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Background: In the Chinese coal industry, widespread blame avoidance behavior (BAB) greatly impacts coal mine accidents. Therefore, it is necessary to stop the BAB of coal mine managers and raise the management level of coal mine enterprises for the safe development of Chinese coal industry. Methods: Based on the semi-structured interviews and questionnaire surveys (20 middle-level managers in coal mines), this paper used the Grounded Theory and Nvivo Software qualitative research methodology to open, spindle, and selectively encode the interview data. Then, an index system of factors influencing BAB of coal mine managers was constructed. The influence degree, affected degree, centrality degree, cause degree of each influencing factor were calculated and the hierarchical model of influencing factors of BAB of coal mine managers was established by the DEMATEL-ISM method which is a decision support tool used to evaluate and analyze the interdependencies between influencing factors. Results: Index system of factors influencing BAB of coal mine managers included four levels and 12 influencing factors: individual, organizational, institutional environmental, and situational factors. The hierarchical model identified eight causal factors and four consequential factors, of which safety management (15.355), work attitude (14.380), and work group performance (14.281) in the top three of the centrality rankings are the key factors affecting the avoidance behavior of coal mine managers; A 3-level multilevel structure was constructed to reflect the interactions among the factors influencing the BAB of coal mine managers in terms of direct, indirect, and root causes, and corresponding improvement measures were proposed. Conclusion: This study offers a theoretical complement and practical guidance for stopping BAB of coal mine managers.

The treatment strategy for blast injuries is closely linked to the clinical outcome of blast injury casualties. However, the application of military surgery experience to blast injuries caused by production safety accidents is relatively uncommon. In this study, the authors present 2 cases of blast injuries caused by one gas explosion, both cases involved individuals of the same age and gender and experienced similar degree of injury. The authors highlight the importance of using a military surgery treatment strategy, specifically emphasizing the need to understand the concept of damage control and disposal. It is recommended that relevant training in this area should be strengthened to improve the clinical treatment of such injuries. This study provides a valuable reference for healthcare professionals dealing with blast injuries.

Purpose: Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods. Methods: This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Non-normally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher’s exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Results: A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time (p

Objectives: To address the lack of research on the prevalence of carbapenem-resistant Enterobacterales (CREs) in Xinjiang, China, and elucidate the genomic characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) ST11-KL30. Methods: CREs were collected in Xinjiang from 2021 to 2023. The antimicrobial susceptibility testing of carbapenems was performed via agar dilution method. Whole-genome sequencing was completed on the Illumina platform, and subsequent genomic analyses of CRKP, such as sequencing typing, K-locus and O-locus identification, virulence score assessment, and phylogenetic analysis, were performed. The virulence of CRKP isolates was determined in vitro and in vivo, and biofilm formation was assessed by crystal violet staining. Additionally, the virulence plasmid was reconstructed, and the formation of CRKP ST11-KL30 was revealed based on genome data from public database. Results: Eighty-five CRE isolates were collected, among which CRKP was most prevalent (68/85). KPC was the most dominant carbapenemase (60/68) in CRKP, while NDM-type carbapenemase was more prevalent in other species. ST11 was the dominant CRKP clone and was phylogenetically divided into three clusters: ST11-KL64, ST11-KL47 and ST11-KL30. CRKP ST11-KL30 is a novel recombinant clone that harbours a pK2044-like virulence plasmid and can be derived from ST11-KL64 by obtaining an ∼57 kb region from ST29-KL30. Compared to ST11-KL47 and ST11-KL64, ST11-KL30 had lower virulence, but had enhanced biofilm formation. Conclusions: We describe the prevalence of CRE prevalence southern Xinjiang and report the emergence of a region-specific clone. Our findings underscore the potential dissemination of ST11-KL30, which warrants increased monitoring in the future.

This study innovatively evaluated ecological civilization in China from the perspective of environment and health. A Composite Environmental Health Index (CEHI) was constructed based on the Driving force-Pressure-State-Impact-Response (DPSIR) and Coupling Coordination Degree (CCD) models. Results showed that significant and sustained improvements were observed in the ecological environment after ecological civilization, while economic development continued to progress at a steady pace. However, the advancement in population health (impact subsystem), exhibited comparatively modest progress, potentially linked to issues such as demographic aging and the enduring consequences of past exposure to environmental pollutants. At the provincial level, the regional development was uneven. The CEHI performance was highest in the eastern regions, followed by the central regions, with the western regions showing the least progress. Beijing, Guangdong, Jiangsu, Shanghai, and Zhejiang emerged as top performers with higher CEHI scores, which can be attributed to their favorable geographical positioning and the response subsystem. Conversely, northeastern regions (Heilongjiang, Jilin, and Liaoning) and northwestern regions (Shaanxi, Gansu, Ningxia, and Qinghai) experienced limited advancements in post-ecological civilization implementation. For these underperforming regions, there is a pressing need to intensify efforts aimed at enhancing their response subsystems. In summary, China's pursuit of ecological civilization has yielded significant successes, potentially offering valuable insights for other nations striving for sustainable development. The ecological civilization model's integration of ecological environmental protection into economic, political, cultural, and social constructs may serve as a meaningful reference for the sustainable development of other countries.

This study aims to investigate the phase composition, microstructure, and mechanical properties of three refractory high-entropy alloys (RHEAs): Al7(NbTiZr)93, Al7(NbTiZrMo)93, and Al7(NbTiZrTa)93. The as-cast Al7(NbTiZr)93 alloy exhibits a single-phase BCC structure, with a yield strength (YS) of 1050 MPa at room temperature. The addition of Mo and Ta leads to the formation of Al7(NbTiZrMo)93 and Al7(NbTiZrTa)93 alloys with BCC-B2 and B2-FCC dual-phase structures, whose YS values reach 1741 MPa and 2350 MPa, respectively. At 800 °C, trace amounts of ordered B2 phase are generated in the Al7(NbTiZr)93 matrix, and the YS decreases from 1050 MPa at room temperature to 219 MPa at 800 °C. In the Al7(NbTiZrMo)93 alloy, the 10 nm B2 precipitates grow to several hundred nanometers, and the YS decreases to 431 MPa after compression at 800 °C. In the Al7(NbTiZrTa)93 alloy, the grid B2-FCC structure at room temperature transforms into a disordered BCC structure at 800 °C, yet possessing the YS of 908 MPa and demonstrating acceptable ductility. Moreover, Ta exhibits the better structural and performance matching than Mo in AlNbTiZr-based RHEAs. Therefore, it opens up new prospects for regulating the structure and high-temperature performance of AlNbTiZr-based RHEAs.

Current evidence suggests that the intestine as the new frontier for human health directly impacts both our physical and mental health. Therefore, it is highly desirable to develop the intelligent tool for the enhanced diagnosis and treatment of intestinal diseases. During the past 20 years, capsule robots have opened new avenues for research and clinical applications, potentially revolutionizing human health monitor, disease diagnosis and treatment. In this review, we summarize the research progress of edible multifunctional capsule robots in intestinal diseases. To begin, we introduce the correlation between the intestinal microbiome, intestinal gas and human diseases. After that, we focus on the technical structure of edible multifunctional robots. Subsequently, the biomedical applications in the monitoring, diagnosis and treatment of intestinal diseases are discussed in detail. Last but not least, the main challenges of multifunctional capsule robots during the development process are summarized, followed by a vision for future development opportunities.

