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IntroductionLow-grade gliomas (LGG) represent a heterogeneous and complex group of brain tumors. Despite significant progress in understanding and managing these tumors, there are still many challenges that need to be addressed. Glycosylation, a common post-translational modification of proteins, plays a significant role in tumor transformation. Numerous studies have demonstrated a close relationship between glycosylation modifications and tumor progression. However, the biological function of glycosylation-related genes in LGG remains largely unexplored. Their potential roles within the LGG microenvironment are also not well understood.MethodsWe collected RNA-seq data and scRNA-seq data from patients with LGG from TCGA and GEO databases. The glycosylation pathway activity scores of each cluster and each patient were calculated by irGSEA and GSVA algorithms, and the differential genes between the high and low glycosylation pathway activity score groups were identified. Prognostic risk profiles of glycosylation-related genes were constructed using univariate Cox and LASSO regression analyses and validated in the CGGA database.ResultsAn 8 genes risk score signature including ASPM, CHI3L1, LILRA4, MSN, OCIAD2, PTGER4, SERPING1 and TNFRSF12A was constructed based on the analysis of glycosylation-related genes. Patients with LGG were divided into high risk and low risk groups according to the median risk score. Significant differences in immunological characteristics, TIDE scores, drug sensitivity, and immunotherapy response were observed between these groups. Additionally, survival analysis of clinical medication information in the TCGA cohort indicated that high risk and low risk groups have different sensitivities to drug therapy. The risk score characteristics can thus guide clinical medication decisions for LGG patients.ConclusionOur study established glycosylation-related gene risk score signatures, providing new perspectives and approaches for prognostic prediction and treatment of LGG.

The oxidation of coal at room temperature provides the initial heat source for spontaneous coal combustion (CSC). In the CSC theoretical study, exploring the active substances in coal that can be oxidized at room temperature is a complex problem. Previous thermal decomposition experiments have found that coal after pyrolysis contains active sites that can exist stably in inert gases and be oxidized at room temperature. Thus it is speculated that there may also be primary active sites that are forced to be stored under inert media in coal. In order to explore the primary active sites of coal, the vacuum drying technology is applied. Based on that, the water in the raw coal can reach the boiling point under the low-temperature environment of negative vacuum pressure to complete the removal of water and gas. Under different experimental conditions (coal, desorption temperature, oxidation temperature, particle size), the cyclic oxidation online monitoring technology is used to design and implement the room temperature oxidation experiment of the desorbed coal samples. At the same time, the reaction mechanism is analyzed by the corresponding low-temperature nitrogen adsorption, XPS, ESR experiments. After vacuum desorbed, the oxidation experiments under cyclic conditions show that the massive gaseous oxidation products such as CO and CO2 will be formed in the process of raw oxidation at room temperature, and the gases appear and accumulate soon after oxygen is introduced, which proves that coal oxidation can occur at room temperature. The room temperature oxidation experiment after the desorption of raw coal indicates that there are a large number of active sites affected by water-gas masking in the raw coal. They are unable to undergo the oxidation exothermic processes, while the coal after the desorption of water and gas under negative pressure exposes massive active sites and forms a channel conducive to oxygen transport and reaction, which rapidly occur oxidation exothermic phenomenon and lead to the rise of coal temperature. Therefore, the active structure leading to the spontaneous warming of the raw coal is found, and the experiments extend the view of room temperature oxidation of the active sites from the particular case state of the pyrolysis to the general state. From the comparison of gas product generation, it can be seen that CO, which is not easy to be adsorbed by pores, is produced quickly at the moment of contact between the primary active site and oxygen. Therefore, it can be concluded that CO is more suitable as an intuitive gas evaluation index of the concentration of the active sites compared with CO2. The room temperature oxidation of the primary active sites of coal helps reveal the mechanism of coal spontaneous combustion and provides a solution to the problem of spontaneous combustion during gas extraction in high-gas mines and the problem of CO over-limit in low-rank coal mines.

