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Abstract Background In tumor treatment, protein tyrosine kinase inhibitors (TKIs) have been extensively utilized. However, the efficacy of TKI is significantly compromised by drug resistance. Consequently, finding an effective solution to overcome TKI resistance becomes crucial. Reactive oxygen species (ROS) are a group of highly active molecules that play important roles in targeted cancer therapy including TKI targeted therapy. In this review, we concentrate on the ROS-associated mechanisms of TKI lethality in tumors and strategies for regulating ROS to reverse TKI resistance in cancer. Main body Elevated ROS levels often manifest during TKI therapy in cancers, potentially causing organelle damage and cell death, which are critical to the success of TKIs in eradicating cancer cells. However, it is noteworthy that cancer cells might initiate resistance pathways to shield themselves from ROS-induced damage, leading to TKI resistance. Addressing this challenge involves blocking these resistance pathways, for instance, the NRF2-KEAP1 axis and protective autophagy, to promote ROS accumulation in cells, thereby resensitizing drug-resistant cancer cells to TKIs. Additional effective approaches inducing ROS generation within drug-resistant cells and providing exogenous ROS stimulation. Conclusion ROS play pivotal roles in the eradication of tumor cells by TKI. Harnessing the accumulation of ROS to overcome TKI resistance is an effective and widely applicable approach. Graphical Abstract

Abstract Postoperative neurological dysfunction (PND) is one of the most common complications after a total aortic arch replacement (TAAR). Electrical impedance tomography (EIT) monitoring of cerebral hypoxia injury during TAAR is a promising technique for preventing the occurrence of PND. This study aimed to explore the feasibility of electrical impedance tomography (EIT) for warning of potential brain injury during total aortic arch replacement (TAAR) through building the correlation between EIT extracted parameters and variation of neurological biomarkers in serum. Patients with Stanford type A aortic dissection and requiring TAAR who were admitted between December 2021 to March 2022 were included. A 16-electrode EIT system was adopted to monitor each patient’s cerebral impedance intraoperatively. Five parameters of EIT signals regarding to the hypothermic circulatory arrest (HCA) period were extracted. Meanwhile, concentration of four neurological biomarkers in serum were measured regarding to time before and right after surgery, 12 h, 24 h and 48 h after surgery. The correlation between EIT parameters and variation of serum biomarkers were analyzed. A total of 57 TAAR patients were recruited. The correlation between EIT parameters and variation of biomarkers were stronger for patients with postoperative neurological dysfunction (PND(+)) than those without postoperative neurological dysfunction (PND(−)) in general. Particularly, variation of S100B after surgery had significantly moderate correlation with two parameters regarding to the difference of impedance between left and right brain which were MRAIabs and TRAIabs (0.500 and 0.485 with p

Abstract Background Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. Methods Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium’s genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. Results We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005–1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy’s effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973–1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658–1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941–1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). Conclusion In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.

BackgroundAccumulating evidence reveals mitochondrial dysfunction exacerbates intestinal barrier dysfunction and inflammation. Despite the growing knowledge of mitochondrial dysfunction and ulcerative colitis (UC), the mechanism of mitochondrial dysfunction in UC remains to be fully explored.MethodsWe integrated 1137 UC colon mucosal samples from 12 multicenter cohorts worldwide to create a normalized compendium. Differentially expressed mitochondria-related genes (DE-MiRGs) in individuals with UC were identified using the “Limma” R package. Unsupervised consensus clustering was utilized to determine the intrinsic subtypes of UC driven by DE-MiRGs. Weighted gene co-expression network analysis was employed to investigate module genes related to UC. Four machine learning algorithms were utilized for screening DE-MiRGs in UC and construct MiRGs diagnostic models. The models were developed utilizing the over-sampled training cohort, followed by validation in both the internal test cohort and the external validation cohort. Immune cell infiltration was assessed using the Xcell and CIBERSORT algorithms, while potential biological mechanisms were explored through GSVA and GSEA algorithms. Hub genes were selected using the PPI network.ResultsThe study identified 108 DE-MiRGs in the colonic mucosa of patients with UC compared to healthy controls, showing significant enrichment in pathways associated with mitochondrial metabolism and inflammation. The MiRGs diagnostic models for UC were constructed based on 17 signature genes identified through various machine learning algorithms, demonstrated excellent predictive capabilities. Utilizing the identified DE-MiRGs from the normalized compendium, 941 patients with UC were stratified into three subtypes characterized by distinct cellular and molecular profiles. Specifically, the metabolic subtype demonstrated enrichment in epithelial cells, the immune-inflamed subtype displayed high enrichment in antigen-presenting cells and pathways related to pro-inflammatory activation, and the transitional subtype exhibited moderate activation across all signaling pathways. Importantly, the immune-inflamed subtype exhibited a stronger correlation with superior response to four biologics: infliximab, ustekinumab, vedolizumab, and golimumab compared to the metabolic subtype.ConclusionThis analysis unveils the interplay between mitochondrial dysfunction and the immune microenvironment in UC, thereby offering novel perspectives on the potential pathogenesis of UC and precision treatment of UC patients, and identifying new therapeutic targets.

Abstract Histone lactylation has been reported to involve in tumorigenesis and development. However, its biological regulatory mechanism in endometrial carcinoma (EC) is yet to be reported in detail. In the present study, we evaluated the modification levels of global lactylation in EC tissues by immunohistochemistry and western blot, and it was elevated. The non-metabolizable glucose analog 2-deoxy-d-glucose (2-DG) and oxamate treatment could decrease the level of lactylation so as to inhibit the proliferation and migration ability, induce apoptosis significantly, and arrest the cell cycle of EC cells. Mechanically, histone lactylation stimulated USP39 expression to promote tumor progression. Moreover, USP39 activated PI3K/AKT/HIF-1α signaling pathway via interacting with and stabilizing PGK1 to stimulate glycolysis. The results of present study suggest that histone lactylation plays an important role in the progression of EC by promoting the malignant biological behavior of EC cells, thus providing insights into potential therapeutic strategies for endometrial cancer.

Abstract Background Lung cancer is the leading cause of cancer-related death worldwide. The sex differences in the occurrence and fatality rates of non-small cell lung cancer (NSCLC), along with its association with estrogen dependence, suggest that estrogen receptors (ERs) contribute to the development of NSCLC. However, the influence of G protein-coupled estrogen receptor (GPER1) on NSCLC remains to be determined. Escape from ferroptosis is one of the hallmarks of tumor discovered in recent years. In this context, the present study evaluated whether GPER1 promotes NSCLC progression by preventing ferroptosis, and the underlying mechanism through which GPER1 protects against ferroptosis was also explored. Methods The effects of GPER1 on the cytotoxicity of H2O2, the ferroptosis inducer RSL3, and Erastin were assessed using the CCK8 assay and plate cloning. Lipid peroxidation levels were measured based on the levels of MDA and BODIPY™581/591C11. GPER1 overexpression and knockdown were performed and G1 was used, and the expression of SCD1 and PI3K/AKT/mTOR signaling factors was measured. Immunofluorescence analysis and immunohistochemistry were performed on paired specimens to measure the correlation between the expression of GPER1 and SCD1 in NSCLC tissues. The effect of GPER1 on the cytotoxicity of cisplatin was measured in vitro using the CCK8 assay and in vivo using xenograft tumor models. Results GPER1 and G1 alleviated the cytotoxicity of H2O2, reduced sensitivity to RSL3, and impaired lipid peroxidation in NSCLC tissues. In addition, GPER1 and G1 promoted the protein and mRNA expression of SCD1 and the activation of PI3K/AKT/mTOR signaling. GPER1 and SCD1 expression were elevated and positively correlated in NSCLC tissues, and high GPER1 expression predicted a poor prognosis. GPER1 knockdown enhanced the antitumor activity of cisplatin in vitro and in vivo. Conclusion GPER1 prevents ferroptosis in NSCLC by promoting the activation of PI3K/AKT/mTOR signaling, thereby inducing SCD1 expression. Therefore, treatments targeting GPER1 combined with cisplatin would exhibit better antitumor effects. Graphical Abstract

