Search

Modulating autophagy and mitophagy, vital cellular quality control systems, offer therapeutic potential for critical illnesses. However, limited drug screening options hinder progress. We present a novel assay using the photoswitchable fluorescent reporter, mito-Kaede, to quantify mitophagy flux. Mito-Kaede's superior UV-induced photoconversion and brightness post-conversion make it ideal for prolonged mitochondrial dynamics tracking. Its specificity in responding to mitophagy, confirmed by parkin-knockout cells, adds value. When coupled with a custom fluid exchange system, enabling efficient medium changes, precise mitophagy observations become feasible. This mitophagy assay, alongside our methodological insights, can decipher mitophagy's role in pathology and supports drug screening efforts.

This study focuses on the impact of education on health and health inequalities in rural areas of China. Education significantly enhances economic status and health, driving economic growth and improving public health standards. Integral to the “Healthy China Strategy,” it provides essential guidance for public policy and underscores the need for strategic human capital investments to achieve these goals. The study utilizes data from the China Family Panel Studies (CFPS) spanning 2010–2020 and employs the average educational level within counties as an instrumental variable. The causal impact of education on health and health inequalities is estimated using the two-stage least squares (2SLS) method. The findings reveal a significant positive correlation between enhancing education levels and health improvements. Specifically, after controlling for endogeneity, the duration of individual education significantly improves both subjective and objective health outcomes. It reduces health inequalities, with these effects being more pronounced among women and low-income groups. Mechanistically, education positively impacts health primarily by altering health behaviors and social network levels and reducing health inequalities through socio-economic factors. This paper provides important implications for public policy, suggesting that enhancing educational investments can drive economic development and improve population health standards.

Background: Cold environments pose serious threats on human health, with increased risk for myocardial infarction, stroke, frostbite, and hypothermia. Acquired cold acclimation is required to minimize cold-induced injures and to improve metabolic health. However, the underlying mechanisms remain to be fully elucidated. Objective: We aimed to identify critical amino acids involved in cold acclimation and unmask the regulatory mechanisms. Methods: A total of twenty male participants were recruited and followed up after 3 months’ natural cold exposure. Cold-induced vasodilation (CIVD) tests and clinical biochemical analysis were performed at baseline and after 3-months cold exposure, whilst blood samples were collected, and plasma amino acids were analyzed by targeted metabolomics. To further confirm the effect of lysine on cold tolerance and explain the latent mechanism, mice were challenged with chronic cold exposure for 7 days with lysine supplement, then core and local surface temperature as well as thermogenesis activity were detected. Results: Continuous cold exposure shortened the CIVD onset time and increased the average finger temperature. Levels of the plasma lysine and glycine were decreased in both humans and mice. Venn analysis from three datasets revealed that lysine was the only significantly changed plasma amino acid, which strongly correlated with the altered CIVD. Moreover, mice sustained a relatively higher core temperature and surface temperature in the back, tail and paws upon lysine supplementation. Furthermore, lysine supplementation increased the level of histone H3K18cr and promoted the gene and protein expression of Cpt1a, Cpt2 and Cyp27a1 in liver. Conclusion: Our work identified lysine as a critical amino acid for the remodeling of hepatic histone crotonylation that facilitates cold acclimation.

Abstract In recent years, with the unremitting advancement of higher education reform, academics have been experiencing stress associated with conducting scientific research. In this study focusing on university teachers in China, we adopted a stepwise regression method and reviewed related literature to construct a mechanism of academic stress and occupational burnout. Specifically, we tested job satisfaction and relative deprivation as mediating and moderating variables and conducted empirical research on 1239 teachers from 15 universities in eastern, central, and western China. Our findings show that: (1) academic stress has a significant positive effect on occupational burnout; (2) job satisfaction has a partial role as the intermediary agent between academic stress and occupational burnout; and (3) relative deprivation positively moderates the relationship between academic stress and job satisfaction, indicating that teachers in universities and colleges are also affected by relative deprivation and the perception of inequity. These findings have significant value in the management of higher education and academic research.

