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Chien-An Chen,1,2,&ast; Chung-Han Ho,3– 5,&ast; Yu-Cih Wu,3 Yi-Chen Chen,3 Jhi-Joung Wang,3 Kuang-Ming Liao6 1Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, 71004, Taiwan; 2Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, 71004, Taiwan; 3Department of Medical Research, Chi Mei Medical Center, Tainan, 71004, Taiwan; 4Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, 71005, Taiwan; 5Cancer Center, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, 11696, Taiwan; 6Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, 72263, Taiwan&ast;These authors contributed equally to this workCorrespondence: Kuang-Ming Liao, Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, 72263, Taiwan, Tel +886 6 726 3333, Email abc8870@yahoo.com.twPurpose: The incidence of aspergillosis is increasing, and the risk factors for infection include cancer, admission to the intensive care unit, chronic pulmonary diseases, immunocompromised status, and taking immunomodulatory drugs. There are limited data about the incidence of aspergillosis in patients with different types of cancer. The aim of our study was to survey the incidence of aspergillosis in different cancer types from 2006 to 2017.Patients and Methods: Data were collected from the Taiwan Cancer Registry database and International Classification of Diseases, 9th, 10th Revision, and Clinical Modification codes for diagnosing aspergillosis. Patients with a history of aspergillosis before cancer were excluded, and the secondary outcome was the risk of mortality in cancer patients with and without aspergillosis after 1 year.Results: Among 951 cancer patients with a diagnosis of aspergillosis, there were 614 hematopoietic and reticuloendothelial system patients, 100 lung cancer patients, and 73 lymphoma cancer patients. The overall incidence rates of aspergillosis tended to increase significantly from 2006 to 2017 (from 3.50 to 13.37 per 10,000 person-years, p value: < 0.0001). Regarding sex, the incidence rates of aspergillosis in males and females were 12.52 and 7.53 per 10,000 person-years, respectively. Patients with a diagnosis of aspergillosis had a 2.30-fold (95% CI: 2.14– 2.48, p value: < 0.0001) higher risk of mortality than those without aspergillosis.Conclusion: The incidence of aspergillosis was increased in cancer patients, and cancer patients with aspergillosis had a significantly higher risk of mortality than those without aspergillosis.Keywords: aspergillosis, cancer patients, Taiwan Cancer Registry, incidence rate

Abstract Color centers, arising from zero-dimensional defects, exploit quantum confinement to access internal electron quantum degrees of freedom, holding potential for quantum technologies. Despite intensive research, the structural origin of many color centers remains elusive. In this study, we employ in-situ cathodoluminescence scanning transmission electron microscopy combined with integrated differential phase contrast imaging to examine how defect configuration in tungsten sulfide determines color-center emission. Using an 80-kV accelerated electron beam, defects were deliberately produced, visualized, excited in situ and characterized in real time in monolayer WS2 within hBN|WS2 | hBN heterostructures at 100 K. These color centers were simultaneously measured by cathodoluminescence microscopy and differentiated by machine learning. Supported by DFT calculations, our results identified a crucial sulfur vacancy configuration organized into featured vacancy pairs, generating stable and bright luminescence at 660 nm. These findings elucidate the atomic-level structure-exciton relationship of color centers, advancing our understanding and quantum applications of defects in 2D materials.

The laser direct energy deposition (L-DED) is well-suited for metal manufacturing, offering advantages of excellent performance, high precision, intricate structures and material flexibility, etc. In this study, the microstructure and mechanical property of Ti–6Al–4V alloy were investigated using L-DED under various printing parameters. A large-area, high-resolution Electron Backscatter Diffraction (EBSD) mapping technique, enabling to characterize the coarse columnar β-grains with individual crystals up to a centimeter along the building direction, and the sub-grain acicular α′ phase down to 50 nm in the same image, was utilized to analyze the crystalline phases and their lattice orientations in additively manufactured Ti–6Al–4V parts. The microstructure evolution, involving the high temperature β grain structures, β+α phase transformation, as well as acicular α′ martensitic phases, were studied during the periodically attenuated thermal cycles of L-DED. The formation of the “fish-scale” morphology results primarily from the radically different α phase in size between the interior and edges of the “fish-scale” morphology. Additionally, the effect of processing parameters, i.e., scanning speed and laser power, on microstructures and mechanical properties is discussed in detail.

Abstract With the increase in mining depth and intensity, dynamic disasters such as rockburst in mines are becoming more severe. Deep resource extraction is characterized by a high in-situ stress geological environment, closely associated with geological dynamic disasters. However, there is currently no quantitative analysis method for the correlation between the two. In this study, an elastic energy density calculation method is employed, considering the dissipative effect of the self-weight stress field on the tectonic stress field. The remaining energy, referred to as impact energy, is used to classify the risk of coal seam impact, providing a computational method for rapid assessment of impact risk before mining production. The proposed calculation method is compared with 22 mine impact engineering practices in the literature, showing accurate predictions for 21 mines. Since measuring in-situ stress and coal seam physical and mechanical properties is a preliminary work in coal seam extraction, the comprehensive analysis of these data holds significant research and practical value.

Background: Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidptosis, was discovered. However, the detailed biological and clinical impact of disulfidptosis and related regulators remains largely unknown. Methods: In this work, we first enrolled pancancer datasets and performed multi-omics analysis, including gene expression, DNA methylation, copy number variation and single nucleic variation profiles. Then we deciphered the biological implication of disulfidptosis in clear cell renal cell carcinoma (ccRCC) by machine learning. Finally, a novel agent targeting at disulfidptosis in ccRCC was identified and verified. Results: We found that disulfidptosis regulators were dysregulated among cancers, which could be explained by aberrant DNA methylation and genomic mutation events. Disulfidptosis scores were depressed among cancers and negatively correlated with epithelial mesenchymal transition. Disulfidptosis regulators could satisfactorily stratify risk subgroups in ccRCC, and a novel subtype, DCS3, owning with disulfidptosis depression, insensitivity to immune therapy and aberrant genome instability were identified and verified. Moreover, treating DCS3 with NU1025 could significantly inhibit ccRCC malignancy. Conclusion: This work provided a better understanding of disulfidptosis in cancers and new insights into individual management based on disulfidptosis.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous chronic respiratory condition, and skeletal muscle dysfunction is one of its common complications, mainly clinically manifested as decreased muscle strength and endurance, altered muscle fiber type and decreased skeletal muscle mass. Mitochondrial damage is one of the key factors causing skeletal muscle dysfunction. Mitochondria not only provide energy for skeletal muscle, but also participate in reactive oxygen species (ROS) production, autophagy and protein turnover, which is of great significance to maintain the normal function of skeletal muscle. This study elucidated the mitochondrial changes in skeletal muscle dysfunction in patients with COPD, the mechanism of mitochondrial damage in skeletal muscle dysfunction in patients with COPD, and the potential effects of exercise rehabilitation training on mitochondrial damage in skeletal muscle in patients with COPD, in order to further clarify the relationship between mitochondria and skeletal muscle function, and to provide a reference for optimizing the exercise rehabilitation program for skeletal muscle dysfunction in COPD. The mitochondrial changes of skeletal muscle dysfunction in COPD mainly include impairment of the mitochondrial respiratory chain, a surge in mitochondrial autophagy, and a decreased in mitochondrial biogenesis. The mechanisms underlying mitochondrial damage of skeletal muscle dysfunction in COPD mainly include increasing skeletal muscle degradation, decreasing of skeletal muscle production and interfering with skeletal muscle differentiation. The potential effects of exercise rehabilitation training regulating mitochondrial damage in COPD skeletal muscle mainly include repairing the respiratory chain of skeletal muscle mitochondria in COPD patients, regulating mitophagy of skeletal muscle mitochondria, and promote the mitochondrial biogenesis of skeletal muscle in patients with COPD. Future research still needs to explore the key role of mitochondria in maintaining the normal functional structure of skeletal muscle, the mechanism of COPD skeletal muscle dysfunction, and the specific mechanism of exercise rehabilitation training in regulating mitochondrial damage to improve COPD skeletal muscle dysfunction, so as to provide a reference for exercise rehabilitation training in COPD skeletal muscle dysfunction.

