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Chien-Hui Pan,1,2 Tzen-Yuh Chiang,2 Hui-Chi Hsieh,1 Ya-Huei Wang3,4 1Education Center, National Cheng Kung University Hospital, Tainan, Taiwan; 2Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan; 3Department of Applied Foreign Languages, Chung Shan Medical University, Taichung, Taiwan; 4Department of Medical Education, Chung Shan Medical University Hospital, Taichung, TaiwanCorrespondence: Ya-Huei Wang, Chung Shan Medical University, Department of Applied Foreign Languages, 110, Sec. 1, Jian-Koa N. Road, Taichung, 402, Taiwan, Tel +886-4-24730022 Ex 12003, Email yhuei@csmu.edu.twObjective: In Taiwanese clinical and healthcare environments, there is a dearth of appropriate and effective tools to evaluate clinical teachers’ occupational well-being. Therefore, this study aimed to develop a culturally adapted scale, a Taiwanese version of the Clinical Teachers’ Occupational Well-Being Dimensions Scale (CTOWDS), to accurately measure the occupational well-being of clinical teachers in Taiwan.Methods: Following a comprehensive literature review and expert panel discussions, the study developed the CTOWDS and conducted exploratory factor analysis (EFA) with 346 participants using SPSS to identify its underlying dimensional structure and psychometric properties. Confirmatory factor analysis (CFA) was then performed with 255 participants using AMOS to validate the EFA results. The study also assessed internal consistency, convergent and discriminant validities, and goodness-of-fit indexes to ensure that the scale was valid and reliable in the Taiwanese cultural setting.Results: The EFA refined the scale from 51 to 29 items across five dimensions: personal qualities (11 items), academic research and career development pressure (6 items), teaching experience (4 items), learning experience (4 items), and teaching and communication pressure (4 items). These five dimensions explained 65.279% of the total variance. The CFA confirmed the five dimensions and 29 items, with good convergent and discriminant validities, goodness-of-fit indexes, and Cronbach’s alpha values exceeding 0.70.Conclusion: The findings affirm the utility of the developed CTOWDS as a reliable and culturally relevant instrument for assessing the occupational well-being of clinical teachers.Keywords: occupational well-being, clinical teachers, scale development, psychometric validation

Yen-Hsun Huang,1 Hsien-Chih Chiou,1 Chun-Hung Pan,1,2 I-Shuan Wang,1 Ya-Tang Liao,3 Sheng-Siang Su,1 Chiao-Chicy Chen,4– 6 Chian-Jue Kuo1,4,5 1Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; 2Department of Psychology, National Chengchi University, Taipei, Taiwan; 3Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 4Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 6Department of Psychiatry, Mackay Memorial Hospital, Taipei, TaiwanCorrespondence: Chian-Jue Kuo, Department of General Psychiatry, Taipei City Psychiatric Center, 309 Sung-Te Road, Taipei, 110, Taiwan, Email tcpckuo@seed.net.twBackground: Patients with asthma experience more physical, psychological, and financial burdens; a link between asthma and suicidality has been reported in research.Purpose: This study analyzed the medical utilization and comorbidity before their self-injurious behavior in patients with asthma.Methods: We enrolled 186,862 patients newly diagnosed with asthma between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 500 case subjects had ever conducted self-injurious behaviors during the study period. Based on a nested case-control study, each case was matched with 10 controls derived from the asthma cohort to analyze differences between them and their medical use models.Results: The results indicated that, compared to the control group, the cases presented higher frequencies of outpatient visits and hospitalizations. Regarding comorbidity, the cases had more cardiovascular diseases (adjusted odds ratio [aOR]=1.58; p< 0.001), bipolar disorder (aOR=2.97; p< 0.001), depression (aOR=4.44; p< 0.001), and sleep disorder (aOR=1.83; p< 0.001) than the controls.Conclusion: The evidence-based information serves as a reference for medical staff to reduce the occurrence of self-injurious behavior in patients with asthma.Keywords: self-injurious behavior, asthma, medical utilization, psychiatric comorbidity, physical comorbidity

Chih-Hong Pan,1,2,* Kai-Jen Chuang,3,4,* Jen-Kun Chen,5 Ta-Chih Hsiao,6 Ching-Huang Lai,2 Tim P Jones,7 Kelly A BéruBé,8 Gui-Bing Hong,9 Kin-Fai Ho,10,11 Hsiao-Chi Chuang12,13 1Institute of Occupational Safety and Health, Council of Labor Affairs, Executive Yuan, 2School of Public Health, National Defense Medical Center, 3School of Public Health, College of Public Health and Nutrition, 4Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 5Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, 6Graduate Institute of Environmental Engineering, National Central University, Taoyuan, Taiwan; 7School of Earth and Ocean Sciences, 8School of Biosciences, Cardiff University, Cardiff, Wales, UK; 9Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan; 10Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 11Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 12School of Respiratory Therapy, College of Medicine, 13Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Abstract: Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP. Keywords: glycolysis, iTRAQ, metabolism, nanoparticles, S100-A9

Chih-Hong Pan,1,2,* Wen-Te Liu,3,4,* Mauo-Ying Bien,4,5 I-Chan Lin,6 Ta-Chih Hsiao,7 Chih-Ming Ma,8 Ching-Huang Lai,2 Mei-Chieh Chen,9 Kai-Jen Chuang,10,11 Hsiao-Chi Chuang3,4 On behalf of the Taiwan CardioPulmonary Research (T-CPR) Group 1Institute of Labor, Occupational Safety and Health, Ministry of Labor, 2School of Public Health, National Defense Medical Center, 3Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, 4School of Respiratory Therapy, College of Medicine, 5Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, 6Department of Ophthalmology, Shuang Ho Hospital, Taipei Medical University, Taipei, 7Graduate Institute of Environmental Engineering, National Central University, Taoyuan, 8Department of Cosmetic Application and Management, St Mary’s Junior College of Medicine, Nursing and Management, Sanxing, 9Department of Microbiology and Immunology, College of Medicine, 10Department of Public Health, School of Medicine, College of Medicine, 11School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Abstract: Although the health effects of zinc oxide nanoparticles (ZnONPs) on the ­respiratory system have been reported, the fate, potential toxicity, and mechanisms in biological cells of these particles, as related to particle size and surface characteristics, have not been well elucidated. To determine the physicochemical properties of ZnONPs that govern cytotoxicity, we investigated the effects of size, electronic properties, zinc concentration, and pH on cell viability using human alveolar-basal epithelial A549 cells as a model. We observed that a 2-hour or longer exposure to ZnONPs induced changes in cell viability. The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs. Proteomic profiling of A549 exposed to ZnONPs for 2 and 4 hours was used to determine the biological mechanisms of ZnONP toxicity. p53-pathway activation was the core mechanism regulating cell viability in response to particle size. Activation of the Wnt and TGFß signaling pathways was also important in the cellular response to ZnONPs of different sizes. The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences. These results suggested that the size and surface characteristics of ZnONPs might play an important role in their observed cytotoxicity. This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles. Keywords: aluminium-doped zinc oxide, nanoparticle, pH, toxicology, WNT pathway, zeta potential

INTRODUCTION: Hip fractures entail a growing economic burden on the health care system. Study is warranted to further our understanding of its patterns and to create increased awareness in health care providers and the public. MATERIALS AND METHODS: Data was extracted from the ongoing National Orthopaedic Registry of Malaysia (NORM), for the period June 2008 till December 2009. Patients aged 50 years and above without previous pathological fracture hip fractures were included in the study. RESULTS: Most hip fracture patients were 70 years and above (69.5%) with a mean (SD) age of 73.8 (10.3) years. Females represented the majority of the patients in this study (68.4%). Low energy trauma (i.e. trivial fall) was to the main mechanism of hip fractures in this study (81.3%). CONCLUSIONS: Aging adults should be made aware of timely preventive strategies (including osteoporosis prevention) fall prevention measures, and encouraged to maintain physically active lifestyles.