Summary: To understand heart aging at the single-cell level, we employed single-cell dual omics (scRNA-seq and scATAC-seq) in profiling non-myocytes (non-CMs) from young, middle-aged, and elderly mice. Non-CMs, vital in heart development, physiology, and pathology, are understudied compared to cardiomyocytes. Our analysis revealed aging response heterogeneity and its dynamics over time. Immune cells, notably macrophages and neutrophils, showed significant aging alterations, while endothelial cells displayed moderate changes. We identified distinct aging signatures within the cell type, including differential gene expression, transcription factor activity, and motif variation. Sub-cluster analysis revealed intra-cell type heterogeneity, characterized by diverse aging patterns. The senescence-associated secretory phenotype emerged as a key aging-related phenotype. Moreover, aging significantly influenced cell-cell communication, especially impacting a fibroblast sub-cluster with high expression of ERBB4. This study elucidates the complex cellular and molecular landscape of cardiac aging and offers guidance for potential therapeutic avenues to treat aging-related heart diseases.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) can be achieved by ectopic expression of cardiac transcription factors (TFs) via viral vectors. However, risks like genomic mutations, viral toxicity, and immune response limited its clinical application. Transactivation of endogenous TFs emerges as an alternative approach that may partially mitigate some of the risks. In this study, we utilized a modified CRISPRa/dCas9 strategy to transactivate endogenous reprogramming factors MEF2C, GATA4, and TBX5 (MGT) to induce iCMs from both mouse and human fibroblasts. We identified single-guide RNAs (sgRNAs) targeting promoters and enhancers of the TFs capable of activating various degrees of endogenous gene expression. CRISPRa-mediated Gata4 activation, combined with exogenous expression of Mef2c and Tbx5, successfully converted fibroblasts into iCMs. Despite extensive sgRNA screening, transactivation of Mef2c and Tbx5 via CRISPRa remained less effective, potentially due to de novo epigenetic barriers. While future work and refined technologies are needed to determine whether cardiac reprogramming could be achieved solely through CRISPRa activation of endogenous factors, our findings provide proof of concept that reliance on exogenous TFs for reprogramming can be reduced through CRISPRa-mediated activation of endogenous factors, particularly Gata4, offering a novel strategy to convert scar-forming fibroblasts into iCMs for regenerative purposes.

Most commercially available red wines undergo alcoholic fermentation by Saccharomyces yeasts, followed by a second fermentation with the lactic acid bacteria Oenococcus oeni once the initial process is complete. However, this traditional approach can encounter complications in specific scenarios. These situations pose risks such as stalled alcoholic fermentation or the growth of undesirable bacteria while the process remains incomplete, leaving residual sugars in the wine. To address these challenges and the issue of low acidity prevalent in warmer viticultural regions, several novel alternatives are available. The alternatives involve the combined use of Lachancea thermotolerans to increase the acidity of the musts, lactic acid bacteria (Oenococcus oeni and Lactiplantibacillus plantarum) to ensure malic acid stability during early alcoholic fermentation stages, and Saccharomyces cerevisiae to properly complete alcoholic fermentation. The study showed variations in the final chemical parameters of wines based on the microorganisms used.

Summary: We aim to investigate muscle ARNT-like protein 1 (BMAL1) regulation of syntaxin17 (STX17) in mouse hippocampal neurons, focusing on autophagy and amyloid-β (Aβ) deposition. Autophagosome-lysosome fusion in APP/PS1 hippocampal tissues was observed using transmission electron microscopy, while mRNA levels of LC3II and P62 were measured via reverse-transcription PCR (RT-PCR) after Amyloid precursor protein (APP) overexpression. STX17, linked to autophagy and differentially expressed in Alzheimer’s disease (AD) brains, was knocked down or overexpressed to assess its effects. The results showed that reduced STX17 impairs autophagosome-lysosome fusion, leading to abnormal Aβ deposition. Coimmunoprecipitation (Co-IP) and immunofluorescence confirmed STX17 interaction with SNAP29 and VAMP8 to form SNARE complexes. Furthermore, BMAL1 binding to STX17 was examined using luciferase assays. Circadian rhythm disturbances and decreased BMAL1 expression in APP/PS1 mice were noted, while BMAL1 overexpression upregulated STX17 expression and promoted autophagy to reduce Aβ deposition. Thus, the BMAL1 protein can promote STX17 transcription to induce STX17-SNAP29-VAMP8 complex formation to clear intracellular Aβ through autophagy.

Background: Several clinical neuroimaging studies have reported structural and functional brain abnormalities associated with peripheral inflammatory cytokines or kynurenine pathway metabolites in patients with depression. However, it is not clear whether the abnormal findings are changes that are intrinsic to depression or whether they are caused by confounding factors such as age, illness duration, or medication. Methods: To exclude confounding factors, we used chronic unpredictable mild stress (CUMS) rat model and magnetic resonance T1/T2 mapping to investigate the microstructural characteristics of the prefrontal cortex (PFC), hippocampus and corpus callosum and further explored the association between peripheral blood depression-related indicators and microstructural characteristics. Results: The results revealed that the T2 relaxation time of the corpus callosum was significantly decreased in the CUMS model compared to the control group. Additionally, positive correlations were found between the levels of inflammatory cytokines (interleukin (IL)-1 and IL-6) and the T1 relaxation time of the corpus callosum and between the level of IL-6 and the T1 relaxation time of the PFC. Conclusion: Our study demonstrates that the microstructural abnormality of the corpus callosum is an intrinsic change that accompanies depression and also provides robust evidence that the microstructural characteristics of the corpus callosum and PFC associated with inflammatory cytokines in peripheral blood play an important role in the fundamental pathophysiological mechanism of depression.

Sepsis is a critical condition characterized by a systemic inflammatory response to infection, often leading to severe vascular dysfunction and high mortality. One of the hallmarks of vascular dysfunction in sepsis is increased vascular permeability and the loss of pericytes, which are essential for maintaining vascular integrity. Despite the significance of pericyte loss in sepsis, the primary type of cell death responsible and the underlying molecular mechanisms remain incompletely understood. This study aims to elucidate these mechanisms by focusing on ferroptosis, a form of programmed cell death, and its regulation through the Hippo/ACSL4 axis. Our research confirmed significant pericyte loss in patients with sepsis. Through advanced single-cell analysis and proteomics, ferroptosis was identified as a key differentiating cell death type between sepsis and sham samples. Further metabolomics analysis revealed that Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) plays a pivotal role in the ferroptosis of pericytes during sepsis. In vitro experiments demonstrated that downregulation of ACSL4 effectively reduced lipopolysaccharide (LPS)-induced lipid peroxidation, restored pericyte viability, and improved endothelial permeability. In vivo studies with pericyte-specific ACSL4 knockout mice showed a marked decrease in pericyte loss and enhanced vascular barrier function following sepsis induction. To translate these findings into potential therapeutic strategies, we developed pericyte-targeting liposomes encapsulating ACSL4 shRNA adenovirus. These liposomes successfully restored pulmonary vascular barrier function and significantly reduced pericyte loss in septic conditions. The results of this study underscore the crucial role of ACSL4 in mediating ferroptosis in pericytes and highlight the therapeutic potential of targeting ACSL4 to mitigate vascular dysfunction in sepsis.