Summary: Background: Since the initial identification of the Severe Fever with Thrombocytopenia Syndrome (SFTS) in ticks in rural areas of China in 2009, the virus has been increasingly isolated from a diverse array of hosts globally, exhibiting a rising trend in incidence. This study aims to conduct a systematic analysis of the temporal and spatial distribution of SFTS cases, alongside an examination of the infection rates across various hosts, with the objective of addressing public concerns regarding the spread and impact of the disease. Methods: In this systematic review and meta-analysis, an exhaustive search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Medline, CNKI, WanFang, and CQVIP. The literature search was confined to publications released between January 1, 2009, and May 29, 2023. The study focused on collating data pertaining to animal infections under natural conditions and human infection cases reported. Additionally, species names were unified using the National Center for Biotechnology Information (NCBI) database. The notification rate, notification death rate, case fatality rate, and infection rates (or MIR) were assessed for each study with available data. The proportions were pooled using a generalized linear mixed-effects model (GLMM). Meta-regressions were conducted for subgroup analysis. This research has been duly registered with PROSPERO, bearing the registration number CRD42023431010. Findings: We identified 5492 studies from database searches and assessed 238 full-text studies for eligibility, of which 234 studies were included in the meta-analysis. For human infection data, the overall pooled notification rate was 18.93 (95% CI 17.02–21.05) per ten million people, the overall pooled notification deaths rate was 3.49 (95% CI 2.97–4.10) per ten million people, and the overall pooled case fatality rate was 7.80% (95% CI 7.01%–8.69%). There was an increasing trend in notification rate and deaths rate, while the case fatality rate showed a significant decrease globally. Regarding animal infection data, among 94 species tested, 48 species were found to carry positive nucleic acid or antibodies. Out of these, 14 species were classified under Arthropoda, while 34 species fell under Chordata, comprising 27 Mammalia and 7 Aves. Interpretation: This systematic review and meta-analysis present the latest global report on SFTS. In terms of human infections, notification rates and notification deaths rates are on the rise, while the case fatality rate has significantly decreased. More SFTSV animal hosts have been discovered than before, particularly among birds, indicating a potentially broader transmission range for SFTSV. These findings provide crucial insights for the prevention and control of SFTS on a global scale. Funding: None.

BackgroundHypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension.MethodsThis is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored.ResultsSixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 [interquartile range, 3.1–23.3] minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury.ConclusionPerioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration.Clinical trial registrationhttps://www.chictr.org.cn/showprojEN.html?proj=134260, CTR2200055929.

Diffusion-controlled cyclic voltammograms at fast scan rates show peak shifts, as well as decreases in the peak currents from predicted diffusion-controlled currents, especially when the currents are large in a low concentration of supporting electrolytes. This has been conventionally recognized as an IR-drop effect due to solution resistance on the peaks, as well as a heterogeneously kinetic effect. It is also brought about by the negatively capacitive currents associated with charge transfer reactions. The reaction product generates dipoles with counterions to yield a capacitance, the current of which flows oppositely to that of the double-layer capacitance. The three effects are specified here in the oxidation of a ferrocenyl derivative using fast scan voltammetry. The expression for voltammograms complicated with IR-drop is derived analytically and yields deformed voltammograms. The peak shift is approximately linear with the IR-voltage, but exhibits a convex variation. The dependence of some parameters on the peaks due to the IR-drop is compared with those due to the negative capacitance. The latter is more conspicuous than the former under conventional conditions. The two effects cannot be distinguished specifically except for variations in the conductance of the solution.

Abstract Urban commercial centres are the most concentrated areas of economic activity. Understanding the spatial distribution pattern and comprehensive strength of urban commercial centres is important to guide the reasonable graded allocation of urban commercial space, spatial structure optimization and sustainable development of the commercial economy. Herein, mobile phone signalling data are used to identify the functional connection between recreational and residential places and local spatial autocorrelation analysis is used to identify the 24 commercial centres in the central city of Hefei. The comprehensive strength evaluation system of commercial centres is constructed from their basic conditions and customer consumption behaviours, and their comprehensive strength indices are accordingly measured and graded. The spatial distribution characteristics of commercial centres at all levels are analysed, and optimisation suggestions are made for the whole area and region. The following conclusions are drawn from the results of this study. (1) Compared to traditional single-perspective evaluations, the developed comprehensive strength evaluation system considers supply and demand perspectives for commercial centres, providing a more holistic and accurate portrayal of the strengths of various centres within a region. (2) The current commercial centres are characterised by ‘large dispersion and small concentration’ in spatial and hierarchical distribution. (3) The commercial centres in Hefei have formed a relatively complete ‘first, second, and third level’ commercial centre system, with the first level as the core and relying on the urban road system to form a network spatial connection. (4) Most of the commercial centres are concentrated in the First Ring Road, Swan Lake in the Government Affairs District and Binhu Century Town Estate, while most areas north of the Second Ring Road and Binhu New District still lack large-scale commercial centres. This study provides a technical reference for analysing urban commercial spatial structure patterns and provides decision support for optimising the spatial layout of urban commercial service functions.

Abstract Background Bladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied. Methods To examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed. Results JorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 μM, respectively. JorA-induced significantly changed proteins were enriched in “cancer-related pathways” and “EGFR-related signaling pathways”, which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were − 8.153 and − 7.264 kcal/mol, respectively). Conclusions The marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy. Graphical Abstract

Chronoamperometric curves for the oxidation of a ferrocenyl derivative via a potential step, calculated using the Cottrell equation, showed less diffusion-controlled currents on a platinum wire electrode. This lower deviation cannot be explained via Butler–Volmer heterogeneous kinetics, but was ascribed to the negatively capacitive current associated with a redox reaction. The deviation in fully oxidized electrical potential corresponds to the non-zero concentration at the electrode surface, which cannot be predicted using the Nernst equation. This equation expresses the relationship between the electrical potential and activity at the electrode surface rather than the concentration. The diffusion equation determines the relationship between the current and surface concentration rather than activity. Negative capacitance or a non-zero concentration may arise from structure formation on the electrode owing to dipole–dipole interactions, which are similar to the generation of double-layer capacitance, including frequency dispersion. Following this concept, we derive expressions for a lowered diffusion-controlled current and time-dependent surface concentration. The negatively capacitive current shows the time dependence of t−0.9, which is similar to the decay of double-layer capacitive currents. The surface concentration decays with t−0.4-dependence.

AbstractExploring the driving factors behind urban polycentricity is of paramount significance for advancing the implementation of urban polycentric strategies. In this, paper takes 41 cities in the China’s Yangtze River Delta region are taken as the research objects, and the degree of urban polycentricity is measured using non-parametric and social network methods. Then, the geographic probe method is applied to reveal the driving factors of the spatial differentiation of urban polycentricity. The research results showed that (1) the distribution of hot and cold spots of the urban polycentricity index was roughly the same between 2006 and 2015, while and the distribution of hot and cold spots of the urban polycentricity index varied greatly between 2015 and 2020. (2) In 2010, the proportions of the secondary and industry tertiary industries and the topographic relief were the main driving factors of urban polycentricity. By 2020, the population size and topographic relief were the key drivers of urban polycentricity.

Quenched Co-based ribbon strips are widely used in the fields of magnetic amplifier, magnetic head material, magnetic shield, electric reactor, inductance core, sensor core, anti-theft system label, and so on. In this study, Co-based composite CoFeNiSiB ribbon strips with a micron width were fabricated by micro-electro-mechanical systems (MEMS) technology. The carbon and FeCoGa nanofilms were deposited for surface modification. The effect of carbon and FeCoGa nanofilm coatings on the crystal structure, surface morphology, magnetic properties, and magnetoimpedance (MI) effect of composite ribbon strips were systematically investigated. The results show that the surface roughness and coercivity of the composite ribbon strips are minimum at a thickness of the carbon coating of 60 nm. The maximum value of MI effect is 41% at 2 MHz, which is approximately 2.4 times greater than plain ribbon and 1.6 times greater than FeCoGa-coated composite ribbon strip. The addition of a carbon layer provides a conductive path for high frequency currents, which effectively reduces the characteristic frequency of the composite ribbon strip. The FeCoGa coating is able to close the flux path and reduce the coercivity, which, in turn, increases the transverse permeability and improves the MI effect. The findings indicate that a successful combination of carbon layer and magnetostrictive FeCoGa nanofilm layer can improve the MI effect and magnetic field sensitivity of the ribbon strips, demonstrating the potential of the composite strips for local and micro area field sensing applications.

The present study was aimed to verify whether an integrating of wearable activity tracker device and a social media intervention strategy would be better than a standalone social media intervention for improving physical activity (PA) and reducing sedentary time for Chinese postgraduate population. A total of 42 full-time postgraduate students participated in this study, which were randomized to receive a 4-week social media intervention through WeChat either with (Wearable Device group) or without (control group) a wearable activity tracker device. Energy expenditure, step counts, moderate to vigorous physical activity time (MVPA) and sedentary time were assessed before and after the intervention. Besides, anthropometric parameters of body weight, body mass index, body fat rate, waist-to-hip ratio, as well as self-reported quality of life were also evaluated. It was found that both energy expenditure and step counts were significantly increased, while sedentary time was significantly reduced during the post-intervention test compared to the baseline test for Wearable Device group. No significant difference of PA was found for the control group. The results demonstrated that the integrating of wearable activity tracker device and a social media intervention was effective in promoting PA, while a standalone social media intervention may have no effect on the influence of PA for Chinese postgraduates.