Abstract Nasopharyngeal carcinoma (NPC) is the most common cancer originating in nasopharynx. Metabolic reprogramming plays a critical role in tumor progression. Exploring mechanisms underlying metabolic reprogramming contributes to deeper understanding of NPC pathogenesis. Here, we found downregulation of RORA and SPLUNC1 in NPC, and RORA downregulation indicates poor prognosis. RORA binds to SPLUNC1 promoter to induce its transcription, and RORA overexpression inhibits cell proliferation and glycolysis by directly upregulating SPLUNC1. UBR5 inhibits RORA via promoting RORA ubiquitination and degradation, and UBR5 silencing represses proliferation and glycolysis in NPC. Additionally, METTL14, which is highly expressed in NPC, facilitates UBR5 mRNA stability by promoting its m6A modification through IGF2BP2. UBR5/RORA/SPLUNC1 axis facilitates M2 polarization by activating the GPR132 signaling. UBR5 silencing inhibits tumor growth, glycolysis and M2 polarization through RORA/SPLUNC1 signaling in mice. In conclusion, UBR5 promotes proliferation, glycolysis and M2 polarization by metabolically reprograming NPC cells through suppression of the RORA/SPLUNC1 signaling.

The maritime kill chain constitutes the core of the current joint maritime combat system, representing the practical application of the OODA loop in the context of informationized warfare. It embodies the operational mechanism of the joint combat system, where information flow dominates energy flow in a closed-loop operation. Determining the critical nodes of the maritime kill chain is the prerequisite for achieving comprehensive maritime dominance. Currently, the assessment of key nodes within maritime kill chains employs theoretical analysis and complex network methods. Complex network analysis techniques, which often utilize a node-by-node deletion approach to evaluate node importance, suffer from issues such as low search efficiency and limited applicability to small-scale systems. This paper takes the NIFC-CA system as an example to construct a typical maritime kill chain model. The importance of kill chain nodes is ranked using a complex network assessment method of integration centrality, and key nodes are identified. Additionally, graph theory and network analysis tools from Python’s Network library are utilized during the assessment to significantly enhance the computational efficiency.

Abstract Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8+ T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in vivo experiments demonstrate that circE7 suppresses the function and activity of T cells by downregulating the transcription of LGALS9, which encodes the galectin-9 protein. The molecular mechanism involves circE7 binding to acetyl-CoA carboxylase 1 (ACC1), promoting its dephosphorylation and thereby activating ACC1. Activated ACC1 reduces H3K27 acetylation at the LGALS9 gene promoter, leading to decreased galectin-9 expression. Notably, galectin-9 interacts with immune checkpoint molecules TIM-3 and PD-1, inhibiting the secretion of cytotoxic cytokines by T cells and promoting T cell apoptosis. Here, we demonstrate a mechanism by which HPV promotes immune evasion in HNSCC through a circE7-driven epigenetic modification and propose a potential immunotherapy strategy for HNSCC that involves the combined use of anti-PD-1 and anti-TIM-3 inhibitors.

Abstract Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs. Graphical abstract

Fundus tessellation, commonly observed in individuals with myopia and among the elderly, represents a fundus alteration easily discernible and assessable. Long-term monitoring has revealed that fundus tessellation may persist unchanged for extended periods or progress, potentially leading to more severe fundus lesions and diminished visual quality. The clinical significance of fundus tessellation is not only as an early indicator and predictor of myopic macular degeneration(MMD), but also, to some extend, as a helpful assistance in early identification and mechanism research of the other ocular and systemic disease, including glaucoma, diabetic retinopathy, age-related macular degeneration, cognitive impairment, and Down syndrome. Currently, artificial intelligence(AI)has achieved remarkable results in detecting, grading, and quantifying fundus tessellation. Therefore, this paper discusses the ocular and systemic diseases related to changes in fundus tessellation, their underlying mechanisms, and advancements in AI-based identification and quantification of fundus tessellation, aiming to contribute to future research endeavors.

Abstract Pyroptosis is a type of programmed cell death characterized by cell swelling and osmotic lysis, resulting in cytomembrane rupture and release of immunostimulatory components, which play a role in several pathological processes. Significant cellular responses to various stimuli involve the formation of inflammasomes, maturation of inflammatory caspases, and caspase-mediated cleavage of gasdermin. The function of pyroptosis in disease is complex but not a simple angelic or demonic role. While inflammatory diseases such as sepsis are associated with uncontrollable pyroptosis, the potent immune response induced by pyroptosis can be exploited as a therapeutic target for anti-tumor therapy. Thus, a comprehensive review of the role of pyroptosis in disease is crucial for further research and clinical translation from bench to bedside. In this review, we summarize the recent advancements in understanding the role of pyroptosis in disease, covering the related development history, molecular mechanisms including canonical, non-canonical, caspase 3/8, and granzyme-mediated pathways, and its regulatory function in health and multiple diseases. Moreover, this review also provides updates on promising therapeutic strategies by applying novel small molecule inhibitors and traditional medicines to regulate pyroptosis. The present dilemmas and future directions in the landscape of pyroptosis are also discussed from a clinical perspective, providing clues for scientists to develop novel drugs targeting pyroptosis.

Abstract Tumor cells possess complex immune evasion mechanisms to evade immune system attacks, primarily through metabolic reprogramming, which significantly alters the tumor microenvironment (TME) to modulate immune cell functions. When a tumor is sufficiently immunogenic, it can activate cytotoxic T-cells to target and destroy it. However, tumors adapt by manipulating their metabolic pathways, particularly glucose, amino acid, and lipid metabolism, to create an immunosuppressive TME that promotes immune escape. These metabolic alterations impact the function and differentiation of non-tumor cells within the TME, such as inhibiting effector T-cell activity while expanding regulatory T-cells and myeloid-derived suppressor cells. Additionally, these changes lead to an imbalance in cytokine and chemokine secretion, further enhancing the immunosuppressive landscape. Emerging research is increasingly focusing on the regulatory roles of non-tumor cells within the TME, evaluating how their reprogrammed glucose, amino acid, and lipid metabolism influence their functional changes and ultimately aid in tumor immune evasion. Despite our incomplete understanding of the intricate metabolic interactions between tumor and non-tumor cells, the connection between these elements presents significant challenges for cancer immunotherapy. This review highlights the impact of altered glucose, amino acid, and lipid metabolism in the TME on the metabolism and function of non-tumor cells, providing new insights that could facilitate the development of novel cancer immunotherapies.

Abstract Clinical trials and studies have implicated that E3 ubiquitin ligase BTBD3 (BTB Domain Containing 3) is a cancer-associated gene. However, the role and underlying mechanism of BTBD3 in colorectal cancer (CRC) is not fully understood yet. Herein, our study demonstrated that the mRNA and protein levels of BTBD3 were decreased in CRC tissues and associated with TYPO3 and Wnt/β-catenin pathway. Our results showed that circRAE1 knockdown and TYRO3 overexpression activated Wnt/β-catenin signaling pathway and the EMT process-associated markers, indicating that circRAE1/miR-388-3p/TYRO3 axis exacerbated tumorigenesis of CRC by activating Wnt/β-catenin signaling pathway. In addition, overexpression of BTBD3 reduced CRC cell migration and invasion in vitro and inhibited tumor growth in vivo. Our data demonstrated that BTBD3 suppressed CRC progression through negative regulation of the circRAE1/miR-388-3p/TYRO3 axis and the Wnt/β-catenin pathway. Our data further confirmed that BTBD3 bound and ubiquitinated β-catenin and led to β-catenin degradation, therefore blocked the Wnt/β-catenin pathway and suppressed the CRC tumorigenesis. This study explored the mechanism of BTBD3 involved in CRC tumorigenesis and provided a new theoretical basis for the prevention and treatment of CRC.

The abradable sealing Al2024/hBN composites were produced by hot-pressing sintering. The influence of ball milling time on the microstructure and mechanical properties was investigated. The results show that, the Al2024/hBN composites sintered by hot-pressing sintering have a relatively higher density and hardness, up to 2.52 g/cm3 and HR15Y 90, respectively. With the extension of ball milling time, the microstructure of the composites significantly changes from the spherical particle to the lamellar structure, the friction coefficient and volume wear rate reduce, reaching the minimum of 0.32 and 2.3×10−3mm3·m−1·N−1, respectively. The maximum bending force increases with the ball milling time, from 1.2 kN to 2.3 kN in the three-point bending test at room temperature.