The exact mechanism underlies the development of neuropathic pain is not yet completely understood. Mitogen and stress-activated kinase 1 (MSK-1) is an important downstream kinase of the mitogen-activated protein kinase (MAPK). It has been extensively studied in the central nervous system, but whether MSK-1 is associated with the neuropathic pain remains elusive. In this experiment, Lumbar 5 spinal nerve ligation (SNL) was used to establish a neuropathic pain condition in the rats. Western blotting, qRT-PCR, immunohistochemistry, intrathecal catheterization and drugs delivery were evaluated to study the physiological responses of the animals. The results showed that SNL resulted in elevated phosphorylated MSK-1 (p-MSK-1) expression in the ipsilateral dorsal root ganglion (DRG) and the spinal dorsal horn in rats, while total MSK-1 (t-MSK-1) did not change significantly. Intrathecal injection of the MSK-1 inhibitor SB747651A partially reversed established neuropathic pain. Additionally, intrathecal administration of MSK-1 siRNA either preoperatively or 7 days postoperatively relieves the development and maintenance of pain, respectively. Meanwhile, the expression levels of p-H3S10, a downstream target of MSK-1, also displayed a significant increase after SNL. And these changes could be reversed by using MSK-1 siRNA. Collectively, the increase of MSK-1 induced by SNL participates in the development and maintenance of neuropathic pain by regulating the expression of p-H3S10 in DRG and spinal dorsal horn. Concentrating on MSK-1 may result in a novel approach to the treatment of neuropathic pain.

There is growing evidence that the imbalance of inflammatory cytokines plays an important role in the pathophysiological mechanism of depression. However, the effects of inflammatory cytokines on the whole brain in patients with depression are still not fully elucidated. The present study aimed to investigate the relationship between inflammatory cytokines and cerebral magnetic resonance imaging (MRI) features using voxel-based whole-brain analysis in patients with depression. A total of 60 patients with depression and 60 healthy controls (HCs) were included. Interleukin-1 was positively correlated with gray matter volume (GMV) in the left putamen and negatively correlated with regional homogeneity (ReHo) and degree centrality (DC) in the left anterior cingulate cortex. Interleukin-6 was positively correlated with GMV in the right superior parietal lobule and ReHo in the left pallidum and putamen. Interferon-α was negatively correlated with DC in the left postcentral gyrus. The ReHo in the left pallidum in depressed patients was lower than that in HCs. The FCs based on the left pallidum as the seed in depressed patients were significantly reduced. The imaging features of the left pallidum had good performance (area under the curve: 0.891) for identifying depressed patients. Inflammatory cytokines are associated with cerebral imaging features in patients with depression and in particular, the abnormal imaging features of the left pallidum may be a potential neuroimaging biomarker of depression.

Objective: This study aimed to investigate the effects of fermitin family member 1 (FERMT1) on epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) via the EGFR/AKT/β-catenin and EGFR/ERK pathways. Methods: The expression of FERMT1 encoding protein kindlin-1 in HCC tissues was determined by immunohistochemistry, and FERMT1 mRNA expression in HCC tissues and cell lines was analyzed by qRT-PCR. After the FERMT1 expression of SNU182 and SNU387 interfered with siRNA, the cell viability, invasion, migration, and EMT were tested by CCK-8, transwell invasion, scratching, immunofluorescence/WB, respectively. Similarly, the effects of FERMT1 on the viability and metastasis of HCC were investigated in transplanted tumor and lung metastasis mouse models. The protein expressions of EGFR/AKT/β-catenin and EGFR/ERK pathways were analyzed by WB. In addition, the relationship between FERMT1 and EGFR was further determined by immunofluorescence double staining and Co-IP. Results: FERMT1 was significantly upregulated in HCC, and silencing FERMT1 inhibited the viability, invasion, migration, and EMT of HCC. Silencing FERMT1 also inhibited the activation of EGFR/AKT/β-catenin and EGFR/ERK pathways. In addition, inhibition of EGFR, AKT, or ERK confirmed that EGFR/AKT/β-catenin and EGFR/ERK pathways were involved in the promoting effects of FERMT1 on HCC. Co-IP and immunofluorescence experiments confirmed the targeting relationship between FERMT1 and EGFR. Conclusion: FERMT1 was highly expressed in HCC and promoted viability, invasion, migration, and EMT of HCC by targeting EGFR to activate the EGFR/AKT/β-catenin and EGFR/ERK pathways. Our study revealed the role of FERMT1 in HCC and suggested that FERMT1 exerts biological effects through activating the EGFR/AKT/β-catenin and EGFR/ERK pathways.

In order to improve English learning efficiency, this paper constructs a deep learning model of semantic orientation exploration based on English V+able corpus distribution and semantic roles. This article combines the practical needs of English learning and establishes an ILP model with the optimization objective of minimizing spectrum resource occupation. A traffic grooming based time aware multipath RSA algorithm (HMRSA-TG) is proposed to solve the standardization problem of English speech recognition. To improve the system efficiency of intelligent English learning systems, a traffic grooming based time aware multipath RSA algorithm (HMRSA-TG) is proposed. Through research, it has been verified that the semantic orientation exploration deep learning model based on the distribution of semantic roles in English V+able corpora can effectively improve the effectiveness of English speech learning. The corpus model proposed in this paper can provide a reliable benchmark database for many speech problem learners and play an important role in English translation software in recognizing input speech with different accents

Understanding salt and water transport mechanisms in reverse osmosis (RO) under high pressures and salinities is critical to advancing RO-based brine management technologies. In this study, we investigate the dependence of salt permeance and partitioning on feed salinity and applied pressure. Salt partitioning coefficients were determined using a novel high-pressure quartz crystal microbalance (QCM), and salt permeances were collected using a lab-scale high-pressure dead-end cell. Our results show that salt permeance decreases with respect to feed concentration, in contrast to conventional theories for charged RO membranes. We further show salt partitioning coefficients do not change with applied hydrostatic pressure but are dependent on feed salt concentration. We use non-equilibrium molecular dynamics simulations to show that these trends are explained by salinity and pressure-induced changes to the structure of the polyamide layer, namely osmotic deswelling and compaction. Changes in the polyamide layer thickness and pore size alter the frictional interactions of ions, affecting membrane performance at larger salinities and pressures. These results provide new insights on how structure-performance relationships affect salt transport at higher pressures.

Manganese (Mn) is necessary for various biological processes, yet its function in innate immunity has been less studied, especially in fish. Stimulator of interferon (IFN) genes (STING) is an essential factor for IFN induction in virus infection. Our study demonstrated that Mn2+ increases the ability of zebrafish to resist spring viraemia of carp virus (SVCV) infection by enhancing the expression of STING. Further mechanistic studies indicated that Mn2+ promotes the expression of STING by increasing its ubiquitination. Furthermore, Mn2+treatment promoted STING-mediated activation of IFN and reversed the decrease in STING protein induced by SVCV. Collectively, our findings showed the vital involvement and necessity of Mn2+ in protecting fish against SVCV infection.

Summary: Sarcopenia, characterized by the loss of muscle mass and function, is a critical health issue in nursing home residents. Given the high prevalence of sarcopenia in care settings, effective screening is crucial. This study compared the diagnostic accuracy of two conventional sarcopenia screening tools, SARC-F and SARC-CalF, and developed an alternative tool, SEAC, specifically for nursing home residents. In a sample of 679 older adults from Zhejiang Province, SARC-CalF exhibited better sensitivity and diagnostic accuracy compared to SARC-F. The SEAC tool, incorporating strength, exhaustion, assistance in walking, and calf circumference, demonstrated the highest diagnostic accuracy and sensitivity among the three screening tools. These findings suggest that SEAC could serve as a valuable tool for large-scale sarcopenia screening in nursing homes, potentially improving early detection and management of sarcopenia in this vulnerable population.

