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Abstract This paper presents a method of rotor position estimation for switched reluctance motors suitable for saturation. The effects of saturation as well as voltage changes are taken into account at the same time. It is based on the inductance in the unsaturated region. When the phase inductance is equal to the threshold, it is defined as a characteristic point. Meanwhile the characteristic pulse signal is triggered. Different inductance intersection thresholds are determined when the phase current and bus voltage change. The rotor position is estimated by interval speed. Compared with the traditional inductance method, the position estimation error is smaller. Finally, the correctness and effectiveness of the proposed method are verified by simulation and experiments.

Abstract Objective To explore the relationship between vessel invasion (VI) and clinicopathological features and prognosis in patients with gastric cancer (GC). Methods A total of 3600 cases of patients with GC who underwent radical gastrectomy in gastrointestinal surgery department of the First Affiliated Hospital of Naval Medical University from June 2014 to June 2019 were retrospectively analyzed, and filtering them based on specific inclusion and exclusion criteria. To reduce the possibility of selection bias about the impact of VI, patients were divided into two groups according to the presence or absence of it, and performed a one-to-one propensity score matching (PSM), resulting in 724 patients in each group. In the analysis of data from 3,205 GC patients was employed to examine inter-group variations in VI positivity across diverse clinicopathological factors. Both univariate and multivariate Cox regression models were applied to investigate the correlation between clinicopathological factors and prognosis. The findings were further illustrated through the plotting of Kaplan-Meier survival curves. Results 3205 patients were included in this study, of which 989 (30.9%) were VI-positive and 2216 (69.1%) were VI-negative. VI-positive group was found to be significantly associated with age, body mass index (BMI), pTNM stage, tumor location, perineural invasion (PI), Lauren classfication and tumor deposit (TD) (P

There is an urgent demand for the development of new resource-saving and high-efficiency cryogenic refrigeration technologies against the historical backdrop of increasing scarcity of resources and energy. Magnetic refrigeration technology based on the magnetocaloric effect (MCE) of magnetic materials is a promising approach to address helium resource constraints and improve energy efficiency. Here, a brilliant cryogenic magnetic refrigerant with a large low-field MCE and excellent refrigeration performance is presented. Benefiting from the enhanced ferromagnetism and low saturation magnetic field, the peaks of magnetic entropy change, refrigeration capacity, and adiabatic temperature change of Eu(Ti,Nb,Zr)O3 compounds reach 19.6 J·kg−1·K−1, 87.6 J·kg−1, and 5.5 K, respectively, for a field change of 0−1 T. Magnetic refrigeration experiments on a Gifford‒McMahon (GM)/magnetic hybrid refrigerator further demonstrated that EuTi0.8375Nb0.0625Zr0.1O3 is an excellent magnetic refrigerant operating near the liquid helium temperature. An appropriate amount of this magnetic refrigerant can significantly improve the refrigeration performance of the hybrid refrigerator. The cooling power in hybrid refrigeration mode is improved by a maximum of 52% over that in pure GM/HoCu2 mode at 4.2 K and 0.5 Hz. In addition, the cooling efficiency at 4.2 K is more than 40% greater than that of the pure GM/HoCu2 refrigerator.

Exogenous gibberellic acid was applied to regulate fruit growth of grapes to acquire high quality seedless berries. The vascular bundles provide the pathway of water and nutrient transport into the fruit and play an important role in berry growth and sugar accumulation. Therefore, changes in berry size and quality are closely related to the structure and function of the vascular tissue. In this study, 10-year-old “Shine Muscat” grape vines were treated with GA3 in grapevine production. Based on previous research and experimental environmental conditions, four treatments were applied: elongating cluster（5 mg L−1 GA3 on Apr. 28）+ seedless（25 mg L−1 GA3 on May. 24）+ expanding（50 mg L−1 GA3 on Jun. 7） (T1), seedless（25 mg L−1 GA3 on May. 24）+ expanding（50 mg L−1 GA3 on Jun. 7） (T2), expanding（50 mg L−1 GA3 on Jun. 7） (T3) and water (CK). Compared to CK, all fruits treated with GA3 had greater berry size. In addition, GA3 treated grapes had greater vascular bundle areas, including the areas of both phloem and xylem, as well as a greater number of vessels compared to control fruit. During the first rapid growth stage, water transport into the grape was rapid and did not differ among treatments. During veraison, the water transport rate among the four treatments differed, and the rank of speed was T2>T3>CK>T1. Therefore, we found that GA3 treatment can significantly promote the differentiation of vascular tissues and improve water transport capacity and phloem sugar unloading; T2 promoted the development of vascular bundles, enhanced water transport speed and phloem sugar unloading of fruit after veraison, and increased berry size.

