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Abstract Nucleotide-binding oligomerization domain 2 (NOD2) is an immune sensor crucial for eliciting the innate immune responses. Nevertheless, discrepancies exist regarding the effect of NOD2 on different types of cancer. This study aimed to investigate these function of NOD2 in melanoma and its underlying mechanisms. We have validated the tumor suppressor effect of NOD2 in melanoma. NOD2 inhibited the proliferation of melanoma cells, hindering their migration and invasion while promoting the onset of apoptosis. Our study showed that NOD2 expression is closely related to pyrimidine and folate metabolism. NOD2 inhibits thymidylate synthase (TYMS) expression by promoting K48-type ubiquitination modification of TYMS, thereby decreasing the resistance of melanoma cells to 5-fluorouracil (5-FU) and capecitabine (CAP). TYMS was identified to form a complex with Polo-like Kinase 1 (PLK1) and activate the PLK1 signaling pathway. Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.

Abstract The host limits Mycobacterium tuberculosis (Mtb) by enriching copper in high concentrations. This research investigates how Mtb escapes copper stress. The membrane protein encoded by Mtb Rv0102, when its homolog in M. smegmatis (MSMEG_4702) was knocked out, resulted in a fourfold decrease in intracellular copper levels and enhanced tolerance to elevated extracellular copper concentrations. Similarly, knockout mutants of its homolog in M. marinum (MMAR_0267) showed increased virulence in zebrafish and higher bacterial load within macrophages. In THP-1 cells infected with MMAR_0267 deletion mutants, the intracellular survival of these mutants increased, along with reduced THP-1 cell apoptosis. Deficiency in copper down-regulated the transcriptional level of the virulence factor CFP-10 in M. marinum, suppressed cytosolic signaling via the macrophage STING pathway, leading to decreased production of IFN-β and reduced cell apoptosis. In conclusion, these findings highlight the significant impact of copper on the survival and reproduction of mycobacteria, underscoring the importance of studying mycobacterial adaptation mechanisms in copper-rich environments.

Abstract Background and aim Appendiceal adenocarcinoma, an exceedingly rare malignancy, sparks debate on the optimal surgical approach—appendectomy or right hemicolectomy—for early-stage cases. This study aims to investigate the impact of these two surgical methods on the survival prognosis of patients with early appendiceal adenocarcinoma. Method Utilizing a multicenter medical database, we gathered data from 168 patients diagnosed with T1 stage appendiceal adenocarcinoma admitted between January 2008 and January 2015. This study aims to compare the impact of different treatment modalities on the prognosis of appendiceal adenocarcinoma in these two groups. Result In patients diagnosed with T1 appendiceal adenocarcinoma, the survival prognosis was not significantly improved with right hemicolectomy compared to appendectomy. Out of one hundred twenty-seven patients undergoing right colon resection, only three exhibited lymphatic metastasis, resulting in a rate of 2.3%. Conclusion Simple appendectomy can fulfill the objective of achieving radical tumor resection, rendering right hemicolectomy unnecessary.

AbstractAlthough the gut microbial metabolites exhibit potential effects on coronary heart disease (CHD), the underlying mechanism remains unclear. In this study, the active gut microbial metabolites acting on CHD and their potential mechanisms of action were explored through a network pharmacological approach. We collected a total of 208 metabolites from the gutMgene database and 726 overlapping targets from the similarity ensemble approach (SEA) and SwissTargetPrediction (STP) database, and ultimately identified 610 targets relevant to CHD. In conjunction with the gutMGene database, we identified 12 key targets. The targets of exogenous substances were removed, and 10 core targets involved in CHD were eventually retained. The microbiota–metabolites–targets–signalling pathways network analysis revealed that C-type lectin receptor signalling pathway, Lachnospiraceae, Escherichia, mitogen-activated protein kinase 1, prostaglandin-endoperoxidase synthase 2, phenylacetylglutamine and alcoholic acid are notable components of CHD and play important roles in the development of CHD. The results of molecular docking experiments demonstrated that AKT1-glycocholic acid and PTGS2-phenylacetylglutamine complexes may act on C-type lectin receptor signalling pathways. In this study, the key substances and potential mechanisms of gut microbial metabolites were analysed via network pharmacological methods, and a scientific basis and comprehensive idea were provided for the effects of gut microbial metabolites on CHD.

Abstract The pathogenesis of Alzheimer's disease (AD) remains unclear, but revealing individual differences in functional connectivity (FC) may provide insights and improve diagnostic precision. A hierarchical clustering-based autoencoder with functional connectivity was proposed to categorize 82 AD patients from the Alzheimer's Disease Neuroimaging Initiative. Compared to directly performing clustering, using an autoencoder to reduce the dimensionality of the matrix can effectively eliminate noise and redundant information in the data, extract key features, and optimize clustering performance. Subsequently, subtype differences in clinical and graph theoretical metrics were assessed. Results indicate a significant inter-subject heterogeneity in the degree of FC disruption among AD patients. We have identified two neurophysiological subtypes: subtype I exhibits widespread functional impairment across the entire brain, while subtype II shows mild impairment in the Limbic System region. What is worth noting is that we also observed significant differences between subtypes in terms of neurocognitive assessment scores associations with network functionality, and graph theory metrics. Our method can accurately identify different functional disruptions in subtypes of AD, facilitating personalized treatment and early diagnosis, ultimately improving patient outcomes.

Abstract A protocol for trans-hydroboration of indole derivatives using heterogeneous photocatalysis with NHC-borane has been developed, addressing a persistent challenge in organic synthesis. The protocol, leveraging high crystalline vacancy-engineered polymeric carbon nitride as a catalyst, enables diastereoselective synthesis, expanding substrate scope and complementing existing methods. The approach emphasizes eco-friendliness, cost-effectiveness, and scalability, making it suitable for industrial applications, particularly in renewable energy contexts. The catalyst’s superior performance, attributed to its rich carbon-vacancies and well-ordered structure, surpasses more expensive homogeneous alternatives, enhancing viability for large-scale use. This innovation holds promise for synthesizing bioactive compounds and materials relevant to medicinal chemistry and beyond.

