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Abstract Background Migraine is one of the most common diseases worldwide while current treatment options are not ideal. New therapeutic classes of migraine, the calcitonin gene-related peptide (CGRP) antagonists, have been developed and shown considerable effectiveness and safety. The present study aimed to systematically evaluate the efficacy and safety of atogepant, a CGRP antagonist, for migraine prophylaxis from the results of randomized controlled trials (RCTs). Methods The Cochrane Library, Embase, PubMed and https://www.clinicaltrials.gov/ were searched for RCTs that compared atogepant with placebo for migraine prophylaxis from inception of the databases to Feb 1, 2024. Outcome data involving efficacy and safety were combined and analyzed using Review Manager Software version 5.3 (RevMan 5.3). For each outcome, risk ratios (RRs) or standardized mean difference (SMD) were calculated. Results 4 RCTs with a total of 2813 subjects met our inclusion criteria. The overall effect estimate showed that atogepant was significantly superior to placebo in terms of the reduction of monthly migraine (SMD − 0.40, 95% CI -0.46 to -0.34) or headache (SMD − 0.39, 95% CI -0.46 to -0.33) days, the reduction of acute medication use days (SMD − 0.45, 95% CI -0.51 to -0.39) and 50% responder rate (RR 1.66, 95% CI 1.46 to 1.89), while no dose-related improvements were found between different dosage groups. For the safety, significant number of patients experienced treatment-emergent adverse events (TEAEs) with atogepant than with placebo (RR 1.10, 95% CI 1.02–1.21) while there was no obvious difference between the five dosage groups. Most TEAEs involved constipation (RR 2.55, 95% CI 1.91–3.41), nausea (RR 2.19, 95% CI 1.67–2.87) and urinary tract infection (RR 1.49, 95% CI 1.05–2.11). In addition, a high dosage of atogepant may also increase the risk of treatment-related TEAEs (RR 1.64, 95% CI 1.02–2.63) and fatigue (RR 3.07, 95% CI 1.13–8.35). Conclusions This meta-analysis suggests that atogepant is effective and tolerable for migraine prophylaxis including episodic or chronic migraine compared with placebo. It is critical to weigh the benefits of different doses against the risk of adverse events in clinical application of atogepant. Longer and multi-dose trials with larger sample sizes are required to verify the current findings.

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting millions of people worldwide, with no effective treatment currently available. In recent decades, various traditional Chinese medicines (TCMs) and their active ingredients have shown the potential to attenuate the pathogenesis of AD in cellular and animal models. However, the effects of TCM formulas, which are typically administered in practice, have been less studied. This study aims to investigate the therapeutic effects of several formulas consisting of 4 components herbal components: catalpol, puerarin, gastrodin, and borneol, on streptozotocin (STZ)-induced AD models in cells and rats. The new object recognition (NOR), elevated plus maze (EMP), and Morris water maze (MWM) tests were used to evaluate the cognitive functions of rats. Golgi staining, Haematoxylin and Eosin (HE) staining, and Nissl staining analyses were employed assess the physiology of hippocampal tissues. Gene expression profiles were analyzed used transcriptomics and reverse transcription quantitative polymerase chain reaction analysis, while protein expression levels were determined using immunoblotting, immunohistochemical, and immunofluorescence. The production of cytokines was evaluated with enzyme-linked immunosorbent assay. The results demonstrated that the combined administration of these 4 components (CPGB) had superior mitigating effects on AD cell model, as evidenced by the reduced pro-inflammatory cytokine production and decreased deposition of Aβ protein. Further in vivo and in vitro experiments confirmed that varying doses of CPGB formula effectively ameliorated STZ-induced cognitive deficits, as shown by NOR, MWM, and EMP tests, as well as pathological changes in hippocampal tissues and a 3-dimensional brain neurovascular unit (3D-NVU) model, including decreased deposition of Aβ protein and formation of plaques. Transcriptome sequencing and analysis identified 35 genes with significantly altered expression levels due to STZ and CPGB treatment in hippocampal tissues, which were enriched in the Tlr4/Myd88/NF-κB signaling pathway. Interference with this pathway significantly influenced the therapeutic effects of CPGB in the 3D-NVU model. Collectively, these findings suggest that the combined administration of catalpol, puerarin, gastrodin, and borneol offers superior therapeutic effects on AD by modulating the Tlr4/Myd88/NF-κB signaling pathway. This study strengthens the theoretical foundation for using TCMs to treat AD, proving new insights and references for alleviating and treating AD.

ABSTRACT: Improving immune function is an important indicator for establishing cold adaptation in broilers. In the study, to explore the effects and molecular mechanisms of intermittent and mild cold stimulation (IMCS) on the immune function of broilers, CIRP and TRPM8, induced by cold stimulation, as well as the NF-κB and MAPK pathways which play an important role in immune response, were selected to investigate. A total of 192 one-day-old broilers (Ross 308) were selected and randomly divided into the control group (CC) and the cold stimulation group (CS). The broilers in CC were raised at normal feeding temperature from d 1 to 43, while the broilers in CS were subjected to cold stimulation from day 15 to 35, with a temperature 3 °C below that of the CC group for 5 h, at 1 d intervals. The results showed that IMCS had little effect on the broiler hearts, and the myocardial structure was not damaged. On d 22, IMCS significantly increased the mRNA levels of CIRP, TRPM8, P65, P38, COX-2, TNF-α, IFN- γ, IL-6, IL-10, and the protein levels of CIRP, P65, P38, IL-1β and iNOS in the hearts, and the levels of CIRP and all cytokines in the serum (P ≤ 0.05). The mRNA and protein levels of IκB-α were significantly reduced (P ≤ 0.05). On d 36, the mRNA levels of TRPM8, P65, ERK, and IL-10 in the hearts and the content of COX-2 in the serum in CS were increased significantly (P ≤ 0.05), while the mRNA levels of IκB-α, P38, and IL-1β were decreased significantly (P ≤ 0.05). On d 43, IMCS significantly upregulated the mRNA levels of TRPM8, IFN- γ, IL-4, IL-6, IL-10, and the protein levels of IκB-α, P38, and the levels of iNOS, TNF-α, IL6 and IL10 in the serum (P ≤ 0.05); whereas it significantly downregulated CIRP, JNK, P38, iNOS, TNF-α mRNA levels, and CIRP, P65, ERK, JNK, IL1β and iNOS protein levels (P ≤ 0.05). Therefore, IMCS can enhance broiler immune function through co-regulation of CIRP and TRPM8 on the NF-κB and MAPK pathways, which facilitate the cold adaptation in broilers.

Abstract Objectives Pituitary abscess (PA) accounts for only 0.3–0.5% of sellar masses, and the lack of specific clinical symptoms makes diagnosing PA difficult without a surgical biopsy. In clinical practice, PA is often mistaken for cystic pituitary adenoma, craniopharyngioma, and Rathke’s cyst. Thus, this study aims to investigate challenges in diagnosing PA and evaluate the importance of combining intraoperative surgery with postoperative antibiotic treatment. Methods We conducted a retrospective analysis of 19 patients diagnosed with PA through histopathology. All patients underwent transsphenoidal surgery (TSS) for pituitary adenomas after undergoing comprehensive preoperative evaluations, including routine tests, endocrine assay, and imaging examination. Furthermore, we compared different treatments for pituitary abscess (PA) to determine the most effective approach for achieving a favorable prognosis. Results The most prevalent symptom of PA was headache, especially in the frontal–temporal and vertex regions, ranging from mild to moderate severity. Hypopituitarism-related symptoms were also frequently observed, including hypaphrodisia, cold sensitivity, fatigue, weight loss, polyuria, and amenorrhea. Twelve patients exhibited abnormalities in endocrinology examinations. Diagnosing PA correctly is challenging. In our study, none of the patients were correctly diagnosed with PA prior to surgery, and many sellar lesions were misdiagnosed. The favorable prognosis was largely attributed to surgical intervention and active postoperative antibiotic therapy. Conclusions Given the lack of clarity in preoperative diagnosis, typical intraoperative findings and effective antibiotics treatment are more indicative of the correct diagnosis than other tests. In terms of therapy, optimal surgical intervention and active postoperative antibiotic treatment contribute to resolving the challenges posed by PA.