Objective: Type 2 diabetes (T2DM) is a significant risk factor for coronary heart disease (CHD). This study aimed to assess the variations in biomarkers associated with CHD in T2DM patients across different age groups in the Han Chinese population. Methods: A strict selection process was employed, involving three groups: a control group (n = 300) with no medical history, a new-onset T2DM group (n = 300), and a new-onset T2DM + CHD group (n = 300). Participants in each group were further categorized based on age: Group 1 (75 years). Fasting glucose, hemoglobin A1c (HbA1c), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), ApoB/ApoA1 ratio, lipoprotein(a) [Lp(a)], high-sensitivity C-reactive protein (hsCRP), and homocysteine (HCY) levels were analyzed in all groups. Results: Both T2DM and T2DM + CHD groups exhibited elevated levels of TG, TC, LDL-C, ApoB, ApoB/ApoA1, Lp(a), hsCRP, and HCY, alongside decreased levels of HDL-C and ApoA1 in comparison to the control group. Notably, when comparing the T2DM to the T2DM + CHD groups, significant increases were noted in ApoB, Lp(a), and hsCRP levels in the T2DM + CHD group, whereas other biomarkers did not show significant differences. Across all age groups, the patterns remained consistent, with the T2DM and T2DM + CHD groups showing elevated levels of TG, TC, LDL-C, ApoB, ApoB/ApoA1, Lp(a), hsCRP, and HCY, and decreased levels of HDL-C and ApoA1 compared to their respective age-matched control groups. Furthermore, within each age category, significant increases in ApoB, Lp(a), and hsCRP were specifically observed with advancing age in the T2DM + CHD group, with Lp(a) and hsCRP levels showing particularly notable elevations, underscoring their potential as significant indicators of CHD risk in the T2DM population. Conclusion: Lp(a) and hsCRP may serve as valuable risk biomarkers for the development of CHD in T2DM patients. Understanding the variations in these biomarkers across different age groups can assist in risk assessment and the development of personalized management strategies for CHD in T2DM patients.

Humans appear to be endowed with the ability to readily share attention with interactive partners through the utilization of social direction cues, such as eye gaze and biological motion (BM). Here, we investigated the specialized brain mechanism underlying this fundamental social attention ability by incorporating different types of social (i.e., BM, gaze) and non-social (arrow) cues and combining functional magnetic resonance imaging (fMRI) with a modified central cueing paradigm. Using multi-voxel pattern analysis (MVPA), we found that although gaze- and BM-mediated attentional orienting could be decoded from neural activity in a wide range of brain areas, only the right anterior and posterior superior temporal sulcus (aSTS and pSTS) could specifically decode attentional orienting triggered by social but not non-social cues. Critically, cross-category MVPA further revealed that social attention could be decoded across BM and gaze cues in the right STS and the right superior temporal gyrus (STG). However, these regions could not decode attentional orienting across social and non-social cues. These findings together provide evidence for the existence of a specialized social attention module in the human brain, with the right STS/STG being the critical neural site dedicated to social attention.

Additive manufacturing (AM) technology facilitates the creation of complex structures, where the printing path significantly impacts thermal distribution, subsequently influencing stress distribution and structural deformation. The primary challenge in path planning is to determine a printing turn angle that ensures uniform thermal distribution, thereby minimizing structural deformation while maintaining printing efficiency. To address this issue, we propose a composite function, which comprehensively characterizes the effects of the printing turn angle and the length of the printing path on the printing results. Combining a specific cubic porous structure, we calculate the maximum (Pmax) and minimum (Pmin) values of the composite function P, and compare the structural deformation and stress of the Pmax and Pmin paths with those of the typical Pzigzag path. Finite element method (FEM) simulation and experimental validation show that the Pmax path achieves significantly lower structural deformation and residual stress compared to the Pzigzag path and Pmin path.

Globally, plastic pollution threatens human health, particularly affecting the hearts of offspring exposed to maternal environmental factors early in development. Few studies have specifically addressed sex-specific cardiac injury in offspring resulting from maternal exposure to polystyrene nanoplastics (PS-NPs). This study investigates the potential cardiac injury in offspring following maternal exposure to 1 mg/L PS-NPs. Pregnant C57BL/6J mice were exposed to PS-NPs until 3 weeks postpartum to establish a maternal exposure model. Heart tissues were collected and weighed, and the transcriptomes of the offspring hearts were sequenced and analyzed using high-throughput RNA sequencing. Immunohistochemical staining was performed to assess the effects of PS-NPs on cardiac immune infiltration, fibrosis, and apoptosis in the offspring. PS-NPs caused a significant reduction in heart and body weight in female offspring compared to males. Additionally, PS-NPs induced sex-specific transcriptional reprogramming and metabolic disruptions in the offspring. PS-NPs also induced significant fibrosis, apoptosis, and increased CD68+ macrophage infiltration in offspring hearts. Notably, PS-NPs induced distinct cardiovascular diseases in the offspring. Fluid shear stress and atherosclerosis were significantly enriched in PS-NP-treated male offspring, while viral myocarditis was predominantly enriched in PS-NP-treated females. Our findings suggest that PS-NPs induce cardiotoxicity in offspring by disrupting metabolism, impairing immunity, and triggering fibrosis and apoptosis, with sex-specific differences. This study provides novel insights and a foundation for understanding sex-specific pharmacological differences and interventions in PS-NP-induced cardiovascular disease in offspring.

Background: Although microwave ablation (MWA) has been shown to be an effective treatment for lung malignancies (LM), there is no effective way to predict pneumothorax or pleural effusion after MWA so that timely measures can be taken to prevent it. Methods: This study comprised LM patients undergoing MWA at Affiliated Hospital of Nantong University from January 2013 to September 2023. Patients before May 2023 constituted the training set (n = 340), while data from May to September served as the test set (n = 58). Unformatted and formatted data extracted from electronic medical records (EMR) were utilized for model construction. Predictors for pneumothorax or pleural effusion were determined through univariate analysis and backward stepwise regression in the training set. Six ML algorithms were employed to create four models based on the research timeframe. Evaluation of the four models was performed using receiver operating characteristic (ROC) analysis, area under the ROC curve (AUC), and 10-fold cross validation. Findings: A total of 398 patients (216 aged 70 or above, 271 males) were included, with 23.37 % (93/398) experiencing pneumothorax and 33.42 % (133/398) developing pleural effusion. Across all four predictive models, Logistic Regression (LR) demonstrated optimal predictive performance in the test set, with AUC values of 0.727 for Model Ⅰ, 0.876 for Model Ⅱ, 0.895 for Model Ⅲ, and 0.807 for Model Ⅳ. Interpretation: ML models effectively predict post-MWA pneumothorax or pleural effusion.