Objectives: When the traditional abrasive flow machining (AFM) technology is used to process workpieces with complex shapes and inner walls of the tunnels, the machining quality of the workpiece surface tends to be uneven in each directions. To address this, the vibration assistance is added to traditional abrasive flow machining, forming a wavy machining track on the workpiece surface. This technique generates interwoven scratch textures, reduces the roughness value of the workpiece surface in all directions, and improves the surface quality and material removal efficiency converging the surface roughness. Methods: By rotating a cam to drive a connecting rod, vibration is induced in a round tube, altering the flow field distribution characteristics of the fluid abrasive and the mode of abrasive phase movement. This enables a new relative movement between the fluid abrasive and the workpiece surface. The principle of vibration-assisted machining and the scratching effect of abrasive particles on the workpiece surface were analyzed. At the same time, different frequencies and amplitudes were achieved by varying the motor speed and adjusting the long and short half-axes of the elliptical cam. A test platform for vibration-assisted abrasive flow machining was built to study the effects of abrasive flow rate, amplitude, and frequency on workpiece surface roughness and topography. Results: (1) After 2, 4, and 6 processing cycles without vibration, the surface roughness of the Cu-1 workpiece was reduced to 0.187, 0.123, and 0.112 μm, respectively. After 2, 4 and 6 processing cycles with vibration, the surface roughness of the Cu-4 workpiece decreased from an initial 0.230 μm to 0.139, 0.114, and 0.106 μm, respectively. The surface roughness of the workpiece polished with vibration was lower than that without vibration. At the same time, under non-vibration conditions, the transverse fringes of the original surface of Cu-1 after machining remained visible, although its surface roughness were significantly reduced. When Cu-4 was processed for 6 times under vibration condition, the transverse stripes on the original Cu-4 surface were almost completely removed, and some fine circular scratches appeared, resulting in a relatively ideal machining surface. (2) The cam speed directly corresponded to vibration frequency, higher cam speeds resulted in higher frequencies. When the Cu-2 workpiece was machined at a cam speed of 150 r/min, its surface roughness decreased slowly and steadily. At the cam speed of 225 r/min, the Cu-3 workpiece was experienced a longer micro-cutting length between abrasive particles and the workpiece, resulting in lower surface roughness compared to those of Cu-2. When Cu-4, polished at a higher cam speed, these appeared a significant reduction in surface roughness, decreasing to 0.166, 0.130. and 0.106 μm in the order of Cu-2 > Cu-3 > Cu-4. Higher cam speeds produced more scratches on the workpiece surface under the same flow rate, leading to longer arc scratches and smaller curvature radii. (3) When Cu-3, Cu-7 and Cu-8 workpieces were processed for the same times with three different cam sizes, the surface roughness of Cu-3 slowly reduced to 0.130 μm with L76 cam. The Cu-7 was machined with L47 cam at lower amplitude and relatively stable vibration, had lower surface roughness of 0.111 μm, which was lower than that of Cu-3. The Cu-8 was machined with L102 cam, the connecting rod swings greatly, the vibration was extremely unstable, and the surface roughness of the workpiece changed little. The L76 cam had the larger and more intense amplitude on Cu-3, and the curvature radius of the scratch formed by the machining was larger, and the direction angle of the scratches formed by the abrasive particles on the Cu-3 surface was closer to the original direction angle of scratches of the workpiece. The vibration amplitude of the L47 cam was small, and the scratch amplitude on the Cu-7 workpiece was smaller, and the cutting condition was more stable and the surface roughness was lower. However, the machining of Cu-8 by L102 cam destroyed the surface morphology of the workpiece. (4) The abrasive flow rates for the Cu-3, Cu-6 and Cu-5 workpieces were 38, 28, and 19 mm/s, respectively. After processing, the surface roughness were 0.130, 0.156, and 0.178μm, respectively. Under the same vibration machining conditions, the higher the abrasive flow rate, the lower the workpiece surface roughness, and the relationship between the surface roughness of each workpiece after machining was Cu-5 > Cu-6 >Cu-3. Moreover, there were scratches on the workpiece surface with a certain angle from the original scratches, and the relationship between the curvature radius of the scratch on the surface of the workpiece was Cu-3 > Cu-6 > Cu-5. Conclusions: Compared with traditional abrasive flow machining, vibration-assisted abrasive flow machining extends the cutting path of abrasive particles on the workpiece surface, forming cross scratches and reducing the surface roughness of the workpiece. The higher the vibration frequency, the longer the micro-cutting length between abrasive particles and the workpiece surface, the lower the surface roughness of the workpiece. With the increase of abrasive flow rate, the cutting effect of the abrasive particles on the workpiece surface is enhanced, leading to greater reductions in surface roughness.

Cold and Hot syndrome, also known as “ZHENG” in Mandarin, is a fundamental theory in traditional Chinese medicine (TCM) and plays a pivotal role in the differentiation of diseases in TCM. Diseases are treated with varying formulas according to the specific syndrome differentiations in TCM. A way of the principles followed in TCM medical strategy is “cold herbs for hot syndrome, and hot herbs for cold syndrome.” Therefore, from the perspective of cold/hot syndrome, we summarizes the present research regarding the characteristics and mechanisms of cold/hot herbs (including herbs with cool and warm properties) in digestive system diseases, respiratory diseases, and autoimmune diseases, among others. As novel technologies have advanced, various methods, such as those based on network target, machine learning, and deep learning, have emerged to reveal the mechanisms underlying cold/hot syndrome and cold/hot herbs. With the help of these technologies, it has been found that cold and hot herbs, as well as formulae with cold or hot intentions, have similarities and differences in the treatment of these diseases. In conclusion, cold and cool may have stronger antibacterial, antiviral, and anti-inflammatory effects, whereas hot and warm herbs may specifically enhance immune regulation. With the assistance of advancing data algorithms, uncovering the mechanisms of cold/hot herbs may accelerate and provide a new research paradigm for further achieving precision in TCM.

The study of the hydro-chemical characteristics of burnt rock aquifers helps to distinguish the hydraulic connections between different aquifers. Taking Zhangjiamao Coal Mine in Shenfu Mining Area as an example, 29 groups of water samples were collected from weathered bedrock, bedrock, 2−2 coal burned rock and 3−1 coal burned rock aquifers, and the hydro-chemical characteristics and control factors in the study area were analyzed by comprehensive use of statistical analysis, Piper trilinear diagram, Gibbs model and hybrid model, and the source of main ions was determined, based on which the contact relationship of each aquifer was identified. The results indicated that the total dissolved solids (TDS) of the weathered bedrock and the 2−2 coal burnt rock aquifer were close, slightly lower than the TDS of the bedrock aquifer, while the TDS of the 3−1 coal burnt rock aquifer was the highest, showing a trend of gradually increasing TDS with the increase of aquifer depth. The cations in the weathered bedrock and the 2−2 coal burnt rock aquifer were mainly Ca2+, while the cations in the bedrock and 3−1 coal burnt rock aquifer were mainly Na+; the anions in the weathered bedrock, 2−2 coal burnt rock, and 3−1 coal burnt rock aquifers were mainly HCO3−, while the bedrock aquifers were mainly HCO3−, and SO42−. The hydro-chemical types of weathered bedrock, 2−2 coal burnt rock, and 3−1 coal burnt rock aquifers were mainly HCO3−Ca type, HCO3−Ca and HCO3−Ca·Mg type, HCO3−Ca and HCO3−Na·Mg type. The hydro-chemical composition of weathered bedrock and 2−2 coal burnt rock aquifer was mainly controlled by water rock interaction, while the hydro-chemical composition of bedrock and 3−1 coal burnt rock aquifer was mainly influenced by both water rock interaction and concentration. The main ions of 3−1 coal burned rock, bedrock, weathered bedrock and 2−2 coal burned rock aquifer were respectively from the dissolution of silicate rock salt, the dissolution of silicate rock and evaporite rock salt, and the weathering dissolution of silicate rock and carbonate rock salt. At the same time, the reverse cation exchange interaction effect occurred in the groundwater disasters of each aquifer. Multiple indicator results showed that the ion composition of the weathered bedrock and the aquifer of the 2−2 coal fired rock was similar, and there was a strong hydraulic connection. There may be a direct contact relationship locally, which is different from the ion composition of the aquifer of the 3−1 coal fired rock. There is a certain barrier layer between them, and the hydraulic connection between them is weak.

