Discovery of a novel ROS-based signature for predicting prognosis and immunosuppressive tumor microenvironment in lung adenocarcinoma.

The role of reactive oxygen species (ROS) is critical in the emergence and progression of lung adenocarcinoma (LUAD), affecting cell survival, proliferation, angiogenesis, and metastasis. Further investigations are needed to elucidate these effects' precise pathways and devise therapeutic approaches targeting ROS. Moreover, the expression pattern and clinical significance of the ROS-related genes in LUAD remain elusive. Through comprehensive analysis incorporating 1494 LUAD cases from The Cancer Genome Atlas, six Gene Expression Omnibus series, and a Chinese LUAD cohort, we identified a ROS-related signature with substantial predictive value in various LUAD patient cohorts. The ROS-related signature has demonstrated a significant negative relationship with antitumor immunity and dendritic cell maturation and activation. Moreover, The ROS-related signature showed predictive value on immunotherapy outcomes across multiple types of solid tumors, including LUAD. These findings reinforce the ROS-related signature as a predictive tool for LUAD and provide new insights into its link with antitumor immunity and immunotherapy efficacy. These results have implications for refining clinical assessments and tailoring immunotherapeutic strategies for patients with LUAD.

Single-cell analysis identifies critical regulators of spermatogonial development and differentiation in cattle-yak bulls.

Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.

One-step hydrothermal synthesis of a Ni3S2-FeMoO4 nanowire-nanosheet heterostructure array for synergistically boosted oxygen evolution reaction.

A key factor for boosting oxygen evolution reaction (OER) is the design of heterostructures with steerable defects and interfaces, which can optimize the surface electronic structures and achieve efficient water splitting to produce hydrogen fuel. Herein, we propose a novel one-step hydrothermal approach to fabricate hierarchical Ni3S2 nanowires with an S-doped FeMoO4 nanosheet heterostructure array in situ on Ni-Fe foam (NFF) as a self-standing electrode for synergistically boosted OER. The metalloid Ni3S2 nanowires with good conductivity support the FeMoO4 nanosheets and act as high-speed paths for the charge transfer. Numerous ultrathin S-doped FeMoO4 nanosheets are uniformly distributed on each Ni3S2 nanowire to form heterostructures with larger specific surface area and more revealable active sites, and a strong synergistic effect is created at the heterostructure interfaces to further promote the OER dynamics. Additionally, the NFF serves as the conductive support substrate and simultaneously provides the Ni and Fe sources for the self-growing Ni3S2-FeMoO4, leading to a structurally-integrated electrode with low contact resistance, fast mass transfer, and good stability. Therefore, the Ni3S2-FeMoO4/NFF electrode offers a low overpotential of 331 mV to achieve 500 mA cm-2 and long-term stability at 100 mA cm-2 level for more than 40 h. This work provides insight into the heterostructure of molybdate and sulfide, and a deep understanding of the significance of the synergism in OER operation.

A single-cell characterised signature integrating heterogeneity and microenvironment of lung adenocarcinoma for prognostic stratification.

BACKGROUND: The high heterogeneity of tumour and the complexity of tumour microenvironment (TME) greatly impacted the tumour development and the prognosis of cancer in the era of immunotherapy. In this study, we aimed to portray the single cell-characterised landscape of lung adenocarcinoma (LUAD), and develop an integrated signature incorporating both tumour heterogeneity and TME for prognosis stratification. METHODS: Single-cell tagged reverse transcription sequencing (STRT-seq) was performed on tumour tissues and matched normal tissues from 14 patients with LUAD for immune landscape depiction and candidate key genes selection for signature construction. Kaplan-Meier survival analyses and in-vitro cell experiments were conducted to confirm the gene functions. The transcriptomic profile of 1949 patients from 11 independent cohorts including nine public datasets and two in-house cohorts were obtained for validation. FINDINGS: We selected 11 key genes closely related to cell-to-cell interaction, tumour development, T cell phenotype transformation, and Ma/Mo cell distribution, including HLA-DPB1, FAM83A, ITGB4, OAS1, FHL2, S100P, FSCN1, SFTPD, SPP1, DBH-AS1, CST3, and established an integrated 11-gene signature, stratifying patients to High-Score or Low-Score group for better or worse prognosis. Moreover, the prognostically-predictive potency of the signature was validated by 11 independent cohorts, and the immunotherapeutic predictive potency was also validated by our in-house cohort treated by immunotherapy. Additionally, the in-vitro cell experiments and drug sensitivity prediction further confirmed the gene function and generalizability of this signature across the entire RNA profile spectrum. INTERPRETATION: This single cell-characterised 11-gene signature might offer insights for prognosis stratification and potential guidance for treatment selection. FUNDING: Support for the study was provided by National key research and development project (2022YFC2505004, 2022YFC2505000 to Z.W. and J.W.), Beijing Natural Science Foundation (7242114 to J.X.), National Natural Science Foundation of China of China (82102886 to J.X., 81871889 and 82072586 to Z.W.), Beijing Nova Program (20220484119 to J.X.), NSFC general program (82272796 to J.W.), NSFC special program (82241229 to J.W.), CAMS Innovation Fund for Medical Sciences (2021-1-I2M-012, 2022-I2M-1-009 to Z.W. and J.W.), Beijing Natural Science Foundation (7212084 to Z.W.), CAMS Key lab of translational research on lung cancer (2018PT31035 to J.W.), Aiyou Foundation (KY201701 to J.W.). Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MOCP2022003 to J.X.).