Background: In recent decades, the quality of male semen has decreased worldwide. Air pollution has been linked to lower semen quality in several studies. However, the effects of atmospheric pollutants on different semen characteristics have not always been consistent. The aim of this study was to investigate the association between the Air Quality Index (AQI) and six atmospheric pollutants (PM2.5, PM10, SO2, NO2, CO, and O3), semen quality, and their key exposure window periods. Methods: This study included 1711 semen samples collected at the reproductive clinics of the First Affiliated Hospital of Shanxi Medical University in Taiyuan, Shanxi, China, from October 10, 2021, to September 30, 2022. We evaluated the association of AQI and six atmospheric pollutants with semen quality parameters throughout sperm development and three key exposure windows in men using single-pollutant models, double-pollutant models, and subgroup analyses of semen quality-eligible groups. Results: Both the single-pollutant model and subgroup analyses showed that PM, CO, and O3 levels were negatively correlated with total and progressive motility. At 70–90 d before semen collection, CO exposure and semen volume (β =-1.341, 95 % CI: −1.805, −0.877, P

The universal contamination of arable land with potentially toxic elements (PTEs) poses a severe threat to food security and jeopardizes worldwide efforts to meet the United Nations Sustainable Development Goals (SDGs). How to obtain more reliable concentrations of PTEs in regional agricultural soils is a priority problem to be solved. Multispectral satellite remote sensing, with its advantages of high spatial and temporal resolution, broad coverage, and low cost, offers the potential to acquire spatial distribution of PTEs in agricultural soils over large areas. However, owing to the complexity of soil environments and the insufficiency of spectral information, the mechanism for retrieving concentrations of PTEs in agricultural soils via multispectral satellites is not yet clear, and the accuracy needs to be improved. In this study, we aimed to assess whether employing a fusion of spectral information and environmental covariates, results in more accurate retrievals of PTEs, specifically chromium (Cr) and mercury (Hg), in croplands than does employing spectral information alone. Three machine learning algorithms—kernel-based support vector machine (SVM), neural network-based back propagation neural network (BPNN), and tree-based extreme gradient boosting (XGBoost)—were developed to retrieve Cr and Hg concentrations in agricultural soils. The results showed that the fusion of spectral information and environmental covariates combined with the XGBoost model performed best in retrieving both Cr and Hg concentrations in agricultural soils with coefficient of determination (R2) values of 0.73 and 0.74, respectively. Environmental covariates were important variables for determining Cr and Hg concentrations in agricultural soils, but the ability to retrieve these element concentrations by utilizing spectral information alone was limited. High Cr concentrations occurred in central towns and southern hilly mountains. High Hg concentrations were detected in the northwestern region and southern hilly mountains. The potential of fusing spectral information and environmental covariates to precisely retrieve PTE concentrations in agricultural soils can serve as a reference for agricultural soil health information monitoring worldwide.

Theanine (N-ethyl-γ-glutamine), as a unique non-protein amino acid, plays vital roles in abiotic stress resistance, while its roles in biotic stress resistance are still unclear. Gray mold caused by Botrytis cinerea is a major disease in strawberries. Effects of theanine on the development of gray mold, cell-wall and phenylpropanoid metabolisms in strawberries were investigated in this study. Results showed that 5 mmol L−1 theanine treatment reduced disease incidence and severity of gray mold in strawberries with antifungal activity in vitro. Meanwhile, theanine treatment enhanced the accumulation of phenolic compounds and lignin, especially ellagic acid, cyanidin, and quercetin, which was associated with increased phenylpropanoid pathway related enzyme activities. Moreover, theanine induced callose deposition and suppressed cell- wall disassembling enzymes, accompanied by higher levels of water insoluble pectin, hemicellulose and cellulose. Therefore, theanine treatment could alleviate decay of B. cinerea-inoculated strawberries by regulating phenylpropanoid and cell-wall metabolisms, maintaining higher levels of phenolic compounds and cell-wall components, thereby contributing to disease resistance and cell-wall structure integrity.

Ovarian cancer (OC) is one of the leading causes of death from malignancy in women and lacks safe and efficient treatment. The novel biomaterial, recombinant humanized collagen type III (rhCOLIII), has been reported to have various biological functions, but its role in OC is unclear. This study aimed to reveal the function and mechanism of action of rhCOLIII in OC. We developed an injectable recombinant human collagen (rhCOL)-derived material with a molecular weight of 45 kDa, with a stable triple helix structure, high biocompatibility, water solubility and biosafety. The anti-tumor activity of rhCOLIII was comprehensively evaluated through in vitro and in vivo experiments. In vitro, our results showed that rhCOLIII inhibited the proliferation, migration, and invasion of ovarian cancer cells (OCCs), and induced apoptosis. In addition, rhCOLIII not only inhibited autophagy of OCCs but also increased the expression of MHC-1 molecule within OCCs. To further elucidate the mechanism of rhCOLIII in OC, we conducted joint analysis of RNA-Seq and proteomics, and found that rhCOLIII exerted anti-tumor function and autophagy inhibition by downregulating Glutathione S-transferase P1 (GSTP1). Furthermore, various rescue experiments were designed to demonstrate that rhCOLIII suppressed autophagy and proliferation of OCCs by mediating GSTP1. In vivo, we found that rhCOLIII could inhibit tumor growth and promote CD8+ T cell infiltration. Our results indicate that rhCOLIII has great anti-tumor potential activity in OC, and induces protective anti-tumor immunity by regulating autophagy through GSTP1. These findings illustrate the potential therapeutic prospects of rhCOLIII for OC treatment.

Escalated aggression represents a frequent and severe form of violence, sometimes manifesting as antisocial behavior. Driven by the pressures of modern life, escalated aggression is of particular concern due to its rising prevalence and its destructive impact on both individual well-being and socioeconomic stability. However, a consistent neural circuitry underpinning it remains to be definitively identified. Here, we addressed this issue by comparing brain alterations between individuals with escalated aggression and those without such behavioral manifestations. We first conducted a meta-analysis to synthesize previous neuroimaging studies on functional and structural alterations of escalated aggression (325 experiments, 2997 foci, 16,529 subjects). Following-up network and functional decoding analyses were conducted to provide quantitative characterizations of the identified brain regions. Our results revealed that brain regions constantly involved in escalated aggression were localized in the subcortical network (amygdala and lateral orbitofrontal cortex) associated with emotion processing, the default mode network (dorsal medial prefrontal cortex and middle temporal gyrus) associated with mentalizing, and the salience network (anterior cingulate cortex and anterior insula) associated with cognitive control. These findings were further supported by additional meta-analyses on emotion processing, mentalizing, and cognitive control, all of which showed conjunction with the brain regions identified in the escalated aggression. Together, these findings advance the understanding of the risk biomarkers of escalated aggressive populations and refine theoretical models of human aggression.

Specific algal polysaccharides exhibit significant anti-allergic activity. B cell class switch recombination (CSR) is a crucial step in food allergies, however, the role of polysaccharides in regulating CSR remains unclear. To investigate the regulation of B cell CSR by algal polysaccharides, an in vitro IgE-type CSR cell model was used to screen for active algal polysaccharides, and four active polysaccharides were identified. In a food allergy mouse model, Undaria pinnatifida polysaccharides (UPP) and phosphoryl oligosaccharides (POS) suppressed allergic responses and reduced the proliferation of IgE+ B cells. Transcriptome sequencing of B cells identified LCN2 as a potential target of POS, and inhibition of LCN2 blocked the activity of POS on CSR. These findings demonstrated the efficacy of POS in regulating B cell CSR and alleviating allergic responses and revealed the underlying mechanisms. This work provided data and theoretical support for the development of polysaccharide-based functional foods for individuals with allergies.