Abstract Background Health workforce projection models are integral components of a robust healthcare system. This research aims to review recent advancements in methodology and approaches for health workforce projection models and proposes a set of good practice reporting guidelines. Methods We conducted a systematic review by searching medical and social science databases, including PubMed, EMBASE, Scopus, and EconLit, covering the period from 2010 to 2023. The inclusion criteria encompassed studies projecting the demand for and supply of the health workforce. PROSPERO registration: CRD 42023407858. Results Our review identified 40 relevant studies, including 39 single countries analysis (in Australia, Canada, Germany, Ghana, Guinea, Ireland, Jamaica, Japan, Kazakhstan, Korea, Lesotho, Malawi, New Zealand, Portugal, Saudi Arabia, Serbia, Singapore, Spain, Thailand, UK, United States), and one multiple country analysis (in 32 OECD countries). Recent studies have increasingly embraced a complex systems approach in health workforce modelling, incorporating demand, supply, and demand–supply gap analyses. The review identified at least eight distinct types of health workforce projection models commonly used in recent literature: population-to-provider ratio models (n = 7), utilization models (n = 10), needs-based models (n = 25), skill-mixed models (n = 5), stock-and-flow models (n = 40), agent-based simulation models (n = 3), system dynamic models (n = 7), and budgetary models (n = 5). Each model has unique assumptions, strengths, and limitations, with practitioners often combining these models. Furthermore, we found seven statistical approaches used in health workforce projection models: arithmetic calculation, optimization, time-series analysis, econometrics regression modelling, microsimulation, cohort-based simulation, and feedback causal loop analysis. Workforce projection often relies on imperfect data with limited granularity at the local level. Existing studies lack standardization in reporting their methods. In response, we propose a good practice reporting guideline for health workforce projection models designed to accommodate various model types, emerging methodologies, and increased utilization of advanced statistical techniques to address uncertainties and data requirements. Conclusions This study underscores the significance of dynamic, multi-professional, team-based, refined demand, supply, and budget impact analyses supported by robust health workforce data intelligence. The suggested best-practice reporting guidelines aim to assist researchers who publish health workforce studies in peer-reviewed journals. Nevertheless, it is expected that these reporting standards will prove valuable for analysts when designing their own analysis, encouraging a more comprehensive and transparent approach to health workforce projection modelling.

Aiming at the restricted oxygen environment of coal mine, this paper focus on the whole process from physical adsorption to chemical reaction between coal and oxygen, and quantum chemical calculations investigate the potentiating or inhibiting effects of different active groups on the amount of oxygen adsorbed and thermally released from the main coal structure, and experimentally investigate the effect of oxygen concentration (OC) on the transformation relationship between active functional groups and active sites. The results showed the coal side-chain structure has an effect on the heat release characteristics of the aromatic ring in the process of oxygen adsorption, and the heat of adsorption of the aromatic ring with alkyl and aldehyde side-chains reaches 422.706 kJ/mol. The relationship between carbon oxide release and temperature at different OC all conformed to the exponential function model, and the apparent activation energy was positively correlated with the OC. The increase of OC narrows the gap between the production and consumption rates of active sites, which is helpful for the further understanding of the coal spontaneous combustion (CSC).

Abstract Background Intervertebral disc cell fibrosis has been established as a contributing factor to intervertebral disc degeneration (IDD). This study aimed to identify fibrosis-related diagnostic genes for patients with IDD. Methods RNA-sequencing data was downloaded from Gene Expression Omnibus (GEO) database. The diagnostic genes was identified using Random forest based on the differentially expressed fibrosis-related genes (DE-FIGs) between IDD and control samples. The immune infiltration states in IDD and the regulatory network as well as potential drugs targeted diagnostic genes were investigated. Quantitative Real-Time PCR was conducted for gene expression valifation. Results CEP120 and SPDL1 merged as diagnostic genes. Substantial variations were observed in the proportions of natural killer cells, neutrophils, and myeloid-derived suppressor cells between IDD and control samples. Further experiments indicated that AC144548.1 could regulate the expressions of SPDL1 and CEP120 by combininghsa-miR-5195-3p and hsa-miR-455-3p, respectively. Additionally, transcription factors FOXM1, PPARG, and ATF3 were identified as regulators of SPDL1 and CEP120 transcription. Notably, 56 drugs were predicted to target these genes. The down-regulation of SPDL1 and CEP120 was also validated. Conclusion This study identified two diagnostic genes associated with fibrosis in patients with IDD. Additionally, we elucidated their potential regulatory networks and identified target drugs, which offer a theoretical basis and reference for further study into fibrosis-related genes involved in IDD.

