Search

Abstract A post hoc subgroup analysis has suggested potential therapeutic benefits of prasinezumab, a humanized monoclonal anti-α-synuclein antibody, in patients with rapidly progressing Parkinson’s disease (PD), despite initial trials showing limited impact on primary outcomes. Caution is needed due to the retrospective nature of subgroup analyses, and potential confounding factors that may have influenced the observed treatment effects in specific patient subsets. Critical considerations are provided here for designing and implementing preclinical studies and clinical trials involving monoclonal antibodies, suggesting that future research should prioritize refining preclinical models and optimizing biomarker-based patient selection to reduce risks of false trial outcomes, eventually advancing antibody-based therapies in PD effectively and safely.

Abstract Background and aims Previous studies have confirmed that alcohol can increase the sensitivity of the pancreas to stressors and exacerbate the severity of pancreatitis when excessive alcohol intake is combined with other causes. In the current work, this study attempted to explore how does alcohol regulate cerulein-induced acute pancreatitis, especially before inflammation occurs. Methods Proteomics was performed to analyze the differentially expressed proteins in pancreatic tissues from a rat model of pancreatitis. The metabolite levels in the pancreatic tissue, serum of rats and serum of persons with a history of alcohol consumption were detected by LC‒MS/MS. In the present study the impact of etomoxir (a carnitine palmitoyl-transferase 1A-specific inhibitor) treatment on AR42J cells treated with alcohol and the effect of etomoxir injection on the inflammatory response in an alcohol + cerulein-induced AAP rat model was evaluated. Results When treated with the same amount of cerulein, the rats that ingested alcohol presented with more severe pancreatitis. The proteomics results revealed that the fatty acid degradation pathway was closely related to the development of alcoholic acute pancreatitis, and CPT1A exhibited the greatest increase (approximately twofold increase). The products (acylcarnitines) of CPT1A were changed in the serum of persons with a history of alcohol consumption. Etomoxir treatment mitigates the influence of alcohol stimulation on the aberrant expression of proteins associated with oxidative stress, increased ROS production, mitochondrial ultrastructural alterations and mitochondrial dysfunction in AR42J cells. Etomoxir injection reduced the inflammatory response in the AAP rat model. Conclusion Alcohol upregulates CPT1A protein expression in pancreatic tissue, resulting in abnormal lipid metabolism. The products of lipid metabolism, ROS, contribute to mitochondrial ultrastructural alterations and mitochondrial dysfunction. These changes act as sentinel events that regulate acute pancreatitis.

Abstract Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exosomes in osteogenic differentiation and their potential therapeutic effects on osteoporosis. Exosomes were extracted from BMSCs. Bone marrow-derived macrophages (BMDMs) were cultured and internalized with BMSCs-derived exosomes. Real-time quantitative PCR was used to detect the expression of macrophage surface markers and tripartite motif (TRIM) family genes. BMDMs were co-cultured with human osteoblasts to assess osteogenic differentiation. Western blot was performed to analyze the ubiquitination of triggering receptor expressed on myeloid cell 1 (TREM1) mediated by TRIM25. An ovariectomized mice model was established to evaluate the role of TRIM25 and exosomes in osteoporosis. Exosomes were successfully isolated from BMSCs. BMSCs-derived exosomes upregulated TRIM25 expression, promoting M2 macrophage polarization and osteogenic differentiation. TRIM25 facilitated the ubiquitination and degradation of TREM1. Overexpression of TREM1 reversed the enhanced M2 macrophage polarization and osteogenic differentiation caused by TRIM25 overexpression. TRIM25 enhanced the protective effect of BMSCs-derived exosomes against bone loss in mice. These findings suggested that BMSCs-derived exosomes promoted osteogenic differentiation by regulating M2 macrophage polarization through TRIM25-mediated ubiquitination and degradation of TREM1. This mechanism might provide a novel approach for treating osteoporosis.

In this work, we investigate the microstructures and mechanical properties evolution on a novel carbon-based maraging steel with the compositions of Fe–10Mn-0.25C–1Cr–2Mo wt%, through hot and cold rolling following by heat treatment. The composition was designed through thermodynamic modelling to achieve a combination of high strength and high tensile elongation through the development of fine tempered martensite with carbide strengthening, and the transformation induced plasticity (TRIP) from the reverted austenite. After hot and cold deformation, a solution treatment at 870 °C followed by quenching gave a martensitic structure with 5% retained austenite. The microstructure and tensile properties were then investigated in detail as a function of ageing time at 510 °C. The kinetics of austenite reversion were much more rapid, with a peak in austenite content after only 5h, giving a maximum volume fraction of ∼26%, with a sharp reduction for longer ageing times. The best tensile properties were obtained after an 8 h age with only ∼16.5% of reverted austenite, which provided a UTS of 1560 MPa (220 MPa contributed by TRIP) and an elongation of 14.5%. While the smallest grain size was attained after 16 h of aging, accompanied by an exceedingly low volume fraction of reverted austenite (∼2.1%) for the TRIP effect, the UTS decreased to 1356 MPa, with a slightly improved elongation of 15.7%. The results show that achieving the optimal mechanical properties requires balancing the volume fraction of reverted austenite for the TRIP effect with the grain size to enhance both strength and ductility.

Abstract Background Short term results of the change of center of rotation (COR) after Bryan cervical disc replacement (CDR) have been reported. However, there is a lack of long-term studies focusing on the COR and its influences on facet joint degeneration. Objective To evaluate the long-term clinical and radiographic results of Bryan CDR, and to explore the influence of deviated COR on facet joint degeneration at index level. Methods It is a retrospective follow up study conducted in China. Eighty-three consecutive patients who received single-level Bryan CDR were retrospectively reviewed. Clinical evaluation included Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), and Odom’s scale. Radiographic evaluation underwent before surgery, at early follow-up (3 months) and last follow-up (10 years). The radiographic parameters included range of motion (ROM), location of COR presented by the coordinates (COR-x, COR-y), and facet joint degeneration score. Correlation analysis was conducted between changes of COR and facet joint degeneration score. Results Fifty-nine patients were included, with an average age of 44.6 ± 7.4 years. The mean follow-up time was 135.7 ± 12.4 (120–155) months. JOA score, NDI and Odom’s scale showed significant improvements at last follow-up. The ROM was well preserved through follow-up. 33 patients (55.9%) showed deterioration of facet joint degeneration at index level. The increment of facet joint degeneration score at index level was strongly correlated with the change of COR-x (r = 0.758, P

Abstract The controlled shock wave (CSW) fracturing is an effective method for enhancing permeability of coal seam to promote gas extraction. Based on Fick’s law, Darcy’s law, the ideal gas law and the Langmuir equation, a damage-seepage-deformation coupling mathematical model of CSW fracturing in coal seam combined with the maximum tensile stress and the Mohr-Coulomb criterion is established. This model is implemented into COMSOL Multiphysics to simulate the coal seam CSW fracturing and subsequent gas extraction. When the shock wave and isotropic in-situ stress are applied on the borehole wall, the coal damage zone is an annular shape, and the permeability in the damage zone increases sharply. The CSW can effectively increase the efficiency of gas extraction and reduce the gas pressure and gas content in coal seam. With the increase of CSW action times, the damage in coal mass reaches a threshold and tends to be stable after several shocks. The damage area and the gas extraction efficiency are positively correlated with the shock intensity. Under the anisotropic ground stress, the larger diversity of the stress in different directions is, the more obvious damage extension in the fractured coal along the maximum stress direction is. Ground stress can inhibit the extension of cracks in the CSW fractured coal seam. This inhibition effect becomes more obvious with the increase of in-situ stress. Parameters are substantiated of controlled shock wave impact on the coal seam, which ensures increased methane extraction from low-permeability reservoirs, are substantiated.