Electron beam–directed energy deposition (EB–DED) has emerged as a promising wire-based metal additive manufacturing technique. However, the effects of EBs on pendant droplets at wire tips have not yet been determined. The aim of this study is to enhance the understanding of this action by analyzing the mechanism of droplet oscillation. The pendant droplet oscillation phenomenon hinders the stable transfer of droplets to the molten pool and limits the feasibility of manufacturing complex lattice structures by EB–DED. Hence, another aim of this study is to create an oscillation suppression method. An escalating asymmetric amplitude is the main characteristic of droplet oscillation. The primary oscillation-inducing force is the recoil force generated from the EB-acted local surface of the droplet. The physical mechanism of this force is the rapid increase and uneven distribution of the local surface temperature caused by the partial action of the EB. The prerequisites for droplet oscillation include vacuum conditions, high power densities, and bypass wire feeding processes. The proposed EB–dynamic surrounding melting (DSM) method can be applied to conveniently and effectively suppress oscillations, enable the accurate transfer of droplets to the molten pool, and achieve stable processes for preparing the strut elements of lattice structures. Lowering the temperature and improving the uniformity of its distribution are the mechanisms of oscillation suppression in EB–DSM. In this study, the physical basis for interpreting the mechanism by which EBs act on droplets and the technical basis for using EB–DED to prepare complex lattice structure parts are provided.

Objective: Accurate infant brain parcellation is crucial for understanding early brain development; however, it is challenging due to the inherent low tissue contrast, high noise, and severe partial volume effects in infant magnetic resonance images (MRIs). The aim of this study was to develop an end-to-end pipeline that enabled accurate parcellation of infant brain MRIs. Methods: We proposed an end-to-end pipeline that employs a two-stage global-to-local approach for accurate parcellation of infant brain MRIs. Specifically, in the global regions of interest (ROIs) localization stage, a combination of transformer and convolution operations was employed to capture both global spatial features and fine texture features, enabling an approximate localization of the ROIs across the whole brain. In the local ROIs refinement stage, leveraging the position priors from the first stage along with the raw MRIs, the boundaries of the ROIs are refined for a more accurate parcellation. Results: We utilized the Dice ratio to evaluate the accuracy of parcellation results. Results on 263 subjects from National Database for Autism Research (NDAR), Baby Connectome Project (BCP) and Cross-site datasets demonstrated the better accuracy and robustness of our method than other competing methods. Conclusion: Our end-to-end pipeline may be capable of accurately parcellating 6-month-old infant brain MRIs.

This work investigates the effect of Ru on the precipitation of the topologically close-packed (TCP) phase from the γ-γʹ microstructural degradation analysis. The addition of Ru is found to delay the precipitation time of the TCP phase from 100 h to 1000 h after thermal exposure at 950 °C. The effect of Ru on the γ-γʹ microstructural degradation is also investigated. Adding Ru slightly decreases the coarsening rate of the γʹ size and promotes the reduction of the volume fraction of γʹ phase. The reduction of the volume fraction of γʹ phase causes the ''inverse partitioning'' effect and increases the solution limit of the TCP forming element in the matrix. These help inhibit the precipitation of the TCP phases in Ni-based single crystal superalloys during thermal exposure.

In this work, a two-stage rolling method with varied temperature and strain rate was proposed for powder metallurgy (PM) Ti–47Al–2Cr–2Nb-0.2W alloy sheets based on the guidance of processing map and microstructure evolution. Compared with conventional rolling at a high temperature and a low strain rate, the TiAl alloy exhibited enhanced plastic deformability through the implementation of the two-stage rolling method, resulting in a higher cumulative true strain. Microstructure analysis revealed significant grain refinement in the rolled sheet. During the first stage of hot rolling with high temperatures and low strain rates, the softening behavior caused by dynamic recovery (DRV) and dynamic recrystallization (DRX) is conducive to the plastic deformation in the second stage rolling (low temperatures and high strain rates). In addition, the formation of mechanical twins further promotes DRX behavior. The softening mechanism of α2 phase is DRV, and that of γ phase is continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX).

The mechanism of pore evolution in vacuum electron beam joints of Mo-14Re alloy has been thoroughly investigated. Microscopic characterization methods, including Optical Microscopy (OM) and Scanning Electron Microscopy (SEM), were employed to explore the evolution mechanism of pore defects at different locations. Weld defects were further characterized using Energy Dispersive Spectroscopy (EDS) and Transmission Electron Microscopy (TEM), providing insights into their formation mechanisms. The findings reveal that pores along grain boundaries are the result of MoO and CO bubble aggregation. Non-equilibrium solidification of the melt triggers chemical reactions, transforming MoO and CO bubbles into MoO3 and C, with lower melting points. MoO3 and C persist in the pores, leading to the formation of grain boundary gas hole defects. On the other hand, intragranular pore defects stem from an abundance of pores within the matrix material. Upon entry of gas from these pores into the molten pool, its escape is impeded due to the intense influence of the molten pool. After the molten pool completes the cooling and solidification process, the gas remains within the crystal, resulting in intragranular pore defects.

Ultrafine-grained microstructure was successfully obtained in Mg–6Al–3Sn–1Zn (ATZ631) alloy by multi-pass high-speed rolling (HSR) at a rolling speed of 1100 m/min and a rolling temperature of 400 °C. The grain refinement mechanism of ATZ631 alloy during HSR was investigated, which is attributed to mechanically fragmented grains and twinning-induced dynamic recrystallization (TDRX). During the initial stages of rolling, the initial coarse grains are refined by the intersection of twins. With increasing strain, the grain refinement mechanism is the typical dynamic recovery and TDRX. In general, twins are filled with a high density of dislocations and nano-sized precipitates at the dislocations, which can accelerate DRX by increasing the driving force or particle-stimulated nucleation (PSN) within the twins. Subsequently, the coarse grains are refined by forming fine DRXed grains via dislocation entanglement, dislocation rearrangement, and dislocation absorption. As the process proceeds, grain boundaries (GBs) migration is suppressed by the precipitates at the GBs of new DRXed grains. Thus, the growth of the DRXed grains can be inhibited. Finally, ultrafine-grained microstructure with an average size of ∼116 nm is obtained. Moreover, the new grains formed by TDRX exhibit random orientation during this process, indicating that the basal texture gets effectively weakened by increasing the fraction of DRXed grains. These findings bring forward the microstructural evolution during dynamic precipitation and DRX, thus providing a novel notion for improving microstructures and grain refinement in Mg alloys.

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia (CNS-ALL). Integrin α6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression. The targeted peptide D(RWYD) (abbreviated RD), with nanomolar affinity to integrin α6 was identified by peptide scanning techniques such as alanine scanning, truncation, and D-substitution. Herein, we developed a therapeutic nanoparticle based on the integrin α6-targeted peptide for treating CNS-ALL. The self-assembled proapoptotic nanopeptide D(RWYD)-D(KLAKLAK)2-GD(FFY) (abbreviated RD-KLA-Gffy) contains the integrin α6-targeted peptide RD, the well-known proapoptotic peptide D(KLAKLAK)2 (abbreviated KLA), and the self-assembling tetrapeptide GD(FFY) (abbreviated Gffy). The functional mechanism of RD-KLA-Gffy is clarified using different experiments. Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis, thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity. Moreover, the combined use of RD-KLA-Gffy and methotrexate (MTX) shows a potent antitumor effect in treating CNS-ALL, indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX, which shows promise for application in CNS-ALL therapy.

Cadmium (Cd) is an environmental pollutant that has neurotoxic properties, which poses serious threats to human health and the development of poultry farming. Chlorogenic acid (CGA) is a dietary polyphenol exhibit various biological activities such as antioxidant, anti-inflammatory, and autophagy regulation. In addition, CGA can penetrate the blood-brain barrier and exert neuroprotective effects. This study explored the mechanism of CGA in alleviating Cd-induced cerebral cortical neuron injury in chickens. The results showed that in vivo, CGA reduced the Cd level and alleviated Cd-induced histopathological and ultrastructural damages in the chicken cerebral cortex. Further research has found that CGA alleviated Cd-induced incomplete autophagy and activation of the AMPK-ULK1 pathway. In vitro, AMPK inhibitors (Compound C) could alleviate Cd-induced incomplete autophagy in chicken cerebral cortical neurons. In addition, CGA alleviated the decreased viability, incomplete autophagy, and activation of the AMPK-ULK1 pathway induced by Cd in chicken cerebral cortical neurons. In summary, CGA can alleviate Cd-induced cerebral cortical neuron injury in chickens, which is related to CGA alleviating Cd-induced incomplete autophagy by inhibiting the AMPK-ULK1 pathway.

