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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.

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

The processing body (P-Body) is a membrane-less organelle with stress-resistant functions. Under stress conditions, cells preferentially translate mRNA that favors the stress response, resulting in a large number of transcripts unfavorable to the stress response in the cytoplasm. These non-translating mRNAs aggregate with specific proteins to form P-Bodies, where they are either stored or degraded. The protein composition of P-Bodies varies depending on cell type, developmental stage, and external environmental conditions. This review primarily elucidates the protein composition in plants and the assembly of P-Bodies, and focuses on the mechanisms by which various proteins within the P-Bodies of plants regulate mRNA decapping, degradation, translational repression, and storage at the post-transcriptional level in response to ethylene signaling and abiotic stresses such as drought, high salinity, or extreme temperatures. This overview provides insights into the role of the P-Body in plant abiotic stress responses.

Abstract Purpose This study aimed to compare the clinical outcomes and differences in biomechanical characteristics between the femoral neck system (FNS) and cannulated cancellous screws (CCSs) in the treatment of femoral neck fractures. Methods This study retrospectively analysed a cohort of 38 registered cases of femoral neck fractures treated surgically with either the FNS (n = 17) or CCSs (n = 21) between January 2020 and December 2023. Indicators such as fluoroscopy frequency, length of hospital stay, and fracture healing time were compared between the two groups. Functional status was evaluated via the Harris hip score (HHS) and visual analogue scale (VAS), whereas prognosis was assessed based on changes in the neck shaft angle and femoral neck shortening. Additionally, six sets of femoral neck fracture models were developed based on Pauwels angles of 30°, 40°, 50°, 60°, 70°, and 80°. Two experimental groups, FNS and CCS, were established, and a joint reaction force of 1800 N was applied to the proximal femur. The displacement, stress, and stiffness of the components of interest in the different models were tested and compared. Results The distributions of all the baseline characteristics were similar between the two groups (p > 0.05). The FNS group presented significantly shorter fluoroscopy frequency, length of hospital stay, and fracture healing time (p

Introduction: Morphological abnormalities of erythrocytes/red blood cells (RBCs), e.g., increased acanthocytes, in Parkinson’s disease (PD) have been reported previously, although the underlying mechanisms remain to be characterized. In this study, the potential roles of α-synuclein (α-syn), a protein critically involved in PD and highly abundant in RBCs, were studied in PD patients as well as in a PD mouse model. Methods: Transgenic [PAC-Tg (SNCAA53T), A53T] mice overexpressing A53T mutant α-syn and SNCA knockout mice were employed to characterize the effect of α-syn on RBC morphology. In addition to A53T and SNCA knockout mice, the morphology of RBCs of PD patients was also examined using scanning electron microscopy. The potential roles of α-syn were further investigated in cultured RBCs and mice. Results: Morphological abnormalities of RBCs and increased accumulation of aggregated α-syn on the RBC membrane were observed in PD patients. A similar phenomenon was also observed in A53T mice. Furthermore, while mice lacking α-syn expression showed a lower proportion of acanthocytes, treating RBCs derived from SNCA knockout mice with aggregated α-syn resulted in a higher percentage of acanthocytes. In a follow-up proteomic investigation, several major classes of proteins were identified as α-syn-associated proteins on the RBC membrane, seven of which were calcium-binding proteins. Applying aggregated α-syn to the RBC membrane directly induced extracellular calcium influx along with morphological changes; both observations were adequately reversed by blocking calcium influx. Conclusions: This study demonstrated that α-syn plays a critical role in PD-associated morphological abnormalities of RBCs, at least partially via a process mediated by extracellular calcium influx.

The regeneration of maxillofacial bone defects associated with diabetes mellitus remains challenging due to the occlusal loading and hyperglycemia microenvironment. Herein, we propose a material-structure-driven strategy through the additive manufacturing of degradable Zn–Mg–Cu gradient scaffolds. The in situ alloying of Mg and Cu endows Zn alloy with admirable compressive strength for mechanical support and uniform degradation mode for preventing localized rupture. The scaffolds manifest favorable antibacterial, angiogenic, and osteogenic modulation capacity in mimicked hyperglycemic microenvironment, and Mg and Cu promote osteogenic differentiation in the early and late stages, respectively. In addition, the scaffolds expedite diabetic maxillofacial bone ingrowth and regeneration by combining the metabolic regulation effect of divalent metal cations and the hyperboloid and suitable permeability of the gradient structure. RNA sequencing further reveals that RAC1 might be involved in bone formation by regulating the transport and uptake of glucose related to GLUT1 in osteoblasts, contributing to cell function recovery. Inspired by bone healing and structural cues, this study offers an essential understanding of the designation and underlying mechanisms of the material-structure-driven strategy for diabetic maxillofacial bone regeneration.

Abstract Background Although RANK‐LRANK interaction is essential for osteoclastogenesis, the mechanisms by which cancer cells invade bone tissues and initiate osteolytic metastasis remain unclear. Here, we show that the hyperactivation of RelB fosters prostate cancer (PCa) osteolytic metastasis by coordinating interleukin‐8 (IL‐8) and calcium‐binging protein A4 (S100A4). Methods The factors promoting PCa bone metastasis were investigated in sera from PCa patients and tumour tissues derived from nude mice using immunohistochemical analysis and enzyme‐linked immunosorbent assays (ELISA). Cell mobility and mineralization were quantified using BioStation CT and Osteolmage assay. The relative cistrome was investigated in advanced PCa cells by standard transcriptional analyses, including the luciferase reporter response, site‐directed mutagenesis, and chromatin immunoprecipitation (ChIP) assay. PCa cell‐initiated tumour formation, expansion, and bone metastasis were validated in mice using multiple approaches, including orthotopic, intraskeletal, and caudal arterial implantation models. Results IL‐8 and S100A4 correlated with patient Gleason scores and bone metastasis. RelB upregulated IL‐8, facilitating androgen receptor (AR)‐independent growth. RelB‐Sp1 interaction enhanced epithelial‐mesenchymal transition (EMT) by activating Snail and Twist. RelB‐NFAT1c super‐enhancer upregulated S100A4 in the organization of the cytoskeleton and bone metastasis. The RelB‐IL‐8‐S100A4 signalling axis was confirmed to promote osteolytic metastasis in nude mice. Conclusion RelB‐IL‐8 reciprocally promoted EMT by activating inflammatory signalling and inactivating AR signalling. IL‐8 is essential for provoking PCa metastasis but insufficient to drive bone metastasis. IL‐8‐S100A4 cooperation was necessary for metastatic cells to target the bone. Highlights RelB activates inflammatory signalling by upregulating IL‐8 and suppressing AR. RelB upregulates S100A4 by cooperating with NFATC1. IL‐8 boosts EMT by activating Snail 1 and Twist 1, and S100A4 exacerbates osteolytic metastasis via calcium consumption. RelB harnesses IL‐8 and S100A4 to drive PCa osteolytic metastasis.

Abstract Objective This study aimed to assess the functions of cell division cycle protein 45 (CDC45) in Non-small cell lung cancer (NSCLC) cancer and its effects on stemness and metastasis. Methods Firstly, differentially expressed genes related to lung cancer metastasis and stemness were screened by differential analysis and lasso regression. Then, in vitro, experiments such as colony formation assay, scratch assay, and transwell assay were conducted to evaluate the impact of CDC45 knockdown on the proliferation and migration abilities of lung cancer cells. Western blotting was used to measure the expression levels of related proteins and investigate the regulation of CDC45 on the cell cycle. Finally, in vivo model with subcutaneous injection of lung cancer cells was performed to verify the effect of CDC45 on tumor growth. Results This study identified CDC45 as a key gene potentially influencing tumor stemness and lymph node metastasis. Knockdown of CDC45 not only suppressed the proliferation and migration abilities of lung cancer cells but also caused cell cycle arrest at the G2/M phase. Further analysis revealed a negative correlation between CDC45 and cell cycle-related proteins, stemness-related markers, and tumor mutations. Mouse experiments confirmed that CDC45 knockdown inhibited tumor growth. Conclusion As a novel regulator of stemness, CDC45 plays a role in regulating lung cancer cell proliferation, migration, and cell cycle. Therefore, CDC45 may serve as a potential target for lung cancer treatment and provide a reference for further mechanistic research and therapeutic development.