Abstract As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains XBB.1.5-specific sequence changes, relative to the original BNT162b2 backbone, in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation and adopts a flexible, predominantly open, state, with high affinity for the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose series in naive mice. Strong S-specific Th1 CD4+ and IFNγ+ CD8+ T cell responses were also observed. These findings, together with real world performance of the XBB.1.5-adapted vaccine, suggest that preclinical data for the monovalent Omicron XBB.1.5-adapted BNT162b2 was predictive of protective immunity against dominant SARS-CoV-2 strains.

Abstract Lymphocyte activating gene-3 (LAG3) is a distinctive T cell co-receptor that is expressed on the surface of lymphocytes. It plays a special inhibitory immune checkpoint role due to its unique domain and signaling pattern. Our aim is to explore the correlation between LAG3 in cancers and physiological processes related to a range of cancers, as well as build LAG3-related immunity and prognostic models. By comprehensively using of datasets and methods from TCGA, GTE-x and GEO databases, cBioPortal, HPA, Kaplan-Meier Plotter, Spearman, CellMinerTM, we delved deeper into the potential impact of the LAG3 in cancer development. These include expression differences, Localization of tumor cell subsets, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways and prognosis. Furthermore, we explored LAG3 interactions with different drugs. LAG3 is highly expressed in ACC (p

Abstract Background Breast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of anoikis. Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear. Method This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a prognostic model. Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells. Results One hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan–Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels. Conclusion ARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.

According to previous studies, D-dimer levels are associated with the prognosis of patients with pancreatic cancer (PC). However, the results of current studies are limited and controversial. Therefore, we performed this meta-analysis to assess the relationship between D-dimer levels and prognostic and pathological characteristics of PC patients. We first searched the databases of PubMed, Embase, The Cochrane Library, Web Of Science, CBM, VIP, CNKI and Wanfang to identify available studies. The relationship between pretreatment d-dimer levels and prognosis in PC patients was assessed using the combined hazard ratio (HR) and 95% confidence interval (CI). The combined odds ratio (OR) and 95% confidence interval (CI) were used in assessing the relationship between pathological characteristics and d-dimer levels in PC patients. Stata 12.0 software was used for all statistical analyses. In total, we included 13 studies involving 2777 patients. The results showed that elevated pre-treatment d -dimer levels were significantly associated with OS deterioration (HR = 1.46 95% CI: 1.34–1.59; p

Abstract Background A cost-effective Escherichia coli expression system has gained popularity for producing virus-like particle (VLP) vaccines. However, the challenge lies in balancing the endotoxin residue and removal costs, as residual endotoxins can cause inflammatory reactions in the body. Results In this study, porcine parvovirus virus-like particles (PPV-VLPs) were successfully assembled from Decreased Endotoxic BL21 (BL21-DeE), and the effect of structural changes in the lipid A of BL21 on endotoxin activity, immunogenicity, and safety was investigated. The lipopolysaccharide purified from BL21-DeE produced lower IL-6 and TNF-α than that from wild-type BL21 (BL21-W) in both RAW264.7 cells and BALB/c mice. Additionally, mice immunized with PPV-VLP derived form BL21-DeE (BL21-DeE-VLP) showed significantly lower production of inflammatory factors and a smaller increase in body temperature within 3 h than those immunized with VLP from BL21-W (BL21-W-VLP) and endotoxin-removed VLP (ReE-VLP). Moreover, mice in the BL21-DeE-VLP immunized group had similar levels of serum antibodies as those in the BL21-W-VLP group but significantly higher levels than those in the ReE-VLP group. Furthermore, the liver, lungs, and kidneys showed no pathological damage compared with the BL21-W-VLP group. Conclusion Overall, this study proposes a method for producing VLP with high immunogenicity and minimal endotoxin activity without chemical or physical endotoxin removal methods. This method could address the issue of endotoxin residues in the VLP and provide production benefits.