To address the challenge of retrieving subcanopy topography using single-baseline single-polarization TanDEM-X interferometric synthetic aperture radar (InSAR) data, we propose a novel InSAR processing framework. Our methodology begins by employing the SINC model to estimate the penetration depth (PD). Subsequently, we establish a linear relationship between PD and phase center height (PCH) to generate a wall-to-wall PCH product. To achieve this, spaceborne light detection and ranging (LiDAR) data are employed to capture the elevation bias between actual ground elevation and InSAR-derived elevation. Finally, the subcanopy topography is derived by subtracting the PCH from the conventional InSAR-based digital elevation model (DEM). Moreover, this approach enables the simultaneous estimation of forest height from single-baseline TanDEM-X data by combining the estimated PD and PCH components. The approach has been validated against airborne LiDAR scanning (ALS) data over four diverse sites encompassing different forest types, terrain conditions, and climates. The derived subcanopy topography in the boreal and hemiboreal forest sites (Krycklan and Remningstorp) demonstrated notable improvement in accuracy. Additionally, the winter acquisitions outperformed the summer ones in terms of inversion accuracy. The achieved root-mean-square errors (RMSEs) for the winter scenarios were 2.45 m and 3.83 m, respectively, representing a 50% improvement over the InSAR-based DEMs. The forest heights are also close to the ALS measurements, with RMSEs of 2.70 m and 3.33 m, respectively. For the Yanguas site in Spain, characterized by rugged terrain, subcanopy topography in forest areas was estimated with an accuracy of 4.27 m, a 35% improvement over the original DEM. For the denser tropical forest site, only an average elevation bias could be corrected.

Abstract Background METTL3 plays a significant role as a catalytic enzyme in mediating N6-methyladenosine (m6A) modification, and its importance in tumour progression has been extensively studied in recent years. However, the precise involvement of METTL3 in the regulation of translation in non-small cell lung cancer (NSCLC) remains unclear. Results Here we discovered by clinical investigation that METTL3 expression is correlated with NSCLC metastasis. Ablation of METTL3 in NSCLC cells inhibits invasion and metastasis in vitro and in vivo. Subsequently, through translatomics data mining and experimental validation, we demonstrated that METTL3 enhances the translation of aromatase (CYP19A1), a key enzyme in oestrogen synthesis, thereby promoting oestrogen production and mediating the invasion and metastasis of NSCLC. Mechanistically, METTL3 interacts with translation initiation factors and binds to CYP19A1 mRNA, thus enhancing the translation efficiency of CYP19A1 in an m6A-dependent manner. Pharmacological inhibition of METTL3 enzymatic activity or translation initiation factor eIF4E abolishes CYP19A1 protein synthesis. Conclusions Our findings indicate the crucial role of METTL3-mediated translation regulation in NSCLC and reveal the significance of METTL3/eIF4E/CYP19A1 signaling as a promising therapeutic target for anti-metastatic strategies against NSCLC. Graphical abstract

Abstract Background Subclinical hypothyroidism (SCH) is linked to dyslipidaemia and adverse pregnancy outcomes. However, the impact of dyslipidaemia on the outcome of pregnancy in SCH is unclear. Methods We enrolled 36,256 pregnant women and evaluated their pregnancy outcomes. The following data was gathered during the first trimester (≤ 13+ 6 weeks of gestation): total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), high-density lipoprotein (HDL-C), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations. The reference ranges for lipids were estimated to range from the 5th to the 95th percentile. Logistic regression assessed the relationships between dyslipidaemia and adverse pregnancy outcomes, including abortion, preeclampsia/eclampsia, low birth weight, foetal growth restriction, premature rupture of foetal membranes, gestational hypertension, preterm birth, macrosomia and gestational diabetes mellitus (GDM). Additionally, the best thresholds for predicting adverse pregnancy outcomes based on TSH, FT4, and lipid levels were determined using receiver operating characteristic curves. Results In the first trimester, LDL-C > 3.24 mmol/L, TG > 1.92 mmol/L, HDL-C 5.39 mmol/L were used to define dyslipidaemia. In this cohort, 952 (3.56%) patients were diagnosed with SCH, and those who had dyslipidaemia in the first trimester had higher incidences of gestational hypertension (6.59% vs. 3.25%), preeclampsia/eclampsia (7.14% vs. 3.12%), GDM (22.53% vs. 13.77%), and low birth weight (4.95% vs. 2.08%) than did those without dyslipidaemia. However, after adjusting for prepregnancy body mass index (pre-BMI), dyslipidaemia was no longer related to these risks. Furthermore, elevated TG dyslipidaemia in SCH patients was connected to an enhanced potential of gestational hypertension (odds ratio [OR]: 2.687, 95% confidence interval [CI]: 1.074 ~ 6.722), and elevated LDL-C dyslipidaemia correlated with increased preeclampsia/eclampsia risk (OR: 3.172, 95% CI: 1.204 ~ 8.355) after accounting for age, smoking status, alcohol use, pre-BMI, and levothyroxine use. Additionally, the combination of TC, TG, LDL-C, pre-BMI, and TSH exhibited enhanced predictive capabilities for gestational hypertension, preeclampsia/eclampsia, and GDM. Values of 0.767, 0.704, and 0.706 were obtained from the area under the curve. Conclusions Among pregnant women with SCH, dyslipidaemia in early pregnancy was related to elevated risks of adverse pregnancy consequences. The combined consideration of age, pre-BMI, TSH, and lipid levels in the first trimester could be beneficial for monitoring patients and implementing interventions to reduce adverse pregnancy outcomes.

BackgroundFor Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments.MethodsWe utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs.ResultsSubtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. ConclusionsThe findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.

Abstract The visible light localization system holds great promise as a highly accurate indoor positioning method. However, it still suffers deficiencies including high latency and power consumption, and large area cost. To address these issues, a high energy efficient spiking localization system inspired by the biological spatial representation system is presented. This system utilizes an optical neuromorphic sensor, consisting of a compact NbOx‐based threshold switching memristor and a photoresistor. The key lies in the system's ability to convert analog light information into electrical spikes, resembling the behavior of sensory neurons, which enables the encoding of light illuminance through spiking frequency. Consequently, the system achieves high uniformity, high linearity (≈10%), and high sensitivity (≈1.1 kHz Lux−1 and ≈72.7 kHz cm−1 for light illuminance and distance detection, respectively), indicating its potential suitability for visible light localizations. By leveraging a spiking neural network classifier, the system successfully distinguishes locations with different illuminances. After 150 epochs, it achieves an accuracy of 97%, showcasing the feasibility of using the spiking localization system in real‐world applications. The approach of spike‐based light positioning is a leap forward toward the development of future compact, highly energy‐efficient visible light localization systems.