Introduction: The liver is the only organ capable of full regeneration in mammals. However, the exact mechanism of gut microbiota and metabolites derived from them relating to liver regeneration has not been fully elucidated.Methods: To demonstrate how the gut-liver axis contributes to liver regeneration, using an LC-QTOF/MS-based metabolomics technique, we examine the gut microbiota-derived metabolites in the gut content of C57BL/6J mice at various points after 2/3 partial hepatectomy (PHx). Compound identification, multivariate/univariate data analysis and pathway analysis were performed subsequently. The diversity of the bacterial communities in the gastrointestinal content was measured using 16S rRNA gene sequencing. Then, the integration analysis of gut microbiota and metabolome was performed.Results: After 2/3 PHx, the residual liver proliferated quickly in the first 3 days and had about 90% of its initial weight by the seventh day. The results of PLS-DA showed that a significant metabolic shift occurred at 6 h and 36 h after 2/3 PHx that was reversed at the late phase of liver regeneration. The α and β-diversity of the gut microbiota significantly changed at the early stage of liver regeneration. Specifically, Escherichia Shigella, Lactobacillus, Akkermansia, and Muribaculaceae were the bacteria that changed the most considerably during liver regeneration. Further pathway analysis found the most influenced co-metabolized pathways between the host and gut bacteria including glycolysis, the TCA cycle, arginine metabolism, glutathione metabolism, tryptophan metabolism, and purine and pyrimidine metabolism. Specifically, steroid hormone biosynthesis is the most significant pathway of the host during liver regeneration.Discussion: These findings revealed that during liver regeneration, there was a broad modification of gut microbiota and systemic metabolism and they were strongly correlated. Targeting specific gut bacterial strains, especially increasing the abundance of Akkermansia and decreasing the abundance of Enterobacteriaceae, may be a promising beneficial strategy to modulate systemic metabolism such as amino acid and nucleotide metabolism and promote liver regeneration.

ObjectiveBy utilizing machine learning, we can identify genes that are associated with recurrence, invasion, and tumor stemness, thus uncovering new therapeutic targets.MethodsTo begin, we obtained a gene set related to recurrence and invasion from the GEO database, a comprehensive gene expression database. We then employed the Weighted Gene Co-expression Network Analysis (WGCNA) to identify core gene modules and perform functional enrichment analysis on them. Next, we utilized the random forest and random survival forest algorithms to calculate the genes within the key modules, resulting in the identification of three crucial genes. Subsequently, one of these key genes was selected for prognosis analysis and potential drug screening using the Kaplan-Meier tool. Finally, in order to examine the role of CDC20 in lung adenocarcinoma (LUAD), we conducted a variety of in vitro and in vivo experiments, including wound healing assay, colony formation assays, Transwell migration assays, flow cytometric cell cycle analysis, western blotting, and a mouse tumor model experiment.ResultsFirst, we collected a total of 279 samples from two datasets, GSE166722 and GSE31210, to identify 91 differentially expressed genes associated with recurrence, invasion, and stemness in lung adenocarcinoma. Functional enrichment analysis revealed that these key gene clusters were primarily involved in microtubule binding, spindle, chromosomal region, organelle fission, and nuclear division. Next, using machine learning, we identified and validated three hub genes (CDC45, CDC20, TPX2), with CDC20 showing the highest correlation with tumor stemness and limited previous research. Furthermore, we found a close association between CDC20 and clinical pathological features, poor overall survival (OS), progression-free interval (PFI), progression-free survival (PFS), and adverse prognosis in lung adenocarcinoma patients. Lastly, our functional research demonstrated that knocking down CDC20 could inhibit cancer cell migration, invasion, proliferation, cell cycle progression, and tumor growth possibly through the MAPK signaling pathway.ConclusionCDC20 has emerged as a novel biomarker for monitoring treatment response, recurrence, and disease progression in patients with lung adenocarcinoma. Due to its significance, further research studying CDC20 as a potential therapeutic target is warranted. Investigating the role of CDC20 could lead to valuable insights for developing new treatments and improving patient outcomes.

Major depression is a complex psychiatric disorder that includes genetic, neurological, and cognitive factors. Early detection and intervention can prevent progression, and help select the best treatment. Traditional clinical diagnosis tends to be subjective and misdiagnosed. Based on this, this study leverages clinical scale assessments and sequencing data to construct disease prediction models. Firstly, data undergoes preprocessing involving normalization and other requisite procedures. Feature engineering is then applied to curate subsets of features, culminating in the construction of a model through the implementation of machine learning and deep learning algorithms. In this study, 18 features with significant differences between patients and healthy controls were selected. The depression recognition model was constructed by deep learning with an accuracy of 87.26 % and an AUC of 91.56 %, which can effectively distinguish patients with depression from healthy controls. In addition, 33 features selected by recursive feature elimination method were used to construct a prognostic effect model of patients after 2 weeks of treatment, with an accuracy of 75.94 % and an AUC of 83.33 %. The results show that the deep learning algorithm based on clinical and sequencing data has good accuracy and provides an objective and accurate method for the diagnosis and pharmacodynamic prediction of depression. Furthermore, the selected differential features can serve as candidate biomarkers to provide valuable clues for diagnosis and efficacy prediction.

This study uses an icing model, combining heat transfer with fluid flow and considering the roughness effect, to investigate the influence of liquid water content (LWC) and droplet median volume diameter (MVD) on the ice distribution and anti-icing heat estimation of a wind turbine blade airfoil through the numerical approach. The findings indicate that the simulated ice distribution can have excellent agreement with experimental data. Owing to variations of droplet collection efficiency and heat flux, the increase in LWC and MVD will amplify the fluctuations in ice accretion distribution, which will be prone to ice horns. Owing to high LWC increasing water film flow range, the jumping point of anti-icing heat flux is closer to the trailing edge. Owing to large MVD increasing droplet collection efficiency, the quantity of ice accumulation through solidification ascends to demand higher anti-icing heat flux. The peak anti-icing heat flux is more evidently influenced by LWC than that by MVD, due to the variations in heat flux, induced by water film evaporation and solidification. The findings offer valuable insights into the flow and heat transfer physics for wind turbine anti/de-icing design.

Abstract A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model, treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs) were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (vFAOs). Consistently, treatment with arecoline reduced the expression of CD31 in vFAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

Abstract This cross-sectional study aims to investigate the prevalence and causes of visual impairment (VI) and blindness in Jiangsu Province, China in 2022 during the COVID-19 pandemic. Participants (n = 13,208, aged 18–93) underwent comprehensive ocular examinations. The prevalence and causes of binocular VI (presenting visual acuity [VA] ≥ 20/400 and

There is a growing demand for tea harvesting robots due to the harsh harvesting environment and rising in labor costs. Despite considerable efforts by the research community, the robustness to hilly field environment and the harvesting efficiency of the device in mechanical harvesting of bulk tea remain unimproved. To lay the foundation for automated tea harvesting, this paper proposes an integrated system of bulk tea harvesting robots with autonomous profiling logic based on computer vision. A saliency detection algorithm is applied to detect tender leaves, and a target localization system is designed with it. Moreover, a depth cue-based profiling logic and the corresponding pose adjustment strategy for cutting tool are detailed. And an actuator driven by a combination of motors is developed to provide a precise and flexible motion control to the cutting tool. Additionally, the standard position of the RGB-D camera, accuracy and timeliness of the profiling operation are confirmed by the field experiment. The results of field experiment show that the average harvesting accuracy is 87.7%, and failure rate is controlled within 15%. An analysis of failure causes reveals that damage and cutting failure are the primary reasons for the unsuccessful harvesting.