Abstract Background We aimed to observe the effect of radiotherapy on the expression of immune checkpoint molecule CEACAM1 in patients with glioma and the therapeutical effect of radiotherapy combined with blockade of CEACAM1 in mice with intracranial gliomas. Methods The expression of CEACAM1 on T-lymphocytes in the peripheral blood of patients with glioma was detected before and after radiotherapy; GL261 murine glioma cells (stably transfected with the luciferase gene) were implanted in the right caudate nucleus of C57BL/6 mice, and tumour growth was observed using the small animal in vivo imaging system. Mice were divided into 4 groups: (1) the isotype control; (2) the radiotherapy; (3) the anti-CEACAM1 treatment; and (4) the combination therapy. The survival of mice after treatment was recorded; the expression of CEACAM1 on murine glioma cells was detected by immunohistochemistry before and after radiotherapy; flow cytometry was adopted to detect CD8+ T-cells (Treg) (CD4+FoxP3+CD25+) among mouse brain-infiltrating T-cells; serum levels of IFN-γ and IL-10 were detected by ELISA; proliferation and apoptosis were observed by immunohistochemistry; Retrospective RNA-seq data analysis was conducted in a cohort of 325 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 702 patients in The Cancer Genome Atlas (TCGA) database. Results The expression of CEACAM1 on CD4+ and CD8+ T-cells in the peripheral blood of patients with glioma was significantly higher 1 week after radiotherapy than before radiotherapy and was further increased 1 month after radiotherapy. Combined therapy notably inhibited the growth of intracranial tumours in mice and prolonged their survival time, with some mice being capable of surviving long-term (> 90 d). Immunohistochemistry revealed that the expression of CEACAM1 in murine glioma tissues after radiotherapy was elevated in a time-dependent manner. Flow cytometry analysis showed an increase in mouse brain-infiltrating CD8+ T-lymphocytes, a decrease in Treg cells, and an increase in CD8+ T/Treg cells after treatment. ELISA demonstrated the elevated levels of IFN and decreased levels of IL-10 in the serum of mice in the combination therapy group. Conclusions Radiotherapy combined with CEACAM1 inhibitors resulted in strong and durable anti-tumour immune responses against murine glioma and long-term survival of some mice. Hence, this study is expected to offer new effective immunotherapy strategies against glioma.

In order to understand the driving characteristics of electric heavy-duty trucks in practical application scenarios and promote their usage to replace diesel trucks, this study analyzed the actual usage of electric and diesel heavy-duty trucks in a steel factory based on vehicle-monitoring data and remote online monitoring data and estimated the emission reduction potential of the application of electric trucks by using a mileage-based method and the greenhouse gas emission model. The results showed that the electric heavy-duty trucks in the steel factory mostly operated for over 14 h, with a vehicle kilometers traveled (VKT) of 50–300 km each day, which could meet most of the demands of the transportation of the steel industry. The average daily energy consumption for most trucks falls within the range of 210–230 kWh/100 km, with higher consumption in winter than in summer, which can save approximately 18–26% in operating costs compared with diesel trucks. It is estimated that the usage of these electric heavy-duty trucks can achieve an annual reduction of 115.8 tons of NOx emissions, 0.7 tons of PM emissions, and 18,000 tons of CO2 emissions. To further promote the application of electric heavy-duty trucks in China, several policy suggestions, such as introducing priority road-right policies, promoting vehicle and battery leasing markets, and exempting zero-emission vehicles during heavy pollution days, were proposed.

Abstract Background PDZ-binding kinase (PBK) encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. There is evidence that overexpression of this gene is associated with tumorigenesis. However, the role of PBK in hepatocellular carcinoma (HCC) remains unclear. Therefore, we evaluated the prognostic role of PBK and its correlation with immune infiltrates in hepatocellular carcinoma. Methods The expression of PBK in pan-cancers was studied by Onconmine and TIMER. The expression of PBK in HCC patients and its relationship with clinicopathological characteristics were analyzed using The Gene Expression Profiling Interactive Analysis (GEPIA), The human protein atlas database (HPA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of PBK in HCC patients. The relationship between PBK and prognosis of HCC was performed by GEPIA and Kaplan Meier plotter web tool. The correlations between the clinical characteristics and overall survival were analyzed by Univariate Cox regression and Multivariate Cox hazards regression to identify possible prognostic factors for HCC patients. LinkedOmics was applied to investigate co-expression associated with PBK and to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The network map of PBK and related genes is constructed by GeneMANIA. Finally, TIMER and TISIDB were used to analyze the correlations between PBK and tumor-infiltrating immune cells. Results Multiple database analysis shows that PBK was highly expressed in many types of tumors, including hepatocellular carcinoma, and was significantly related to tumor stage (P=0.0089), age (P=0.0131), and race (P=0.0024) of HCC patients. The receiver operating characteristic (ROC) curve analysis showed that PBK had high diagnostic potential to HCC in GSE76427 (AUC=0.8799), GSE121248 (AUC=0.9224), GSE62232 (AUC=0.9975), and GSE84402 (AUC=0.9541). Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062–2.311, P= 0.024). The Protein–protein interaction network showed that PBK significantly interacted with LRRC47, ARAF, LGALS9B, TTK, DLG1, and other essential genes. Furthermore, enrichment analysis showed that PBK and co-expressed genes participated in many biological processes, cell composition, molecular functions, and pathways in HCC. Finally, the immune infiltration analysis by TIMER and TISIDB indicated that a significant tightly correlation between PBK and macrophages, neutrophils, as well as chemokines and receptors. Conclusions High expression of PBK is significantly correlated with poor survival and immune infiltrates in hepatocellular carcinoma. Our study suggests that PBK can be used as a biomarker of poor prognosis and potential immune therapy target in hepatocellular carcinoma.