In order to predict the surface movement and deformation caused by coal seam mining, a mining subsidence estimation system is designed and developed with the help of C# language and ArcGIS Engine component tool library based on the probability integration method of polar coordinate system. The system is applicable to irregularly shaped mining workings, and is capable of predicting the subsidence, horizontal movement, horizontal deformation, tilt and curvature of various points on the surface of the mining area after different mining times, and post-process the prediction results to draw the surface movement and deformation cloud map. Taking 308 working face mining of a mine in Shaanxi Province as an example, the probability integral parameters are selected according to the mining conditions and formation lithology of the working face and are substituted into the system to predict the surface movement and deformation, and the results are compared with the measured surface movement and deformation. The results show that the relative error between the predicted surface subsidence value and the measured subsidence value is less than 10%, and the subsidence basin shape is basically consistent with the reality. The predicted result of the system is relatively reliable, and has certain applicability to the mining subsidence prediction.

Abstract The study aims to explore the relationship among metacognition (MC), fear of disease of progression (FoP), psychological distress (PD), and quality of life (QoL), and verify whether FoP and PD have a chain mediating effect between MC and QoL. 231 hematologic tumor patients in a large tertiary hospital were investigated by using Meta-Cognitions Questionnaire-30, Fear of Progression Questionnaire-Short Form, Hospital Anxiety and Depression Scale, and Functional Assessment of Cancer Therapy scale. Data analyses were performed using IBM SPSS (version 25.0) and the PROCESS macro (version 4.1). The results showed that the direct impact of MC on QoL was not statistically significant. However, the indirect influence of MC on QoL manifest through the independent influences of PD and FoP, as well as the chain mediating effect of “PD → FoP.” In addition, all four dimensions of QoL (physical, social and family, emotional, and functional) satisfy the chain mediation model, except for the social and family domain. These insights advance our comprehension of the intricate interplay between MC and QoL, underscoring the importance of improving MC to alleviate patients' PD, mitigate FoP, and ultimately improve the QoL of hematologic tumor patients.

Abstract Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal–amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

Extraction of methane hydrate from subseafloor reservoir may potentially trigger seabed slides and induce subsidence. To address the problems, it is crucial to properly characterize the phase equilibrium condition of pore hydrate and the shear strength of the soil. As one of the key constitutive components, the phase equilibrium condition enforces a constraint over pore gas pressure, temperature and unhydrated water content. Such a constraint, however, has been traditionally ignored in analyzing the mechanical behavior of hydrate-bearing soil. In this paper, a series of stepwise hydrate dissociation tests was performed, and the phase equilibrium condition of pore hydrate was determined, providing an effective way to evaluate the unhydrated water content during hydrate dissociation. Meanwhile, a series of direct shear tests was also conducted to explore the shear strength characteristics of the soil. It is shown that the shear strength of the hydrate-bearing soil can be significantly influenced by pore gas pressure, unhydrated water content, hydrate saturation and several other factors. In particular, the measured shear strength depends upon the initial water content of the sample, pointing to a potential problem that the shear strength could be wrongly determined if not properly interpreted. A shear strength criterion, which enforces the equilibrium condition of pore hydrate, is developed for hydrate-bearing soil, establishing a link between the equilibrium condition and the shear strength. The proposed equation describes well the shear strength characteristics of hydrate-bearing soils, remarkably unifying the effects of pore pressure, temperature, water content and hydrate saturation.

Abstract In the quest for sustainable energy materials, wood is discovered to be a potential piezoelectric material. However, the rigidity, poor stability, and low piezoelectric properties of wood impede its development. Here, we obtained a superelastic roasted wood nanogenerator (RW‐NG) by unraveling ray tissues through a sustainable roasting strategy. The increased compressibility of roasted wood intensifies the deformation of cellulose microfibrils, significantly enhancing the piezoelectric effect in wood. Roasted wood (15 × 15 × 15 mm3, longitudinal × radial × tangential) can generate a voltage and current outputs of 1.4 V and 14.5 nA, respectively, which are more than 70 times that of natural wood. The wood sample can recover 90% of its shape after 5000 compressions at 65% strain, exhibiting excellent elasticity and stability. Importantly, roasted wood does not add any toxic substances and can be safely applied on the human skin as a self‐powered sensor for detecting body movements. Moreover, it can also be assembled into self‐powered wooden floors for energy harvesting. These indicate that roasted wood has great potential for sustainable sensing and energy conversion.

Rechargeable aqueous alkaline Zn-Ni batteries (AZNBs) are considered a potential contender for energy storage fields and portable devices due to their inherent safety, high output voltage, high theoretical capacity and environmental friendliness. Despite the facilitated development of AZNBs by many investigations, its practical application is still restricted by inadequate energy density, sluggish kinetics, and poor stability. Therefore, Ni-based cathodes with boosted redox chemistry and enhanced structural integrity is essential for the high-performance AZNBs. Herein, this review focus on critical bottlenecks and effective design strategies of the representative Ni-based cathode materials. Specifically, nanostructured optimization, defect engineering, ion doping, heterostructure regulation and ligand engineering have been employed from the fundamental aspects for high-energy and long-lifespan Ni-based cathodes. Finally, further exploration in failure mechanism, binder-free battery configurations, practical application scenarios, as well as battery recycling are considered as valuable directions for the future development of advanced AZNBs.

Background Nasopharyngeal carcinoma (NPC) is a distinct subtype of head and neck cancer which is prevalent in south of China and southeastern of Asia. Consistent activation of interferon (IFN) signaling, and impairment of T cell mediated antitumor immunity is frequent in NPC. Forkhead box A1 (FOXA1) is one of the earliest discovered pioneer factors, which can open up compact chromatin structures to facilitate the binding of other proteins to chromatin.Methods By using RNA sequencing, it was discovered that FOXA1 suppresses the activation of the interferon signaling pathway and the expression of the related interferon-responsive genes in NPC cells. The effect of FOXA1 on programmed death-ligand 1 (PD-L1) expression in C666-1 and HK1 cells under conditions with or without IFN-γ was detected through quantitative PCR (qPCR), western blot, and flow cytometry. After co-culturing T cells with IFN-γ-treated NPC cells in vitro, apoptosis of CD8+ T cells and the expression of cytotoxic cytokines were assessed by flow cytometry. The cytotoxic effects of T cells on tumor cells in nude mice were measured by tumorigenesis in nude mice and adoptive T cell therapy. The effects of IFN-γ on the expression and nuclear localization of STAT1, as well as the colocalization of FOXA1 with STAT1 were detected by immunofluorescence, qPCR, western blot, and co-immunoprecipitation experiments.Results In this study, we reported that loss of FOXA1, a pioneer factor downregulated in NPC, results in activation of IFN signaling in NPC cells. Repression of FOXA1 facilitates IFN-γ induced PD-L1 expression, whereas overexpression of FOXA1 exerts the opposite effect. Mechanistically, FOXA1 interacts with STAT1 and inhibits IRF1 expression and binding to PD-L1 promoter on IFN-γ treatment. Co-culture with FOXA1-silenced NPC cells promotes apoptosis of in vitro activated tumor-specific CD8+T cells and reduces the expression of cytotoxic effector molecules. Furthermore, overexpression of FOXA1 increases the therapeutic efficacy of PD-L1 antibody (atezolizumab) against NPC in nude mice receiving adoptive T-cell therapy.Conclusions We demonstrated that FOXA1 prevents tumor immune evasion by inhibiting IFN-γ induced PD-L1 expression in NPC cells. Our research findings provide new insights into the immunotherapeutic biomarkers and targets for NPC, which is important for the clinical application of programmed cell death protein-1/PD-L1 antibodies in NPC.