Against the background of the increasing separation of natural and human geography, gradual disintegration of the comprehensive disciplinary characteristics of geography, and weakening of the social influence of geographers, the domestic geography community has recently been discussing the possibility of integrating natural and human geography and the possible paths for doing so. In response, this study proposes an analysis framework of Ecological Economic Geography conducive to the integration of physical and human geography. Furthermore, this study advocates a focus on the dynamic change of "human" as a giant system with complex links of economy, technology, and institutional systems, and its two-way feedback relationship with the ecosystem. By exploring the coupling and regulation mechanisms of human and natural systems in the context of environmental and technological change, this study seeks the best answer to human sustainable development in the comprehensive balance. To clarify the research perspective and ideas of Ecological Economic Geography, we select the following three cases: i) the centennial evolution of the ecological economic system of Mulberry-dyke and Fish-pond System, ii) the systematic cascade of the "digital-energy-water" in data centers, and iii) the humanistic perspective of ecological restoration planning. With a focus on the analytical framework of the "pattern-process-relationship-pathway," this study proposes four research topics on which Ecological Economic Geography needs to focus, specifically, the coupling pattern of ecosystems and economic systems, process and impact of different factor flows between different systems, regional complexity of ecological and economic coupling systems, and sustainable development pathway of the ecological economic system. Accordingly, the development of Ecological Economic Geography may strengthen the mutual collaboration between scholars of the natural world and the humanities, promote the integration of geographic disciplines, and enhance the ability of geography to solve extensive problems.

Rock shed is an effective protection measure against rockfall. To investigate the influences of falling rock’s shape and impact angle on the impact effect of the cushioned rock shed, a modeling approach for a rock shed with a cushion layer using PFC-FLAC. The granular cushion is modeled as an aggregate of discrete non-cohesion particles, while the concrete plate and the beam are modeled as zones. The falling rock with different sphericities and impact angles is modeled as a rigid assembly. The numerical model is validated by comparing the simulation results with experimental and numerical results from previous literature. This model is applied to analyze the effects of rock shape and impact angle on the dynamic interaction effects between falling rock and cushioned rock shed, including the impact force, transmitted bottom force, penetration depth, and plate deflection. The numerical results show that the variation in the falling rock’s shape has different effects on the falling rock with different impact angles. These findings could support rock shed design by revealing the limitations of the assumptions in the past research, which may result in unsafe rock sheds for some rockfall cases.

Abstract With the shift of coal seam mining to the deep, the in-situ stress of coal and rock mass increases gradually. High ground stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different crushing states than low stress conditions. In order to study the blasting expansion rule of rock mass with cavity under high ground stress and the rock mass fracture state under different side stress coefficients. In this paper, the effective range of blasting and the stress distribution under blasting load are analyzed theoretically. The RHT (Riedel-Hiermaier-Thoma) model is used to numerically simulate the blasting process of rock mass with cavity under different ground stress, and the influence of ground stress and lateral pressure coefficient on the crack growth of rock mass is studied. The results show that when there is no ground stress, the damage cracks in rock mass are more concentrated in the horizontal direction and the fracture development tends to the direction where the holes are located, which confirms the guiding effect and stress concentration effect of the holes in rock mass, which helps to promote the crack penetration between the hole and the hole. The length difference of horizontal and vertical damage cracks in rock mass increases with the increase of horizontal and vertical stress difference. Under the same lateral stress coefficient, the larger the horizontal and vertical stress difference is, the stronger the inhibition effect on crack formation is. For blasting of rock mass with high ground stress, the crack formation length between gun holes decreases with the increase of stress level, and the crack extends preferentially in the direction of higher stress. Therefore, the placement of gun holes along the direction of greater stress and the shortening of hole spacing are conducive to the penetration of cracks between gun holes and empty holes. The research can provide reference for rock breaking behavior of deep rock mass blasting.

Objective To investigate the effect of down-regulating adenosine deaminase acting on RNA-1(ADAR1) on the radiosensitivity of lung adenocarcinoma cells. Methods Lentiviral transfection was used to establish an ADAR1 knockdown cell line based on A549 cells.Then the cells were divided into negative control (shNC) and ADAR1 knockdown (shADAR1) groups, which were followed by a single-dose irradiation of 0 Gy and 6 Gy X-rays.Western blotting and RT-PCR were utilized to detect the expression of ADAR1 at protein and mRNA levels, respectively.CCK-8 assay, wound healing assay and Transwell migration assay were applied to measure cell proliferation and migration abilities.Meanwhile, clone formation assay was performed to detect the effect of down-regulating ADAR1 on the radiosensitivity of A549 cells.Flow cytometry and Western blotting were conducted to detect the expression levels of apoptosis and apoptosis-related proteins Bax and Bcl-2.Immunofluorescence assay and Western blotting were used to detect the expression level of γ-H2AX.Comet assay was performed to detect the level of cellular DNA damage.Twelve female nude mice (4~6 weeks old, weighing 16~18 g) were divided into shNC group, shADAR1 group, shNC+ionizing radiation (IR) group and shADAR1+IR group, with 3 mice in each group.The growth of tumor of different groups was observed with subcutaneous tumorigenesis assay. Results Western blotting and RT-qPCR showed that the protein and mRNA expression of ADAR1 were significantly reduced in A549 shADAR1 cells (P < 0.05).CCK-8 assay, wound healing assay and Transwell migration assay indicated that down-regulation of ADAR1 inhibited the proliferation and migration abilities of A549 cells, and this inhibition trend became more obvious (P < 0.01) after IR.Cell clone formation assay showed that the clone formation rate of both groups was decreased, with the increase of radiation dose.But the number of formed clones was lower in the shADAR1 group than the shNC group.Flow cytometry and Western blotting displayed that down-regulation of ADAR1 increased the apoptotic rate and Bax expression in A549 cells (P < 0.01) and decreased Bcl-2 expression (P < 0.05), and the apoptotic rate and Bax protein level were further increased in A549 shADAR1 cells after IR (P < 0.01), and the Bcl-2 protein level was further decreased (P < 0.01).The number of γ-H2AX foci and protein level in A549 shADAR1 cells were significantly increased after IR (P < 0.05), and the results of comet assay showed that the DNA damage was more obvious in A549 shADAR1 cells after IR (P < 0.01).Subcutaneous tumorigenesis assay in nude mice showed that the growth of subcutaneous tumour of A549 shADAR1 cells was significantly inhibited after IR (P < 0.01). Conclusion Down-regulation of ADAR1 significantly inhibits the proliferation and migration of A549 cells after IR and promotes apoptosis and DNA damage, and thereby increases the radiosensitivity of lung adenocarcinoma cells.

Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls. This study presents a systematic outcrop research of fracture pattern variations in a complicated rock slope, and the qualitative and quantitative study of the complex phenomena impact on three-dimensional (3D) discrete fracture network (DFN) modeling. As the studies of the outcrop fracture pattern have been so far focused on local variations, thus, we put forward a statistical analysis of global variations. The entire outcrop is partitioned into several subzones, and the subzone-scale variability of fracture geometric properties is analyzed (including the orientation, the density, and the trace length). The results reveal significant variations in fracture characteristics (such as the concentrative degree, the average orientation, the density, and the trace length) among different subzones. Moreover, the density of fracture sets, which is approximately parallel to the slope surface, exhibits a notably higher value compared to other fracture sets across all subzones. To improve the accuracy of the DFN modeling, the effects of three common phenomena resulting from vegetation and rockfalls are qualitatively analyzed and the corresponding quantitative data processing solutions are proposed. Subsequently, the 3D fracture geometric parameters are determined for different areas of the high-steep rock slope in terms of the subzone dimensions. The results show significant variations in the same set of 3D fracture parameters across different regions with density differing by up to tenfold and mean trace length exhibiting differences of 3–4 times. The study results present precise geological structural information, improve modeling accuracy, and provide practical solutions for addressing complex outcrop issues.