The causal association between circulating cytokines with the risk of frailty and sarcopenia under the perspective of geroscience.

Introduction: Circulating cytokines were considered to play a critical role in the initiation and propagation of sarcopenia and frailty from observational studies. This study aimed to find the casual association between circulating cytokines and sarcopenia and frailty from a genetic perspective by two-sample Mendelian randomization (MR) analysis. Methods: Data for 41 circulating cytokines were extracted from the genome-wide association study dataset of 8,293 European participants. Inverse-variance weighted (IVW) method, MR-Egger, and weighted median method were applied to assess the relationship of circulating cytokines with the risk of aging-related syndromes and frailty. Furthermore, MR-Egger regression was used to indicate the directional pleiotropy, and Cochran's Q test was used to verify the potential heterogeneity. The "leave-one-out" method was applied to visualize whether there was a causal relationship affected by only one anomalous single-nucleotide polymorphisms. Results: Genetic predisposition to increasing levels of interleukin-10 (IL-10), IL-12, and vascular endothelial growth factor (VEGF) was associated with the higher risk of low hand grip strength according to the IVW method [R = 1.05, 95% CI = 1.01-1.10, P = 0.028, false discovery rate (FDR)-adjusted P = 1.000; OR = 1.03, 95% CI = 1.00-1.07, P = 0.042, FDR-adjusted P = 0.784; OR = 1.02, 95% CI = 1.00-1.05, P = 0.038, FDR-adjusted P = 0.567]. Furthermore, genetically determined higher macrophage colony-stimulating factors (M-CSFs) were associated with a lower presence of appendicular lean mass (OR = 1.01, 95% CI = 1.00-1.02, P = 0.003, FDR-adjusted P = 0.103). Monokine induced by interferon-γ (MIG) and tumor necrosis factor-beta (TNF-ß) were associated with a higher risk of frailty (OR = 1.03, 95% CI = 1.01-1.05, P < 0.0001, FDR-adjusted P = 0.012; OR = 1.01, 95% CI = 1.00-1.03, P = 0.013, FDR-adjusted P = 0.259). In this study, we did not find heterogeneity and horizontal pleiotropy between the circulating cytokines and the risk of frailty and sarcopenia. Conclusion: Genetic predisposition to assess IL-10, IL-12, and VEGF levels was associated with a higher risk of low hand grip strength and M-CSF with the presence of appendicular lean mass. The high levels of TNF-ß and MIG were associated with a higher risk of frailty. More studies will be required to explore the molecular biological mechanisms underlying the action of inflammatory factors.

Prediction performance comparison of biomarkers for response to immune checkpoint inhibitors in advanced non-small cell lung cancer.

