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Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients’ survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC. Esophageal squamous-cell carcinomas (ESCC) have poor prognosis, and detailed molecular profiles are necessary to identify prognostic markers. Here the authors analyse 60 ESCC patient samples using scRNA-seq, TCR-seq and genomics; they find mucosal immunity markers associated with survival and immunosuppressive microenvironments.

Esophageal squamous cell carcinoma (ESCC) is prevalent in some geographical regions of the world. ESCC development presents a multistep pathogenic process from inflammation to invasive cancer; however, what is critical in these processes and how they evolve is largely unknown, obstructing early diagnosis and effective treatment. Here, we create a mouse model mimicking human ESCC development and construct a single-cell ESCC developmental atlas. We identify a set of key transitional signatures associated with oncogenic evolution of epithelial cells and depict the landmark dynamic tumorigenic trajectories. An early downregulation of CD8 + response against the initial tissue damage accompanied by the transition of immune response from type 1 to type 3 results in accumulation and activation of macrophages and neutrophils, which may create a chronic inflammatory environment that promotes carcinogen-transformed epithelial cell survival and proliferation. These findings shed light on how ESCC is initiated and developed. The multistep processes involved in the evolution of inflammation to invasive esophageal squamous cell carcinoma (ESCC) is unclear. Here, the authors report a mouse model of ESCC and the role of interplay between carcinogen-transformed epithelial cells and their microenvironment in ESCC development.

Approximately half of the world’s 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1–E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28 . The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer. Oesophageal squamous-cell carcinoma (ESCC) is a leading cause of cancer death, and half of ESCC cases occur in China. Here, the authors provide an in depth genomic landscape for this disease and identify specific mutation signatures—one of which is linked to alcohol intake.

Background The exploration of age-related clinical features and adverse outcomes of non-disabling ischemic cerebrovascular disease (NICE) has been largely unaddressed in current research. This study aimed to analyze the differences in clinical characteristics and prognostic outcomes of NICE across various age groups, utilizing data from the Xi’an Stroke Registry Study in China. Methods The age distribution of NICE was categorized into four groups: age ≤ 54 years, age 55–64 years, age 65–74 years, and age ≥ 75 years. Multivariate Cox logistic regression analysis was employed to evaluate the 1-year risk of outcome events in each age group of patients with NICE. A subgroup analysis was conducted to explore interaction factors influencing age-dependent outcomes in patients with NICE. Results This study included 1,121 patients with NICE aged between 23 and 96 years, with an average age of 63.7 ± 12.2 years. Patients aged ≥ 75 years had a higher proportion of women, lower education levels, and a greater likelihood of having urban employee medical insurance. Those aged < 55 years had a higher prevalence of smoking, while individuals aged > 65 years showed a higher prevalence of comorbidities. Furthermore, there was a significant decrease in body mass index among patients aged ≥ 75 years. Laboratory tests indicated well-controlled blood lipids, liver function, and inflammation across all age groups, but renal function was notably reduced in patients with NICE aged ≥ 75 years. Adjusting for potential confounding factors revealed a significant increase in the one-year risk of all-cause mortality and poor prognosis among patients aged ≥ 75 years compared to those aged < 55 years, with no significant gender difference observed. Subgroup analysis indicated that patients with NICE who consumed alcohol were more prone to experience all-cause mortality with advancing age. Conclusions Age significantly influences the clinical characteristics and prognostic outcomes of NICE patients. Clinicians should consider age-specific characteristics when diagnosing, treating, and developing prevention strategies. Tailored prevention and treatment strategies for different age groups can enhance prognosis and reduce adverse outcomes in NICE patients.

Different extracts of Angelica dahuricae were available for whitening or treating vitiligo clinically. They showed inhibitory or activating effects on tyrosinase, a rate-limiting enzyme of melanogenesis. This study aimed to identify active compounds on tyrosinase in water extract of Angelica dahurica Radix. We applied spectrum-effect relationship and component knock-out methods to make it clear. HPLC was used to obtain the specific chromatograms. The effects on tyrosinase activity were examined by measuring the oxidation rate of levodopa in vitro. Partial least squares method was used to examine the spectrum-effect relationships. The knocked-out samples were prepared by HPLC method, and the identification of knocked-out compounds was conducted by the high performance liquid chromatography-four stage rod-electrostatic field orbit trap high resolution mass spectrometry. Results showed that S6, S14, S18, S21, S35, S36, S37, S40, and S41 were positively correlated to inhibitory activity of Angelica dahuricae on tyrosinase whereas S9, S11, S8, S12, S22, and S30 were negatively correlated. When the concentration of each sample was 1 g·mL−1, equal to the amount of raw medicinal herbs, oxypeucedanin hydrate, imperatorin, cnidilin, and isoimperatorin had inhibitory effects on tyrosinase activity whereas byakangelicin and bergapten had activating effects.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are among the leading causes of optic neuritis. This study aimed to examine differences in macular retinal structure and microvascular characteristics between affected and unaffected eyes in individuals with NMOSD and MOGAD. This cross-sectional study enrolled both eyes of patients diagnosed with optic neuritis (ON)secondary to NMOSD (22 patients: 36 NMOSD-ON eyes and 8 NMOSD-NON eyes), MOGAD (23 patients: 34 MOG-ON eyes and 12 MOG-NON eyes), and 20 age- and sex-matched healthy controls (HCs, 40 eyes) recruited from the First Affiliated Hospital of Northwest University (Xi'an No.1 Hospital) between February 2023 and January 2025. Microvascular density (MVD), vascular density (VD), blood flow area (BFA), and macular ganglion cell-inner plexiform layer (GCIPL) thickness were measured and analyzed. Both NMOSD-ON and MOG-ON eyes showed significant reductions in MVD of radial peripapillary capillary plexus (RPCP); MVD, VD, and BFA of superficial vascular complex (SVC); BFA of deep vascular complex (DVC); and GCIPL thickness compared with HCs ( < 0.001). Compared with MOG-ON eyes, NMOSD-ON eyes demonstrated a greater reduction in BFA of choriocapillaris (CC) ( = 0.040). In MOG-NON eyes, the MVD of RPCP; the MVD, VD, and BFA of SVC; the BFA of DVC; and the GCIPL thickness were significantly lower than those in HCs, but remained higher than in MOG-ON eyes. In NMOSD-ON eyes, all MVD and VD parameters, SVC BFA, and GCIPL thickness were inversely correlated with best-corrected visual acuity (BCVA) and Expanded Disability Status Scale (EDSS) scores ( < 0.05). In MOG-ON eyes, SVC MVD, VD, and GCIPL thickness were inversely correlated with BCVA and disease duration, while RPCP MVD and SVC BFA were inversely correlated only with BCVA. Both NMOSD and MOGAD cause macular structural and microvascular damage associated with reduced BCVA. Decreased CC BFA may aid in distinguishing NMOSD from MOGAD.