Background It has been demonstrated that nintedanib can inhibit the proliferation of gastric cancer cells, but the specific mechanism of action is unclear. Objective Investigating the changes of key factors involved in gene transcription and post-transcriptional regulation during the process of treating gastric cancer with nintedanib. Methods In this study, we performed transcriptome sequencing on gastric cancer cell groups treated with nintedanib and control groups. The SUVA (Splice sites Usage Variation Analysis) software was used to identify differential alternative splicing (AS) events between the nintedanib-treated group and the control group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to assess the functional differences and pathways associated with these events. Finally, a co-expression regulatory network of differentially expressed RNA-binding proteins (RBPs) and differentially spliced genes was established. Results: A total of 915 differential AS events were identified between the two groups, and these differential genes were closely related to the apoptosis pathway. Further analysis revealed that differential RBPs (TAGLN2, TAGLN, SRSF6, PKM, SRSF2, NOC2L, IPO4, C1QBP, DHX9) may affect the anti-proliferative effect of nintedanib on gastric cancer cells by regulating downstream genes involved in cell proliferation and angiogenesis (NR4A1, BBC3, IFI27) through alternative splicing. Conclusion This study systematically identified important changes in alternative splicing and RNA-binding proteins during the process of nintedanib-induced apoptosis in gastric cancer cells. It innovatively revealed the mechanisms of action of nintedanib in gastric cancer cells and expanded the selection of new targets for gastric cancer treatment.

Abstract Background With the popularization of robotic surgical systems in the field of surgery, robotic gastric cancer surgery has also been fully applied and promoted in China. The Chinese Guidelines for Robotic Gastric Cancer Surgery was published in the Chinese Journal of General Surgery in August 2021. Methods We have made a detailed interpretation of the process of robotic gastric cancer surgery regarding the indications, contraindications, perioperative preparation, surgical steps, complication, and postoperative management based on the recommendations of China’s Guidelines for Robotic Gastric Cancer Surgery and supplemented by other surgical guidelines, consensus, and single-center experience. Results Twenty experiences of perioperative clinical management of robotic gastric cancer surgery were described in detail. Conclusion We hope to bring some clinical reference values to the front-line clinicians in treating robotic gastric cancer surgery. Trial registration The guidelines were registered on the International Practice Guideline Registration Platform ( http://www.guidelines-registry.cn ) (registration number: IPGRP-2020CN199).

Abstract This study aimed to develop a deep learning model to predict the risk stratification of all-cause death for older people with disability, providing guidance for long-term care plans. Based on the government-led long-term care insurance program in a pilot city of China from 2017 and followed up to 2021, the study included 42,353 disabled adults aged over 65, with 25,071 assigned to the training set and 17,282 to the validation set. The administrative data (including baseline characteristics, underlying medical conditions, and all-cause mortality) were collected to develop a deep learning model by least absolute shrinkage and selection operator. After a median follow-up time of 14 months, 17,565 (41.5%) deaths were recorded. Thirty predictors were identified and included in the final models for disability-related deaths. Physical disability (mobility, incontinence, feeding), adverse events (pressure ulcers and falls from bed), and cancer were related to poor prognosis. A total of 10,127, 25,140 and 7086 individuals were classified into low-, medium-, and high-risk groups, with actual risk probabilities of death of 9.5%, 45.8%, and 85.5%, respectively. This deep learning model could facilitate the prevention of risk factors and provide guidance for long-term care model planning based on risk stratification.

In the present work, a novel high-V high-Mn twinning induced plasticity (TWIP) steel for cryogenic storage tank applications was developed. Furthermore, innovative two-stage cooling processes encompassing ultra-fast cooling and the subsequent furnace cooling were proposed. Effects of cooling process on the microstructure and mechanical properties of the experimental steel were investigated. It was observed that with the change in cooling process (the initial temperature of furnace cooling rised gradually), the dwell time of hot-rolled plates above 600 °C was extended. The extension in dwell time facilitated the precipitation of secondary phase particles, leading to the change in average diameter and volume fraction of secondary phase particles. The yield strength increased with the increasing initial temperature of furnace cooling due to the combined effect of small-sized secondary phase particles inside the grains and large-sized ones located at the grain boundaries. The occurrence of intergranular cracking, primarily caused by the presence of large-sized secondary phase particles at the grain boundaries, was the main factor responsible for the significant reduction in total elongation. The small-sized secondary phase particles inside the grains inhibited deformation twinning, while the large-sized ones at the grain boundaries weaken the binding force between grain boundaries, which ultimately resulted in a decrease in cryogenic impact toughness. The implementation of two-stage cooling processes effectively mitigated the trade-off between yield strength and cryogenic impact toughness, offering a novel approach and valuable insights for optimizing the strength and toughness characteristics of cryogenic high-Mn steels.

