) and their combinations. This paper provides a comprehensive exploration of various MOF-based glucose sensors, encompassing monometallic MOF sensors as well as multi-metal MOF combinations. These approaches demonstrate improved glucose detection capabilities, facilitated by the augmented surface area and availability of active sites within the MOF structures. Furthermore, the paper delves into the application of MOF complexes and derivatives in enzyme-free glucose sensing. Derivatives incorporating carbon or metal components, such as carbon cloth synthesis, rGO-MOF composites, and core-shell structures incorporating noble metals, exhibit enhanced electrochemical performance. Additionally, the integration of MOFs with foams or biomolecules, such as porphyrins, enhances the electrocatalytic properties for glucose detection. Finally, this paper concludes with an outlook on the future development prospects of enzyme-free glucose MOF sensors.

Malus asiatica as a natural host of apple scar skin viroid in China.

Malus asiatica (Rosaceae, Malus) is a small deciduous tree, which has been cultivated in China more than 450 years (Jin, 2019). M. asiatica is deeply favored by consumers because of its sweet taste and high nutritional attributes, rich in vitamins, minerals and dietary fiber (Xue et al, 2013). Although the M. asiatica annual output is nearly 30 000 kg, it still cannot meet the market demand in China (Jin, 2019). In August 2021, the virus-like symptom such as colored spots on fruit epidermis of M. asiatica were observed in an orchard of Langfang (38°42'16.88″N, 116°39'15.23″E) of Hebei province, China. To investigate whether this symptom is related to virus infection, the symptomatic sample was subjected to small RNA sequencing. Total RNA was extracted from branch bark of a symptomatic tree using an RNAprep Pure Plant Kit (TianGen, China), The extracted RNA was used to construct a small RNA library using NEBNext® Multiplex Small RNA Library Prep Set for Illumina® (Set 1), (NEB, USA), then the resulting library was sequenced using Illumina novoseq 6000 (Illumina, USA) at Tianjin Novogene company (China). A total of 14,685,616 sequence reads were obtained. After filtering the low-quality reads, polyA, adaptor contaminants, fragments < 18 nt and > 26 nt, and reads matching apple genome, the number of reads reduced to 392,883. Finally, assembly of these clean reads generated 225 non-redundant contigs with Velvet software and 55 assembled contigs were aligned to Refseq viral database of NCBI by Bowtie software. One viral contig with length of 329 nt showed 98.48% significant similarity to genome sequences of Hohhot isolate of ASSVd (ASSVd-Hohhot) (GenBank Accession No. MZ476527.1) (Yuan et al, 2022). We then used a specific primer pair (ASSVd-F: 5'-G G T A A A C A C C G T G C G G T T C C-3'; ASSVd-R: 5'-G G G A A A C A C C A A T T G T G T T T T A-3') for reverse transcription (RT)-PCR to amplify the genome sequence of ASSVd. A 330 bp amplified product was cloned into the pGEM-T easy vector (Promega, USA), then sequenced by Sanger sequencing using T7 primer by Sangon Biotech (Shanghai) Co., Ltd. in China. The sequence of ASSVd has been deposited in the GenBank datebase (GenBank Accession No. ON093255). Blast analysis showed that the sequence had highest identity (326/330, 98.79%) with ASSVd-Hohhot (GenBank Accession No. MZ476527.1) (Yuan et al, 2022). To confirm the pathogenicity of ASSVd, fifteen healthy cucumber seedlings were inoculated mechanically with the extracts of ASSVd-infected branch bark of M. asiatica. There were no obvious symptoms were observed at 14 days post inoculation (dpi), however, the result of RT-PCR and Sanger sequencing showed four cucumber samples were positive for ASSVd. In addition, another 19 randomly collected M. asiatica samples with or without clear symptoms from Langfang were detected by RT-PCR, and ten (52.6%) of them were confirmed the presence of ASSVd. And all ten positive samples were symptomatic, while nine nonsymptomatic M. asiatica samples tested negative. The positive amplicons were cloned into the pGEM-T easy vector and sequenced using T7 primer by Sanger sequencing. All of the sequences were essentially identical to one another (GenBank Accession No. ON093255), which indicates that the positive samples are indeed ASSVd infected. To the best of our knowledge, this is the first report of ASSVd infection in M. asiatica, which expands our understanding of the host range of ASSVd.