Hypoketotic hypoglycemia due to dysregulated insulin secretion is the most common cause of persistent hypoglycemia in children. However, this type of hypoglycemia can also result from defects in the insulin signaling pathway. Distinguishing between the two is important for informing treatment decisions. Here we describe the case of a 10-year-old female with fasting and postprandial hypoglycemia who was found to have a missense variant in the INSR gene, which we functionally characterized. The proband presented with fasting and postprandial hypoglycemia at age six. Diagnostic evaluation was consistent with hypoketotic hypoglycemia suspected to be due to hyperinsulinism, and she was treated with diazoxide. Whole exome sequencing identified a maternally inherited heterozygous missense variant in INSR. Phenotypic studies on the mother were consistent with postprandial hypoglycemia. Phosphorylated Akt and ERK1/2 levels were higher at baseline and in response to stimulation with insulin in 3T3-L1 cells expressing mutant INSR compared to cells expressing wild type INSR. Thus, herein we present a heterozygous missense variant in INSR (c.1151A>G, p.Asn384Ser) that results in constitutive and increased activation of the human insulin receptor, leading to both fasting and postprandial hypoglycemia.

Efforts to increase the number of filters are driven by the demand for miniaturized spectrometers and multispectral imaging. However, processes that rely on sequential fabrication of each filter are cost ineffective. Herein, we introduce an approach to produce at least 16 distinct filters based on a single low-resolution lithographic step with minimum feature size of 0.6 μm. Distinct from grayscale lithography, we employ standard binary lithography but achieve height variations in polymeric resist through a post-development reflow process. The resulting transparent polymeric films were incorporated in Fabry–Perot cavity structures with cavity thickness ranging from 90 to 230 nm to produce transmittance across the visible spectrum. This binary lithography and reflow (BLR) process demonstrates control of the dielectric layer thickness down to ∼15 nm. This new process provides a cost-effective alternative to traditional techniques in fabricating microscopic transmission filters, and other applications where precise thickness variation across the substrate is required.

[Objective] Against the backdrop of tightening incremental land resources, urban development is gradually shifting from relying on the external expansion of incremental land supply to focusing on the intensive model of redevelopment of stock land. This article attempts to explore the impact of incremental land expansion and redevelopment of stock land on urban economic growth at different stages of urban development, in order to provide useful references for the improvement of urban land supply policies. [Methods] Based on the panel data of 284 prefecture level cities from 2009 to 2021 in China, dual fixed effects and threshold effects model were constructed to explore the impact of incremental land expansion and stock land redevelopment on urban economic growth, threshold effects were analyzed at different stages of urban development and scale heterogeneity was analyzed. [Results] (1) The marginal contribution of redevelopment of stock land to economic growth is higher than that of incremental land expansion, and the impact is significant. (2) In the process of urban development, the expansion of incremental land and the redevelopment of existing land both have a population urbanization and per capita GDP threshold effect on urban economic growth. With the continuous improvement of population urbanization and per capita GDP level, the marginal contribution of incremental land expansion to urban economic growth continues to decline, while the marginal contribution of stock land redevelopment to economic growth continues to rise and gradually exceeds that of incremental land expansion. In terms of heterogeneity analysis, the above two threshold effects exist in cities of different scales, and have the same development trend as the national sample. Among them, the threshold value for large cities is higher than the national threshold value, and the national threshold value is higher than the threshold value for small and medium-sized cities. [Conclusion] The traditional externally expanding urban development model relying on incremental land expansion is unsustainable, and cities are gradually entering the era of stock; However, cities of different scales enter the stage of stock development at different times. It is necessary to adopt differentiated land supply strategies for different cities in order to better leverage the driving role of land resources on urban economy.

Abstract Psychiatric syndromes are common following recovery from Coronavirus Disease 2019 (COVID-19) infection. This study investigated the prevalence and the network structure of depression, insomnia, and suicidality among mental health professionals (MHPs) who recovered from COVID-19. Depression and insomnia were assessed with the Patient Health Questionnaire (PHQ-9) and Insomnia Severity Index questionnaire (ISI7) respectively. Suicidality items comprising suicidal ideation, suicidal plan and suicidal attempt were evaluated with binary response (no/yes) items. Network analyses with Ising model were conducted to identify the central symptoms of the network and their links to suicidality. A total of 9858 COVID-19 survivors were enrolled in a survey of MHPs. The prevalence of depression and insomnia were 47.10% (95% confidence interval (CI) = 46.09–48.06%) and 36.2% (95%CI = 35.35–37.21%), respectively, while the overall prevalence of suicidality was 7.8% (95%CI = 7.31–8.37%). The key central nodes included “Distress caused by the sleep difficulties” (ISI7) (EI = 1.34), “Interference with daytime functioning” (ISI5) (EI = 1.08), and “Sleep dissatisfaction” (ISI4) (EI = 0.74). “Fatigue” (PHQ4) (Bridge EI = 1.98), “Distress caused by sleep difficulties” (ISI7) (Bridge EI = 1.71), and “Motor Disturbances” (PHQ8) (Bridge EI = 1.67) were important bridge symptoms. The flow network indicated that the edge between the nodes of “Suicidality” (SU) and “Guilt” (PHQ6) showed the strongest connection (Edge Weight= 1.17, followed by “Suicidality” (SU) - “Sad mood” (PHQ2) (Edge Weight = 0.68)). The network analysis results suggest that insomnia symptoms play a critical role in the activation of the insomnia-depression-suicidality network model of COVID-19 survivors, while suicidality is more susceptible to the influence of depressive symptoms. These findings may have implications for developing prevention and intervention strategies for mental health conditions following recovery from COVID-19.

Abstract Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.

Abstract Water body (WB) extraction is the basic work of water resources management. Tibetan Plateau is one of the largest alpine lake systems in the world. However, research on the characteristics of water bodies (WBs) is mainly focused on large and medium WBs due to spatial resolution. This research presents a dataset containing a 2-m resolution map of WBs in 2020 based on Gaofen-1 data, and morphometric and landscape indices of WBs across the Tibetan Plateau. The Swin-UNet model is well performed with overall accuracy at 98%. The total area of WBs is 56354.6 km2 across Tibetan Plateau in 2020. The abundance compared with that from size-abundance relationship indicate WBs in the Tibetan Plateau conformed to the classic power scaling law. We evaluate the influence of spatial-resolution in WB extraction, which shows the dataset could be valuable to fill the gap of existing WBs map, especially for small waters. The dataset is valuable for revealing the spatial patterns of WBs, and understanding the impacts of climate change on water resources in Plateau.

Abstract Triptolide (TPL) is a compound sourced from Tripterygium wilfordii Hook. F., a traditional Chinese medicinal herb recognized for its impressive anti-inflammatory, anti-angiogenic, immunosuppressive, and antitumor qualities. Notwithstanding its favorable attributes, the precise mechanism through which TPL influences tumor cells remains enigmatic. Its toxicity and limited water solubility significantly impede the clinical application of TPL. We offer a comprehensive overview of recent research endeavors aimed at unraveling the antitumor mechanism of TPL in this review. Additionally, we briefly discuss current strategies to effectively manage the challenges associated with TPL in future clinical applications. By compiling this information, we aim to enhance the understanding of the underlying mechanisms involved in TPL and identify potential avenues for further advancement in antitumor therapy.

Abstract Background Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear. Methods RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein. Results We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5′-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma. Conclusions These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma.