Abstract With the advancement of the reform and opening up, the non-state Sectors (NSS) in China and Vietnam have developed rapidly. The ruling parties, which used to have comprehensive control over politics, economy, and society, have now found it difficult to control the new economic space. To effectively control NSS, the Communist Party of China and the Communist Party of Vietnam have attempted to embed themselves in NSS by expanding grassroots party organizations. In this process, they have adopted different strategies and procedures, resulting in two distinct models: China’s expansion model, which is characterized by a proactive approach combining rigidity and flexibility, and Vietnam's expansion model, which is characterized by a flexible approach with a focus on soft cooperation. This study compares the formation, nature, and main characteristics of the two models for party organization expansion in China and Vietnam, hoping to provide a more comprehensive and objective understanding of the developments in China and Vietnam, preliminarily elucidate, from an academic perspective, the operational model of party-building in NSS in the two countries, and enrich the theoretical research on the continuous expansion of the existing Leninist parties in the new era.

Abstract Racial and ethnic disparities persist in cancer survival rates across the United States, despite overall improvements. This comprehensive analysis examines trends in 5-year relative survival rates from 2002–2006 to 2015–2019 for major cancer types, elucidating differences among racial/ethnic groups to guide equitable healthcare strategies. Data from the SEER Program spanning 2000–2020 were analyzed, focusing on breast, colorectal, prostate, lung, pancreatic cancers, non-Hodgkin lymphoma, acute leukemia, and multiple myeloma. Age-standardized relative survival rates were calculated to assess racial (White, Black, American Indian/Alaska Native, Asian/Pacific Islander) and ethnic (Hispanic, Non-Hispanic) disparities, utilizing period analysis for recent estimates and excluding cases identified solely through autopsy or death certificates. While significant survival improvements were observed for most cancers, notable disparities persisted. Non-Hispanic Blacks exhibited the largest gain in breast cancer survival, with an increase of 5.2% points (from 77.6 to 82.8%); however, the survival rate remained lower than that of Non-Hispanic Whites (92.1%). Colorectal cancer survival declined overall (64.7–64.1%), marked by a 6.2% point drop for Non-Hispanic American Indian/Alaska Natives (66.3–60.1%). Prostate cancer survival declined across all races, with Non-Hispanic American Indian/Alaska Natives showing a decrease of 7.7% points (from 96.9 to 89.2%). Lung cancer, acute leukemia, and multiple myeloma showed notable increases across groups. Substantial racial/ethnic disparities in cancer survival underscore the notable need for tailored strategies ensuring equitable access to advanced treatments, particularly addressing significant trends in colorectal and pancreatic cancers among specific minority groups. Careful interpretation of statistical significance is warranted given the large dataset.

Abstract Background Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood. Methods To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT–qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT–qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1’s regulation of autophagy in GC. Results Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo. Conclusion PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC. Graphical Abstract

C2H2 zinc finger protein is widely involved in the occurrence and development of cancer. However, the function and mechanism of most C2H2 zinc finger proteins in breast caner (BC) remains unclear. Here, we reported the expression prognosis of C2H2 type zinc finger protein ZNF775 in BC patients and its possible biological mechanism. First, multiple public databases showed that ZNF775 was significantly overexpressed in BC tissues. Interestingly, high expression of ZNF775 was significantly associated with a better prognosis. Immunohistochemistry were used for verification, and the expression of ZNF775 was consistent with the databases. Considering the large heterogeneity of different breast cancer cells, we temporarily selected MCF-7 cell line for verification. In vitro overexpression experiments showed that overexpression of ZNF775 significantly inhibited the proliferation and migration of MCF-7 BC cell. We further combined RNA-sequencing (RNA-seq) and CUT & Tag, and found that overexpression of ZNF775 can down-regulate the expression of most genes in the Wnt signaling pathway. The cBioportal database showed that ZNF775 was negatively correlated with the expression of Wnt5a, suggesting that its downstream target was likely Wnt5a. Finally, we discovered that Wnt5a could partially reverse the inhibitory effect of ZNF775 on MCF-7 BC cell migration through transwell migration experiments. In conclusion, our findings will provide new ideas for the diagnosis, treatment and prognosis assessment of BC in the future.

There is increasing evidence that chronic stress (CS), which occurs when the body is exposed to prolonged stressors, significantly impairs learning and memory. Dopamine (DA) plays a critical role in learning and memory in the hippocampus through the activation of D1-like receptors (D1R). However, the specific roles of DA and D1R in the hippocampal dentate gyrus (DG), particularly in CS-induced changes in spatial learning and memory, are not well understood. In this study, we established a CS rat model through the random application of various stressors. We assessed spatial learning and memory using the Morris water maze (MWM) and measured DA concentration and the amplitude of field excitatory postsynaptic potentials (fEPSP) in the DG during the MWM test in freely moving rats. We also examined the involvement of D1R in spatial learning and memory by microinjecting its antagonist (SCH23390) into the DG, and then analyzed the expressions of phosphorylated (p-) Ca2+/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and cAMP-response element binding protein (CREB) in the DG using Western blot. During the MWM test, compared with the control group, the escape latency was increased, and the percentage of distance in target quadrant and the number of platform crossings were decreased, in addition, the increase of fEPSP amplitude in the DG was significantly attenuated in CS group. In the control group, the DA concentration in the DG was significantly increased during the MWM test, and this response was enhanced in the CS group. Microinjection of SCH23390 into the DG significantly improved the spatial learning and memory impairments in CS rats, and reversed the inhibitory effect of CS on increase of fEPSP amplitude in the DG during the MWM test. Furthermore, SCH23390 partially reversed the inhibitory effects of CS on the expressions of p-CaMKII, p-PKA, and p-CREB in the DG. Our findings suggest that overactivation of the DA-D1R system in the hippocampal DG impairs spatial learning and memory and related synaptic plasticity in CS rats via downregulation of PKA-CREB signaling pathway.

BackgroundStress urinary incontinence (SUI), the most common form of urinary incontinence, is a condition that affects many women. It is characterized by involuntary urine leakage during activities that increase abdominal pressure, such as sneezing, coughing, or physical exertion, according to the International Continence Society. SUI affects patients’ quality of life and causes depression and emotional disorders, which negatively influences physical and mental health. The participants in the studies in this review comprised women with mild to moderate SUI, because there are more female patients than male patients, and most patients with severe SUI are treated surgically. Moreover, after retrieval, there were no systematic reviews or network meta-analyses (NMAs) of conservative treatments, such as electroacupuncture (EA), in women with mild to moderate SUI. ObjectiveThis study aims to investigate the efficacy of electroacupuncture among women with mild to moderate SUI using an NMA. MethodsRandomized clinical trials related to conservative treatments for SUI will be searched in 5 English and 3 Chinese literature databases: EMBASE, PubMed, Cochrane, Web of Science, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), WanFang, and the Chinese BioMedical Literature Database. The search period for these 8 electronic databases will be from 2002 to 2022. The PROSPERO database and the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) database will also be searched. Two reviewers will independently complete the research selection. After screening the studies, 2 other researchers will extract the data, and the quality of the included studies will be evaluated according to the quality standards specified in the Cochrane Collaboration Tool (version 2). The primary outcomes will be the change in urine leakage determined by a 1-hour pad test and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) scores at baseline and at the conclusion of the follow-up. The secondary outcomes will be 72-hour incontinence episodes, residual bladder volume, effective rate, urodynamic indexes, and other reported measurements. Stata (version 14.0; StataCorp) and Review Manager (RevMan version 5.3; Cochrane) will be implemented for data synthesis and meta-analysis. ResultsThe results are not yet accessible because this is a protocol for a systematic review and meta-analysis. The protocol was registered on INPLASY on February 22, 2023. By April 6, 2023, we had completed the literature search of the 8 databases and completed the selection and data extraction of the articles. ConclusionsThe results of this systematic review will demonstrate the efficacy of EA among women with mild to moderate SUI. The results will provide evidence for clinicians and guideline makers to choose suitable treatments for SUI. Trial RegistrationInternational Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) 202320098; https://inplasy.com/inplasy-2023-2-0098/ International Registered Report Identifier (IRRID)DERR1-10.2196/55870