Fibrosis, a disease characterized by an excess accumulation of extracellular matrix components, could lead to organ failure and death, and is to blame for up to 45 % of all fatalities in developed nations. These disorders all share the common trait of an unchecked and increasing accumulation of fibrotic tissue in the affected organs, which leads to their malfunction and eventual failure, even if their underlying causes are highly diverse and, in some cases, remain unclear. Numerous studies have identified activated myofibroblasts as the common cellular elements ultimately responsible for the replacement of normal tissues with nonfunctional fibrotic tissue. The transforming growth factor-β pathway, for instance, plays a significant role in practically all kinds of fibrosis. However, there is no specific drug for the treatment of fibrosis, several medications with anti-hepatic fibrosis properties are still in the research and development stages. Peptide, which refers to a substance consisting of 2–50 amino acids, is characterized by structural diversity, low toxicity, biological activities, easy absorption, specific targeting, few side effects, and has been proven to be effective in anti-fibrosis. Here, we summarized various anti-fibrosis peptides in fibrosis including the liver, lungs, kidneys, and other organs. This review will provide a new insight into peptide mediated anti-fibrosis and is helpful to creation of antifibrotic medications.

Background: Diabetic nephropathy (DN) is the main reason for renal failure in terminal stage. Studies have shown that long-chain non-coding RNA (LncRNA) improves DN by regulating microRNA (miR). The study intended to investigate the role of MALAT1/miR-206 on high glucose (HG)-induced inflammation, oxidative stress and cell death of renal tubular epithelial cells (RTECs). Methods: HG-intervened HK-2 cells to establish DN cell model. Transfection effect was confirmed by qRT-PCR and MALAT1, NLRP3, Caspase-1, IL-1β, GSMDD-N and miR-206 were tested. Western blot was performed to test the proteins in NLRP3, Caspase-1, IL-1β and GSMDD-N, and to observe the pyroptosis. Elisa kit was applied to detect TNF-α, IL-6 and MCP-1. Results: Double luciferase report experiment and RNA immunoprecipitation (RIP) confirmed that MALAT1 could bind to miR-206. HG induced MALAT1 in HK-2 cells increased. Knocking down MALAT1 could reduce TNF-α, IL-6 and MCP-1. In HG-intervened HK-2 cells, the over-expressed miR-206 transfected into the cells was consistent with the changes of inflammatory factors and cytokines after knock-down MALAT1. Conclusion: Up-regulation MALAT1 could reverse the inhibition of miR-206 on pyroptosis and inflammatory response. MALAT1 can improve HG-induced HK-2 pyroptosis by targeting miR-206, which is expected to be a latent target to treat DN in clinic.

The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-caused pneumonia (Coronavirus disease −19, COVID-19), has resulted in a global health emergency. However, there is no vaccine or effective antiviral treatment against the newly emerged coronavirus and identifying the available therapeutics as soon as possible is critical for the response to the spread of SARS-CoV-2. Shufeng Jiedu Capsule (SFJDC), a well-known prescription of Traditional Chinese Medicine (TCM) in China, has been widely used in treating upper respiratory tract infections and acute lung injury, owing to its immunomodulatory and anti-inflammatory effects. Despite the definite evidence of effective use of SFJDC in the diagnosis and treatment of pneumonia caused by SARS-CoV-2, the underlying action mechanism remains unknown. Currently, a systematic study integrated with absorption, distribution, metabolism and excretion (ADME) evaluation, target prediction, network construction and functional bioinformatics analyses is proposed to illustrate the potential immune and anti-inflammatory mechanisms of SFJDC against SARS-CoV-2. Additionally, to further validate the reliability of the interactions and binding affinities between drugs and targets, docking, Molecular dynamics Simulations (MD) simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area approach (MM-PBSA) calculations were carried out. The results demonstrate that SFJDC regulates the immunomodulatory and anti-inflammatory related targets on multiple pathways through its active ingredients, showing the potential anti-novel coronavirus effect. Overall, the work can provide a better understanding of the therapeutic mechanism of SFJDC for treating SARS-CoV-2 pneumonia from multi-scale perspectives, and may also offer a valuable clue for developing novel pharmaceutical strategies to control the current coronavirus.

