Search

Abstract As one of the main occupational hazards, welding fumes can cause oxidative damage and induce series of diseases, such as COPD or asthma. To clarify the effects of the metal fume ultrafine particulates (MF-UFPs) of welding fumes on oxidative damage, UFPs were collected by melt inert gas (MIG) and manual metal arc (MMA) welding, and the composition was confirmed. Human bronchial epithelial 16HBE cells were treated with 0–1000 µg/cm2 MF-UFPs to analyse the cytotoxicity, oxidative stress and cytokines. The protein and mRNA expression of Keap1-Nrf-2/antioxidant response elements (AREs) signalling pathway components were also analysed. After 4 h of treatment, the cell viability decreased 25% after 33.85 and 32.81 µg/cm2 MIG/MMA-UFPs treated. The intracellular ATP concentrations were also decreased significantly, while LDH leakage was increased. The decreased mitochondrial membrane potential and increased ROS suggested the occurrence of oxidative damage, and the results of proteome profiling arrays also showed a significant increase in IL-6 and IL-8. The expression of AREs which related to antioxidant and anti-inflammatory were also increased. These results indicate that the MF-UFPs can cause oxidative stress in 16HBE cells and activate the Nrf-2/ARE signalling pathway to against oxidative damage.

Introduction: Patients undergoing hemodialysis (HD) are highly vulnerable during the COVID-19 pandemic. We aimed to investigate the risk factors associated with the severity of COVID-19 and death after the complete liberalization of epidemic control in China. Methods: We followed the outcomes of the HD patients of Central Hospital of Dalian University of Technology, from December 6, 2022, to January 8, 2023. The non-contrast-enhanced chest computed tomography (CT) was performed on all COVID-19-infected hospitalized patients. We recorded the patient’s clinical characteristics, demographic features, vaccination history, treatments, and lung lesions. Odds ratios and 95% confidence intervals were calculated using logistic regression models to identify independent risk factors for COVID-19-related severity and mortality. Results: This study included a total of 858 HD patients, of which 660 were infected with COVID-19. The mean age was (55.61 ± 14.61) years, with a median (interquartile range) dialysis duration of 44.5 (69.5) months. Over half (60%) of the study participants were male, and the majority had hypertension as a comorbidity. Multivariable analysis revealed that age, pre-dialysis diastolic pressure, fever, white blood cell (WBC) count, potassium, β2-microglobulin level, and calcium were independent risk factors for disease severity, while platelets, urea nitrogen, serum chlorine and creatinine were identified as independent protective factors. Furthermore, total iron-binding capacity and vaccination were found to be independent protective factors against mortality, and WBC count was an independent risk factor for in-hospital mortality (p < 0.05). The most frequent CT finding among hospitalized patients with chest symptoms was patchy shadow or pleural effusion, observed in 64.8% of cases. More than half of the patients exhibited bilateral lung lesions, and over 60% involved two or more lobes. Conclusion: The majority of HD patients are susceptible to COVID-19. Demographic, clinical features, and laboratory indicators can be used to predict the severity and mortality associated with COVID-19. Our findings will assist clinicians in identifying markers for the early detection of high mortality risk in HD patients with COVID-19.

Abstract. Background:. Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening. Methods:. We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial. Results:. This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios. Conclusion:. This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

BackgroundNatural pyrethrins have long been widely used in the fields of environmental and household hygiene. Studies have reported that natural pyrethrins have potential liver toxicity, but their specific mechanisms are still unclear yet. ObjectiveTo explore the effect of natural pyrethrins on DNA damage in human liver cells. MethodsThis study used human liver cell QSG7701 as an in vitro testing model. After exposure to DMSO and a series of concentrations of natural pyrethrins (5, 10, 20, and 40 μg·mL−1) for 6 and 24 h, reactive oxygen species (ROS) was detected by fluorescence microscopy using a fluorescence probe, thiobarbituric acid reactive substance (TBARS) by colorimetric method using a microplate reader, DNA damage by comet assay through observing DNA fragment migration under microscope, and phospho H2AX (γH2AX) and 8-oxoguanine (8-oxoG) by immunofluorescence assay using a laser confocal microscope. ResultsAs the exposure concentration of natural pyrethrins increased, the fluorescence intensity of ROS significantly increased in a concentration-dependent manner. The differences in ROS between the 10 μg·mL−1 and above groups and the control group were statistically significant (P

Oxidative stress is a crucial concept in redox biology, and significant progress has been made in recent years. Excessive levels of reactive oxygen species (ROS) can lead to oxidative damage, heightening vulnerability to various diseases. By contrast, ROS maintained within a moderate range plays a role in regulating normal physiological metabolism. Choosing suitable animal models in a complex research context is critical for enhancing research efficacy. While rodents are frequently utilized in medical experiments, they pose challenges such as high costs and ethical considerations. Alternatively, non-rodent model organisms like zebrafish, Drosophila, and C. elegans offer promising avenues into oxidative stress research. These organisms boast advantages such as their small size, high reproduction rate, availability for live imaging, and ease of gene manipulation. This review highlights advancements in the detection of oxidative stress using non-rodent models. The oxidative homeostasis regulatory pathway, Kelch‐like ECH‐associated protein 1-Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2), is systematically reviewed alongside multiple regulation of Nrf2-centered pathways in different organisms. Ultimately, this review conducts a comprehensive comparative analysis of different model organisms and further explores the combination of novel techniques with non-rodents. This review aims to summarize state-of-the-art findings in oxidative stress research using non-rodents and to delineate future directions.

Lung cancer, which is a leading cause of cancer-related deaths worldwide, frequently metastasizes to the bones, significantly diminishing patients’ quality of life and complicating treatment strategies. This study aims to develop an advanced 3D Mask R-CNN model, enhanced with the ConvNeXt-V2 backbone, for the automatic segmentation of bone tumors and identification of lung cancer metastasis to support personalized treatment planning. Data were collected from two hospitals: Center A (106 patients) and Center B (265 patients). The data from Center B were used for training, while Center A’s dataset served as an independent external validation set. High-resolution CT scans with 1 mm slice thickness and no inter-slice gaps were utilized, and the regions of interest (ROIs) were manually segmented and validated by two experienced radiologists. The 3D Mask R-CNN model achieved a Dice Similarity Coefficient (DSC) of 0.856, a sensitivity of 0.921, and a specificity of 0.961 on the training set. On the test set, it achieved a DSC of 0.849, a sensitivity of 0.911, and a specificity of 0.931. For the classification task, the model attained an AUC of 0.865, an accuracy of 0.866, a sensitivity of 0.875, and a specificity of 0.835 on the training set, while achieving an AUC of 0.842, an accuracy of 0.836, a sensitivity of 0.847, and a specificity of 0.819 on the test set. These results highlight the model’s potential in improving the accuracy of bone tumor segmentation and lung cancer metastasis detection, paving the way for enhanced diagnostic workflows and personalized treatment strategies in clinical oncology.