Despite reported influences of the intratumoral microbiome on cancer progression, its role in this subtype remains unclear. This study aimed to characterize the microbial landscape and signatures of kidney renal clear cell carcinoma using RNA-Seq data from The Cancer Genome Atlas. Following microbial decontamination, differential microbial analysis was conducted between tumorous and adjacent non-tumorous samples. Compared to non-tumorous samples, tumorous microbiota exhibited reduced α and β diversity and distinct phylum-level communities. Differential microbial analysis between patients exhibiting long and short overall survival revealed ten significant differential microbial genera, with six genera correlating with a positive prognosis (Plasmodium, Babesia, Toxoplasma, Cytobacillus, Alicyclobacillus, Verrucomicrobium) and four with a negative prognosis (Colletotrichum, Leuconostoc, Gluconobacter, and Parabacteroides). Employing Cox regression analysis and support vector machines, a prognosis-related microbiome risk signature was developed, achieving an AUC of 0.809. Based on this risk signature, two microbiome-based subtypes were found to be significantly associated with distinct clinical prognoses and immune microenvironments. These findings were corroborated by significant correlations between prognostic-relevant microorganisms and 30 immune-related differentially expressed genes. Specifically, microbial genera associated with a negative prognosis were linked to a pro-tumor acute inflammatory immune response, whereas genera related to a positive prognosis were associated with an anti-tumor adaptive immune response. In conclusion, microbiome-based subtyping revealed correlations between tumor microbiome, clinical prognosis, and tumor microenvironment, indicating intratumoral microbiota as a promising prognostic biomarker for kidney renal clear cell carcinoma.

Abstract Background Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. The intercellular communication in post-infarction angiogenesis remains unclear. Methods In this study, we explored the role and mechanism of action of M2 macrophage-derived exosomes (M2-exos) in angiogenesis after MI. M2-exos were harvested and injected intramyocardially at the onset of MI. Two distinct endothelial cells (ECs) were cultured with M2-exos to explore the direct effects on angiogenesis. Results We showed that M2-exos improved cardiac function, reduced infarct size, and enhanced angiogenesis after MI. Moreover, M2-exos promoted angiogenesis in vitro; the molecules loaded in the vesicles were responsible for its proangiogenic effects. We further validated that higher abundance of miR-132-3p in M2-exos, which recapitulate their functions, was required for the cardioprotective effects exerted by M2-exos. Mechanistically, miR-132-3p carried by M2-exos down-regulate the expression of THBS1 through direct binding to its 3´UTR and the proangiogenic effects of miR-132-3p were largely reversed by THBS1 overexpression. Conclusion Our findings demonstrate that M2-exos promote angiogenesis after MI by transporting miR-132-3p to ECs, and by binding to THBS1 mRNA directly and negatively regulating its expression. These findings highlight the role of M2-exos in cardiac repair and provide novel mechanistic understanding of intercellular communication in post-infarction angiogenesis.

Abstract As a facilitator of smart upgrading, digital twin (DT) is emerging as a driving force in prognostics and health management (PHM). Faults can lead to degradation or malfunction of industrial assets. Accordingly, DT-driven PHM studies are conducted to improve reliability and reduce maintenance costs of industrial assets. However, there is a lack of systematic research to analyze and summarize current DT-driven PHM applications and methodologies for industrial assets. Therefore, this paper first analyzes the application of DT in PHM from the application field, aspect, and hierarchy at application layer. The paper next deepens into the core and mechanism of DT in PHM at theory layer. Then enabling technologies and tools for DT modeling and DT system are investigated and summarized at implementation layer. Finally, observations and future research suggestions are presented.

Abstract With the continuous increase of mining in depth, the gas extraction faces the challenges of low permeability, great ground stress, high temperature and large gas pressure in coal seam. The controllable shock wave (CSW), as a new method for enhancing permeability of coal seam to improve gas extraction, features in the advantages of high efficiency, eco-friendly, and low cost. In order to better utilize the CSW into gas extraction in coal mine, the mechanism and feasibility of CSW enhanced extraction need to be studied. In this paper, the basic principles, the experimental tests, the mathematical models, and the on-site tests of CSW fracturing coal seams are reviewed, thereby its future research directions are provided. Based on the different media between electrodes, the CSW can be divided into three categories: hydraulic effect, wire explosion and excitation of energetic materials by detonating wire. During the process of propagation and attenuation of the high-energy shock wave in coal, the shock wave and bubble pulsation work together to produce an enhanced permeability effect on the coal seam. The stronger the strength of the CSW is, the more cracks created in the coal is, and the greater the length, width and area of the cracks being. The repeated shock on the coal seam is conducive to the formation of complex network fracture system as well as the reduction of coal seam strength, but excessive shock frequency will also damage the coal structure, resulting in the limited effect of the enhanced gas extraction. Under the influence of ground stress, the crack propagation in coal seam will be restrained. The difference of horizontal principal stress has a significant impact on the shape, propagation direction and connectivity of the CSW induced cracks. The permeability enhancement effect of CSW is affected by the breakage degree of coal seam. The shock wave is absorbed by the broken coal, which may hinder the propagation of CSW, resulting in a poor effect of permeability enhancement. When arranging two adjacent boreholes for CSW permeability enhancement test, the spacing of boreholes should not be too close, which may lead to negative pressure mutual pulling in the early stage of drainage. At present, the accurate method for effectively predicting the CSW permeability enhanced range should be further investigated.

Abstract Background Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. Methods We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. Results We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. Conclusions Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC. Graphical abstract The mechanism of circ0003692 in suppressing metastasis of GC. FNDC3B-267aa encoded by circ0003692 interacted with c-Myc and promoted the proteasomal degradation of c-Myc, thereby down-regulated c-Myc-Snail/Slug axis and EMT pathway.