The coronavirus disease 2019 (COVID-19) pandemic underscores the critical need to integrate immunomics within the One Health framework to effectively address zoonotic diseases across humans, animals, and environments. Employing advanced high-throughput technologies, this interdisciplinary approach reveals the complex immunological interactions among these systems, enhancing our understanding of immune responses and yielding vital insights into the mechanisms that influence viral spread and host susceptibility. Significant advancements in immunomics have accelerated vaccine development, improved viral mutation tracking, and broadened our comprehension of immune pathways in zoonotic transmissions. This review highlights the role of animals, not merely as carriers or reservoirs, but as essential elements of ecological networks that profoundly influence viral epidemiology. Furthermore, we explore how environmental factors shape immune response patterns across species, influencing viral persistence and spillover risks. Moreover, case studies demonstrating the integration of immunogenomic data within the One Health framework for COVID-19 are discussed, outlining its implications for future research. However, linking humans, animals, and the environment through immunogenomics remains challenging, including the complex management of vast amounts of data and issues of scalability. Despite challenges, integrating immunomics data within the One Health framework significantly enhances our strategies and responses to zoonotic diseases and pandemic threats, marking a crucial direction for future public health breakthroughs.

With the increasing penetration of distributed energy in the distribution network, it is urgent to study how to ensure the stable and reliable operation of the power grid under fault conditions. To solve this problem, this study proposes a method for partitioning distribution network islands and reconstructing faults considering the Conditional Value at Risk (CVaR). This method aims to enhance the resilience of the distribution network and the recovery capability of critical loads. Initially, a partitioning model for distribution network islands based on depth-first and breadth-first search algorithms was constructed. Building upon this partitioning, a fault reconstruction method for distribution networks that considers CVaR was developed. This method utilizes CVaR theory to transform costs and quantifies the risk that the uncertainty of distributed energy resources poses to distribution network reconstruction strategies. Finally, the effectiveness of the proposed method is demonstrated using an improved IEEE 33-node system, generating typical fault scenarios.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly significant infectious disease that poses a substantial threat to the global pig industry. In recent years, the NADC30-like strain has gradually emerged as prevalent in China, causing a profound impact on the country’s pig farming industry. Therefore, it is important to conduct an in-depth study on the characteristics and gene functions of the NADC30-like strain. An infectious cDNA clone is an indispensable tool for investigating the functions of viral genes. In this current study, we successfully isolated a NADC30-like strain and constructed its full-length infectious cDNA clone. The utilization of this clone will facilitate our investigation into the viral replication, pathogenesis, and immune response associated with the PRRSV NADC30-like strain.

The objective of this study was to explore the effects and mechanisms of the combination of isobavachalcone (IBC) and doxorubicin (DOX) on the progression of anaplastic thyroid cancer (ATC). Cell viability of 8505C and CAL62 cells was observed by CCK-8 assay. Kits were used to detect the presence of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and cellular iron. Protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was detected using western blot, and CD31 was detected through immunofluorescence. Tumor xenograft models of 8505C cells were constructed to observe the effect of IBC and DOX on ATC growth in vivo. The co-administration of IBC and DOX exhibited a synergistic effect of suppressing the growth of 8505C and CAL62 cells. The concurrent use of IBC and DOX resulted in elevated iron, ROS, and MDA levels, while reducing GSH levels and protein expression of SLC7A11 and GPX4. However, the Fer-1 ferroptosis inhibitor effectively counteracted this effect. In vitro and in vivo, the inhibitory effect on ATC cell proliferation and tumor growth was significantly enhanced by the combination of IBC and DOX. The combination of IBC and DOX can inhibit the growth of ATC by activating ferroptosis, and might prove to be a potent chemotherapy protocol for addressing ATC.

Nocardia farcinica is an aerobic gram-positive bacterium that is pathogenic to humans. It usually causes local and adjacent tissues’ diseases at the entry of infection (most commonly occur in the lungs, skin, or central nervous system), which can also spread to other organs through the bloodstream such as joints, kidneys, and liver. However, these infections are often seen as opportunistic that occur in immunocompromised patients. Here, we report for the first time two immunocompetent patients lacking evidence of local infections, with multiple lymph node enlargements and fever as main clinical manifestations, finally diagnosed as nocardiosis by Metagenomic Next-Generation Sequencing testing (mNGS) from formalin-fixed and paraffin-embedded (FFPE) lymph node tissue, after all the other standard tests were negative. Both patients recovered after receiving anti-nocardia therapies. These two cases indicates that in healthy population, there may be more potential nocardia infections than we expected. Multiple lymph node enlargements and fever suggest a possibility of nocardiosis, especially in patients with fever of unknown origin (FUO). mNGS detection from FFPE lymph node tissue is an accurate, reliable and traceable method for diagnosis of nocardiosis.