Background/purpose: Previous epidemiological studies have associated interstitial lung disease (ILD) with rheumatoid arthritis (RA), yet the causality of this relationship remains uncertain. This study aimed to investigate the genetic causal link between ILD and RA.Methods: Genome-wide association study (GWAS) statistics for ILD and RA were collected from public datasets. Relevant single-nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship between the two conditions. The MR analysis primarily used the inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression methods. Sensitivity analyses, including MR-Egger, leave-one-out, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate the heterogeneity and pleiotropy. Replication analyses using Asian datasets were also conducted to enhance the robustness of our findings.Results: In the European population, RA was found to increase the risk of ILD by 9.6% (OR: 1.096, 95% CI: 1.023–1.174, p = 0.009). Conversely, ILD was associated with a 12.8% increased risk of RA (OR: 1.128, 95% CI: 1.013–1.256, p = 0.029). Replication analyses from Asian GWAS further supported these findings, particularly the increased risk of ILD attributable to RA (OR: 1.33, 95% CI: 1.18–1.49, p-value

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

Background: Colorectal cancer (CRC) is one of the most common malignancies, and pyroptosis exerts an immunoregulatory role in CRC. Although the location of the primary tumor is a prognostic factor for patients with CRC, the mechanisms of pyroptosis in left- and right-sided CRC remain unclear. Methods: Expression and clinical data were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Differences in clinical characteristics, immune cell infiltration, and somatic mutations between left- and right-sided CRC were then compared. After screening for differentially expressed genes, Pearson correlation analysis was performed to select pyroptosis-related genes, followed by a gene set enrichment analysis. Univariate and multivariate Cox regression analyses were used to construct and validate the prognostic model and nomogram for predicting prognosis. Collected left- and right-sided CRC samples were subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate the expression of key pyroptosis-related genes. Results: Left- and right-sided CRC exhibited significant differences in clinical features and immune cell infiltration. Five prognostic signatures were identified from among 134 pyroptosis-related differentially expressed genes to construct a risk score-based prognostic model, and adverse outcomes for high-risk patients were further verified using an external cohort. A nomogram was also generated based on three independent prognostic factors to predict survival probabilities, while calibration curves confirmed the consistency between the predicted and actual survival. Experiment data confirmed the significant differential expression of five genes between left- and right-sided CRC. Conclusion: The five identified pyroptosis-related gene signatures may be potential biomarkers for predicting prognosis in left- and right-sided CRC and may help improve the clinical outcomes of patients with CRC.

Abstract Background Nasopharyngeal carcinoma (NPC) is a relatively common type of cancer in Southern China, with local recurrence or distant metastases even after radical treatment; consequently, it is critical to identify the patients at higher risk for these events beforehand. This study aimed to assess the prognostic value of regional lymph node density (RLND) associated nomograms in NPC and to evaluate the utility of nomograms in risk stratification. Methods A total of 610 NPC patients without distant metastases (425 in the training and 185 in the validation cohort) were enrolled. The MRI-identified nodal features and clinical characteristics were documented, and the RLND was calculated. Cox analyses were conducted to identify prognostic-associated factors. Nomograms were generated based on the multivariate analysis results. The predictive accuracy and discriminative ability of the nomogram models were determined using the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve; the results were compared with those of the tumor-node-metastasis (TNM) classification. Decision curve analysis (DCA) and C-index were used to assess the prognostic effect and added discriminative ability of RLND. We also estimated the optimal RLND-based nomogram score cut-off values for survival prediction. Results RLND was an independent predictor of overall survival (OS) and disease-free survival (DFS), with hazard ratios of 1.36 and 1.30, respectively. RLND was utilized in the construction of nomograms, alongside other independent prognostic factors. The RLND-based nomogram models presented a more effective discriminative ability than the TNM classification for predicting OS (C-index, 0.711 vs. 0.680) and DFS (C-index, 0.681 vs. 0.669), with favorable calibration and consistency. The comparison of C-index values between the nomogram models with and without RLND provided substantiation of the crucial role RLND plays in these models. DCA confirmed the satisfactory clinical practicability of RLND. Moreover, the nomograms were used to categorize the patients into three groups (high-, middle-, and low-risk), and the Kaplan–Meier curves showed significant differences in prognosis between them (p

Abstract To detect circulating tumor cells (CTCs) in the peripheral blood of patients with tumor, and to analyze the significance of CTC detection in tumor diagnosis and monitoring. In the present study, peripheral blood was collected from 125 patients with tumor, and CTCs were isolated and identified. Differences in CTC number and subtype detection were analyzed for different tumor diseases and stages. CTCs were detected in 122 of the 125 patients with tumor, with a positive rate of 97.6%. The number of CTCs increases in patients with vascular metastasis. The number of mesenchymal CTCs increases in patients with lymph node or vascular metastasis. The average ratio of epithelial CTCs in each positive sample decreases in the later stages of cancer compared with the earlier stages, while the average ratio of mesenchymal CTCs increases in the later stages of cancer compared with the earlier stages. The results showed that CTCs with mesenchymal phenotypes are closely related to lymph node or vascular metastasis. CTC detection can help with early diagnosis of tumor diseases. Continuous monitoring of changes in CTCs number and subtypes can assist clinical judgment of tumor disease development status and prognosis.

Abstract Background The pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been found to have increased expression in the joints of patients with RA compared to healthy individuals. However, the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and RA remained unknown. In this study, two-sample Mendelian randomization (MR) was used to investigate the causal relationship between IL-17 and RA. Methods Summary statistics for RA (14,361 RA cases and 43,923 healthy controls) and IL-17 (3,301 samples) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. Then we used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality. MR and MVMR analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods, which were applied to the genetic instrumental variables (IVs) of IL-17A/IL-17 RA, IL-17C/IL-17 RC, and IL-17D/IL-17RD and RA. For assessing the robustness of the results, we also carried out a sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO). Results Two-sample MR Analysis showed the causal relationship between IL-17A/IL-17RA and RA. The presence of genetically high IL-17A/IL-17RA may increase the risk of RA (IL-17A(OR = 1.095; 95% C.I., 0.990-1.210, p.adj = 0.013), IL-17RA(OR = 1.113, 95%CI = 1.006-1.231, p.adj = 0.006)). However, the results indicated that IL-17C/IL-17RC, and IL-17D/IL-17RD demonstrated no causal impact on RA (IL-17C(OR = 1.007, 95%CI = 0.890-1.139, p.adj = 0.152), IL-17RC(OR = 1.006, 95%CI = 0.904-1.119, p.adj = 0.152), IL-17D(OR = 0.979, 95%CI = 0.843-1.137, p.adj = 0.130), IL-17RD(OR = 0.983, 95%CI = 0.876-1.104, p.adj = 0.129)). Furthermore, MVMR analysis shown that IL-17RA(OR = 1.049, 95% CI: 0.997-1.102, p.adj = 0.014) was associated with increased risk of RA. Sensitivity analysis showed no heterogeneity and pleiotropy, suggesting that the above results were robust and reliable. Conclusion The MR analysis provides evidence that IL-17A/IL-17RA are risk factors for RA. This emphasizes the importance of intervention on IL-17A/IL-17RA in patients with RA. Developing drugs that limit IL-17A may reduce the risk of RA.