Abstract Background There are numerous complex barriers and facilitators to continuously wearing hearing protection devices (HPDs) for noise-exposed workers. Therefore, the present study aimed to investigate the relationship between HPD wearing behavior and hearing protection knowledge and attitude, HPD wearing comfort, and work-related factors. Method A cross-sectional study was conducted with 524 noise-exposed workers in manufacturing enterprises in Guangdong Province, China. Data were collected on hearing protection knowledge and attitudes, HPD wearing comfort and behavior, and work-related factors through a questionnaire. Using structural equation modeling (SEM), we tested the association among the study variables. Results Among the total workers, 69.47% wore HPD continuously, and the attitudes of hearing protection (26.17 ± 2.958) and total HPD wearing comfort (60.13 ± 8.924) were satisfactory, while hearing protection knowledge (3.54 ± 1.552) was not enough. SEM revealed that hearing protection knowledge had direct effects on attitudes (β = 0.333, p

BackgroundExcessive oxidative stress is one of the key pathophysiological mechanisms underlying migraine, and increasing antioxidant intake has proven to be an effective strategy for the prevention and improvement of migraine symptoms. To explore the relationship between the composite dietary antioxidant index (CDAI) and the occurrence of migraine attacks.MethodsCross-sectional data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999–2004 were utilized. Logistic regression, stratified analysis, and restricted cubic spline (RCS) models were employed to investigate the association between CDAI and migraine attacks.ResultsA total of 8,137 adults aged ≥20 were enrolled, comprising 1,610 patients with migraine and 6,527 non-migraine individuals. After adjusting for all covariates, CDAI was negatively correlated with migraine. In the overall participants, compared with the CDAI Q1 (−5.83 to −2.14) group, the adjusted odds ratio (OR) for migraine in Q3 (−0.59 to 1.53) and Q4 (1.53–44.63) groups were 0.71 [95% confidence interval (95% CI): 0.54–0.92, p = 0.011] and 0.64 (95% CI: 0.47–0.87, p = 0.005), respectively. After stratifying by age and gender, the protective effect was more pronounced in females aged 20–50, with adjusted OR for Q3 (−0.59 to 1.53) and Q4 (1.53–44.63) groups of 0.60 (95% CI: 0.40–0.90, p = 0.013) and 0.48 (95% CI: 0.30–0.78, p = 0.003), respectively. The RCS curve indicated a nonlinear relationship between CDAI and migraine in females aged 20–50, with a threshold of 0.006.ConclusionCDAI is negatively correlated with migraine attacks, and a higher CDAI may be an effective protective factor in preventing migraine attacks, especially in women aged 20–50.

The pre-stressed flexible cable-supported photovoltaic (PV) systems (FCSPSs) are gradually becoming the preferred PV structure for large-span and mountain photovoltaic power plants. The wind-induced response of FCSPSs under negative wind conditions is more pronounced than under positive wind conditions. In this study, a series of two-way fluid-structure interaction (FSI) coupling numerical simulations are conducted to investigate the effect of ground anchors on the wind-induced vibration response of FCSPSs. Firstly, an analysis approach for wind-induced vibration coefficients of FCSPSs is established, involving model equivalency, coefficient definitions, model creation, and grid and solution settings. Secondly, modal analysis is performed on FCSPSs by varying the stiffness ratio (SR) of the ground anchor. Subsequently, changes in support reaction, ground anchor tension, translational displacement, and rotational displacement, as well as the wind field variation in the fluid domain under wind load, are evaluated for SR values ranging from 0 to 5. Finally, a quantitative evaluation of the wind-induced vibration coefficient in the FCSPS is conducted for different SR values. The results indicate that the configuration of ground anchor cables significantly mitigates the support reaction and displacement response of the FCSPS under negative wind conditions. Moreover, the stiffness ratio of the ground anchor has a relatively minor impact on wind-induced vibration coefficients (reaction force, displacement).

ObjectivesTo prospectively explore the association of maternal serum 25(OH)D levels with the infant’s gut microbiota in Chinese populations, and to evaluate its potential influence on the dynamic change patterns of offspring’s gut microbiota from 1 to 6 months old.MethodsEighty-seven mother-infant dyads (vitamin D insufficient group vs. normal group = 59 vs. 28) were included in this longitudinal study. Two fecal samples were collected for the included infant at home by the parents at 1 month of age (“M1 phase”) and 6 months of age (“M6 phase”). Gut microbiota were profiled by 16S rRNA gene sequencing. We performed mixed effects models on alpha diversity metrics, PERMANOVA tests on beta diversity distances, and linear discriminant analysis (LDA) to identify differently abundant taxa.ResultsWe observed significantly lower Pielou’s evenness and Shannon diversity in the vitamin D insufficient group in the M6 phase (p = 0.049 and 0.015, respectively), but not in the M1 phase (p > 0.05), and the dynamic changes in alpha diversity from 1 to 6 months old were significantly different according to maternal vitamin D status (p 2.0, p

Abstract Background We aimed to identify some potential biomarkers for elderly osteoporosis (OP) by integral analysis of lncRNA and mRNA expression data. Methods A total of 8 OP cases and 5 healthy participants were included in the study. Fasting peripheral venous blood samples were collected from individuals, and total RNA was extracted. RNA-seq library was prepared and sequenced on the Illumina HiSeq platform. Differential gene expression analysis was performed using “DESeq2” package in R language. Functional enrichment analysis was conducted using the “clusterProfiler” package, and the cis- and trans-regulatory relationships between lncRNA and target mRNA were analyzed by the lncTar software. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through the MCODE plugin in Cytoscape. Results We identified 897 differentially expressed lncRNAs (DELs) and 1366 differentially expressed genes (DEGs) between normal and OP samples. After co-expression network analysis and cis-trans regulatory genes analysis, we identified 69 candidate genes regulated by lncRNAs. Then we further screened 7 genes after PPI analysis. The target gene DOCK4, trans-regulated by two lncRNAs, was found to be significantly upregulated in OP samples. Additionally, 4 miRNAs were identified as potential regulators of DOCK4. The potential diagnostic value of DOCK4 and its two trans-regulatory lncRNAs was supported by ROC analysis, indicating their potential as biomarkers for OP. Conclusion DOCK4 is a potential biomarker for elderly osteoporosis diagnostic. It is identified to be regulated by two lncRNAs and four miRNAs.

Abstract Magma intrusion has an important influence on the physical and mechanical properties of coal and rock. In the area of magma intrusion, disasters such as gas outburst are prone to occur. Revealing its invasion law will be conducive to disaster management and energy development. For this purpose, changes in industrial analysis components of coal, mineral composition, major oxides, trace elements, and rare earth elements of coal under the thermal metamorphism of magma intrusion were analyzed. It is found that the moisture and volatile matter contents of the thermally affected coals in the mining face are generally lower than that of normal coals, while moisture and volatile matter contents are reduced towards to the magma intrusion contact. For example, the moisture and volatile matter of coal sample M01 decreased by 64.6% and 38.6% respectively compared with coal sample M05. During magma intrusion, some minerals remain on the surface of the coal body, resulting in changes in the mineral composition of the coal body. The decrease in carbon atom net spacing, the increase in crystallite aggregation and ductility, and aromaticity in thermally affected coals have a positive impact on the improvement of coal metamorphism. Due to the influences of magmatic intrusion, the variation rules of major oxides in coal are different, and the closer to the magmatic intrusion zone, the easier the major oxides are to be depleted. However, magma intrusion will not lead to the loss of all major oxides in thermally affected coals, such as content of CaO is 54.8%, which is higher than that of coal not affected by magmatic hydrothermal fluid. Most of the trace elements in the thermally affected coals of the No. 9 coal seam are depleted. The contents of rare earth elements are low on the whole coalbasis, with an average of 29.48 μg/g, and the distribution pattern towards to magmatic intrusion shows a wide and gentle “V” curve with left high and right low, showing the characteristics of enrichment of light rare earth elements.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, the role of circRNAs in ccRCC progression remains elusive. Methods The differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were screened using circRNA microarrays and the candidate target was selected based on circRNA expression level using weighted gene correlation network analysis (WGCNA) and the gene expression omnibus (GEO) database. CircPDHK1 expression in ccRCC and adjacent noncancerous tissues (n = 148) were evaluated along with clinically relevant information. RT-qPCR, RNase R digestion, and actinomycin D (ActD) stability test were conducted to identify the characteristics of circPDHK1. The subcellular distribution of circPDHK1 was analyzed by subcellular fractionation assay and fluorescence in situ hybridization (FISH). Immunoprecipitation-mass spectrometry (IP-MS) and immunofluorescence (IF) were employed to evaluate the protein-coding ability of circPDHK1. ccRCC cells were transfected with siRNAs, plasmids or lentivirus approach, and cell proliferation, migration and invasion, as well as tumorigenesis and metastasis in nude mice were assessed to clarify the functional roles of circPDHK1 and its encoded peptide PDHK1-241aa. RNA-sequencing, western blot analysis, immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) assays were further employed to identify the underlying mechanisms regulated by PDHK1-241aa. Results CircPDHK1 was upregulated in ccRCC tissues and closely related to WHO/ISUP stage, T stage, distant metastasis, VHL mutation and Ki-67 levels. CircPDHK1 had a functional internal ribosome entry site (IRES) and encoded a novel peptide PDHK1-241aa. Functionally, we confirmed that PDHK1-241aa and not the circPDHK1 promoted the proliferation, migration and invasion of ccRCC. Mechanistically, circPDHK1 was activated by HIF-2A at the transcriptional level. PDHK1-241aa was upregulated and interacted with PPP1CA, causing the relocation of PPP1CA to the nucleus. This thereby inhibited AKT dephosphorylation and activated the AKT-mTOR signaling pathway. Conclusions Our data indicated that circPDHK1-encoded PDHK1-241aa promotes ccRCC progression by interacting with PPP1CA to inhibit AKT dephosphorylation. This study provides novel insights into the multiplicity of circRNAs and highlights the potential use of circPDHK1 or PDHK1-241aa as a therapeutic target for ccRCC.