Abstract Background Underlying liver disease is correlated with hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV) infection. However, the impact of hepatic inflammation and fibrosis on the patients’ prognoses remains unclear. Methods The clinicopathological data of 638 HBV-infected patients with early-stage HCC between 2017 and 2019 were prospectively collected. Hepatic inflammation and fibrosis were evaluated by experienced pathologists using the Scheuer score system. Survival analysis was analyzed using the Kaplan–Meier analysis. Results Application of the Scheuer scoring system revealed that 50 (7.9%), 274 (42.9%), and 314 (49.2%) patients had minor, intermediate, and severe hepatic inflammation, respectively, and 125 (15.6%), 150 (23.5%), and 363 (56.9%) patients had minor fibrosis, advanced fibrosis, and cirrhosis, respectively. Patients with severe hepatitis tended to have a higher rate of HBeAg positivity, higher HBV-DNA load, elevated alanine aminotransferase (ALT) levels, and a lower proportion of capsule invasion (all Pp

Abstract Developing facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial. However, originate chirality from the distorted structure around heptagon-containing polyarenes is largely overlooked, the enantioselective construction of all-carbon heptagon-containing polyarenes remains a challenge. Herein, we present a highly enantioselective synthesis route for fabricating all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross–coupling of benzyl bromides and N-arylsulfonylhydrazones. A wide range of nonplanar, saddle-shaped tribenzocycloheptene derivatives are efficiently prepared in high yields with excellent enantioselectivities using this approach. In addition, stereochemical stability experiments show that these saddle-shaped tribenzocycloheptene derivatives have high inversion barriers.

Abstract Rheumatoid arthritis (RA) is a persistent autoimmune condition characterized by synovitis and joint damage. Recent findings suggest a potential link to abnormal lactate metabolism. This study aims to identify lactate metabolism-related genes (LMRGs) in RA and investigate their correlation with the molecular mechanisms of RA immunity. Data on the gene expression profiles of RA synovial tissue samples were acquired from the gene expression omnibus (GEO) database. The RA database was acquired by obtaining the common LMRDEGs, and selecting the gene collection through an SVM model. Conducting the functional enrichment analysis, followed by immuno-infiltration analysis and protein–protein interaction networks. The results revealed that as possible markers associated with lactate metabolism in RA, KCNN4 and SLC25A4 may be involved in regulating macrophage function in the immune response to RA, whereas GATA2 is involved in the immune mechanism of DC cells. In conclusion, this study utilized bioinformatics analysis and machine learning to identify biomarkers associated with lactate metabolism in RA and examined their relationship with immune cell infiltration. These findings offer novel perspectives on potential diagnostic and therapeutic targets for RA.

Abstract Objective It has been demonstrated that IDO1, a target of immune checkpoint inhibition, functions as an oncogene in the majority of human malignancies. IDO1’s function in human pan-cancers hasn’t been thoroughly studied, though. Materials and methods The Kaplan–Meier (K-M) and COX analyses were applied to the survival analysis. Furthermore, we used Spearman’s correlation analysis to examine the associations between IDO1 and microsatellite instability (MSI), DNA methyltransferases (DNMTs), tumor mutational burden (TMB), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers. Moreover, immunohistochemical analysis and qRT-PCR were used to evaluate IDO1’s expression in pan-cancer cells. Results The findings of this study reveal that IDO1 has abnormal expression in a number of malignancies and is related to the prognosis for UVM, LGG, KIRP, GBM, LAML, OV, READ, MESO, SARC, SKCM, and HNSC. Furthermore, the aberrant IDO1 expression was connected to the TMB, MSI, MMR, drug sensitivity, immune cells infiltrating, and tumor immune microenvironment across a variety of cancer types. The PCR results showed that in contrast to normal cells, IDO1 was found to be significantly highly expressed in breast cancer cells and hepatocellular carcinoma cells, and significantly lowly expressed in gastric cancer cells. Conclusion The clinical treatment of IDO1 is now better supported by a theoretical basis and guidelines provided by our study.