Abstract Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer. Graphical Abstract

Abstract Incorporating hydrophilic and charged porous nanofillers to prepare high-performance thin film nanocomposite (TFN) nanofiltration (NF) membranes is an effective method to achieve efficient water treatment. In this study, we synthesize the sulfonated covalent organic framework nanosheets (S-CONs) with higher hydrophilicity and electronegativity by immobilizing sulfonic acid groups (–SO3H) on TpPa-1 nanosheets. The S-CONs are incorporated in the PA layer by interfacial polymerization (IP) reaction. The results indicated that the S-CONs could modulate the hydrophilicity, thickness, and electronegativity of TFN-NF membranes. At the optimal addition of S-CONs (0.006 g), the pure water permeance increases to 8.84 $${\rm{L}}\cdot{\rm{m}}^{-2}\cdot{\rm{h}}^{-1}\cdot{\rm{bar}}^{-1}$$ L ⋅ m − 2 ⋅ h − 1 ⋅ bar − 1 , which is about 1.75 times than the TFC membrane, with a high Na2SO4 rejection reaching 98.97%. The improvement of the separation performance mainly results from the reduction of PA layer thickness (from ~178.00–198.00 to ~100.00–128.00 nm) and the increase of surface electronegativity (from −20.37 to −44.41 mV at pH = 7.00). More interestingly, the amide bond formed between the S-CONs and TMC improved the chlorine resistance of the membranes. This study reveals the potential of using functionalized 2D CONs as nanofillers to modify TFC membranes for efficient nanofiltration.

Abstract This study aimed to assess the impact of light perception presence or absence on visual function recovery in patients with traumatic optic neuropathy (TON). A retrospective analysis was conducted on the clinical data of 206 TON patients. Based on the presence or absence of light perception after injury, patients were categorized into a light perception group and a non-light perception group. A comparison was made between the two groups regarding visual acuity recovery before and after treatment. The non-light perception group comprised 63 patients, with a treatment effectiveness rate of 39.68%. The light perception group consisted of 143 patients, with a treatment effectiveness rate of 74.83%. The difference between the two groups was statistically significant (χ2 = 23.464, P

Abstract In this study, a new short‐term wind power prediction model based on a temporal convolutional network (TCN) and the Informer model is proposed to solve the problem of low prediction accuracy caused by large wind speed fluctuations in short‐term prediction. First, an input feature selection method based on the maximum information coefficient is proposed after considering the problem of information interference caused by excessively large input features. A dynamic time planning method is used to select the optimal input step of historical power. Then, the combined forecasting model composed of TCN and the Informer is constructed in accordance with the numerical weather forecast and historical power data. Lastly, the pinball loss function is used to expand the prediction model into a quantile regression model, measure the effect of volatility, quantify the volatility range of prediction, and finally, obtain a deterministic prediction result. The actual measured data of wind farms in the Bohai Sea area are selected for analysis and calculation. The results show that the prediction model proposed in this study achieves better accuracy in deterministic prediction and interval prediction than the traditional model.

Wafer-scale rare-earth iron garnet (RIG) single crystal thick films were fabricated on 3-in. gadolinium gallium garnet (GGG) substrates using liquid phase epitaxy. The terahertz transmittance of the RIG crystals improved after removing the GGG substrate by polishing. The time-domain spectra at Terahertz (THz) frequencies indicate the existence of a magneto-optical effect in RIG samples. The results indicate that the RIG samples exhibit a high refractive index of ∼4.50 within the 0.1–1.0 THz frequency range, a transmittance of around 40%, and an absorption rate of only 10–50 cm−1. The Faraday rotation angles of the thick single-crystal films of the RIG samples were measured using a THz-TDS system. The RIG has a thickness of ∼330 μm. The Faraday rotation angles of RIG crystals at THz frequencies can reach up to 16° when an external magnetic field of 0.18 T is applied. The Verdet constants of the RIG sample were calculated to be ∼120°/mm/T. To improve the transmittance of the RIG sample, epoxy resin and polymethylpentene (TPX) were used as anti-reflective films. The transmittance of the RIG sample increased by ∼5% for the 80 μm thick epoxy and about 10% for the 320 μm thick TPX. Therefore, this RIG single crystal thick film can achieve a low loss, a high transmittance, and a strong magneto-optical effect in the terahertz region with the cooperation of a reflection-reducing film. It is expected to have wide applications in terahertz magnetic polarization conversion, non-reciprocal phase shifters, and isolators.

ObjectiveThis study focuses on the innovative application of Automated Machine Learning (AutoML) technology in cardiovascular medicine to construct an explainable Coronary Artery Disease (CAD) prediction model to support the clinical diagnosis of CAD.MethodsThis study utilizes a combined data set of five public data sets related to CAD. An ensemble model is constructed using the AutoML open-source framework AutoGluon to evaluate the feasibility of AutoML in constructing a disease prediction model in cardiovascular medicine. The performance of the ensemble model is compared against individual baseline models. Finally, the disease prediction ensemble model is explained using SHapley Additive exPlanations (SHAP).ResultsThe experimental results show that the AutoGluon-based ensemble model performs better than the individual baseline models in predicting CAD. It achieved an accuracy of 0.9167 and an AUC of 0.9562 in 4-fold cross-bagging. SHAP measures the importance of each feature to the prediction of the model and explains the prediction results of the model.ConclusionThis study demonstrates the feasibility and efficacy of AutoML technology in cardiovascular medicine and highlights its potential in disease prediction. AutoML reduces the barriers to model building and significantly improves prediction accuracy. Additionally, the integration of SHAP enhances model transparency and explainability, which is critical to ensuring model credibility and widespread adoption in cardiovascular medicine.

Abstract Cardiac hypertrophy is an adaptive response to stressors such as high cardiac workload, which might lead to abnormal cardiac function and heart failure. Previous studies have indicated that macrophage migration inhibitory factor (MIF) might play a protective role in cardiac hypertrophy. Here, we aimed to illustrate the mechanism of MIF in protecting against pressure overload‐induced cardiac hypertrophy. Transverse aortic constriction (TAC) mouse model was established and we found that overexpression of MIF protected against pressure overload‐induced cardiac hypotrophy in TAC treated mice, as evidenced by significantly decreased the heart weight. In addition, transthoracic echocardiography showed that overexpression of MIF restored ejection fraction in TAC‐treated mice. While TAC treatment resulted in a much larger cardiomyocyte size in mice, MIF overexpression notably decreased the cardiomyocyte size. Next, we demonstrated that MIF overexpression promoted the expression of miR‐29b‐3p which further downregulated the expression of its downstream target HMG box protein 1 (HBP1). Overexpression of HBP1 reversed the effect of MIF in alleviating Ang‐II induced oxidative stress in cardiomyocytes. In conclusion, our findings suggest that MIF could attenuate pressure overload‐induced cardiac hypertrophy through regulating the miR‐29b‐3p/HBP1 axis.

Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with strong invasiveness and poor prognosis. Previous studies have demonstrated the significant role of USP14 in various solid tumors. However, the role of USP14 in the regulation of HCC development and progression remains unclear. Methods We discovered through GEO and TCGA databases that USP14 may play an important role in liver cancer. Using bioinformatics analysis based on the Cancer Genome Atlas (TCGA) database, we screened and identified USP14 as highly expressed in liver cancer. We detected the growth and metastasis of HCC cells promoted by USP14 through clone formation, cell counting kit 8 assay, Transwell assay, and flow cytometry. In addition, we detected the impact of USP14 on the downstream protein kinase B (AKT) and epithelial-mesenchymal transition (EMT) pathways using western blotting. The interaction mechanism between USP14 and HK2 was determined using immunofluorescence and coimmunoprecipitation (CO-IP) experiments. Results We found that sh-USP14 significantly inhibits the proliferation, invasion, and invasion of liver cancer cells, promoting apoptosis. Further exploration revealed that sh-USP14 significantly inhibited the expression of HK2. Sh-USP14 can significantly inhibit the expression of AKT and EMT signals. Further verification through immunofluorescence and CO-IP experiments revealed that USP14 co-expressed with HK2. Further research has found that USP14 regulates the glycolytic function of liver cancer cells by the deubiquitination of HK2. USP14 regulates the autophagy function of liver cancer cells by regulating the interaction between SQSTM1/P62 and HK2. Conclusions Our results indicate that USP14 plays a crucial role in the carcinogenesis of liver cancer. We also revealed the protein connections between USP14, HK2, and P62 and elucidated the potential mechanisms driving cancer development. The USP14/HK2/P62 axis may be a new therapeutic biomarker for the diagnosis and treatment of HCC.

ABSTRACT: To investigate the potential protective effect of prior cold stimulation on broiler intestine induced by acute cold stress (ACS). A total of 384 one-day-old broilers were divided into control (CON), ACS, cold stimulation Ⅰ (CS3+ACS), and cold stimulation Ⅱ (CS9+ACS) groups. Broilers in CON and ACS groups were reared normally, and birds in CS3+ACS and CS9+ACS groups were reared at 3℃ and 9℃ below CON group for 5 h, respectively, on alternate days from d 15 to 35. Broilers in ACS, CS3+ACS, and CS9+ACS groups were subjected to 10℃ for 24 h on d 43. Eventually, small intestine tissues were collected for histopathological observation and indexes detection. The results showed that intestinal tissues in all ACS-broilers exhibited inflammatory cell infiltrates, microvilli disruption, reduced villus length in jejunum and increased crypt depth in jejunum and ileum. Whereas these phenomena were relatively light in CS3+ACS group. Compared to CON group, mRNA expression of the TLR4/MyD88/NF-κB pathway-related genes (TLR4, MyD88, NF-κBp65, COX-2, iNOS, PTGEs, TNF-α), Th1/Th17-derived cytokines (IL-1β, IL-2, IL-8, IL-12, IFN-γ, IL-17), and HSPs (HSP40, HSP60, HSP70, HSP90) was upregulated (P < 0.05), and that of Th2-deviated cytokines (IL-4, IL-6, IL-10, IL-13) and IκBα was downregulated (P < 0.05) in small intestine in almost all ACS-broilers. Compared to ACS group, mRNA expression of most of the TLR4/MyD88/NF-κB pathway-related genes, Th1/Th17-derived cytokines, and HSPs was downregulated and that of Th2-derived cytokines was upregulated in CS3+ACS group (P < 0.05). Protein expression levels of TLR4, MyD88, p-p65/p65, p-IκBα/IκBα, IKK, TNF-α, IL-1β, IL-10, and HSPs were similar to their mRNA expression. The concentration of sIgA and activities of CAT, SOD, and GSH-px were decreased and MDA and H2O2 were increased in ACS and CS9+ACS groups compared to CON group (P < 0.05). Therefore, cold stress caused oxidative stress and inflammation, leading to gut immune dysfunction; while mild cold stimulation at 3℃ below normal rearing temperature alleviated cold stress-induced intestinal injure and dysfunction by modulating the TLR4/MyD88/NF-κB pathway in broilers.

Abstract Goethite nanoparticles modified biochar (FBC) could address the weak effectiveness of conventional biochar commonly to process heavy metal(loids) (HMs) co-contamination with different charges. However, few studies have focused on the change of soil mechanical properties after stabilization. In this study, FBC was synthesized to stabilize simultaneously arsenic (As (V)) (anions) and cadmium (Cd (II)) (cations) in co-contaminated soils. Batch adsorption, leaching toxicity, geotechnical properties and micro-spectroscopic tests were comprehensively adopted to investigate the stabilization mechanism. The results showed that FBC could immobilize As (V) mainly through redox and surface precipitation while stabilizing Cd (II) by electrostatic attraction and complexation, causing soil agglomeration and ultimately making rougher surface and stronger sliding friction of contaminated soils. The maximum adsorption capacity of FBC for As (V) and Cd (II) was 31.96 mg g−1 and 129.31 mg g−1, respectively. Besides, the dosages of FBC required in contaminated soils generally were approximately 57% higher than those in contaminated water. FBC promoted the formation of small macroaggregates (0.25–2 mm) and the shear strengths of co-contaminated soils by 21.40% and 8.34%, respectively. Furthermore, the soil reutilization level was significantly improved from 0.14–0.46 to 0.76–0.83 after FBC stabilization according to TOPSIS method (i.e., technique for order preference by similarity to an ideal solution). These findings confirm the potential of FBC in immobilizing As (V) and Cd (II) of co-contaminated soils and provide a useful reference for green stabilization and remediation of HMs co-contaminated sites. Graphical Abstract

Assessing the spatiotemporal evolution characteristics of habitat quality, human footprint, and coupling coordination between two systems in continuous cycles and on national scales is of great significance to maintaining biodiversity and sustainable development. This study took China as an example, based on land-use data from 2000 to 2020, using the Integrated Valuation of Ecosystem Services and Tradeoffs—Habitat Quality (InVEST-HQ) model and the human footprint framework, coupling trend analysis methods such as Theil–Sen Median Analysis, Mann–Kendall Test, and Grid Transition Matrix (GTM) Method and combining the four-quadrant model and the coupling coordination degree model (CCDM) to reveal the spatiotemporal evolution characteristics of habitat quality, human footprint, and CCDM in China for 21 consecutive years and the response relationship between the two systems of habitat quality and human footprint. The results show that the land cover change area from 2000 to 2020 accounted for 4.2% of the total area. Both habitat quality and human footprints exhibit apparent spatial heterogeneity along the “Hu Line” and generally fall into two evolutionary stages: “degradation–improvement”. The proportions of degradation and improvement were 14.37% and 8.36%, respectively, and the mutation point was in the year 2013; the average human footprint increased by 16.75%, and the increased and decreased area proportions were 63.40% and 21.53%, respectively. The mutation occurred in 2014. The right side of the “Hu Line” primarily hosts areas with high values of the coordinated coupling index of human footprints and habitat quality systems. The four quadrants generally have the following characteristics: “quadrant IV on the right is dominant, quadrants II and III on the left are dominant, and quadrant I is located in the transition zone of the ‘Hu Line’”. The coupling coordination degree (CCD) and human footprints have a weak, nonlinear “inverted U-shaped” relationship. This study provides compelling evidence for the spatiotemporal evolution and coupling relationship between habitat quality and human footprint in China, provides scientific decision-making support for biodiversity protection and sustainable economic development, and maintains the bottom line of ecological security for a beautiful China.

Biopolymers have become popular in geotechnical engineering as they provide a carbon-neutral alternative for soil solidification. Xanthan gum (XG) and jute fiber (JF) were selected to solidify the Yellow River dredged soil. The mechanical behavior of solidified dredged soil (SDS) was investigated using a series of uniaxial compression and splitting tension tests at different XG and JF contents and fiber lengths. The results indicate that on the 28th day, the unconfined compressive strength (UCS) values of SDS samples reached 2.83 MPa and splitting tensile strength (STS) of 0.763 MPa at an XG content of 1.5%. When the JF content was greater than 0.9%, the STS of the SDS samples decreased. This is because that the large fiber content weakened the cementation ability of XG. The addition of JF can significantly increase the strain at peak strength of SDS samples. There is a linear relationship between the UCS and STS of the dredged soils solidified by XG and JF. Microanalysis shows that the strength of SDS samples was improved mainly via the cementation of XG itself and the network structure formed by JF with soil particles. The dredged soil reinforced by XG and JF shows better mechanical performance and has great potential for application.

Objectives Hypoxia is a physiological state characterized by reduced oxygen levels in organs and tissues. It is a common clinicopathological process and a major cause of health problems in highland areas. Heart rate variability (HRV) is a measure of the balance in autonomic innervation to the heart. It provides valuable information on the regulation of the cardiovascular system by neurohumoral factors, and changes in HRV reflect the complex interactions between multiple systems. In this review, we provide a comprehensive overview of the relationship between high-altitude hypoxia and HRV. We summarize the different mechanisms of diseases caused by hypoxia and explore the changes in HRV across various systems. Additionally, we discuss relevant pharmaceutical interventions. Overall, this review aims to provide research ideas and assistance for in-depth studies on HRV. By understanding the intricate relationship between high-altitude hypoxia and HRV, we can gain insights into the underlying mechanisms and potential therapeutic approaches to mitigate the effects of hypoxia on cardiovascular and other systems. Methods The relevant literature was collected systematically from scientific database, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu Scholar, as well as other literature sources, such as classic books of hypoxia. Results There is a close relationship between heart rate variability and high-altitude hypoxia. Heart rate variability is an indicator that evaluates the impact of hypoxia on the cardiovascular system and other related systems. By improving the observation of HRV, we can estimate the progress of cardiovascular diseases and predict the impact on other systems related to cardiovascular health. At the same time, changes in heart rate variability can be used to observe the efficacy of preventive drugs for altitude related diseases. Conclusions HRV can be used to assess autonomic nervous function under various systemic conditions, and can be used to predict and monitor diseases caused by hypoxia at high altitude. Investigating the correlation between high altitude hypoxia and heart rate variability can help make HRV more rapid, accurate, and effective for the diagnosis of plateau-related diseases.

Previous studies have demonstrated the effectiveness of a novel three-layer landfill cover system constructed with recycled concrete aggregates (RCAs) without geomembrane in both laboratory and field. However, no systematic investigation has been carried out to optimize the combination of the particle sizes for fine-grained RCAs (FRC) and coarse-grained RCAs (CRC) that can be used for the three-layer landfill cover system. The aim of this paper is to assist engineers in designing the three-layer landfill cover system under a rainfall of 100-year return period in humid climate conditions using an easily controlled soil parameter D10 of RCAs. The numerical study reveals that when D10 of FRC increases from 0.05 mm to 0.16 mm, its saturated permeability increases by 10 times. As a result, a larger amount of rainwater infiltrates into the cover system, causing a higher lateral diversion in both the top FRC and middle CRC layers. No further changes in the lateral diversion are observed when the D10 value of FRC is larger than 0.16 mm. Both the particle sizes of FRC and CRC layers are shown to have a minor influence on the percolation under the extreme rainfall event. This implies that the selection of particle sizes for the FRC and CRC layers can be based on the availability of materials. Although it is well known that the bottom layer of the cover system should be constructed with very fine-grained soils if possible, this study provides an upper limit to the particle size that can be used in the bottom layer (D10 not larger than 0.02 mm). With this limit, the three-layer system can still minimize the water percolation to meet the design criterion (30 mm/yr) even under a 100-year return period of rainfall in humid climates.

Potential toxic elements (PTEs), including Pb, Cr, Cd, Ni, Cu, As, and Mo, are common pollutants in ion-adsorption rare earth mines (IAREEMs), and atmospheric deposition is an important method of PTE migration. However, the level of PTE atmospheric deposition in and around IAREEMs remains unknown. We established 25 stations at typical sites in the Ganzhou city of southeast China. An exposure assessment model was used to evaluate the health risks for adults and children. The results show that the concentration and fluxes of atmospheric deposition of PTEs follow the order of Pb > Cu > Cr > Ni > As > Mo > Cd, and most PTEs present no human health risk. However, due to the high toxicty of As, it poses both carcinogenic and non-carcinogenic risks to children as indicated by the analysis of an exposure assessment model of heavy rare earth minerals in Longnan county, Ganzhou city. The As concentration in atmospheric deposition ranged from 3.18 to 251.87 mg kg−1, and the As atmospheric fluxes in atmospheric deposition ranged from 0.11 to 39.4 mg m−2 y−1. This is because As-rich materials (e.g., arsenic-adsorbing clay zones and chernovite-(Y) (Y[AsO4])) are exposed in fully weathered layers, and the formed suspended particulate matter is transported into the atmosphere at Longnan county. Consequently, restoring vegetation to reduce particulate matter transport is an important method for controlling the spread of pollutants. These results provide significant insights into pollution characteristics and prevention in and around mining areas under the influence of atmospheric deposition.

Marigold oleoresin is an oil-soluble natural colorant mainly extracted from marigold flowers. Xinjiang of China, India, and Zambia of Africa are the three main production areas of marigold flowers. Therefore, this study utilized ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technology, combined with Global Natural Products Social Molecular Networking (GNPS) and multivariate statistical analysis, for the qualitative and discriminant analysis of marigold oleoresin obtained from three different regions. Firstly, 83 compounds were identified in these marigold oleoresin samples. Furthermore, the results of a principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) indicated significant differences in the chemical compositions of the marigold oleoresin samples from different regions. Finally, 12, 23, and 38 differential metabolites were, respectively, identified by comparing the marigold oleoresin from Africa with Xinjiang, Africa with India, and Xinjiang with India. In summary, these results can be used to distinguish marigold oleoresin samples from different regions, laying a solid foundation for further quality control and providing a theoretical basis for assessing its safety and nutritional aspects.

Myocardial infarction (MI) impaired both cardiac functions and peripheral arteries. The changes in normal and shear stresses in the peripheral artery wall are of importance for understanding the progression of MI-induced heart failure (HF). The aim of the study is to investigate the corresponding changes of normal and shear stresses. The coronary artery ligation was used to induce the MI in Wistar rats. The analysis of wall mechanics and hemodynamics was performed based on in vivo and in vitro measurements. Myocardial infarction increased wall stiffness in elastic carotid and muscular femoral arteries significantly albeit different changes occurred between the two vessels from 3 to 6 weeks postoperatively. Moreover, the hemodynamic analysis showed the gradually deteriorated wall shear stress, oscillatory shear index and relative residence time in the two arteries. This study probably shed light on understanding the interaction between abnormal systemic circulation and peripheral mechanics and hemodynamics during the development of MI-induced HF.

The combination of chemical stabilization and fiber reinforcement can simultaneously improve the strength and ductility of dredged sediment. The polypropylene fiber (PF) and straw fiber (SF) were respectively used as artificial and natural reinforcements of cement-stabilized dredged sediment (CDS). A series of unconfined compressive strength (UCS) tests were conducted to investigate the effects of cement content, fiber content, fiber length and water content on the mechanical properties of PF-reinforced CDS (CPFDS) and SF-reinforced CDS (CSFDS). Furthermore, the cementation-reinforcement mechanism was explored and analyzed via macro failure characteristics and micro interfacial morphologies inside typical CPFDS and CSFDS samples. The results showed that increasing cement content or decreasing water content significantly improved the UCS and aggravated the brittleness of CPFDS and CSFDS. The suitable addition of PF can effectively improve the UCS of CDS, while incorporating SF exhibited the opposite role. The maximum 7d-, 28d-, 60d- and 90d-UCS of CPFDS were respectively 17.7%, 43.6%, 10.7% and 9.7% higher than that of CDS. The optimum length of PF inside CPFDS and SF inside CSFDS was 3 mm and 5–10 mm, respectively. Both incorporating PF or SF can effectively improve the ductility of CDS. Based on the proposed parameters of total-water/cement ratio and fiber cementation factor, the effective strength development models of CPFDS and CSFDS considering cement content, fiber content, water content and curing time were empirically established. The fiber “bridge” effect and interfacial friction between fiber and cemented soil particles were mainly responsible for the strength evolution and ductility improvement of CPFDS and CSFDS.

The phase inversion tape casting has been widely used to fabricate open straight porous supports for solid oxide fuel cells (SOFCs), which can offer better gas transmission and minimize the concentration polarization. However, the overall weak strength of the macro-porous structure still limits the applications of these SOFCs. In this work, a novel SOFC supported by an ordered porous cathode membrane with a four-layer configuration containing a finger-like porous 3 mol% yttria- stabilized zirconia (3YSZ)-La0.8Sr0.2Co0.6Fe0.4O3−δ (LSCF) catalyst, porous 8 mol% yttria-stabilized zirconia (8YSZ)-LSCF catalyst, and dense 8YSZ porous 8YSZ-NiO catalyst is successfully prepared by the phase inversion tape casting, dip-coating, co-sintering, and impregnation process. The flexural strength of the open straight porous 3YSZ membrane is as high as 131.95 MPa, which meets the requirement for SOFCs. The cathode-supported single cell shows a peak power density of 540 mW cm−2 at 850 °C using H2 as the fuel. The degradation mechanism of the SOFC is investigated by the combination of microstructure characterization and distribution of relaxation times (DRT) analysis.

An anticlinal structure with an axis plane along Yanhe river and a strike of about 330° is developed in the bedrock strata within the main urban area of AnSai County. In the bedrock strata, there are generally two groups of tensile joints parallel to the fold axis plane (320°-340°) and vertical (40°-60°), and two groups of conjugate shear joints diagonally intersecting the fold axis. The first group of conjugate shear joint planes struck direction near N-S (0°-10°) and near E-W (80°-90°), while the second group of conjugate shear joint planes strikes direction 100°-120° and 200°-210°. The multiple groups of joints with different strike directions developed in the bedrock have a strong control effect on the development of the collapse structure control plane with the same strike distribution in the study area. In the first group of conjugate shear joints, the near E-W (80°-90°) distributed joint planes control strongly the most developed collapse structure control planes in the study area, and it has the highest correlation with the development of rock collapse in the study area. Secondly, two groups of tensile joint planes control two groups of highly developed rock collapse structural control planes with the same strike, and the second group of conjugate shear joint planes controls two groups of relatively less developed rock collapse structural control planes with the same strike.

In a comparison of modified nanoscale zero-valent iron (NZVI), bare NZVI used to remediate deep contaminated groundwater source areas has more advantages. However, the influence of injected bare NZVI deposition on the permeability of aquifer remains unclear, together with which are still the key factors of engineering cost and contamination removal. Hence, this study sought to assess a method of measuring hydraulic conductivity with a constant head device and to examine the permeability loss mechanism of NZVI injected into different saturated porous media, using column tests. The results showed that it was feasible to determine hydraulic conductivity by the constant head device. The permeability loss caused by NZVI injection increased with a decrease in the grain size of the porous media, and was determined by the amount and distribution of NZVI deposition. The NZVI distribution area had a good linear correlation with dispersivity of the porous media. Additionally, although surface clogging occurred in all porous media, the amount of NZVI deposition at the injection point was largest in fine sand, so that its permeability loss was the most; this was more likely to cause hydraulic fracturing and expand the area of the contaminant source zone. These results have implications for NZVI field injection for successful groundwater remediation. HIGHLIGHTS The amount and distribution of NZVI deposition determines permeability loss.; NZVI distribution area has a good positive linear correlation with dispersivity of the porous media.; Coarse and medium sand were classified as mix clogging, while fine sand was surface clogging.;

Rapidly predicting and revealing the spatiotemporal characteristics and driving factors of land-use changes in carbon storage within megacities under different scenarios is crucial to achieving sustainable development. In this study, Jinan City (JNC) is taken as the study area, and the Markov-FLUS-InVEST model is utilized to predict and analyze the spatiotemporal variation in carbon storage in 2030 under three scenarios, namely, the natural development scenario (S1), the ecological conservation scenario (S2), and the economic development scenario (S3). The drivers of carbon storage changes were identified using an optimal parameter-based geographic detection (OPGD) model. The findings indicate that (1) land use from 2010 to 2018 shows a trend of continuous expansion of construction land and reduction in arable land. (2) The main types of carbon pools were cropland, forest, and grassland, accounting for more than 96% of the total amount. Carbon storage showed a decreasing trend from 2010 to 2018, and the main type of carbon pool that decreased was cropland. The center of gravity of carbon storage increases and decreases was located in the southern Lixia District, and the center of gravity of increase and decrease moved to the southwest by 3057.48 m and 1478.57 m, respectively. (3) From 2018 to 2030, the reductions in carbon stocks were 3.20 × 106 t (S1), 2.60 × 106 t (S2), and 4.26 × 106 t (S3), and the carbon release was about 9 times (S1), 4 times (S2), and 10 times (S3) that of the carbon sink. (4) The contribution of slope (A2) ∩ nighttime light index (B6) and elevation (A1) ∩ nighttime light index (B6) to the regional heterogeneity of carbon stocks was the largest among the interaction drivers. To sum up, this study deepens the simulation of spatial and temporal dynamics of carbon storage under land-use changes in megacities and the related driving mechanism, which can provide the basis for scientific decision-making for cities to conduct territorial spatial planning and ecological protection and restoration.

Abstract The periodic‐phase‐diagram similarity method is proposed to identify the frequency of weak harmonic signals. The key technology is to find a set of optimal coefficients for Duffing system, which leads to the periodic motion under the influence of weak signal and strong noise. Introducing the phase diagram similarity, the influences of strong noise on the similarity of periodic phase diagram are discussed. The principle of highest similarity of periodic phase diagram with the same frequency is detected by discussing the persistence of similarity of periodic motion phase diagram under the strong noise and the periodic‐phase‐diagram similarity method is constructed. The weak signals of early fault and strong noise are input into Duffing system to obtain the identified system. The stochastic subharmonic Melnikov method is extended to obtain the conditions of the optimal coefficients for the identified system. Based on the results, the constructed frequency conversion harmonic weak signals are considered to form a datum periodic system. With the change of frequency in the datum periodic system, the phase diagram similarity of the two constructed systems can be calculated. Based on the periodic‐phase‐diagram similarity method, the frequency of weak harmonic signals can be identified by the principle of highest similarity of periodic phase diagram with the same frequency. The results of numerical simulation and the early fault diagnosis results of actual bearings verify the feasibility of the periodic‐phase‐diagram similarity method. The accuracy of the detection effect is 97%, and the minimum signal‐to‐noise ratio is −80.71 dB.

Sit-to-stand is a common activity in daily life. It is difficult for the elderly and patients with lower limb disorders to complete this motion due to limb pain, muscle weakness, partial loss of motor control function, and physical defects in joints. An STS assistive device is a piece of automated medical equipment that can facilitate rehabilitation training for patients with lower limb disorders and improve their lower limb function. In this paper, we introduce a 3-DOF series type STS assistive device. First, we selected 26 healthy adults to carry out an STS transfer experiment, and we obtained the trajectory and velocity of each joint and the law of plantar pressure during STS motion. Second, based on the above kinematics and dynamics law, a 3-DOF series mechanism was designed. Through forward and inverse kinematics analysis, the relationship between the end-effector and the linear actuator was established. The trajectory planning of the end-effector was carried out according to the natural STS transfer trajectory, and the law of the linear actuator was obtained. The trajectory planning was verified by ADAMS. Finally, the Arduino controller was used to build the control system of the STS assistive device, and the prototype experiment was carried out.

In the Sanjiang Plain, agricultural drainage ditches effectively alleviate agricultural non-point source nitrogen pollution. However, limited information is known about the characteristics of bidirectional trans-ports of nitrogen between sediment and overlying and pore water in different patterns of ditches undergoing seasonal freezing-thawing cycles. It is vital to better understand nitrogen interception and purification by ecological ditches. In order to clarify the interception of ecological ditches on internal and external nitrogen, overlying water and sediment samples of two typical agricultural ditches were collected and analyzed in Sanjiang Plain during the growing seasons of 2015–2017. The results indicated that the N-NO3− in overlying water, which was higher than N-NH4+, was the dominant inorganic nitrogen, whilst, in the sediment, N-NH4+ was much higher than N-NO3−, which should be attributed to the soil’s adsorption of N-NH4+. In contrast to the dryland ditch, the paddy ditch had a more significant amount of inorganic nitrogen both in overlying water and sediment, which means that the non-point source nitrogen pollution caused by paddy fields was more severe than that of drylands. Compared with dryland ditches, N-NH4+ in the sediment of pad ditches seemed to be much easier to migrate to a deeper layer, which may cause a greater risk of nitrogen pollution to groundwater. Both in the overlying water and the sediment of ditches, nitrogen content fluctuated during different periods, and inter-annual variation was noticeable, which results means that estimation or prediction of the non-point source pollution output needs to extend the monitoring period and increase sampling frequency to reduce the great uncertainty. The findings may provide a foundation for forecasting agricultural nitrogen pollution and guide best management practices (BMPs) of non-point source nitrogen pollution control in seasonally frozen areas.

Acoustic-resolution photoacoustic microscopy (AR-PAM) is a promising imaging modality that renders images with ultrasound resolution and extends the imaging depth beyond the optical ballistic regime. To achieve a high lateral resolution, a large numerical aperture (NA) of a focused transducer is usually applied for AR-PAM. However, AR-PAM fails to hold its performance in the out-of-focus region. The lateral resolution and signal-to-noise ratio (SNR) degrade substantially, thereby leading to a significantly deteriorated image quality outside the focal area. Based on the concept of the synthetic-aperture focusing technique (SAFT), various strategies have been developed to address this challenge. These include 1D-SAFT, 2D-SAFT, adaptive-SAFT, spatial impulse response (SIR)-based schemes, and delay-multiply-and-sum (DMAS) strategies. These techniques have shown progress in achieving depth-independent lateral resolution, while several challenges remain. This review aims to introduce these developments in SAFT-based approaches, highlight their fundamental mechanisms, underline the advantages and limitations of each approach, and discuss the outlook of the remaining challenges for future advances.

Abstract Increasing evidence supports that ferroptosis plays an important role in tumor growth inhibition. Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, has been shown to induce ferroptosis in hepatocellular carcinoma (HCC). However, some hepatoma cell lines are less sensitive to sorafenib-induced ferroptotic cell death. Glutathione S-transferase zeta 1 (GSTZ1), an enzyme in the catabolism of phenylalanine, suppresses the expression of the master regulator of cellular redox homeostasis nuclear factor erythroid 2-related factor 2 (NRF2). This study aimed to investigate the role and underlying molecular mechanisms of GSTZ1 in sorafenib-induced ferroptosis in HCC. GSTZ1 was significantly downregulated in sorafenib-resistant hepatoma cells. Mechanistically, GSTZ1 depletion enhanced the activation of the NRF2 pathway and increased the glutathione peroxidase 4 (GPX4) level, thereby suppressing sorafenib-induced ferroptosis. The combination of sorafenib and RSL3, a GPX4 inhibitor, significantly inhibited GSTZ1-deficient cell viability and promoted ferroptosis and increased ectopic iron and lipid peroxides. In vivo, the combination of sorafenib and RSL3 had a synergic therapeutic effect on HCC progression in Gstz1 −/− mice. In conclusion, this finding demonstrates that GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in HCC cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.

The preparation of lanthanide-transition metal clusters containing multiple lanthanide atoms remains challenging. Here, the authors present the controlled on-surface formation of ligand-stabilized heterometallic Ce/Au clusters containing two, three and four Ce atoms bridged by Au adatoms.

BackgroundsAlthough there are a certain number of studies dedicated to the disturbances of the dopaminergic system induced by traumatic brain injury (TBI), the associations of abnormal dopaminergic systems with post-traumatic anxiety and depressive disorders and their underlying mechanisms have not been clarified yet. In the midbrain, dopaminergic neurons are mainly situated in the substantia nigra (SN) and the ventral tegmental area (VTA). Thus, we selected SN and VTA as regions of interest and performed a seed-based global correlation to evaluate the altered functional connectivity throughout the dopaminergic system post-TBI.MethodsThirty-three individuals with TBI and 21 healthy controls were recruited in the study. Anxiety and depressive symptoms were examined by the Hospital Anxiety and Depression Scale. All MRI data were collected using a Siemens Prisma 3.0 Tesla MRI system. The volume of SN and the global functional connectivity of the SN and VTA were analyzed.ResultsIn the present study, patients with TBI reported more anxiety and depressive symptoms. More importantly, some structural and functional alterations, such as smaller SN and reduced functional connectivity in the left SN, were seen in individuals with TBI. Patients with TBI had smaller substantia nigra on both right and left sides, and the left substantia nigra was relatively small in contrast with the right one. Among these findings, functional connectivity between left SN and left angular gyrus was positively associated with post-traumatic anxiety symptoms and negatively associated with depressive symptoms.ConclusionsThe TBI causes leftward lateralization of structural and functional alterations in the substantia nigra. An impaired mesocortical functional connectivity might be implicated in post-traumatic anxiety and depression.

Introduction It remains unclear whether acute perioperative myocardial injury (APMI) increases mortality in the elderly. This study aimed to investigate APMI’s association with mortality within 90 days after hip fracture repair in elderly patients. Materials and Methods This prospective study enrolled elderly patients admitted to the department of Traumatology and Orthopaedics in XXX Hospital, who underwent surgery in 2018–2019 with a 90-day follow-up. According to survival status within 90 days, survival and death groups were constituted. Clinical, demographic, and laboratory indicators and 90-day mortality post-surgery were recorded. APMI’s association with 90-day mortality post-surgery was analyzed by logistic regression. Results Totally 248 participants were enrolled, including 224 and 24 in the survival and death groups, respectively, for a mortality rate of 9.7%. Compared with surviving individuals, the death group was older [81 (75–86) vs 87 (82–89) years], and had higher incidence rates of APMI (24.6% vs 58.3%), intertrochanteric fractures (41.1% vs 62.5%), preoperative atrial fibrillation (8.9% vs 29.2%), and dementia (73.7% vs 95.8%) (all P< .05). They also showed higher pre-injury frail scale scores [1 (0–2) vs 3 (1–4)] and Nottingham hip fracture scores (NHFSs) [4 (4–5) vs 6.5 (5–7)], lower Glomerular filtration [62 (46.1–78.6) vs 44.37 (35–61.92) ml/min], and reduced odds of glomerular filtration rate

Background: Exosomes are well-known natural nanovesicles, that represent one of the recently discovered modes of intercellular communication due to their ability to transmit cellular components. Exosomes have been reported to have potential as natural vectors for carrying functional small RNAs and delivering chemotherapeutic agents to diseased cells. In this study, we aimed to investigate the role of exosomes in carrying miRNA for targeting tumor cells.Methods: We present a novel method for engineering exosomes with functional miR-317b-5b to target tumor cells. MiR-317b-5b exerts its anti-tumor function via its expression in tumors. RT-qPCR was performed to assess the levels of miR-371b-5p, FUT-4. Western blot was performed to measure the levels of CD9, CD81, and FUT-4 proteins. Confocal microscopy was used to observe the internalization of miR-317b-5b in tumor cells. CCK-8, EdU, flow cytometry, wound-healing migration and transwell assays were performed to evaluate cell viability, proliferation, migration, and invasion, respectively.Results: Our findings illustrated that miR-317b-5b-loaded engineered exosomes were internalized by tumor cells. MiR-317b-5b was overexpressed in tumor cells treated with miR-317b-5b-loaded engineered exosomes. The internalization of miR-317b-5b in tumor cells was accompanied by changes of cell viability, proliferation, apoptosis, and migratory and invasive capability. We found that miR-317b-5b-loaded engineered exosomes were presence in tumor tissue sections and miR-317b-5b was overexpressed in tumor tissues of osteosarcoma tumor-bearing mice infected with miR-317b-5b-loaded engineered exosomes. MiR-317b-5b-loaded engineered exosomes had the anti-tumor efficiency in vivo.Conclusion: Our findings show that miR-317b-5b-loaded engineered exosomes can be used as nanocarriers to deliver drug molecules such as miR-317b-5b both in vitro and in vivo to exert its anti-tumor functions.

Water deterioration and eutrophication caused by phosphorus (P) contamination necessitates P removal from polluted water, and has been a research focus since the second half of last century. In this study, novel mesoporous micropheres based on silicon and calcium (Ca) was prepared as an adsorbent by direct pyrolysis to enrich and remove P. The maximum adsorption capacities of the prepared adsorbents were 356.34 and 496.73 mg g−1 P−PO43− for potassium phosphate (K3PO4) and potassium dihydrogen phosphate (KH2PO4) solutions, respectively, and adsorption equilibrium was attained rapidly in less than 30 min. The Langmuir isotherm and pseudo-second-order kinetic model adequately fit the adsorption process for K3PO4 solution, while the Langmuir isotherm and pseudo-first-order kinetic appropriately fit the KH2PO4 solution. The adsorption of P was due to the reaction between Ca2+ and PO43−, forming different phosphates. Addition of interfering ions had no significant effect on the adsorption ability of the prepared adsorbents. The proposed adsorbent was successfully applied to remove P from real wastewater. Notably, this new Ca-modified mesoporous silicon micropheres is an excellent adsorbent for treating wastewater containing low P content, providing an effective approach for facile preparation of P adsorbents and exhibiting promising P removal from wastewater.

BackgroundReducing peritoneal recurrence after radical surgery is an important choice to improve the prognosis of patients with advanced gastric cancer. Intraoperative intraperitoneal chemotherapy has the potential to be a promising treatment strategy. In the present study, we conducted a multi-center, randomized, controlled clinical study to evaluate the efficacy and safety of intraoperative intraperitoneal chemotherapy using sustained-release fluorouracil implants plus radical gastrectomy and adjuvant chemotherapy for cTNM stage III gastric cancer.MethodsThe patients were randomized into intraperitoneal chemotherapy group (sustained-release fluorouracil implants administration after standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy) and control group (standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy). A total of 122 patients from three centers were enrolled from September 2015 to February 2017.ResultsOne hundred and two eligible patients completed the treatment course. The median follow-up time was 41.7 months (36.1–52.9 months). The 3-year progression-free survival rate and overall survival of patients in the intraperitoneal chemotherapy group were 43.9% and 49.1%, respectively, which were significantly better than those of the control group, 31.0% and 38.4%. In the intraperitoneal chemotherapy group, the number of cases with peritoneal recurrence was significantly less than that of the control group, 9 cases (17.3%) vs. 19 cases (44.2%). There were neither significant differences between the groups in the incidence of hematogenous metastasis, lymph node metastasis, nor local metastasis.ConclusionFor cTNM stage III gastric cancer, intraoperative sustained-release fluorouracil implants after radical resection combined with postoperative adjuvant chemotherapy, could significantly reduce the risk of peritoneal recurrence and prolong PFS.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier (NCT02269904).

Documents have revealed that leaves, barks and woods from oak trees are rich in phenols, yet little is known about them in Mongolian oak (Quercus mongolica) cups, the by-product waste with large biomass. In the present work, composition analysis through total phenols, flavonoids and tannins, and condensed tannins, and HPLC profiles and antioxidant assessment by DPPH, ABTS, reducing power, ORAC and CAA were performed to evaluate oak cup crude extracts and the resulting four fractions (Fr. I, Fr. II, Fr. III and Fr. IV) prepared by HPD-100 macroporous resin chromatography. Among the optimal 50% ethanol crude extract (ECE) and its subsequent four fractions, Fr. II, on the basis of the oak cups, collected the majority of total phenols, flavonoids and tannins, and condensed tannins from ECE though lower contents of all compositions than those in Fr. III when based on the extract with an exception of condensed tannins. And the highlight of Fr. II is that it possessed the strongest antioxidant ability from the perspective of extract. These findings imply that composition of condensed tannins as well as its contents might take dominate role in antioxidant ability of oak cups. This was further corroborated through HPLC profiles as compositions in ECE and the four fractions are all distinguished from each other. HPLC also exhibited the great enrichment of ellagic acid in Fr. III. Moreover, the correlation analysis indicated that there is exclusive correlation existed between total flavonoids and antioxidant assays among all composition analysis including ellagic acid, which further confirmed the main influencing factor to antioxidant ability of oak cup may be composition of condensed tannins as well as its contents because the condensed tannins were constituted by flavonoid units, and ellagic acid may not be a strong antioxidant contributor in oak cups. Therefore, Fr. II should be chosen as the best fraction to be further explored. In addition, this established HPD-100 macroporous resin chromatography procedure could be developed as a simple and effective procedure for preparation of ellagic acid from oak cups. Keywords: Mongolian oak (Quercus mongolica) cups, Flavonoids, Condensed tannins, Antioxidant activities, Macroporous resin, HPLC

Lower limb rehabilitation exoskeleton robots (LLRERs) play a positive role in lower limb rehabilitation and assistance for patients with lower limb disorders, and they are helpful to improve patients’ physical status. More and more experiments pay more attention to the kinematic and dynamic data characteristics of different patient groups. However, it is not clear whether these devices have broad adaptability and their clinical significance, so it is necessary to summarize and analyze these research results. This paper summarizes the LLRERs prototype and product in recent years, also compares the advantages and disadvantages of the theory and technology used in these research, and compares the functional characteristics of the devices, finally summarizes the aspects of the LLRERs to be improved. These devices apply advanced theories, techniques or structures, as well as human kinematics and dynamics data. However, due to the complexity of human body characteristics and movement rules, the theory or technology applied in the study design of LLRERs remains to be further studied, which can be improved in many aspects, such as improve the human-computer cooperation of equipment or carry out clinical trials. This paper can provide reference for researchers and designers in the future study, as well as understanding and selecting LLRERs for all kinds of therapist and patients.

Even after being abandoned for many years, a large number of weathered crust elution-deposited rare earth (WCED-RE) tailings continue to release ammonia nitrogen (AN) pollution into their surrounding environments. However, the influences of particle size distribution and clay minerals on AN pollution caused by these tailings have been insufficiently studied, and its causes are poorly understood. In this study, soil samples at different depths (5, 7, 9, 11 and 14 m) were collected from a rare earth tailing in Ganzhou City, Jiangxi Province, China. Particles were screened by size into six groups (2–1, 1–0.5, 0.5–0.25, 0.25–0.1, 0.1–0.075 and < 0.075 mm), and AN forms were extracted. The results showed that as soil particle size decreases, both soil specific surface area and clay content increase, leading to stronger AN enrichment ability. With increased sampling depth, the distribution of clay across the six particle fractions became more uniform, such that the accumulation of AN in soil with fine particle size was less obvious. Clay minerals with different capacities for AN enrichment vary with sampling depth. This variation is responsible for the profile of AN distribution in the mine, where AN first increases and then decreases as vertical depth is increased. Although AN content was highest at 11 m, water soluble AN content was higher in the upper part of the completely weathered layer (5 and 7 m), which poses a higher environmental risk. This study provides significant information to deepen our understanding of the distribution characteristics of AN and its main influencing factors, as well as a foundation for the prevention and remediation of nitrogen pollution from WCED-RE tailings.

Landslide is one of the most widely distributed surface morphological landscapes, and it can cause a series of major economic and human losses. Field monitoring and limit equilibrium methods were applied to investigate Baota Mountain landslide stability, and soil volumetric water content, different scales of rainfall data, and landslide displacements were monitored using various equipment. The theoretical factor of safety was also calculated for the landslide. Finally, the theoretical results were validated by monitoring data in the field. The results demonstrate that soil volumetric water content experienced the greatest change with time at a depth of 0.2 m and then 1 m; however, the change in soil volumetric water content was relatively small with time at a soil depth ranging from 2.0 m to 4.0 m. Soil volumetric water content also did not change with time at a soil depth of 5.0 m and below. In addition, the retardation effect was found in different depths of volumetric water content for continuous rainfall. The safety factors were 2.713 and 1.133 for landslide No. 1 and landslide No. 2, respectively. These results indicate that landslide No. 1 is relatively stable, but there is a probability of the occurrence of movement in landslide No. 2. The monitoring displacement data indicate that landslide No.1 was in a relatively stable state between 2008 and 2013, and this result was in accordance with the value of theoretical calculation. This study provided relevant parameters for numerical simulation of landslides in loess areas.

Lung cancer remains the leading cause of cancer mortality because of highly malignant and metastatic potential. The current status of lung cancer treatment is limited, and more treatment options are needed. Interesting, antipsychotic drugs have been reported to show anti-cancer effects. In this present study, we investigated the anticancer potential of penfluridol (PF), an anti-schizophrenic drug, in lung cancer and its underlying mechanism in vitro and in vivo. In vitro, it could inhibit the viability of various lung cancer cells with G0/G1 phase arrest via increasing the expression level of p21/p27 and decreasing the expression levels of cyclin-CDK complex. Meanwhile, cell-cycle arrest causes DNA repair in the nucleus, which was associated with the upregulation of H2A.X and p-H2A.X. Moreover, PF could also decrease mitochondrial membrane potential and increase reactive oxygen species levels in the lung cancer cells. These results implied that PF might induce the mitochondria-mediated intrinsic apoptosis. In addition, PF inhibits the migration and invasion of lung cancer cells via downregulation of FAK-MMP signaling. In vivo, oral administration of PF at concentration of 10 mg/kg inhibited tumor growth in A549 xenograft model. Notably, PF is an approved drug and the price is exceedingly cheap, so this study demonstrates the potential of PF to treat lung cancer.

Abstract A flavonoids-rich extract of Scutellaria baicalensis shoots and its eight high content flavonoids were investigated for their inhibitory effects against α-glucosidase and α-amylase. Results show that abilities of the extract in inhibiting the two enzymes were obviously higher than those of acarbose. Moreover, inhibitory abilities of all the eight individual flavonoids against the two enzymes show exactly a same order (i.e., apigenin > baicalein > scutellarin > chrysin > apigenin-7-O-glucuronide > baicalin > chrysin-7-O-glucuronide > isocarthamidin-7-O-glucuronide), and their structure–activity relationship could be well-interpretated by the refined assign-score method. Furthermore, based on the inhibitory abilities and their contents in the extract, it was found that the eight flavonoids made predominant contributions, among which baicalein and scutellarin played roles as preliminary contributors, to overall inhibitory effects of the extract against the two enzymes. Beyond these, contributions of the eight flavonoids to the overall enzyme inhibitory activity were compared with those to the overall antioxidant activity characterized in our recent study, and it could be inferred that within the basic flavonoid structure the hydroxyl on C-4′ of ring B was more effective than that on C-6 of ring A in enzyme inhibitory activities while they behaved inversely in antioxidant activities; scutellarin and apigenin contributed more to the overall enzyme inhibitory activity, and baicalin and scutellarin, to the overall antioxidant activity of the extract; and flavonoids of the extract, apart from directly inhibiting enzymes, might also be conducive to curing type 2 diabetes via scavenging various free radicals caused by increased oxidative stresses.