Abstract Background Mutations in CHCHD2 have been linked to Parkinson’s disease, however, their exact pathophysiologic roles are unclear. The p32 protein has been suggested to interact with CHCHD2, however, the physiological functions of such interaction in the context of PD have not been clarified. Methods Interaction between CHCHD2 and p32 was confirmed by co-immunoprecipitation experiments. We studied the effect of p32-knockdown in the transgenic Drosophila and Hela cells expressing the wild type and the pathogenic variants of hCHCHD2. We further investigated the rescue ability of a custom generated p32-inhibitor in these models as well as in the human fibroblast derived neural precursor cells and the dopaminergic neurons harboring hCHCHD2-Arg145Gln. Results Our results showed that wildtype and mutant hCHCHD2 could bind to p32 in vitro, supported by in vivo interaction between human CHCHD2 and Drosophila p32. Knockdown of p32 reduced mutant hCHCHD2 levels in Drosophila and in vitro. In Drosophila hCHCHD2 models, inhibition of p32 through genetic knockdown and pharmacological treatment using a customized p32-inhibitor restored dopaminergic neuron numbers and improved mitochondrial morphology. These were correlated with improved locomotor function, reduced oxidative stress and decreased mortality. Consistently, Hela cells expressing mutant hCHCHD2 showed improved mitochondrial morphology and function after treatment with the p32-inhibitor. As compared to the isogenic control cells, large percentage of the mutant neural precursor cells and dopaminergic neurons harboring hCHCHD2-Arg145Gln contained fragmented mitochondria which was accompanied by lower ATP production and cell viability. The NPCs harboring hCHCHD2-Arg145Gln also had a marked increase in α-synuclein expression. The p32-inhibitor was able to ameliorate the mitochondrial fragmentation, restored ATP levels, increased cell viability and reduced α-synuclein level in these cells. Conclusions Our study identified p32 as a modulator of CHCHD2, possibly exerting its effects by reducing the toxic mutant hCHCHD2 expression and/or mitigating the downstream effects. Inhibition of the p32 pathway can be a potential therapeutic intervention for CHCHD2-linked PD and diseases involving mitochondrial dysfunction.

Abstract With an estimated one million new cases reported annually, gastric cancer (GC) ranks as the fifth most diagnosed malignancy worldwide. The early detection of GC remains a major challenge, and the prognosis worsens either when patients develop resistance to chemotherapy or radiotherapy or when the cancer metastasizes. The precise pathogenesis underlying GC is not well understood, which further complicates its treatment. Circular RNAs (circRNAs), a recently discovered class of noncoding RNAs that originate from parental genes through “back-splicing”, have been shown to play a key role in various biological processes in both eukaryotes and prokaryotes. CircRNAs have been linked to cardiovascular diseases, diabetes, hypertension, Alzheimer's disease, and the occurrence and progression of tumors. Prior studies have established that circRNAs play a crucial role in GC, impacting tumorigenesis, diagnosis, progression, and therapy resistance. This review aims to summarize how circRNAs contribute to GC tumorigenesis and progression, examine their roles in the development of drug resistance, discuss their potential as biotechnological drugs, and summarize their response to therapeutic drugs and microorganism in GC.

Cu2Te-based materials are a type of superionic conductor belonging to the class of phonon-liquid electron-crystal materials and have achieved high ZT values by doping and nanostructuring. However, it is easy to form copper vacancies in Cu2Te which leads to an excessive carrier concentration and then results in a low Seebeck coefficient. Hence, controlling copper ion migration and optimizing carrier concentration is essential to improve the thermoelectric performance of Cu2Te. This paper reports high-performance Cu2TeAg2Te composite with high application value in the low-middle temperature region, which is achieved by fine tuning the carrier concentration using Fe addition and non-stoichiometric Te, as well as controlling the thermal conductivity of composite. A high ZT of ∼1.2 is obtained in AgCu0.97Fe0.03Te0.96 at a low temperature of 573 K. Meanwhile, the phase transition mechanism of Cu2TeAg2Te and its effect on the thermoelectric transport performance are revealed that go beyond nanostructuring and single-doping, which provides a strong theoretical basis for research and performance improvement of thermoelectric materials in this system.

This paper gives a definition of the Industrial Internet and expounds on the academic connotation of the future Industrial Internet. From this foundation, we outline the development and current status of the Industrial Internet in China and globally. Moreover, we detail the avant-garde paradigms encompassed within the National Natural Science Foundation of China (NSFC)’s “Future Industrial Internet Fundamental Theory and Key Technologies” research plan and its corresponding management strategies. This research initiative endeavors to enhance interdisciplinary collaborations, aiming for a synergistic alignment of industry, academia, research, and practical implementations. The primary focus of the research plan is on the pivotal scientific challenges inherent to the future industrial internet. It is poised to traverse the “first mile”, encompassing foundational research and pioneering innovations specific to the industrial internet, and seamlessly bridges to the “last mile”, ensuring the effective commercialization of scientific and technological breakthroughs into tangible industrial market applications. The anticipated contributions from this initiative are projected to solidify both the theoretical and practical scaffolding essential for the cultivation of a globally competitive industrial internet infrastructure in China.

Electroencephalographic (EEG) source imaging (ESI) is a powerful method for studying brain functions and surgical resection of epileptic foci. However, accurately estimating the location and extent of brain sources remains challenging due to noise and background interference in EEG signals. To reconstruct extended brain sources, we propose a new ESI method called Variation Sparse Source Imaging based on Generalized Gaussian Distribution (VSSI-GGD). VSSI-GGD uses the generalized Gaussian prior as a sparse constraint on the spatial variation domain and embeds it into the Bayesian framework for source estimation. Using a variational technique, we approximate the intractable true posterior with a Gaussian density. Through convex analysis, the Bayesian inference problem is transformed entirely into a series of regularized ${L}_{{2}{p}}$ -norm ( ${0} < {p} < {1}$ ) optimization problems, which are efficiently solved with the ADMM algorithm. Imaging results of numerical simulations and human experimental dataset analysis reveal the superior performance of VSSI-GGD, which provides higher spatial resolution with clear boundaries compared to benchmark algorithms. VSSI-GGD can potentially serve as an effective and robust spatiotemporal EEG source imaging method. The source code of VSSI-GGD is available at https://github.com/Mashirops/VSSI-GGD.git.