Objective To measure the trade-off between risk of complications versus patient improvement in pain and function in orthopaedic surgeons’ decisions about whether to undertake total knee arthroplasty (TKA).Methods A discrete choice experiment asking surgeons to make choices between experimentally-designed scenarios describing different levels of operative risk and dimensions of pain and physical function. Variation in preferences and trade-offs according to surgeon-specific characteristics were also examined.Results The experiment was completed by a representative sample of 333 orthopaedic surgeons (n=333): median age 52 years, 94% male, 91% fully qualified. Orthopaedic surgeons were willing to accept substantial increases in absolute risk associated with TKA surgery for greater improvements in a patient’s pain and function. The maximum risk surgeons were willing to accept was 40% for reoperation and 102% for the need to seek further treatment from a general practitioner or specialist in return for a change from postoperative severe night-time pain at baseline to no night-time pain at 12 months. With a few exceptions, surgeon-specific characteristics were not associated with how much risk a surgeon is willing to accept in a patient undergoing TKA.Conclusion This is the first study to quantify risk-benefit trade-offs among orthopaedic surgeons performing TKA, using a discrete choice experiment. This study provides insight into the risk tolerance of surgeons.

This paper selects two typical compounds containing organic sulfur as model compounds. Then, by analyzing the chromatograms of gaseous low-temp oxidation products and GC/MS of the extractable matter of the oxidation residue, we summarizing the mechanism of low-temp sulfur model compound oxidation. The results show that between 30 °C to 80 °C, the interaction between diphenyl sulfide and oxygen is mainly one of physical adsorption. After 80 °C, chemical adsorption and chemical reactions begin. The main reaction mechanism in the low-temp oxidation of the model compound diphenyl sulfide is diphenyl sulfide generates diphenyl sulfoxide, and then this sulfoxide is further oxidized to diphenyl sulphone. A small amount of free radicals is generated in the process. The model compound cysteine behaves differently from diphenyl sulfide. The main reaction low-temp oxidation mechanism involves the thiol being oxidized into a disulphide and finally evolving to sulfonic acid, along with SO2 being released at 130 °C and also a small amount of free radicals. We also conducted an experiment on coal from Xingcheng using X-ray photoelectron spectroscopy (XPS). The results show that the major forms of organic sulfur in the original coal sample are thiophene and sulfone. Therefore, it can be inferred that there is none or little mercaptan and thiophenol in the original coal. After low-temp oxidation, the form of organic sulfur changes. The sulfide sulfur is oxidized to the sulfoxide, and then the sulfoxide is further oxidized to a sulfone, and these steps can be easily carried out under experimental conditions. What’s more, the results illustrate that oxidation promotes sulfur element enrichment on the surface of coal.

The structure and distribution of organic sulfur in coals of different rank and different sulfur content were studied by combining mild organic solvent extraction with XPS technology. The XPS results have shown that the distribution of organic sulfur in coal is related to the degree of metamorphism of coal. Namely, thiophenic sulfur content is reduced with decreasing metamorphic degree; sulfonic acid content rises with decreasing metamorphic degree; the contents of sulfate sulfur, sulfoxide and sulfone are rarely related with metamorphic degree. The solvent extraction and GC/MS test results have also shown that the composition and structure of free and soluble organic sulfur small molecules in coal is closely related to the metamorphic degree of coal. The free organic sulfur small molecules in coal of low metamorphic degree are mainly composed of aliphatic sulfides, while those in coal of medium and high metamorphic degree are mainly composed of thiophenes. Besides, the degree of aromatization of organic sulfur small molecules rises with increasing degree of coalification.

Abstract Cytotherapy is a strategy to deliver modified cells to a diseased tissue, but targeting solid tumours remains challenging. Here we design macrophages, harbouring a surface glypican-3-targeting peptide and carrying a cargo to combat solid tumours. The anchored targeting peptide facilitates tumour cell recognition by the engineered macrophages, thus enhancing specific targeting and phagocytosis of tumour cells expressing glypican-3. These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO). The OMVs facilitate internalization through caveolin-mediated endocytosis, and to maintain a suitable nanostructure, C16-ceramide induces membrane invagination and exosome generation, leading to the release of cargo-packed RILOs through exosomes. RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment.