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Abstract Background Hypertension, sleep disorders, and depression represent notable public health issues, and their interconnected nature has long been acknowledged. The objective of this study is to explore the interplay between sleep disorders and depression in the context of hypertension. Methods This cross-sectional study involved 42,143 participants aged 18 and above from the NHANES database across seven survey cycles between 2005 and 2018. After excluding those with missing data on depression, sleep disorders, and hypertension, as well as incomplete main variables, 33,383 participants remained. We used weighted logistic regression to examine the relationship between sleep disorders, depression, and hypertension. Additionally, we assessed the interaction between sleep disorders and depression on hypertension using both multiplicative and additive approaches to quantify their combined effect. Results Compared to individuals without sleep disorders, those with sleep disorders have an increased risk of hypertension (OR = 1.51, 95% CI: 1.37–1.67). Furthermore, individuals with depression experience a significantly higher risk of hypertension compared to those with sleep disorders alone (OR = 2.34, 95% CI: 1.95–2.80). Our study reveals a positive interaction between sleep disorders and depression in relation to hypertension risk (OR = 1.07, 95% CI: 1.02–1.13). In addition, we observed the quantitative additive interaction indicators (RERI = 0.73, 95% CI: 0.56 ~ 0.92; API = 0.31, 95% CI: 0.11 ~ 0.46; SI = 2.19, 95% CI: 1.08–3.46) influencing hypertension risk. Furthermore, our research also identified that individuals with less than 7 h of sleep, a sleep latency period between 5 and 30 min, or a latency period exceeding 30 min experience a significantly increased risk of hypertension. Conclusions Our research uncovered separate links between sleep disorders, depression, and hypertension prevalence. Moreover, we identified an interaction between depression and sleep disorders in hypertension prevalence. Enhancing mental well-being and tackling sleep disorders could help prevent and manage hypertension. Yet, more investigation is required to establish causation and clarify mechanisms.

Background: Gerberae Piloselloidis Herba (GPH) exhibits notable efficacy in alleviating allergic asthma. Previous studies in our research have identified a mixture of luteolin, arbutin, and marmesin as effective components of GPH in treating allergic asthma. However, the underlying mechanism remains unclear. This study aims to elucidate the molecular mechanism of these active components. Method: Using an ovalbumin (OVA)-induced allergic asthma mouse model, various treatment groups were administered, including GPH, the active component mixture (termed ''Mixture'') containing luteolin, arbutin, and marmesin, and a positive drug (dexamethasone, DEX). Relevant indices were assessed, including behavioral characteristics, inflammatory cell counts, cytokine levels, histopathological examination of lung tissue, apoptosis, and expression of key proteins such as Caspase-3, Bax, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt. The effect of the Mixture on the PI3K/Akt signaling pathway was further verified using the PI3K inhibitor LY294002. Results: The Mixture significantly alleviated asthma symptoms, decreased IgE levels, cytokine levels (IL-4, IL-5, IL-13 and TNF-α), and the number of inflammatory cells in serum or bronchoalveolar lavage fluid (BALF), leading to the alleviation of lung pathological lesions. Additionally, the Mixture reduced the expression of Bax and Caspase-3 while increasing Bcl-2 expression, resulting in mitigated apoptosis in lung tissue. Furthermore, there appeared a decrease in the levels of PI3K and p-PI3K, as well as the ratio of p-Akt to Akt in the Mixture group, indicating the suppression of PI3K and Akt phosphorylation. Interestingly, the effects of the Mixture were comparable to those of GPH, LY294002, or the combination of LY294002 with the Mixture. Conclusion: The study confirms that the Mixture containing luteolin, arbutin, and marmesin indeed alleviates allergic asthma induced by OVA in mice by suppressing the PI3K/Akt signaling pathway. These findings highlight the potential of the GPH-derived Mixture as a novel therapeutic for the treatment of allergic asthma.

BackgroundDespite the known associations of dietary magnesium intake and estimated glomerular filtration rate (eGFR) with cardiovascular diseases, their combined effects on stroke risk remain unclear. Therefore, this study aims to explore the associations of dietary magnesium intake and eGFR with stroke risk.MethodsThe National Health and Nutrition Examination Survey (NHANES) data of 37,637 adult participants (≥18 years) from 2003 to 2018 was analyzed. Dietary magnesium intake was categorized as low (≤ 254 mg/day) and normal (> 254 mg/day) based on experimental data. Multiple logistic regression analyses and interaction tests were conducted to assess the associations of dietary magnesium intake and eGFR with stroke risk, with a focus on the interaction between different chronic kidney disease (CKD) stages based on eGFR levels and dietary magnesium intake. Additional analyses included multiplicative interaction analysis, restricted cubic spline analysis, and subgroup evaluations by age, sex, and ethnicity.ResultsDietary magnesium intake and eGFR were inversely correlated with the risk of stroke. Participants with low dietary magnesium intake had a higher stroke risk than those with normal magnesium intake (odds ratio [OR] 1.09, 95% confidence interval [CI]: 1.03–1.42). Likewise, low eGFR was associated with an elevated stroke risk compared with normal eGFR (OR 1.56, 95% CI: 1.15–2.13). Furthermore, the two factors showed a multiplicative interaction effect on stroke risk (OR 1.05, 95% CI: 1.01–1.09). We observed a significant interaction between stage G3 CKD and low dietary magnesium intake (OR 1.05, 95% CI: 1.01–1.09), suggesting a potential association with stroke risk. However, similar associations were not observed for stages G4 and G5, possibly due to the smaller number of participants with G4 and G5 CKD. The restricted cubic spline analysis revealed a non-linear relationship between dietary magnesium intake, eGFR, and stroke risk. The interaction between magnesium deficiency and low eGFR persisted in participants aged >60 years, as well as in females, non-Hispanic Black people, and people of other races.ConclusionDietary magnesium intake and eGFR correlate negatively with stroke prevalence. Moreover, there was an interaction between dietary magnesium intake and stroke prevalence across different CKD stages. Further large-scale prospective studies are needed to analyze the potential relationship between dietary magnesium intake, eGFR, and stroke.

Locomotion disorder caused by spinal cord injury (SCI) leads to a considerably decreased quality of people's lives. Although there are no known cure methods for SCI, a lower extremity exoskeleton (LEE) has a perspective to restore the locomotion ability of SCI patients. Statistics show that the number of published articles on LEEs has exponentially increased over the past 20 years; however, no reviews have been conducted to summarize these studies comprehensively. To fill up this open gap, a comprehensive review from engineering to clinical standpoint is carried out, which is based on the preferred reporting items for systematic reviews and meta-analyses’ methods, including their structural designs, drive forms, control methods, and clinical assessments. A systematic discussion among them is performed while considering the main scientific and technical aspects. The analysis indicates that the actuator configuration, motor selection, state transition, trajectory tracking, transparency implementation, and clinical factor design in exoskeleton development are full of challenges, which should be investigated in more technical efforts in the future.