To date, despite extensive research, the prognosis of advanced osteosarcoma has not improved significantly. Thus, patients experience a reduced survival rate, suggesting that a reevaluation of current treatment strategies is required. Recently, in addition to routine surgery, chemotherapy and radiotherapy, researchers have explored more effective and safer treatments, including targeted therapy, immunotherapy, anti-angiogenesis therapy, metabolic targets therapy, and nanomedicine therapy. The tumorigenesis and development of osteosarcoma is closely related to angiogenesis. Thus, anti-angiogenesis therapy is crucial to treat osteosarcoma; however, recent clinical trials found that it has insufficient efficacy. To solve this problem, the causes of treatment failure and improve treatment strategies should be investigated. This review focuses on summarizing the pathophysiological mechanisms of angiogenesis in osteosarcoma and recent advances in anti-angiogenesis treatment of osteosarcoma. We also discuss some clinical studies, with the aim of providing new ideas to improve treatment strategies for osteosarcoma and the prognosis of patients.

BackgroundThe development of internet technology has greatly increased the ability of patients with chronic obstructive pulmonary disease (COPD) to obtain health information, giving patients more initiative in the patient-physician decision-making process. However, concerns about the quality of website health information will affect the enthusiasm of patients’ website search behavior. Therefore, it is necessary to evaluate the current situation of Chinese internet information on COPD. ObjectiveThis study aims to evaluate the quality of COPD treatment information on the Chinese internet. MethodsUsing the standard disease name “慢性阻塞性肺疾病” (“chronic obstructive pulmonary disease” in Chinese) and the commonly used public search terms “慢阻肺” (“COPD”) and “肺气肿” (“emphysema”) combined with the keyword “治疗” (“treatment”), we searched the PC client web page of Baidu, Sogou, and 360 search engines and screened the first 50 links of the website from July to August 2021. The language was restricted to Chinese for all the websites. The DISCERN tool was used to evaluate the websites. ResultsA total of 96 websites were included and analyzed. The mean overall DISCERN score for all websites was 30.4 (SD 10.3; range 17.3-58.7; low quality), no website reached the maximum DISCERN score of 75, and the mean score for each item was 2.0 (SD 0.7; range 1.2-3.9). There were significant differences in mean DISCERN scores between terms, with “chronic obstructive pulmonary disease” having the highest mean score. ConclusionsThe quality of COPD information on the Chinese internet is poor, which is mainly reflected in the low reliability and relevance of COPD treatment information, which can easily lead consumers to make inappropriate treatment choices. The term “chronic obstructive pulmonary disease” has the highest DISCERN score among commonly used disease search terms. It is recommended that consumers use standard disease names when searching for website information, as the information obtained is relatively reliable.

Abstract Lithium-ion batteries (LIBs) and plastics are pivotal components of modern society; nevertheless, their escalating production poses formidable challenges to resource sustainability and ecosystem integrity. Here, we showcase the transformation of spent lithium cobalt oxide (LCO) cathodes into photothermal catalysts capable of catalyzing the upcycling of diverse waste polyesters into high-value monomers. The distinctive Li deficiency in spent LCO induces a contraction in the Co−O6 unit cell, boosting the monomer yield exceeding that of pristine LCO by a factor of 10.24. A comprehensive life-cycle assessment underscores the economic viability of utilizing spent LCO as a photothermal catalyst, yielding returns of 129.6 $·kgLCO −1, surpassing traditional battery recycling returns (13–17 $·kgLCO −1). Solar-driven recycling 100,000 tons of PET can reduce 3.459 × 1011 kJ of electric energy and decrease 38,716 tons of greenhouse gas emissions. This work unveils a sustainable solution for the management of spent LIBs and plastics.

In the present work, cast iron was used as the carbon source to fabricate WC particle gradient-reinforced W–Cu composites. The results revealed that the surface layer of W–Cu composites after carbonization can be divided into a complete carbonization zone and core-shell structure transition zone, the thickness of the carbonized layer increased gradually with the extension of treatment time. In addition to the W phase and Cu phase, WC and Fe3W3C phases are formed in the surface layer. The hardness and compressive strength of the surface layer show a trend of first increasing and then decreasing, and the arc erosion resistance of the surface layer gradually improves with the treatment time extending. The C atoms diffusion relationship between carbonization layer thickness (D), sintering temperature (T), and treatment time (t) of W–Cu composites with cast iron can be fitted as follows: D=1.9287×1013texp(‐929231RT).

Abstract Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China.

BackgroundThere is a link between cardiovascular diseases and intestinal permeability, but it is not clear. This review aimed to elucidate intestinal permeability in cardiovascular diseases by meta-analysis.MethodsMultidisciplinary electronic databases were searched from the database creation to April 2023. All included studies were assessed for risk of bias according to the Joanna Briggs Institute Critical Appraisal Checklist. The heterogeneity of each study was estimated using the I2 statistic, and the data were analyzed using Review Manager 5.3 and Stata 16.0.ResultsIn total, studies in 13 pieces of literature were included in the quantitative meta-analysis. These studies were conducted among 1,321 subjects mostly older than 48. Patients had higher levels of intestinal permeability markers (lipopolysaccharide, d-lactate, zonulin, serum diamine oxidase, lipopolysaccharide-binding protein, intestinal fatty acid binding protein, and melibiose/rhamnose) than controls (standard mean difference SMD = 1.50; 95% CI = 1.31–1.88; p

Background Osteosarcoma is the most common primary malignant bone tumor, but its pathogenesis remains unclear. Ubiquitin-specific processing peptidase 22 (USP22) is reported to be highly expressed and associated with tumor malignancy and prognosis in cancers. However, the role and mechanism of USP22 in osteosarcoma is not fully understood. This study aims to investigate the function and potential mechanism of USP22 in osteosarcoma using bioinformatics analysis combined with experimental validation. Methods We first integrated transcriptomic datasets and clinical information of osteosarcoma from GEO and TCGA databases to assess the expression and prognostic value of USP22 in osteosarcoma. Then, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify USP22-related co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways of USP22 co-expressed genes. To validate the accuracy of bioinformatics analyses, we downregulated USP22 expression in osteosarcoma cell line Sao-2 using siRNA and assessed its effect on cell proliferation, migration, invasion, apoptosis, and regulation of key signaling pathways. Results We found that USP22 was highly expressed in osteosarcoma tissues and correlated with poor prognosis in osteosarcoma patients. USP22 also showed potential as a diagnostic marker for osteosarcoma. In addition, 344 USP22-related co-expressed genes were identified, mainly involved in signaling pathways such as glycolysis, oxidative phosphorylation, spliceosome, thermogenesis, and cell cycle. The in vitro experiments confirmed the accuracy and reliability of bioinformatics analyses. We found that downregulation of USP22 could inhibit Sao-2 cell proliferation, migration, invasion, and induce apoptosis. Furthermore, downregulation of USP22 significantly reduced aerobic glycolysis levels in Sao-2 cells and inhibited the expression of key enzymes and transporters in aerobic glycolysis pathways such as HK2, PKM2, and GLUT1. Conclusions USP22 plays a critical role in the occurrence, development, and prognosis of osteosarcoma. USP22 could influence Sao-2 cell proliferation, apoptosis, migration, and invasion by regulating the glycolysis pathway, thereby promoting osteosarcoma progression. Therefore, USP22 may be a potential therapeutic target for the treatment of osteosarcoma.