BackgroundThrough its extensive connection with the cortex, the thalamus constitutes the hub of cortico-subcortical circuits and participants in multi-dimensional functions. However, the differential involvements of thalamic functional connectivity in chronic capsular and pontine stroke are still unknown.MethodsThe research recruited 66 left-lesion chronic stroke patients, including 46 capsular strokes (CS) and 20 pontine stroke (PS) patients, and 67 normal controls (NC). The thalamic subfields functional connectivities were compared between groups using a two-way repeated analysis of variance (ANOVA), corrected for confounders including age, gender, education and scanners. Spearman partial correlation was used to explore the potential association between altered thalamic FC and clinical variables.ResultsThe ipsilesional thalamus of CS patients had abnormally decreased FC with widespread cognitive-related areas while increased FC with visual- and somatic-motor areas. In contrast, the ipsilesional thalamus of PS patients mainly demonstrated increased FC in these sensorimotor areas. Even in the contralesional thalamus, we observed similar (with the ipsilesional) but less extensive functional dysconnectivity patterns in both the CS and PS patients (P < 0.05, corrected using family-wise error [FWE] at the voxel level). Finally, we found significant group x subfields interactions on thalamic functional connectivity, where capsular vs. pontine stroke demonstrate varied functional dysconnectivity with specific thalamic subfields. Finally, a weak correlation was found between FC of both ipsilesional/contralesional thalamic subfields and motor, working and verbal memory.ConclusionsThe thalamic functional dysconnectivity after chronic stroke are lesion-location and subfields dependent. Moreover, functional dysconnectivity were shown in both the ipsilesional and contralesional thalamus with similar patterns.

BackgroundAcute ischemic stroke (AIS) is an acute brain injury caused by sudden occlusion of a blood vessel. Endovascular therapy is the most effective way to restore blood flow. However, despite the restoration of blood flow in some patients, their clinical prognosis often remains unsatisfactory. Albumin has shown neuroprotective effects in animal models of AIS. Therefore, this study aims to evaluate the safety, feasibility, and efficacy of local arterial infusions of 20% human serum albumin solution as an adjuvant therapy after endovascular therapy in patients with AIS.MethodsThis study is a prospective, therapeutic exploratory, non-randomized, open-label, phase 1 clinical trial testing the use of 20% human serum albumin solution injected via the artery immediately after successful reperfusion in patients with AIS. The study is divided into two stages. In the first stage, a single-dose-finding will explore the maximum safe dose according to the 3 + 3 dose escalation principle;, with the maximum dose being 0.60 g/kg. After recanalizing the occluded blood vessel, human serum albumin solution will be injected into the internal carotid artery region through a guiding catheter for 30 min. The second stage involves an albumin adjuvant therapy cohort (AT) and an endovascular treatment lonely cohort (ET). The AT cohort will encompass at least 15 additional participants to complete safety trials at the maximum safe dose determined in the first stage. The ET cohort will include well-matched patients receiving endovascular therapy alone, derived from a contemporaneous prospective registry, who will be excluded from having cardiopulmonary disorders and from receiving any neuroprotective therapy. The primary outcome of this study will be symptomatic intracranial hemorrhage. Efficacy outcomes will include the proportion of patients with the progression of cerebral infarction volume, a modified Rankin Scale of 0–2 on day 90 after randomization. An exploratory secondary outcome will be the analysis of thromboinflammatory and neuroprotective molecule profiles.ConclusionThis pilot trial aims to explore the safety and efficacy of arterial infusion of an albumin solution after occlusive vessel opening in AIS. The results will provide data parameters for subsequent tests on the arterial infusion of albumin solutions.Clinical trial registrationClinicalTrials.gov, NCT05953623.

Abstract Cistrome‐wide association studies (CWAS) are pivotal for identifying genetic determinants of diseases by correlating genetically regulated cistrome states with phenotypes. Traditional CWAS typically develops a model based on cistrome and genotype data to associate predicted cistrome states with phenotypes. The random effect cistrome‐wide association study (RECWAS), reevaluates the necessity of cistrome state prediction in CWAS. RECWAS utilizes either a linear model or marginal effect for initial feature selection, followed by kernel‐based feature aggregation for association testing is introduced. Through simulations and analysis of prostate cancer data, a thorough evaluation of CWAS and RECWAS is conducted. The results suggest that RECWAS offers improved power compared to traditional CWAS, identifying additional genomic regions associated with prostate cancer. CWAS identified 102 significant regions, while RECWAS found 50 additional significant regions compared to CWAS, many of which are validated. Validation encompassed a range of biological evidence, including risk signals from the GWAS catalog, susceptibility genes from the DisGeNET database, and enhancer‐domain scores. RECWAS consistently demonstrated improved performance over traditional CWAS in identifying genomic regions associated with prostate cancer. These findings demonstrate the benefits of incorporating kernel methods into CWAS and provide new insights for genetic discovery in complex diseases.

The visual search for product packaging involves intricate cognitive processes that are prominently impacted by learned associations derived from extensive long-term experiences. The present research employed EEG technology and manipulated the color display of reference pictures on beverage bottles to explore the underlying neurocognitive pathways. Specifically, we aimed to investigate the influence of color-flavor association strength on the visual processing of such stimuli as well as the in-depth neural mechanisms. The behavioral results revealed that stimuli with strong association strength triggered the fastest response and the highest accuracy, compared with the stimuli with weak association strength and the achromatic ones. The EEG findings further substantiated that the chromatic stimuli evoked a more pronounced N2 component than achromatic ones, and the stimuli with strong association strength elicited larger P3 and smaller N400 amplitudes than the ones with weak association strength. Additionally, the source localization using sLORETA showed significant activations in the inferior temporal gyrus. In conclusion, our research suggests that (1) color expectations would guide visual search process and trigger faster responses to congruent visual stimuli, (2) both the initial perceptual representation and subsequent semantic representation play pivotal roles in effective visual search for the targets, and (3) the color-flavor association strength potentially exerts an impact on visual processing by modulating memory accessibility.

The bidirectional DC-DC converter was selected as the research object. Based on the connection topology of energy storage and consumption components in the hybrid energy storage system, power demand indicators were determined for different energy flow directions, and the parameters of the main converter components and appropriate circuit components were established. A circuit model of buck/boost was constructed, and an adaptive fast terminal sliding mode control strategy was designed. The controller parameters were optimized using an improved genetic algorithm. Different control parameters have different control effects. In order to obtain better voltage output characteristics,the parameters of the adaptive fast terminal sliding mode control strategy were optimized.The proposed method can be verified to exhibit good control performance through simulation.

Abstract The theory and technology of rock bolting are fundamental research topics for strata control in civil and mining engineering. Rebar bolts are commonly used for roadway primary support in underground coal mine. To adapt to deep resource mining, a new left threaded rebar bolt has been developed. Compared to conventional rebar bolts, the result of installation test showed that the new bolt reduced of 41.5% and 57.9% in stirring resistance force and torque, respectively. In laboratory pullout tests, PVC and aluminum sleeves were used to simulate weak and medium strength surrounding rocks. The average peak pullout force, displacement at the peak load and energy absorption increased by 27%, 107% and 108%, respectively, using PVC sleeve; and increased by 113%, 109% and 212%, respectively, using aluminum sleeve. Field tests were conducted under soft coal, hard coal and medium strength rock geo-conditions. Different borehole depths were selected to precisely calculate the average anchorage performance of the new bolt. Results showed that the average peak pullout force of the new bolt increased by 37%, 38% and 28%, respectively, under different surrounding rock conditions. Moreover, based on on-site test results, the pullout curves in field-testing were summarised and classified into 6 different patterns, which were discussed from a viewpoint of causality mechanism. The research findings validate that the newly developed bolt has better anchorage performance compared to conventional rebar bolts, making it a new anchorage material for deep resource mining.

ObjectiveTo discover the appropriate temperature and time conditions for takeout containers using the specific migration test.MethodsThe time from ordering food to food delivery and finally food consumption was acquired from consumers through field surveys. Thereafter， the duration of the testing condition was assessed using the acquired data. Real foods were used to simulate the actual use of takeout containers， and temperature changes were recorded using an automatic recorder.ResultsBased on information from the field survey， the 2 h of food contact in takeout containers was simulated. The temperature recordings revealed that the average temperature in takeout containers ranged from 71-79 ℃.ConclusionTo analyze the specific migration volume of takeout containers， a specific migration test temperature of 100 ℃ or reflux temperature （95% ethanol） can be employed for 2 h.