In the field of remote sensing image denoising, the current mainstream methods usually only consider using clean or noisy images to guide the network in the training phase. Most of them only apply to specific types of noise, and the denoising effect is not satisfactory enough, with problems such as artifacts and noise residues. In this article, we endeavor to deal with a wide range of noise types, preserving as much detailed information in the image as possible and aiming to address the relevant limitations. Inspired by contrastive learning, we propose a remote sensing image denoising framework based on contrastive learning, named RSID-CR, which constructs positive and negative sample pairs between clean, noisy, and denoised images. Then, we construct a joint loss function consisting of reconstruction loss and contrastive regularization as a guide signal to train the denoising network, such that the denoised image is pushed closer to the clean image and farther away from the noisy image in the feature space. We conduct extensive experiments on two public datasets for five types of noise often present in remote sensing images. In addition, we validate our method using two real noisy remote sensing datasets. The experimental results indicate that our proposed method achieves satisfactory outcomes.

The burgeoning field of large language models (LLMs), exemplified by DALL-E and Stable Diffusion, has made image generation a reality. However, the computationally intensive GPU training these models necessitate incurs substantial financial burdens. Moreover, while a plethora of image datasets are accessible, specialized anime avatar datasets remain elusive and are often entangled in copyright disputes. This scarcity presents a significant research opportunity: developing a cost-effective, user-friendly anime avatar generation technique that circumvents these challenges. This paper introduces a novel method for creating animated avatars, leveraging the deep convolutional generative adversarial network(DCGAN) architecture and enhanced with Self-Attention (SA) and Spectral Normalization (SN), termed the SA+SN-DCGAN. The integration of the SA mechanism into the generator significantly elevates the quality of the output. Meanwhile, the application of SN to the discriminator effectively combats the notorious vanishing or exploding gradients, and thereby diminishing the likelihood of over-fitting. Our methodology involved sourcing anime avatars from reputable public domains and standardizing them using OpenCV. A meticulous grid search was employed to fine-tune model hyper-parameters. After 300 epochs of rigorous training, the generator and discriminator achieved stable error rates, with the synthesized images closely mirroring the fidelity of authentic avatars. Comparative evaluations against prevailing models underscore the SA+SN_DCGAN method’s superiority in producing highly realistic anime avatars, affirming its exceptional overall performance. This study not only contributes a novel solution to the domain of anime avatar generation but also paves the way for future research in the field.

The growing demand for lithium, driven by the widespread adoption of electric vehicles and renewable energy storage systems, has sparked interest in developing low-grade lithium resources. This comprehensive review explores the types, distribution, extraction technologies, challenges, and future prospects of low-grade lithium resources. This article focuses on low-grade lithium sources such as clays, brines, coal, and coal by-products, and analyzes the principles, advantages, and limitations of key extraction techniques, including acid-alkaline leaching, bioleaching, adsorption, and membrane separation. Furthermore, this review discusses the technical, economic, and environmental sustainability challenges associated with developing low-grade lithium resources and proposes corresponding strategies. Future research should focus on improving the selectivity and efficiency of extraction and processing technologies, optimizing separation processes, and developing green and cost-effective extraction methods. Establishing supportive policy frameworks, strengthening international cooperation, and knowledge sharing are crucial for promoting the sustainable development of low-grade lithium resources. This review provides stakeholders with comprehensive insights and recommendations for addressing the growing lithium demand and achieving the Sustainable Development Goals.

Given the increasing importance of effectively identifying synergistic changes between PM2.5 and O3 and comprehensively analyzing their impact on air quality management in China, we employ the Sen+Mann–Kendall (Sen+M-K) trend test in this study to examine the temporal and spatial variation trends of PM2.5 and O3 in the Yangtze River Delta (YRD), from 2003 to 2020. We identified the regions where these pollutants exhibited synergistic changes and established the pathways between the pollutants and their potential drivers, using geographically weighted random forest algorithms and structural equation modeling. The study results revealed as follows: (1) Overall, the PM2.5 concentrations show a decreasing trend, while the O3 concentrations exhibit an increasing trend, in the YRD. Analysis of the combined trends indicates that approximately 95% of the area displays opposing trends for PM2.5 and O3, with only about 4% in the southern region showing synergistic trends for both pollutants. (2) Drought and the average temperature are the main drivers of the changes in PM2.5 and O3 concentrations in areas experiencing synergistic changes. Their combined effects alleviate the aggregation of PM2.5 and reduce the formation of VOCs, indirectly reducing the generation of pollutants. The negative effect of the average temperature on the O3 concentration may indicate the existence of nonlinear effects and complex interaction effects between the drivers. NOx and VOCs play important dual roles in the generation and conversion of pollutants, although their overall impact is smaller than meteorological factors. They produce significant indirect effects through their interaction with meteorological and other human factors, further affecting the concentrations of PM2.5 and O3. In areas without coordinated changes, the main impact of meteorological factors remains unchanged, and the relationship between the two anthropogenic emission sources and their effects on PM2.5 and O3 are complex, with different directions and levels involved. This study provides detailed insights into the drivers of air quality changes in the YRD and offers a scientific basis for environmental management authorities to develop more comprehensive and targeted strategies for balancing the control of PM2.5 and O3 pollution.

Ion-adsorbing rare earth tailings (IRETs) contain a large amount of clay minerals, which are a potential source of silicon and aluminum for the preparation of zeolite materials. The complexity of the tailings’ composition and the impurity composition are the main difficulties in the controllable preparation of zeolite. Herein, IRETs were treated by classification activation technology for the preparation of IRET-ZEO, which was used for the removal of heavy metal Pb2+ in water. A new method of resource utilization of ion-type rare earth tailings is realized by “treating waste with waste”. The results showed that the IRETs were classified and then thermally activated, and the optimal activation parameter was calcination at 850 °C for 1 h. The optimal NaOH concentration used in the crystallization process was 5 mol/L, with a crystallization time of 3 h and a crystallization temperature of 85 °C, and the crystallization product was zeolite A. The removal rate of the Pb2+ solution with an initial concentration of 100 mg/L was as high as 96.7% in an acidic solution with a pH value from 2 to 5.5. In particular, when the solution pH was higher than 4.2, the adsorption rate of Pb2+ was close to 100%. The IRET-ZEO showed a fast adsorption rate (5 min to reach adsorption equilibrium), a large adsorption capacity (378.35 mg/g), excellent acid resistance, and selectivity and regenerability for Pb2+. This work provides a new strategy for the green resource utilization of IRETs and the treatment of lead-containing wastewater.

ABSTRACTIt is critical to understand the mechanisms and impacts of global climate change in cryosphere and polar environment. Here we describe the design and progress of the remote sensing products we have developed to monitor these changes. We obtain datasets by combining multi-sensor remote sensing systems with field validation systems, and then develop a methodological system that combines multiple sources and calibration technologies to address the challenges of data heterogeneity in dynamically monitoring key parameters. This global change and response special project supported by the National Key Research and Development Program of China, named ‘observation and inversion of critical parameters of changes in the cryosphere and polar environment’, providing comprehensive records of essential elements of the cryosphere through long-term satellite records. The multi-team is completing the project and collecting data from multi-sensor to create remote sensing data products that include records of changes in the cryosphere, such as permafrost, glaciers, ice sheet mass balance, seasonal snow accumulation, sea ice, and albedo changes. Finally, the existing ground- and space-based observing system can be improved to provide dynamic monitoring of key parameters in the cryosphere and changes in the polar environment.