The neoantigens derived from transposable elements - A hidden treasure for cancer immunotherapy.

Neoantigen-based therapy is a promising approach that selectively activates the immune system of the host to recognize and eradicate cancer cells. Preliminary clinical trials have validated the feasibility, safety, and immunogenicity of personalized neoantigen-directed vaccines, enhancing their effectiveness and broad applicability in immunotherapy. While many ongoing oncological trials concentrate on neoantigens derived from mutations, these targets do not consistently provoke an immune response in all patients harboring the mutations. Additionally, tumors like ovarian cancer, which have a low tumor mutational burden (TMB), may be less amenable to mutation-based neoantigen therapies. Recent advancements in next-generation sequencing and bioinformatics have uncovered a rich source of neoantigens from non-canonical RNAs associated with transposable elements (TEs). Considering the substantial presence of TEs in the human genome and the proven immunogenicity of TE-derived neoantigens in various tumor types, this review investigates the latest findings on TE-derived neoantigens, examining their clinical implications, challenges, and unique advantages in enhancing tumor immunotherapy.

Comparative analysis of the gut bacteria and fungi in migratory demoiselle cranes (Grus virgo) and common cranes (Grus grus) in the Yellow River Wetland, China.

Introduction: Gut microbiota are closely related to the nutrition, immunity, and metabolism of the host and play important roles in maintaining the normal physiological activities of animals. Cranes are important protected avian species in China, and they are sensitive to changes in the ecological environment and are thus good environmental indicators. There have been no reports examining gut fungi or the correlation between bacteria and fungi in wild Demoiselle cranes (Grus virgo) and Common cranes (Grus grus). Related research can provide a foundation for the protection of rare wild animals. Methods: 16S rRNA and ITS high-throughput sequencing techniques were used to analyze the gut bacterial and fungal diversity of Common and Demoiselle cranes migrating to the Yellow River wetland in Inner Mongolia. Results: The results revealed that for gut bacteria α diversity, Chao1 index in Demoiselle cranes was remarkably higher than that in Common cranes (411.07 ± 79.54 vs. 294.92 ± 22.38), while other index had no remarkably differences. There was no remarkable difference in fungal diversity. There were marked differences in the gut microbial composition between the two crane species. At the phylum level, the highest abundance of bacteria in the Common crane and Demoiselle crane samples was Firmicutes, accounting for 87.84% and 74.29%, respectively. The highest abundance of fungi in the guts of the Common and Demoiselle cranes was Ascomycota, accounting for 69.42% and 57.63%, respectively. At the genus level, the most abundant bacterial genus in the Common crane sample was Turicibacter (38.60%), and the most abundant bacterial genus in the Demoiselle crane sample was Catelicoccus (39.18%). The most abundant fungi in the Common crane sample was Penicillium (6.97%), and the most abundant fungi in the Demoiselle crane sample was Saccharomyces (8.59%). Correlation analysis indicated that there was a significant correlation between gut bacteria and fungi. Discussion: This study provided a research basis for the protection of cranes. Indeed, a better understanding of the gut microbiota is very important for the conservation and management of wild birds, as it not only helps us to understand their life history and related mechanisms, but also can hinder the spread of pathogenic microorganisms.

Analysis of Alterations in Intestinal Flora in Chinese Elderly with Cardiovascular Disease and Its Association with Trimethylamine.

To investigate the changes in the intestinal flora in the Chinese elderly with cardiovascular disease (CVD) and its correlation with the metabolism of trimethylamine (TMA), the intestinal flora composition of elderly individuals with CVD and healthy elderly individuals was analyzed using 16S rRNA sequencing, the TMA levels in the feces of elderly were detected using headspace-gas chromatography (HS-GC), and four kinds of characterized TMA-producing intestinal bacteria in the elderly were quantified using real-time fluorescence quantitative polymerase chain reaction (qPCR). The results showed that Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and Verrucomicrobia are the dominant microorganisms of the intestinal flora in the Chinese elderly. And there were significant differences in the intestinal bacteria composition between healthy elderly individuals and those with CVD, accompanied by a notable difference in the TMA content. The richness and diversity of the intestinal flora in the elderly with CVD were higher than those in the healthy elderly. Correlation analysis indicated that certain significantly different intestinal flora were associated with the TMA levels. Our findings showed a significant difference in TMA-producing intestinal flora between healthy elderly individuals and those with CVD. The TMA levels were found to be positively and significantly correlated with Klebsiella pneumoniae, suggesting that this bacterium is closely linked to the production of TMA in the elderly gut. This may have implications for the development and progression of CVD in the elderly population.