Objective To investigate the consistency between mismatch repair proyeins expressions detected by immunohistochemistry (IHC) and microsatellite instability(MSI) identified by next-generation sequencing (NGS), and evaluate the correlation of these results with the clinical characteristics of Chinese colorectal cancer (CRC). Methods Using IHC and NGS to identify mismatch repair (MMR) and MSI status in CRC, and assessing the consistency between these different detection methods. Results The concordance rate of MSI status detected by IHC and NGS was 98.36%, indicating good agreement (Kappa=0.856). Certain pathogenic or likely pathogenic germline variants were present in the pMMR/MSI-H subtype. The co-deficiency of MLH1 and PMS2 was most common in the dMMR/MSS subtype. Patients with inconsistent typing were more likely to have early-onset right-sided colon cancer (P

Abstract Background Severe asthma places a large burden on patients and society. The characteristics of patients with severe asthma in the Chinese population remain unclear. Methods A retrospective review was conducted in patients with severe asthma. Demographic and clinical data were collected. Patients were grouped according to phenotypes in terms of exacerbations, body mass index (BMI) and fixed airway obstruction (FAO) status, and the characteristics of different groups were compared. Comorbidities, factors that influence asthma phenotypes, were also analyzed in the study. Results A total of 228 patients with severe asthma were included in our study. They were more likely to be overweight or obese. A total of 41.7% of the patients received GINA step 5 therapy, and 43.4% had a history of receiving regular or intermittent oral corticosteroids (OCS). Severe asthmatic patients with comorbidities were prone to have more asthma symptoms and decreased quality of life than patients without comorbidities. Patients with exacerbations were characterized by longer duration of asthma, poorer lung function, and worse asthma control. Overweight or obese patients tended to have more asthma symptoms, poorer lung function and more asthma-related comorbidities. Compared to patients without FAO, those in the FAO group were older, with longer duration of asthma and more exacerbations. Conclusion The existence of comorbidities in patients with severe asthma could result in more asthma symptoms and decreased quality of life. Patients with exacerbations or with overweight or obese phenotypes were characterized by poorer lung function and worse asthma control. Patients with FAO phenotype tended to have more exacerbations.

Abstract Background Shugoshin-1 (SGOL1) is a mammalian ortholog of Shugoshin in yeast and is essential for precise chromosome segregation during mitosis and meiosis. Aberrant SGOL1 expression was reported to be closely correlated with the malignant progression of various tumors. However, the expression pattern and biological function of SGOL1 in clear cell renal cell carcinoma (ccRCC) are unclear. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provide mRNA expression data and outcome information for ccRCC patients. Immunohistochemistry (IHC) of ccRCC tissue chips verified SGOL1 protein expression in ccRCC patients. Data processing and visualization were performed with the UALCAN, TISIDB, TIMER, GSCA, LinkedOmics, and starBase databases. Gene Ontology (GO) annotation and gene set enrichment analysis (GSEA) were used to identify SGOL1-related biological functions and signaling pathways. Immune infiltration analysis was performed using the TISIDB database, ssGSEA algorithm, and TCGA-KIRC cohort. The biological role of SGOL1 in ccRCC was investigated using a series of in vitro cytological assays, including the MTT assay, EdU staining assay, flow cytometry analysis, Transwell assay, and wound healing assay. Results SGOL1 was highly expressed in ccRCC and linked to adverse clinicopathological parameters and unfavorable prognosis. Multivariate logistic regression and nomogram calibration suggested that SGOL1 might serve as an independent and reliable prognostic predictor of ccRCC. Functional enrichment analysis indicated that SGOL1 may be involved in the cell cycle, the p53 pathway, DNA replication, and T-cell activation. Furthermore, tumor microenvironment (TME) analysis suggested that SGOL1 was positively associated with Treg infiltration and immune checkpoint upregulation. In addition, we identified a potential SNHG17/PVT1/ZMIZ1-AS1-miR-23b-3p-SGOL1 axis correlated with ccRCC carcinogenesis and progression. Finally, we demonstrated that SGOL1 promoted ccRCC cell proliferation, migratory capacity, and invasion in vitro. Conclusions SGOL1 potentially functions as an oncogene in ccRCC progression and might contribute to the immunosuppressive TME by increasing Treg infiltration and checkpoint expression, suggesting that targeting SGOL1 could be a novel therapeutic strategy for the treatment of ccRCC patients.