Background Rheumatoid arthritis (RA) is the most common autoimmune system diseases in our world. More studies in recent years have shown that FCRL gene polymorphisms is closely related to autoimmune diseases. It is suggested that genetic factors play a crucial role in the pathogenesis of this disease. In this study, we aimed to investigate the relationship between FCRL1 rs2050568, FCRL3 rs2317230 and FCRL6 rs58240276 polymorphisms and RA risk in the Chinese Han population. 506 with RA patients and 509 healthy controls were recruited in this study, and the single nucleotide polymorphisms (SNPs) was successfully genotyped using the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for age and gender were conducted to assess these SNPs polymorphisms and RA risk. The multifactor dimensionality reduction (MDR) method was conducted to analyze SNP-SNP interaction. Results Our results revealed that there no significant association was observed between the allele and genotype frequencies among these SNPs and RA risk (all p  > 0.05). Straified analysis by age and gender, the results confirmed that FCRL1 rs2050568 T/T genotype enhanced the risk of RA in females ( p  = 0.014). The G/T - T/T genotype of FCRL3 rs2317230 was correlated with a decreased RA risk in males ( p  = 0.021). We also observed that the C/T-T/T genotype of FCRL6 rs58240276 was increased the risk of RA in the group at age >  54 years ( p  = 0.016). In addition, FCRL1 rs2050568-TT, FCRL6 rs58240276-TT and FCRL1 rs2050568-TT, FCRL3 rs2317230-TT, FCRL6 rs58240276-TT are the best models for multi-site MDR analysis ( p  < 0.05), and the two best models mentioned above and classes RA have the most significant correlation. Conclusions Our study demonstrated that FCRL1 rs2050568, FCRL3 rs2317230, and FCRL6 rs58240276 polymorphisms were correlated with RA susceptibility in the Chinese Han population.

Spherical bearings are widely applied in high-speed railway bridges (HSRBs) in China. The experimental and computational analyses were carried out to help understand the damage mechanism of these bearings under earthquake loading. A shaking table test of scaled HSRB specimen (installed with spherical bearings) was performed under the simulated earthquake action, and the intensities were, respectively, 0.15 g, 0.20 g, 0.32 g, and 0.38 g (common intensities in China) of actual earthquakes in accordance with similarity relationships. After investigating and analyzing results of the shaking table test, it is shown that no damage occurred to movable bearings in all experimental earthquake scenarios, while slight damage could be found in fixed bearings at 0.32 g earthquake. Moreover, a finite element (FE) model of the prototype HSRB was established and validated. The damage degree of spherical bearings in stronger earthquakes (i.e., 0.40 g to 1.00 g) was studied through this validated FE model. The numerical results showed that the fixed bearing was completely damaged at 0.80 g earthquake, while only moderate damage occurred to the movable bearing at that intensity.

Rheumatoid arthritis (RA), an autoimmune systemic inflammatory disease, largely resulted from genetic factor. Our purpose was to explore the association for and genetic variants with RA susceptibility in the Chinese Han population. A total of 508 RA patients and 494 controls were involved in this case-control study; single-nucleotide polymorphisms (SNPs) genotyping was identified by the Agena MassARRAY platform. The relationship between polymorphisms and RA susceptibility was calculated using the Pearson's Chi-square test with odds ratios and 95% confidence intervals (CIs) in multiple genetic models. The Pearson's Chi-square test and Student's -test were used for sample basic characteristic analysis. And linkage disequilibrium (LD) analysis and haplotype analysis were performed by logistic regression analysis. The result from this study showed that rs2072472 ( ) was an increased risk factor of RA (adjusted OR = 1.41, = 0.011). Stratified analysis indicated SNPs rs10490571, rs956730, rs3917318 of , and SNPs rs4851527, rs719250, rs3218896, rs3218977, rs2072472 of had impacts on RA risk after stratification based on gender and average age (54 years). Finally, haplotype analysis revealed that A A haplotype in was related to a decreased RA risk (adjusted OR = 0.79; 95% CI = 0.65-0.94; = 0.010). Yet, rs3917225( ) and rs11674595( ) were not significant in RA association analysis. We determined SNPs (rs3917318, rs956730, rs1049057) of and SNPs (rs3218977, rs719250, rs4851527, rs3218896, rs2072472) of were correlated with the RA susceptibility in the Chinese Han population.