Single cell and bulk RNA sequencing identifies tumor microenvironment subtypes and chemoresistance-related IGF1+ cancer-associated fibroblast in gastric cancer.

BACKGROUND: The tumor microenvironment (TME) significantly influences prognosis and drug resistance in various tumors, yet its heterogeneity and the mechanisms affecting therapeutic response remain unclear in gastric cancer (GC). METHODS: The heterogenous TME were explored with single-cell RNA-sequencing (scRNA-seq) data of 50 primary GC samples. We then identified four GC TME subtypes with nonnegative matrix factorization (NMF) and constructed a pearson nearest-centroid classifier based on subtype-specific upregulated genes. Genomic features and clinical significance of four subtypes were comprehensively evaluated. We reclustered fibroblasts to identify cancer-associated fibroblast (CAF) subtype associated with poor clinical outcomes. RT-qPCR and double immunofluorescence staining were applied to validate the findings. Cellchat analysis elucidated potential molecular mechanisms of the CAF subtype in GC disease progression and chemotherapy resistance. FINDINGS: The GC TME exhibited high heterogeneity, influencing chemo-sensitivity. Four TME-based subtypes predicting response to immunotherapy and chemotherapy were identified and validated in 1406 GC patients. Among which, ISG1 subtype displayed higher fibroblasts infiltration and heightened oncogenic pathways, and inferior response to chemotherapy with unfavorable prognosis. Microsatellite instability-high (MSI-H) GCs within four TME subtypes showed immunological heterogeneity. We then reported an IGF1-overexpressing CAF was associated with chemo-resistance and GC recurrence. Cell communication analysis revealed IGF1+ CAF may induce drug-resistant phenotypes in tumor cells through IGF1-α6ß4 integrin ligand-receptor binding and activation of EMT biological process. INTERPRETATION: We identified four TME-based subtypes with different clinical outcomes and IGF1+ CAFs contributing to poor clinical outcomes in GC, which might provide guidance for individualized treatment and facilitate the development of novel therapeutic targets.

Global trends and hotspots in Cyclin-dependent Kinase Subunit 2 research from 1999 to 2022: A bibliometric and visualized analysis.

BACKGROUND: Cyclin-dependent Kinase Subunit 2 is a protein closely related to the regulation of the cell cycle. In recent years, there has been an increasing number of research articles on this topic. However, there is a lack of comprehensive synthesis and evaluation in the field of CKS2 research. This study aims to summarize and visualize the literature distribution, research hotspots, and development trends of CKS2 based on bibliometric methods. METHODS: Publications from 1999 to 2022 were extracted from the Web of Science. Citespace was used to analyze the relevant information of each article. RESULTS: A total of 138 publications focused on CKS2 showed a positive growth trend from 1999 to 2022 and were published by 27 countries. The most prolific countries are China and the USA. The most prolific institution is Scripps Research Institute. The most prolific author is Steven I. Reed from Scripps Research Institute. The most cited article is published by Todd R Golub. The most cited author is Hanna-Stina Martinsson-Ahlzen. The journal with the most published articles is International Journal of Oncology. The high frequency keywords suggest that expression and function of CKS2 in cancer are dominated topics. The clusters and burst words suggest that expression and function of CKS2 still active in the future. CONCLUSION SUBSECTIONS: The results of this bibliometric analysis provide information on the state and trends in CKS2 from 1999 to 2022. It is helpful for scholars to pinpoint hot issues and discover new areas of study.

Design and implementation of high sampling rate and multichannel wireless recorder for EEG monitoring and SSVEP response detection.