Abstract Cisplatin (DDP)-based chemoradiotherapy is one of the standard treatments for nasopharyngeal carcinoma (NPC). However, the sensitivity and side effects of DDP to patients remain major obstacles for NPC treatment. This research aimed to study DDP sensitivity regulated by cancer-associated fibroblasts (CAFs) through modulating ferroptosis. We demonstrated that DDP triggered ferroptosis in NPC cells, and it inhibited tumor growth via inducing ferroptosis in xenograft model. CAFs secreted high level of FGF5, thus inhibiting DDP-induced ferroptosis in NPC cells. Mechanistically, FGF5 secreted by CAFs directly bound to FGFR2 in NPC cells, leading to the activation of Keap1/Nrf2/HO-1 signaling. Rescued experiments indicated that FGFR2 overexpression inhibited DDP-induced ferroptosis, and CAFs protected against DDP-induced ferroptosis via FGF5/FGFR2 axis in NPC cells. In vivo data further showed the protective effects of FGF5 on DDP-triggered ferroptosis in NPC xenograft model. In conclusion, CAFs inhibited ferroptosis to decrease DDP sensitivity in NPC through secreting FGF5 and activating downstream FGFR2/Nrf2 signaling. The therapeutic strategy targeting FGF5/FGFR2 axis from CAFs might augment DDP sensitivity, thus decreasing the side effects of DDP in NPC treatment.

Improving vegetable yield and optimizing its quality through nutrient management have long been central to plant nutrition and horticultural science. Copper (Cu) is recognized as an essential trace element that promotes plant growth and development. However, the mechanisms by which Cu influences nitrogen (N) metabolism remain largely unknown, with limited studies exploring the interaction between Cu and varying nitrate-to-ammonium (nitrate/ammonium) ratios. In this study, Chinese cabbage was exposed to two Cu concentrations (0 and 0.02 mg L-1) in combination with three nitrate/ammonium ratios (10/90, 50/50, and 90/10) under hydroponic conditions. The results showed that Cu application increased plant biomass, nitrate reductase (NR) and glutamine synthetase (GS) enzyme activities, the expression of NR (NIA) and GS2 (Gln2) genes, and N content in both shoots and roots. Additionally, Cu treatment decreased nitrate and free amino acid contents, as well as the expression of nitrate transporters NRT1.1 and NRT2.1 in roots while increasing these four parameters in shoots. Additionally, these effects were significantly modulated by the nitrate/ammonium ratios. In conclusion, Cu may facilitate nitrate transportation, enhance nitrate reduction, promote ammonium assimilation, and influence the transformation of organic N compounds, highlighting its potential role in improving N metabolism in Chinese cabbage.

IntroductionCasuarina equisetifolia is a common protective forest in coastal areas. However, artificial C. equisetifolia forests cannot self-renew, mainly due to the accumulation of allelochemicals. Endophytic bacteria may alleviate the root growth inhibition caused by allelochemicals in C. equisetifolia seedlings. B. amyloliquefaciens and B. aryabhattai were endophytic bacteria with strong allelopathy in C. equisetifolia root. The allelopathy mechanism of these two endophytes and their interaction with C. equisetifolia remains to be studied.MethodsWhole-genome sequencing of B. amyloliquefaciens and B. aryabhattai isolated from the roots of allelochemical-accumulating C. equisetifolia was performed using Illumina Hiseq and PacBio single-molecule sequencing platforms. Sterile seedlings of C. equisetifolia were treated with either individual or mixed bacterial cultures through root drenching. Transcriptional and metabolomics analyses were conducted after 3 days of infection.Results and discussionWhole-genome sequencing of Bacillus aryabhattai and Bacillus amyloliquefaciens showed that the two strains contained various horizontal gene transfer elements such as insertion sequence, prophage and transposon. In addition, these two strains also contain numerous genes related to the synthesis and catabolism of allelochemicals. After these two strains of bacteria were individually or mixed infected with C. equisetifolia, metabolomics and transcriptomic analysis of C. equisetifolia showed the 11 important secondary metabolite biosynthesis among them alkaloids biosynthesis, phenylpropanoid and terpenes biosynthesis and related genes were putatively regulated. Correlation analysis revealed that 48 differentially expressed genes had strong positive correlations with 42 differential metabolites, and 48 differentially expressed genes had strong negative correlations with 36 differential metabolites. For example, CMBL gene showed positive correlations with the allelochemical (-)-Catechin gallate, while Bp10 gene showed negative correlations with (-)-Catechin gallate.ConclusionThe intergenerational accumulation of allelochemicals may induce horizontal gene transfer in endogenic bacteria of Casuarina equisetifolia root. Endophytic Bacillus plays an allelopathic role by assisting the host in regulating gene expression and the production and/or variety of allelochemicals. This comprehensive study sheds light on the intricate genetic and metabolic interactions between Bacillus endophytes and C. equisetifolia. These findings provide insights into endophyte-mediated allelopathy and its potential uses in plant biology and forest sustainability.

Extracting road network maps for high-resolution remote sensing images is a critical and challenging remote sensing topic, with significant importance for traffic navigation, disaster management, autonomous driving, and urban planning. Although deep learning has demonstrated its powerful feature extraction capabilities in image processing tasks, including road extraction, existing road extraction algorithms still have some limitations. In particular, semantic segmentation-based methods often lack supervision of the connection relationships between roads and topological correctness constraints, resulting in fragmented and poorly connected road network graphs. Moreover, graph-based methods lack effective supervision strategies for vertex misdetection issues. To deal with these issues, we propose a deeply supervised vertex network (DSVNet) for road network graph extraction. First, to effectively supervise road vertices, we design a road vertex supervision module that yields improved vertex prediction accuracy. Second, to merge the benefits of segmentation-based methods and graph-based methods, we establish a parallel semantic segmentation branch based on the vertex querying task, thereby achieving enhanced road extraction accuracy. Furthermore, we introduce deformable attention into the model to boost its performance and computational efficiency. We validate the effectiveness of DSVNet on two large-scale public datasets. A large number of experimental results show that our research approach achieves the best road detection performance.

BackgroundMelanotic schwannoma (MS), a rare variant of peripheral nerve sheath tumor, is especially infrequent when originating from the peritoneum. Its definitive diagnosis relies on postoperative histopathological examination and immunohistochemical analysis, while preoperative diagnosis is difficult.Case presentationIn the present study, we reported a rare case of giant MS in the retroperitoneum, which was previously misdiagnosed before surgery. However, intraoperative exploration revealed it was retroperitoneal tumor. The tumor had invaded the abdominal aorta and bilateral common illiac artery walls. A surgical resection was subsequently executed, and postoperative histopathological examination confirmed it as a MS.ConclusionThe incidence of peritoneal MS is extremely rare, and surgical resection remains the preferred treatment modality. Given the absence of established guidelines for postoperative adjuvant therapy, long-term follow-up becomes imperative to accumulate valuable clinical expertise.

Recently, KTaO3 (KTO)-based 5d two-dimensional electron gases (2DEGs), characterized by robust spin–orbit coupling, have emerged as promising candidates for future spintronic devices. However, the carrier mobility of KTO-based 2DEGs is typically lower than that of SrTiO3-based 2DEGs, which limits their further development. It is imperative to explore the underlying causes of diminished carrier mobility and devise strategies to augment it. In addition, the genesis of magnetism within KTO-based 2DEGs remains ambiguous. In this study, the 2DEG within the amorphous-EuTiO3/KTO (a-ETO/KTO) heterostructure demonstrates a high electron mobility of 289.1 cm2 V−1 s−1, which exhibits a significant decrease as the film growth temperatures increase. This decrease can be primarily ascribed to electron scattering by impurities, which is induced by the amplified interfacial element interdiffusion at a higher film growth temperature. In addition, the magnetism of 2DEGs for samples grown at different temperatures shows an increasing trend with growth temperatures, which is predominantly derived from the interdiffusion of Eu atoms. This study provides an in-depth analysis of the origin of magnetic ordering and reduced mobility in KTO-based 2DEGs, which will promote the further development of 2DEGs for future applications in electronic devices.