In this study, lemon peel residue powders were modified by microwave, high-speed shear and ultra-fine grinding, respectively, to improve its quality and the comprehensive utilization rate of lemon processing by-products. The morphological structure and thermal stability before and after modification were characterized by scanning electron microscopy, Fourier infrared spectroscopy and thermogravimetric analysis. The physicochemical and functional properties were measured to evaluate the overall quality of the lemon peel residue powders after different modifications. The results showed that the structure of lemon peel residue powders was loosened after these three modifications and the main functional groups were not significantly changed after the modification. The thermal stability of lemon peel residue powders was significantly improved after microwave and high-speed shear modification (P

Abstract Background Chinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015–2017 that covered all 31 mainland Chinese provinces. Methods A total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000—500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500–100 m) and B (

Abstract Developing in situ/operando spectroscopic techniques with high sensitivity and reproducibility is of great importance for mechanistic investigations of surface-mediated electrochemical reactions. Herein, we report the fabrication of highly ordered rhombic gold nanocube superlattices (GNSs) as substrates for surface-enhanced infrared absorption spectroscopy (SEIRAS) with significantly enhanced SEIRA effect, which can be controlled by manipulating the randomness of GNSs. Finite difference time domain simulations reveal that the electromagnetic effect accounts for the significantly improved spectroscopic vibrations on the GNSs. In situ SEIRAS results show that the vibrations of CO on the Cu2O surfaces have been enhanced by 2.4 ± 0.5 and 18.0 ± 1.3 times using GNSs as substrates compared to those on traditional chemically deposited gold films in acidic and neutral electrolytes, respectively. Combined with isotopic labeling experiments, the reaction mechanisms for C-C coupling of CO electroreduction on Cu-based catalysts are revealed using the GNSs substrates.

Mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer’s disease (AD), with a high risk of converting to AD. We propose a classification framework with a data augment method to identify MCI converter (MCI-C) and MCI non-converter (MCI-NC). Resting-state functional magnetic resonance images (rs-fMRI) from Alzheimer’s Disease Neuroimaging Initiative (ADNI) are processed as augmented resting-state functional connectivity by staggered sliding window (SSW) method proposed by us under Human Connectome Project (HCP) multi-modal parcellation. The HCP brain atlas provides a more detailed cortical parcellation of the brain, allowing for more precise localization of brain regions related to MCI and AD. Finally, the framework archive 88% accuracy in the task of identifying MCI-C. 46 brain regions are suggested as potential MCI-to-AD biomarkers.

Abstract Understanding the structure-stability relationship of catalysts is imperative for the development of high-performance electrocatalytic devices. Herein, we utilize operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) to quantitatively monitor the evolution of Cu single-atom catalysts (SACs) during the electrochemical reduction of CO2 (CO2RR). Cu SACs are converted into 2-nm Cu nanoparticles through a reconstruction process during CO2RR. The evolution rate of Cu SACs is highly dependent on the substrates of the catalysts due to the coordination difference. Density functional theory calculations demonstrate that the stability of Cu SACs is highly dependent on their formation energy, which can be manipulated by controlling the affinity between Cu sites and substrates. This work highlights the use of operando ATR-SEIRAS to achieve mechanistic understanding of structure-stability relationship for long-term applications.

Returning livestock manure to the cropland as organic fertilizer is a sustainable and environmentally friendly treatment method, but its application also alters the soil microenvironment. However, the impact of soil microbial community disturbance and pollutant accumulation from different types of organic fertilizers remains largely unknown in South China. To fill this gap, we investigated the effects of organic fertilizers, including chicken manure, pig manure and vermicompost on the soil bacterial and fungal communities and environmental risks. The results show that applying organic fertilizer effectively increases the soil nutrient content. High-throughput sequencing of bacteria and fungi showed that the application of different organic fertilizers had differential effects on microbial community structure, with the highest number of microbe-specific OTUs in the vermicomposting treatment. Additionally, this study found no risk of heavy metal (Cu, Zn, Pb, Cr and Cd) contamination from short-term organic fertilizer application, but there was a risk of antibiotic (ENR and CHL) contamination. Functional microorganisms regulating heavy metals and antibiotics were identified by RDA analysis. This study facilitates the screening of types of organic fertilizers that can be safely returned to the field as well as developing strategies to regulate functional microbes.

As a well-known classical Chinese medicine prescription, Shengxian Decoction (SXD) has been applied for a century to treat cardiovascular diseases, especially coronary heart disease (CHD), but the potentially effective compounds and underlying mechanisms remain unclear. With ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology analysis, the potential effective compounds of SXD and their pharmacological mechanisms against CHD were identified and revealed. 57 effective compounds with favorable pharmacokinetic characteristics and biological activities were screened through UPLC-Q-TOF/MS analysis, database and literature mining, interacting with 96 CHD-related targets to support potential synergistic therapeutic actions. Systematic analysis of the PPI network and microarray data further revealed six core targets, including TNF, IL-1β, IL-6, TP53, VEGFA and PTGS2, which were mainly involved in fluid shear stress and atherosclerosis, lipid and atherosclerosis, PI3K-Akt signaling pathway et al. Moreover, the proposed contribution indexes of effective compounds indicated these compounds, including isoferulic acid, quercetin, calycosin, ferulic acid, kaempferol, calycosin 7-O-glycoside, formononetin, astragaloside IV and saikosaponin D, as the core compounds of SXD. The molecular docking results confirmed that those core compound-target pairs exhibited strong binding energy. Furthermore, we validated that SXD significantly alleviated myocardial tissue injury in CHD rats and reversed H/R-induced decreases in H9c2 cell viability by attenuating the production of TNF, IL-6 and IL-1β, and reducing cardiomyocyte apoptosis via down-regulating the TP53, caspase3 and cytochrome C mRNA expression levels as well as caspase3, caspase9 and cytochrome C protein expression levels according to RT-qPCR and Western blot results. Our findings explained the pharmacological mechanisms underlying the effectiveness of SXD in the treatment of CHD, and laid a foundation for future basic and clinical research of SXD.