Dasatinib, a tyrosine kinase inhibitor, has been approved for first‐line treatment of leukemia and has also been evaluated for use in numerous other cancers. However, its role in gastric cancer (GC) remains unclear. Therefore, the aim of this study was to investigate how dasatinib suppresses the growth of GC cells and interacts with chemotherapeutic drugs. The results showed that, in the presence of dasatinib, proliferation of GC cells decreased and apoptosis increased, and that Fas‐associated death domain protein and caspase‐8 are essential to dasatinib‐induced cell apoptosis in GC. In addition, we found that dasatinib increased the expression of death receptor 5 (DR5) in GC cells. Dasatinib enhanced apoptosis induced by tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) in GC cells. Moreover, increased DR5 expression facilitated dasatinib‐induced apoptosis; the dasatinib‐induced increase in DR5 expression was mediated by CCAAT/enhancer‐binding protein homologous protein (CHOP). Furthermore, dasatinib also synergized with TRAIL to induce apoptosis via DR5 in GC cells. Our results show that dasatinib promoted TRAIL‐mediated apoptosis via upregulation of CHOP‐dependent DR5 expression in GC, suggesting that DR5 induction can be used as an indicator of dasatinib sensitivity.

Investigation of flavonoids-rich extract from Scutellaria baicalensis shoots shows that 15 of the 19 flavonoids detected with UPLC-Q-TOF-MS were identified, and it exhibited high antioxidant abilities with IC50 at 70.81, 35.34 and 33.27 μg/mL in DPPH, ABTS and CAA assays, respectively. An order of antioxidant abilities in scavenging DPPH· and ABTS+· of eight high content flavonoids in the extract was the same, and it could be well-explained by a preliminary assign-score method we created in structure-activity relationship analyses specific for flavonoids, revealing that double bonds and phenolic hydroxyls on rings A and B are augmentors, and sugar moiety is an attenuator influencing antioxidant capacity but might contribute positively in CAA assays. In addition, three of the eight flavonoids (baicalein, baicalin and scutellarin) made contributions of 58.33%, 60.36% and 51.41% to overall antioxidant activity of the flavonoids-rich extract in DPPH, ABTS and CAA assays, respectively, thus were determined as the primary or marker flavonoids of Scutellaria baicalensis shoots.

Acer truncatum leaves (ATL) have long been used in China as a substitutional tea with health benefits. However, little is known about the antioxidant capacities as well as its bioactive components. The present study was to investigate constitutive phenolic compositions and evaluate antioxidant activities of ATL through its whole growing season. The results showed that all seasonal ATL samples contained remarkable phenols, tannins and flavonoids, and exhibited high antioxidant capacities. Constitutive levels of total phenols, tannins and flavonoids, and three individual phenolic compounds, namely 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), methyl gallate (MG), and quercetin-3-O-l-rhamnoside (QR), and DPPH· and ABTS+· scavenging capacities were all significantly higher in both the beginning (S4) and ending (S11) months than those in the middle months (S5–S10), resulting in a consistent seasonal saddle-shaped pattern. Since S4 and S11 showed significant differences in oxygen radical absorbance capacity (ORAC) values but not in total flavonoids, and there was no significant correlation between ORAC and total flavonoids, it can be inferred that total flavonoids contributed less to the ORAC values than total phenols and tannins did. Correlation analyses further revealed that total phenols, tannins and flavonoids were the main contributors to antioxidant ability, and PGG, MG and QR were found to be the key components of phenols (including tannins and flavonoids) in ATL. Gallic acid was first discovered in ATL, and high levels of PGG and QR (both higher than 1 g/100 g d.w. in April) were corroborated through HPLC analysis. Impressive antioxidant abilities of S4 and S11 were further demonstrated by cellular antioxidant assay, and flavonoids showed stronger antioxidant capacity in the cellular level than other phenolic compositions. In conclusion, seasonal dynamics of constitutive levels of phenolic components lead to alterations of antioxidant capacities in ATL, and November and April were the ideal harvesting time with highest levels of phenols and antioxidant capacity.

Nanomaterials embedded in nanofiltration membranes have become a promising modification technology to improve separation performance. As a novel representation of two-dimensional (2D) nanomaterials, MXene has nice features with a strong negative charge and excellent hydrophilicity. Our previous research showed that MXene nanosheets were added in the aqueous phase, which enhanced the permeselectivity of the membrane and achieved persistent desalination performance. Embedding the nanomaterials into the polyamide layer through the organic phase can locate the nanomaterials on the upper surface of the polyamide layer, and also prevent the water layer around the hydrophilic nanomaterials from hindering the interfacial polymerization reaction. We supposed that if MXene nanosheets were added in the organic phase, MXene nanosheets would have more negative contact sites on the membrane surface and the crosslinking degree would increase. In this study, MXene were dispersed in the organic phase with the help of ultrasound, then MXene nanocomposite nanofiltration membranes were achieved. The prepared MXene membranes obtained enhanced negative charge and lower effective pore size. In the 28-day persistent desalination test, the Na2SO4 rejection of MXene membrane could reach 98.6%, which showed higher rejection compared with MXene embedded in aqueous phase. The results of a long-time water immersion test showed that MXene membrane could still maintain a high salt rejection after being soaked in water for up to 105 days, which indicated MXene on the membrane surface was stable. Besides MXene membrane showed high rejection for high-concentration brine and good mono/divalent salt separation performance in mono/divalent mixed salt solutions. As a part of the study of MXene in nanofiltration membranes, we hoped this research could provide a theoretical guidance for future research in screening different addition methods and different properties.

Landslide disasters have occurred frequently in the Chinese Loess Plateau (CLP) due to increased agricultural irrigation. To explore the spatiotemporal relationship between landslides and mechanisms at the Heifangtai terrace, the HFT irrigated area was selected as a typical case study to investigate the fundamental mechanism of the irrigation-induced landslide in the CLP. Multi-temporal remote sensing images, topographic maps, and unmanned aerial vehicle (UAV) photogrammetry data were used to investigate the evolution progress of landslides. Moreover, the evolution mechanism was discussed through topographic analysis, field monitoring, and laboratory testing. The results showed that erosion, collapse, and sliding had occurred at different scales and at different locations in the past 50 years. With an average retrogressive speed of 9.6 × 103 m2 per year, the tableland decreased by 4.9 × 105 m2 from 1967 to 2018, accounting for about 4.5% of its total area. Over 20 landslides and collapses were extracted in the Dangchuan section in the past four years. More than 5.48 × 105 m3 of loess slipped with an average volume of 381 m3 per day. The evolutionary process of the irrigation-induced landslide, which features retrogression, lateral extension, and clustering, began with local failure and ended in a series of slidings. The increase of groundwater level was a slow process, which is the reason for the lagged occurrence of the landslide. The influence of rainfall and irrigation on slope stability was greater than that of the periodic change of the groundwater level. The triggering effect of irrigation and rainfall on the landslide had a time lag due to slow loess infiltration, and the time response among irrigation, rainfall, and groundwater level was 4–6 months. Our findings provide guidance, concerning the planning and controlling of landslide disasters, which is of critical value for human and construction safety.

Abstract We aim to perform a systematic review and meta-analysis to examine the prognostic value of decompressive craniectomy (DC) in patients with traumatic intracranial hypertension. PubMed, EMBASE, Cochrane Controlled Trials Register, Web of Science, http://clinicaltrials.gov/ were searched for eligible studies. Ten studies were included in the systematic review, with four randomized controlled trials involved in the meta-analysis, where compared with medical therapies, DC could significantly reduce mortality rate [risk ratio (RR), 0.59; 95% confidence interval (CI), 0.47–0.74, P

Abstract Peroxiredoxins (Prxs) play an essential role in the antioxidant activity and symbiotic capacity of Mesorhizobium huakuii. A mutation in the M. huakuii prxA gene (encoding a Prx5‐like peroxiredoxin) was generated by homologous recombination. The mutation of prxA did not affect M. huakuii growth, but the strain displayed decreased antioxidative capacity under organic cumene hydroperoxide (CUOOH) conditions. The higher resistance of the prxA mutant strain compared with the wild‐type strain to more than 1 mmol/L H2O2 was associated with a significantly higher level of glutathione reductase activity and a significantly lower level of intracellular hydrogen peroxide content. Real‐time quantitative PCR showed that under 1 mmol/L H2O2 conditions, expression of the stress‐responsive genes katG and katE was significantly upregulated in the prxA mutant. Although the prxA mutant can form nodules, the symbiotic ability was severely impaired, which led to an abnormal nodulation phenotype coupled to a 53.25% reduction in nitrogen fixation capacity. This phenotype was linked to an absence of bacteroid differentiation and deregulation of the transcription of the symbiotic genes nifH, nifD, and fdxN. Expression of the prxA gene was induced during symbiosis. Thus, the PrxA protein is essential for antioxidant capacity and symbiotic nitrogen fixation, playing independent roles in bacterial differentiation and cellular antioxidative systems.