Abstract Objective This study aims to compare the feasibility and effectiveness of automatic deep learning network and radiomics models in differentiating low tumor stroma ratio (TSR) from high TSR in pancreatic ductal adenocarcinoma (PDAC). Methods A retrospective analysis was conducted on a total of 207 PDAC patients from three centers (training cohort: n = 160; test cohort: n = 47). TSR was assessed on hematoxylin and eosin-stained specimens by experienced pathologists and divided as low TSR and high TSR. Deep learning and radiomics models were developed including ShuffulNetV2, Xception, MobileNetV3, ResNet18, support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and logistic regression (LR). Additionally, the clinical models were constructed through univariate and multivariate logistic regression. Kaplan–Meier survival analysis and log-rank tests were conducted to compare the overall survival time between different TSR groups. Results To differentiate low TSR from high TSR, the deep learning models based on ShuffulNetV2, Xception, MobileNetV3, and ResNet18 achieved AUCs of 0.846, 0.924, 0.930, and 0.941, respectively, outperforming the radiomics models based on SVM, KNN, RF, and LR with AUCs of 0.739, 0.717, 0.763, and 0.756, respectively. Resnet 18 achieved the best predictive performance. The clinical model based on T stage alone performed worse than deep learning models and radiomics models. The survival analysis based on 142 of the 207 patients demonstrated that patients with low TSR had longer overall survival. Conclusions Deep learning models demonstrate feasibility and superiority over radiomics in differentiating TSR in PDAC. The tumor stroma ratio in the PDAC microenvironment plays a significant role in determining prognosis. Critical relevance statement The objective was to compare the feasibility and effectiveness of automatic deep learning networks and radiomics models in identifying the tumor-stroma ratio in pancreatic ductal adenocarcinoma. Our findings demonstrate deep learning models exhibited superior performance compared to traditional radiomics models. Key points • Deep learning demonstrates better performance than radiomics in differentiating tumor-stroma ratio in pancreatic ductal adenocarcinoma. • The tumor-stroma ratio in the pancreatic ductal adenocarcinoma microenvironment plays a protective role in prognosis. • Preoperative prediction of tumor-stroma ratio contributes to clinical decision-making and guiding precise medicine. Graphical Abstract

Abstract Background The development of deep learning (DL) algorithms for use in dentistry is an emerging trend. Periodontitis is one of the most prevalent oral diseases, which has a notable impact on the life quality of patients. Therefore, it is crucial to classify periodontitis accurately and efficiently. This systematic review aimed to identify the application of DL for the classification of periodontitis and assess the accuracy of this approach. Methods A literature search up to November 2023 was implemented through EMBASE, PubMed, Web of Science, Scopus, and Google Scholar databases. Inclusion and exclusion criteria were used to screen eligible studies, and the quality of the studies was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. Random-effects inverse-variance model was used to perform the meta-analysis of a diagnostic test, with which pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) were calculated, and a summary receiver operating characteristic (SROC) plot was constructed. Results Thirteen studies were included in the meta-analysis. After excluding an outlier, the pooled sensitivity, specificity, positive LR, negative LR and DOR were 0.88 (95%CI 0.82–0.92), 0.82 (95%CI 0.72–0.89), 4.9 (95%CI 3.2–7.5), 0.15 (95%CI 0.10–0.22) and 33 (95%CI 19–59), respectively. The area under the SROC was 0.92 (95%CI 0.89–0.94). Conclusions The accuracy of DL-based classification of periodontitis is high, and this approach could be employed in the future to reduce the workload of dental professionals and enhance the consistency of classification.

Globally intensified lake eutrophication, attributed to excessive anthropogenic nitrogen loading, emerges as a significant driver of submerged vegetation degradation. Consequently, the impact of nitrogen on the decline of submerged macrophytes has received increasing attention. However, a functional trait-based approach to exploring the response of submerged macrophytes to nitrogen loading and its environmental feedback mechanism was unclear. Our study utilized two different growth forms of submerged macrophytes (canopy-forming Myriophyllum spicatum, and rosette-forming Vallisneria natans) to established “submerged macrophytes-water–sediment” microcosms. We assessed the influence of nitrogen loading, across four targeted total nitrogen concentrations (original control, 2, 5, 10 mg/L), on plant traits, water parameters, sediment properties, enzyme activities, and microbial characteristics. Our findings revealed that high nitrogen (10 mg/L) adversely impacted the relative growth rate of fresh biomass and total chlorophyll content in canopy-forming M. spicatum, while the chlorophyll a/b and free amino acid content increased. On the contrary, the growth and photosynthetic traits of resource-conservative V. natans were not affected by nitrogen loading. Functional traits (growth, photosynthetic, and stoichiometric) of M. spicatum but not V. natans exhibited significant correlations with environmental variables. Nitrogen loading significantly increased the concentration of nitrogen components in overlying water and pore water. The presence of submerged macrophytes significantly reduced the ammonia nitrogen and total nitrogen both in overlying water and pore water, and decreased total organic carbon in pore water. Nitrogen loading significantly inhibited sediment extracellular enzyme activities, but the planting of submerged macrophytes mitigated their negative effects. Furthermore, rhizosphere bacterial interactions were less compact compared to bare control, while eukaryotic communities exhibited increased complexity and connectivity. Path modeling indicated that submerged macrophytes mitigated the direct effects of nitrogen loading on overlying water and amplified the indirect effects on pore water, while also attenuating the direct negative effects of pore water on extracellular enzymes. The findings indicated that the restoration of submerged vegetation can mitigate eutrophication resulting from increased nitrogen loading through species-specific changes in functional traits and direct or indirect feedback mechanisms in the water–sediment system.

ObjectiveThis study analyzed the current research hotspots and future development trends of the therapeutic effects of microRNA on PNI axonal regeneration through bibliometric methods. Moreover, the current advantages and disadvantages of this field as well as future development prospects are discussed in depth.MethodsCiteSpace V and VOSviewer were used as bibliometric tools to complete the analysis of the research focus and direction of the published articles. To supplement, sort out, and summarize, we analyzed the research status of the study on the application of microRNAs for axonal regeneration after peripheral nerve injury from 2013 to 2023.ResultsA total of 207 publications were retrieved from the Web of Science database. After exclusion and screening, a final selection of 174 articles that met the research criteria. These 174 articles were authored by a total of 846 individuals, representing 24 countries and 199 institutions. Additionally, this study presents information on the annual publication output, country distribution, top 5 contributing authors, top 5 most cited articles, and top 10 contributing institutions.ConclusionAs one of the hottest topics today, microRNAs have become the current research hotspot in neural inflammation, neural cell repair and regeneration, neural protection, and functional recovery. With more investment in research in this field, more high-quality articles will be published in both domestic and international outstanding journals, which will bring a new era for the treatment of peripheral nerve injury.

Given the friction and drag reduction effects observed in various biological hexagonal structures in nature, a new design was implemented on the rubber surface of the stator of a submersible screw pump. This design featured a multilayer concentric hexagonal groove structure. Furthermore, a composite multilayer hexagonal structure integrating grooves and pits was also developed and applied. This study investigated the influence of groove layer number, groove depth, pit depth, and multilayer hexagonal groove texture arrangement on the rubber surface flow characteristics. Additionally, the pressure field state, the degree of influence on the oil film-bearing capacity, and the biomimetic and hydrodynamic lubrication theories were tested using the finite element analysis method. Tribological experiments were conducted on nanosecond laser-processed rubber textures under simulated liquid lubrication conditions, reflecting actual shale oil well experiments. These experiments aimed to investigate the influence of multilayer hexagonal shape parameters on the tribological characteristics of the stator-rotor friction pair of a submersible screw pump. The results indicated that with a constant overall size, a multilayer hexagonal structure with ~0.1 mm groove depth enhanced the oil film-bearing capacity, providing significant friction and drag reduction. For composite textures, a deeper pit depth within the study area enhanced the oil film-bearing capacity. Furthermore, a gradient arrangement of groove textures featuring wider outer grooves and shallower depth exhibited superior performance in terms of bearing capacity.

The effects of complex well conditions in shale oil wells on the swelling and tribological properties of high-acrylonitrile stator rubber used in screw pumps were investigated in this study. Tests were conducted considering the combined effects of immersion medium, temperature, and duration. The key parameters measured included mass change rate, volume change rate, hardness, elongation at break, tensile strength, surface micro-morphology of the rubber after thermal expansion and swelling, friction coefficient, and wear quantity. The results indicated that in the actual well fluids, the mass change rate of high-acrylonitrile rubber ranged from −1.08% to 1.29%, with a maximum volume change rate of 2.78%. In diesel oil, the greatest mass change rate of the rubber was 4.68%, and the volume change rate did not exceed ±1%, indicating superior swelling resistance. In both actual well fluids and diesel oil, the maximum decreases in hardness were 8.7% and 9.5%, respectively. Tensile strength and elongation at break decreased with increasing immersion temperature, with elongation at break in 80 °C diesel oil decreasing by over 50%, indicating a significant decline in the tensile properties of the rubber. The average friction coefficient of rubber specimens immersed in actual well fluids at three temperatures, as well as in diesel oil at 25 and 50 °C, decreased compared with the high-acrylonitrile rubber without thermal expansion and swelling. However, the average friction coefficient of rubber specimens immersed in diesel oil at 80 °C increased. The wear quantity of the rubber increased following immersion in both media. Additionally, the friction coefficient and wear quantity of the rubber increased with increasing immersion temperatures. The results of the study can offer valuable insights into assessing the durability of properties in high-acrylonitrile stator rubber under complex well conditions.

Pimpinella candolleana is known as Miao ethnic herbal medicine in Guizhou for the treatment of icteric hepatitis, acute cholecystitis and other diseases. To investigate the chemical constituents of P. candolleana and their anti-inflammatory activities, the chemical constituents from the 70% ethanol extract of P. candolleana were separated by silica gel, Sephadex LH-20, Toyopearl HW-40F, Toyopearl HW-40C, ODS and other column chromatography technologies, and their structures were elucidated by extensive spectroscopic analysis such as nuclear magnetic resonance (NMR) and mass spectrum (MS). The inflammatory cell model, built by LPS-induced RAW264.7 macrophage cells, was used to evaluate the anti-inflammatory activity. The results were as follows: (1) Twenty compounds from P. candolleana were isolated and identified of including vanillin (1), sesamin (2), 2-methyl-2-hydroxy-5-methoxy berz (d) hydrofuran-3-one (3), procatechin (4), 1,5-dihydroxy-2,3-dimethoxyxanthone (5), isorhamnetin (6), kaempferol (7), 8-hydroxy-2-methylchromone (8), luteolin (9), quercetin (10), 1-O-β-D-glucopyranosyl-(2S,3S,4R,8E)-2-［(2′R)-2′-hydroxypalmitoylamino］-8-octadecene-1,3,4-triol (11), isorhamnetin-3-O-β-D-galactopyranoside (12), isoquercitrin (13), norswertianolin (14), luteolin-6-C-α-L-arabinoside (15), kaempferol-3-O-β-D-galactopyranoside (16), kaempferol-7-O-β-D-glucopyranoside (17), luteolin-7-O-β-D-glucopyranoside (18), isovitexin (19), rutin (20). Compounds 1, 3, 4, 6, 7, 10, 13, 16, 18, and 20 were obtained from this plant for the first time. (2) The anti-inflammatory results showed that compounds 2-10, 12, 18 and 19 could significantly inhibit the LPS-induced NO content in RAW264.7 cells (P

ObjectiveTo explore the different processes of the themes and emotional evolution of various stakeholders in the network public opinion of sudden public health emergencies at different stages of the public opinion evolution lifecycle.MethodsThis paper proposes a cross-platform analysis method for online public opinion during the public health emergencies based on stakeholders. Firstly, data from multiple platforms are collected and integrated. Secondly, stakeholders are categorized and the stages of public opinion evolution are determined based on stakeholder theory and lifecycle theory. Finally, the Latent Dirichlet Allocation (LDA)+Word2vec model and Convolutional Neural Network (CNN) model are used to analyze the themes and emotional evolution of stakeholders during different stages of public opinion evolution.ResultsThere are differences in the evolution patterns of different types of stakeholders. The evolution process of stakeholders' focus points exhibits a two-stage transition from concentration to divergence. The focus points of stakeholders are closely associated with their respective social domains. The emotions of the public undergo a three-stage process of positive-negative-positive change.ConclusionsThis study can provide a reference for the government to have a more comprehensive understanding of the development trend of public opinion and reduce the negative impact of public opinion.

Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here, the authors show that low-dose nicotine promotes SIRT1 deacetylation of NAMPT and enhanced NAMPT activity which boosts NAD generation and improves age related symptoms.

Background: To evaluate the chemotherapy toxicity of 5-fluorouracil (5-FU) in the treatment of invasive moles. Methods: We conducted a retrospective study of therapeutic satisfaction, recurrence, and toxicity in 17 patients treated with 5-FU in the Zhuzhou Central Hospital, from 2015 to 2020. Results: After a single-agent 5-FU treatment a complete remission of low-risk invasive moles was observed, and remission of high-risk invasive moles reached rates of 76.5%. After 4–5 chemotherapy cycles, 5-FU reduced serum human chorionic gonadotropin (hCG) to normal levels in invasive moles. Furthermore, a toxicity assessment revealed that 5-FU chemotherapy has low toxicity and is generally acceptable for patients. Conclusions: 5-FU offers high efficacy in both low-risk and high-risk invasive moles, with low chemotherapy toxicity.

This paper proposes an analytical model of the double-stator spoke-type permanent magnet vernier machine (DSSTVM) using the subdomain method (SDM), which can be used to calculate the magnetic field distribution and corresponding electromagnetic parameters of the DSSTVM. The whole field domain is divided into several subdomains according to the magnetic characteristics of each region, within which Laplace’s and Poisson’s equations are solved accordingly in terms of magnetic vector potential (MVP). Then, the corresponding magnetic flux density distribution, back electromotive force (EMF), and electromagnetic torque of the DSSTVM can be obtained. Ultimately, finite element analysis (FEA) is adopted to validate the proposed analytical model’s effectiveness for quickly predicting the no-load and on-load performances of the DSSTVM.

Introduction:Cynanchum auriculatum (CA) is usually used to treat digestive disorders, such as anorexia, enteritis, dysentery, and indigestion. Functional dyspepsia (FD) is characterized by a group of symptoms associated with the gastroduodenal region. Recent pharmacological studies have demonstrated the efficacy of CA for treating FD. However, the pharmacokinetics (PK) and tissue distribution of CA in physiological and FD states is still unclear. The present study aimed to clarify the differences in PK parameters and tissue distribution of the four major active components of CA (baishouwu benzophenone, deacylmet-aplexigenin, qingyangshengenin, and syringic acid) under both physiological and FD states.Methods: For this, normal and FD rats were orally administered 10 mg/kg CA extract. Then, plasma and tissue (heart, liver, spleen, lung, kidney, brain, stomach, and small intestine) samples were obtained. The four active components of CA in rat plasma and tissues were quantified by developing and validating a fast and reliable ultra–high–performance liquid chromatography–mass spectrometry method.Results: The area under the plasma concentration–time curve from time zero to time t (AUC0-t) of baishouwu benzophenone was significantly lower in the FD group than in the normal group (p < 0.01). The FD group had significantly lower (p < 0.001) apparent volume of distribution and plasma clearance of qing-yangshengenin and significantly higher (p < 0.05) AUC0-t of deacylmetaplexigenin and qingyangshengenin. The four active components were rapidly distributed into various tissues, and the main target organs of CA activity were the stomach and small intestine. In addition, baishouwu benzophenone, deacylmetaplexigenin, and qingyangshengenin could cross the blood-brain barrier, indicating that the brain may be another target organ in the treatment of FD.Discussion: These results indicate that the pathological state of FD alters the PK behavior and tissue distribution characteristics of baishouwu benzophenone, deacylmetaplexigenin, qingyangshengenin, and syringic acid in the CA extract, providing an experimental basis for the role of CA in FD treatment.

Abstract Submerged macrophytes play a key role in the restoration of shallow eutrophic lakes. However, in some subtropical lakes, benthivorous fishes dominate the fish assemblages and influence the growth of submerged plants. A comprehensive understanding of the direct and indirect effects of benthivorous fishes on submerged plants is important. We conducted mesocosm experiments to examine the effects of three densities of benthivorous fish, Misgurnus anguillicaudatus, on the water properties, the growth, asexual reproduction, and the germination of turions of Potamogeton crispus L. Our results showed that fish disturbance increased TN, TP, PO4–P, NH4–N, and NO3–N of the water, raising the extinction coefficient K, Chl a, and the periphyton biomass. Benthivorous fish disturbance reduced the total biomass, root length, relative growth rate (RGR), and branching number while increasing the plant height of P. crispus. The P stoichiometric homeostasis coefficient (HP) (except turions) and HN was lower in plant tissues due to fish disturbance. Benthivorous fish disturbances promoted turions formation (e.g., increased turions total numbers and biomass) of P. crispus. Moreover, P. crispus exhibited transgenerational plasticity for benthivorous fish affecting turion emergence. The maximum final germination rate occurred only when fish density in the mother plant grow experiment matched that in the turion germination experiment. Turions generated by P. crispus disturbed by low‐density fish exhibited increased germination rates. Our findings suggest that controlling benthivorous fish reduces its indirect and direct effects on submerged vegetation, facilitating the successful restoration of these plants.

Abstract Background Being among the most common malignancies worldwide, hepatocellular carcinoma (HCC) accounting for the third cause of cancer mortality. The regulation of cell death is the most crucial step in tumor progression and has become a crucial target for nearly all therapeutic options. Cuproptosis, a copper-induced cell death, was recently reported in Science. However, its primary function in carcinogenesis is still unclear. Methods Cuproptosis-related lncRNAs significantly associated with overall survival (OS) were screened by stepwise univariate Cox regression. The signature of cuproptosis-related lncRNAs for HCC prognosis was constructed by the LASSO algorithm and multivariate Cox regression. Further Kaplan–Meier analysis, proportional hazards model, and ROC analysis were performed. Functional annotation was performed using gene set enrichment analysis (GSEA). The relationship between prognostic cuproptosis-related lncRNAs and HCC prognosis was further explored by GEPIA( http://gepia.cancer-pku.cn/ ) online analysis tool. Finally, we used the ESTIMATE and XCELL algorithms to estimate stromal and immune cells in tumor tissue and cast each sample to infer the underlying mechanism of cuproptosis-related lncRNAs in the tumor immune microenvironment (TIME) of HCC patients. Results Four cuproptosis-related lncRNAs were used to construct a prognostic lncRNA signature, which was an independent factor in predicting OS in HCC patients. Kaplan–Meier curves showed significant differences in survival rates between risk subgroups (p = 0.002). At the same time, we found that the expression levels of most immune checkpoint genes increased with increasing risk scores. Tumorigenesis and immunological-related pathways were primarily enhanced in the high-risk group, as determined by GSEA. The results of drug sensitivity analysis showed that compared with patients in the high-risk group, the IC50 values of erlotinib and lapatinib were lower in patients in the low-risk group, while the opposite was true for sunitinib, paclitaxel, gemcitabine, and imatinib. We also found that elevated AL133243.2 expression was significantly associated with worse OS and disease-free survival (DFS), more advanced T stage and higher tumor grade, and reduced immune cell infiltration, suggesting that HCC patients with low AL133243.2 expression in tumor tissues may have a better response to immunotherapy. Conclusion Collectively, the cuproptosis-associated lncRNA signature can serve as an independent predictor to guide individual treatment strategies. Furthermore, AL133243.2 is a promising marker for predicting immunotherapy response in HCC patients. This data may facilitate further exploration of more effective immunotherapy strategies for HCC.

Abstract Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and leptomeningeal metastases (LM). We conducted a retrospective study to comprehensively assess the clinical characteristics and risk factors of patients with advanced NSCLC who develop PM and LM. Patients with advanced NSCLC were enrolled. These patients were then divided into three groups for analysis: patients without BM (No-BM), patients with PM and patients with LM. Data on clinical characteristics of each patient at the time of diagnosis advanced NSCLC were extracted and analyzed. In addition, prediction models were developed and evaluated for PM and LM. A total of 592 patients were enrolled in the study. BM was present in 287 patients (48.5%). Among them, 185 and 102 patients had PM or LM. Patients with LM had a higher proportion of EGFR exon 21point mutations (L858R) compared to patients with No-BM and PM (p

Abstract The mRNA vaccine has provided a promising approach for cancer immunotherapies. However, only a few mRNA vaccines have been developed against colon adenocarcinoma (COAD). Screening potential targets for mRNA vaccines from numerous candidates is a substantial challenge. Considering the tumor heterogeneity, only a subset of patients might respond to vaccinations. This study was conducted to identify potential candidates for mRNA vaccines, and distinguish appropriate subgroups of COAD patients for vaccination. A total of five tumor antigens with prognostic values were identified, including IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5. The COAD patients were stratified into five immune subtypes (IS1‐IS5), according to consensus clustering analysis. Higher tumor mutation burden (TMB) was observed in IS1 and IS5 subtypes. The IS1 and IS5 subtypes have shown the baseline of immune‐hot tumor microenvironment, while other subtypes displayed immune desert phenotype. Distinct expressions of immune checkpoints (ICPs)‐related genes and immunogenic cell death (ICD) modulators were observed among five immune subtypes. Finally, the immune landscape was conducted to narrow the immune components for better personalized mRNA‐based vaccination. The IFIT3, PARP9, TAP1, STAT1, and OAS2 were confirmed as hub genes, and COAD patients with higher expressions of these genes might be more appropriate for mRNA vaccination. In conclusion, the IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5 were identified as potential candidates for developing mRNA vaccines against COAD, and patients in IS1 and IS5 subtypes might respond better to mRNA vaccination.

Abstract Background Burnout occurs frequently in nurses and seems more common in nurses providing palliative care. However, to our knowledge, there is a lack of understanding regarding the factors influencing burnout among palliative nurses in China. Methods A cross-sectional design was conducted. A total of 331 palliative nurses from 25 hospitals participated in this study. Anonymous data were collected through a self-designed social-demographic questionnaire, the Nursing Burnout Scale, the Perceived Social Support Scale, the General Self-Efficacy Scale, the Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Independent sample t tests, one-way ANOVA, Pearson correlations, and multiple linear regressions were performed to identify the related factors of the three dimensions of burnout. Results In the results of multiple linear regression, resilience, health condition, coping style, and pessimistic personality were common related factors; in addition, end-of-life care training, social support, and income satisfaction were statistically significantly associated with burnout. These factors could explain 38.6%, 27.8%, and 34.5% of the total variance in emotional exhaustion, depersonalization, and reduced personal accomplishment, respectively. Conclusions The findings of this study help policy makers and nurse managers better understand burnout among palliative nurses in China. The results highlighted the importance of implementing culture-oriented training programs, providing perceived organizational support, and building a reasonable salary system to decrease burnout among palliative nurses, increase the quality of nursing and promote the development of Chinese palliative care.

Retinal ganglion cell (RGC) damages are common in glaucoma, causing atrophy of the optic papilla, visual field damage, and visual loss. Transient receptor potential vanilloid 4 (TRPV4) is significantly expressed in the eyeball and is sensitive to mechanical and osmotic pressure. However, the specific role and mechanism of TRPV4 in glaucoma and RGC progression remain unclear. TRPV4 expression was detected in RGCs under different pressure culture conditions. We also explored the pressure effect on TRPV4 expression and the role and mechanism behind the functional regulation of RGCs. Immunofluorescence staining, western blotting, and TUNEL were utilized in this study. Our results established that TRPV4 was expressed in RGCs. TRPV4 expression was decreased at 40 mmHg and 60 mmHg, and the expression of BAX at 40 mmHg, 60 mmHg. Additionally, the expression of caspase 9 protein increased at 40 mmHg with the pressure increase compared with the conventional culture group. TUNEL staining revealed that the apoptosis rate of RGCs was elevated at 40 mmHg and 60 mmHg, compared with the traditional culture group. Therefore, the expression of BAX and caspase 9 increased, along with the apoptosis rate of RGCs compared with the control group. However, after TRPV4 antagonist treatment, the expression of BAX and caspase 9 decreased, and the apoptosis rate of RGCs decreased. Thus, TRPV4 may affect the mitochondrial apoptosis pathway, such as BAX and caspase 9, leading to the apoptosis of RGCs. The antagonists of TRPV4 could provide a new idea for clinically treating acute glaucoma.

Peripherally inserted central venous catheters (PICCs) are widely used in cardiology because they are convenient, effective, and safe. However, PICC implantation in patients with mirror-image dextrocardia who have thoracic tumors has not yet been reported. In this case report, we describe a 46-year-old patient with lung cancer who had a thoracic inclination and left pulmonary artery compression of the superior vena cava. PICC implantation under B-ultrasound guidance was planned. Because of the anatomical differences caused by mirror-image dextrocardia, we investigated the optimal position and measurement method for the tip of the PICC according to the compression site of the vascular lumen through a multidisciplinary team approach. Electrocardiography-assisted tip positioning combined with postoperative chest X-ray positioning was performed for accurate positioning.

Super-wetting interface materials have shown great potential for applications in oil–water separation. Hydrogel-based materials, in particular, have been extensively studied for separating water from oily wastewater due to their unique hydrophilicity and excellent anti-oil effect. In this study, a superhydrophilic and underwater superoleophobic bamboo cellulose hydrogel-coated mesh was fabricated using a feasible and eco-friendly dip-coating method. The process involved dissolving bamboo cellulose in a green alkaline/urea aqueous solvent system, followed by regeneration in ethanol solvent, without the addition of surface modifiers. The resulting membrane exhibited excellent special wettability, with superhydrophilicity and underwater superoleophobicity, enabling oil–water separation through a gravity-driven “water-removing” mode. The super-wetting composite membrane demonstrated a high separation efficiency of higher than 98% and a permeate flux of up to 9168 L·m−2·h−1 for numerous oil/water mixtures. It also maintained a separation efficiency of >95% even after 10 cycles of separation, indicating its long-term stability. This study presents a green, simple, cost-effective, and environmentally friendly approach for fabricating superhydrophilic surfaces to achieve oil–water separation. It also highlights the potential of bamboo-based materials in the field of oil–water separation.

It has been a long-cherished wish in biomedicine research to have an imaging tool to visualize gene expression, with good spatiotemporal resolution, in rodent and primate animals noninvasively and longitudinally. To this purpose, we here present a novel genetic encoded magnetic resonance imaging reporter, i.e., GEM reporter, for noninvasive visualization of cell-specific gene expression. The GEM reporter was developed through codon modification of a bacteria-originated manganese (Mn) binding protein, allowing the sequestration of endogenous Mn in local tissues. When expressed in bacteria, plant and animals, GEM reporter can robustly produce high image contrast in T1-weighted MRI without additional substrates or contrast agents. Importantly, GEM reporter can be tracked inherently by MRI in specific cells and tissues. These findings support GEM reporter as a versatile marker for deciphering gene expression spatiotemporally in living subjects.

Abstract Background and study aims Multiple surgical approaches have been studied and accepted for the removal of highly downward migrated lumbar disc herniation (LDH). Here, we investigated the efficacy and safety of full-endoscopic foraminoplasty for highly downward migrated LDH. Patients and methods Thirty-seven patients with highly down-migrated LDH treated by the full-endoscopic foraminoplasty between January 2018 and January 2020 were retrospectively investigated. Clinical parameters were evaluated preoperatively and 1, 6, and 12 months postoperatively, using pre- and post-operative Oswestry Disability Index (ODI) scores for functional improvement, visual analog scale (VAS) for leg and back pain, and modified MacNab criteria for patients satisfactory. Results Thirty-seven patients with highly downward migrated LDH were successfully removed via the transforaminal full-endoscopic discectomy. The average VAS back and leg pain scores were significantly reduced from 7.41 ± 1.17 and 8.68 ± 1.06 before operation to 3.14 ± 0.89 and 2.70 ± 0.46 at postoperative 1 month, and 1.76 ± 0.59 and 0.92 ± 0.28 at postoperative 12 months, respectively (P

This study aims to evaluate the distribution of pesticide residues in mango fruits and the contribution to chronic dietary exposure risks. 42 kinds of pesticides were analyzed with gas chromatography (GC) and ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The contribution to chronic dietary exposure risks for children and adult were calculated using point assessment approach. The cumulative risks were calculated with the method of relative potency factor (RPF). 44.1% of the whole mango samples and 35.3% of the pulp samples contained one or more pesticide residues. The most frequently detected pesticide was imidacloprid, and the detection rates in whole mango and pulp were 21.6% and 19.6%, respectively. According to the MRLs in China, the exceedance rates of pyraclostrobin, clothianidin, imidacloprid and difenoconazole in whole mango and pulp were 6.9% and 1.0%, 5.9% and 1.0%, 3.0% and 2.0%, 2.0% and 2.0%, respectively. The detection rate and exceedance rate of pesticide in non-bagged mango varieties (‘Tainong’, ‘Guifei’) were much higher than those in bagged mango variety (‘Jinhuang’). Pesticide residue levels in whole mango were mostly higher than those in pulp. In some mango samples, the residues of pesticides possessing strong systemic conductibility (neonicotinoid, trizoles and etc.) in pulp were higher than those in whole mango. These pesticides only detected in pulp of some mango samples. 7.9% of the pulp samples contained four or more pesticide residues, and the percentage was much higher (20.6%) in whole mango samples. The values of %ADI of all detected individual pesticides and pesticide groups (neonicotinoid and trizoles) for children and adult were far below 100%. The contribution of pesticide residues through mango to the chronic dietary risk was extremely low.

As microgrids develop rapidly, more inverters are adopted to achieve DC/AC or AC/DC/AC conversion of distributed generators (DGs). The virtual synchronous generator (VSG) control has started to replace the traditional droop control for inverters. In order to restore the frequency to its nominal value, most existing secondary frequency control (SFC) methods are based on frequency measurements. However, while reducing the rate of change of frequency (ROCOF), virtual inertia also slows down the convergence of frequency-based SFC. Therefore, this paper proposes a new distributed hierarchical control for fast frequency restoration. Based on the real-time VSG control at the bottom level, a novel frequency restoration control is designed. The power reference values generated by the proposed control can accelerate the frequency restoration with accurate power sharing. Meanwhile, by designing event-triggering conditions, parallel inverter controllers only need to communicate with neighbors at the event-triggered moments. Simulations have been performed in MATLAB/Simulink environment. Furthermore, the proposed control has also been tested on the experiment platform, which contains practical physical circuits and real-time controllers. Both simulation and experiment results verify the effectiveness of the proposed control strategy.

Background: Sheng-Mai San extracts (SMSE), derived from a Chinese medicine formula Sheng-Mai San, benefits prevention and treatment of cardiovascular disease. However, it remains unknown how SMSE exerts its effects on chronic intermittent hypoxia (CIH)-induced heart injury. Objective: This study aims to evaluate the efficacy of SMSE on CIH-induced heart injury by suppressing oxidative damage and promoting glucose energy metabolism. Methods: The CIH-induced model was established through the mice being placed in a hypoxic chamber with 7 to 8% O2. Then, such indexes as cardiac function, histopathological changes, creatine kinase (CK), superoxide dismutase (SOD) and myeloperoxidase (MPO) and malondialdehyde (MDA) were measured. Lastly, the influence on energy metabolism was explored through determining the ratio of ATP/ADP, concentrations of pyruvate and lactic acid, ATPase activities and levels of proteins including pyruvate kinase M2 (PKM2), fructose 6-phosphate kinase (6-FPK) and pyruvate dehydrogenase kinase 4 (PDK4). Results: SMSE could obviously improve cardiac function and histopathological changes of heart tissue; reduce CK and MPO activities as well as MDA and lactic acid contents; increase SOD and ATPase activities, the ratio of ATP/ADP and pyruvate concentration; and regulate the protein expression of PKM2, 6-FPK and PDK4. Conclusion: SMSE could attenuate CIH-induced heart injury via suppressing oxidative damage and regulating glucose metabolism.

Background: Findings on the usefulness of massage therapy (MT) in postoperative pain management are often inconsistent among studies. Objectives: This study’s aim is to conduct a meta-analysis of randomized controlled trials (RCT) to clarify the effects of massage therapy in the treatment of postoperative pain. Methods: Three databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were searched for RCTs published from database inception through January 26, 2021. The primary outcome was pain relief. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. The random-effect model was used to calculate the effect sizes and standardized mean difference (SMD) with 95 % confidential intervals (CIs) as a summary effect. The heterogeneity test was conducted through I2. Subgroup and sensitivity analyses were used to explore the source of heterogeneity. Possible publication bias was assessed using visual inspection of funnel plot asymmetry. Results: The analysis included 33 RCTs and showed that MT is effective in reducing postoperative pain (SMD, −1.32; 95 % CI, −2.01 to −0.63; p = 0.0002; I2 = 98.67 %). A similar significant effect was found for both short (immediate assessment) and long terms (assessment performed 4–6 weeks after the MT). Remarkably, we found neither the duration per session nor the dose had an impact on the effect of MT and there seemed to be no difference in the effects of different MT types. In addition, MT seemed to be more effective for adults. Furthermore, MT had better analgesic effects on cesarean section and heart surgery than orthopedic surgery. Limitations: Publication bias is possible due to the inclusion of studies in English only. Additionally, the included studies were extremely heterogeneous. Double-blind research on MT is difficult to implement, and none of the included studies is double-blind. There was some heterogeneity and publication bias in the included studies. In addition, there is no uniform evaluation standard for the operation level of massage practitioners, which may lead to research implementation bias. Conclusions: MT is effective in reducing postoperative pain in both short and long terms.

Abstract Background Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. Methods Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.

Background: Pyroptosis is an important component of the tumor microenvironment and associated with the occurrence and progression of cancer. As the expression of pyroptosis-related genes and its impact on the prognosis of colon cancer (CC) remains unclear, we constructed and validated a pyroptosis-related genes signature to predict the prognosis of patients with CC.Methods: Microarray datasets and the follow-up clinical information of CC patients were obtained from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Candidate genes were screened out for further analysis. Various methods were combined to construct a robust pyroptosis-related genes signature for predicting the prognosis of patients with CC. Based on the gene signature and clinical features, a decision tree and nomogram were developed to improve risk stratification and quantify risk assessment for individual patients.Results: The pyroptosis-related genes signature successfully discriminated CC patients with high-risk in the training cohorts. The prognostic value of this signature was further confirmed in independent validation cohort. Multivariable Cox regression and stratified survival analysis revealed this signature was an independent prognostic factor for CC patients. The decision tree identified risk subgroups powerfully, and the nomogram incorporating the gene signature and clinical risk factors performed well in the calibration plots.Conclusion: Pyroptosis-related genes signature was an independent prognostic factor, and can be used to predict the prognosis of patients with CC.

Fiber optic Fabry–Pérot sensors have been widely developed with unique advantages, such as ease of reuse, resistance to electromagnetic interference, light weight, and their ability to work in extreme environments. There are many demodulation methods that can be applied to fiber optic Fabry–Pérot sensors, including the intensity demodulation method, spectral demodulation, and the phase carrier method, but these demodulation methods cannot meet the requirements that take into account range, speed, and dynamic and static demodulation capabilities. In view of these problems, this paper uses nonlinear differential equations to solve the problem of simultaneous measurement of a large number of ranges and dynamic and static parameters. The measuring interferometer in the demodulation module was built using a polarizing interferometer, which avoids the difficulty in optical wedge processing when using a Fizeau interferometer. Regarding the problems of high and low signal-to-noise ratios of the generated signal, for the problem that the introduction of dispersion in the crystal causes the demodulation result of the traditional demodulation method to be wrong, a nonlinear differential equation is proposed to achieve the correct demodulation of the fiber optic sensor: the slow demodulation speed problem. This paper designs the acquisition, transmission, and processing system based on digital signal processing and a field-programmable gate array, which provide a hardware platform for real-time demodulation. Finally, experiments to test the resolution, linearity, stability, and repeatability of the interferometer were carried out on the designed demodulation system.

Background: Fatty acid metabolism (FAM)-related genes play a key role in the development of stomach adenocarcinoma (STAD). Although immunotherapy has led to a paradigm shift in STAD treatment, the overall response rate of immunotherapy for STAD is low due to heterogeneity of the tumor immune microenvironment (TIME). How FAM-related genes affect TIME in STAD remains unclear.Methods: The univariate Cox regression analysis was performed to screen prognostic FAM-related genes using transcriptomic profiles of the Cancer Genome Atlas (TCGA)-STAD cohort. Next, the consensus clustering analysis was performed to divide the STAD cohort into two groups based on the 13 identified prognostic genes. Then, gene set enrichment analysis (GSEA) was carried out to identify enriched pathways in the two groups. Furthermore, we developed a prognostic signature model based on 7 selected prognostic genes, which was validated to be capable in predicting the overall survival (OS) of STAD patients using the univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analyses. Finally, the “Estimation of STromal and Immune cells in MAlignant Tumours using Expression data” (ESTIMATE) algorithm was used to evaluate the stromal, immune, and ESTIMATE scores, and tumor purity of each STAD sample.Results: A total of 13 FAM-related genes were identified to be significantly associated with OS in STAD patients. Two molecular subtypes, which we named Group 1 and Group 2, were identified based on these FAM-related prognostic genes using the consensus clustering analysis. We showed that Group 2 was significantly correlated with poor prognosis and displayed higher programmed cell death ligand 1 (PD-L1) expressions and distinct immune cell infiltration patterns. Furthermore, using GSEA, we showed that apoptosis and HCM signaling pathways were significantly enriched in Group 2. We constructed a prognostic signature model using 7 selected FAM-related prognostic genes, which was proven to be effective for prediction of STAD (HR = 1.717, 95% CI = 1.105–1.240, p < 0.001). After classifying the patients into the high- and low-risk groups based on our model, we found that patients in the high-risk group tend to have more advanced T stages and higher tumor grades, as well as higher immune scores. We also found that the risk scores were positively correlated with the infiltration of certain immune cells, including resting dendritic cells (DCs), and M2 macrophages. We also demonstrated that elevated expression of gamma-glutamyltransferase 5 (GGT5) is significantly associated with worse OS and disease-free survival (DFS), more advanced T stage and higher tumor grade, and increased immune cell infiltration, suggesting that STAD patients with high GGT5 expression in the tumor tissues might have a better response to immunotherapy.Conclusion: FAM-related genes play critical roles in STAD prognosis by shaping the TIME. These genes can regulate the infiltration of various immune cells and thus are potential therapeutic targets worthy of further investigation. Furthermore, GGT5 was a promising marker for predicting immunotherapeutic response in STAD patients.

Abstract Background There is a huge controversy about whether xenograft or allograft in the “immune-privileged” brain needs immunosuppression. In animal studies, the prevailing sophisticated use of immunosuppression or immunodeficient animal is detrimental for the recipients, which results in a short lifespan of animals, confounds functional behavioral readout of the graft benefits, and discourages long-term follow-up. Methods Neuron-restricted neural progenitor cells (NPCs) were derived from human embryonic stem cells (ESCs, including H1, its gene-modified cell lines for better visualization, and HN4), propagated for different passages, and then transplanted into the brain of immunocompetent rats without immunosuppressants. The graft survivals, their cell fates, and HLA expression levels were examined over time (up to 4 months after transplantation). We compared the survival capability of NPCs from different passages and in different transplantation sites (intra-parenchyma vs. para- and intra-cerebroventricle). The host responses to the grafts were also investigated. Results Our results show that human ESC-derived neuron-restricted NPCs survive extendedly in adult rat brain parenchyma with no need of immunosuppression whereas a late-onset graft rejection seems inevitable. Both donor HLA antigens and host MHC-II expression level remain relatively low with little change over time and cannot predict the late-onset rejection. The intra-/para-cerebroventricular human grafts are more vulnerable to the immune attack than the intrastriatal counterparts. Prevention of graft hyperplasia by using hypoproliferative late passaged human NPCs further significantly extends the graft survival time. Our new data also shows that a subpopulation of host microglia upregulate MHC-II expression in response to the human graft, but fail to present the human antigen to the host immune system, suggestive of the immune-isolation role of the blood–brain barrier (BBB). Conclusions The present study confirms the “immune privilege” of the brain parenchyma and, more importantly, unveils that choosing hypoproliferative NPCs for transplantation can benefit graft outcome in terms of both lower tumor-genic risk and the prolonged survival time without immunosuppression.