Abstract Objection Investigating the key genes and mechanisms that influence stemness in lung adenocarcinoma. Methods First, consistent clustering analysis was performed on lung adenocarcinoma patients using stemness scoring to classify them. Subsequently, WGCNA was utilized to identify key modules and hub genes. Then, machine learning methods were employed to screen and identify the key genes within these modules. Lastly, functional analysis of the key genes was conducted through cell scratch assays, colony formation assays, transwell migration assays, flow cytometry cell cycle analysis, and xenograft tumor models. Results First, two groups of patients with different stemness scores were obtained, where the high stemness score group exhibited poor prognosis and immunotherapy efficacy. Next, LASSO regression analysis and random forest regression were employed to identify genes (PBK, RACGAP1) associated with high stemness scores. RACGAP1 was significantly upregulated in the high stemness score group of lung adenocarcinoma and closely correlated with clinical pathological features, poor overall survival (OS), recurrence-free survival (RFS), and unfavorable prognosis in lung adenocarcinoma patients. Knockdown of RACGAP1 suppressed the migration, proliferation, and tumor growth of cancer cells. Conclusion RACGAP1 not only indicates poor prognosis and limited immunotherapy benefits but also serves as a potential targeted biomarker influencing tumor stemness.

Abstract Background The occurrence of epithelial-mesenchymal transition (EMT) and immune evasion is considered to contribute to poor prognosis in lung adenocarcinoma (LUAD). Therefore, this study aims to explore the key oncogenes that promote EMT and immune evasion and reveal the expression patterns, prognostic value, and potential biological functions. Methods Firstly, we identified gene modules associated with EMT and Tumor Immune Dysfunction and Exclusion (TIDE) through weighted gene co-expression network analysis (WGCNA). Next, we utilized differential analysis and machine learning to identify the key genes and validate them. Moreover, we analyzed the correlation between key genes and tumor microenvironment remodeling, drug sensitivity, as well as mutation frequency. Furthermore, we explored and validated their malignant biological characteristics through in vitro experiments and clinical samples. Finally, potential drugs for LUAD were screened based on CMap and validated through experiments. Results Firstly, WGCNA analysis revealed that red and green modules were highly correlated with EMT and TIDE. Among them, upregulated expression of SPOCK1 was observed in lung adenocarcinoma tissues and was associated with poor prognosis. Additionally, patients in the high SPOCK1 group showed more activation of malignant oncogenic pathways, higher infiltration of immunosuppressive components, and a higher frequency of mutations. The knockdown of SPOCK1 suppressed invasion and metastasis capabilities of lung adenocarcinoma cells, and the high expression of SPOCK1 was associated with low infiltration of CD8+ T cells. Therapeutic aspects, SPOCK1 can be a candidate indicator for drug sensitivity and CMap showed that VER-155008 was the drug candidate with the largest perturbation effect on the SPOCK1 expression profile. In vitro and in vivo experiments validated the cancer-inhibitory effect of VER-155008 in LUAD. Conclusion This study revealed through comprehensive bioinformatics analysis and experimental analysis that SPOCK1 can promote EMT and immune escape in LUAD, and it may serve as a promising candidate prognostic biomarker and therapeutic target for LUAD.

Pulmonary immune system, constituted with innate immune and adaptive immune, defenses against pathogens, eliminates senescent cells, and maintains pulmonary physiological homeostasis. The physiological changes in immune system were known as “immune senescence” with increasing age, characterized by increased susceptibility to infection and cancer, reduced response to vaccines, and accompanied by chronic low-grade inflammation. T lymphocytes, B lymphocytes and NK cell immune senescence are the main phenotype of immune senescence. T lymphocytes senescence characterized by immune deficiency and inflammation, caused by thymus degeneration, mitochondrial dysfunction, genetic and epigenetic changes, protein homeostasis imbalance with increasing age. B lymphocytes senescence phenotype is mainly manifested with the decrease of B lymphocytes quantity and quality, and the deficiency in transformation and recombination with increasing age. Meanwhile, with increasing age, NK cells showed changes in cell function, number of cells, and proportion of NK cell subsets. In recent years, a large number of studies have found that the above immune aging changes with increasing age promoted occurrence and development of pulmonary diseases, especially chronic obstructive pulmonary disease (COPD), lung cancer. Even more, there were new therapeutic approach that target to “immunosenescence” have been developed clinically, such as immunotherapy for patients with COPD and lung cancer. However, there are some confusion about the regulatory mechanism of immune senescence in lung diseases and clinical real world. Therefore, this article reviews immune aging, mechanisms of immune aging in the development and progression of lung diseases, mainly included COPD, lung cancer, as well as current immunotherapy targeting to immune senescence, problems, and future directions.

PurposeThis study investigates the impact of elastic improvements to the artificial ankle joint insert on prosthesis biomechanics to reduce the risk of prosthesis loosening in TAR patients.MethodsCT data of the right ankle was collected from one elderly female volunteer. An original TAR model (Model A) was developed from CT images and the INBONE II implant system. The development of the new inserts adopts an elastic improvement design approach, where different geometric configurations of flexible layers are inserted into the traditional insert. The structure can be divided into continuous flexible layers and intermittent flexible layers. The flexible layers aim to improve the elasticity of the component by absorbing and dispersing more kinetic energy. The newly designed inserts are used to replace the original insert in Model A, resulting in the development of Models B-D. A finite element model of gait analysis was based by gait parameters. Discrepancies in micromotion and contact behaviour were analysed during the gait cycle, along with interface fretting and articular surface stress at 50% of the gait cycle.ResultsIn terms of micromotion, the improved elastic models showed reduced micromotion at the tibial-implant interfaces compared to the original model. The peak average micromotion decreased by 12.1%, 13.1%, and 14.5% in Models B, C, and D, respectively. The micromotion distribution also improved in the improved models, especially in Model D. Regarding contact areas, all models showed increased contact areas of articular surfaces with axial load, with Models B, C, and D increasing by 26.8%, 23.9%, and 24.4%, respectively. Contact stress on articular surfaces increased with axial load, reaching peak stress during the late stance phase. Models with continuous flexible layer designs exhibited lower stress levels. The insert and the talar prosthetic articular surfaces showed more uniform stress distribution in the improved models.ConclusionImproving the elasticity of the insert can enhance component flexibility, absorb impact forces, reduce micromotion, and improve contact behavior. The design scheme of continuous flexible layers is more advantageous in transmitting and dispersing stress, providing reference value for insert improvement.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers of human, the tumor-related death of which ranks third among the common malignances. N6­methyladenosine (m6A) methylation, the most abundant internal modification of RNA in mammals, participates in the metabolism of mRNA and interrelates with ncRNAs. In this paper, we overviewed the complex function of m6A regulators in HCC, including regulating the tumorigenesis, progression, prognosis, stemness, metabolic reprogramming, autophagy, ferroptosis, drug resistance and tumor immune microenvironment (TIME). Furthermore, we elucidated the interplay between m6A modification and non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Finally, we summarized the potential of m6A regulators as diagnostic biomarkers. What’s more, we reviewed the inhibitors targeting m6A enzymes as promising therapeutic targets of HCC. We aimed to help understand the function of m6A methylation in HCC systematically and comprehensively so that more effective strategies for HCC treatment will be developed.