Summary: The tumor-associated mucin MUC1 is overexpressed in almost all types of epithelial tumor tissues, making it an attractive target antigen for cancer immunotherapy. Here we present a protocol to prepare MUC1 glycopeptide vaccines and to evaluate immunization effects in mice. We describe steps for synthesizing glycopeptide antigen and conjugating it with carrier protein to make vaccine candidates. We then detail procedures for mice immunization, antibody response evaluation, and cellular immune response.For complete details on the use and execution of this protocol, please refer to Cai et al.1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Fagopyrum dibotrys, belonging to the family Polygonaceae and genus Fagopyrum, is used in traditional Chinese medicine and is rich in beneficial components, such as flavonoids. As its abundant medicinal value has become increasingly recognized, its excessive development poses a considerable challenge to wild germplasm resources, necessitating artificial cultivation and domestication. Considering these factors, a high-quality genome of F. dibotrys was assembled and the evolutionary relationships within Caryophyllales were compared, based on which 58 individual samples of F. dibotrys were re-sequenced. We found that the samples could be categorized into three purebred populations and regions distributed at distinct elevations. Our varieties were cultivated from the parental populations of the subpopulation in central Yunnan. F. dibotrys is speculated to have originated in the high-altitude Tibetan Plateau region, and that its combination with flavonoids can protect plants against ultraviolet radiation; this infers a subpopulation with a high accumulation of flavonoids. This study assembled a high-quality genome and provided a theoretical foundation for the future introduction, domestication, and development of cultivated varieties of F. dibotrys.

Abstract Background Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. Methods A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow‐up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random‐effects meta‐analyses. Results Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear p

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly, the exact pathogenesis of which remains incompletely understood, and effective preventive and therapeutic drugs are currently lacking. Cholesterol plays a vital role in cell membrane formation and neurotransmitter synthesis, and its abnormal metabolism is associated with the onset of AD. With the continuous advancement of imaging techniques and molecular biology methods, researchers can more accurately explore the relationship between cholesterol metabolism and AD. Elevated cholesterol levels may lead to vascular dysfunction, thereby affecting neuronal function. Additionally, abnormal cholesterol metabolism may affect the metabolism of β-amyloid protein, thereby promoting the onset of AD. Brain cholesterol levels are regulated by multiple factors. This review aims to deepen the understanding of the subtle relationship between cholesterol homeostasis and AD, and to introduce the latest advances in cholesterol-regulating AD treatment strategies, thereby inspiring readers to contemplate deeply on this complex relationship. Although there are still many unresolved important issues regarding the risk of brain cholesterol and AD, and some studies may have opposite conclusions, further research is needed to enrich our understanding. However, these findings are expected to deepen our understanding of the pathogenesis of AD and provide important insights for the future development of AD treatment strategies targeting brain cholesterol homeostasis.

Background Comprehensive blood lipoprotein profiles and their association with incident coronary heart disease (CHD) among racially and geographically diverse populations remain understudied. Methods and Results We conducted nested case–control studies of CHD among 3438 individuals (1719 pairs), including 1084 White Americans (542 pairs), 1244 Black Americans (622 pairs), and 1110 Chinese adults (555 pairs). We examined 36 plasma lipids, lipoproteins, and apolipoproteins, measured by nuclear magnetic resonance spectroscopy, with incident CHD among all participants and subgroups by demographics, lifestyle, and metabolic health status using conditional or unconditional logistic regression adjusted for potential confounders. Conventionally measured blood lipids, that is, total cholesterol, triglycerides, low‐density lipoprotein‐cholesterol, and high‐density lipoprotein‐cholesterol, were each associated with incident CHD, with odds ratios (ORs) being 1.33, 1.32, 1.24, and 0.79 per 1‐SD increase among all participants. Seventeen lipoprotein biomarkers showed numerically stronger associations than conventional lipids, with ORs per 1‐SD among all participants ranging from 1.35 to 1.57 and a negative OR of 0.78 (all false discovery rate

Abstract Objective PD-L1, a target of immune checkpoint blockade, has been proven to take the role of an oncogene in most human tumors. However, the role of PD-L1 in human pan-cancers has not yet been fully investigated. Materials and methods Pan-cancer analysis was conducted to analyze expression, genetic alterations, prognosis analysis, and immunological characteristics of PD-L1. Estimating the correlation between PD-L1 expression and survival involved using pooled odds ratios and hazard ratios with 95% CI. The Kaplan–Meier (K-M) technique, COX analysis, and receiver operating characteristic (ROC) curves were applied to the survival analysis. Additionally, we investigated the relationships between PD-L1 and microsatellite instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers using Spearman's correlation analysis. Also, immunohistochemical analysis and qRT-PCR were employed in evaluating PD-L1’s protein and mRNA expression in pan-caner. Results PD-L1 showed abnormal mRNA and protein expression in a variety of cancers and predicted prognosis in cancer patients. Furthermore, across a variety of cancer types, the aberrant PD-L1 expression was connected to the MSI, MMR, TMB, drug sensitivity, and tumor immune microenvironment (TIME). Moreover, PD-L1 was significantly correlated with infiltrating levels of immune cells (T cell CD8 + , neutrophil, and so on). Conclusion Our study provides a better theoretical basis and guidance for the clinical treatment of PD-L1.