BACKGROUND: The aim of the present study was to compare the predictive accuracy of PD-L1 immunohistochemistry (IHC), tissue or blood tumor mutation burden (tTMB, bTMB), gene expression profile (GEP), driver gene mutation, and combined biomarkers for immunotherapy response of advanced non-small cell lung cancer (NSCLC). METHODS: In part 1, clinical trials involved with predictive biomarker exploration for immunotherapy in advanced NSCLC were included. The area under the curve (AUC) of the summary receiver operating characteristic (SROC), sensitivity, specificity, likelihood ratio and predictive value of the biomarkers were evaluated. In part 2, public datasets of immune checkpoint inhibitor (ICI)-treated NSCLC involved with biomarkers were curated (N = 871). Odds ratio (OR) of the positive versus negative biomarker group for objective response rate (ORR) was measured. RESULTS: In part 1, the AUC of combined biomarkers (0.75) was higher than PD-L1 (0.64), tTMB (0.64), bTMB (0.68), GEP (0.67), and driver gene mutation (0.51). Combined biomarkers also had higher specificity, positive likelihood ratio and positive predictive value than single biomarkers. In part 2, the OR of combined biomarkers of PD-L1 plus TMB (PD-L1 cutoff 1%, 0.14; cutoff 50% 0.13) was lower than that of PD-L1 (cutoff 1%, 0.33; cutoff 50% 0.24), tTMB (0.28), bTMB (0.48), EGFR mutation (0.17) and KRAS mutation (0.47), for distinguishing ORR of patients after immunotherapy. Furthermore, positive PD-L1, tTMB-high, wild-type EGFR, and positive PD-L1 plus TMB were associated with prolonged progression-free survival (PFS). CONCLUSION: Combined biomarkers have superior predictive accuracy than single biomarkers for immunotherapy response of NSCLC. Further investigation is warranted to select optimal biomarkers for various clinical settings.

Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy.

Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built a neural network incorporating factors associated with neoantigen production, presentation, and recognition, which exhibited potential for differentiating cancer patients likely to benefit from ICIs. Our findings highlight the clinical utility of evaluating HLA-I tumor antigen presentation capacity and describe how ICI response may depend on HLA-mediated immunity.

Real-world outcomes of chemoimmunotherapy and selective RET inhibitors in Chinese patients with RET fusion-positive non-small cell lung cancer.

Background: Rearranged during transfection (RET) gene fusion is a target for non-small cell lung cancer (NSCLC) treatment, and RET inhibitors are approved for advanced NSCLC. The role of immune checkpoint inhibitors (ICIs) in RET fusion-positive NSCLC remains controversial. This retrospective study analyzed the efficacy of ICIs and RET inhibitors in Chinese patients with RET fusion-positive NSCLC. Methods: Data from patients diagnosed with advanced NSCLC harboring RET fusion from Jan 2017 to Sep 2021 were analyzed. Clinicopathological characteristics and outcomes of ICIs and RET inhibitors treatments were collected. Results: Seventy-five patients with RET fusion-positive advanced NSCLC were identified. The median age of patients was 57 years, half of the patients were female (50.3%), and most were non-smokers or light smokers (72%). Of the cancer types diagnosed in study patients, the KIF5B-RET fusion subtype accounted for 73.3% (55/75), twelve patients (16%) had CCDC6-RET fusion, and three (4%) had NCOA4-RET fusion. Sixteen patients were treated with ICIs. In previously untreated patients, we observed an objective response rate (ORR) of 71.4% and median progression free survival (PFS) of 7.5 months in seven assessable patients. Of four patients with PD-L1 overexpression (>50%) one received pembrolizumab and the other three patients received pemetrexed, carboplatin, and pembrolizumab or camrelizumab. In these patients, the ORR was 75% and disease control rate was 100%. Fifteen patients received selective RET inhibitors (pralsetinib and selpercatinib), resulting in an ORR of 53.3% (8/15) and median PFS of 10.0 months (95% CI 5.2-14.9). Conclusions: ICIs for PD-L overexpression and treatment naive patients offer comparable benefits for RET fusion-positive NSCLC, warranting further investigation.

Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening.