Aeration is an important factor to regulate composting efficiency and nitrogen loss. This study is aimed to compare the effects of different aeration modes (continuous and intermittent) and aeration rate on nitrogen conversion and bacterial community in composting from dehydrated sludge and corn straw. Results showed that the intermittent aeration mode at same aeration volume was superior to the continuous aeration mode in terms of NH3 emission reduction, nitrogen conversion and germination index (GI) improvement. Intermittent aeration mode with 1200 L/h (aeration 5 min, stop 15 min) [K5T15 (V1200)] and 300 L/h of continuous aeration helped to the conservation of nitrogen fractions and accelerate the composting process. However, it was most advantageous to use 150 L/h of continuous aeration to reduce NH3 emission and ensure the effective composting process. The aeration mode K5T15 (V1200) showed the fastest temperature rise, the longer duration of thermophilic stage and the highest GI (95%) in composting. The cumulative NH3 emission of intermittent aeration mode was higher than continuous aeration mode. The cumulative NH3 emission of V300 was 23.1% lower than that of K5T15 (V1200). The dominant phyla in dehydrated sludge and corn straw composting were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. The dominant phylum in the thermophilic stage was Firmicutes (49.39%~63.13%), and the dominant genus was Thermobifida (18.62%~30.16%). The relative abundance of Firmicutes was greater in the intermittent aeration mode (63.13%) than that in the continuous aeration mode (57.62%), and Pseudomonas was dominant in composting with lower aeration rate and the lowest NH3 emission. This study suggested that adjustment to the aeration mode and rate could affect core bacteria to reduce the nitrogen loss and accelerate composting process.

Abstract Organ regeneration necessitates precise coordination of accelerators and brakes to restore organ function. However, the mechanisms underlying this intricate molecular crosstalk remain elusive. In this study, the level of proenkephalin-A (PENK-A), expressed by renal proximal tubular epithelial cells, decreases significantly with the loss of renal proximal tubules and increased at the termination phase of zebrafish kidney regeneration. Notably, this change contrasts with the role of hydrogen peroxide (H2O2), which acts as an accelerator in kidney regeneration. Through experiments with penka mutants and pharmaceutical treatments, we demonstrate that PENK-A inhibits H2O2 production in a dose-dependent manner, suggesting its involvement in regulating the rate and termination of regeneration. Furthermore, H2O2 influences the expression of tcf21, a vital factor in the formation of renal progenitor cell aggregates, by remodeling H3K4me3 in renal cells. Overall, our findings highlight the regulatory role of PENK-A as a brake in kidney regeneration.

Abstract Background Porous cages are considered a promising alternative to high-density cages because their interconnectivity favours bony ingrowth and appropriate stiffness tuning reduces stress shielding and the risk of cage subsidence. Methods This study proposes three approaches that combine macroscopic topology optimization and micropore design to establish three new types of porous cages by integrating lattices (gyroid, Schwarz, body-centred cubic) with the optimized cage frame. Using these three porous cages along with traditional high-density cages, four ACDF surgical models were developed to compare the mechanical properties of facet articular cartilage, discs, cortical bone, and cages under specific loads. Results The facet joints in the porous cage groups had lower contact forces than those in the high-density cage group. The intervertebral discs in all models experienced maximum stress at the C5/6 segment. The stress distribution on the cortical bone surface was more uniform in the porous cage groups, leading to increased average stress values. The gyroid, Schwarz, and BCC cage groups showed higher average stress on the C5 cortical bone. The average stress on the surface of porous cages was higher than that on the surface of high-density cages, with the greatest difference observed under the lateral bending condition. The BCC cage demonstrated favourable mechanical stability. Conclusion The new porous cervical cages satifies requirements of low rigidity and serve as a favourable biological scaffold for bone ingrowth. This study provides valuable insights for the development of next-generation orthopaedic medical devices.

Abstract Background N6-methyladenosine (m6A) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development of diseases. However, their significance in pulpitis remains largely unknown. Here, we sought to identify and validate the m6A RNA regulatory network in pulpitis. Methods Gene expression data for m6A regulators in human pulpitis and normal pulp tissues from public GEO databases were analyzed. Bioinformatics analysis including Gene ontology (GO) functional, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed by R package, and Cytoscape software was used to study the role of m6A miRNA-mRNA regulatory network in pulpitis. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of key m6A regulators in collected human pulpitis specimens. Results Differential genes between pulpitis and normal groups were found from the GEO database, and further analysis found that there were significant differences in the m6A modification-related genes ALKBH5, METTL14, METTL3, METTL16, RBM15B and YTHDF1. And their interaction relationships and hub genes were determined. The hub m6A regulator targets were enriched in immune cells differentiation, glutamatergic synapse, ephrin receptor binding and osteoclast differentiation in pulpitis. Validation by qRT-PCR showed that the expression of methylases METTL14 and METTL3 was decreased, thus these two genes may play a key role in pulpitis. Conclusion Our study identified and validated the m6A RNA regulatory network in pulpitis. These findings will provide valuable resource to guide the mechanistic and therapeutic analysis of the role of key m6A modulators in pulpitis.

Ion conductive membranes (ICMs) with highly conductive proton selectivity are of significant importance and greatly desired for energy storage devices. However, it is extremely challenging to construct fast proton-selective transport channels in ICMs. Herein, a membrane with highly conductive proton selectivity was fabricated by incorporating porous carbon sieving nanospheres with a hollow structure (HCSNs) in a polymer matrix. Due to the precise ion sieving ability of the microporous carbon shells and the fast proton transport through their accessible internal cavities, this advanced membrane presented a proton conductivity (0.084 S·cm−1) superior to those of a commercial Nafion 212 (N212) membrane (0.033 S·cm−1) and a pure polymer membrane (0.049 S·cm−1). The corresponding proton selectivity of the membrane (6.68 × 105 S·min·cm−3) was found to be enhanced by about 5.9-fold and 4.3-fold, respectively, compared with those of the N212 membrane (1.13 × 105 S·min·cm−3) and the pure membrane (1.56 × 105 S·min·cm−3). Low-field nuclear magnetic resonance (LF-NMR) clearly revealed the fast proton-selective transport channels enabled by the HCSNs in the polymeric membrane. The proposed membrane exhibited an outstanding energy efficiency (EE) of 84% and long-term stability over 1400 cycles with a 0.065% capacity decay per cycle at 120 mA·cm−2 in a typical vanadium flow battery (VFB) system.

Abstract Background Anti‐folate drug pemetrexed is a vital chemotherapy medication for non‐small cell lung cancer (NSCLC). Its response varies widely and often develops resistance to the treatment. Therefore, it is urgent to identify biomarkers and establish models for drug efficacy evaluation and prediction for rational drug use. Methods A total of 360 subjects were screened and 323 subjects were recruited. Using metabolomics in combination with machine learning methods, we are trying to select potential biomarkers to diagnose NSCLC and evaluate the efficacy of pemetrexed in treating NSCLC. Furtherly, we measured the concentration of eight metabolites in the tryptophan metabolism pathway in the validation set containing 201 subjects using a targeted metabolomics method with UPLC‐MS/MS. Results In the discovery set containing 122 subjects, the metabolic profile of healthy controls (H), newly diagnosed NSCLC patients (ND), patients who responded well to pemetrexed treatment (S) and pemetrexed‐resistant patients (R) differed significantly on the PLS‐DA scores plot. Pathway analysis showed that glycine, serine and threonine metabolism occurred in every two group comparisons. TCA cycle, pyruvate metabolism and glycerolipid metabolism are the most significantly changed pathways between ND and H group, pyruvate metabolism was the most altered pathway between S and ND group, and tryptophan metabolism was the most changed pathway between S and R group. We found Random forest method had the maximum area under the curve (AUC) and can be easily interpreted. The AUC is 0.981 for diagnosing patients with NSCLC and 0.954 for evaluating pemetrexed efficiency. Conclusion We compared eight mathematical models to evaluate pemetrexed efficiency for treating NSCLC. The Random forest model established with metabolic markers tryptophan, kynurenine and xanthurenic acidcan accurately diagnose NSCLC and evaluate the response of pemetrexed.