Age-related cataract (ARC) is the predominant cause of global blindness, linked to the progressive aging of the lens, oxidative stress, perturbed calcium homeostasis, hydration irregularities, and modifications in crystallin proteins. Currently, surgical intervention remains the sole efficacious remedy, albeit carrying inherent risks of complications that may culminate in irreversible blindness. It is urgent to explore alternative, cost-effective, and uncomplicated treatment modalities for cataracts. Lanosterol has been widely reported to reverse cataracts, but the mechanism of action is not yet clear. In this study, we elucidated the mechanism through which lanosterol operates in the context of cataract reversal. Through the targeted suppression of sterol regulatory element-binding protein 2 (SREBP2) followed by lanosterol treatment, we observed the restoration of lipid metabolism disorders induced by SREBP2 knockdown in lens epithelial cells (LECs). Notably, lanosterol exhibited the ability to effectively counteract amyloid accumulation and cellular apoptosis triggered by lipid metabolism disorders. In summary, our findings suggest that lanosterol, a pivotal intermediate in lipid metabolism, may exert its therapeutic effects on cataracts by influencing lipid metabolism. This study shed light on the treatment and pharmaceutical development targeting Age-related Cataracts (ARC).

ObjectiveTo study test time and temperature of specific migration tests for hot drink cup through a questionnaire and a laboratory real temperature measurement method.MethodsThe consumption habits of consumers were investigated by means of questionnaires， the estimated time of contact with food during the general actual use of the hot drink cup was obtained， and the migration time required for the specific migration quantity test of the hot drink cup was obtained. Using real food to reproduce the actual use of the hot drink cup in a simulated consumption environment， and using an automatic temperature recorder to record the temperature changes during the test， the migration temperature required for the specific migration test of the hot drink cup was obtained.ResultsAccording to the survey results of consumers’ consumption habits in a restaurant， most consumers， in the process of eating in the restaurant， had an actual contact time with a hot drink cup of 1 h. According to the temperature measurement results during the actual use of the hot drink cup， its average temperature in different conditions within 1 h was 60 ℃-66 ℃.ConclusionAccording to a questionnaire and measured temperatures， it is recommended that a specific migration test condition of 70 ℃ for 1 h is selected. This study on specified migration conditions， including duration and temperature， was conducted through investigation and measurements and can be used as a reference to relevant testing institutions and laboratories when testing dine-in hot drink cups.

Rock burst is one of the disasters that seriously affect the safe and effective mining of coal in mine mining. It is of great significance and value to study the principle and technology of bolt anti-impact support to prevent and control the rock burst disaster in roadway. Through the summary and analysis of the geological conditions and failure characteristics of the rock burst of the whole coal body in the roadway, it is considered that the hard roof and hard coal seam are the important geological characteristics of this type of rock burst, and the overall slippage of the coal body in the roadway is the main impact failure characteristics. On this basis, taking the sliding coal body of roadway side as the research object, the mechanical model of roof-roadway-floor composite structure is established, and the limit equilibrium equation of horizontal sliding of roadway side coal body is established, and each parameter is analyzed. The results show that due to the rebound of the roof, the vertical pressure of the roadway side coal body is reduced, and the roadway side coal body is pushed into the roadway by the tectonic stress to cause rock burst. Based on the occurrence mechanism model, it is considered that the current bolt support design system has some shortcomings in preventing and controlling the rock burst of the coal body in the roadway. Based on its occurrence and failure characteristics, the design principle of bolt anti-impact support for the overall slippage type rock burst of the coal body in the roadway is established, that is, the anchoring ends of the roof and bottom bolts are respectively penetrated into the stable roof and floor, and the long anchor cable is used to replace the middle side bolt to provide the anti-impact effect of bolt support. Based on the newly established design method of bolt anti-scour support, taking the anti-scour support of 7305 working face of Kongzhuang Coal Mine in Datun Mining Area as the engineering background, the anti-scour design is adopted in the bolt support of roadway side in the wide coal pillar section. The roof and bottom bolts and reinforcing anchor cables are anchored inside the roof and floor, which can effectively absorb the sliding kinetic energy of the coal body and improve the safety.

Objective To investigate the impact of daidzein (DAI) on the pyroptosis of renal tubular epithelial cells induced by high glucose by regulating NOD-like receptor protein 3 (NLRP3)/caspase-1 signal pathway. Methods HK-2 cells were divided into control group (NC group) (5.5 mmol/L D-glucose), HG group(30 mmol/L D-glucose), DAI-L, DAI-M, DAI-H groups (HK-2 cells were incubated with 30 mmol/L D-glucose and 25, 50, 100 μmol/L DAI,respectively), and DAI-H+LPS group (HK-2 cells were incubated with 30 mmol/L D-glucose, 100 μmol/L DAI and 1 μg/mL LPS). MTT assay was applied to detect the cytotoxicity and proliferation of HK-2 cells; the apoptosis of HK-2 cells was detected by flow cytometry. The level of interleukin-1β (IL-1β) and inter-leukin-18 (IL-18) in HK-2 cells was detected by ELISA. The morphology of pyroptosis cells was observed by scanning electron microscope. Immunofluorescence staining was applied to detect pyroptosis related proteins. The expression of NLRP3, cleaved casase-1 and GSDMD-N was detected by Western blot. Results In NC group, the cells were spherical with regular boundaries, while in HG group, the cells swelled and became larger with irregular boundaries; the OD value (490 nm) of HK-2 cells in HG group was obviously lower than that in NC group(P＜0.05), the apoptosis rate, IL-1β, IL-18 contents, NLRP3, cleaved casase-1, GSDMD-N protein level of HK-2 cells were obviously higher (P＜0.05); After DAI treatment, the swelling of cells was alleviated, the A value (490 nm) of HK-2 cells increased significantly (P＜0.05), the apoptosis rate of HK-2 cells, IL-1 β, IL-18 content, NLRP3, cleaved-caspase-1 and GSDMD-N protein levels were significantly decreased(P＜0.05) and the therapeutic effect of DAI was dose-dependent; LPS eliminated the beneficial effect of DAI-H on high glucose induced apoptosis of renal tubular epithelial cells. Conclusions DAI may alleviate pyroptosis of renal tubular epithelial cells induced by high glucose through inhibition of NLRP3/caspase-1 signaling pathway.

The association of thyroid hormone antibodies and glycolipid metabolism indicators with Type 2 diabetes mellitus (T2DM) was explored. As the disease worsens, the levels of thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), and thyroid-stimulating hormone (TSH) was increased, and the levels of total tri-iodothyronine (TT3) and total thyroxine (TT4) was decreased (P < 0.001). The severe, medium, and light group had higher level of high-density lipoprotein (HDL), lower level of total cholesterol (TC), low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1c), triacylglycerol (TAG), and fasting blood sugar (FBG) than the control group (P ＜ 0.05). The level of HDL was lower in the severe group than the light group and the medium group, but the levels of TC, LDL, HbA1c, TAG, and FBG were increased with the progress of T2DM (P ＜ 0.001). The levels of TGAb, TPOAb, and TSH in patients with T2DM were positively correlated with the levels of TC, LDL, HbA1c, TAG, and FBG (P < 0.05), and were negatively correlated with HDL levels (P < 0.05). The life quality score was lower in the severe group than the light and the medium group (P < 0.001). Among the above indicators, the predictive value of TT3, TT4, and HbA1c in T2DM was better. Clinically, detecting the levels of thyroid hormone antibodies and glycolipid metabolism indicators had a certain predictive value for the severity of T2DM.