Introduction: The collection and process of human brain activity signals play an essential role in developing brain-computer interface (BCI) systems. A portable electroencephalogram (EEG) device has become an important tool for monitoring brain activity and diagnosing mental diseases. However, the miniaturization, portability, and scalability of EEG recorder are the current bottleneck in the research and application of BCI. Methods: For scalp EEG and other applications, the current study designs a 32-channel EEG recorder with a sampling rate up to 30 kHz and 16-bit accuracy, which can meet both the demands of scalp and intracranial EEG signal recording. A fully integrated electrophysiology microchip RHS2116 controlled by FPGA is employed to build the EEG recorder, and the design meets the requirements of high sampling rate, high transmission rate and channel extensive. Results: The experimental results show that the developed EEG recorder provides a maximum 30 kHz sampling rate and 58 Mbps wireless transmission rate. The electrophysiological experiments were performed on scalp and intracranial EEG collection. An inflatable helmet with adjustable contact impedance was designed, and the pressurization can improve the SNR by approximately 4 times, the average accuracy of steady-state visual evoked potential (SSVEP) was 93.12%. Animal experiments were also performed on rats, and spike activity was captured successfully. Conclusion: The designed multichannel wireless EEG collection system is simple and comfort, the helmet-EEG recorder can capture the bioelectric signals without noticeable interference, and it has high measurement performance and great potential for practical application in BCI systems.

Serum neutrophil gelatinase-associated lipocalin as a potential biomarker for cognitive decline in spinal cord injury.

Objective: Neutrophil gelatinase-associated lipoprotein (NGAL), a protein encoded by the lipocalcin-2 (LCN2) gene, has been reported to be involved in multiple processes of innate immunity, but its relationship with spinal cord injury (SCI) remains unclear. This study set out to determine whether NGAL played a role in the development of cognitive impairment following SCI. Methods: At the Neck-Shoulder and Lumbocrural Pain Hospital, a total of 100 SCI patients and 72 controls were enrolled in the study through recruitment. Through questionnaires, baseline data on the participants' age, gender, education level, lifestyle choices (drinking and smoking) and underlying illnesses (hypertension, diabetes, coronary heart disease, and hyperlipidemia) were gathered. The individuals' cognitive performance was evaluated using the Montreal Cognitive Scale (MoCA), and their serum NGAL levels were discovered using ELISA. Results: The investigation included 72 controls and 100 SCI patients. The baseline data did not differ substantially between the two groups, however the SCI group's serum NGAL level was higher than the control group's (p < 0.05), and this elevated level was adversely connected with the MoCA score (p < 0.05). According to the results of the ROC analysis, NGAL had a sensitivity of 58.24% and a specificity of 86.72% for predicting cognitive impairment following SCI. Conclusions: The changes in serum NGAL level could serve as a biomarker for cognitive impairment in SCI patients, and this holds true even after taking in account several confounding variables.

A bibliometric analysis of intra-articular injection therapy for knee osteoarthritis from 2012 to 2022.

Knee osteoarthritis (KOA) is the most common joint disease worldwide and, with the progression of an aging population, is one of the most important causes of disability worldwide. Its main symptoms include articular cartilage damage, periarticular pain, swelling, and stiffness. Intra-articular (IA) injections offer many advantages over systemic administration and surgical treatment, including direct action on the target joint to improve local bioavailability, reduce systemic toxicity, and lower costs. This study analyzed KOA intra-articular injection treatment and its hot literature and research horizons using bibliometric methodologies and graphical tools to aid future research. We performed a bibliometric analysis of 2360 publications in the Web of Science core collection using CiteSpace software. The United States (28.26% of publications) and China (18%) had the biggest publications. Rush University was the most active institution, but Boston University had the greatest citation/publication rate (65.77), suggesting a high literature standard. The majority of publications were in Osteoarthritis and cartilage. Bannuru RR was the most referenced author, while Filardo, Giuseppe was the most productive author. Studies in platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), and microsphere formulation are likely to be future research hotspots. The current scientometric study provides an overview of KOA intra-articular injection therapy studies from 2012 to 2022. This study outlines the current research hotspots and potential future research hotspots in the field of intra-articular injection treatment for KOA and may serve as a resource for researchers interested in this topic.

Comparative analysis of the gut bacteria of the relict gull (Larus Relictus) and black-necked grebe (Podiceps Nigricollis) in Erdos Relic Gull National Nature Reserve in Inner Mongolia, China.