Summary: Both therapeutic hypothermia and neural stem cells (NSCs) transplantation have shown promise in neuroprotection and neural repair after brain injury. However, the effects of therapeutic hypothermia on neuronal differentiation of NSCs are not elucidated. In this study, we aimed to investigate whether mild hypothermia promoted neuronal differentiation in cultured and transplanted human NSCs (hNSCs). A significant increase in neuronal differentiation rate of hNSCs was found when exposed to 35°C, from 33% to 45% in vitro and from 7% to 15% in vivo. Additionally, single-cell RNA sequencing identified upregulation of RNA-binding motif protein 3 (RBM3) in neuroblast at 35°C, which stabilized the SRY-box transcription factor 11 (SOX11) mRNA and increased its protein expression, leading to an increase in neuronal differentiation of hNSCs. In conclusion, our study highlights that mild hypothermia at 35°C enhances hNSCs-induced neurogenesis through the novel RBM3-SOX11 signaling pathway, and provides a potential treatment strategy in brain disorders.

BackgroundWith the rapid development of technology, artificial intelligence (AI) has been widely used in the diagnosis and prognosis prediction of a variety of diseases, including cardiovascular disease. Facts have proved that AI has broad application prospects in rapid and accurate diagnosis.ObjectiveThis study mainly summarizes the research on the application of AI in the field of cardiovascular disease through bibliometric analysis and explores possible future research hotpots.MethodsThe articles and reviews regarding application of AI in cardiovascular disease between 2000 and 2023 were selected from Web of Science Core Collection on 30 December 2023. Microsoft Excel 2019 was applied to analyze the targeted variables. VOSviewer (version 1.6.16), Citespace (version 6.2.R2), and a widely used online bibliometric platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references, and keywords in this field.ResultsA total of 4,611 articles were selected in this study. AI-related research on cardiovascular disease increased exponentially in recent years, of which the USA was the most productive country with 1,360 publications, and had close cooperation with many countries. The most productive institutions and researchers were the Cedar sinai medical center and Acharya, Ur. However, the cooperation among most institutions or researchers was not close even if the high research outputs. Circulation is the journal with the largest number of publications in this field. The most important keywords are “classification”, “diagnosis”, and “risk”. Meanwhile, the current research hotpots were “late gadolinium enhancement” and “carotid ultrasound”.ConclusionsAI has broad application prospects in cardiovascular disease, and a growing number of scholars are devoted to AI-related research on cardiovascular disease. Cardiovascular imaging techniques and the selection of appropriate algorithms represent the most extensively studied areas, and a considerable boost in these areas is predicted in the coming years.

Abstract In this work, via engineering the conformation of cobalt active center in cobalt phthalocyanine molecular catalyst, the catalytic efficiency of electrochemical carbon monoxide reduction to methanol can be dramatically tuned. Based on a collection of experimental investigations and density functional theory calculations, it reveals that the electron rearrangement of the Co 3d orbitals of cobalt phthalocyanine from the low-spin state (S = 1/2) to the high-spin state (S = 3/2), induced by molecular conformation change, is responsible for the greatly enhanced CO reduction reaction performance. Operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy measurements disclose accelerated hydrogenation of CORR intermediates, and kinetic isotope effect validates expedited proton-feeding rate over cobalt phthalocyanine with high-spin state. Further natural population analysis and density functional theory calculations demonstrate that the high spin Co2+ can enhance the electron backdonation via the d xz /d yz −2π* bond and weaken the C-O bonding in *CO, promoting hydrogenation of CORR intermediates.

Abstract Introduction To observe the clinical efficacy of ultrasound-guided stellate ganglion block (SGB) + extracorporeal shock wave therapy (ESWT) for limb spasticity in patients with ischemic stroke. Methods A total of 60 patients with post-stroke limb spasticity in our hospital were selected and randomly divided into four groups (n = 15). In the control group, patients received routine rehabilitation training. Based on routine rehabilitation training, SGB group patients underwent ultrasound-guided SGB, ESWT group patients received ESWT, and SGB + ESWT group patients received ultrasound-guided SGB combined with ESWT. The total treatment course was one month. The Modified Barthel Index (MBI) score, Fugl-Meyer Assessment and upper limb rehabilitation training system were applied to evaluate the activities of daily living, upper limb motor function and upper limb performance before and after treatment. Finally, the improvement after treatment was compared among different groups. Results After treatment, compared with the control group, the MBI score and the upper limb score based on Fugl-Meyer Assessment in the SGB, ESWT, and SGB + ESWT groups were significantly increased (P 0.05). In terms of upper limb performance ability, patients in the SGB, ESWT and SGB + ESWT groups had better fitting degree, participation and exertion of exercise than those in the control group, and the SGB + ESWT group patients had the same movement trajectory as robots. Conclusion Ultrasound-guided SGB and ESWT can reduce the muscle tension of patients, alleviate spasticity, promote the motor function of the upper limb, and improve the working performance of patients. However, the effect of SGB combined with ESWT is better.

Aiming at the problem of long slopes and weak power grids along the railway in high altitude mountainous areas, an optimization method of power supply mode and access to external power grid of CZ railway traction station is proposed. First, combined with the terrain and altitude along the railway and the characteristics of the regional power grid, a sample library of the power supply mode and access to external power grid of CZ railway traction station is designed. Secondly, combined with the train operation diagram and line ramp parameters, the full-day periodic load of each power supply arm is simulated. Then, according to the sample library, a “source-net-load” integrated simulation model is constructed in Simulink. Then, the three-phase voltage unbalance evaluation model of the power system is constructed in combination with relevant standards. Finally, the optimal wiring scheme is selected by using the evaluation model and the simulated voltage unbalance index.