Abstract Retinal thickness is related to Parkinson’s disease (PD), but its association with the severity of PD is still unclear. We conducted a Mendelian randomized (MR) study to explore the association between retinal thickness and PD. For the two-sample MR analysis, the summary statistics obtained from genome-wide association studies on the thickness of Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) were employed as exposure, while the summary statistics associated with PD were used as the outcome. The primary approach utilized was inverse variance weighted. To correct for multiple testing, the false discovery rate (FDR) was employed. For sensitivity analysis, an array of robust MR methods was utilized. We found genetically predicted significant association between reduced RNFL thickness and a reduced risk of constipation in PD (odds ratio [OR] = 0.854, 95% confidence interval [CI] (0.782, 0.933), P

Abstract Background Pancreatic cancer (PC) is a malignant tumor with extremely poor prognosis, exhibiting resistance to chemotherapy and immunotherapy. Nowadays, it is ranked as the third leading cause of cancer-related mortality. Glycation is a common epigenetic modification that occurs during the tumor transformation. Many studies have demonstrated a strong correlation between glycation modification and tumor progression. However, the expression status of glycosylation-related genes (GRGs) in PC and their potential roles in PC microenvironment have not been extensively investigated. Method We systematically integrated RNA sequencing data and clinicopathological parameters of PC patients from TCGA and GTEx databases. A GRGs risk model based on glycosylation related genes was constructed and validated in 60 patients from Pancreatic biobank via RT-PCR. R packages were used to analyze the relationships between GRGs risk scores and overall survival (OS), tumor microenvironment, immune checkpoint, chemotherapy drug sensitivity and tumor mutational load in PC patients. Panoramic analysis was performed on PC tissues. The function of B3GNT8 in PC was detected via in vitro experiments. Results In this study, we found close correlations between GRGs risk model and PC patients’ overall survival and tumor microenvironment. Multifaceted predictions demonstrated the low-risk cohort exhibits superior OS compared to high-risk counterparts. Meanwhile, the low-risk group was characterized by high immune infiltration and may be more sensitive to immunotherapy or chemotherapy. Panoramic analysis was further confirmed a significant relationship between the GRGs risk score and both the distribution of PC tumor cells as well as CD8 + T cell infiltration. In addition, we also identified a unique glycosylation gene B3GNT8, which could suppress PC progression in vitro and in vivo. Conclusion We established a GRGs risk model, which could predict prognosis and immune infiltration in PC patients. This risk model may provide a new tool for PC precision treatment.

Abstract Coal and gas outburst is a complex dynamic disaster during coal underground mining. Revealing the disaster mechanism is of great significance for accurate prediction and prevention of coal and gas outburst. The geo-dynamic system of coal and gas outburst is proposed. The framework of geo-dynamic system is composed of gassy coal mass, geological dynamic environment and mining disturbance. Equations of stress–damage–seepage interaction for gassy coal mass is constructed to resolve the outburst elimination process by gas extraction with boreholes through layer in floor roadway. The results show the occurrence of outburst is divided into the evolution process of gestation, formation, development and termination of geo-dynamic system. The scale range of outburst occurrence is determined, which provides a spatial basis for the prevention and control of outburst. The formation criterion and instability criterion of coal and gas outburst are established. The formation criterion F 1 is defined as the scale of the geo-dynamic system, and the instability criterion F 2 is defined as the scale of the outburst geo-body. According to the geo-dynamic system, the elimination mechanism of coal and gas outburst—‘unloading + depressurization’ is established, and the gas extraction by boreholes through layer in floor roadway for outburst elimination is given. For the research case, when the gas extraction is 120 days, the gas pressure of the coal seam is reduced to below 0.4 MPa, and the outburst danger is eliminated effectively.

Abstract Objective The traditional treatment of rheumatoid arthritis (RA) has some side effects. We aimed to explore the effect of metformin treatment on the expression of HMGB1, cytokines, T cell subtypes and the clinical outcomes in RA patients. Methods The present prospective cohort study recruited 124 RA patients (metformin group) who were treated with metformin and conventional therapy (methotrexate, hydroxychloroquine sulfate and sulfasalazine) and 98 RA patients (conventional therapy group) who were only treated with conventional therapy. All subjects were admitted from December 2018 to December 2021 and continuous medication for 90 days. The serum high mobility group box 1 (HMGB1), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometric were used to analyze the expression of CD4+ and CD8+. Demographic and clinical statistics including age, body mass index (BMI), sex, course of disease, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), visual analogue score (VAS)and disease activity score (DAS)-28 were collected. Results The serum levels of HMGB1, CRP, IL-6, CD4+ expression and CD4+/CD8+ ratio were significantly increased in patients with DAS-28 score ≥ 2.6. The serum HMGB1 and cytokines levels of metformin group declined more quickly during the study time. Pearson’s analysis supported that a positive correlation existed between the HMGB1 and IL-6, TNF-α, CRP, CD4+, CD4+/CD8+ ratio, and VAS scores. HMGB1 could be a potential diagnostic biomarker for RA patients in active phase. Serum HMGB1 (95% CI 1.133–1.397, P

Abstract Objectives Work-related musculoskeletal disorders (WMSDs) have become one of the major occupational health problems. Lots of auto workers in China are exposed to WMSDs. However, there are few systematic review and meta-analysis about WMSDs in this field. This study aimed to evaluate the prevalence of WMSDs among these workers. Methods This study was carried out using the Systematic Reviews and Meta-analyses method under the most up to date PRISMA guidelines. A literature search was conducted for studies on the epidemiology of WMSDs among auto workers in China from inception to August 2022, using English and Chinese databases (China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine Disc, China Science and Technology Journal Database, PubMed, and Web of Science). All statistical analyses were performed using STATA V.16.0. Results Out of the 849 references identified, 26 articles were were eligible for inclusion, of which 12 reported the overall 12-month prevalence of WMSDs, while 14 stated the 12-month prevalence of WMSDs on body regions. The overall 12-month prevalence rate of WMSDs among workers was 53.1% [95% Confidence Interval (CI) = 46.3% to 59.9%]. The lower back/waist was the body region affected most (36.5%, 95%CI = 28.5% to 44.5%). The definition on WMSDs of “Chinese version” resulted in a high prevalence of WMSDs. Obesity, high educational level, long job tenure, female, logistic workers, and foundry workers are factors that led to a high prevalence rate of WMSDs in the lower back/waist. Conclusions This study showed a high prevalence rate of WMSDs among auto workers in China. Thus, it is necessary to pay particular stress to them. Several effective measures should be taken to prevent these workers from WMSDs. Trial registration This review was registered on PROSPERO (registration number CRD42023467152).

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, with a highly aggressive phenotype and poor prognosis. RNA binding proteins (RBPs) play crucial roles in post-transcriptional gene regulation and have been implicated in tumorigenesis. RBPs have the potential to become a new therapeutic target for ccRCC. In this study, we screened and validated that insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) as an RBP, was down-regulated in ccRCC tissues and cell lines. Functionally, we verified that IGF2BP2 significantly suppressed the migration and invasion ability of ccRCC in vitro and in vivo. Mechanistically, RIP-seq and actinomycin D experiments results showed that IGF2BP2 enhanced the expression of Creatine Kinase B (CKB) by binding to CKB mRNA and enhancing its mRNA stability. Thus, IGF2BP2 inhibited ccRCC metastasis through enhancing the expression of CKB. Taken together, these finding suggests that IGF2BP2 is a novel metastasis suppressor of ccRCC and may serve as a potential therapeutic target.