Janus membranes with superwetting play an important role in many fields, such as oil/water separation, unidirectional fluid transportation, microfluidic devices, intelligent ion valve, mass/heat transfer applications, etc. Although there has been some progress in the preparation of the Janus membranes with unidirectional penetration, it still remains a great difficulty for facile fabrication of two dimensional Janus membranes with a large pore structure and stable bubble unidirectional transport in the water. Herein, a signal-layer Janus membrane with superwetting is fabricated via the method of liquid-regulated hydrophobic modification strategy. The resultant Janus mesh achieves underwater unidirectional penetration. Namely, Underwater bubbles can pass unidirectionally from superhydrophobic side to hydrophilic side, but are blocked from passing through in the opposite direction. Thus, this Janus membrane with the unidirectional underwater bubbles penetration “diode” performance. We believe this work can promote the development of multi-dimensional Janus materials for fluid directional transport.

Ciprofloxacin is ubiquitous and poses a potential threat to aquatic ecosystems. However, the comprehensive effect of prolonged ciprofloxacin exposure on the submerged clonal plant Vallisneria natans (Lour.) Hara remains unknown. Growth and physiological responses in V. natans exposed to ciprofloxacin at concentrations of 0, 0.05, 0.25, 1.25, 2.5, 5 and 10 mg/L were repeatedly evaluated on Days 7, 14, 28, 42 and 56. V. natans maintained good growth properties under 0.05–0.25 mg/L ciprofloxacin treatments, while the inhibition effect on plant growth induced by higher-concentration treatments increased over time. The IC50 values of ciprofloxacin for growth endpoints ranged from 1.6 mg/L to 5.3 mg/L and displayed time-dependent decreases. Pigment contents were significantly stimulated by ciprofloxacin on Day 7 but decreased to varying degrees as the exposure time was extended. Soluble protein and hydrogen peroxide content rose significantly over the first 14 days of treatment with 0.25–10 mg/L ciprofloxacin but decreased under 1.25–10 mg/L ciprofloxacin treatments since Day 28. Antioxidants including superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase and proline functioned well in mitigating oxidative stress under different ciprofloxacin concentrations, lowering the comprehensive toxic effects of ciprofloxacin on V. natans during the period from Day 14 to Day 42, as evidenced by decreased IBR (integrated biomarker response) values. However, the toxic pressure of ciprofloxacin on V. natans peaked on Day 56. These findings suggest that exposure time can influence the responses of V. natans exposed to ciprofloxacin and that IBR can be employed to evaluate the integrated impacts of prolonged ciprofloxacin contamination in aquatic settings.

Prostate cancer (PCa) is the most common cancer in men in the western world, but the lack of specific and sensitive markers often leads to overtreatment of prostate cancer which eventually develops into castration-resistant prostate cancer (CRPC). Novel protein markers for diagnosis and management of CRPC will be promising. In this review, we systematically summarize and discuss the expression pattern of emerging proteins in tissue, cell lines, and serum when castration-sensitive prostate cancer (CSPC) progresses to CRPC; focus on the proteins involved in CRPC growth, invasion, metastasis, metabolism, and immune microenvironment; summarize the current understanding of the regulatory mechanisms of emerging proteins in CSPC progressed to CRPC at the molecular level; and finally summarize the clinical applications of emerging proteins as diagnostic marker, prognostic marker, predictive marker, and therapeutic marker.

Abstract Background Dysregulated miRNAs are involved in carcinogenesis of the breast and may be used as prognostic biomarkers and therapeutic targets during the cancer process. The purpose of this study was to explore the effect of miR-105-3p on the tumourigenicity of breast cancer and its underlying molecular mechanisms. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to detect the expression of miR-105-3p in breast cancer tissues and cell lines. The impacts of miR-105-3p on the proliferation, migration, invasion and apoptosis of human breast cancer cells (MCF-7 and ZR-75-30) were evaluated by CCK-8 assays, Transwell chamber assays, TUNEL assays and western blot analyses. In addition, bioinformatics and luciferase reporter assays were used to determine the target genes of miR-105-3p. Results The expression of miR-105-3p was elevated in breast cancer tissues and increased with tumour severity. Downregulation of miR-105-3p could inhibit cell proliferation, suppress cell migration/invasion, and promote cell apoptosis in MCF-7 and ZR-75-30 cells. Furthermore, Golgi integral membrane protein 4 (GOLIM4) was identified as the direct target gene of miR-105-3p by bioinformatics and luciferase reporter assays. In addition, silencing GOLIM4 restored the anti-breast cancer effects induced by miR-105-3p downregulation. Conclusions MiR-105-3p acts as an oncogene to promote the proliferation and metastasis of breast cancer cells by targeting GOLIM4, which provides a new target for the prevention and treatment of breast cancer.

Although Polygonum orientale L. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.

Series-winding three-phase PMSMs have a higher bus voltage utilization than the conventional three-phase PMSMs with star connection. This topology is suitable for applications with a limited bus voltage. However, the zero-sequence current controller will reduce the bus voltage utilization of the series-winding PMSMs, which causes problems in the flux-weakening controller design. The conventional flux-weakening control algorithms will cause the series-winding PMSMs to enter the overmodulation region early and degrade the performance of the zero-sequence current suppression algorithm. In this paper, a new flux-weakening controller with a dynamic fundamental voltage limit (FW-DFVL) is designed for the series-winding three-phase PMSM traction system. Firstly, the space vector modulation method combines the proposed virtual zero-sequence vectors to realize both the fundamental current generation and the zero-sequence current suppression. The accurate bus voltage utilization in the fundamental current subspace can be derived from the proposed modulation method. Secondly, the gradient descent method generates the flux-weakening d-axis reference current with the dynamic fundamental voltage, which will converge faster than the conventional PI-based flux-weakening control scheme. Thirdly, the flux-weakening controller in the overmodulation region is also designed where the zero-sequence current will no longer be suppressed. The bus voltage utilization is Vdc in this operation mode. Finally, both the simulation and experimental results are utilized to verify the effectiveness of the proposed FW-DFVL, where faster dynamic performance and higher bus utilization are observed.

The Thomson scattering diagnostic of the HL-2A tokamak device was upgraded to improve its multi-point diagnostic capability, including new collection optics, fibers bundles, and data analysis code. The small old collection lens was replaced by a six-piece lens with a Cooke optical design. The aperture of its first standard sphere face is 310.125 mm, which successfully increases the amount of collected scattering light by about three times. The new collection optic module allows for up to twenty-six spatial points. A kind of Y-type fiber bundle has also been used to ensure that the fiber end-face matches the image of the laser beam exactly. Additionally, the new data analysis code can provide preview results in seconds. Finally, the multi-point Te diagnostic ability has been significantly improved.