Water shortages are serious in northwest China due to the level of social and economic development, engineering, resource shortages, and other factors being restricted, so the conflict between supply and demand for water resources is prominent in different regions and different water use sectors. Therefore, Pingliang City was selected as the research object in this study. The membership function was introduced, and an interactive algorithm to correct model parameters based on the fairness constraint was derived. An uncertain multi-objective fuzzy programming model was also established. The results show that the optimal allocation of water will be 38,051.9~40,740 × 104 m3 and 39,938.4~41,317.5 × 104 m3 under a normal year (p = 50%) and a dry year (p = 75%) in 2025, respectively, and the corresponding water shortage rates will be 4.2% and 6.7%. In 2035, the optimal water allocation will be 45,644.1~49,245.9 × 104 m3 and 46,442.4~50,044.2 × 104 m3 and the water shortage rates will be 7.0% and 7.0%, respectively. The proportion of groundwater supply will decrease by 8.8% and 13.8% in 2025 and 2035 after the optimal allocation, the proportion of surface water supply will increase by 9.6% and 12.2%, and the proportion of reclaimed water will increase by −0.78% and 2.1%, respectively. The results can provide a technical reference for the development and utilization of water resources in other cities and similar areas in semi-arid regions.

BackgroundOlder patients with cancer experience cognitive impairment and a series of neurocognitive symptoms known as chemobrain due to chemotherapy. Moreover, older populations are disproportionately affected by chemobrain and heightened negative mental health outcomes after cytotoxic chemical drug therapy. Chinese acupuncture is an emerging therapeutic option for chemotherapy-induced cognitive impairment in older patients with cancer, despite limited supporting evidence. ObjectiveOur study aims to directly contribute to the existing knowledge of this novel Chinese medicine mode in older patients with cancer enrolled at the Department of Oncology/Chinese Medicine, Nanjing First Hospital, China, thereby establishing the basis for further research. MethodsThis study involves a 2-arm, prospective, randomized, assessor-blinded clinical trial in older patients with cancer experiencing chemobrain-related stress and treated with Chinese acupuncture from September 30, 2023, to December 31, 2025. We will enroll 168 older patients with cancer with clinically confirmed chemobrain. These participants will be recruited through screening by oncologists for Chinese acupuncture therapy and evaluation. Electroacupuncture will be performed by a registered practitioner of Chinese medicine. The electroacupuncture intervention will take about 30 minutes every session (2 sessions per week over 8 weeks). For the experimental group, the acupuncture points are mainly on the head, limbs, and abdomen, with a total of 6 pairs of electrically charged needles on the head, while for the control group, the acupuncture points are mainly on the head and limbs, with only 1 pair of electrically charged needles on the head. ResultsEligible participants will be randomized to the control group or the experimental group in 1:1 ratio. The primary outcome of this intervention will be the scores of the Montreal Cognitive Assessment. The secondary outcomes, that is, attentional function and working memory will be determined by the Digit Span Test scores. The quality of life of the patients and multiple functional assessments will also be evaluated. These outcomes will be measured at 2, 4, 6, and 8 weeks after the randomization. ConclusionsThis efficacy trial will explore whether Chinese electroacupuncture can prevent chemobrain, alleviate the related symptoms, and improve the quality of life of older patients with cancer who are undergoing or are just going to begin chemotherapy. The safety of this electroacupuncture intervention for such patients will also be evaluated. Data from this study will be used to promote electroacupuncture application in patients undergoing chemotherapy and support the design of further real-world studies. Trial RegistrationClinicalTrials.gov NCT05876988; https://clinicaltrials.gov/ct2/show/NCT05876988 International Registered Report Identifier (IRRID)DERR1-10.2196/53853

Tamoxifen (TAM) resistance remains a major obstacle in the treatment of advanced breast cancer (BCa). In addition to the competitive inhibition of the estrogen receptor (ER) signaling pathway, damping of mitochondrial function by increasing reactive oxygen species (ROS) is critical for enhancing TAM pharmacodynamics. Here, we showed that RelB contributes to TAM resistance by inhibiting TAM-provoked ferroptosis. TAM-induced ROS level promoted ferroptosis in TAM-sensitive cells, but the effect was alleviated in TAM-resistant cells with high constitutive levels of RelB. Mechanistically, RelB inhibited ferroptosis by transcriptional upregulating glutathione peroxidase 4 (GPX4). Consequently, elevating RelB and GPX4 in sensitive cells increased TAM resistance, and conversely, depriving RelB and GPX4 in resistant cells decreased TAM resistance. Furthermore, suppression of RelB transcriptional activation resensitized TAM-resistant cells by enhancing ferroptosis in vitro and in vivo. The inactivation of GPX4 in TAM-resistant cells consistently resensitized TAM by increasing ferroptosis-mediated cell death. Together, this study uncovered that inhibition of ferroptosis contributes to TAM resistance of BCa via RelB-upregulated GPX4.

IntroductionApplication of organic fertilizers affects soil properties and microbial communities, which in turn alters soil N transformation processes. Unfortunately, it is not clear how the difference in the character of the organic fertilizer DOM affects the soil nitrogen retention capacity and its microbial processes.MethodsAccording to the principle of equal nutrients, the treatments of chemical fertilizer alone (treatment CF), chemical fertilizer with organic fertilizer DOM hydrophilic components (treatment H), and chemical fertilizer with organic fertilizer DOM hydrophobic components (treatment P) were set up, where the characteristics of soil nitrogen transformation and changes in microbial community structure were studied with soil culture conditions for 24 days.ResultsIt was discovered that the addition of organic fertilizer DOM components (H and P) slowed nitrification rate and increased protease activity resulting in a higher NH4+-N content compared to the CF treatment. The DOM addition (H and P) increased the microbial biomass nitrogen (MBN) levels in the soil and increased the soil nitrogen pool capacity.ConclusionsMoreover, the carbon use efficiency of the hydrophilic components is higher than that of the hydrophobic components, resulting in its further increase in nitrogen reservoir capacity and higher nitrogen retention capacity. Network analysis showed that the addition of organic fertilizer DOM hydrophilic components increased network complexity and synergy between microorganisms. In combination with random forest analysis, it was shown that Sphingomonas and Massilia were key species influencing soil nitrogen retention capacity and nitrogen availability characteristics.