The effective containment of fission products (FPs) within tri-structural isotropic (TRISO) fuel particles is crucial for the safety and efficiency of High Temperature Gas-cooled Reactors (HTGRs). Combining multi-scale (µm to nm) and multi-dimensional (2D and 3D) analysis, this study focuses on the migration mechanisms of silver (Ag), for which the Ag-110 m FP isotope is radiotoxic, facilitated by reactions with palladium (Pd) alloys and the silicon carbide (SiC) layer at elevated temperatures (1300–1500 °C). Three primary pathways for Ag migration are identified: (1) diffusion in solid palladium silicide to form (Pd,Ag)2Si, (2) infiltration through cracks and pores in the carbon phase, and (3) liquid phase migration along SiC grain boundaries. Especially at temperatures above the melting point of Pd2Si (1404 °C), a ‘dissolution-recrystallisation’ mechanism is proposed of the Ag-Pd-Si liquid phase migrating along SiC grain boundaries. The study employs state-of-the-art in-situ heating transmission electron microscopy (TEM) techniques to directly observe the dynamic migration processes of Pd silicide within SiC, providing unprecedented insights into the liquid behaviour in TRISO fuel. These findings highlight the significant role of liquid phases in determining the transport of FPs through the TRISO-SiC which is vital for developing strategies that enhance the safety and efficacy of HTGRs.

This paper briefly summarizes the importance, current situation and existing problems of earthquake science popularization in primary and secondary schools, and focuses on the development path of earthquake science popularization based on STEAM education concept. On the basis of clarifying the main purpose, service target group of earthquake science popularization education, and effective popular science content and form, this paper applies the concept of STEAM education to propose the effective path of earthquake science popularization in primary and secondary schools. Taking the junior high school section as an example to make a specific case analysis, this paper suggests to build an earthquake science popularization ecosystem from the perspective of STEAM education. STEAM education is an interdisciplinary education concept that integrates science, technology, engineering, arts and mathematics, emphasizing the integration of disciplines. It is a new form of learning in which taking projects as the main line, teachers as the lead, and students as the main body. This study argues that STEAM education needs to be integrated into the earthquake science popularization, and a high-quality science education system should be constructed, covering both on- and off-campus educational activities and active learning ability, so as to create an ecosystem suitable for the development of science popularization education.

Abstract Background Circular RNAs (circRNAs) are critical regulators in the progression of tumors. This experimental design aimed to explore the mechanism of circ-10720 in non-small cell lung cancer (NSCLC). Methods We used RT-qPCR to measure circ-10720 expression in clinical samples and analyzed its relationship with the clinicopathological characteristics of NSCLC patients. The expression levels of microRNA-1238 (miR-1238) and Zinc Finger E-box-binding Homeobox 2 (ZEB2) in clinical samples were detected by RT-qPCR. NSCLC cells were transfected with relevant plasmids or sequences. Circ-10720, miR-1238, and ZEB2 expressions in cells were analyzed via RT-qPCR or western blot. Cell proliferation, apoptosis, migration, and invasion were assessed with CCK-8, flow cytometry, and transwell assay, respectively. The protein expression of ZEB2 and epithelial–mesenchymal transition (EMT)-related markers (E-cadherin, Vimentin, N-cadherin) were detected via western blot. Xenograft assay was used to determine the effect of circ-10720 on NSCLC in vivo. Circ-10720 and ZEB2 expressions in tumors were detected using RT-qPCR or Western blot. Immunohistochemistry was used to evaluate E-cadherin and N-cadherin expression in tumors. Finally, the binding relationship between miR-1238 with circ-10720 or ZEB2 was verified by the bioinformatics website, dual luciferase reporter assay, RNA pull-down assay, and RIP assay. Results Circ-10720 was upregulated in NSCLC and correlated with TNM stage of NSCLC patients. MiR-1238 was lowly expressed but ZEB2 was highly expressed in NSCLC. Circ-10720 silencing suppressed the proliferation, metastasis, and EMT of NSCLC cells. Mechanically, circ-10720 was a competitive endogenous RNA (ceRNA) for miR-1238, and ZEB2 was a target of miR-1238. circ-10720-modulated ZEB2 via competitively binding with miR-1238 to control NSCLC progression. In addition, circ-10720 knockdown suppressed tumor growth in vivo. Conclusions Circ-10720 acts as a ceRNA to adsorb miR-1238 and modulate ZEB2 to facilitate the proliferation, migration, invasion, and EMT of NSCLC cells. Graphical Abstract

Background and objective Malnutrition is commonly associated with poor prognosis in patients with malignant tumors. The neutrophil-to-lymphocyte ratio (NLR) is an indicator of inflammation in the body and predicts the risk of malnutrition in a variety of diseases; however, its association with malnutrition in lung cancer patients is unclear. The aim of this study is to clarify the association between NLR and nutritional status in stage IV primary lung cancer and to further determine the optimal NLR cut-off that best predicts the risk of malnutrition. Methods A retrospective analysis of 209 patients admitted to the Department of Medical Oncology, Tianjin Medical University General Hospital with a primary diagnosis of stage IV lung cancer from May 2019 to February 2021 was performed, and the nutritional risk screening 2002 (NRS 2002) was used to examine their nutritional status. Patient demographic information, pathology, Karnofsky performance status (KPS) score, body mass index (BMI), comorbidities and clinical biochemical indicators were also included. The correlation between NLR and NRS 2002 was investigated. Receiver operating characteristic (ROC) curve was used to determine the best NLR cut-off predi cting malnutrition risk. Multivariable Logistic regression was used to assess the association between NLR and malnutrition risk. Results The rate of patients with stage IV primary lung cancer at nutritional risk was 36.36% (76/209). A significant positive correlation was observed between NLR values and NRS 2002 risk score (r=0.765, P3.94 group had a significantly higher risk of malnutrition compared to those in the NLR≤3.94 group (69.49% vs 23.33%, P

Abstract Background The relationship between handgrip strength (HGS) and depression in patients undergoing hemodialysis (HD) was unknown. Therefore, we aimed to clarify this association in a cohort of patients. Methods HGS was used as a representative indicator of muscle strength and was measured with a handheld dynamometer. Depressive symptoms were assessed with the self-reported Patient Health Questionnaire-9. A multivariable logistic regression model and restricted cubic spline analysis were used to assess the relationship between HGS and depression. Results The prevalence of depression in our study was 34% in 568 Chinese patients undergoing HD. Compared with patients in the lowest tertiles of absolute and weighted HGS, patients in the highest tertiles of HGS had an approximately 59% lower [odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.24–0.68; OR = 0.41, 95%CI = (0.24–0.69)] prevalence of depressive symptoms after multivariate adjustments. Besides, the risk of depression in hemodialysis patients decreased by 33% (OR = 0.67, 95%CI = 0.53–0.85) and 32% (OR = 0.68, 95%CI = 0.54–0.85) for each standard deviation increase in absolute HGS and weighted HGS, respectively. The prevalence of depressive symptoms decreased with both increasing absolute HGS and weighted HGS after multivariate adjustments (p for trend 0.05). Conclusions This study suggests that lower handgrip strength, a simple and modifiable parameter, is associated with a higher prevalence of depression in Chinese patients undergoing HD. Considering that depression is often unrecognized or underdiagnosed in HD patients, lowered muscle strength should be an important indicator and incentive for medical staff to screen for depression.