Appropriate exercise such as voluntary wheel-running can induce physiological cardiac hypertrophy. Notch1 plays an important role in cardiac hypertrophy; however, the experimental results are inconsistent. In this experiment, we aimed to explore the role of Notch1 in physiological cardiac hypertrophy. Twenty-nine adult male mice were randomly divided into a Notch1 heterozygous deficient control (Notch1+/− CON) group, a Notch1 heterozygous deficient running (Notch1+/− RUN) group, a wild type control (WT CON) group, and a wild type running (WT RUN) group. Mice in the Notch1+/− RUN and WT RUN groups had access to voluntary wheel-running for two weeks. Next, the cardiac function of all of the mice was examined by echocardiography. The H&E staining, Masson trichrome staining, and a Western blot assay were carried out to analyze cardiac hypertrophy, cardiac fibrosis, and the expression of proteins relating to cardiac hypertrophy. After two-weeks of running, the Notch1 receptor expression was decreased in the hearts of the WT RUN group. The degree of cardiac hypertrophy in the Notch1+/− RUN mice was lower than that of their littermate control. Compared to the Notch1+/− CON group, Notch1 heterozygous deficiency could lead to a decrease in Beclin-1 expression and the ratio of LC3II/LC3I in the Notch1+/− RUN group. The results suggest that Notch1 heterozygous deficiency could partly dampen the induction of autophagy. Moreover, Notch1 deficiency may lead to the inactivation of p38 and the reduction of β-catenin expression in the Notch1+/− RUN group. In conclusion, Notch1 plays a critical role in physiologic cardiac hypertrophy through the p38 signaling pathway. Our results will help to understand the underlying mechanism of Notch1 on physiological cardiac hypertrophy.

Plant fermentation extracts (PFEs) produced from fermenting various fruits and vegetables by microorganisms have traditionally been consumed as healthy beverages in Asia. Herein, the immunomodulatory activities of a novel polysaccharide (AP) isolated from PFE were examined in RAW264.7 cells. The results showed that AP was composed of Rha, Xyl, Man and Glu in a molar ratio of 9.7:27.6:8.81:53.85 and the average molecular weight was 4.81 × 105 Da. Our data showed that AP could significantly enhance the phagocytic activity of RAW264.7 cells and their ability to release NO, TNF-α, IL-6 and IL-10. Furthermore, AP could significantly up-regulate the mRNA expression of iNOS, cytokines (TNF-α, IL-6, IL-10) and pattern recognition receptors (TLR2, MR, GR, CR3 and SR). Western blotting demonstrated that the regulation of NO and TNF-α were mediated through the NF-κB and MAPK signalling pathways. These findings helped to elucidate the immunomodulatory properties of the polysaccharide AP and PFE.

Abstract Background Clonal plants are important in maintaining wetland ecosystems. The main growth types of clonal plants are the guerrilla and phalanx types. However, little is known about the effects of these different clonal growth types on plant plasticity in response to heterogeneous resource distribution. We compared the growth performance of clonal wetland plants exhibiting the two growth forms (guerrilla growth form: Scirpus yagara, Typha orientalis, Phragmites australis and Sparganium stoloniferum; phalanx growth form: Acorus calamus, Schoenoplectus tabernaemontani and Butomus umbellatus) grown in soil substrates that were either homogeneous or heterogeneous but had the same total amount of nutrients. Results We found that the morphological traits (plant height, ramet number, spacer diameter and length) and biomass accumulation of the guerrilla clonal plants (T. orientalis) were significantly enhanced by heterogeneity, but those of the phalanx clonal plants (A. calamus, S. tabernaemontani and B. umbellatus) were not. The results showed that the benefits of environmental heterogeneity to clonal plants may be correlated with the type of clonal structure. Conclusions Guerrilla clonal plants, which have a dispersed, flexible linear structure, are better suited to habitats with heterogeneous resources. Phalanx clonal plants, which form compact structures, are better suited to habitats with homogeneous resources. Thus, wetland clonal species with the guerrilla clonal structure benefit more from soil nutrient heterogeneity.

The non-apoptotic cell death processes including pyroptosis and ferroptosis have been implicated in the progression and therapeutic responses of pancreatic adenocarcinoma (PAAD). However, the extent to which pyroptosis and ferroptosis influence tumor biology remains ambiguous, especially in PAAD, which is characterized with “cold” immunity. Considering the heterogeneity among different patients, it was more practical to quantify distinct cell death profiles in an individual tumor sample. Herein, we developed a pyroptosis-ferroptosis (P-F) score for PAAD patients in The Cancer Genome Atlas (TCGA) database. A high P-F score was associated with active immune phenotype, decreased genomic alterations, and significantly longer survival. Good accuracy of the P-F score in predicting overall survival (OS) was further confirmed in the TCGA-PAAD, ICGC-PACA-CA, and E-MTAB-6134 cohorts. Besides, one immunotherapy cohort (IMvigor210 dataset) has verified that patients with high P-F scores exhibited significant advantages in therapeutic responses and clinical benefits. The sensitivity to chemotherapeutics was analyzed through the Genomics of Drug Sensitivity in Cancer (GDSC), and patients with low P-F score might be more sensitive to paclitaxel and 5-fluorouracil. Collectively, the P-F score based on the systematic evaluation of cell death profiles could serve as an effective biomarker in predicting the outcomes and responses of PAAD patients to treatments with chemotherapeutic agents or immunotherapies.

Abstract The relationships between producers (e.g., macrophytes, phytoplankton and epiphytic algae) and snails play an important role in maintaining the function and stability of shallow ecosystems. Complex relationships exist among macrophytes, epiphytic algae, phytoplankton, and snails. We studied the effects of snail communities (consisting of Radix swinhoei, Hippeutis cantori, Bellamya aeruginosa, and Parafossarulus striatulus) on the biomass of phytoplankton and epiphytic algae as well as on the growth of three species of submerged macrophytes (Hydrilla verticillata, Vallisneria natans, and one exotic submerged plant, Elodea nuttallii) in a 90‐day outdoor mesocosm experiment conducted on the shore of subtropical Lake Liangzihu, China. A structural equation model showed that the snail communities affected the submerged macrophytes by grazing phytoplankton and epiphytic algae (reduction in phytoplankton Chl‐a and epiphytic algal abundance), enhancing the biomass of submerged macrophytes. Highly branched macrophytes with high surfaces and morphologies and many microhabitats supported the most snails and epiphytic algae (the biomass of the snail communities and epiphytic algae on H. verticillata was greater than that on V. natans), and snails preferred to feed on native plants. Competition drove the snails to change their grazing preferences to achieve coexistence.

Abstract Background Aging‐associated osteoporosis is frequently seen in the elderly in clinic, but efficient managements are limited because of unclear nosogenesis. The current study aims to investigate the role of melatonin on senescent bone marrow stromal cells (BMSCs) and the underlying regulating mechanism. Methods Melatonin levels were tested by ELISA. Gene expression profiles were performed by RNA‐sequencing, enrichment of H3K36me2 on gene promoters was analyzed by Chromatin Immunoprecipitation Sequencing (ChIP‐seq), and chromatin accessibility was determined by Assay for Transposase‐Accessible Chromatin with high‐throughput sequencing (ATAC‐seq). Osteogenesis of BMSCs in vitro was measured by Alizarin Red and Alkaline Phosphatase staining, and in vivo effects of melatonin was assessed by histological staining and micro computed tomography (micro‐CT) scan. Correlation of NSD2 expression and severity of senile osteoporosis patients were analyzed by Pearson correlation. Results Melatonin levels were decreased during aging in human bone marrow, accompanied by downregulation of the histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2) expression in the senescent BMSCs. Melatonin stimulated the expression of NSD2 through MT1/2‐mediated signaling pathways, resulting in the rebalancing of H3K36me2 and H3K27me3 modifications to increase chromatin accessibility of the osteogenic genes, runt‐related transcription factor 2 (RUNX2) and bone gamma‐carboxyglutamate protein (BGLAP). Melatonin promoted osteogenesis of BMSCs in vitro, and alleviates osteoporosis progression in the aging mice. In clinic, severity of senile osteoporosis (SOP) was negatively correlated with melatonin level in bone marrow, as well as NSD2 expression in BMSCs. Similarly, melatonin remarkably enhanced osteogenic differentiation of BMSCs derived from SOP patients in vitro. Conclusions Collectively, our study dissects previously unreported mechanistic insights into the epigenetic regulating machinery of melatonin in meliorating osteogenic differentiation of senescent BMSC, and provides evidence for application of melatonin in preventing aging‐associated bone loss.