The gut microbiota promotes host health by maintaining homeostasis and enhancing digestive efficiency. The gut microflora in wild birds affects host physiological characteristics, nutritional status, and stress response. The relict gull (Larus Relictus, a Chinese national first-class protected species) and the black-necked grebe (Podiceps Nigricollis, a secondary protected species) bred in the Ordos Relic Gull National Nature Reserve share similar feeding habits and living environments but are distantly related genetically. To explore the composition and differences in the gut microbiota of these two key protected avian species in Erdos Relic Gull National Nature Reserve and provide a basis for their protection, 16S rRNA gene high-throughput sequencing was performed and the gut microbial diversity and composition of the relict gull (L. Relictus) and black-necked grebe (P. Nigricollis) was characterized. In total, 445 OTUs (operational taxonomic units) were identified and classified into 15 phyla, 22 classes, 64 orders, 126 families, and 249 genera. Alpha diversity analysis indicates that the gut microbial richness of the relict gull is significantly lower than that of the black-necked grebe. Gut microbe composition differs significantly between the two species. The most abundant bacterial phyla in these samples were Proteobacteria, Firmicutes, Fusobacteria, and Bacteroidetes. The prominent phylum in the relict gull was Proteobacteria, whereas the prominent phylum in the black-necked grebe was Firmicutes. The average relative abundance of the 17 genera identified was greater than 1%. The dominant genus in the relict gull was Escherichia-Shigella, whereas Halomonas was dominant in the black-necked grebe. Microbial functional analyses indicate that environmental factors exert a greater impact on relict gulls than on black-necked grebes. Compared with the relict gull, the black-necked grebe was able to use food more efficiently to accumulate its nutrient requirements, and the gut of the relict gull harbored more pathogenic bacteria, which may be one reason for the decline in the relict gull population, rendering it an endangered species. This analysis of the gut microbial composition of these two wild avian species in the same breeding grounds is of great significance, offers important guidance for the protection of these two birds, especially relict gulls, and provides a basis for understanding the propagation of related diseases.

Clinical Study on the Treatment of Non-isotropic Cervical Spondylosis by Neck Pain Granules Combined with Tuina.

BACKGROUND: Cervical spondylotic radiculopathy is a common form of cervical spondylosis caused by degeneration of the cervical spine. Currently, non-surgical treatment is the preferred treatment method, and Chinese medicine is widely used. OBJECTIVE: To investigate the effect of radiculopathy spondylosis by tuina spinning and lifting technique. EXPERIMENTAL DESIGN: We conducted a 12-week, open-label, analyst-blinded, randomized clinical trial ( 2 weeks of intervention plus 10 weeks of observational follow-up ). A total of 25 patients with radiculopathy were collected, and data was analyzed during the treatment and recovery period. INTERVENTIONS: Neck pain granules group: a package of oral neck pain granules after meals, three times a day, treatment for 2 weeks; neck pain granules combined with massage lifting technique, treatment group: use, massage lifting technique treatment, once every two days, normal take neck pain granules, treatment for 2 weeks. All cases were followed up for 2.5 months. Main monitoring indicators: Visual Analog Scale, Neck Dysfunction Index score, and Tanaka jiu ( Tanaka Yasuhisa Cervical Spondylosis Symptom Scale ) were recorded on time, and statistical statistics were made. RESULT: The scores of VAS and NDI were significantly more effective in the neck pain granules combined with the tuina group than in the neck pain granules group, while the Tanaka Yasuhisa Cervical Spondylosis Symptom Scale was not significantly different between the two groups. CONCLUSION: The treatment effect of neck pain granules combined with tuina was significantly better than that of traditional Chinese medicine alone.

GepLiver: an integrative liver expression atlas spanning developmental stages and liver disease phases.

Chronic liver diseases usually developed through stepwise pathological transitions under the persistent risk factors. The molecular changes during liver transitions are pivotal to improve liver diagnostics and therapeutics yet still remain elusive. Cumulative large-scale liver transcriptomic studies have been revealing molecular landscape of various liver conditions at bulk and single-cell resolution, however, neither single experiment nor databases enabled thorough investigations of transcriptomic dynamics along the progression of liver diseases. Here we establish GepLiver, a longitudinal and multidimensional liver expression atlas integrating expression profiles of 2469 human bulk tissues, 492 mouse samples, 409,775 single cells from 347 human samples and 27 liver cell lines spanning 16 liver phenotypes with uniformed processing and annotating methods. Using GepLiver, we have demonstrated dynamic changes of gene expression, cell abundance and crosstalk harboring meaningful biological associations. GepLiver can be applied to explore the evolving expression patterns and transcriptomic features for genes and cell types respectively among liver phenotypes, assisting the investigation of liver transcriptomic dynamics and informing biomarkers and targets for liver diseases.