In order to achieve multi-objective optimization for a permanent magnet water pump motor in heavy commercial vehicles, we propose a strategy based on response-surface methodology and the improved sparrow algorithm (CGE-SSA). Firstly, the output capacity of the pump during actual operation was tested with an experimental bench to determine the design parameters of the motor, and then its modeling was completed using Ansys Maxwell 2022r2 software. Secondly, the response-surface model was established by taking the parameters of permanent magnet width, rib width, and slot width as optimization parameters and the output torque (Ta), torque ripple (Tr), and back electromotive force (EMF) amplitude as optimization objectives. Meanwhile, three methods—namely, circular sinusoidal chaotic mapping, improved golden sinusoidal strategy, and adaptive weight coefficients—were used to improve the convergence speed and accuracy of the sparrow search algorithm (SSA). Finally, the multi-objective optimization of the permanent magnet synchronous motor was completed using the improved sparrow algorithm. A comparative analysis of the motor’s output before and after optimization showed that the torque pulsation and reverse electromotive force of the motor were significantly improved after optimization.

In the context of the deep-sea transportation supply chain, this paper addresses the complex decision-making problem of vessel allocation and carbon emission optimization for container shipping routes. A bi-level programming model is established, with the upper level aiming to minimize the total operational cost and the lower level focusing on minimizing carbon emissions. Using an example of an operator with five different types of vessels, a genetic algorithm is employed to determine the optimal vessel allocation scheme. The results indicate that the vessel allocation scheme obtained through multiple iterations of the model effectively reduces both carbon emissions and operational costs. Under the condition that the preset labor cost increases year by year, the use of model optimization can significantly reduce the growth of total operating costs. This paper provides theoretical support and practical guidance for shipping companies aiming to optimize decision-making in order to reduce operational costs and carbon emissions.

In advanced non-small cell lung cancer (NSCLC), V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation is highly malignant and has poor prognosis, and currently Dabrafenib in combination with Trametinib is approved for first-line treatment of patients with BRAF V600 mutation. In addition to mutations, BRAF fusion can also occur. With the development of gene detection, the detection of BRAF fusion is gradually increasing, but there is a lack of effective therapeutic strategies for BRAF fusion. In this paper, we review the clinical characteristics, mechanism of action, and clinical treatment of BRAF fusion to provide a basis for the treatment of BRAF fusion in NSCLC patients.

The growing demands for electrochemical energy storage systems is driving the exploration of novel devices, with lithium-ion capacitors (LICs) emerging as a promising strategy to achieve both high energy density and fast charge capability. However, the low capacitance of commercial activated carbon (AC) cathode based on anion absorption/desorption limits LIC applications. Herein, commercial graphite is proposed as the cathode to construct an innovative AC (−)//graphite (+) system. The graphite cathode functions as anion hosting, allowing reversible intercalation/de-intercalation of anions into/from its interlayers. The as-designed AC (−)//graphite (+) full cell achieves stable cycling with 90.6% capacity retention after 200 cycles at 0.1 A g−1 and a prolonged lifespan with 87.5% capacity retention after 5000 cycles at 0.5 A g−1 with the upper cut-off voltage of 5.0 V, yielding a high average Coulombic efficiency (CE) of 99.3%. Moreover, the full cell exhibits a high energy density (>200 Wh kg−1) and power density of 7.7 kW kg−1 (calculated based on active mass in both electrodes). These performances exceed most LICs based on anions absorption/desorption on the surface of AC cathodes. This work explores an effective electrode revolution with the assistance of anion intercalation/de-intercalation chemistry for developing novel LICs with high energy and power densities.

Graphene oxide (GO) has attracted huge attention in biomedical sciences due to its outstanding properties and potential applications. In this study, we synthesized GO using our recently developed 1-pyrenebutyric acid-assisted method and assessed how the GO as a filler influences the mechanical properties of GO–gelatine nanocomposite dry films as well as the cytotoxicity of HEK-293 cells grown on the GO–gelatine substrates. We show that the addition of GO (0–2%) improves the mechanical properties of gelatine in a concentration-dependent manner. The presence of 2 wt% GO increased the tensile strength, elasticity, ductility, and toughness of the gelatine films by about 3.1-, 2.5-, 2-, and 8-fold, respectively. Cell viability, apoptosis, and necrosis analyses showed no cytotoxicity from GO. Furthermore, we performed circular dichroism, X-ray diffraction, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy analyses to decipher the interactions between GO and gelatine. The results show, for the first time, that GO enhances the mechanical properties of gelatine by forming non-covalent intermolecular interactions with gelatine at its amorphous or disordered regions. We believe that our findings will provide new insight and help pave the way for potential and wide applications of GO in tissue engineering and regenerative biomedicine.

Abstract Each step in angiogenesis is regulated by the extracellular matrix (ECM). Accumulating evidence indicates that ageing-related changes in the ECM driven by cellular senescence lead to a reduction in neovascularisation, reduced microvascular density, and an increased risk of tissue ischaemic injury. These changes can lead to health events that have major negative impacts on quality of life and place a significant financial burden on the healthcare system. Elucidating interactions between the ECM and cells during angiogenesis in the context of ageing is neceary to clarify the mechanisms underlying reduced angiogenesis in older adults. In this review, we summarize ageing-related changes in the composition, structure, and function of the ECM and their relevance for angiogenesis. Then, we explore in detail the mechanisms of interaction between the aged ECM and cells during impaired angiogenesis in the older population for the first time, discussing diseases caused by restricted angiogenesis. We also outline several novel pro-angiogenic therapeutic strategies targeting the ECM that can provide new insights into the choice of appropriate treatments for a variety of age-related diseases. Based on the knowledge gathered from recent reports and journal articles, we provide a better understanding of the mechanisms underlying impaired angiogenesis with age and contribute to the development of effective treatments that will enhance quality of life.

Abstract Calcium‐magnesium‐aluminium‐silicate (CMAS) attack is a longstanding challenge for yttria stabilized zirconia (YSZ) thermal barrier coatings (TBCs) particularly at higher engine operating temperature. Here, a novel microstructural design is reported for YSZ TBCs to mitigate CMAS attack. The design is based on a drip coating method that creates a thin layer of nanoporous Al2O3 around YSZ columnar grains produced by electron beam physical vapor deposition (EB‐PVD). The nanoporous Al2O3 enables fast crystallization of CMAS melt close to the TBC surface, in the inter‐columnar gaps, and on the column walls, thereby suppressing CMAS infiltration and preventing further degradation of the TBCs due to CMAS attack. Indentation and three‐point beam bending tests indicate that the highly porous Al2O3 only slightly stiffens the TBC but offers superior resistance against sintering in long‐term thermal exposure by reducing the intercolumnar contact. This work offers a new pathway for designing novel TBC architecture with excellent CMAS resistance, strain tolerance, and sintering resistance, which also points out new insight for assembly nanoporous ceramic in traditional ceramic structure for integrated functions.