Abstract The progression of urothelial bladder cancer (UC) is a complicated multi-step process. We perform a comprehensive multi-omics analysis of 448 samples from 190 UC patients, covering the whole spectrum of disease stages and grades. Proteogenomic integration analysis indicates the mutations of HRAS regulated mTOR signaling to form urothelial papilloma rather than papillary urothelial cancer (PUC). DNA damage is a key signaling pathway in the progression of carcinoma in situ (CIS) and related to APOBEC signature. Glucolipid metabolism increase and lower immune cell infiltration are associated with PUC compared to CIS. Proteomic analysis distinguishes the origins of invasive tumors (PUC-derived and CIS-derived), related to distinct clinical prognosis and molecular features. Additionally, loss of RBPMS, associated with CIS-derived tumors, is validated to increase the activity of AP-1 and promote metastasis. This study reveals the characteristics of two distinct branches (PUC and CIS) of UC progression and may eventually benefit clinical practice.

Abstract Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics and are well-known to undergo several different PTMs. Here, we show that cofilin-1 is conjugated by SUMO1 both in vitro and in vivo. Using mass spectrometry and biochemical and genetic approaches, we identify the N-terminal α-amino group as the SUMO-conjugation site of cofilin-1. Common to conventional SUMOylation is that the N-α-SUMOylation of cofilin-1 is also mediated by SUMO activating (E1), conjugating (E2), and ligating (E3) enzymes and reversed by the SUMO deconjugating enzyme, SENP1. Specific to the N-α-SUMOylation is the physical association of the E1 enzyme to the substrate, cofilin-1. Using F-actin co-sedimentation and actin depolymerization assays in vitro and fluorescence staining of actin filaments in cells, we show that the N-α-SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization. This covalent conjugation by SUMO at the N-α amino group of cofilin-1, rather than at an internal lysine(s), serves as an essential PTM to tune cofilin-1 function during regulation of actin dynamics.

Background and aimStandardized approach to postoperative adjuvant therapy for hepatocellular carcinoma (HCC) remains elusive. This study endeavors to examine the effects of postoperative PD-1 adjuvant therapy on the short-term and long-term prognosis of patients at a heightened risk of post-surgical recurrence.MethodsThe data of HCC patients who underwent hepatectomy at our center from June 2018 to March 2023 were collected from the hospital database. Propensity score matching (PSM) was employed to perform a 1:1 match between the postoperative anti-PD-1 antibody group and the postoperative non-anti-PD-1 antibody group. Kaplan-Meier method was utilized to compare the overall survival (OS) and recurrence-free survival (RFS) between the two groups. Cox regression analysis was conducted to identify the prognostic factors affecting patient outcomes. Subgroup analyses were performed for different high-risk factors.ResultsAmong the 446 patients included in the study, 122 patients received adjuvant therapy with postoperative anti-PD-1 antibodies. After PSM, the PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year OS rates of 93.1%, 86.8%, 78.2%, and 51.1%, respectively, while the non-PD-1 group had rates of 85.3%, 70.2%, 47.7%, and 30.0%. The PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year RFS rates of 81.7%, 77.0%, 52.3%, and 23.1%, respectively, whereas the non-PD-1 group had rates of 68.4%, 47.7%, and 25.8% in 1-year, 2-year, 3-year. A multifactorial Cox regression analysis revealed that postoperative PD-1 use was a prognostic protective factor associated with OS and RFS. Subgroup analysis results indicated that HCC patients with high recurrence risks significantly benefited from postoperative anti-PD-1 antibody treatment in terms of OS and RFS.ConclusionFor HCC patients with high-risk recurrence factors and undergoing hepatectomy, postoperative adjuvant therapy with anti-PD-1 antibodies can effectively improve their survival prognosis.

Abstract Background Limited data suggest that chronic obstructive pulmonary disease (COPD) patients have pathologic elevated epicardial adipose tissue (EAT), which is splanchnic fat tissue with anti-inflammatory properties and regulating free fatty acids functions. Therefore, there is a need for meta-analysis to explore the relationship between EAT and COPD. Methods Online databases were systematically searched for studies about EAT in COPD patients published up to October 5th, 2022. The EAT data of the COPD patient group and the control group were included. Trial sequential analysis (TSA) and meta-analysis were applied to assess the difference in EAT between patients with and without COPD. TSA software and Stata 12.0 were used in all statistical analyses. Results The final analysis included 5 studies (n = 596 patients). COPD patients had significantly more EAT than control subjects (SMD: 0.0.802; 95% CI: 0.231, 1.372; P = 0.006; TSA-adjusted 95% CI 1.20, 1.80; P

Abstract Background CEA and systemic inflammation were reported to correlate with proliferation, invasion, and metastasis of colorectal cancer. This study investigated the prognostic significance of the preoperative CEA and systemic inflammation response index (C-SIRI) in patients with resectable colorectal cancer. Methods Two hundred seventeen CRC patients were recruited from Chongqing Medical University, the first affiliated hospital, between January 2015 and December 2017. Baseline characteristics, preoperative CEA level, and peripheral monocyte, neutrophil, and lymphocyte counts were retrospectively reviewed. The optimal cutoff value for SIRI was defined as 1.1, and for CEA, the best cutoff values were 4.1 ng/l and 13.0 ng/l. Patients with low levels of CEA (

In order to reduce the sintering temperature of the Mo–Cu composites, solution combustion synthesis was used to fabricate ultrafine Mo–Cu composite powders, in which Mo and Cu mixed uniformly. Firstly, solution combustion synthesis was conducted to prepared molybdenum and copper oxides composite powders. However, the residual carbon in the as-synthesized precursors requires additional calcination in nitrogen atmosphere during the reduction process to obtain pure Mo–Cu composite powders. Then the Mo–Cu composites were fabricated by liquid phase sintering at low temperatures of 1050–1180 °C using the Mo–Cu composite powders. The Mo–20Cu and Mo–30Cu composites can reach a relative density of >95% after sintering at a low temperature of 1100 °C, which may be attributed to both the small particle size of Mo and the high uniformity of Mo and Cu distribution.