Hexafluoropropylene oxide trimer acid (HFPO-TA) is an emerging environmental pollutant that can accumulate in air and surface water. Currently, it has been widely used in fluoropolymer industry, which could cause serious environmental pollution. Due to the high bioaccumulation, the accumulation of pollutants may have an adverse effect on the normal physiological function of the kidneys. However, the toxic effects of HFPO-TA on the kidney are unknown. In this study, we investigated the toxic effects of HFPO-TA exposure on the rat kidney and its mechanism of action. Male SD rats were divided into 4 groups: control group (Ctrl group), L group (0.125 mg/kg/d), M group (0.5 mg/kg/d) and H group (2 mg/kg/d). After 14 consecutive days of gavage, periodic acid‑silver methenamine (PASM) and hematoxylin-eosin (HE) staining were used to examine the structure of the kidneys. We also used transcriptome sequencing (RNA-seq) to identify differentially expressed genes (DEGs) in the testes of rats in both the control and high dose groups. Besides, expression of key proteins was analyzed by immunohistochemistry. The results indicated that HFPO-TA can lead to injured renal capsule, change glomerular shape and have a significant impact on the protein expression levels of AQP2, p-AQP2 and PPARα. Additionally, the level of total cholesterol (TC) was obviously decreased after HFPO-TA exposure. RNA-seq analysis showed that HFPO-TA primarily affected peroxisome proliferator-activated receptor (PPAR) signaling pathway that is associated with lipid metabolism and cyclic adenosine monophosphate (cAMP) signaling pathway. In summary, exposure to HFPO-TA can lead to kidney damage and lipid metabolism disorders.

Background: Meteorin (METRN) is expressed predominantly in the central nervous system (CNS), where it functions by regulating glial cell differentiation and promoting axonal elongation. Nonetheless, its function within tumors is still not well understood. In this study, we focused on investigating its expression across various cancers and delving deeper into how METRN expression correlates with prognosis and immune infiltration. Methods: We explored METRN expression patterns in pan-cancers utilizing data obtained from the UCSC Xena and TCGA. In addition, analyses of survival and clinical association were conducted for tumors where METRN could affect the prognosis. Subsequently, nomogram models were constructed for sarcoma (SARC) and prostate adenocarcinoma (PRAD) to verify METRN's prognostic value in tumors. Furthermore, we also discussed the link between METRN and immune infiltration. As far as mechanisms are concerned, functional enrichment analysis was conducted to analyze the functional components and signaling pathways involved in METRN. Results: This study found that METRN was abnormally expressed in various tumors, closely connected with the prognosis and clinical characteristics of several tumors, and had good prognostic value. Moreover, analysis of immune infiltration revealed that METRN interacts with multiple immune cells, with alterations in the immune microenvironment potentially influencing tumor prognosis. Enrichment analysis indicates that METRN may influence tumorigenesis and progression through immune-related pathways. Conclusion: To sum up, our study demonstrates that METRN can be a prospective predictive biomarker in diverse cancer types and a promising target for cancer immunotherapy for pan-cancer.

Cigarette smoke, a complex mixture produced by tobacco combustion, contains a variety of carcinogens and can trigger DNA damage. Overactivation of c-MET, a receptor tyrosine kinase, may cause cancer and cellular DNA damage, but the underlying mechanisms are unknown. In this work, we investigated the mechanisms of cigarette smoke extract (CSE) induced malignant transformation and DNA damage in human bronchial epithelial cells (BEAS-2B). The results demonstrated that CSE treatment led to up-regulated mRNA expression of genes associated with the c-MET signaling pathway, increased expression of the DNA damage sensor protein γ-H2AX, and uncontrolled proliferation in BEAS-2B cells. ATR, ATR, and CHK2, which are involved in DNA damage repair, as well as the phosphorylation of c-MET and a group of kinases (ATM, ATR, CHK1, CHK2) involved in the DNA damage response were all activated by CSE. In addition, CSE activation promotes the phosphorylation modification of ATR, CHK1 proteins associated with DNA damage repair. The addition of PHA665752, a specific inhibitor of c-MET, or knock-down with c-MET both attenuated DNA damage, while overexpression of c-MET exacerbated DNA damage. Thus, c-MET phosphorylation may be involved in CSE-induced DNA damage, providing a potential target for intervention in the prevention and treatment of smoking-induced lung diseases.

This study focuses on the scientific problem of whether farmland scale utilization is feasible in China and which areas of farmland are suitable for scale utilization. Based on multi-source data, we adopted TOPSIS and Hotspot analysis models to quantitatively evaluate and reveal the spatio-temporal evolution law of the suitability for farmland scale utilization in China over the past 30 years, and then used matrix grouping method to carried out the regulatory zoning. The findings suggested that: (1) The spatio-temporal differentiation of suitability for farmland scale utilization in China was significant from 1990 to 2020, 68 % of counties and 81 % of farmland resources were suitable for scale utilization. (2) In terms of spatial pattern, the suitability showed the distribution characteristics of high in the north and low in the south, high in the east and low in the west. In terms of time change, the farmland endowment suitability decreased slightly over the past 30 years, the natural environment suitability was basically stable, the socio-economic suitability increased steadily, and the comprehensive suitability showed a continuous and slow upward trend. (3) The priority development zone, suitable development zone and remediation regulate zone for farmland scale utilization in China accounted for 29.82 %, 31.19 % and 38.99 %, respectively. The regulatory zoning indicated that the suitability level of farmland scale utilization in China needed to be further improved. This study can provide scientific reference for the optimal allocation and utilization mode adjustment of farmland resources in different regions of China, which is of great valuable for promoting the sustainable utilization of farmland resources and ensuring food security in China.

The accumulation of advanced glycosylation end products (AGEs) from food in the body disrupts normal physiological insulin activity and causes insulin resistance. This study compared the effects of ten types of polyphenols on AGEs production in both chemical and food models. It also investigated the impact of polyphenols on AGEs-induced insulin resistance in HepG2 cell models. Results showed that luteolin had the strongest inhibitory effect on fluorescent AGEs in the three chemical models. Rutin exhibited the most potent capacity to inhibit AGEs in biscuit models. Moreover, rutin alleviated the glucose metabolism disorders induced by representative AGEs (methylglyoxal-modified bovine serum albumin, MGO-BSA) in HepG2 cells. Mechanistic studies revealed that rutin could inhibit the phosphorylation of insulin receptor substrate 1 (IRS1) and the activity of suppressor of cytokine signaling 3 (SOCS3), while activating the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) to alleviate the MGO-BSA-induced insulin resistance in HepG2 cells.

