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Abstract Background Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive. Methods The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry. Results In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB. Conclusions The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.

Understanding the hydrochemical characteristics and genesis mechanisms of strontium-rich groundwater is pivotal for supporting the exploitation and utilization of natural strontium-rich groundwater. In this research, 27 groundwater samples were collected. By analyzing major ion chemistry and strontium isotope data, and considering the hydrogeological context, various analytical approaches, including multivariate statistics, ion ratios, and isotopes, were used to reveal the characteristics and genesis mechanisms of strontium-rich groundwater in the study area. The findings indicate that the predominant hydrochemical type of groundwater is HCO3-Ca, with Ca2+ and HCO3− as the primary cations and anions. The hydrochemistry of the strontium-rich groundwater is predominantly influenced by rock weathering processes. A combination of factors, including ion exchange, and anthropogenic activities, shapes the compositional characteristics of the groundwater in the region. The dissolution of calcite due to weathering emerges as the principal source of strontium in the groundwater. While ion exchange processes are not conducive to strontium enrichment in groundwater, their effect is relatively limited. The impact of human activities on the groundwater is minor.

Silica/solution-polymerized butadiene-styrene rubber (SSBR)/natural rubber (NR) compo-sites were prepared by mechanical mixing method with silane coupling agent, bis[3-(triethoxysilyl)propyl]tetrasulfide (Si 69) and 3-mercaptopropyl-ethyoxyl-di(tridecyl-pentamethoxy)-silane (Si 747), as modifier and the effect of types and addtion amounts of silane coupling agent on the microstructure, curing characteristics, processing performance, physical and mechanical performance, dynamic mechanical properties, tire performance, and the relationship between structure and performance of the composite. The results showed that compared with the composite just only modified by Si 69, the incorporation of Si 747 resulted in the scorch time and optimum curing time of the composite shorten signi-ficantly, and the curing rate improved gradually with the increase in the addition amount of Si 747; the synergistic modification of Si 69 and Si 747 made the physical and mechanical properties, tensile strength, resilience and modulus at 300% of the composite all reduced; when the addition amount of Si 747 increased, the apparent activation energy which was used to characterize the temperature dependence of storage modulus of the composite reduced gradually; the dispersion of silica in the composite improved significantly after the addition of Si 747; the loss factor (tan δ) of the composite modified by Si 747 alone at 0 ℃ increased significantly and tan δ at 60 ℃ decreased significantly; the rolling resistance of the tire improved gradually with the increase in the addition amount of Si 747.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, continues to rise with rapid economic development and poses significant challenges to human health. No effective drugs are clinically approved. MASLD is regarded as a multifaceted pathological process encompassing aberrant lipid metabolism, insulin resistance, inflammation, gut microbiota imbalance, apoptosis, fibrosis, and cirrhosis. In recent decades, herbal medicines have gained increasing attention as potential therapeutic agents for the prevention and treatment of MASLD, due to their good tolerance, high efficacy, and low toxicity. In this review, we summarize the pathological mechanisms of MASLD; emphasis is placed on the anti-MASLD mechanisms of Chinese herbal formula (CHF), especially their effects on improving lipid metabolism, inflammation, intestinal flora, and fibrosis. Our goal is to better understand the pharmacological mechanisms of CHF to inform research on the development of new drugs for the treatment of MASLD.

Aiming at the problems of unbalanced brightness of lung cell images and achieving accurate segmentation of abnormal cell contour difficultly, an abnormal cell segmentation model based on U-Net was proposed, which combined the dense connection mechanism and attention mechanism. Firstly, U-Net with encoder-decoder structure was used to segment abnormal cells. Secondly, the dense block was introduced into U-Net to improve the propagation ability between features and extract more characteristic information of abnormal cells. Finally, the attention mechanism was used to increase the weight of abnormal cell regions and reduce the interference of the imbalance of brightness to the model. The experimental results show that the IoU value and Dice similarity coefficient achieved by this method are 0.6928 and 0.8060, respectively. Compared with other models, this proposed method is able to segment low-contrast regions and abnormal cells with diverse shapes.

Abstract Backgroud The current diagnostic criteria for refractory Mycoplasma pneumoniae pneumonia (RMPP) among Mycoplasma pneumoniae Pneumonia (MPP) are insufficient for early identification, and potentially delayed appropriate treatment. This study aimed to develop an effective individualized diagnostic prediction nomogram for pediatric RMPP. Methods A total of 517 hospitalized children with MPP, including 131 with RMPP and 386 without RMPP (non-RMPP), treated at Lianyungang Maternal and Child Health Care Hospital from January 2018 to December 2021 were retrospectively enrolled as a development (modeling) cohort to construct an RMPP prediction nomogram. Additionally, 322 pediatric patients with MPP (64 with RMPP and 258 with non-RMPP, who were treated at the Affiliated Hospital of Xuzhou Medical University from June 2020 to May 2022 were retrospectively enrolled as a validation cohort to assess the prediction accuracy of model. Univariable and multivariable logistic regression analyses were used to identify RMPP risk factors among patients with MPP. Nomogram were generated based on these risk factors using the rms package of R, and the predictive performance was evaluated based on receiver operating characteristic (ROC) curves and using decision curve analysis (DCA). Results Multivariate analysis revealed five significant independent predictors of RMPP among patients with MPP: age (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.08–1.33, P = 0.038), fever duration (HR 1.34, 95%CI 1.20–1.50, P

BackgroundSpecies domestication is generally characterized by the exploitation of high-impact mutations through processes that involve complex shifting demographics of domesticated species. These include not only inbreeding and artificial selection that may lead to the emergence of evolutionary bottlenecks, but also post-divergence gene flow and introgression. Although domestication potentially affects the occurrence of both desired and undesired mutations, the way wild relatives of domesticated species evolve and how expensive the genetic cost underlying domestication is remain poorly understood. Here, we investigated the demographic history and genetic load of chicken domestication.ResultsWe analyzed a dataset comprising over 800 whole genomes from both indigenous chickens and wild jungle fowls. We show that despite having a higher genetic diversity than their wild counterparts (average π, 0.00326 vs. 0.00316), the red jungle fowls, the present-day domestic chickens experienced a dramatic population size decline during their early domestication. Our analyses suggest that the concomitant bottleneck induced 2.95% more deleterious mutations across chicken genomes compared with red jungle fowls, supporting the "cost of domestication" hypothesis. Particularly, we find that 62.4% of deleterious SNPs in domestic chickens are maintained in heterozygous states and masked as recessive alleles, challenging the power of modern breeding programs to effectively eliminate these genetic loads. Finally, we suggest that positive selection decreases the incidence but increases the frequency of deleterious SNPs in domestic chicken genomes.ConclusionThis study reveals a new landscape of demographic history and genomic changes associated with chicken domestication and provides insight into the evolutionary genomic profiles of domesticated animals managed under modern human selection.