Background. The long-term exposure to ultraviolet radiation (UVR) raises oxidative stress and chronic inflammation levels, which in turn has a series of deleterious effects on skin health, such as sunburn, photoaging, and skin cancer. Hence, our study was determined to investigate the effects and mechanisms of epigallocatechin gallate (EGCG) in zebrafish and human skin fibroblasts (HSF) cells to alleviate ultraviolet-induced photoaging. Methods. The 4 days postfertilization (dpf) zebrafish larvae and HSF cells were treated with 10 J/cm2 UVA + 30 mJ/cm2 UVB, or 25, or 50 μM EGCG for 72 hr. The indicators involving in oxidative stress, inflammatory, and photoaging were measured by the kits, ELISA Kits and western blot methods. Results. EGCGs protect against UVR-induced skin damage in zebrafish and HSF cells. EGCG markedly decreased the reactive oxygen species (ROS), malondialdehyde, 8-OHdG levels, increased superoxide dismutase (SOD) activity, and significantly inhibited inflammatory factors levels including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), interleukin-6 (IL-6) in zebrafish, and HSF cells irradiated with UVR. We found that EGCG could reduce UVR-induced p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation and effectively inhibited the activity of the transcriptional factor nuclear factor-κB (NF-κB), thereby reducing the protein-1 (AP-1), TNF-α, IL-1α, IL-6, and matrix metalloproteinase-1 (MMP-1) expressions, which are critical mediators of skin aging cascade causing the photoaging. Conclusion. These results validate that EGCG for protection of photoaging in zebrafish and HSF cells induced by UVR, which is closely related to the regulation of p38 MAPK/NF-κB, AP-1 signaling pathway which relieve oxidative stress, inflammation, and collagen degradation.

ABSTRACTThe adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Summary: TRPA1 is pivotal in cold hypersensitivity, but its regulatory mechanisms in inflammatory cold hyperalgesia remain poorly understood. We show here that the upregulation of SUMO1-conjugated protein levels in a complete Freund’s adjuvant (CFA)-induced inflammatory pain model enhances TRPA1 mRNA stability, ultimately leading to increased expression levels. We further demonstrate that hnRNPA1 binds to TRPA1 mRNA, and its SUMOylation, upregulated in CFA-induced inflammatory pain, contributes to stabilizing TRPA1 mRNA by accumulating hnRNPA1 in the cytoplasm. Moreover, we find that wild-type hnRNPA1 viral infection in dorsal root ganglia neurons, and not infection with the SUMOylation-deficient hnRNPA1 mutant, can rescue the reduced ability of hnRNPA1-knockdown mice to develop inflammatory cold pain hypersensitivity. These results suggest that hnRNPA1 is a regulator of TRPA1 mRNA stability, the capability of which is enhanced upon SUMO1 conjugation at lysine 3 in response to peripheral inflammation, and the increased expression of TRPA1 in turn underlies the development of chronic inflammatory cold pain hypersensitivity.

BackgroundColorectal cancer (CRC) remains a major global health concern, with significant morbidity and mortality rates. In this study, we aimed to develop a comprehensive blood indicator based on systemic inflammation and nutritional condition to predict the prognosis of resectable CRC patients.MethodsA retrospective cohort of 210 CRC patients who underwent radical resection at the First Affiliated Hospital of Chongqing Medical University, China, between January 2015 and December 2017, was included in the analysis. Baseline characteristics, preoperative blood markers, including neutrophil count, monocyte count, lymphocyte count, platelets, albumin, and CEA were retrospectively reviewed. Various blood indicators, such as NLR, PLR, MLR, SIRI and OPNI were calculated. The least absolute shrinkage and selection operator (LASSO) method was employed to select indicators to establish a novel comprehensive biomarker (named PSI). Kaplan-Meier survival curves and log-rank tests were used to evaluate the prognostic impact of preoperative OPNI, SIRI, and PSI. Univariate and multivariate Cox regression model were conducted to identify independent prognostic factors for CRC. The receiver operating characteristic (ROC) method assessed the predictive ability of PSI, stage, OPNI, and SIRI.ResultsPatients with higher preoperative OPNI and lower SIRI values had significantly better overall survival (OS). PSI was identified as an independent prognostic factor for OS in both univariate and multivariate analysis. Patients with medium (28.3-43.4) and high (>43.4) PSI scores exhibited superior OS compared to those with low (≤ 28.3) PSI scores. PSI showed higher predictive ability (AUC: 0.734) than individual indicators alone (OPNI: 0.721, SIRI: 0.645, stage: 0.635).ConclusionThe novel indicator, PSI, based on preoperative SIRI and OPNI, demonstrated significant prognostic value for resectable CRC patients. PSI outperformed individual indicators and could serve as a reliable tool for prognostic evaluation in CRC patients.

Cardiovascular disease (CVD) has no socioeconomic, topographical, or sex limitations as reported by the World Health Organization (WHO). The significant drivers of CVD are cardio-metabolic, behavioral, environmental, and social risk factors. However, some significant risk factors for CVD (e.g., a pitiable diet, tobacco smoking, and a lack of physical activities), have also been linked to an elevated risk of cardiovascular disease. Lifestyles and environmental factors are known key variables in cardiovascular disease. The familiarity with smoke goes along with the contact with the environment: air pollution is considered a source of toxins that contribute to the CVD burden. The incidence of myocardial infarction increases in males and females and may lead to fatal coronary artery disease, as confirmed by epidemiological studies. Lipid modification, inflammation, and vasomotor dysfunction are integral components of atherosclerosis development and advancement. These aspects are essential for the identification of atherosclerosis in clinical investigations. This article aims to show the findings on the influence of CVD on the health of individuals and human populations, as well as possible pathology and their involvement in smoking-related cardiovascular diseases. This review also explains lifestyle and environmental factors that are known to contribute to CVD, with indications suggesting an affiliation between cigarette smoking, air pollution, and CVD.

Ethnopharmacological relevance: Pinellia ternata (Thunb.) Breit. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. It's drawing worldwide interests in medicinal applications owing such as anti-diarrhea, lipid-lowering, anti-tumor, anti-cough, expectorant, anti-gastric ulcer, etc. Aim of the study: This review aims to provide useful information on the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Pinellia ternata to help increase its efficiency. In addition, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Data was obtained through a systematic search of published literature and online databases such as Google Scholar, Web of Science, PubMed, Science Direct, and Sci-Finder. The botanical names were confirmed using the World Flora Online and chemical structures were drawn using the ChemBio Draw Ultra Version 19.0 Software. Results: Pinellia ternata is distributed in regions of China and other areas. Pinellia ternata and its compound preparations can be used for cough, vomiting, gastric ulcer and other diseases. Approximately 212 chemical constituents have been isolated from Pinellia ternata, including alkaloids, volatile oils, amino acids, organic acids, flavonoids, cerebrosides, phenylpropanoids and other compounds. Considerable pharmacological experiments in vitro and in vivo have demonstrated that Pinellia ternata possessed antitumor effect, antitussive effects, antiasthmatic effects, increasing resistance to gastric ulcer, and antidiarrheal effect. However, these extracts can also lead to various toxicities such as irritant toxicity, cardiotoxicity, hepatotoxicity and embryonic toxicity. Considerable experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Pinellia ternata. Conclusions: Pinellia ternata is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Pinellia ternata. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.

Abstract Objectives Large hepatocellular carcinoma (LHCC) is prone to short‐term recurrence and poor long‐term survival after hepatectomy, and there is still a lack of effective neoadjuvant treatments to improve recurrence‐free survival (RFS) and overall survival (OS). We retrospectively analyzed the efficacy of preoperative transcatheter arterial chemoembolization (TACE) in solitary LHCC (≥5 cm). Materials and Methods A multicenter medical database was used to analyze preoperative TACE's effects on RFS, OS, and perioperative complications in patients with solitary LHCC who received surgical treatment from January 2005 to December 2015. The patients were divided into Group A (5.0–9.9 cm) and Group B (≥10 cm), with 10 cm as the critical value, and the effect of preoperative TACE on RFS, OS and perioperative complications was assessed in each subgroup. Results In the overall population, patients with preoperative TACE had better RFS and OS than those without preoperative TACE. However, after stratifying the patients into the two HCC groups, preoperative TACE only improved the survival outcomes of patients with Group B (≥10 cm). Multivariate Cox‐regression analysis showed that lack of preoperative TACE was an independent risk factor for RFS and OS in the overall population and in Group B but not in Group A. Conclusions Preoperative TACE is beneficial for patients with solitary HCC (≥10 cm).

Duodenal cancer (DC) has complex subtypes and undergoes complicated morphological changes throughout progression, so understanding the molecular basis is crucial. Here, the authors perform a proteogenomics analysis of 156 DCs, revealing molecular subtypes as well as the roles of smoking, AARS1 and PARP1.

The progression of oesophageal squamous cell carcinoma (ESCC) from early to advanced stages requires comprehensive molecular characterisation. Here, the authors perform a proteogenomics analysis of ESCC patient samples across nine histopathological stages and three phases, identifying key alterations and paths for progression.

To avoid the problem of insufficient flexibility of the power grid along the cz railway due to source-load fluctuations, a distributionally robust optimization method considering flexibility is proposed in this paper. Firstly, Wasserstein distance is used to establish the uncertainty set of flexibility demand caused by source-load fluctuation, and a risk-cost model of insufficient flexibility is constructed to couple to the objective function. Combined with the flexibility chance constraint, the flexibility over-limit probability is limited to a certain confidence level in the fuzzy set, and a distributionally robust chance constraint optimization model based on Wasserstein distance is established. Then, the proposed model is transformed into a linear programming problem to be solved by dual theory and inner approximation transformation. Finally, a simulation study of the power grid along the CZ railway is carried out to verify the correctness and effectiveness of the model. The experimental results show that the proposed method can improve the flexibility capacity of the system without sacrificing economy.

Seashore saline soil is a kind of soil formed after the sediments flowing into the sea with surface runoff or shallow sea sediments lifted up by wind and waves, flocculated and deposited in the intertidal zone under the action of tides and ocean currents, and finally exposed to the sea surface as the result of continuously silting up. The seashore saline soil in Guangdong Province is rich in resources, mainly distributed in Zhanjiang, Zhuhai, Jiangmen, Shantou and other places, and has an extremely important strategic position in the coastal economic development. Seashore saline soil is one of the main types of low and medium yielding fields, and the soils are characterized by high salt content and salinization. Due to the high nutrient content, rich soil organic matter and high potential fertility, they can become good fields through appropriate improvement measures. The management strategies of seashore saline soil utilization include isolating seawater from invading farmland again through engineering measures; improving drainage and irrigation conditions, applying rainwater dewatering and desalination technology, using artificial dewatering and desalination technology, planting combined wtih dewatering and desalination technology and other measures to drain and reduce salt. The sustainable utilization of seashore saline soil can be realized through soil improvement, scientific fertilization, root strengthening cultivation, selection of rice varieties resistant to salt or aquatic crop rotation and other technical measures. The seashore saline soil is an important reserve resource for the future development of arable land in Guangdong Province, and the full development and utilization of seashore saline soil is of great significance in increasing the sown area of grain, expanding arable land resources and ensuring food security. Based on the current situation of seashore saline soils in Guangdong, it is proposed to attach great imporntance to the special investigation of eashore saline soil resources, strengthen financial investment, promote scientific research, and establish long-term positioning observation stations for comprehensive management.

Abstract Background The “missing” link of complex and multifaceted interplay among endogenous retroviruses (ERVs) transcription, chronic immuno-inflammation, and the development of psychiatric disorders is still far from being completely clarified. The present study was aimed to investigate the mechanism of protective role of inhibiting ERVs on reversing microglial immuno-inflammation in basolateral amygdala (BLA) in chronic stress-induced negative emotional behaviors in mice. Methods Male C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for 6 w. Negative emotional behaviors were comprehensively investigated to identify the susceptible mice. Microglial morphology, ERVs transcription, intrinsic nucleic acids sensing response, and immuno-inflammation in BLA were assessed. Results Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors, and accompanied with significant microglial morphological activation, murine ERVs genes MuERV-L, MusD, and IAP transcription, cGAS–IFI16–STING pathway activation, NF-κB signaling pathway priming, as well as NLRP3 inflammasome activation in BLA. Antiretroviral therapy, pharmacological inhibition of reverse transcriptases, as well as knocking-down the ERVs transcriptional regulation gene p53 significantly inhibited microglial ERVs transcription and immuno-inflammation in BLA, as well as improved the chronic stress-induced negative emotional behaviors. Conclusions Our results provided an innovative therapeutic approach that targeting ERVs-associated microglial immuno-inflammation may be beneficial to the patients with psychotic disorders.