Water pricing is the key to maximizing the economic and social benefits of the water transfer project. In this study, we propose the extended linear expenditure system-water price tolerance index (ELES-WPTI) model that combines the ELES model and the WPTI method for water pricing. Firstly, the ELES model is used to estimate the price elasticity of water demand and the basic demand for farmers of different income levels. Secondly, the WPTI method is used to simulate and analyze the affordability of farmers of different income levels for agricultural water under the dynamic change of water price standards. Finally, the ELES-WPTI model is applied to the Yinda-Jihuang (YJ) Project, China, to determine the appropriate agricultural water price. The results reveal that the farmers in the DH district have slightly higher affordability of water price than that in HL District. As water consumption should account for less than 15% of the total production cost and 10% of the net income, the affordable water price is determined to be 237 $/hm² in the DH district and 205 $/hm² in the HL district, respectively. HIGHLIGHTS A new method extended linear expenditure system-water price tolerance index (ELES-WPTI) for water pricing is presented.; The study simulated and analyzed the farmers’ affordability of different income levels for agricultural water.; The ELES-WPTI model is first applied to the Yinda-Jihuang (YJ) Project, China.;

Abstract Objective Post-dialysis fatigue (PDF) is an important problem in patients undergoing maintenance hemodialysis (MHD); however, evidence of the association between serum calcium after dialysis and the risk of PDF is limited and controversial. We explored this association among patients receiving MHD. Methods We carried out a case–control study of patients in the dialysis unit of Dalian Municipal Central Hospital between December 2019 and January 2020, including 340 patients with PDF and 270 patients without PDF. PDF was assessed by a \validated self-administered questionnaire. Clinical variables were tested for multicollinearity using variance inflation factor analysis. Corrected serum calcium levels were categorized into three groups, with the lowest tertile used as the reference category. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for PDF risk were estimated using an unconditional logistic regression model. Result After adjusting for potential confounders, corrected serum calcium levels showed a significant positive association with the risk of PDF (ORT3vs.T1 = 1.61, 95% CI = 1.01–2.58). Notably, after stratification by age, corrected serum calcium was also positively associated with the risk of PDF in patients aged ≥ 65 years (ORT3vs.T1 = 4.25, 95% CI 1.66–11.46). Furthermore, a significant linear trend and interaction were also observed (P

Abstract Objective Aging is a complicated process that triggers age‐related disease susceptibility through intercellular communication in the microenvironment. While the classic secretome of senescence‐associated secretory phenotype (SASP) including soluble factors, growth factors, and extracellular matrix remodeling enzymes are known to impact tissue homeostasis during the aging process, the effects of novel SASP components, extracellular small noncoding RNAs (sncRNAs), on human aging are not well established. Methods Here, by utilizing 446 small RNA‐seq samples from plasma and serum of healthy donors found in the Extracellular RNA (exRNA) Atlas data repository, we correlated linear and nonlinear features between circulating sncRNAs expression and age by the maximal information coefficient (MIC) relationship determination. Age predictors were generated by ensemble machine learning methods (Adaptive Boosting, Gradient Boosting, and Random Forest) and core age‐related sncRNAs were determined through weighted coefficients in machine learning models. Functional investigation was performed via target prediction of age‐related miRNAs. Results We observed the number of highly expressed transfer RNAs (tRNAs) and microRNAs (miRNAs) showed positive and negative associations with age respectively. Two‐variable (sncRNA expression and individual age) relationships were detected by MIC and sncRNAs‐based age predictors were established, resulting in a forecast performance where all R2 values were greater than 0.96 and root‐mean‐square errors (RMSE) were less than 3.7 years in three ensemble machine learning methods. Furthermore, important age‐related sncRNAs were identified based on modeling and the biological pathways of age‐related miRNAs were characterized by their predicted targets, including multiple pathways in intercellular communication, cancer and immune regulation. Conclusion In summary, this study provides valuable insights into circulating sncRNAs expression dynamics during human aging and may lead to advanced understanding of age‐related sncRNAs functions with further elucidation.

Natural pyrethrins (NPs), one kind of bio-pesticide, have been widely used in organic agriculture and ecological environment studies. Studies have shown that NPs may affect the metabolism of rat liver and human hepatocytes; nevertheless, the toxic effects of NPs on the liver and the related mechanisms are still incompletely understood. In this research, we utilized three types of human liver cells to investigate the mechanism of NPs’ induction of oxidative stress. The results showed that NPs exhibit noteworthy cytotoxic effects on human liver cells. These effects are characterized by the induction of LDH release, mitochondrial collapse, and an increased production of ROS and MDA content, subsequently activating the Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2- related factor 2 (Keap1/Nrf-2) pathway. The ROS inhibitor N-acetyl-L-cysteine (NAC) can alleviate ROS/Nrf2-mediated oxidative stress. In addition, the siRNA knockdown of Nrf-2 exacerbated the injury, including ROS production, and inhibited cell viability. In summary, the ROS-mediated Keap1/Nrf-2 pathway could be an important regulator of NP-induced damage in human liver cells, which further illustrates the hepatotoxicity of NPs and thereby contributes to the scientific basis for further exploration.

The existing singularity avoidance methods have deficiencies, such as the conditionality of the online conversion of the assembly modes (AMs) and the kinematically redundant manipulator with the predicament of the prototype design and added complexity of the mechanism. To address these issues, a method to determine a singularity-free inner workspace through offline conversion of the AMs of the 3-RRR planar parallel manipulator (PPM) is presented. Based on the geometric relations among rods of the manipulator during the occurrence of singularity, and the singular points at or near the boundary of the workspace are permitted, the AMs and ranges of the orientation angle of the moving platform corresponding to the inner singularity-free workspace are determined through a three-dimensional search method. The simulation and experimental comparisons indicate that singular-free paths related to the constant or variable orientation angle of the moving platform can be planned on the singularity-free inner workspace.

Abstract Bioorthogonal chemistry reactions occur in physiological conditions without interfering with normal physiological processes. Through metabolic engineering, bioorthogonal groups can be tagged onto cell membranes, which selectively attach to cargos with paired groups via bioorthogonal reactions. Due to its simplicity, high efficiency, and specificity, bioorthogonal chemistry has demonstrated great application potential in drug delivery. On the one hand, bioorthogonal reactions improve therapeutic agent delivery to target sites, overcoming off-target distribution. On the other hand, nanoparticles and biomolecules can be linked to cell membranes by bioorthogonal reactions, providing approaches to developing multi-functional drug delivery systems (DDSs). In this review, we first describe the principle of labeling cells or pathogenic microorganisms with bioorthogonal groups. We then highlight recent breakthroughs in developing active targeting DDSs to tumors, immune systems, or bacteria by bioorthogonal chemistry, as well as applications of bioorthogonal chemistry in developing functional bio-inspired DDSs (biomimetic DDSs, cell-based DDSs, bacteria-based and phage-based DDSs) and hydrogels. Finally, we discuss the difficulties and prospective direction of bioorthogonal chemistry in drug delivery. We expect this review will help us understand the latest advances in the development of active targeting and multi-functional DDSs using bioorthogonal chemistry and inspire innovative applications of bioorthogonal chemistry in developing smart DDSs for disease treatment.

STRN-ALK fusion is a rare ALK rearrangement identified in non-small cell lung cancer (NSCLC) patients. Here, we reported a case of lung adenocarcinomas with brain metastasis, harboring STRN-ALK fusion, responded well to ensartinib. This case report could provide more information for the therapeutic strategy selecting of NSCLC patients harboring STRN-ALK fusion.