Abstract Introduction In this study, we aimed to evaluate the predictive value of circulating lymphocyte subsets and inflammatory indexes in response to neoadjuvant chemoradiotherapy (NCRT) in patients with rectal mucinous adenocarcinomas (MACs). Methods Rectal MAC patients who underwent NCRT and curative resection at Fujian Medical University Union Hospital's Department of Colorectal Surgery between 2016 and 2020 were included in the study. Patients were categorized into good and poor response groups based on their pathological response to NCRT. An independent risk factor‐based nomogram model was constructed by utilizing multivariate logistic regression analysis. Additionally, the extreme gradient boosting (XGB) algorithm was applied to build a machine learning (ML)‐based predictive model. Feature importance was quantified using the Shapley additive explanations method. Results Out of the 283 participants involved in this research, 190 (67.1%) experienced an unfavorable outcome. To identify the independent risk factors, logistic regression analysis was performed, considering variables such as tumor length, pretreatment clinical T stage, PNI, and Th/Tc ratio. Subsequently, a nomogram model was constructed, achieving a C‐index of 0.756. The ML model exhibited higher prediction accuracy than the nomogram model, achieving an AUROC of 0.824 in the training set and 0.762 in the tuning set. The top five important parameters of the ML model were identified as the Th/Tc ratio, neutrophil to lymphocyte, Th lymphocytes, Gross type, and T lymphocytes. Conclusion Radiochemotherapy sensitivity is markedly influenced by systemic inflammation and lymphocyte‐mediated immune responses in rectal MAC patients. Our ML model integrating clinical characteristics, circulating lymphocyte subsets, and inflammatory indexes is a potential assessment tool that can provide a reference for individualized treatment for rectal MAC patients.

Abstract Background N6‐methyladenosine (m6A) modification is essential for modulating RNA processing as well as expression, particularly in the context of malignant tumour progression. However, the exploration of m6A modification in nasopharyngeal carcinoma (NPC) remains very limited. Methods RNA m6A levels were analysed in NPC using m6A dot blot assay. The expression level of methyltransferase‐like 14 (METTL14) within NPC tissues was analysed from public databases as well as RT‐qPCR and immunohistochemistry. The influences on METTL14 expression on NPC proliferation and metastasis were explored via in vitro as well as in vivo functional assays. Targeted genes of METTL14 were screened using the m6A and gene expression profiling microarray data. Actinomycin D treatment and polysome analysis were used to detect the half‐life and translational efficiency of ANKRD22. Flow cytometry, immunofluorescence and immunoprecipitation were used to validate the role of ANKRD22 on lipid metabolism in NPC cells. ChIP‐qPCR analysis of H3K27AC signalling near the promoters of METTL14, GINS3, POLE2, PLEK2 and FERMT1 genes. Results We revealed METTL14, in NPC, correlating with poor patient prognosis. In vitro and in vivo assays indicated METTL14 actively promoted NPC cells proliferation and metastasis. METTL14 catalysed m6A modification on ANKRD22 messenger ribonucleic acid (mRNA), recognized by the reader IGF2BP2, leading to increased mRNA stability and higher translational efficiency. Moreover, ANKRD22, a metabolism‐related protein on mitochondria, interacted with SLC25A1 to enhance citrate transport, elevating intracellular acetyl‐CoA content. This dual impact of ANKRD22 promoted lipid metabolism reprogramming and cellular lipid synthesis while upregulating the expression of genes associated with the cell cycle (GINS3 and POLE2) and the cytoskeleton (PLEK2 and FERMT1) through heightened epigenetic histone acetylation levels in the nucleus. Intriguingly, our findings highlighted elevated ANKRD22‐mediated histone H3 lysine 27 acetylation (H3K27AC) signals near the METTL14 promoter, which contributes to a positive feedback loop perpetuating malignant progression in NPC. Conclusions The identified METTL14‐ANKRD22‐SLC25A1 axis emerges as a promising therapeutic target for NPC, and also these molecules may serve as novel diagnostic biomarkers.

BackgroundResearch on the mental health and quality of life (hereafter QOL) among fire service recruits after the end of the COVID-19 restrictions is lacking. This study explored the network structure of depression, anxiety and insomnia, and their interconnections with QOL among fire service recruits in the post-COVID-19 era.MethodsThis cross-sectional study used a consecutive sampling of fire service recruits across China. We measured the severity of depression, anxiety and insomnia symptoms, and overall QOL using the nine-item Patient Health Questionnaire (PHQ-9), seven-item Generalized Anxiety Disorder scale (GAD-7), Insomnia Severity Index (ISI) questionnaire, and World Health Organization Quality of Life-brief version (WHOQOL-BREF), respectively. We estimated the most central symptoms using the centrality index of expected influence (EI), and the symptoms connecting depression, anxiety and insomnia symptoms using bridge EI.ResultsIn total, 1,560 fire service recruits participated in the study. The prevalence of depression (PHQ-9 ≥ 5) was 15.2% (95% CI: 13.5–17.1%), while the prevalence of anxiety (GAD-7 ≥ 5) was 11.2% (95% CI: 9.6–12.8%). GAD4 (“Trouble relaxing”) had the highest EI in the whole network model, followed by ISI5 (“Interference with daytime functioning”) and GAD6 (“Irritability”). In contrast, PHQ4 (“Fatigue”) had the highest bridge EI values in the network, followed by GAD4 (“Trouble relaxing”) and ISI5 (“Interference with daytime functioning”). Additionally, ISI4 “Sleep dissatisfaction” (average edge weight = −1.335), which was the central symptom with the highest intensity value, had the strongest negative correlation with QOL.ConclusionDepression and anxiety were important mental health issues to address among fire service recruits in the post-COVID-19 era in China. Targeting central and bridge symptoms identified in network analysis could help address depression and anxiety among fire service recruits in the post-COVID-19 era.

Abstract Purpose To explore the impact of excluding the external iliac node (EIN) from the clinical target volume (CTV) during preoperative radiotherapy in T4b rectal cancer with anterior structure invasion. Methods We retrospectively identified 132 patients with T4b rectal cancer involving the anterior structures who received radiotherapy followed by surgery between May 2010 and June 2019. Twenty-nine patients received EIN irradiation (EIN group), and 103 did not (NEIN group). Failure patterns, survival and toxicities were compared between the two groups. Results The most common failure was distant metastasis (23.5%). 11 (8.3%) patients developed locoregional recurrence, 10 (9.7%) patients were in the NEIN group, and 1 (3.4%) was in the EIN group (P = 0.34). The EIN region failure was rare (1/132, 0.8%). The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 96.3% vs. 90.5%, 82.1% vs.73.7%, 75.9% vs. 78.0% and 72.4% vs. 68.3% (all P > 0.05) for the EIN group and NEIN group, respectively. The incidence of grade 3–4 acute toxicity in the lower intestine was significantly higher in the EIN group than in the NEIN group (13.8% vs. 1.9%, P = 0.02). The Dmax, V35 and V45 of the small bowel was decreased in the NEIN group compared to the EIN group. Conclusions Exclusion of the EIN from the CTV in T4b rectal cancer with anterior structure invasion could reduce lower intestinal toxicity without compromising oncological outcomes. These results need further evaluation in future studies.

As an important part of strategic emerging industries, the new-generation information technology plays a major leading role in the overall and long-term development of the economy and society. The new-generation information technology industry is also the cornerstone for cultivating new quality productivity, and is an important starting point for opening up new fields and tracks for development and for shaping new momentum and advantages. Based on the implications of the new-generation information technology industry, this study sorts out the global development trend of the new-generation information technology industry, summarizes the current status and development trend of the industry in China, and analyzes the opportunities and challenges faced by the industry. Moreover, focusing on the requirements of high-quality development of the new-generation information technology industry, the study proposes the following countermeasures and suggestions: (1) improving the integrated strategic system and capabilities while adhering to a system engineering thinking; (2) strengthening the research of key core technologies to strengthen the basic capacity of the industry; (3) promoting the integrated and clustered development of industries, highlighting enterprises as the main body; (4) constructing an open innovation ecosystem based on scenario-driven innovation; and (5) promoting the coordinated development of production, education, research, application, and funds to cultivate a high-level talent team.