Recent mechanistic studies have indicated that combinations of radiotherapy (RT) plus immunotherapy (via CSF-1R inhibition) can serve as a strategy to overcome RT resistance and improve the survival of glioma mice. Given the high mortality rate for glioma, including low-grade glioma (LGG) patients, it is of critical importance to investigate the mechanism of the combination of RT and immunotherapy and further translate the mechanism from mouse studies to improve survival of RT-treated human glioma patients. Using the RNA-seq data from a glioma mouse study, 874 differentially expressed genes (DEGs) between the group of RT-treated mice at glioma recurrence and the group of mice with combination treatment (RT plus CSF-1R inhibition) were translated to the human genome to identify significant molecular pathways using the KEGG enrichment analysis. The enrichment analysis yields statistically significant signaling pathways, including the phosphoinositide 3-kinase (PI3K)/AKT pathway, Hippo pathway, and Notch pathway. Within each pathway, a candidate gene set was selected by Cox regression models as genetic biomarkers for resistance to RT and response to the combination of RT plus immunotherapies. Each Cox model is trained using a cohort of 295 RT-treated LGG patients from The Cancer Genome Atlas (TCGA) database and validated using a cohort of 127 RT-treated LGG patients from the Chinese Glioma Genome Atlas (CGGA) database. A four-DEG signature (ITGB8, COL9A3, TGFB2, JAG1) was identified from the significant genes within the three pathways and yielded the area under time-dependent ROC curve AUC = 0.86 for 5-year survival in the validation set, which indicates that the selected DEGs have strong prognostic value and are potential intervention targets for combination therapies. These findings may facilitate future trial designs for developing combination therapies for glioma patients.

In this study, the hydrolysis products of chitin, COS1 and COS2, had degrees of deacetylation of 5.9% and 85.7%, respectively. Notably, 50 mg/(kg·d) COS1 and COS2 significantly increased the levels of immunoglobulins (IgG and IgM), cytokines (IL-6 and IFN-γ), and the antioxidant activities (SOD and CAT) in cyclophosphamide-induced mice, and upregulated the mRNA expression of cytokines in the spleen. COS1 activated the MAPK signaling pathways of related proteins (ERK, p-ERK, JNK, and p-JNK). After COS1 and COS2 intervention, the gut microbial structure of immunosuppressed mice changed, increasing the abundance of key bacteria such as, Dubosiella, Romboutsia, and Turicibacter, and decreasing the abundance of key bacteria such as, Escherichia-Shigella and Helicobacter. Notably, COS1 exhibited a higher immunoregulatory activity than COS2, which may be associated with the acetyl groups in COS1. COS1 can be developed as an immunomodulatory agent in functional foods and medicine to improve immunity.

Summary: Background: Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. Methods: In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. Findings: We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome–related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92–0.98). Interpretation: In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. Funding: National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

Ozone (O3) is an important urban air pollutant having strong correlations with respiratory diseases. Several lines of evidence suggest that O3 exposure causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Inhibitory innate immune receptors, such as NLRP12, have been demonstrated to alleviate inflammation, but the functional role for NLRP12 in O3-induced lung inflammatory inflammation remains to be reported. Here, we determined whether NLRP12 took a protective role in O3-induced AHR and pulmonary inflammation via the suppression of canonical NF-κB. C57BL/6 J mice were exposed to filtered air (FA) or 0.25, 0.50 and 1.00 ppm (3 h/day for 5 consecutive days) followed by detection of airway resistance, white blood cells, total proteins, and cytokines. Meanwhile, NLRP12 in lung tissue were detected by real time PCR. Moreover, we also examined protein expression of NLRP12 and key biomarkers of NF-κB pathway. It was shown that 24 h post O3 exposure, AHR as wells as total cells, proteins, and cytokines contents in BALF of mice were increased compare to those of FA controls in a dose-dependent manner. Notably, O3-induced AHR and lung inflammation were associated with significant decrease in pulmonary NLRP12 and upregulation of phosphorylated IRAK1, p65 and IκBα in canonical NF-κB pathway. Intratracheal administration of NLRP12-overexpresing adenovirus 4 days prior to O3 exposure alleviated AHR and lung inflammation, and inhibited canonical NF-κB pathway activation. The findings from this study indicate that NLRP12 attenuates O3-induced AHR and pulmonary inflammation, possibly through regulating canonical NF-κB pathway. This provides a novel target for the prevention and treatment of lung diseases induced by O3 exposure.

Nitrogen-doped carbon quantum dots (N-CQDs) are nanocomposites that can be synthesized by the hydrothermal method. In this work, N-CQDs with the size of 3.2 ± 1.7 nm was prepared from 1 g citric acid and 2 g urea precursor in 10 mL water. Electrochemiluminescence (ECL) of the prepared N-CQDs with K2S2O8 as a coreactant was found to reach a high ECL efficiency up to 109% relative to that of the Ru(bpy)32+/K2S2O8, coreactant system, revealing their great potential for electroanalysis. It is probably because that N elements were doped well in this N-CQDs and increased presence of surface states per mass of N-CQDs. From the spooling ECL spectroscopy, it can be found that the ECL spectra exhibited both a red shift compared with their photoluminescence (PL) spectrum and a wavelength shift during the potentiodynamic scan in the ECL evolution and devolution processes, due to various emissive excited states of N-CQDs leading to higher ECL efficiency. This work gives an insight into development of high ECL efficiency N-CQDs for bioanalytical and light emitting applications.

Background: Alzheimer’s disease (AD) is an incurable neurodegenerative disease primarily affecting the elderly population. The therapy of AD depends heavily on an early diagnosis. In this study, our primary objective is to evaluate the classification framework, which combines graph theory and machine learning techniques for functional magnetic resonance imaging (fMRI), to distinguish AD, early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and healthy control (HC). Methods: A novel multi-feature selection method, incorporating the dual graph theoretical approach, is proposed for classification. This method utilizes three different feature selection methods after brain areas selection through graph-theory analyses in 96 subjects with brain parcellation by using the joint human connectome project multimodal parcellation (J-HCPMMP) of 180 areas per hemisphere. Results: The classification results show that the optimal features selected by the minimal redundancy maximal relevance (MRMR) based on support vector machine linear (SVM-linear) from graph measures for 36 areas of 360 areas. The classification accuracies for identifying HC vs. EMCI, HC vs. LMCI, HC vs. AD, EMCI vs. LMCI, LMCI vs. AD, and EMCI vs. AD, are 85.60%, 92.90%, 96.80%, 83.30%, 84.90% and 89.50%, respectively. Conclusion: The results indicate that the combination of graph measures and machine learning in fMRI connectivity analysis might be helpful for the diagnosis of AD, especially the use of local measures, which may better reflect functional changes in local brain regions because of cognitive impairment.