Evaluation of multiple immune cells and patient outcomes in esophageal squamous cell carcinoma.

Recent reports indicate that immune cells in solid cancers have significant predictive and therapeutic value. IgG4 is a subclass of IgG and we recently found that it exerted an inhibitory effect in tumor immunity. We aimed to assess the significance of IgG4 and T cell subtypes in tumor prognosis. We investigated the density, distribution and relationship of five immune markers CD4, CD8, Foxp3, IL-10 and IgG4 with multiple immunostaining method in 118 esophageal squamous cell carcinoma (ESCC) together with clinical data. The relationship among different immune cell types and with clinical data were analyzed with Kaplan-Meier survival analysis and Cox proportional hazards model to identify independent risk factors among immune and clinicopathological parameters. Five-year survival rate of these patients treated with surgery reached 61%. Higher number of CD4+ plus CD8+ T cells predicted better prognosis (p=0.01) in tertiary lymphoid structure (TLS) and could add to the value of TNM staging. Density of the newly identified immune inhibitor IgG4+ B lymphocytes was found positively correlated to that of CD4+ cells (p=0.02) and IL-10+ cells (p=0.0005), but number of infiltrating IgG4+ cells by itself was not an independent factor for prognosis. However, increased serum concentration of IgG4 indicated a poor prognosis of ESCC (p=0.03). 5-year survival rate of esophageal cancer after surgery has been significantly improved. Increased T cells in TLS predicted better survival, suggesting that T cells in TLS may actively participate in anti-tumor immunity. Serum IgG4 could be a useful predictor of prognosis.

Flexibility-aware graph model for accurate epitope identification.

Structural flexibility is an intrinsic characteristics of a protein upon interacting with other molecules, which mainly comes from the movement of a residue's side chain, backbone and even an entire domain. Considering this property can be very helpful in protein binding analysis, such as epitope identification during antibody-antigen interaction. Unfortunately, to our knowledge, no approach is available at studying the dynamicity of protein binding from the computational perspective. We are pioneering a new perspective of exploring protein binding sites with considering the structural flexibility, particularly from the epitopes identification angle in antibody-antigen binding. To this end, we first obtained protein antigen structures with epitopes available, and built residue-level graphs of antigens. These graphs were highly densified subsequently by incorporating the structural flexibility. Later, the edge enriched graphs were clustered into overlapping subgraphs and were classified as epitope or non-epitope by a graph convolutional network. Experiments on epitope identification shown that the proposed flexibility-aware model markedly outperformed existing approaches by lifting the F1-score to 0.656, making a remarkable increment of 16.3% compared to the state-of-the-art. A quick study on generic protein binding site prediction also made a noteworthy improvement with increasing the F1-score by 8%. The superior performance obtained from both the specific and generic protein interaction analysis demonstrate that incorporating flexibility in computational models is helpful to strength the capability of identifying epitopes as well as general protein binding sites. This seminal study can be inspiring and promising to the wide range of protein interaction analysis.

Effects of Fluid Shear Stress on Human Intervertebral Disc Nucleus Pulposus Cells Based on Label-Free Quantitative Proteomics.

Objective: To explore the possible mechanism of fluid shear stress on human nucleus pulposus cells based on label-free proteomics technology. Methods: The human nucleus pulposus cell line was purchased and subcultured in vitro. The Flexcell STR-4000 multiflow field cell fluid shear stress loading culture system was used to apply continuous laminar fluid shear stress (12 dyne/cm2, 45 mins) to the monolayer adherent cells. Those without mechanical loading were used as the control group, and those subjected to fluid shear loading were used as the experimental group. Differential protein expression was identified using mass spectrometry identification technology, and bioinformatics analysis was performed using Gene Ontology GO (Gene Ontology) and Kyoto Encyclopedia of Genes and Genomes KEGG (Kyoto Encyclopedia of Genes and Genomes). Results: The proteomics results of the experimental group and the control group showed that the total number of mass spectra was 638653, the number of matched mass spectra was 170110, the total number of identified peptides was 32050, the specific peptide was 30564, and the total number of identified proteins was 4745. Comparing the two groups, 47 proteins were significantly differentially expressed, namely, 25 upregulated proteins and 22 downregulated proteins. Bioinformatics analysis showed that significantly different proteins were mainly manifested in cellular process, biological regulation, metabolic process, binding, catalytic activity, cellular components (cell part), organelle part (organelle part), and other molecular biological functions. Conclusion: Using proteomics technology to screen human nucleus pulposus cells after fluid shear stress loading, the differential protein expression provides a basis for further exploration of the mechanism of mechanical factors on nucleus pulposus.