Abstract Lung adenocarcinoma (LUAD) is a common type of malignant tumor with poor prognosis and high mortality. In our previous studies, we found that estrogen is an important risk factor for LUAD, and different estrogen statuses can predict different prognoses. Therefore, in this study, we constructed a prognostic signature related to estrogen reactivity to determine the relationship between different estrogen reactivities and prognosis. We downloaded the LUAD dataset from The Cancer Genome Atlas (TCGA) database, calculated the estrogen reactivity of each sample, and divided them into a high-estrogen reactivity group and a low-estrogen reactivity group. The difference in overall survival between the groups was significant. We also analyzed the status of immune cell infiltration and immune checkpoint expression between the groups. We analyzed the differential gene expression between the groups and screened four key prognostic factors by the least absolute shrinkage and selection operator (LASSO) regression and univariable and multivariable Cox regression. Based on the four genes, a risk signature was established. To a certain extent, the receiver operating characteristic (ROC) curve showed the predictive ability of the risk signature, which was further verified using the GSE31210 dataset. We also determined the role of estrogen in LUAD using an orthotopic mouse model. Additionally, we developed a predictive nomogram combining the risk signature with other clinical characteristics. In conclusion, our four-gene prognostic signature based on estrogen reactivity had prognostic value and can provide new insights into the development of treatment strategies for LUAD.

Abstract Background Endometrial cancer (EC) is one of the worldwide gynecological malignancies. Endoplasmic reticulum (ER) stress is the cellular homeostasis disturbance that participates in cancer progression. However, the mechanisms of ER Stress on EC have not been fully elucidated. Method The ER Stress-related genes were obtained from Gene Set Enrichment Analysis (GSEA) and GeneCards, and the RNA-seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The risk signature was constructed by the Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis. The significance of the risk signature and clinical factors were tested by time-dependent receiver operating characteristic (ROC) curves, and the selected were to build a nomogram. The immunity correlation was particularly analyzed, including the related immune cells, pathways, and immune checkpoints. Functional enrichment, potential chemotherapies, and in vitro validation were also conducted. Result An ER Stress-based risk signature, consisting of TRIB3, CREB3L3, XBP1, and PPP1R15A was established. Patients were randomly divided into training and testing groups with 1:1 ratio for subsequent calculation and validation. Based on risk scores, high- and low-risk subgroups were classified, and low-risk subgroup demonstrated better prognosis. The Area Under Curve (AUC) demonstrated a reliable predictive capability of the risk signature. The majority of significantly different immune cells and pathways were enriched more in low-risk subgroup. Similarly, several typical immune checkpoints, expressed higher in low-risk subgroup. Patients of the two subgroups responded differently to chemotherapies. Conclusion We established an ER Stress-based risk signature that could effectively predict EC patients’ prognosis and their immune correlation.

This is an essay in the field of mineral processing engineering. In addition to the valuable elements copper and tungsten, there are still valuable fluorite resources in the newly discovered ore bodies of Kafang Branch of Yunnan Tin Group. The grade of fluorite in copper and tungsten flotation tailings is as high as 31.98%, the fluorite is coarse medium grain embedded, and the liberation degree is more than 95%. Besides quartz and feldspar, the gangue minerals are mainly hedenbergite with weak magnetism. During beneficiation tests, magnetic separation has been first conducted to remove the hedenbergite into magnetic gangue minerals, which reduces the interference on fluorite flotation process. Then flotation tests have been conducted using “one roughing- two scavenging- six cleaning” process, during which acidified sodium silicate as collector, sodium oleate as collector and return the middlings to scavenging 1, and a fluorite concentrate assaying 96.27% CaF2 with operation recovery of 88.85% has been obtained, which realized the efficient and comprehensive utilization of fluorite resources in Kafang mining area.

As the global ecological environment faces serious challenges, ecological protection has attracted global attention. As a basic industry of the national economy, China’s total forestry output value is 8.04 trillion RMB in 2022. This study aims to assess the impact of ecological protection on high-quality forestry development and find its mechanism by using provincial panel data from 2010 to 2021 in China. The variables of environmental regulation and urbanization level were introduced. The benchmark regression model, mediation effect model and threshold effect model were employed for empirical analysis. The results show that: (1) The estimated ecological protection coefficient is 0.146. The ecological protection level significantly promotes high-quality forestry development; (2) The effect is more significant in the western region and the area with higher forest coverage. The estimated coefficients are 1.392 and 0.745. It is less affected by the marginal effect of the ecological protection level in the east; (3) The estimated environmental regulation coefficient is −0.021. Ecological protection promotes high-quality forestry development by reducing environmental regulations; (4) The impact increases with the level of urbanization. The p-value of the double threshold is 0.073. Therefore, policy recommendations are proposed to strengthen ecological protection and promote high-quality forestry development.

In order to explore the feasibility of using algae to treat the fly ash leachate from a safe landfill site, leachate samples taken from a certain safe landfill site in Wenzhou City were treated with two different microalgae, Chlorella vulgaris and Scenedesmus obliquus, and the effectiveness of each treatment was evaluated in terms of its efficiency of pollutant removal. The effects of conditions such as pretreatment of leachate by sterilization, the initial concentration of leachate, and the addition of nutrients on pollutant removal efficiency and algae growth were studied. Sterilization of the leachate was found to have a relatively small impact on the growth of C. vulgaris and S. obliquus, as well as the removal of pollutants from the leachate. Therefore, sterilization treatment may not be necessary for engineering applications. Algal growth and the removal of pollutants were optimal when the leachate was used at a concentration of 10%, but when the leachate concentration was 30% or higher, the growth of both algae was weakened. The inclusion of 0.2 g/L K2HPO4·3H2O and 0.06 g/L ammonium ferric citrate in the system led to higher algal growth and pollutant removal. The chlorophyll a levels of C. vulgaris and S. obliquus were 555.53% and 265.15%, respectively, and the nitrogen removal rates were also the highest, reaching 59.51% and 56.69%, respectively. This study optimized the cultivation conditions of a microalgae treatment leachate system, providing technical support and a theoretical basis for the practical engineering of a harmless treatment of leachate.

We utilize a femtosecond laser-inscribed small-period long-period fiber grating (SP-LPFG) to induce a nonlinear polarization rotation (NPR) effect for mode-locking pulses in a normal dispersion erbium-doped fiber laser (EDFL). The SP-LPFG has a length of 2.5 mm and a period of 25 μm. At wavelengths of 1556 nm and 1561 nm, it exhibits polarization-dependent loss (PDL) values of 20 dB and 14.5 dB, respectively, sufficient to trigger the NPR mechanism. With the pump power increased to 500 mW, the laser achieves normal dispersion mode-locked pulses centered at 1575 nm in the L-band, with a 3 dB bandwidth of 1.35 nm and a pulse width of 1.61 ps. The radio frequency (RF) spectrum reveals an signal-to-noise ratio (SNR) of up to 63.6 dB, demonstrating the excellent stability of the laser operation. This SP-LPFG holds promising applications, paving the way for efficient, compact, and stable normal dispersion ultrafast fiber lasers.