BACKGROUND: Preeclampsia is a life-threatening disease of pregnancy that lacks effective pharmaceuticals which can target its pathogenesis. Since preeclampsia involves complex pathological processes, including autophagy, this study aims to explore autophagy-related mechanisms of preeclampsia and to screen potential drugs. METHODS: Firstly, the datasets GSE75010, GSE24129, GSE66273, and autophagic genes lists were downloaded from public databases. Then, a weighted gene co-expression network analysis (WGCNA) was applied to filter autophagic-related hub genes of preeclampsia. The differential expression levels of the hub genes were validated with datasets GSE24129 and GSE66273. Next, the GO and KEGG enrichment, protein-protein interacting (PPI) network, as well as the downstream pathways was analyzed via the starBase, STRING and Cytoscape to determine the functions and regulatory network of the hub genes. Additionally, the immune microenvironment of preeclampsia was investigated by the CIBERSORTX database. Finally, three herb ingredients, berberine, baicalein, and luteolin were screened by molecular docking in comparison to pravastatin, metformin, and aspirin, to predict potential drugs for treating preeclampsia. RESULTS: A total of 54 autophagy-related genes were filtered by WGCNA. After filtering with |GS| > 0.5 and |MM| > 0.8, three hub genes, namely PKM, LEP, and HK2, were identified and validated. Among these genes, PKM and LEP were overexpressed in women older than 35 years old ( p<0.05; p<0.05); the expression of PKM, LEP, and HK2 differed remarkably in women with different BMI (all p<0.05); PKM overexpressed in women with hypertension (p<0.05). The regulatory network of hub genes demonstrated that they were mainly enriched in metabolic pathways, including the AMPK signaling pathway, glucagon signaling pathway, adipocytokine signaling pathway, and central carbon metabolism. Then, immune microenvironment analysis turned out that M2 macrophages were reduced in preeclampsia women (p<0.0001) and were negatively correlated with the expression of PKM (r=-0.2, p<0.05), LEP (r=-0.4, p<0.0001), and HK2 (r=-0.3, p<0.001). Lastly, molecular docking showed baicalein and luteolin could bind intimately to hub genes. CONCLUSION: PKM, LEP, and HK2 could be promising biomarkers for preeclampsia, which might regulate the pathogenesis of preeclampsia via metabolism pathways and immune microenvironment. Baicalein and luteolin could be potential therapeutics for preeclampsia.

Deubiquitinating enzyme OTUD4 regulates metastasis in triple-negative breast cancer by stabilizing Snail1.

Metastasis is the primary cause of cancer-related deaths and remains poorly understood. Deubiquitinase OTU domain containing 4 (OTUD4) has been reported to regulate antiviral immune responses and resistance to radio- or chemo-therapies in certain cancers. However, the role of OTUD4 in cancer metastasis remain unknown. Here, we demonstrate that the depletion of OTUD4 in triple-negative breast cancer (TNBC) cells markedly suppress cell clonogenic ability, migration, invasion and cancer stem cell population in vitro as well as metastasis in vivo. Mechanistically, the tumor promoting function of OTUD4 is mainly mediated by deuiquitinating and stabilizing Snail1, one key transcriptional factor in the epithelial-mesenchymal transition. The inhibitory effect of targeting OTUD4 could be largely reversed by the reconstitution of Snail1 in OTUD4-deficient cells. Overall, our study establishes the OTUD4-Snail1 axis as an important regulatory mechanism of breast cancer metastasis and provides a rationale for potential therapeutic interventions in the treatment of TNBC.

Separate and combined effects of famine exposure and menarche age on metabolic syndrome among the elderly: a cross-sectional study in China.

BACKGROUND: Epidemiological studies have revealed multiple risk factors for metabolic syndrome. However, there are no consistent findings on the association between famine exposure, age at menarche, and the prevalence of metabolic syndrome. This cross-sectional study aimed to reveal the individual and combined effects of famine exposure and age at menarche on the prevalence of metabolic syndrome among elderly women. METHODS: Four thousand seven hundred seventy participants between 60 and 93 years of age were selected from the China Health and Retirement Longitudinal Study. Statistical differences between the baseline characteristics of famine exposure, age at menarche, and metabolic syndrome were evaluated using the t-test, F-test, and Chi-square test. Three multivariable-adjusted logistic regression models were used to test the association between famine exposure, age of menarche, and the odds ratio of metabolic syndrome. RESULTS: Two thousand one hundred ninety-eight (46.08%) participants had metabolic syndrome, while 2572 (53.92%) participants did not. Furthermore, 3068 (64.32%) women reported onset of menarche under 15 years of age, while 1702 (35.68%) women reported onset of menarche above 16 years of age. Regarding the separate association of famine exposure and age of menarche with metabolic syndrome, in model three, the adolescence/adulthood famine exposure group vs. no famine exposure group odds ratio was 2.45 (95% CI 2.02, 2.97), and the older than 16 years vs. younger than 15 years group odds ratio was 1.23 (95% CI 1.09, 1.39), which was the highest odds ratio among the three models. Regarding the combined association of famine exposure and age of menarche with metabolic syndrome, in model three, among the age of menarche ≤ 15 years group, the adolescence/adulthood famine exposure vs. no famine exposure group odds ratio was 2.45 (95% CI: 1.91, 3.14); among the menarche age ≥ 16 years group, the adolescence/adulthood famine exposure stages vs. exposed group odds ratio was 3.27 (95% CI: 2.44, 4.38), which was the highest odds ratio among the three models. CONCLUSION: These findings suggested that famine exposure and age at menarche, either separately or in combination, were positively associated with the prevalence of metabolic syndrome among older women.