Optimizing the ecological network structure and enhancing habitat connectivity are key to ensuring urban ecological security, and the combination of urban big data can more accurately reveal the stress effects of the spatial heterogeneity of human activities on ecological connectivity. In recent years, numerous studies have focused on urban ecological networks; however, they have been limited by the accuracy of correction resistance data and the lack of source corridor identification methods, which makes it challenging to establish ecological networks with attributes. Thus, small- and medium-sized urban ecological network construction and connectivity stress analysis are lacking. In this study, a comprehensive resistance surface was constructed based on Point of Interest(POI) data and land use data; an ecological network with quantitative attributes was constructed using the InVEST habitat quality analysis and circuit theory, and the stress factors and disturbance intensity affecting the corridor connectivity of the network were clarified. Three main conclusions were drawn from the above analysis. First, the overall habitat quality of Nansha New District is good, and the centrality of ecological source areas ranges from 26.8 to 69.26. This centrality is inversely correlated with the source area's weighted center of gravity distance and positively correlated with the source area. The connectivity of most ecological corridors is between 17.56 and 92.56 and is inversely proportional to the corridors' length and resistance. Second, the ecological network of Nansha New District consists of 18 high habitat quality sources, 40 optimal ecological corridors, and 125.70 km² of potential corridors, spatially showing an introverted spatial pattern of "dense in the middle and sparse in the north and south." The corridors in the middle are more densely distributed and shorter in length and have higher connectivity and a concentrated distribution of sources. The north and south ends are scattered with low-level sources and the formation of more long-distance corridors with low connectivity. Finally, the main threatening factors of corridor connectivity in Nansha New District are four types of POI facilities, namely, companies, transportation facilities, shopping consumption, and life services. The numbers of corridors mainly coerced by companies, transportation facilities, life services, and shopping consumption POI are 23, 10, 5, and 2, respectively. Reducing and controlling the number of the above four types of POIs in the latent corridors will effectively enhance the connectivity of ecological networks and alleviate the isolation of source areas, reducing the trend of source islanding and habitat fragmentation. The research results can provide a concrete entry point for the maintenance of an excellent ecological background in Nansha New District in terms of spatial scope and facility renovation, which is of practical significance for the construction of a high-quality urban development benchmark.

Abstract Based on the disaster characteristics and the geo-conditions at the scene, in this study, the occurrence mechanism of a serious rock burst accident that occurred in the Tangshan Coal Mine, China, was analysed. Ground stress measurements showed that the mine is in a high ground stress area dominated by horizontal tectonic stress around 33 MPa. Laboratory testing revealed that the coal was a hard seam of 8.3 MPa over bedded by a thick and hard roof stratum with uniaxial compressive strength of 66 MPa. The calculation results indicated that the accident occurred in the roof rebounding area. It is proposed that the hard roof and the hard coal seam formed a seesaw structure around the working face. The vertical pressure relief caused the rib coal mass to lose its clamping forces from the roof and floor and rush into the roadway, resulting in a rock burst accident. Based on the causality mechanism of the rock burst disaster developed in this study, pertinent coal bump prevention measures have been undertaken in practice. Large-diameter boreholes were drilled to eliminate the pivot effect of the seam. Roof blasting was undertaken to prevent the roof from forming a seesaw plank. To summarize, a new causality mechanism for rock burst in coal mines under hard roof and hard seam geo-conditions was developed.

Land subsidence caused by human engineering activities is a serious problem worldwide. We selected Qian’an County as the study area to explore the evolution of land subsidence and predict its deformation trend. This study utilized synthetic aperture radar interferometry (InSAR) technology to process 64 Sentinel-1 data covering the area, and high-precision and high-resolution surface deformation data from January 2017 to December 2021 were obtained to analyze the deformation characteristics and evolution of land subsidence. Then, land subsidence was predicted using the intelligence neural network theory, machine learning methods, time-series prediction models, dynamic data processing techniques, and engineering geology of ground subsidence. This study developed three time-series prediction models: a support vector regression (SVR), a Holt Exponential Smoothing (Holt) model, and multi-layer perceptron (MLP) models. A time-series prediction analysis was conducted using the surface deformation data of the subsidence funnel area of Zhouzi Village, Qian’an County. In addition, the advantages and disadvantages of the three models were compared and analyzed. The results show that the three developed time-series data prediction models can effectively capture the time-series-related characteristics of surface deformation in the study area. The SVR and Holt models are suitable for analyzing fewer external interference factors and shorter periods, while the MLP model has high accuracy and universality, making it suitable for predicting both short-term and long-term surface deformation. Ultimately, our results are valuable for further research on land subsidence prediction.

To accurately estimate the 6D pose of objects, most methods employ a two-stage algorithm. While such two-stage algorithms achieve high accuracy, they are often slow. Additionally, many approaches utilize encoding–decoding to obtain the 6D pose, with many employing bilinear sampling for decoding. However, bilinear sampling tends to sacrifice the accuracy of precise features. In our research, we propose a novel solution that utilizes implicit representation as a bridge between discrete feature maps and continuous feature maps. We represent the feature map as a coordinate field, where each coordinate pair corresponds to a feature value. These feature values are then used to estimate feature maps of arbitrary scales, replacing upsampling for decoding. We apply the proposed implicit module to a bidirectional fusion feature pyramid network. Based on this implicit module, we propose three network branches: a class estimation branch, a bounding box estimation branch, and the final pose estimation branch. For this pose estimation branch, we propose a miniature dual-stream network, which estimates object surface features and complements the relationship between 2D and 3D. We represent the rotation component using the SVD (Singular Value Decomposition) representation method, resulting in a more accurate object pose. We achieved satisfactory experimental results on the widely used 6D pose estimation benchmark dataset Linemod. This innovative approach provides a more convenient solution for 6D object pose estimation.

Development of environment-friendly and efficient aquaculture effluent treatment system is crucial for sustainable intensification of aquaculture, in the face of the rapidly increasing environmental pressure in the mariculture industry. In this study, mariculture wastewater was treated by the anoxic-anaerobic-oxic biochemical treatment system (A2O system) with traditional activated sludge replaced by nitrifying bacteria, denitrification bacteria and phosphorus accumulating bacteria absorbed on PBS carrier biofilms suitable for saline/brackish water. The results showed that biofilm-enhanced A2O system can effectively remove pollutants from aquaculture wastewater. The removal efficiencies of CODMn, NH4+-N, TN and TP in A2O system were approximately 86.3%-90.8%, 97.7%-99.5%, 94.6%-95.2% and 97.0%-98.1%. The results further showed that CODMn, NH4+-N, and TN were mainly removed in anaerobic tank and anoxic tank, while TP was mainly removed in the anoxic tank and oxic tank. The biofilm-enhanced A2O system by adding nitrifying bacteria and phosphorus accumulating bacteria biofilms using PBS as carriers instead of conventional activated sludge could be applied to the treatment of circulating aquaculture wastewater. This study provides a feasible scheme for enhancing the efficiency of A2O system in the treatment of aquaculture tail water, and provides a reference for the immobilization of microorganisms.

Corneal neovascularization (CoNV)is a major cause of blindness in many ocular diseases. Substantial evidence indicates that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of corneal neovascularization. Previous evidence showed that artemisinin may inhibit angiogenesis through down regulation of the VEGF receptors. We designed and synthesized artemisinin derivatives, and validated their inhibitory effect on neovascularization in cell and animal models, and explored the mechanisms by which they exert an inhibitory effect on CoNV. Among these derivatives, P31 demonstrated significant anti-angiogenic effects in vivo and in vitro. Besides, P31 inhibited VEGF-induced HUVECs angiogenesis and neovascularization in rabbit model via AKT and ERK pathways. Moreover, P31 alleviated angiogenic and inflammatory responses in suture rabbit cornea. In conclusion, as a novel artemisinin derivative, P31 attenuates corneal neovascularization and has a promising application in ocular diseases.

IntroductionFood quality is closely related to food safety. Improving food quality, especially staple foods quality, is crucial to ensuring sustainable food safety. China's government is making efforts to improve the quality of staple foods and has improved quality standards of purchase policy for staple food. However, the actual effects of the new quality standards of purchase policy in implementation have not been verified.MethodsBased on this background, applying difference-in-differences models, this paper examines whether the new quality standards of purchase policy can improve the quality of staple food supply based on the wheat market transaction data.Results and discussionThe results show that the new quality standard of purchase policy has a significant positive impact on the quality of staple food supply. The conclusion remains robust through several alternative tests. Further research shows that the new quality standards of purchase policy significantly expand the degree of quality premiums in the market, thereby improving the staple food supply quality. Our research provides an insight for policy or standard makers to change relevant purchase quality limits following consumer demand to ensure sustainable food security.