Background: Considerable morbidity and death are associated with acute kidney damage (AKI) following total aortic arch replacement (TAAR). The relationship between AKI following TAAR and serum magnesium levels remains unknown. The intention of this research was to access the predictive value of serum magnesium levels on admission to the Cardiovascular Surgical Intensive Care Unit (CSICU) for AKI in patients receiving TAAR. Methods: From May 2018 to January 2020, a prospective, observational study was performed in the Guangdong Provincial People's Hospital CSICU. Patients accepting TAAR admitted to the CSICU were studied. The Kidney Disease: Improving Global Outcomes (KDIGO) definition of serum creatinine was used to define AKI, and KDIGO stages two or three were used to characterize severe AKI. Multivariable logistic regression and area under the curve receiver-operator characteristic curve (AUC-ROC) analysis were conducted to assess the predictive capability of the serum magnesium for AKI detection. Finally, the prediction model for AKI was established and internally validated. Results: Of the 396 enrolled patients, AKI occurred in 315 (79.5%) patients, including 154 (38.8%) patients with severe AKI. Serum magnesium levels were independently related to the postoperative AKI and severe AKI (both, P < 0.001), and AUC-ROCs for predicting AKI and severe AKI were 0.707 and 0.695, respectively. Across increasing quartiles of serum magnesium, the multivariable-adjusted odds ratios (95% confidence intervals) of postoperative AKI were 1.00 (reference), 1.04 (0.50-2.82), 1.20 (0.56-2.56), and 6.19 (2.02-23.91) (P for Trend < 0.001). When serum magnesium was included to a baseline model with established risk factors, AUC-ROC (0.833 vs 0.808, P = 0.050), reclassification (P < 0.001), and discrimination (P = 0.002) were further improved. Conclusions: Serum magnesium levels on admission are an independent predictor of AKI. In TAAR patients, elevated serum magnesium levels were linked to an increased risk of AKI. In addition, the established risk factor model for AKI can be considerably improved by the addition of serum magnesium in TAAR patients hospitalized in the CSICU.

Superpixel segmentation is an essential step of object-oriented remote sensing image classification; the accuracy of the superpixel segmentation boundary will directly affect the classification result. Most of the traditional superpixel segmentation algorithms rely on spectral similarity and spatial connectivity to construct superpixels. They cannot find the accurate boundary in the complex scenes, such as the spatial distribution of ground features being relatively broken, and large differences in the size and shape, especially long-thin shape and circular shape. Aiming at this problem, a superpixel segmentation algorithm based on an anisotropic diffusion model named ADS is proposed and applied to image classification. The anisotropic diffusion model originated in thermodynamics has excellent properties in which the diffusion is continuous and smooth and its diffusion speed depends on the medium, which provides convenience for smoothing homogeneous regions and establishing boundary constraints for different ground objects. With this advantage, the diffusion flux model is established to consider the influence of boundary factors and used to simulate the dissimilarity measure with boundary constraints between pixels and seed points by combining the traditional spectral and spatial distance. Then, the seed points of superpixel are optimized under the K-means framework. The effectiveness of the proposed algorithm is tested and verified with different spatial resolutions, such as Landsat 8 with 30 m, Sentinel-2 with 10 m, and SkySat with 0.5 m. A large number of experiments show that the proposed algorithm can better correct the superpixel boundary-fitting deviation problem in complex scenes and effectively promote the improvement of image classification accuracy.

Passive daytime radiative cooling that could provide sub-ambient cooling emerges as a promising technology to reduce household energy consumption. Nonetheless, prevailing studies are predominantly focused on surface cooling, often overlooking its adaptability to enclosed spaces with active cooling technologies. Here we present a multilayer radiative cooling film (J-MRC) with Janus optical properties in the mid-infrared region, consisting of the nanoporous polyethylene films, the polyethylene oxide film, and silver nanowires. The top side of the J-MRC functions as a conventional radiative cooling material to supply sub-ambient surface cooling, while the bottom side with low mid-infrared emissivity transfers limited heat via thermal radiation to the low-temperature enclosures. Our experiments validate that the J-MRC possesses an enhanced space cooling performance in comparison to the conventional radiative cooling film. This work provides a valuable design concept for radiative cooling materials, thereby expanding their practical scenarios and contributing to reduce the carbon emission.

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC. In light of these developments, it has become evident that a deeper understanding of the tumor microenvironment (TME) is crucial. The TME serves a dual function, acting as a promoter of tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression and enabling immune evasion. Consequently, a comprehensive comprehension of the TME and its intricate involvement in the initiation, progression, and metastasis of NPC is imperative for the development of effective anticancer drugs. Moreover, given the complexity of TME and the inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy and circumvent drug resistance. This review aims to provide an in-depth exploration of the TME within the context of EBV-induced NPC, with a particular emphasis on its pivotal role in regulating intercellular communication and shaping treatment responses. Additionally, the review offers a concise summary of drug resistance mechanisms and potential strategies for their reversal, specifically in relation to chemoradiation therapy, targeted therapy, and immunotherapy. Furthermore, recent advances in clinical trials pertaining to NPC are also discussed.

Abstract Background Rectovaginal fistula (RVF) is an abnormal channel formed by epithelial tissue between the anterior wall of the rectum and the posterior wall of the vagina, which manifests as vaginal gassing and defecation. It is one of the common complications of female pelvic surgeries. With the increased number of proctectomies for rectal cancer, the number of postoperative rectovaginal fistulas also increases. Once RVF occurs, the failure rate is still high with various treatments available. RVF causes great suffering to women and is still a major problem in treatment. Therefore, it is significant for female rectal cancer patients to prevent RVF after rectal cancer surgery. In this study, we introduce a new method to prevent RVF during rectal cancer radical operation. Methods In this randomized controlled trial (RCT), all operations are performed according to the principle of total mesorectal excision (TME) radical resection in rectal cancer surgery. All eligible participants will be divided into two groups: the experimental group and the control group. Experimental group: the anterior rectal wall of about 1 cm distal to the anastomosis was dislocated. Before the anastomosis of the rectal end, a fat flap (usually left side) containing the ovarian vascular pedicle was dislocated, measured by 10–15 cm in length and 2 cm in width. The fat flap containing the ovarian vascular pedicle was packed and fixed anterior to the anastomotic stoma with fibrin glue. Control group: surgery will be carried out in accordance with the TME principle. Participants will be compared on several variables, including the incidence of RVF after operation (primary outcomes), the occurrence time of postoperative RVF, the occurrence time of RVF after stoma closure, and other postoperative complications, such as anastomotic leakage, chylous leakage, and intestinal obstruction (secondary outcomes). The follow-up data collection will be conducted according to the follow-up time point, and the baseline data will also be collected for follow-up analysis. By comparing the incidence of rectovaginal leakage between the experimental group and the control group, we aim to explore the feasibility of this method for the prevention of postoperative RVF. Discussion This RCT will explore the feasibility of packing with a laparoscopic dislocated fat flap containing an ovarian vascular pedicle anterior to the anastomotic stoma after rectal cancer surgery to prevent RVF. Trial registration Chinese Clinical Trial Registry (ChiCTR) registration ChiCTR2000031449. Registered on June 26, 2019. All items of the WHO Trial registration data set can be found within the protocol.

Abstract The COVID-19 pandemic and the ensuing widespread lockdown measures have had a negative impact on the mental health of children and adolescents. We thus conducted a meta-analysis of the worldwide prevalence of sleep disturbances in children and adolescents during the COVID-19 pandemic. We performed a systematic literature search of the major international (PubMed, PsycINFO, Web of Science) and Chinese (Chinese Nation Knowledge Infrastructure (CNKI) and WANFANG) databases from their commencement dates to 27 December 2022. Altogether, 57 articles covering 206,601 participants were included in the meta-analysis. The overall prevalence of sleep disturbances was 34.0% (95% confidence interval (CI): 28–41%). The prevalence of parent-reported sleep disturbances during the COVID-19 pandemic was significantly higher than that of self-reported (p = 0.005) sleep disturbances. Epidemiological studies jointly conducted across Asia and Europe had a higher prevalence of sleep disturbances compared to those conducted in Asia, Europe, America, Oceania, or South America alone (p