Ablation of ERO1A induces lethal endoplasmic reticulum stress responses and immunogenic cell death to activate anti-tumor immunity.

Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy efficacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1α (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell immunity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1α and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.

Heat transfer and pressure drop characteristic research of sine wavy flying-wing fins.

In recent years, heat transfer enhancement of heat exchange equipment has attracted more and more attention. In this paper, the heat transfer and pressure drop characteristics of sine wavy flying-wing fins are studied by numerical method. The objective is to improve the integrated heat transfer and pressure drop performance of sine wavy flying-wing fins. The degrees of freedom of fin sizes include fin pitch to fin height ratio fp/fh, fin height to fin wavelength ratio fh/W, fin amplitude to fin pitch ratio 2A/fp and fin inclined angle α. The results show that among the calculated 17 flying-wing fins, the optimal values of fp/fh, fh/W, 2A/fp, and α are 0.5, 0.4, 1.9 and 70° respectively. The optimized SWFWF simulation model is established, and the average JF factor is 1.307, which is about 10.9% higher than that of Fin 05 (JF = 1.18). Multiple linear regression is used to obtain the correlations of flow and heat transfer characteristics of flying-wing fins. The average deviation of the correlations for j and f are 0.85% and 4.9% respectively. The correlations can be used for the design and optimization of sine wavy flying-wing fins.

Multi-omics indicators of long-term survival benefits after immune checkpoint inhibitor therapy.

Molecular indicators of long-term survival (LTS) in response to immune-checkpoint inhibitor (ICI) treatment have the potential to provide both mechanistic and therapeutic insights. In this study, we construct predictive models of LTS following ICI therapy based on data from 158 clinical trials involving 21,023 patients of 25 cancer types with available 1-year overall survival (OS) rates. We present evidence for the use of 1-year OS rate as a surrogate for LTS. Based on these and corresponding TCGA multi-omics data, total neoantigen, metabolism score, CD8+ T cell, and MHC_score were identified as predictive biomarkers. These were integrated into a Gaussian process regression model that estimates "long-term survival predictive score of immunotherapy" (iLSPS). We found that iLSPS outperformed the predictive capabilities of individual biomarkers and successfully predicted LTS of patient groups with melanoma and lung cancer. Our study explores the feasibility of modeling LTS based on multi-omics indicators and machine-learning methods.

Long-term effective remediation of black-odorous water via regulating calcium nitrate sustained-release.

Nitrate addition is reported as a cost-effective method for remediating black-odorous water, which is mainly induced by the deficiency of electron acceptor. However, excessive release of nitrate and lack of long-term effectiveness significantly limited the application of direct nitrate dosing technology. Herein, for remediating black-odorous water, we constructed a nitrate sustained-release ecological concrete (ecoN-concrete), in which calcium nitrate (Ca(NO3)2) was dosed into concrete block to regulate the release of nitrate. The results showed that chemical oxygen demand (COD), turbidity, ammonia, phosphate, and sulfate were significantly removed in an ecoN-concrete-contained reactor fed with black-odorous water, and its removal efficiency was largely dependent on Ca(NO3)2 dosage. Meanwhile, the released nitrate was lower than 25% of its total dosage and nitrite was lower than 1.5 mg/L during 14 days remediation. After three recycles, the removal efficiencies of COD and turbidity by using ecoN-concrete were still more than 85%, indicating an excellent nitrate sustained-release performance of ecoN-concrete, which can be applied for preventing water re-blackening and re-stinking. Further investigation illustrated that the ecoN-concrete (1) decreased the abundance of Desulfovibrio, Desulfomonile, and Desulforhabdus in the phylum of Desulfobacterota to alleviate the odorous gas production and (2) significantly increased the abundance of Bacillus and Thermomonas, which utilized the released-nitrate for consuming organic matters and ammonia. This study provided an artful Ca(NO3)2 dosing strategy and long-term effective method for black-odorous water remediation.

Global burden and trends of transport injuries from 1990 to 2019: an observational trend study.