Humic acids (HA) are a popular soil additive to reduce metal availability, but they have the drawbacks of reduced effectiveness over time and a significant reduction in soil pH. An alkaline humic acid fertilizer (AHAF) combining alkaline additives with HA was developed to overcome such drawbacks. A field experiment was conducted to investigate the effects of different AHAF application rates on the physicochemical properties, bioavailability, accumulation, and translocation of Cd and Zn heavy metals in Sauropus androgynus grown in acidic soil. Based on our results, the 100AF (100% AHAF) treatment significantly increased soil pH, cation exchange capacity (CEC), and organic matter content (OM) after one year of application. Compared with the control treatment (CK), the application of different rates of AHAF resulted in a 37.1–40.3% decrease in soil exchangeable Cd fractions (Exc-Cd) and an increase in the humic acid-bound Cd fractions (HA-Cd) Fe- and Mn-oxide-bound Cd fractions (OX-Cd), and organic matter-bound Cd fractions (OM-Cd) by 9.5–64.6%, 24.8–45.1%, and 158.8–191.2%, respectively (P Stems > Branches > Roots > Edible branches; (Zn) Roots > Stems > Leaves > Branches > Edible branches. The transfer factors (TFs) of Cd and Zn in S. androgynus were classified as follows: TF2 > TF1 > TF3 > TF4. Thus, S. androgynus stems, and roots had a strong ability to transport Cd and Zn to the leaves. Compared with CK, the 100AF treatment significantly increased the BCFs for Zn in all plant parts (except BCFedible branches). In contrast, it significantly decreased all BCFs and TFs for Cd and the TF4 for Zn, effectively reducing Cd and Zn accumulation in the edible branches of S. androgynus. Soil pH, CEC, OM, and HA-M fraction were highly and significantly negatively correlated with Cd and Zn content in edible branches (P

ABSTRACTPeripheral β-amyloid (Aβ), including those contained in the gut, may contribute to the formation of Aβ plaques in the brain, and gut microbiota appears to exert an impact on Alzheimer’s disease (AD) via the gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused on uncovering the potential interactions among gut-derived Aβ in aging, gut microbiota, and AD pathogenesis. To achieve this goal, the expression levels of Aβ and several key proteins involved in Aβ metabolism were initially assessed in mouse gut, with key results confirmed in human tissue. The results demonstrated that a high level of Aβ was detected throughout the gut in both mice and human, and gut Aβ42 increased with age in wild type and mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, the gut microbiome of mice was characterized by 16S rRNA sequencing, and we found the gut microbiome altered significantly in aged APP/PS1 mice and fecal microbiota transplantation (FMT) of aged APP/PS1 mice increased gut BACE1 and Aβ42 levels. Intra-intestinal injection of isotope or fluorescence labeled Aβ combined with vagotomy was also performed to investigate the transmission of Aβ from gut to brain. The data showed that, in aged mice, the gut Aβ42 was transported to the brain mainly via blood rather than the vagal nerve. Furthermore, FMT of APP/PS1 mice induced neuroinflammation, a phenotype that mimics early AD pathology. Taken together, this study suggests that the gut is likely a critical source of Aβ in the brain, and gut microbiota can further upregulate gut Aβ production, thereby potentially contributing to AD pathogenesis.

Abstract. With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.

Abstract Objective To identify DNA methylation and clinical features, and to construct machine learning classifiers to assign the patients with major depressive disorder (MDD) into responders and non-responders after a 2-week treatment into responders and non-responders. Method Han Chinese patients (291 in total) with MDD comprised the study population. Datasets contained demographic information, environment stress factors, and the methylation levels of 38 methylated sites of tryptophan hydroxylase 2 (TPH2) genes in peripheral blood samples. Recursive Feature Elimination (RFE) was employed to select features. Five classification algorithms (logistic regression, classification and regression trees, support vector machine, logitboost and random forests) were used to establish the models. Performance metrics (AUC, F-Measure, G-Mean, accuracy, sensitivity, specificity, positive predictive value and negative predictive value) were computed with 5-fold-cross-validation. Variable importance was evaluated by random forest algorithm. Result RF with RFE outperformed the other models in our samples based on the demographic information and clinical features (AUC = 61.2%, 95%CI: 60.1-62.4%) / TPH2 CpGs features (AUC = 66.6%, 95%CI: 65.4-67.8%) / both clinical and TPH2 CpGs features (AUC = 72.9%, 95%CI: 71.8-74.0%). Conclusion The effects of TPH2 on the early-stage antidepressant response were explored by machine learning algorithms. On the basis of the baseline depression severity and TPH2 CpG sites, machine learning approaches can enhance our ability to predict the early-stage antidepressant response. Some potentially important predictors (e.g., TPH2-10-60 (rs2129575), TPH2-2-163 (rs11178998), age of first onset, age) in early-stage treatment response could be utilized in future fundamental research, drug development and clinical practice.

Abstract Iron gall inks consist of vitriols (sulphates of certain metals), gall nut extracts; and gum Arabic: after exposure to oxygen, dark-colored compounds of the inks are formed. As the complexity of the composition of iron gall inks renders documents susceptible to environmental influences, this causes the handwriting thereon to fade. These add technical difficulties to the protection of iron gall inks. Therefore, it is particularly important to understand the changes in the inks during the aging process. For this reason, iron gall ink-stained paper specimens were subject to an intense analytical program to investigate their chemical and physical modifications after aging (temperature/humidity, temperature, and ultraviolet light aging), commercial iron gall ink was used for this experiment, making the study more applicable. The changes of iron gall inks were evaluated using color variation, color density, absorbance, and X-ray photoelectron spectroscopy (XPS). All results indicate that the temperature, humidity, and UV are harmful to the inks in both physical and chemical terms. Physical damage is mainly the aging of the ink color lightening, color density decreases, of which the color of the samples treated with damp heat for 30 days undergoes the greatest change. The chemical change is represented by the ratio of the concentration of iron ions in different valence states, the amount of Fe3+ in the untreated inks is much greater than that of Fe2+, and the amount of Fe2+ exceeds that of Fe3+ after exposure to different methods of aging. Experiments show that UV light causes the most severe damage to handwriting. The main manifestation thereof is color-fade and the paper surface ink part of the iron ion content changes, with the increase of aging time, the Fe2+ content gradually increases. This experimental study of the changes produced by iron gall inks during aging can provide better technical support for the protection of the ink handwriting.

Wall bushing is the core insulator of 40.5 kV air insulation switchgear, and its insulation performance determines the insulation level and service life of the switchgear. Wall bushing often appears partial discharge, insulation aging, grounded breakdown, and other problems after a period of operation. The main reason is the partial discharge of the equipotential line for the wall bushing. In this paper, the influence of the wall bushing equipotential line on the electric field distribution is systematically analyzed to improve the operating reliability and service life of the 40.5 kV wall bushing. Based on the electric field simulation of the equipotential line, the feasibility of the traditional live detection method is given. The characteristic gas detection method is proposed through air electrolysis, thermal decomposition, early warning of the development trend of the internal suspension defect state. Finally, it proposes corresponding preventive measures to avoid the development of internal suspension defect of wall bushing into a sudden grounding, and ensure the reliability of the system operation.

Abstract The transport of fluid and ions across nanotubes or nanochannels has attracted great attention due to the ultrahigh energy power density and slip length, with applications in water purification, desalination, energy conversion and even ion-based neuromorphic computing. Investigation on individual nanotube or nanochannel is essential in revealing the fundamental mechanism as well as demonstrating the property unambiguously. Surprisingly, while carbon nanotube is the pioneering and one of the most attractive systems for nanofluidics, study on its response and performance under osmotic forcing is lacking. Here, we measure the osmotic energy conversion for individual double-walled carbon nanotube with an inner radius of 2.3 nm. By fabricating a nanofluidic device using photolithography, we find a giant power density (up to 22.5 kW/m2) for the transport of KCl, NaCl, and LiCl solutions across the tube. Further experiments show that such an extraordinary performance originates from the ultrahigh slip lengths (up to a few micrometers). Our results suggest that carbon nanotube is a good candidate for not only ultrafast transport, but also osmotic power harvesting under salinity gradients.