Although introducing high porosity in biomedical Ti alloys can reduce their elastic modulus and promote new bone ingrowth, relieving the stress–shielding effect and implant failure, this also causes a decline in the alloys’ mechanical strength. In this work, a new preparation method for the high–strength and high–porosity Ti65Nb23.33Zr5Ta1.67Fe5 (TNZTF, at.%) alloy was suggested by sintering nanocomposite powder precursor in combination with the use of a space holder technique, in which NH4HCO3 is adopted to achieve a porous structure. The highly porous TNZTF alloy possesses a homogeneous fine–grained microstructure consisting of equiaxed α–Ti and a small amount of FeTi2, the latter of which is distributed in the β–Ti matrix. Through adjusting the mass fraction of NH4HCO3, a novel high–porosity, and high–strength TNZTF alloy with a low modulus was successfully prepared. The porous alloy with the addition of 30 wt.% NH4HCO3 exhibits a porosity of 50.3 ± 0.2%, a maximum strength of 327.3 ± 2.1 MPa, and an elastic modulus of 12.2 ± 0.3 GPa. The strength enhancement is mainly attributed to the unique fine–grained microstructure, which is obtained by the crystallization of the amorphous phase and the ductile–brittle mixed fracture mechanism. The prepared porous TNZTF alloy possesses higher mechanical strength and well–matched elastic modulus, showing great potential as an implant material.

Forest Ecological Product Value Realization (FEPVR) is an important way for China to promote the transition and development of forestry and realize common prosperity. It is critical to assess the effectiveness of FEPVR rationally to obtain a comprehensive understanding of the progress of ecological civilization. Based on the Driver–Pressure–State–Impact–Response (DPSIR) model, in this study, we developed an evaluation index system for FEPVR effectiveness containing five subsystems and 37 indicators and assessed the effectiveness of FEPVR in China from 2011 to 2022 by using the linear weighted sum method, the coupling degree of coordination model, and Spearman’s correlation analysis. The results showed that the composite index increased from 0.1980 in 2011 to 0.6501 in 2022, with a general upward trend, but there is still great potential for improvement. The main contribution was from the Response subsystem. The year 2017 was an important turning point for FEPVR in China because its development started to speed up; the status of coupling coordination between different subsystems was gradually improving but was still at a low level. The relationship between all indicators was dominated by a non-significant correlation (52.4%), and the overall synergistic effect (27.8%) was greater than the trade-off effect (19.8%). This study provides a new perspective for evaluating the effectiveness of FEPVR and a decision-making reference for clarifying the direction of FEPVR optimization.

BackgroundPsoriasis is a highly heterogeneous autoinflammatory disease. At present, heterogeneity in disease has not been adequately translated into concrete treatment options. Our aim was to develop and verify a new stratification scheme that identifies the heterogeneity of psoriasis by the integration of large-scale transcriptomic profiles, thereby identifying patient subtypes and providing personalized treatment options whenever possible.MethodsWe performed functional enrichment and network analysis of upregulated differentially expressed genes using microarray datasets of lesional and non-lesional skin samples from 250 psoriatic patients. Unsupervised clustering methods were used to identify the skin subtypes. Finally, an Xgboost classifier was utilized to predict the effects of methotrexate and commonly prescribed biologics on skin subtypes.ResultsBased on the 163 upregulated differentially expressed genes, psoriasis patients were categorized into three subtypes (subtypes A–C). Immune cells and proinflammatory-related pathways were markedly activated in subtype A, named immune activation. Contrastingly, subtype C, named stroma proliferation, was enriched in integrated stroma cells and tissue proliferation-related signaling pathways. Subtype B was modestly activated in all the signaling pathways. Notably, subtypes A and B presented good responses to methotrexate and interleukin-12/23 inhibitors (ustekinumab) but inadequate responses to tumor necrosis factor-α inhibitors and interleukin-17A receptor inhibitors. Contrastly, subtype C exhibited excellent responses to tumor necrosis factor-α inhibitors (etanercept) and interleukin-17A receptor inhibitors (brodalumab) but not methotrexate and interleukin-12/23 inhibitors.ConclusionsPsoriasis patients can be assorted into three subtypes with different molecular and cellular characteristics based on the heterogeneity of the skin's immune cells and the stroma, determining the clinical responses of conventional therapies.

Currently, the core idea of the refined method of population spatial distribution is to establish a correlation between the population and auxiliary data at the administrative-unit level and, then, refine it to the grid unit. However, this method ignores the advantages of public population spatial distribution data. Given these problems, this study proposed a partition strategy using the natural break method at the grid-unit level, which adopts the population density to constrain the land class weight and redistributes the population under the dual constraints of land class and area weights. Accordingly, we used the dasymetric method to refine the population distribution data. The study established a partition model for public population spatial distribution data and auxiliary data at the grid-unit level and, then, refined it to smaller grid units. This method effectively utilizes the public population spatial distribution data and solves the problem of the dataset being not sufficiently accurate to describe small-scale regions and low resolutions. Taking the public WorldPop population spatial distribution dataset as an example, the results indicate that the proposed method has higher accuracy than other public datasets and can also describe the actual spatial distribution characteristics of the population accurately and intuitively. Simultaneously, this provides a new concept for research on population spatial distribution refinement methods.

Abstract Purpose This study investigated the relationship between breast ultrasound features and lump margin status in breast-conserving patients. Methods A single-institution database and medical records system were searched to identify patients who had undergone breast-conserving surgery between 2015 and 2022. Patients were divided into case and control groups based on their postoperative margin status, and different matching methods [case–control matching (CCM) and propensity score matching (PSM)] were used to match the cases and controls at a ratio of 1:1. Results Before matching, patients with positive margins were more likely to have a tumor with increased blood flow (OR = 2.90, 95% CI 1.83–4.61, p

For the requirements of the multi-means observation and emergency monitoring of space objects, including space debris and near-earth asteroids, this paper analyzes the astronomical observation conditions in the stratosphere, which is the region of the earth’s atmosphere between 18 km and 55 km of altitude. The results reveal that near space has a significantly superior sky background and observation environment than ground-based observation, with the values of transmittance in the visible band and near-infrared bands more than 0.91 and 0.988, respectively. The sky background radiance at 20 km is 2.5% of the ground in the visible band and near-infrared band, which is practical for daytime observation, and there is an advantage in the availability of observable hours without the influence of aerosols and turbulence, etc. Based on near-space aerostats, such as a high-altitude balloon, a new method of space object floating observation has been proposed, including the observation facilities and scheme. The simulation shows that it has an all-weather/all-day ability while adopting multi-band observation. Applying a telescope with 9.5 mag detective ability located on the aerostat, debris with the size of about 0.36 m can be observed at a 1000 km distance and phase angle of 100°, while the near-earth asteroid with the size of about 980 km can be observed at a 5 million km distance and phase angle of 40° during the daytime. With these advantages, the aerostat-based observation would be a beneficial supplement to the ground-based observation network.

Exogenous selenium application could effectively improve the selenium absorption of crops affected by different climatic conditions due to changes in the planting environment and planting conditions. We planted maize at planting densities of 67,500 plants ha−1 (D1) and 75,000 plants ha−1 (D2). Five selenium fertilizer gradients of 0 mg m−2 (Se0), 7.5 mg m−2 (Se1), 15.0 mg m−2 (Se2), 22.5 mg m−2 (Se3), and 30.0 mg m−2 (Se4) were applied to investigate the response of the plants to selenium fertilizer application in terms of the gradient selenium absorption and substance accumulation. With the increase in the amount of selenium fertilizer applied, more of the selenium fertilizer will be absorbed and transported from the leaves to the grains, and the selenium content of the grains will gradually increase and exceed the selenium content of leaves. Under the D2 density in 2022, the selenium content of the grains under Se1, Se2, Se3, and Se4 treatments increased by 65.67%, 72.71%, and 250.53%, respectively, compared with that of Se0. A total of 260.55% of the plants showed a gradient of grain > leaf > cob > stalk from the Se2 treatment, and the overall selenium content of the plants increased first and then decreased. Under the D1 density, compared with the Se0, the dry matter mass of the Se1, Se2, Se3, and Se4 treatments significantly improved by 5.84%, 1.49%, and 14.26% in 2021, and significantly improved by 4.84%, 3.50%, and 2.85% in 2022. The 1000-grain weight under Se2, Se3, and Se4 treatments improved by 8.57%, 9.06%, and 15.56% compared to that under the Se0 treatment, and the yield per ha under the Se2, Se3, and Se4 treatments was 18.58%, 9.09%, and 21.42% higher than that under Se0 treatment, respectively. In addition, a reasonable combination of selenium application rate and density could improve the chlorophyll content and stem growth of dryland maize. This lays a foundation for the efficient application of selenium fertilizer and provides an important reference.