BACKGROUND: Transport injuries (TIs) are a major cause of global disability-adjusted life-years (DALYs) and mortality. In this study, we aimed to assess the global burden and trends of TIs from 1990 to 2019. METHODS: We assessed the annual age-standardised incidence rate (ASIR) and age-standardised DALYs rate of TIs by sex, age, Social Development Index (SDI) and geographical region from 1990 to 2019 from the Global Burden of Disease Study 2019. The changing trends were described by estimated annual percentage changes (EAPCs). RESULTS: Globally, in 2019, the ASIR and age-standardised DALYs rates of TIs were 134 6.06/100 000 (95% UI 11 42.6/100 000-157 5.57/100 000) and 97 7.91/100 000 (86 8.91/100 000-107 6.81/100 000), respectively. From 1990 to 2019, the global ASIR of TIs presented significant upwards trends with the EAPC (0.25%, 95% CI 0.19% to 0.31%), and it was significantly increased in the age groups of 15-49 (0.37%, 95% CI 0.29% to 0.45%), 50-69 (0.40%, 95% CI 0.36% to 0.44%) and 70+ (0.22%, 95% CI 0.17% to 0.28%). Prominent increases in ASIR were detected in middle-SDI areas (0.72%, 95% CI 0.57% to 0.87%), low-middle SDI areas (0.66%, 95% CI 0.59% to 0.72%) and low-SDI areas (0.21%, 95% CI 0.17% to 0.26%). The global age-standardised DALYs rate presented downwards trends with the EAPC (-1.27%, 95% CI -1.35% to -1.2%), and it was significantly decreased in all age groups and SDI areas. CONCLUSION: Globally, TIs still cause a serious burden, and the incidence has significantly increased, especially in people above the age of 14 and in middle-SDI and low-SDI areas, thus necessitating more attention and health interventions.

Enhanced Adhesion of Copper Films on Fused Silica Glass Substrate by Plasma Pre-Treatment.

A non-thermal atmospheric jet plasma pre-treatment technique was introduced to help the growth of extremely sticky copper films on fused silica glass substrates. A tape test was utilized to assess the bonding quality between copper films and fused silica glass substrates. AFM was used to characterize the sample surface roughness and XPS for chemical bonding characterization. The Owens-Wendt method and a Theta Lite Optical Tensiometer were used to analyze the contact angle and surface energy. The results showed that the surface energy greatly increased from 34.6 ± 0.3 mJ·m-2 to 55.9 ± 0.4 mJ·m-2 after 25 s plasma pre-treatment due to the increasing Si-O and Si-N concentrations, which brought about the electrostatic force increasing at the copper/glass interface. After 25 s plasma pre-treatment, the average surface roughness (Sa) grew from 0.8 ± 0.1 nm to 2.4 ± 0.3 nm. With higher surface roughness, there were more spaces and vacancies for the copper atoms to make contact on the bonded surfaces and increase the mechanical bite force. The electrostatic force and the mechanical bite force on the interface helped to form an atomic diffusion connection layer and improved the interactions between the copper film and the glass substrate. The findings in the SEM supported the conclusions stated above. Therefore, the adhesion between copper films and fused silica glass substrates increased by about 20% by 25 s plasma pre-treatment compared with the untreated glass substrate.

Relationship between baseline and changed serum uric acid and the incidence of type 2 diabetes mellitus: a national cohort study.

Objective: To explore the correlation between baseline serum uric acid (SUA) and SUA changes with the incidence of type 2 diabetes mellitus (T2DM) among middle-aged and older individuals. Method: Binary logistic regression was used to calculate the odds ratio (ORs) and 95% confidence intervals (CIs) of the effects of baseline and changes in SUA on the incidence of T2DM. Stratified analysis was conducted based on sex, and the SUA levels were classified into four quartiles to assess the effect of baseline and relative changes in SUA on the incidence of T2DM. Furthermore, interaction analysis was performed between body mass index (BMI) and SUA, age and SUA, and sex and SUA. Results: In the cohort study, the highest quartiles of SUA were significantly correlated with an increased incidence of T2DM among females in model 1 [OR = 2.231 (1.631, 3.050)], model 2 [OR = 2.090 (1.523, 2.867)], model 3 [OR = 2.075 (1.511, 2.849)], and model 4 [OR = 1.707 (1.234, 2.362)]. The highest quartiles of SUA had a statistically significant effect on the incidence of T2DM among all participants in model 1 [OR = 1.601 (1.277, 2.008)], model 2 [OR = 1.519 (1.204, 1.915)], model 3 [OR = 1.597 (1.257, 2.027)], and model 4 [OR = 1.380 (1.083, 1.760)]. Regarding the relative change of SUA, the highest quantiles of SUA were significantly correlated with an increased incidence of T2DM among females in model 1 [OR = 1.409 (1.050, 1.890)], model 2 [OR = 1.433 (1.067, 1.926)], and model 3 [OR = 1.420 (1.056, 1.910)], and there was a statistically significant correlation with incident T2DM among all participants in model 4 [OR = 1.346 (1.079, 1.680)] after adjusting for all covariates. However, there was no significant correlation between baseline, relative, and absolute changes in SUA and the incidence of T2DM among males. The interaction analysis demonstrated that sex, BMI, and the relative changes in SUA had a combined effect on the incidence of T2DM, while age and the changes in SUA had a joint effect on the incidence of T2DM only in females. Conclusion: There was a positive association between SUA and the incidence of T2DM for all participants. However, significant sex differences in incidence were observed only in women, not men.