Antioxidant peptides are currently a hotspot in food science, pharmaceuticals, and cosmetics. In different fields, the screening, activity evaluation, mechanisms, and applications of antioxidant peptides are the pivotal areas of research. Among these topics, the efficient screening of antioxidant peptides stands at the forefront of cutting-edge research. To this end, efficient screening with novel technologies has significantly accelerated the research process, gradually replacing the traditional approach. After the novel antioxidant peptides are screened and identified, a time-consuming activity evaluation is another indispensable procedure, especially in in vivo models. Cellular and rodent models have been widely used for activity evaluation, whilst non-rodent models provide an efficient solution, even with the potential for high-throughput screening. Meanwhile, further research of molecular mechanisms can elucidate the essence underlying the activity, which is related to several signaling pathways, including Keap1-Nrf2/ARE, mitochondria-dependent apoptosis, TGF-β/SMAD, AMPK/SIRT1/PGC-1α, PI3K/Akt/mTOR, and NF-κB. Last but not least, antioxidant peptides have broad applications in food manufacture, therapy, and the cosmetics industry, which requires a systematic review. This review introduces novel technologies for the efficient screening of antioxidant peptides, categorized with a new vision. A wide range of activity evaluation assays, encompassing cellular models, as well as rodent and non-rodent models, are provided in a comprehensive manner. In addition, recent advances in molecular mechanisms are analyzed with specific cases. Finally, the applications of antioxidant peptides in food production, therapy, and cosmetics are systematically reviewed.

In response to the optimal operation of ocean container ships, this paper presents a two-level planning model that takes into account carbon tax policies. This model translates the CO2 emissions of ships into carbon tax costs and aims to minimize the overall operation costs of the ships. In top-level planning, the model considers factors such as speed, cargo load, and energy consumption to establish an objective function and optimization strategy. In bottom-level planning, the model involves ship stability and imposes corresponding constraints. By integrating the two levels of planning, a ship operation optimization model that considers multiple factors is obtained. With practical ocean container ships as cases, through numerical examples and sensitivity analysis, the constraint, stability, and structural feasibility of the constructed model are confirmed. The research results of this paper provide a decision-making basis for optimizing the operation of oceanic container ships.

Purpose To investigate the diurnal variation in subfoveal choroidal thickness (SFCT) during the waking period over three consecutive days in different degrees of myopia and emmetropia. Methods A total of 60 adult volunteers were grouped into low, moderate, high myopia, and emmetropia subgroups. SFCT, axial length (AL), anterior chamber depth (ACD), and intraocular pressure (IOP) were measured every 2 h from 8 AM to 8 PM for three successive days. Results The mean values of daily change amplitude were 3.18 mmHg (IOP), 0.05 mm (AL), 0.17 mm (ACD), and 13.51 μm (SFCT). The values of AL and ACD increased simultaneously with spherical equivalent refraction (SER), but SFCT was the opposite. IOP had a diurnal variation, and there was no difference among the four groups. AL of the high myopia group, ACD of the emmetropia group, and SFCT of each myopia group had diurnal variation over three consecutive days. AL had a high mean value at noon every day, and SFCT had a low mean value at noon every day. Conclusion The choroid thickness of subjects with different degrees of myopia had a significant diurnal variation. The change of diurnal variation between emmetropic and myopic subjects may be one of the causes of myopia.

Immune checkpoint inhibitors (ICIs) have become an important means of cancer treatment, and their application in the clinic is becoming more and more widespread. The adverse reactions caused by ICIs are gradually recognized. Among them, immunotherapy-related diabetes is a rare adverse reaction and type 1 diabetes mellitusis common. With the wide application of ICIs combined with chemotherapy in lung cancer patients, patients with type 2 diabetes mellitus have gradually been discovered during the treatment. However, the effect of continued use of ICIs maintenance therapy on blood glucose and ICIs treatment process in these patients is still unclear. This article reports two cases of type 2 diabetes mellitus induced by immune checkpoint inhibitor combined with chemotherapy, one of whom converted to type 1 diabetes mellitus, in order to increase the understanding of immunotherapy-related diabetes.

Abstract Background Accumulating evidence suggests that LINC00511 acts as an oncogenic long non-coding RNA (lncRNA) in various cancers, including lung adenocarcinoma (LUAD). Hence, we attempted to elucidate the potential role of LINC00511 in LUAD. Methods LINC00511, miR-195-5p, and GCNT3 expression in LUAD was detected by qRT-PCR. Changes in the proliferation, migration, and invasion of LUAD cells after abnormal regulation of LINC00511, miR-195-5p, or GCNT3 were detected by CCK-8, BrdU, wound healing, and transwell assays. Bax and Bcl-2 protein expression was measured by western blotting. Additionally, we identified the targeting effects of LINC00511, miR-195-5p, and GCNT3 using luciferase and RNA immunoprecipitation (RIP) assays. Results LINC00511 and GCNT3 were found to be upregulated in LUAD, while miR-195-5p was downregulated. Silencing LINC00511 or GCNT3 decreased the proliferation, migration, invasion, and Bcl-2 protein content in LUAD cells and increased the expression of Bax. Interference with miR-195-5p promoted malignant proliferation of cancer cells. miR-195-5p expression was affected by LINC00511and targeted GCNT3. Conclusion Silencing LINC00511 promotes GCNT3 expression by inhibiting miR-195-5p and ultimately stimulates the malignant progression of LUAD.

In order to improve the driving performance of four-wheel drive electric vehicles and realize precise control of their speed, a Chaotic Random Grey Wolf Optimization-based PID in-wheel motor control algorithm is proposed in this paper. Based on an analysis of the structural principles of electric vehicles, mathematical and simulation models for the whole vehicle are established. In order to improve the control performance of the hub motor, the traditional Grey Wolf Optimization algorithm is improved. In particular, an enhanced population initialization strategy integrating sine and cosine random distribution factors into a Kent chaotic map is proposed, the weight factor of the algorithm is improved using a sine-based non-linear decreasing strategy, and the population position is improved using the random proportional movement strategy. These strategies effectively enhance the global optimization ability, convergence speed, and optimization accuracy of the traditional Grey Wolf Optimization algorithm. On this basis, the CR-GWO-PID control algorithm is established. Then, the software and hardware of an in-wheel motor controller are designed and an in-wheel motor bench test system is built. The simulation and bench test results demonstrate the significantly improved response speed and control accuracy of the proposed in-wheel motor control system.

Abstract Background Higher serum galectin-3 levels are related to adverse outcomes in different disease states. However, the association of galectin-3 with mortality in the maintenance hemodialysis (HD) population has not been fully described. Thus, we aimed to assess the predictive significance of galectin-3 for all-cause and cardiovascular (CV) mortality through a Chinese maintenance HD population. Methods A prospective cohort study was conducted in five hundred and six patients with end-stage renal disease who underwent hemodialysis at Dalian Central Hospital before December 31, 2014. Serum galectin-3 levels were measured at baseline and classified as high (> 8.65 ng/ml) or low (≤ 8.65 ng/ml) according to the “X-tile” program. Primary and secondary outcomes were all-cause and CV mortality, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazards regression models. Results During the median follow-up of 60 months, there were 188 all-cause deaths and 125 CV deaths. Compared with maintenance HD population with galectin-3 ≤ 8.65 ng/ml, the adjusted HR for all-cause mortality among those with galectin-3 > 8.65 ng/ml was 1.59 (CI: 0.96–2.65, p = 0.07). Furthermore, multivariable analysis showed that maintenance HD patients with galectin-3 > 8.65 ng/ml had a 2.13-fold higher risk of CV death than those with galectin-3 ≤ 8.65 ng/ml (HR = 2.13, 95% CI 1.07–4.26). Conclusion Galectin-3 is an independent predictor of CV mortality in maintenance HD patients.

Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC

Purpose: We aim to present effective and computer aided diagnostics in the field of ophthalmology and improve eye health. This study aims to create an automated deep learning based system for categorizing fundus images into three classes: normal, macular degeneration and tessellated fundus for the timely recognition and treatment of diabetic retinopathy and other diseases.Methods: A total of 1,032 fundus images were collected from 516 patients using fundus camera from Health Management Center, Shenzhen University General Hospital Shenzhen University, Shenzhen 518055, Guangdong, China. Then, Inception V3 and ResNet-50 deep learning models are used to classify fundus images into three classes, Normal, Macular degeneration and tessellated fundus for the timely recognition and treatment of fundus diseases.Results: The experimental results show that the effect of model recognition is the best when the Adam is used as optimizer method, the number of iterations is 150, and 0.00 as the learning rate. According to our proposed approach we, achieved the highest accuracy of 93.81% and 91.76% by using ResNet-50 and Inception V3 after fine-tuned and adjusted hyper parameters according to our classification problem.Conclusion: Our research provides a reference to the clinical diagnosis or screening for diabetic retinopathy and other eye diseases. Our suggested computer aided diagnostics framework will prevent incorrect diagnoses caused by the low image quality and individual experience, and other factors. In future implementations, the ophthalmologists can implement more advanced learning algorithms to improve the accuracy of diagnosis.

Inorganic modified green mudstone (MGM) was prepared from the green mudstone (GM) residue of Fushun West Open Pit Mine and characterized by XRF, XRD, FTIR, and SEM of GM and MGM. According to the calculation of pore size and the BET equation, the pore size and specific surface area of the MGM were larger. The results of adsorption kinetics and isothermal adsorption experiments showed that the adsorption capacity of MGM for phosphate increased from 0.1 mg/g to 0.71 mg/g, which was obviously better than that of GM. The GM and MGM accorded with the quasi-second-order kinetic model. The isothermal adsorption data of GM accorded with the Freundlich model, and the isothermal data of MGM accorded with the Langmuir model, which indicated that the model of GM and MGM was an adsorption process from a double layer to a single layer. Thermodynamic data showed that the increase in temperature was beneficial to the adsorption of MGM. The internal diffusion model showed that due to the change of pore size structure after modification, the number of adsorption sites that could provide phosphate was increased, and at the same time, the change of internal elements led to the extension of the chemical reaction time by 700 min. Because of the ligand exchange and electrostatic interaction between phosphate, GM, and MGM, the adsorption results showed that acidity was better than alkalinity. To improve the recycling ability of MGM, hydrochloric acid with a concentration of 0.1 mol/L was determined as the best phosphorus resolving agent, and the resolving rate was still close to 80% after five cycles. The results showed that the MGM could be a promising adsorbent for the removal of phosphorus, providing a new way for resource utilization of mining waste residue.

BackgroundPulmonary arterial hypertension (PAH) is a fatal disease characterized by pulmonary vascular remodeling and increased pulmonary artery pressure, leading to impaired lung oxygenation, right heart failure, and even death. Although great advances have been made in PAH-targeted medications for pediatric patients, the efficacy and safety of these treatments are controversial.MethodsWe retrieved relevant articles from electronic databases including PubMed, EMBASE, Web of Science, and Cochrane Library until 12 April 2022. To compare the effectiveness and safety of endothelin receptor antagonists (ERAs), phosphodiesterase type 5 Inhibitors (PDE-5i), and prostaglandins (ProA) in the treatment of pediatric PAH, we investigated six hemodynamic parameters, four respiratory parameters, intensive care unit (ICU) stay duration, length of hospital stay, and two safety outcomes.ResultsA total of 27 randomized controlled trials (RCTs) were included in the meta-analysis with 1,574 pediatric participants. The duration of mechanical ventilation was shorter for patients using bosentan, sildenafil, and ProsA, compared with that for patients using the placebo. Bosentan helped to shorten more time for mechanical ventilation than ProsA did, while ProsA was more effective than sildenafil in this respect. As for the length of stay in the ICU, patients administered by ProsA or sildenafil needed shorter ICU stay, compared to those using the placebo, while ProsA was more effective for shortening ICU stay time. In light of safety outcomes, there was a statistically significant difference between the sildenafil and the placebo group. Sildenafil surpassed ProsA in reducing the incidence of pulmonary hypertension (PH) crisis.ConclusionsERAs were more effective than ProsA in shortening the duration of mechanical ventilation, while ProsA were better for shortening the duration of mechanical ventilation and ICU stay than PDE-5i. PDE-5i were found to generate more benefits in decreasing the occurrence of PH crisis, though further investigation is warranted.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=351505.

Abstract Background The role of unresected small lymph nodes (LNs) which may contain metastases for thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed. The aim of the study was to investigate the role of unresected small LNs assessment using computed tomography (CT) in prognostic estimates of pT3N0M0 TESCC patients. Methods Between January 2009 and December 2017, 294 patients who underwent esophagectomy with R0 resection at Sichuan Cancer Hospital were retrospectively examined, and the last follow-up time was July 2018. Patients were classified into CT-suspect and CT-negative groups according to the shortest diameter and the shape (axial ratio) of the unresected small LNs on preoperative CT. The Kaplan–Meier method was used to compare survival differences in prognostic factors. Univariate and multivariate analyses were performed to identify prognostic factors for survival and recurrence. Results Eighty-four patients (28.6%) were classified as CT-suspect group according to the diagnostic criteria; survival analysis suggested that CT-suspect group of patients had a relatively poorer prognosis (P

BackgroundGestational trophoblastic neoplasia is an uncommon disease, whose clinical manifestations are similar to ectopic pregnancy, thus some rare pelvic lesion can be misdiagnosed as ectopic pregnancy.AimsThis study was presented to investigate the characteristics of gestational trophoblastic neoplasia misdiagnosed as ectopic pregnancy and reduce the misdiagnosis.MethodsThe clinicopathological data for 14 cases of gestational trophoblastic neoplasia misdiagnosed as ectopic pregnancy at West China Second Hospital Sichuan University from January 2006 to December 2020 were retrospectively analyzed.ResultsThe main clinical manifestations were amenorrhea, abnormal vaginal bleeding, and abdominal pain. At initial diagnosis, the serum hCG level was >10,000 mIU/mL in 5 patients and 13 points (very high risk). From 14 patients, only 3 had molar pregnancy previously. Only 3 patients had no metastasis at GTN diagnosis (from these 3, only one after molar pregnancy). After chemotherapy alone or in combination with surgery, all patients survived, with a median follow-up of 84 months (23–102 months).ConclusionIf we have positive hCG, without a sonographic topic gestation confirmation, associated with metastatic lesions, the GTN diagnosis should be considered instead of ectopic pregnancy, if the patient have had a pregnancy once during her life.