Carbon storage in terrestrial ecosystems varies with land use changes, and exploring the impact of land use changes on carbon storage in regional terrestrial ecosystems is important for maintaining regional carbon balance. Data on Dalian City’s land use types from 2000 to 2020 are used in this research, to evaluate the spatio-temporal evolution of carbon storage in Dalian. Furthermore, with the scenarios of urban development, natural development, cultivated land protection, and ecological protection in 2030, this study combines the PLUS and InVEST models to emulate the dynamic adjustment at land-use types and the spatio-temporal evolution regarding carbon storage in Dalian City. The investigation shows that: 1) The carbon storage of terrestrial ecosystem in Dalian has been altered as a consequence of changes in land use, and now it shows a general decline during 2000–2020, with reductions amounting to 5.39 × 106 t. 2) From 2000 through 2020, Dalian’s land resources that are utilized for farming, forestry, and grassland decreased to different degrees. The total construction land area increased by 796.47 km2, or 6.38 %, whereas there has been no substantial improvement in water or unused land. 3) The carbon storage reduction in 2030 in comparison to 2020 for the natural development, cultivated land protection, and urban development scenarios, among which the urban development scenario was the largest, was 1.36 × 106t. It suggests that the rapid rate of urbanization and expansion of construction land is an important cause of the decline in carbon storage. 4) The cultivated land protection scenario (CPS) yields the smallest reduction of 6.50 × 105t. The structure of Dalian’s land use type is optimum under the ecological protection scenario (EPS), as seen by the 3.90 × 105t increase in carbon storage under this scenario. It speeds up the rate of recovery of carbon storage and improves the function of carbon sinks in urban terrestrial ecosystems. Hoping to provide the reference to decision makers for ecosystem carbon storage optimization from the view of land use, which is vital for making future land use policies and realizing the “dual carbon” strategic goal.

Summary: Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. We conducted an open-label, phase 2 nonrandomised, externally controlled study to evaluate the efficacy and safety of targeted agents plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) (CHOPX) for PTCL in the front-line setting. Methods: Eligible patients were ≥18 years of age and newly diagnosed PTCL. Patients in the CHOPX group received standard CHOP at Cycle 1. Specific targeted agents were added from Cycle 2, decitabine if TP53mut, azacytidine if TET2/KMT2Dmut, tucidinostat if CREBBP/EP300mut, and lenalidomide if without mutations above. Patients in the CHOP group received CHOP for 6 cycles. The primary endpoint was the complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov, NCT04480099. Findings: Between July 29, 2020, and Sep 22, 2022, 96 patients were enrolled and included for efficacy and safety analysis with 48 in each group. The study met its primary endpoint. CRR at EOT in the CHOPX group was superior to the CHOP group (64.6% vs. 33.3%, OR 0.27, 95%CI 0.12–0.64; p = 0.004). At a median follow-up of 24.3 months (IQR 12.0–26.7), improved median PFS was observed in the CHOPX group (25.5 vs. 9.0 months; HR 0.57, 95%CI 0.34–0.98; p = 0.041). The median OS was similar between two groups (not reached vs. 30.9 months; HR 0.55, 95%CI 0.28–1.10; p = 0.088). The most common grade 3–4 hematological and non-hematological adverse events in the CHOPX group were neutropenia (31, 65%) and infection (5, 10%). Interpretation: Targeted agents combined with CHOP demonstrated effective and safe as first-line treatment in PTCL. Biomarker-driven therapeutic strategy is feasible and may lead to promising efficacy specifically toward molecular features in PTCL. Funding: This study was supported by the National Key Research and Development Program (2022YFC2502600) and the General Program of the Shanghai Municipal Health Commission (202040400).

Background: Stroke is the second leading cause of death for all human beings and poses a serious threat to human health. Environmental exposure to a mixture of metals may be associated with the occurrence and development of stroke, but the evidence in the Chinese population is not yet conclusive. Objectives: This study evaluated the association between stroke risk and 13 metals Methods: Metal concentrations in whole blood samples from 100 stroke cases and 100 controls were measured by ICP-MS. The cumulative impact of mixed metal on stroke risk was investigated by using three statistical models, BKMR, WQS and QGC. Results: The case group had higher concentrations of Mg, Mn, Zn, Se, Sn, and Pb than the control group (p

The improvement and verification of fluid dynamics simulation on temperature uniformity during the heat treatment of ring pieces are investigated in this study. The accuracy of the temperature field model is validated by comparing the simulation results with the measured temperatures. The findings reveal that the vortex generated near the furnace wall during heat treatment significantly affects the uniformity of the temperature field. To improve this, adjustments are made to the placement of ring pieces based on an experimentally validated fluid dynamics simulation model, and subsequent calculations are performed on this adjusted model. It is observed that these adjustments greatly enhance temperature uniformity in the heating process, with a 39.06 % improvement in medium-temperature zone (732.32–743.69 k) within the furnace compared to the original model. Additionally, surface temperatures of ring pieces in another medium-temperature zone (668.89–691.11 k) show a 34.54 % improvement in comparison to those predicted by the original model.

Renal fibrosis represents a pivotal characteristic of chronic kidney disease (CKD), for which effective interventions are currently lacking. The Src kinase activates the phosphatidylinositol-3 kinases (PI3K)/Akt1 pathway to promote renal fibrosis, casting a promising target for anti-fibrosis treatment. Chaihuang-Yishen formula (CHYS), a traditional Chinese medicinal prescription, has a validated efficacy in the treatment of CKD, however, with the underlying mechanism unresolved. This study aimed to uncover the pharmacological mechanisms mediating the effect of CHYS in treating renal fibrosis using network pharmacology followed by experimental validation. The chemical compounds of CHYS were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database or published literature, followed by the prediction of their targets using SwissTargetPrediction software. Disease (CKD/renal fibrosis)-related targets were retrieved from the Genecards database. Protein-protein interaction (PPI) network was generated using the drug-disease common targets and visualized in Cytoscape software. The drug-disease targets were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by Metascape software. Additionally, the compound-target-pathway network was established in Cytosape to identify key compounds, targets, and pathways. Network pharmacology analysis screened out 96 active compounds and 837 potential targets within the 7 herbal/animal medicines of CHYS, among which 237 drug-disease common targets were identified. GO and KEGG analysis revealed the enrichment of fibrosis-related biological processes and pathways among the 237 common targets. Compound-target-pathway network analysis highlighted protein kinases Src and Akt1 as the top two targets associated with the anti-renal fibrosis effects of CHYS. In UUO mice, treatment with CHYS attenuates renal fibrosis, accompanied by suppressed expression and phosphorylation activation of Src. Unlike Src, CHYS reduced Akt1 phosphorylation without affecting its expression. In summary, network pharmacology and in vivo evidence suggest that CHYS exerts its anti-renal fibrosis effects, at least in part, by inhibiting the Src/Akt1 signaling axis.

To evaluate the efficacy of the 18F–AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F–AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe effectively differentiated various stages of liver fibrosis in mini pigs. Blood serum enzymatic tests revealed distinct stages of liver fibrosis, revealing significant increases in AST, ALT, TBIL, and DBIL levels as fibrosis advanced. Notably, ALT levels increased markedly in severe fibrosis patients. A gradual increase in collagen deposition and increasing α-SMA RNA expression and protein levels effectively differentiated between mild and severe fibrosis stages. Pathological examinations and Sirius Red staining confirmed these findings, highlighting substantial increases in collagen accumulation. PET/CT imaging results aligned with histopathological findings, showing that increased radiotracer uptake correlated with fibrosis severity. Assessments of mitochondrial function revealed a decrease in total liver glutathione content and mitochondrial reserve capacity, especially in patients with severe fibrosis. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe is a promising tool for the noninvasive assessment of liver fibrosis, offering potential benefits over traditional diagnostic methods in hepatology.