Efficacy and safety of nab-paclitaxel or combined nab-paclitaxel and immune checkpoint inhibitors in relapsed small-cell lung cancer.

Background: Most patients with small-cell lung cancer (SCLC) experience disease progression after first-line chemotherapy. Notably, nab-paclitaxel monotherapy has antitumor activity in relapsed SCLC. Objective: This study evaluated the efficacy and safety of combined of nab-paclitaxel and immune checkpoint inhibitors (ICIs) in relapsed SCLC. Design: We retrospectively analyzed patients with relapsed SCLC who received nab-paclitaxel or combined nab-paclitaxel and ICIs (anti-programmed death-1, PD-1 or anti-programmed cell death 1 ligand, PD-L1) between February 2017 and September 2021. Methods: Efficacy and safety data were collected from electronic health records. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method and a standard log-rank test. Results: We included 56 patients with relapsed SCLC, of which 29 received nab-paclitaxel alone (Group A), and 27 received combined nab-paclitaxel and ICIs (Group B). Baseline characteristics were similar between the two groups. Group B had a numerically higher objective response rate than Group A (40.7% versus 17.2%; p = 0.052). However, combined nab-paclitaxel and ICIs failed to demonstrate survival superiority over nab-paclitaxel monotherapy [median PFS: 3.2 months versus 2.8 months (p = 0.5225); median OS: 11.0 months versus 9.3 months (p = 0.7298)]. The safety profiles of Groups A and B were both tolerable. Conclusion: This study indicated that compared with nab-paclitaxel monotherapy, combined nab-paclitaxel and ICIs failed to improve survival in relapsed SCLC.

Incidence and characteristics of aqueous misdirection after glaucoma surgery in Chinese patients with primary angle-closure glaucoma.

BACKGROUND: To report the incidence and clinical characteristics of aqueous misdirection (AM) after glaucoma surgery in Chinese patients with primary angle-closure glaucoma. METHODS: Medical records of all patients diagnosed with primary angle-closure glaucoma who underwent glaucoma surgery in the Eye Hospital of Wenzhou Medical University between January 2012 and December 2021 were retrospectively reviewed. Cases of AM were identified through a keyword-based search. The incidence of AM was calculated. Demographic and clinical characteristics of the AM patients were also described. RESULTS: A total of 5044 eyes with primary angle-closure glaucoma were included (mean age 65.81 ± 9.96 years, 68.11% women). Thirty-eight eyes developed AM, presenting an overall incidence of 0.75%. The mean time interval between surgery and first record of AM diagnosis was 2.57 ± 5.24 months (range, 0 day to 24 months). The incidence of AM was significantly higher in patients aged ≤ 40 years (21.28%) and those aged 40-50 years (3.32%), compared to those > 50 years (0.42%) (P < 0.001). AM developed much more frequently among patients with chronic angle-closure glaucoma (1.30%), compared to those with acute angle-closure glaucoma (0.32%, P < 0.001). Eleven eyes (0.37%) developed AM following non-filtering surgery compared to 24 eyes (2.27%) after filtering surgery (P < 0.001). CONCLUSION: The incidence of AM after glaucoma surgery was 0.75% in Chinese patients with primary angle closure glaucoma. Younger age, chronic angle-closure glaucoma, and undergoing filtering surgery, were identified as associated risk factors for developing AM. Phacoemulsification may have less risk of developing AM compared to filtering surgery.