Abstract Background Gastrointestinal stromal tumors (GISTs) are the prevailing sarcomas of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) therapy, exemplified by Imatinib mesylate (IM), constitutes the established adjuvant therapy for GISTs. Nevertheless, post-treatment resistance poses a challenge that all patients must confront. The presence of tumor heterogeneity and secondary mutation mechanisms fail to account for some instances of acquired drug resistance. Certain investigations suggest a strong association between tumor drug resistance and mesenchymal stromal cells (MSC) in the tumor microenvironment, but the underlying mechanism remains obscure. Scarce research has explored the connection between GIST drug resistance and the tumor microenvironment, as well as the corresponding mechanism. Methods Immunofluorescence and fluorescence-activated cell sorting (FACS) methodologies were employed to detect the presence of MSC in GIST samples. The investigation encompassed the examination of MSC migration towards tumor tissue and the impact of MSC on the survival of GIST cells under IM treatment. Through ELISA, western blotting, and flow cytometry analyses, it was confirmed that Transforming Growth Factor Beta 2 (TGF-β2) triggers the activation of the PI3K-AKT pathway by MSC, thereby facilitating drug resistance in GIST. Results Our findings revealed a positive correlation between a high proportion of MSC and both GIST resistance and a poor prognosis. In vitro studies demonstrated the ability of MSC to migrate towards GIST. Additionally, MSC were observed to secrete TGF-β2, consequently activating the PI3K-AKT pathway and augmenting GIST resistance. Conclusions Our investigation has revealed that MSC within GISTs possess the capacity to augment drug resistance, thereby highlighting their novel mechanism and offering a promising target for intervention in GIST therapy.

Abstract Background Nasopharyngeal swabs are taken to determine the causative agent of community acquired pneumonia (CAP), while the reliability of upper respiratory tract sampling as a proxy for lower respiratory tract infections is still unclear. Methods Nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid samples and clinical data were collected from 153 hospitalized children between 3 months and 14 years of age with severe CAP, enrolled from March to June 2019. Written informed consent for the storage and use of the samples for further studies was obtained from the parents or caregivers. Putative pathogens were detected using a sensitive, high-throughput GeXP-based multiplex PCR and qPCR. Results The same bacterial species in paired samples were found in 29 (23.4%) and the same viral species in 52 (27.5%) of the patients. moderate concordance was found for Mycoplasma pneumoniae (ĸ=0.64), followed by Haemophilus influenzae (ĸ=0.42). The strongest discordance was observed for human adenovirus and also for Pseudomonas aeruginosa, the latter was exclusively detected in BAL samples. In the adenovirus cases strong concordance was associated with high viral loads in the NP swabs. Conclusion The variation in concordance in pathogen detection in the upper and lower respiratory tract of children with severe pneumonia is generally high but varies depending on the species. Novel and impactful insights are the concordance between NP and BAL detection for M. pneumoniae and H. influenzae and the strong correlation between high adenoviral loads in NP swabs and detection in BAL fluid.

Halogen-free organophosphorus flame retardants have promising application prospects due to their excellent safety and environmental protection properties. A cobalt-coordinated cyclic phosphonitrile flame retardant (Co@CPA) was synthesized via a hydrothermal method using hexachlorocyclotriphosphonitrile (HCCP), 5-amino-tetrazolium (5-AT), and cobalt nitrate hexahydrate (Co(NO3)2∙6H2O) as starting materials. The structure was characterized using Fourier transform infrared (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). Thermoplastic polyurethane (TPU) composites were prepared by incorporating 10-(2,5-dihydroxyphenyl)-9,10-dihydro-9-oxa-10-phosphame-10-oxide (ODOPB), Co@CPA, and silicon dioxide (SiO2) via melt blending. The flame-retardant performance and thermal stability of the TPU composites were evaluated through limiting oxygen index (LOI), vertical combustion (UL-94), TG, and cone calorimetric (CCT) tests. SEM and Raman spectroscopy were used to analyze the surface morphology and structure of the residual carbon. A synergistic flame-retardant effect of ODOPB and Co@CPA was observed, with the most effective flame retardancy achieved at a TPU:ODOPB:Co@CPA:SiO2 ratio of 75:16:8:1. This composition exhibited an LOI value of 26.5% and achieved a V-0 rating in the UL-94 test. Furthermore, compared to pure TPU, the composite showed reductions in total heat release, CO production, and CO2 production by 6.6%, 39.4%, and 48.9%, respectively. Our research findings suggest that Co@CPA demonstrates outstanding performance, with potential for further expansion in application areas. Different metal-based cyclic phosphonitrile compounds are significant in enriching phosphorus-based fine chemicals.

Summary: Depletion of CD8+ T cells is a major obstacle in immunotherapy; however, the relevant mechanisms remain largely unknown. Here, we showed that prostate cancer (PCa) cell-derived exosomes hamper CD8+ T cell function by transporting interleukin-8 (IL-8). Compared to the low IL-8 levels detected in immune cells, PCa cells secreted the abundance of IL-8 and further accumulated in exosomes. The delivery of PCa cell-derived exosomes into CD8+ T cells exhausted the cells through enhanced starvation. Mechanistically, exosomal IL-8 overactivated PPARα in recipient cells, thereby decreasing glucose utilization by downregulating GLUT1 and HK2 but increasing fatty acid catabolism via upregulation of CPT1A and ACOX1. PPARα further activates uncoupling protein 1 (UCP1), leading to fatty acid catabolism for thermogenesis rather than ATP synthesis. Consequently, inhibition of PPARα and UCP1 restores CD8+ T cell proliferation by counteracting the effect of exosomal IL-8. This study revealed that the tumor exosome-activated IL-8-PPARα-UCP1 axis harms tumor-infiltrating CD8+ T cells by interfering with energy metabolism.

This study proposes a novel approach that combines a Quartet Structure Generation Set (QSGS) algorithm with the Lattice Boltzmann Method (LBM) to investigate effective thermal conductivity in plant fiber materials. The QSGS algorithm is utilized to construct a two-dimensional digital structure of the porous media, enabling the determination of effective thermal conductivity through LBM simulations. The simulation results demonstrate good agreement with experimental data, exhibiting a maximum relative error of only 1.7%. The study examines the influence of key factors on effective thermal conductivity, including temperature, porosity, fiber distribution, and fractal dimension. The effective thermal conductivity increased by approximately 6.1% for each 10 °C increase in temperature between 10 °C and 50 °C. Moreover, the effective thermal conductivity showed an average decrease of 16.3% with each 10% increment in porosity. The increase in thermal conductivity becomes more significant with increasing temperature and decreasing porosity. Conversely, an increased fractal dimension correlates with a decline in effective thermal conductivity. The effective thermal conductivity is influenced synergistically by the directional growth probability of the solid phase and the direction of heat flow. The findings offer valuable insights into thermal conductivity behavior and heat transfer mechanisms in plant fiber porous media.

Tracking-by-detection is a popular paradigm for Multi-Object Tracking (MOT), but the problems of unstable tracking and frequent ID transitions still occur due to the low illumination, point light sources, and high dust in the underground coal mine space. In this respect, this paper proposes a Dark-SORT personnel tracking algorithm for downhole environment characteristics. First, a video image enhancement method is designed to enhance the video image quality and improve the localization accuracy of the detector for the dim and unevenly distributed light environment in the well. Second, an Adaptive Discrete-weighted Attention Module (ADAM) is designed, which consists of an Enhanced Discrete Channel Attention (EDCA) module and an Adaptive Discrete Spatial Attention (ADSA) module. EDCA enables the network to capture richer information at different scales by adaptively processing different channels according to their importance and feature scales. The ADSA approach enhances the linkage between different locations within the same region, combines different pooling strategies to highlight important regions, and reduces the focus on overexposed regions. Finally, the OC-SORT tracking algorithm is introduced to solve the error accumulation problem based on the motion model and incorporate the appearance feature information to improve the stability of target tracking. We conducted a comparison test on the self-built dataset MINE-MOT, and the HOTA, MOTA, DetA, AssA, IDF1, AssRe, and FPS metrics of the Dark-SORT tracking algorithm based on the YOLOv7 target detection model were 67.4, 92.6, 80.3, 46.8, 61.7, 65.7, and 23, respectively, which was the best in terms of accuracy and stability of all the models involved in the test.