The Mongolian medical silver needles often encounter issues of bending, fracturing, and blunting in clinical applications. Similarly, Mongolian warm needles can cause burns on patients due to inaccurate temperature control. In this study, we developed an Ag85Cu15 alloy specifically for acupuncture needles based on material preparation. By incorporating appropriate amounts of Mn and Ti elements, we were able to enhance the mechanical properties and biocompatibility of the acupuncture needles. Compared to commercially available silver needles, this alloy exhibited a significant increase in microhardness up to 210.2 Hv0.2 and an improved tensile strength of 880.2 MPa. Furthermore, we designed a thermoelectric effect-based temperature measurement model for precise control of the warm needle's temperature, enhancing the therapeutic effectiveness of the treatment.

BackgroundThe converter stations of high-voltage direct current (HVDC) transmission lines generate special total electric fields. At present, few investigations have been conducted on total electric fields in the workplace of converter stations from an perspective of occupational health. ObjectiveTo understand the current situation of total electric field strength in the workplace of converter stations. MethodsUsing purposive sampling, a calibrated HDEM-1 direct current (DC) total electric field strength measurement system was used to measure the total electric fields of 12 converter stations serving 6 DC lines in Southeast and Southwest China according to the Measurement method for total electric field strength and ion current density of the converter stations and DC transmission lines (DL/T 1089—2008). The results were evaluated according to occupational exposure limits recommended by The limits of electromagnetic environment at ±800 kV UHV DC converter station (DL/T 275—2012), the American Conference of Governmental Industrial Hygienists (ACGIH), and the International Commission on Non-Ionizing Radiation Protection (ICNIRP). ResultsA total of 615 check points were planned, the total electric field strength was 0.05-37.05 kV·m−1, and the median was 10.45 kV·m−1. The total electric field strength of 39 check points (6.3%) exceeded 25 kV·m−1 (the limits of ACGIH and ICNIRP), and the total electric field strength of 12 check points (2.0%) exceeded 30 kV·m−1 (the limit of DL/T 275—2012). There were statistically significant differences in the total electric field strength values and the proportions of exceeding 25 kV·m−1 between the neutral regions and the positive regions and between the neutral regions and the negative regions (P < 0.01). The proportion of total electric field strength exceeding 30 kV·m−1 in the negative regions was higher than that in the positive regions (P < 0.01). There were no significant differences in the total electric field strength of converter stations at different voltage levels and different altitudes (P > 0.05). There were no significant differences in the proportions of total electric field exceeding 25 kV·m−1 and exceeding 30 kV·m−1 in converter stations at different voltage levels and different altitudes (P > 0.05). ConclusionThe total electric field in some workplace of converter stations exceeds selected limits. Converter station operators may be exposed to high-strength total electric field for a short time.

Abstract Background The close relationship between pain and mental health problems is well-known, and psychological intervention can provide an effective alternative to medication-based pain relief. However, previous studies on the connection between pain and psychological problems, the findings thus far have been inconclusive, limiting the potential for translating psychological interventions into clinical practice. To complement the gap, this study utilized genetic data and Mendelian randomization (MR) to examine the potential relationship between pain in different parts and common mental disorders. Methods Based on the instrumental variables selected from the Genome-wide association study summary statistics of localized pain and mental disorders, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between pain and mental disorders. The inverse-variance weighted MR method and MR-Egger were used as the primary statistical method according to the horizontal pleiotropy and heterogeneity level. We reported the odds ratio to infer the causal effect between pain and mental disorders. F statistic was calculated to measure the statistical efficacy of the analyses. Results Insomnia is causally related to the genetic susceptibility of multisite pain including head (OR = 1.09, 95% CI: 1.06–1.12), neck/shoulder (OR = 1.12, 95% CI: 1.07–1.16), back (OR = 1.12, 95% CI: 1.07–1.18) and hip (OR = 1.08, 95% CI: 1.05–1.10). Reversely, headache (OR = 1.14, 95% CI: 1.05–1.24), neck/shoulder pain (OR = 1.95, 95% CI: 1.03–3.68), back pain (OR = 1.40, 95% CI: 1.22–1.60), and hip pain (OR = 2.29, 95% CI: 1.18–4.45) promote the genetic liability of insomnia. Depression is strongly associated with the predisposition of multisite pain including headache (OR = 1.28, 95% CI: 1.08–1.52), neck/shoulder pain (OR = 1.32, 95% CI: 1.16–1.50), back pain (OR = 1.35, 95% CI: 1.10–1.66) and stomach/abdominal pain (OR = 1.14, 95% CI: 1.05–1.25), while headache (OR = 1.06, 95% CI: 1.03–1.08), neck/shoulder (OR = 1.09, 95% CI: 1.01–1.17), back (OR = 1.08, 95% CI: 1.03–1.14), and stomach/abdominal pain (OR = 1.19, 95% CI: 1.11–1.26) are predisposing factors for depression. Additionally, insomnia is associated with the predisposition of facial, stomach/abdominal, and knee pain, anxiety was associated with the predisposition of neck/shoulder and back pain, while the susceptibilities of hip and facial pain are influenced by depression, but these associations were unidirectional. Conclusions Our results enhance the understanding of the complex interplay between pain and mental health and highlight the importance of a holistic approach to pain management that addresses both physical and psychological factors.

Abstract Background Few studies have focused on the chronic spontaneous behavior of the unfused TL/L curve during follow-up. The purpose of the present study was to explore the behavior of the unfused TL/L curve during a long-term follow-up to identify the risk factors for correction loss. Methods Sixty-four age-matched female AIS patients undergoing selective thoracic fusion were enrolled. Patients were divided into 2 groups according to whether there was correction loss. Risk factors for correction loss of the unfused TL/L curves were analyzed. The relationship and difference between the immediate postoperative thoracic and TL/L Cobb angles were explored. Results The TL/L Cobb angle was 28.17° before surgery, 8.60° after surgery, and 10.74° at the final follow-up, with a correction loss of 2.14°. Each subgroup contained 32 cases. A smaller postoperative TL/L Cobb angle was the only risk factor that was independently associated with TL/L correction loss. In the LOSS group, there was a significant difference and no correlation between the immediate postoperative TL/L and the thoracic Cobb angle. In the NO-LOSS group, there was a moderate correlation and no difference between them. Conclusion A smaller immediate postoperative TL/L Cobb angle may have been associated with TL/L correction loss during the long-term follow-up. Thus, good immediate postoperative spontaneous correction may not mean a satisfactory outcome at the final follow-up after STF. Mismatch between thoracic and TL/L Cobb angles immediately after surgery may also be related to correction loss of the unfused TL/L curves. Close attention should be paid in case of deterioration.

Electronic waste (e-waste) contains valuable rare earth elements (REEs) essential for various high-tech applications, making their recovery crucial for sustainable resource management. This review provides an overview of the occurrence of REEs in e-waste and discusses both conventional and emerging green technologies for their recovery. Conventional methods include physical separation, hydrometallurgy, and pyrometallurgy, while innovative approaches such as bioleaching, supercritical fluid extraction, ionic liquid extraction, and lanmodulin-derived peptides offer improved environmental sustainability and efficiency. The article presents case studies on the extraction of REEs from waste permanent magnets and fluorescent powders, highlighting the specific processes involved. Future research should focus on developing eco-friendly leaching agents, separation materials, and process optimization to enhance the overall sustainability and efficiency of REE recovery from e-waste, addressing both resource recovery and environmental concerns effectively.