This paper aims to investigate a new method that uses buoyant gas mixed with air to control the floating height of scientific balloons. Firstly, the static characteristics and thermophysical properties of mixed-gas balloons are analyzed. Subsequently, the inflation model and the thermal-dynamic coupled model are established. Furthermore, based on theoretical research, a GUI program is compiled to simulate the ascent of mixed-gas balloons. Finally, flight tests are conducted. As the balloon volume expands to the maximum, the vertical velocity begins to decay and eventually oscillates around 0 m/s, which is consistent with the simulation. In addition, there is a noticeable shift in which the balloon starts to float after climbing to the target altitude, and the difference values between the test and the simulation are less than 350 m. Moreover, the trajectory results are similar to the prediction, and the errors of the end position are less than 2.5 km in horizontal distance. Consequently, this paper provides guidance for balloon-designated ceiling height technology which can allow a single balloon system to be used for tests at multiple heights.

Motion object detection (MOD) with freely moving cameras is a challenging task in computer vision. To extract moving objects, most studies have focused on the difference in motion features between foreground and background, which works well for dynamic scenes with relatively regular movements and variations. However, abrupt illumination changes and occlusions often occur in real-world scenes, and the camera may also pan, tilt, rotate, and jitter, etc., resulting in local irregular variations and global discontinuities in motion features. Such complex and changing scenes bring great difficulty in detecting moving objects. To solve this problem, this paper proposes a new MOD method that effectively leverages local and global visual information for foreground/background segmentation. Specifically, on the global side, to support a wider range of camera motion, the relative inter-frame transformations are optimized to absolute transformations referenced to intermediate frames in a global form after enriching the inter-frame matching pairs. The global transformation is fine-tuned using the spatial transformer network (STN). On the local side, to address the problem of dynamic background scenes, foreground object detection is optimized by utilizing the pixel differences between the current frame and the local background model, as well as the consistency of local spatial variations. Then, the spatial information is combined using optical flow segmentation methods, enhancing the precision of the object information. The experimental results show that our method achieves a detection accuracy improvement of over 1.5% compared with the state-of-the-art methods on the datasets of CDNET2014, FBMS-59, and CBD. It demonstrates significant effectiveness in challenging scenarios such as shadows, abrupt changes in illumination, camera jitter, occlusion, and moving backgrounds.

In non-small cell lung cancer (NSCLC), the heterogeneity promotes drug resistance, and the restricted expression of programmed death-ligand 1 (PD-L1) limits the immunotherapy benefits. Based on the mechanisms related to translation regulation and the association with PD-L1 of methyltransferase-like 3 (METTL3), the novel small-molecule inhibitor STM2457 is assumed to be useful for the treatment of NSCLC. We evaluated the efficacy of STM2457 in vivo and in vitro and confirmed the effects of its inhibition on disease progression. Next, we explored the effect of STM2457 on METTL3 and revealed its effects on the inhibition of catalytic activity and upregulation of METTL3 protein expression. Importantly, we described the genome-wide characteristics of multiple omics data acquired from RNA sequencing, ribosome profiling, and methylated RNA immunoprecipitation sequencing data under STM2457 treatment or METTL3 knockout. We also constructed a model for the regulation of the translation of METTL3 and PD-L1. Finally, we found PD-L1 upregulation by STM2457 in vivo and in vitro. In conclusion, STM2457 is a potential novel suppressor based on its inhibitory effect on tumor progression and may be able to overcome the heterogeneity based on its impact on the translatome. Furthermore, it can improve the immunotherapy outcomes based on PD-L1 upregulation in NSCLC.

BackgroundWith the rise and deepening of positive psychology research, theoretical research on job burnout is also deepening worldwide, and some new theoretical models are proposed, such as the burnout-engagement continuum, but there is still a lack of empirical research and application in China. ObjectiveTo analyze the current situation and influencing factors of five profiles in the burnout-engagement continuum in working populations of China: job engagement, ineffective, overextended, disengaged, and burnout. MethodsFrom August to October 2019 and June to September 2020, a total of 27344 subjects of key occupations in six typical industries, including teachers, firefighters, manufacturing workers, medical staff, flight attendants, and traffic police, were selected from 10 provinces (cities) in the eastern, middle, and western regions of China by multistage stratified cluster sampling method for cross-sectional investigation. Maslach Burnout Inventory-General Survey and Core Occupational Stress Scale were used to evaluate job burnout and occupational stress respectively. χ2 test was used to compare rates of count data. Binary logistic regression was used for multivariate analysis of the five profiles. ResultsAmong the subjects, 24.4%, 61.9%, 31.9%, 12.7%, and 11.8% were the prevalence rates of job engagement, ineffective, overextended, disengaged, and burnout, respectively. Flight attendants (35.7%), firefighters (29.0%), traffic police (28.5%), and manufacturing workers (26.5%) had high prevalence rates of job engagement profile. Medical stuff (62.9%) and manufacturing workers (61.8%) had high prevalence rates of ineffective profile. Teachers (39.2%), traffic police (37.2%), and medical stuff (35.5%) had high prevalence rates of overextended profile. Traffic police (17.9%), medical staff (14.3%), and teachers (13.4%) had high prevalence rates of disengaged profile. Traffic police (16.9%), medical staff (13.4%), and teachers (13.3%) had high prevalence rates of burnout profile. The results of multivariate analysis showed that gender, age, education level, marital status, weekly working hours, length of service, income per month, shift work, smoking, drinking, industry, and occupational stress entered into the regression equations of job engagement, ineffective, overextended, disengaged, and burnout. The risks of overextended (OR=1.456-2.970), disengaged (OR=1.306-4.092), and burnout (OR=1.302-4.102) among the high rating groups of the four factors of occupational stress were higher than those among the low rating groups. Flight attendants (OR=0.296) and firefighters (OR=0.329) had lower risks of burnout than teachers, and flight attendants (OR=0.392) and firefighters (OR=0.466) had lower risks of disengaged than teachers. ConclusionAmong the prevalence rates of the five profiles in the burnout-engagement continuum in the 6 typical occupational populations in China, ineffective profile is the highest, followed by overextended, and burnout is the lowest. Gender, age, education level, marital status, weekly working hours, length of service, income per month, shift work, smoking, drinking, industry, and occupational stress have different effects on the five profiles, but industry and occupational stress have greater impacts on job burnout.