The power system frequency is an important indicator that reflects the power system’s operating status. Through real-time detection or prediction, it can effectively ensure stable power system operation. To provide a theoretical basis for the steady-state recovery of thepower system after major disturbances, a deep belief neural network model for predicting the power system’s frequency response mode after major disturbances has been proposed. This model combines deep belief networks with deep neural networks. The feature extraction and learning abilities of deep belief networks were utilized to complete model training and learning. Deep neural networks were utilized to complete data classification and prediction. The load sudden variable is larger, the system frequency fluctuation is greater, the inertia time constant increases less, and the system frequency fluctuation is greater. In simulation testing with a training sample size of 2100 and a testing sample size of 900, the deep belief neural network took 3320 seconds, while the deep neural network took 11523 seconds. The prediction results’ absolute error amplitude of this deep belief neural network is 0.025Hz. It meets the practical needs of frequency response mode prediction in power systems after major disturbances. The study analyzed the impact of load sudden changes and inertia time constants on system frequency, and successfully designed a frequency response mode prediction model for power systems after major disturbances.

Agrochemicals are indispensable materials in agricultural production, used to control or prevent diseases, insects and weeds, and play important roles in ensuring both food security and food safety. Meanwhile, the negative impacts of modern synthetic pesticides on humans and the environment could not be neglected. Thus, the production, registration, application and monitoring of pesticides should be strictly checked to ensure their commercial product quality and safety to human health as well as to the environment. This review summarizes the analytical chemistry involved in the quality control (QC) analysis for commercial formulation, residue analysis, dietary risk assessment and regulation prospects of pesticides. The main concepts and contents of pesticide analytical chemistry are comprehensively introduced and analyzed. In addition, the requirements and criteria of the relevant guidelines from various organizations are discussed. Finally, the research frontier areas and future trending for the invention of new generation of agrochemicals, registration/enforcement, market monitoring and risk management of pesticides are discussed.

Abstract Background The adverse consequences of medial meniscus posterior root tears have become increasingly familiar to surgeons, and treatment strategies have become increasingly abundant. In this paper, the finite element gait analysis method was used to explore the differences in the biomechanical characteristics of the knee joint under different conditions. Methods Based on CT computed tomography and MR images, (I) an intact knee (IK) model with bone, cartilage, meniscus and main ligaments was established. Based on this model, the posterior root of the medial meniscus was resected, and (ii) the partial tear (PT) model, (iii) the entire radial tear (ERT) model, and (iv) the entire oblique tear (EOT) model were established according to the scope and degree of resection. Then, the (v) meniscus repair (MR) model and (vi) partial meniscectomy (PM) model were developed according to the operation method. The differences in stress, displacement and contact area among different models were evaluated under ISO gait loading conditions. Results Under gait loading, there was no significant difference in the maximum stress of the medial and lateral tibiofemoral joints among the six models. Compared with the medial tibiofemoral joint stress of the IK model, the stress of the PM model increased by 8.3%, while that of the MR model decreased by 18.9%; at the same time, the contact stress of the medial tibiofemoral joint of the ERT and EOT models increased by 17.9 and 25.3%, respectively. The displacement of the medial meniscus in the ERT and EOT models was significantly larger than that in the IK model (P

Abstract Objective To explore the psychological experience of Juvenile patient’s parents in Fangcang shelter hospital during the Omicron wave of COVID-19 pandemic. Methods A qualitative study was conducted by using a phenomenological research method. Sixteen parents of juvenile patients with COVID-19 were recruited from National Exhibition and Convention Center (Shanghai, China) Fangcang shelter hospital (FSH) using purposive sampling. Data were collected by face-to-face in-depth interviews over 27 days, from April 9 to May 6, 2022. The interview data were analyzed using Colaizzi seven-step analysis method. Results The psychological experiences of the parents of juvenile patients in the Fangcang shelter hospital were summarized into three themes: "perception regarding the FSH", "worried about the unmet needs of juvenile patients ", and "the psychological burden after discharge". These themes were classified into 9 sub-themes, including the acceptance of FSH, adaptability to FSH, concerns about cross-infection in the FSH, special needs of infants and young children, psychological needs of preschool children, the learning demands of school-age children, concern about re-positive, fear of sequelae, worry about social acceptance. Conclusion Juvenile patients and their parents in the Fangcang shelter hospitals have both positive and negative experiences. It is suggested that facilities for minors should be planned in advance. Humanistic care for adolescent patients and health education for the public are also critical.

Background The coronavirus disease 2019 (COVID-19) pandemic resulted in radical changes in many aspects of life. To deal with this, each country has implemented continuous health measures from the beginning of the outbreak. Discovering how governmental actions impacted public behaviour during the outbreak stage is the purpose of this study. Methods This study uses a hybrid large-scale data visualisation method to analyse public behaviour (epidemic concerns, self- protection, and mobility trends), using the data provided by multiple authorities. Meanwhile, a content analysis method is used to qualitatively code the health measures of three countries with severe early epidemic outbreaks from different continents, namely China, Italy, and the United States. Eight dimensions are coded to rate the mobility restrictions implemented in the above countries. Results (1) Governmental measures did not immediately persuade the public to change their behaviours during the COVID-19 epidemic. Instead, the public behaviour proceeded in a three-phase rule, which is typically witnessed in an epidemic outbreak, namely the wait-and-see phase, the surge phase and the slow-release phase. (2) The strictness of the mobility restrictions of the three countries can be ranked as follows: Hubei Province in China (with an average score of 8.5 out of 10), Lombardy in Italy (7.125), and New York State in the United States (5.375). Strict mobility restrictions are more likely to cause a surge of population outflow from the epidemic area in the short term, whereas the effect of mobility restrictions is positively related to the stringency of policies in the long term. Conclusion The public showed generally lawful behaviour during regional epidemic outbreaks and blockades. Meanwhile public behaviour was deeply affected by the actions of local governments, rather than the global pandemic situation. The contextual differences between the various countries are important factors that influence the effects of the different governments’ health measures.

Abstract A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Shenzhen. We examined the effect of these measures on the prevalence of respiratory pathogens in children. Clinical and respiratory pathogen data were collected for routine care from hospitalized children with acute respiratory infections in Shenzhen Children’s Hospital from July 2018 to January 2022. Nasopharyngeal swabs were collected and respiratory pathogens were detected using standardized clinical diagnostics as part of routine care. Data were analyzed to describe the effects of COVID-19 prevention procedures on other common pathogens. A total of 56,325 children under 14 years of age were hospitalized with an acute respiratory infection during the study period, 33,909 were tested from July 2018 to January 2020 (pre-lockdown), 1168 from February 2020 to May 2020 (lockdown) and 21,248 from July 2020 to January 2022 (post-lockdown). We observed a 37.3% decline of routine care in respiratory infection associated hospital admission in the 19 months’ post-lockdown vs. the 19 months’ pre-lockdown. There were 99.4%, 16.0% and 1.26% reductions measured for Mycoplasma pneumoniae, influenza virus A and adenovirus, respectively. However, a 118.7% and 75.8% rise was found for respiratory syncytial virus (RSV) and human para-influenza virus (HPIV) during the 19 months’ post-lockdown in comparison to the pre-pandemic period. The detection of RSV especially increased in toddlers after the lockdown. Lockdown measures during the COVID-19 pandemic led to a significant reduction of Mycoplasma pneumoniae, influenza virus A and adenovirus infection. In contrast, RSV and HPIV infection increased.