Purpose: The purpose of this paper is to develop a method to automatic classify capsule gastroscope image into three categories to prevent high-risk factors for carcinogenesis, such as atrophic gastritis (AG). The purpose of this research work is to develop a deep learning framework based on transfer learning to classify capsule gastroscope image into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image.Method: In this research work, we proposed deep learning framework based on transfer learning to classify capsule gastroscope image into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image. We used VGG- 16, ResNet-50, and Inception V3 pre-trained models, fine-tuned them and adjust hyperparameters according to our classification problem.Results: A dataset containing 380 images was collected for each capsule gastroscope image category, and divided into training set and test set in a ratio of 70%, and 30% respectively, and then based on the dataset, three methods, including as VGG- 16, ResNet-50, and Inception v3 are used. We achieved highest accuracy of 94.80% by using VGG- 16 to diagnose and classify capsule gastroscopic images into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image. Our proposed approach classified capsule gastroscope image with respectable specificity and accuracy.Conclusion: The primary technique and industry standard for diagnosing and treating numerous stomach problems is gastroscopy. Capsule gastroscope is a new screening tool for gastric diseases. However, a number of elements, including image quality of capsule endoscopy, the doctors’ experience and fatigue, limit its effectiveness. Early identification is necessary for high-risk factors for carcinogenesis, such as atrophic gastritis (AG). Our suggested framework will help prevent incorrect diagnoses brought on by low image quality, individual experience, and inadequate gastroscopy inspection coverage, among other factors. As a result, the suggested approach will raise the standard of gastroscopy. Deep learning has great potential in gastritis image classification for assisting with achieving accurate diagnoses after endoscopic procedures.

In this study, a Bayesian network (BN)-based inhibition model is developed for the rainstorm–landslide–debris flow (R-L-D) disaster chain in the mountainous area of the Greater Bay Area (GBA), China, using the historical disaster data. Twelve nodes are selected for the inhibition model, which are classified into four types, including Hazardous Factor, Response Operation, Disaster Evolution, and Disaster Result. By combining the proposed inhibition with the scenario analysis method, the probabilities of the BN nodes under different rainfall scenarios are analyzed, and then the inhibitory effects of the environmental geological conditions and rescue speed on the R-L-D disaster chain under the most unfavorable rainfall scenario are investigated. On this basis, an inhibition framework consisting of the early warning, inhibition, and measures layers is proposed for the R-L-D disaster chain. The results reveal that under the most unfavorable rainfall scenarios, where the rainfall intensity is greater than 100 mm/d and the rainfall duration is greater than 24 h, the probability of landslides and debris flow is 0.930 and 0.665, respectively. Improving the environmental geological conditions such as slope, lithology and geological structure can greatly inhibit the occurrence of the R-L-D disaster chain. Moreover, the improvement of geological structure conditions is the most significant, and reduces the probability of landslides and debris flow by 0.684 and 0.430, respectively, as well as reducing the probability of death and direct economic loss by 0.411 and 0.619, respectively. Similarly, increasing the rescue speed leads to a reduction in the probability of death and direct economic loss by 0.201 and 0.355, respectively. This study can provide theoretical and practical insights into the prevention and inhibition of the R-L-D disaster chain.

Hierarchically porous carbon (PC) was synthesized by a templating method, using magnesium salts (Mg(HCO3)2, MgC2O4 and MgO) as template precursors and citric acid as carbon precursor. During the carbonization process, besides the production of MgO particles, many gases (e.g., CO2/NO2/H2O) were also released and acted as a porogen to generate pores in carbon. The resulting composite (MgO@C) was subsequently treated with HCl solution to remove the MgO templates, yielding hierarchically porous carbon. The surface oxygen functional groups over porous carbon were characterized by TPD and XPS, which showed that the PC-bic, synthesized using Mg(HCO3)2 as the template precursor, had the highest value among the PCs. As expected, the PC-bic exhibited the best performances for electrocatalytic reduction of 4-nitrophenol, with a peak current of −135.5 μA at −0.679 V. The effects of 4-nitrophenol concentration, buffer solution pH and scanning rate on the electrocatalytic activities, as well as the stability of PC-bic for the reaction were investigated.

Background: Poststroke social isolation could worsen poststroke depression and dampen neurogenesis. (R,S)-ketamine has antidepressant and neuroprotective effects; however, its roles and mechanisms in social isolation–mediated depressive-like behaviors and sensorimotor recovery remain unclear. Methods: Mice were subjected to transient middle cerebral artery occlusion, and then were pair-housed with ovariectomized female mice or were housed isolated (ISO) starting at 3 days postischemia. ISO mice received 2 weeks of (R,S)-ketamine treatment starting at 14 days postischemia. Primary ependymal epithelial cells and choroid plexus epithelial cells were cultured and treated with recombinant human atrial natriuretic peptide (ANP) protein. Results: The poststroke social isolation model was successfully established using middle cerebral artery occlusion combined with poststroke isolation, as demonstrated by a more prominent depression-like phenotype in ISO mice compared with pair-housed mice. (R,S)-ketamine reversed ISO-mediated depressive-like behaviors and increased ANP levels in the atrium. The depression-like phenotype was negatively correlated with ANP levels in both the atrium and plasma. Atrial GLP-1 and GLP-1 receptor signaling was essential to the promoting effects of (R,S)-ketamine on the synthesis and secretion of ANP from the atrium in ISO mice. (R,S)-ketamine also increased ANP and TGF-β1 levels in the choroid plexus of ISO mice. Recombinant human ANP increased TGF-β1 levels in both the primarily cultured ependymal epithelial cells and choroid plexus epithelial cells. Furthermore, (R,S)-ketamine increased TGF-β1 levels in the ischemic hemisphere and promoted striatal neurogenesis and sensorimotor recovery via ANP in ISO mice. Conclusions: (R,S)-ketamine alleviated poststroke ISO-mediated depressive-like behaviors and thus promoted striatal neurogenesis and sensorimotor recovery via ANP.

ObjectivesThe treatment for hepatocellular carcinoma (HCC) remains controversial and limited in elderly patients. Therefore, we aimed to explore treatment choices for the elderly patients (≥ 65years) following surgical resection (SR) versus radiofrequency ablation (RFA) with HCC (single lesion less than 5 cm).MethodsWe used SEER database to identify HCC patients who received treatment of SR/RFA. Kaplan–Meier method and Cox proportional hazards regression method were used to determine the prognostic factors associated with overall survival (OS) and disease-specific survival (DSS). In addition, RFA group and SR group patients were matched with 1:1 propensity score matching (PSM) for diagnosis age, sex, race, marital, American Joint Committee on Cancer (AJCC), grade, radiotherapy, and chemotherapy to decrease the possibility of selection bias. Conditional disease-specific survival (CS) was estimated using the life-table method.ResultsA total of 794 patients who underwent SR and 811 patients who underwent RFA were confirmed from the SEER database. Surgery type was an independent risk factor for HCC. Survival analysis indicated that SR, races, AJCC I, no chemotherapy treatment, and grade I were cumulative risk factors that can significantly improve median survival for HCC (P < 0.05). After PSM analysis, only surgery type was significantly improved median survival of HCC patients (SR vs. RFA, HR: 0.644, 95% CI: 0.482–0.86; P < 0.001). For RFA group, the 2-, 3-, and 5-year CS rates were approximately 71%, 65%, and 62%, respectively, and corresponding to 82%, 80%, and 78% in the SR group.ConclusionSR treatment can provide survival benefits for elderly patients of