BackgroundManufacturing industry is the main body of China's national economy, and manufacturing employees provide solid guarantee and support for the vigorous development of China's manufacturing industry. The research on job burnout of manufacturing employees is helpful to prevent or alleviate the health damage and economic loss caused by job burnout. ObjectiveTo investigate the status and influencing factors of job burnout among manufacturing employees in China, and evaluate the potential mediating effect of job burnout between job stress and depressive symptoms. MethodsA cross-sectional study was performed from August to October 2019 and from June to September 2020 in seven provinces of China. Study participants were recruited from 21 manufacturing companies covering 11 manufacturing subdivisions using multistage stratified cluster sampling. General Burnout Scale, Core Occupational Stress Scale, and Patient Health Questionnaire-9 were used to evaluate job burnout, job stress, and depressive symptoms. Mann-Whitney U test and Kruskal-Wallis H test were used to compare data between two independent samples and multiple independent samples of measurement data; Pearson χ2 test was used to compare the rate of enumeration data; Spearman rank correlation analysis was used to evaluate correlation between selected variables; binary logistic regression was used for multivariate analysis; stepwise regression and bias-corrected Bootstrap method were used to test potential mediating effect. ResultsA total of 10973 valid questionnaires were collected. The M (P25, P75) scores of exhaustions, cynicism, professional efficacy, job burnout, job stress, and depressive symptoms were 1.6 (0.4, 3.0), 1.0 (0.2, 2.2), 4.8 (3.2, 5.7), 1.6 (0.8, 2.5), 45.0 (40.0, 50.0), and 7.0 (4.0, 11.0), respectively. The positive rates of job burnout, job stress, and depressive symptoms were 53.4% (5865/10973), 28.4% (3116/10973), and 29.4% (3231/10973), respectively. The influencing factors of job burnout were gender (versus male; OR for female=0.852), age (versus≤25 years old; ORs for 26-30, 31-40, 41-50, 51-60 years old=0.824, 0.819, 0.738, 0.677), education level (versus junior high school or below; ORs for senior high school/technical secondary school, junior college/vocational college, graduate school or above=1.119, 1.345, 1.331), income per month (versus＜3000 yuan; ORs for 3000-4999, 5000-6999, 7000-8999, 9000-10999, ≥11000 yuan=0.513, 0.470, 0.430, 0.375, 0.411), position (versus assembly line; OR for non-assembly line=0.814), average weekly working hours (versus ≤40 h; ORs for 61-70, ＞70 h=1.199, 1.519), and drinking (versus non-drinking; OR for drinking=1.261). Job burnout was positively correlated with job stress and depressive symptoms (r=0.556, 0.508, P

The utilization of multifunctional composite materials presents significant advantages in terms of system efficiency, cost-effectiveness, and miniaturization, making them highly valuable for a wide range of industrial applications. One approach to harness the multifunctionality of carbon fiber reinforced polymer (CFRP) is to integrate it with a secondary material to form a hybrid composite. In our previous research, we explored the use of carbonaceous material derived from coconut shells as a sustainable alternative to inorganic fillers, aiming to enhance the out-of-plane mechanical performance of CFRP. In this study, our focus is to investigate the influence of carbonized coconut shell particles on the non-structural properties of CFRP, specifically electromagnetic interference (EMI) shielding, thermal stability, and water absorption resistance. The carbonized material was prepared by thermal processing at 400 °C. Varying proportions of carbonized material, ranging from 1% to 5% by weight, were thoroughly mixed with epoxy resin to form the matrix used for impregnating woven carbon fabric with a volume fraction of 29%. Through measurements of scattering parameters, we found that the hybrid composites with particle loadings up to 3% exhibited EMI shielding effectiveness suitable for industrial applications. Also, incorporating low concentrations of carbonized particle to CFRP enhances the thermal stability of hybrid CFRP composites. However, the inclusion of carbonized particle to CFRP has a complex effect on the glass transition temperature. Even so, the hybrid composite with 2% particle loading exhibits the highest glass transition temperature and lowest damping factor among the tested variations. Furthermore, when subjected to a 7-day water immersion test, hybrid composites with 3% or less amount of carbonized particle showed the least water absorption. The favorable outcome can be attributed to good interfacial bonding at the matrix/fiber interface. Conversely, at higher particle concentrations, aggregation of particles and formation of interfacial and internal pores was observed, ultimately resulting in deteriorated measured properties. The improved non-structural functionalities observed in these biocomposites suggest the potential for a more sustainable and cost-effective alternative to their inorganic-based counterparts. This advancement in multifunctional composites could pave the way for enhanced applications of biocomposites in various industries.

IntroductionThe naturalistic stimuli due to its ease of operability has attracted many researchers in recent years. However, the influence of the naturalistic stimuli for whole-brain functions compared with the resting state is still unclear.MethodsIn this study, we clustered gray matter (GM) and white matter (WM) masks both at the ROI- and network-levels. Functional connectivity (FC) and inter-subject functional connectivity (ISFC) were calculated in GM, WM, and between GM and WM under the movie-watching and the resting-state conditions. Furthermore, intra-class correlation coefficients (ICC) of FC and ISFC were estimated on different runs of fMRI data to denote the reliability of them during the two conditions. In addition, static and dynamic connectivity indices were calculated with Pearson correlation coefficient to demonstrate the associations between the movie-watching and the resting-state.ResultsAs the results, we found that the movie-watching significantly affected FC in whole-brain compared with the resting-state, but ISFC did not show significant connectivity induced by the naturalistic condition. ICC of FC and ISFC was generally higher during movie-watching compared with the resting-state, demonstrating that naturalistic stimuli could promote the reliability of connectivity. The associations between static and dynamic ISFC were weakly negative correlations in the naturalistic stimuli while there is no correlation between them under resting-state condition.DiscussionOur findings confirmed that compared to resting-state condition, the connectivity indices under the naturalistic stimuli were more reliable and stable to investigate the normal functional activities of the human brain, and might promote the applications of FC in the cerebral dysfunction in various mental disorders.

Abstract Background Results from observational studies indicate an association between circulating levels of mammalian target of rapamycin (mTOR)-dependent circulating proteins and the risk of multiple sclerosis (MS). However, a causal association has not been fully elucidated. Mendelian randomization (MR) is used to overcome limitations inherent to observational studies, assess the causal association, and minimize bias due to confounding and reverse causation. Methods To explore the causal association between seven mTOR-dependent proteins (AKT, RP-S6K, eIF4E-BP, eIF4A, eIF4E, eIF4G, and PKC-α) and MS, we obtained summary statistics from the genome-wide association study (GWAS) meta-analysis of the International Multiple Sclerosis Genetics Consortium (47,429 patients and 68,374 controls) and the INTERVAL study (genetic associations with 2994 plasma proteins from 3301 healthy individuals). MR analyses were conducted using inverse variance weighted, weighted median estimator, and MR-Egger regression methods/models. Sensitivity analyses were performed to ensure the reliability of the findings. Single nucleotide polymorphisms (SNPs) that are independent (r 2

The Single Event Effect (SEE) of FinFET devices has become one of the challenging issues affecting the reliability of modern electronic systems in space and terrestrial applications. However, the conventional FinFET device simulation steps are tedious and take a long time. This paper proposes a method based on a convolutional neural network (CNN) to predict the single event effect (SEE) of FinFET devices. By entering different particle incidence conditions, the SEE profiles, as well as the characteristic parameters, can be obtained quickly and accurately. The neural network model used in the experiments has a high prediction accuracy. The error of our trained network model in predicting the drain transient current pulse profile is only 0.012, the Mean Square Error (MSE) for predicting the peak drain transient current and total collected charge are only 0.00207 and 0.00084. The total time for training, validation and prediction of the neural network model in this study is 352 seconds, and the prediction time is much shorter, which is much lower than the simulation time of TCAD software. The minimum simulation time of the TCAD simulation software is 1901 seconds, and the simulation requires further modification of the resultant plots of the single event effect transient current curves.