Objective: To investigate the molecular mechanism underlying the protective effect of Solanum tuberosum anthocyanin (STA) on radiation-induced hematopoietic stem/progenitor cell senescence. Methods: C57BL/6 mice were randomly divided into three groups: control, model, STA treatment and STA prevention, and the cell senescence model was constructed by X-ray irradiation. The hemogram of mice in each group were examined using a hematology analyzer after drug administration. Stem cell antigen 1 positive hematopoietic stem/progenitor cells (Sca-1+HSC/HPCs) were isolated and purified from each group by immunomagnetic cell sorting and were stained using a senescence-associated β-galactosidase (SA-β-Gal) kit to calculate the proportion of SA-β-Gal positive cells. The number of mixed lineage colony forming unit (CFU-Mix) was used to evaluate the colony-forming capacity and differentiation potential of hematopoietic stem/progenitor cells. Cell cycle was analyzed by flow cytometry. The mRNA and protein expression of p53 and p21Waf1/Cip1 were detected by quantitative real-time polymerase chain reaction (qPCR) and Western blot. Results: The numbers of red blood cells (RBCs), white blood cells (WBCs) and platelets in the peripheral blood were significantly lower in the model group than in the control group (P < 0.01). In addition, compared with the control group, the proportion of SA-β-Gal positive cells significantly increased (P < 0.01), the number of CFU-Mix significantly fell (P < 0.01), the proportion of G0/G1 phase cells significantly increased, the proportions of G2/M and S phase cells significantly dropped (P < 0.01), and the relative mRNA and protein expression levels of p53 and p21Waf1/Cip1 significantly increased in the model group (P < 0.01). STA could significantly restore the above parameters of mice in the model group irrespective of whether it was administered before or after X-ray radiation, with more pronounced effect being observed in the former case. Conclusion: STA can protect hematopoietic stem/progenitor cells against radiation by regulating the p53-p21Waf1/Cip1 pathway.

CH4 has become the most attractive fuel for solid oxide fuel cells due to its wide availability, narrow explosion limit range, low price, and easy storage. Thus, we present the concept of on-cell reforming via SOFC power generation, in which CH4 and CO2 can be converted into H2 and the formed H2 is electrochemically oxidized on a Ni-BZCYYb anode. We modified the porosity and specific surface area of a perovskite reforming catalyst via an optimized electrostatic spinning method, and the prepared LCMN nanofibers, which displayed an ideal LaMnO3-type perovskite structure with a high specific surface area, were imposed on a conventional Ni-BZCYYb anode for on-cell CH4 reforming. Compared to LCMN nanoparticles used as on-cell reforming catalysts, the NF-SOFC showed lower ohmic and polarization resistances, indicating that the porous nanofibers could reduce the resistances of fuel gas transport and charge transport in the anode. Accordingly, the NF-SOFC displayed a maximum power density (MPD) of 781 mW cm−2 and a stable discharge voltage of around 0.62 V for 72 h without coking in the Ni-BZCYYb anode. The present LCMN NF materials and on-cell reforming system demonstrated stability and potential for highly efficient power generation with hydrocarbon fuels.

The backfill mining method is widely used in mines because of its advantages of environmental protection, safety, and efficiency and includes filling slurry pipeline transportation as an important part. The rheological parameters of filling slurry are important indicators for evaluating the characteristics of filling slurry pipeline transport; these parameters are mainly determined by rheometers at present, while the rheological experimental conditions are usually unavailable at the mine site. Because of its simplicity and speed, mines mainly use a slump test to evaluate the flow properties of a filling slurry. In this paper, we used a mini-slump cone to conduct a slump experiment of filling slurry with different mass fractions and cement–tailings ratios (the two most common variable parameters in filling slurry ratios), established an analytical model between the spread of a mini-slump cone and yield stress, obtained a simplified calculation model according to the shape of the filling slurry after flowing, calculated the yield stress of the slurry based on the simplified model, and compared the theoretical value with the experimental value of the yield stress of the filling slurry under the condition of the same ratio tested by a rheometer. At the same time, the influence law of different mass fractions and cement–sand ratios on the expansion degree of the filling slurry was studied using a two-factor analysis of variance. The results show that the spread is mainly influenced by the mass fraction and unsubstantially affected by the cement–sand ratio. The yield stress of the filling slurry increases with the mass fraction. When the mass fraction is low, the error in the theoretical value relative to the experimental value has a large range, and the error in the theoretical value is within 25%, averaging 16.79%; as the mass fraction increases, this error gradually decreases below 15%, averaging 8.81%. Considering its effect, a correction factor based on the mass fraction was proposed, and the error in the theoretical yield stress value after the correction was reduced below 10%, averaging 3.54%. In this study, the mini-slump cone test not only reduces the experimental material and labor intensity compared with the traditional slump test but also effectively characterizes the yield stress of the slurry, which provides practical guidance for evaluating the flowability of mine filling slurry.

[Purpose/Significance] In the era of big data, the volume of data is growing at an exponential rate. One of the most prominent areas affected by this growth is the field of agriculture. The use of agricultural knowledge graphs, which serve as key infrastructures for managing agricultural knowledge, has expanded significantly. However, as the number of nodes and relationships within these graphs increase, so too does their complexity. This complexity gives rise to new challenges in training and representing such large-scale knowledge graphs. It is therefore of great significance to investigate methods for speeding up the embedding process of agricultural knowledge graphs, while preserving their structural integrity and minimizing resource consumption. This research embarks on a novel exploration to address this issue. It stands out from previous studies by concentrating on a hierarchical representation model for agricultural knowledge graphs. The potential impacts of this research on propelling the advancement of the field and on addressing significant real-world problems are substantial. [Method/Process] To confront this challenge, we propose a hierarchical representation model for agricultural knowledge graphs rooted in the HARP framework. Our model leverages the inherent hierarchical features of the agricultural knowledge graph. It incorporates an improved random walk strategy based on relational paths to semantically model relationship objects within the agricultural knowledge graph. This innovative approach effectively retains the hierarchy and asymmetrical relationship structure of the nodes in the graph, setting our work apart from previous research. The validity of our proposed model is fortified by a strong foundation of theoretical and empirical evidence. [Results/Conclusions] Our experimental results reveal several key findings. First, the hierarchical random walk with path (HRWP) model using the LEIDEN algorithm can preserve the spatial structure more effectively and converge more quickly to the maximum modularity, in comparison to the HARP framework. Second, the fusion model employing HRWP takes less training time than the total training time of both models combined, without significantly affecting the time complexity of the original algorithm. Third, we observed that when traditional algorithms are integrated with HRWP, there is an average improvement of 2% across various indicators, with a substantial enhancement in non-neural network models. Therefore, our proposed model not only accurately represents the agricultural knowledge graph but also effectively reduces the training time. Despite the promising outcomes of our study, there remain areas of potential improvement. One such area is the need for a more detailed discussion on the hierarchical nature of relationship objects in future research. This provides potential avenues for future exploration in this field. The findings of this research carry profound implications for the development of agricultural knowledge management systems, offering an effective approach to handle the burgeoning complexity of knowledge graphs.

In underground coal mines, fibre reinforced polymer (FRP) bolt is ideal for mined rib reinforcements as it can prevent gas explosions caused by shearer frictional spark. With increasing mining depth, small diameter FRP bolts used in shallow underground mining cannot fulfil the rib support requirements. Under the engineering background of deep underground shortwall mining in Wudong coal mine, this paper systematically studies Φ27 mm FRP bolt support for large deformation coal rib. Specimens with a fan-shaped cross-section were used to enable the tensile testing of the bolt rod, the measured average tensile strength of the studied FRP bolt was (486.1 ± 9.6) MPa with a maximum elongation of 5.7%±0.6%. The shear strength of the bolt was measured as approximately 258 MPa using a self-made double shear testing apparatus. Based on the equivalent radial stiffness principle, a laboratory short encapsulation pullout test (SEPT) method for rib bolting has been developed undertaken consideration of the mechanical properties of the coal seam. Results showed that the average peak anchorage forces of the Φ27 mm FRP bolt and Φ20 mm steel rebar bolt were 108.4 and 66.4 kN, respectively, which were agreed with the theoretical calculations and field measurements. Based on theoretical analysis of the loading states of the bolt under site conditions, bolting method of full-length resin grouting was adopted to offset the weaknesses of the FRP bolt. Numerical method was employed to compare the bolting effect using Φ27 mm FRP bolts and steel rebar bolts. Large diameter FRP bolting was determined as the optimum rib support scheme to increase the productivity of the coal mine and to enhance the ground control capability for +425 level mining roadways. This study provides the laboratory testing design and theoretical prediction of large diameter FRP bolts used for rib support in large deformation roadways.