A STING-related prognostic score predicts high-risk patients of colorectal cancer and provides insights into immunotherapy.

BACKGROUND: Targeted therapeutic strategies for advanced colorectal cancer (CRC) have been limited. STING is crucial to the antitumor immunotherapy, for it stimulates IFN signaling to mediate the crosstalk between innate and adaptive immune responses. Emerging evidence suggests that STING also contributes to the prognosis of CRC. However, prognostic models relating to STING have not yet been explored. METHODS: A total of 431 CRC samples from the TCGA database were analyzed to explore the prognostic value of STING-related genes. We trained prognostic models using the multivariate Cox regression. A STING-related prognostic score (SPS) was calculated as the gene expression multiplied by the corresponding coefficients of the final model. A backward stepAIC strategy was adopted to select the optimal model. A nomogram was used to personalize medical decisions for CRC. RESULTS: The expression level of STING was upregulated in the CMS1 subtype (P=0.036). Among STING-related genes, DHX9 (HR =0.72, P=0.01), IRF2 (HR =1.34, P=0.022), and POLR1D (HR =1.23, P=0.038) showed significant prognostic value. The SPS was proven to be an independent risk factor (training: HR =2.9, P=0.00013; validation: HR =3.02, P=0.01), and outperformed random classifiers in identifying high-risk CRC. The high SPS group was characterized by less genomic aberrations, upregulated IL6-JAK-STAT3 and IL2-STAT5 signaling pathways, increased expression of TIM-3, increased infiltration of regulatory T (Treg) cells and T helper 17 (Th17) cells, and decreased infiltration of M0 macrophages. Finally, the nomogram based on the SPS and clinical factors showed good performance in CRC. CONCLUSIONS: SPS is an independent risk factor that could identify high-risk CRC. While ICBs may benefit patients of the CMS1 subtype, for the CMS2, CMS3, and CMS4 subtypes in the high SPS group, STING agonists and immunotherapies targeting the Th17 axis may be beneficial. Finally, the SPS-based nomogram could help advance personalized medical decisions for CRC.

Identification of a Four-Gene-Based SERM Signature for Prognostic and Drug Sensitivity Prediction in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is a highly molecular heterogeneous tumor with poor prognosis. Epithelial-mesenchymal transition (EMT) process and cancer stem cells (CSCs) are reported to share common signaling pathways and cause poor prognosis in GC. Considering about the close relationship between these two processes, we aimed to establish a gene signature based on both processes to achieve better prognostic prediction in GC. METHODS: The gene signature was constructed by univariate Cox and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses by using The Cancer Genome Atlas (TCGA) GC cohort. We performed enrichment analyses to explore the potential mechanisms of the gene signature. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) curves were implemented to assess its prognostic value in TCGA cohort. The prognostic value of gene signature on overall survival (OS), disease-free survival (DFS), and drug sensitivity was validated in different cohorts. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) validation of the prognostic value of gene signature for OS and DFS prediction was performed in the Fudan cohort. RESULTS: A prognostic signature including SERPINE1, EDIL3, RGS4, and MATN3 (SERM signature) was constructed to predict OS, DFS, and drug sensitivity in GC. Enrichment analyses illustrated that the gene signature has tight connection with the CSC and EMT processes in GC. Patients were divided into two groups based on the risk score obtained from the formula. The Kaplan-Meier analyses indicated high-risk group yielded significantly poor prognosis compared with low-risk group. Pearson's correlation analysis indicated that the risk score was positively correlated with carboplatin and 5-fluorouracil IC50 of GC cell lines. Multivariate Cox regression analyses showed that the gene signature was an independent prognostic factor for predicting GC patients' OS, DFS, and susceptibility to adjuvant chemotherapy. CONCLUSIONS: Our SERM prognostic signature is of great value for OS, DFS, and drug sensitivity prediction in GC, which may give guidance to the development of targeted therapy for CSC- and EMT-related gene in the future.