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare disease which is easily misdiagnosed. Vascular endothelial growth factor D (VEGF-D), as the most common biomarker, however, is not so perfect for the diagnosis and severity assessment of LAM. Materials and methods The isobaric tags for relative and absolute quantitation (iTRAQ)-based method was used to identify a cytoskeleton protein, moesin. 84 patients with LAM, 44 patients with other cystic lung diseases (OCLDs), and 37 healthy control subjects were recruited for collecting blood samples and clinical data. The levels of moesin in serum were evaluated by ELISA. The relationships of moesin with lymphatic involvement, lung function, and treatment decision were explored in patients with LAM. Results The candidate protein moesin was identified by the proteomics-based bioinformatic analysis. The serum levels of moesin were higher in patients with LAM [219.0 (118.7–260.5) pg/mL] than in patients with OCLDs (125.8 ± 59.9 pg/mL, P

Abstract Background The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. Methods This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. Results Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66–1.13] compared to 0.60 [0.49–0.73], 0.46 [0.38–0.56] and 0.62 [0.51–0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14–1.84] compared to 1.25 [0.99–1.58], 1.06 [0.85–1.32] and 0.86 [0.69–1.08]) and alcohol consumption (1.22 [1.01–1.48] compared to 1.10 [0.90–1.33], 1.15 [0.96–1.38], and 1.07 [0.91–1.26]). Conclusion We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Objectives: Clinical molecular genetic testing and molecular imaging dramatically increase the quantity of clinical data. Combined with the extensive application of electronic health records, a medical data ecosystem is forming, which calls for big-data-based medicine models. We tried to use big data analytics to search for similar patients in a cancer cohort, showing how to apply artificial intelligence (AI) algorithms to clinical data processing to obtain clinically significant results, with the ultimate goal of improving healthcare management. Methods: In order to overcome the weaknesses of most data processing algorithms that rely on expert labeling and annotation, we uniformly adopted one-hot encoding for all types of clinical data, calculating the Euclidean distance to measure patient similarity and subgrouping via an unsupervised learning model. Overall survival (OS) was investigated to assess the clinical validity and clinical relevance of the model. Results: We took gastric cancers (GCs) as an example to build a high-dimensional clinical patient similarity network (cPSN). When performing the survival analysis, we found that Cluster_2 had the longest survival rates, while Cluster_5 had the worst prognosis among all the subgroups. As patients in the same subgroup share some clinical characteristics, the clinical feature analysis found that Cluster_2 harbored more lower distal GCs than upper proximal GCs, shedding light on the debates. Conclusion: Overall, we constructed a cancer-specific cPSN with excellent interpretability and clinical significance, which would recapitulate patient similarity in the real-world. The constructed cPSN model is scalable, generalizable, and performs well for various data types.

To ensure the stable operation of a wind turbine generator system when the wind speed exceeds the rated value and address the issue of excessive rotor speed during high wind speeds, this paper proposes a novel variable pitch controller strategy based on a back-propagation neural network and optimal control theory to solve this problem. Firstly, a mathematical model for the wind turbine is established and linearized. Then, each optimal sub-controller is designed for different wind speed conditions by optimal theory. Subsequently, a back-propagation neural network is utilized to learn the variation pattern of controller parameters with respect to wind speed. Finally, real-time changes in wind speed are applied to evaluate and adjust controller parameters using the trained back-propagation neural network. The model is simulated in MATLAB 2019b, real-time data are observed, and the control effect is compared with that of a Takagi–Sugeno optimal controller, firefly algorithm optimal controller and fuzzy controller. The simulation results show that the rotor speed overshoot of the optimal controller under the step wind speed is the smallest, only 0.05 rad/s. Under other wind speed conditions, the rotor speed range fluctuates around 4.35 rad/s, and the fluctuation size is less than 0.2 rad/s, which is much smaller than the fluctuation range of other controllers. It can be seen that the back-propagation optimal controller can ensure the stability of the rotor speed above the rated wind speed. At the same time, it has better control accuracy compared to other controllers.