Abstract Background Human papillomavirus (HPV) has been proposed as a potential pathogenetic organism involved in prostate cancer (PCa), but the association between HPV infection and relevant genomic changes in PCa is poorly understood. Methods To evaluate the relationship between HPV genotypes and genomic alterations in PCa, HPV capture sequencing of DNA isolated from 59 Han Chinese PCa patients was performed using an Illumina HiSeq2500. Additionally, whole-exome sequencing of DNA from these 59 PCa tissue samples and matched normal tissues was carried out using the BGI DNBSEQ platform. HPV infection status and genotyping were determined, and the genetic disparities between HPV-positive and HPV-negative PCa were evaluated. Results The presence of the high-risk HPV genome was identified in 16.9% of our cohort, and HPV16 was the most frequent genotype detected. The overall mutational burden in HPV-positive and HPV-negative PCa was similar, with an average of 2.68/Mb versus 2.58/Mb, respectively, in the targeted whole-exome region. HPV-negative tumors showed a mutational spectrum concordant with published PCa analyses with enrichment for mutations in SPOP, FOXA1, and MED12. HPV-positive tumors showed more mutations in KMT2C, KMT2D and ERCC2. Copy number alterations per sample were comparable between the two groups. However, the significantly amplified or deleted regions of the two groups only partially overlapped. We identified amplifications in oncogenes, including FCGR2B and CCND1, and deletions of tumor suppressors, such as CCNC and RB1, only in HPV-negative tumors. HPV-positive tumors showed unique deletions of tumor suppressors such as NTRK1 and JAK1. Conclusions The genomic mutational landscape of PCa differs based on HPV infection status. This work adds evidence for the direct involvement of HPV in PCa etiology. Different genomic features render HPV-positive PCa a unique subpopulation that might benefit from virus-targeted therapy.

Abstract Background Cisplatin is commonly used to treat cervical cancer while drug resistance limits its effectiveness. There is an urgent need to identify strategies that increase cisplatin sensitivity and improve the outcomes of chemotherapy. Results We performed whole exome sequencing (WES) of 156 cervical cancer tissues to assess genomic features related to platinum-based chemoresistance. By using WES, we identified a frequently mutated locus SETD8 (7%), which was associated with drug sensitivity. Cell functional assays, in vivo xenografts tumor growth experiments, and survival analysis were used to investigate the functional significance and mechanism of chemosensitization after SETD8 downregulation. Knockdown of SETD8 increased the responsiveness of cervical cancer cells to cisplatin treatment. The mechanism is exerted by reduced binding of 53BP1 to DNA breaks and inhibition of the non-homologous end joining (NHEJ) repair pathway. In addition, SETD8 expression was positively correlated with resistance to cisplatin and negatively associated with the prognosis of cervical cancer patients. Further, UNC0379 as a small molecule inhibitor of SETD8 was found to enhance cisplatin sensitivity both in vitro and in vivo. Conclusions SETD8 was a promising therapeutic target to ameliorate cisplatin resistance and improve the efficacy of chemotherapy.

High primary rock stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different rock breaking states under different primary rock stress conditions. There are a large number of naturally formed joints in rock mass, due to the limitations of laboratory tests, a numerical model of jointed rock mass was established using LS-DYNA software to investigate the evolution of blasting damage under various in-situ stresses and open joints. In this simulation, using the Lagrange-Euler (ALE) procedure and the equation of state (JWL) that defines explosive materials, the study considered different joint thicknesses (2cm, 4cm, and 6cm), joint angles (0°, 30°, 60°, and 90°), and in-situ stress conditions (lateral stress coefficients of 0.5, 1, and 2, with vertical in-situ stresses of 10MPa and 20MPa), through stress analysis and damage area comparison, the relationship between damage crack propagation and horizontal and vertical stress difference is explored. The research aimed to understand the mechanisms underlying crack initiation and propagation. The results show that: (1) The presence of joints exerts a barrier effect on the expansion and penetration of cracks. When explosion stress waves reach the joint surface, their propagation is impeded, leading to the diffusion of wing cracks at the joint ends. When the lateral stress coefficient and joint angle are the same, an increase in initial in-situ stress results in a reduction in the area of the blasting damage zone. (2) Under the same initial in-situ stress conditions, the area of the blasting damage zone initially increases and then decreases with an increasing joint angle. However, it remains larger than that without a joint, and there exists an optimal angle that maximizes the damage area. In the simulated conditions, the area of damage cracks is greatest when the joint angle is 60° dip angle. (3) The presence of initial in-situ stress has a certain impact on the initiation and expansion of blasting cracks. The degree and nature of this influence are not solely related to the lateral stress coefficient but also depend on the joint's angle and thickness. When in-situ stress is present, the initial in-situ stress field's pressure is not conducive to the initiation and propagation of blasting cracks. However, the existence of a joint has a noticeable guiding and promoting effect on crack propagation, and the pattern of crack propagation is influenced by both joint and in-situ stress conditions.

Mesenchymal stem cells (MSCs) have recently been identified as having potentially therapeutic immunomodulatory properties. MSCs isolated from different oral tissues have similar morphology and immunophenotypes, however, direct comparisons of their gene expression and immunomodulatory properties have not been conducted. We isolated alveolar bone-derived MSCs (aBMSCs), dental pulp stem cells (DPSCs) and gingiva-derived MSCs (GMSCs) from the same patients and compared their immunophenotypes and transcriptomes. Additionally, we compared their production of soluble immunomodulatory cytokines as well as their immunoregulatory properties in coculture with THP-1 human monocytic cells. RNA sequencing revealed distinct gene expression in DPSCs while aBMSCs and GMSCs had less differentially expressed genes. DPSCs also had significantly less secretion of osteopontin compared to aBMSCs and GMSCs. Finally, DPSCs did not exhibit an immunosuppresive effect on THP-1 cells to the same degree as aBMSCs and GMSCs. These findings demonstrate that MSCs from different oral tissues have distinct transcriptomes and immunoregulatory properties.

Linkage disequilibrium (LD) is a fundamental concept in genetics; critical for studying genetic associations and molecular evolution. However, LD measurements are only reliable for common genetic variants, leaving low-frequency variants unanalyzed. In this work, we introduce cumulative LD (cLD), a stable statistic that captures the rare-variant LD between genetic regions, which reflects more biological interactions between variants, in addition to lack of recombination. We derived the theoretical variance of cLD using delta methods to demonstrate its higher stability than LD for rare variants. This property is also verified by bootstrapped simulations using real data. In application, we find cLD reveals an increased genetic association between genes in 3D chromatin interactions, a phenomenon recently reported negatively by calculating standard LD between common variants. Additionally, we show that cLD is higher between gene pairs reported in interaction databases, identifies unreported protein-protein interactions, and reveals interacting genes distinguishing case/control samples in association studies.

Landslides in high-order position areas pose a serious threat to residents located below such areas. Therefore, research on the evolution process and underlying dynamic mechanisms is crucial. The majority of relevant studies are based on landslides that have already occurred; however, the investigation of potential landslides is of higher value. In this study, a progressive potential landslide identification method is proposed with the application of SBAS-InSAR (Small Baseline Subset Interferometric Synthetic Aperture Radar) and subsequently combined with Google Earth, GF-1 (Gaofen-1), GF-2 (Gaofen-2), ZY-3 (Ziyuan-3) and UAV (Unmanned Aerial Vehicle) imagery, and DEM (Digital Elevation Model) for further validation. The proposed method is employed to determine the potential landslide in Tuanjiecun by integrating the multi-period data to simultaneously analyze the evolution and mechanism of the potential landslide. The long short-term memory method is then adopted to predict the evolution trend based on accumulative deformation from SBAS-InSAR. The results suggest that the deformation of Tuanjiecun potential landslide will increase to −238.57 mm. This article provides a new approach for disaster prevention and mitigation by determining a potential landslide using composite remote sensing and predicting the development of the potential landslide on indirect contact monitoring.