The Three Gorges region (TGR) located in the geographic center of China, is a transition zone between mountain and plain areas, and a probable migration corridor for hominins and other mammals between South and North China. Detailed chronological information of paleoanthropological evidence in this area could help us better understand the human evolution in East Asia. The OSL and U-series dating methods are two conventional dating methods generally adopted to date such sites; however, their applications were limited by the dating range—restricted to several hundred of millennia and ambiguous stratigraphic relationship between the archaeological remains and the dating target materials. Cosmogenic nuclide burial dating of quartzite stone artifacts and coupled electron spin resonance and uranium series dating (ESR/U-series) of fossil teeth have the potential to date Early–Middle Pleistocene hominin sites in Asia and were applied increasingly in China in recent years. However, the application of cosmogenic 26Al/10Be burial dating is limited in TGR because most sites are dominated by limestone, leading to the scarcity of the quartz component. In this case, the coupled ESR/U-series method plays a more important role in the establishment of the chronology of human settlement. In TGR, by using the coupled ESR/U-series method, we have dated seven important Early and Middle Pleistocene hominin settlement sites, including Longgupo, Jianshi, Yunxian, Meipu, Bailongdong, Changyang, and Yumidong sites. Based on our dating results, we propose that hominins were settled in TGR probably from the early stage of Early Pleistocene (∼2.5−2.2 Ma) at the Longgupo site to the late Middle Pleistocene to Late Pleistocene of the Yumidong site (∼274−14 ka) and very likely to spread to other parts of East Asia during this time period. In view of the potential of coupled ESR/U-series dating on fossil teeth from the hominin sites in the TGR, future work may consider the micro damage or non-destructive analysis of enamel fragment with the ESR method and laser ablation ICP-MS techniques that will make possible the direct dating of precious human fossils in China.

Obstructive sleep apnea (OSA) is a serious breathing disorder, leading to myocardial infarction, high blood pressure, and stroke. Brain morphological changes have been widely reported in patients with OSA. The pathophysiological mechanisms of cerebral blood flow (CBF) changes associated with OSA are not clear. In this study, 20 patients with OSA and 36 healthy controls (HCs) were recruited, and then pseudo-continuous arterial spin labeling (pCASL) and voxel-based morphometry (VBM) methods were utilized to explore blood perfusion and morphological changes in the patients with OSA. Compared with the HC group, the OSA group showed increased CBF values in the right medial prefrontal cortex (mPFC), left precentral gyrus, and right insula and showed decreased CBF values in the right temporal pole (TP) and the right cerebellum_Crus2. Compared with the HC group, the patients with OSA showed decreased gray matter volume (GMV) in the right dorsal lateral prefrontal cortex (DLPFC), the right occipital pole, and the vermis. There were no significantly increased GMV brain regions found in patients with OSA. Pearson correlation analysis showed that the reduced GMV in the right DLPFC and the right occipital pole was both positively correlated with Mini-Mental State Examination (MMSE) (r = 0.755, p < 0.001; r = 0.686, p = 0.002) and Montreal Cognitive Assessment (MoCA) scores (r = 0.716, p = 0.001; r = 0.601, p = 0.008), and the reduced GMV in the right occipital pole was negatively correlated with duration of illness (r = −0.497, p = 0.036). Patients with OSA have abnormal blood perfusion metabolism and morphological changes in brain regions including the frontal lobe and the cerebellum and were closely related to abnormal behavior, psychology, and cognitive function, which play an important role in the pathophysiological mechanism of OSA.

Aiming to more accurately control the wheel speed of an electric vehicle (EV) driven by four in-wheel motors, a developed whale optimization algorithm-proportional–integral–derivative (KW-WOA-PID) control algorithm is proposed herein. In this study, mathematical and simulation models are built for EVs by analyzing the mechanical structures of EVs driven by four in-wheel motors. Simulations are conducted, and the driving and control requirements for the in-wheel motors are obtained. Then, mathematical and simulation models are built for a specific in-wheel motor. The whale optimization algorithm (WOA) is optimized by kent mapping and the adaptive weight coefficient to improve the ability of the algorithm to jump out of the local optimum and the convergence speed and convergence accuracy of WOA. Then the further simulations are conducted. The simulation results display that the maximum overshoot and adjustment time of the motor under KW-WOA-PID control are significantly optimized. Then, a speed-control bench test system is built for the in-wheel motor, and real-life experiments were conducted. The experimental results verify that KW-WOA-PID has higher control accuracy and a better response performance; accordingly, the developed control algorithm can meet driving requirements. The handling stability of EVs is effectively improved by controlling the motor speed.

Abstract An exceptional phenomenon has been observed that SO2 and NO x in flue gas can be effectively adsorbed over activated carbon with a surprising capacity at cold temperatures with the presence of oxygen. In this study, the adsorption characteristics of NO and SO2 over activated carbon at 80, 20, 0, and − 20 is experimentally investigated. Without the presence of oxygen, adsorption of NO is negligible. In the presence of oxygen, NO can be oxidized to NO2 over activated carbon which leads to the co-adsorption of NO/NO2 within the adsorption bed. Catalytic oxidation of NO over activated carbon can be significantly enhanced at cold temperatures, leading to an extraordinary increase of adsorption capacity of NO. With an initial concentration of NO = 200 ppmv and a space velocity of 5000 h−1, the average specific capacity increases from 3.8 to 169.1 mg/g when the temperature decreases from 80 to – 20 ℃. For NO–O2 co-adsorption, the specific capacity increases along the adsorption bed due to the increasing NO2 concentrations. The adsorption capacity of SO2 is also significantly enhanced at cold temperatures. With an initial concentration of SO2 = 1000 ppmv, the specific capacity increases from 12.9 to 123.1 mg/g when the temperature decreases from 80 to – 20 ℃. A novel low-temperature adsorption (LAS) process is developed to simultaneously remove SO2 and NO x from flue gas with a target of near-zero emission. A pilot-scale testing platform with a flue gas flowrate of 3600 Nm3/h is developed and tested. Emission of both SO2 and NO x is less than 1 ppmv, and the predicted energy penalty is about 3% of the net generation.

Abstract. Background:. Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system. Methods:. We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2. Results:. Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression. Conclusion:. This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

Cancer immunotherapy is becoming an important option for treating patients with cancer in clinic. Given the heterogeneity of tumors between individuals, personalized cancer immunotherapy is the most promising one. Tremendous progresses have been achieved to initialize personalized immunity in patients through delivering tumor-derived neoantigens or adoptive transfer of engineered immune cells such as T cells and nature killer cells. However, the objective response rate and therapeutic efficiency of most personalized immunotherapies are hampered by the biophysical barriers against drug delivery and the limited infiltration of engineered cells into solid tumors. To overcome these limitations, versatile drug delivery systems have been developed to deliver personalized tumor antigens to target and promote intratumoral infiltration of lymphocytes, thus generating a local immunogenic niche to induce potent and durable antitumor immune responses. In this review, we will summarize the major barriers for efficient personalized immunization, highlight our lab and several other groups’ efforts in versatile drug delivery systems for delivering tumor-specific antigens, autologous tumor cell-derived antigens and combining with adoptive transfer of engineered immune cells. At the end of this review, we also look forward to the future development of drug delivery system-based personalized immunotherapy and its challenges for clinical translation.