Abstract Protein ubiquitination is closely related to tumor occurrence and development. The specific role of ubiquitination in endometrial cancer remains largely unclear. Therefore, we constructed a novel endometrial cancer prognostic model based on ubiquitination-related genes. We extracted the expression matrices of ubiquitination-related genes from the Cancer Genome Atlas database, upon which we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain 22 ubiquitination-related genes for the construction of the prognostic model. Survival, regression, clinical correlation, and principal component analyses were performed to assess the performance of the model. Drug sensitivity analysis was performed based on these ubiquitination-related genes. Finally, a prognostic nomogram was constructed based on the prognostic model to quantify patient outcomes. Survival, regression, clinical correlation, and principal component analyses revealed that the performance of the prognostic model was satisfactory. Drug sensitivity analysis provided a potential direction for the treatment of endometrial cancer. The prognostic nomogram could be used to effectively estimate the survival rate of patients with endometrial cancer. In summary, we constructed a new endometrial cancer prognostic model and identified 5 differentially expressed, prognosis-associated, ubiquitination-related genes. These 5 genes are potential diagnostic and treatment targets for endometrial cancer.

In the policy arena of the rapid development of China’s digital village, understanding how internet use enhances the happiness of forest farmers’ families holds theoretical and practical significance for promoting the protection of the ecological environment and the sustainable development of forests. This study utilizes survey data from 2023 on forest farmers in ecologically fragile ethnic areas in China. Based on sustainability, a five-dimensional evaluation index system for the happiness of forest farmers’ families has been constructed. First, the CRITIC-TOPSIS model is employed to calculate the happiness scores of forest farming households. Subsequently, the Tobit model and the mediation effect model are applied to examine and analyze the influencing factors and mechanisms of internet usage on the happiness of forest farmers’ families. The study finds that, first, an increase of one unit in terms of internet use is associated with a 0.031-unit increase in the happiness of forest farmers’ families, and that education, social perception, and policy perception all have a positive effect on the happiness of forest farmers’ families. Second, the mechanism of action suggests that internet use significantly increases forest farmers’ families’ happiness through subjective class identity. Third, further heterogeneity analyses revealed that internet use contributed to the happiness of forest farmers’ families in the male group, the low human capital group, and the group with an ecological forest ranger in the family. Therefore, it is necessary to strengthen the construction of digital rural infrastructure and develop new models such as digital forestry; cultivate and introduce specialized digital talents in rural areas and enhance the digital literacy of forestry farmers; and assist forestry farmers in establishing class identity concepts and social values conducive to the sustainable development of forests and implement ecological values in production practices, thereby improving the happiness of forest farmers’ families.

The North China Plain has a typical winter wheat–summer corn double-cropping pattern. The effects of nutrient deficiency conditions on the root characteristics and yield of summer corn in the double-cropping system were studied for four years. Long-term monotonous fertilization patterns undermine crop rotation systems and are detrimental to the sustainability of agricultural production. To complement the development of rational fertilization strategies by exploring the response of crop rotation systems to nutrient deficiencies, an experiment was conducted in a randomized complete block design consisting of five treatments with three replicates for each treatment: (1) an adequate supply of nitrogen and phosphate fertilizers and potash-deficient treatment (T1); (2) an adequate supply of nitrogen and potash fertilizers and phosphorus-deficient treatment (T2); (3) an adequate supply of phosphorus and potash fertilizers and nitrogen-deficient treatment (T3); (4) nutrient-sufficient treatment for crop growth (T4); and (5) no-fertilizer treatment (CK). The results showed that different nutrient treatments had significant effects on the root length density (RLD), root surface area density (RSAD), and root dry weight density (RDWD) in summer corn. At the physiological maturity stage (R6), the root indexes of RLD, RSAD, and RDWD were significantly higher in the 0–20 cm soil layer in T4 compared to CK, with an increase of 86.2%, 131.4%, and 100.0%, respectively. Similarly, in the 20–40 cm soil layer, the root indexes of T4 were 85.7%, 61.3%, and 50.0% higher than CK, with varied differences observed in the other nutrient-deficient treatments. However, there was no significant difference among the treatments in the 40–60 cm layer except for T4, whose root index showed a difference. The root fresh weight and root dry matter in T4, T3, T2, and T1 were increased to different degrees compared with CK. In addition, these differences in root indexes affected the annual yield of crops, which increased by 20.96%, 21.95%, and 8.14% in T4, T2, and T1, respectively, compared to CK. The spike number and the number of grains per spike of T4 were 10.8% and 8.3% higher than those of CK, which led to the differences in summer corn yields. The 1000-kernel weight of T4, T2, and T1 were 9.5%, 8.8%, and 7.4% higher than that of CK, whereas the determining nutrient was nitrogen fertilizer, and phosphorus fertilizer had a higher effect on yield than potassium fertilizer. This provides a theoretical basis for the effect of nutrient deficiency conditions on yield stability in a double-cropping system.

This work investigated the wear behavior of ultrafine-grained Ti65Nb23.33Zr5Ta1.67Fe5 (at.%, TNZTF) and Ti65Nb23.33Zr5Ta1.67Si5 (at.%, TNZTS) alloys fabricated by high-energy ball milling and spark plasma sintering. Wear tests were conducted in a simulated physiological solution under both reciprocating sliding and fretting wear conditions with different loads, frequencies, and stroke lengths. The microstructures, mechanical properties, and anti-wear properties of the investigated alloys were characterized. The results showed that the TNZTF and TNZTS alloys had much less wear volume than the commonly used Ti-6Al-4V (TC4) alloy and commercially pure titanium (CP-Ti). The TNZTF and TNZTS alloys exhibited much more smooth wear surfaces and shallower wear scars compared with TC4 and CP-Ti. The investigated alloys exhibited different wear mechanisms under the reciprocating sliding wear conditions, while they were similar under the fretting wear conditions. Compared with TC4 and CP-Ti, the fabricated TNZTF and TNZTS alloys showed a substantially higher wear resistance, owing to their ultrafine-grained microstructure and superior hardness. Additionally, the addition of Nb and Zr further enhanced the wear resistance by forming a protective Nb2O5 and ZrO2 oxide film. This work provides guidance for designing new biomedical titanium alloys with excellent wear resistance.

The LBD family is a plant-specific transcription factor family that plays an important role in a variety of biological processes. However, the function of IbLBD genes in sweet potato remains unclear. In this study, we identified a total of 53 IbLBD genes in sweet potato. Genetic structure showed that most of the IbLBD genes contained only two exons. Following the phylogenetic investigation, the IbLBD gene family was separated into Class I (45 members) and Class II (8) members. Both classes of proteins contained relatively conservative Motif1 and Motif2 domains. The chromosomal locations, gene duplications, promoters, PPI network, and GO annotation of the sweet potato LBD genes were also investigated. Furthermore, gene expression profiling and real-time quantitative PCR analysis showed that the expression of 12 IbLBD genes altered in six separate tissues and under various abiotic stresses. The IbLBD genes belonging to Class I were mostly expressed in the primary root, the pencil root, and the leaves of sweet potatoes, while the genes belonging to Class II were primarily expressed in the various sweet potato roots. The IbLBD genes belonging to Class I were mostly expressed in the primary root, the pencil root, and the leaves of sweet potatoes, while the genes belonging to Class II were primarily expressed in the fibrous root, pencil root, and tuber root.