Surface wave tomography is a widely used geophysical method to measuring seismic velocity and anisotropy in the crust and upper mantle. This paper briefly reviewed the history of surface wave tomography, and summarized the principles and advantages of multiple surface wave tomography methods (i.e., two-station method, two-plane-wave method, Eikonal and Helmholtz surface wave tomography, ambient noise tomography, and direct surface wave tomography). The theory and application of the two-station method are straightforward, but this method requires the earthquake and seismic stations to be located in the same great circle. This restriction results in a low lateral resolution phase velocity map for regions where stations are sparse and deployment times short. The two-plane-wave method can overcome the effect of scattering and multipathing of seismic wave propagation on phase velocity dispersions, but this method requires high-quality surface wave waveforms and is usually suitable for regional seismic networks. The Eikonal and Helmholtz surface wave tomography can directly compute the phase velocities and azimuthal anisotropy straightforwardly without any processes of forward modeling and inversion, but this method is limitedly suitable for high-density and orderly seismic arrays. In comparison to the Eikonal surface wave tomography method, the Helmholtz surface wave tomography approach analyzes both the phase and amplitude of the waveform and can produce better results. Ambient noise tomography can obtain high-resolution crustal structure without seismic events. However, this method is difficult to obtain long-period phase velocities, resulting in a lack of constraints on the mantle and lithosphere structure. Direct surface wave tomography can obtain the shear-wave velocity and azimuthal anisotropy from dispersive curves without the inversion process of phase velocity maps. We conducted detailed comparisons of the phase velocity maps at the short-intermediate periods (20～40 s) previously obtained from these surface wave tomography methods in the central-northern, northeastern and southern Tibetan Plateau. The comparisons demonstrated that the Rayleigh and Love wave phase velocity maps from different tomography methods show highly consistency in velocity variation patterns at same periods. The results show that the plateau's interior by characterized with low-velocities in phase velocity maps at intermediate and long periods, whereas relatively high velocities dominate adjacent regions, such as the Qaidam Basin and Sichuan Basin. These features indicate that the Tibetan Plateau's mid-lower crust and upper mantle tend to be weaker and easily deform during the northward movement of the Indian plateau and the barrier of the strong blocks (e.g., the Qaidam Basin and the Alashan Platform). The short periods phase velocity maps (i.e., 20～40 s) reveal that the mid-lower crustal flow of the Tibetan Plateau escapes southward surrounding the weakening zones (i.e., the Red River Fault and the Xianshui River Fault) due to the barrier of the strong Chuandian tectonic block. The Qilian Orogen also shows low velocities in the phase velocity maps at the short-intermediate periods, which is likely due to thermal anomaly with localized mantle upwelling. It is noteworthy that the Rayleigh-wave and Love-wave phase velocities at different period ranges (e.g., 4～200 s) can be obtained via incorporating earthquake surface wave tomography and ambient noise tomography. Those phase velocities can be used as input to inverting three-dimensional shear wave velocities and radial anisotropy models simultaneously. This paper envisions that integrating higher-mode earthquake surface wave tomography, adjoint tomography, and joint inversion could obtain higher resolution and more reliable crustal and upper mantle structures.

With advanced artificial intelligence and deep learning techniques, a growing number of data sources are playing more and more critical roles in planning and operating transportation services. The General Transit Feed Specification (GTFS), with standard open-source data in both static and real-time formats, is being widely used in public transport planning and operation management. However, compared to other extensively studied data sources such as smart card data and GPS trajectory data, the GTFS data lacks proper investigation yet. Utilization of the GTFS data is challenging for both transport planners and researchers due to its difficulty and complexity of understanding, processing, and leveraging the raw data. In this paper, a GTFS data acquisition and processing framework is proposed to offer an efficient and effective benchmark tool for converting and fusing the GTFS data to a ready-to-use format. To validate and test the proposed framework, a multivariate multistep Long Short-Term Memory is developed to predict train delay with minor anomaly in Sydney as a case study. The contribution of this new framework will render great potential for broader applications and deeper research.

High-precision temperature control of large-area blackbodies has a pivotal role in temperature calibration and thermal imaging correction. Meanwhile, it is necessary to correct the temperature difference between the radiating (surface of use) and back surfaces (where the temperature sensor is installed) of the blackbody during the testing phase. Moreover, large-area blackbodies are usually composed of multiple temperature control channels, and manual correction in this scenario is error-prone and inefficient. At present, there is no method that can achieve temperature-automated calibration for a large-area blackbody radiation source. Therefore, this article is dedicated to achieving temperature-automated calibration for a large-area blackbody radiation source. First, utilizing two calibrated infrared thermometers, the optimal temperature measurement location was determined using a focusing algorithm. Then, a three-axis movement system was used to obtain the true temperature at the same measurement location on a large-area blackbody surface from different channels. This temperature was subtracted from the blackbody’s back surface. The temperature difference was calculated employing a weighted algorithm to derive the parameters for calibration. Finally, regarding experimental verification, the consistency error of the temperature measurement point was reduced by 85.4%, the temperature uniformity of the surface source was improved by 40.4%, and the average temperature measurement deviation decreased by 43.8%. In addition, this system demonstrated the characteristics of strong environmental adaptability that was able to perform temperature calibration under the working conditions of a blackbody surface temperature from 100 K to 573 K, which decreased the calibration time by 9.82 times.

Purpose: The difficulty of recanalization for intracranial atherosclerosis–related large vessel occlusion (ICAS-LVO) is closely related to the severity of stenosis. This study sought to investigate the characteristics of enhancement based on high-resolution magnetic resonance imaging (HR-MRI) so as to judge the severity of stenosis. Methods: Sixty-two patients with symptomatic ICAS-LVOs who underwent endovascular treatment were prospectively recruited for HR-MRI (33 patients with severe stenosis and 29 without). The diagnostic agreements in locating occlusion segments were assessed between HR-MRI and angiographic assessment. The severity of atherosclerotic stenosis was evaluated by enhancement grade and quantitative enhancement index. Univariate and multivariate analyses were used to identify the parameters associated with the severity of stenosis. Results: HR-MRI showed good agreement with angiographic assessments for evaluating the occlusion site (κ ​= ​0.97) and length (concordance correlation coefficient ​= ​0.70). Compared with patients without severe stenosis, patients with severe stenosis exhibited higher enhancement index (0.69 versus 0.19; p ​

As the global pursuit of carbon neutrality has intensified, the influence of carbon emission limits on the supply chain has become increasingly evident. The purpose of this study is to investigate the optimal financing options of the supply chain under the carbon emission reduction percentage measure and to provide financing recommendations for carbon-emitting enterprises. This study focuses on a supply chain consisting of a capital-constrained manufacturer and a capital-rich retailer. Under the carbon emission reduction percentage measure, we use the Stackelberg game theory to determine the manufacturer’s and retailer’s optimal decisions for bank financing, zero-interest early payment financing, and in-house factoring financing. Finally, we find a U-shaped relationship between the price sensitivity of commodities and the retailer’s (manufacturer’s) optimal profit. The impact of the carbon emission reduction percentage on the supply chains’ financing decisions follows a quadratic pattern. Carbon emission trading prices exhibit a monotonic influence on the equilibrium financing options of the supply chain. When carbon emissions do not exceed the standards, internal financing becomes more favorable as the carbon emission trading price increases. Conversely, when carbon emissions exceed the standards, external financing becomes more prevalent as the carbon emission trading price increases. The findings assist supply chain managers in selecting the optimal financing method when confronted with carbon emission limitations. These conclusions contribute to the development of more targeted measures and the promotion of green supply chains.

Pervasive computing techniques provides application guidance and support for intelligent transportation systems. On the basis of connected autonomous vehicles, a extended model has been proposed. This paper focuses on studying the effects of the electronic throttle and driver’s memory. In order to show the influence of these two factors on the model, the extended model is studied by theoretical analysis and numerical methods. Stability conditions are obtained by adding perturbation to the linear analysis, the TDGL equation and mKdV equation are derived by nonlinear analysis, which shows that the phase change behavior of traffic jams can be described by both of them. The numerical simulation results show the correctness of the analysis results. Numerical results show that the effects of driver’s memory and electronic throttle play an key role in the stability of traffic flow, which is consistent with the theoretical analysis results.