Abstract Background The importance of multidisciplinary team (MDT) centred on pregnant women with pulmonary hypertension (PH) has been highlighted. However, rare studies have explored its effects on pregnancy outcomes. This study seeks to investigate whether and how the MDT has an effect on the treatment and outcomes of PH pregnant women. Methods A pre- and post-intervention study was conducted based on an interrupted time series design to compare the treatment and outcomes of patients with PH before (pre-MDT) and after (post-MDT) implementation of the MDT. PH was defined as pulmonary artery systolic pressure (sPAP) ≥ 35 mmHg measured by echocardiography or right heart catheterization and sPAP at 35–60 mmHg and over 60 mmHg was defined as mild and severe PH, respectively. All results were analyzed by T-tests, Chi square tests or Fisher exact test and two-sided p value

Abstract Objective This study aimed to assess the correlation between residual hearing and audiologic outcomes after cochlear implant (CI) surgery in patients with cochlear nerve deficiency (CND). Methods This retrospective study included 57 patients with CND who underwent CI surgery. Patients were divided into four groups according to hearing level (80–95, 95–110, 110–120, and >120 dB) and three groups according to residual hearing (entire spectrum hearing, partial spectrum hearing, and no spectrum hearing) based on the measured response at each frequency. Auditory performance (categorical auditory performance [CAP], Infant–Toddler Meaningful Auditory Integration Scale [IT‐MAIS]) and speech perception (speech intelligibility rating [SIR] and meaningful use of speech scale [MUSS]) were assessed before and 2 years after the surgery. Results Forty‐seven (82.5%) patients had complete or total hearing loss (≥95 dB) and 17 (29.8%) had no spectrum hearing before CI surgery. Twenty‐nine (50.9%) patients did not exhibit residual hearing at 4 kHz. All patients demonstrated an improvement in auditory performance and speech perception: the CAP score in the 80–95 dB group was significantly higher than that in the 110–120 and >120 dB groups, and the entire spectrum hearing group showed significantly higher CAP, SIR, and IT‐MAIS scores than the partial spectrum hearing group and significantly higher CAP, SIR, IT‐MAIS, and MUSS scores than the no spectrum hearing group. Conclusion For patients with CND, residual hearing, especially high‐frequency residual hearing, was poor and postoperative audiologic outcomes were significantly associated with the range of residual hearing. Level of Evidence 4

Background: Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease that negatively impacts quality of life, exercise capacity, and mortality. This study sought to investigate the relationship between serum uric acid (UA) level and the disease severity and treatment response of patients with PAH and congenital heart disease (PAH-CHD).Methods: This study included 225 CHD patients and 40 healthy subjects. Serum UA was measured in all patients, and UA levels and haemodynamic parameters were re-evaluated in 20 patients who had received PAH-specific drug treatment for at least 7 ± 1 month.Results: Serum UA levels were significantly higher in PAH-CHD patients than in CHD patients with a normal pulmonary artery pressure and normal subjects (347.7 ± 105.7 μmol/L vs. 278.3 ± 84.6 μmol/L; 347.7 ± 105.7 μmol/L vs. 255.7 ± 44.5 μmol/L, p < 0.05). UA levels in the intermediate and high risk groups were significantly higher than those in the low-risk group (365.6 ± 107.8 μmol/L vs. 311.2 ± 82.8 μmol/L; 451.6 ± 117.6 μmol/L vs. 311.2 ± 82.8 μmol/L, p < 0.05). Serum UA levels positively correlated with mean pulmonary arterial pressure, WHO functional class, pulmonary vascular resistance, and NT-proBNP (r = 0.343, 0.357, 0.406, 0.398; p < 0.001), and negatively with mixed venous oxygen saturation (SvO2) and arterial oxygen saturation (SaO2) (r = −0.293, −0.329; p < 0.001). UA significantly decreased from 352.7 ± 97.5 to 294.4 ± 56.8 μmol/L (p = 0.001) after PAH-specific drug treatment for at least 6 months, along with significant decreases in mean pulmonary arterial pressure and pulmonary vascular resistance and increases in cardiac index and mixed SvO2.Conclusion: Serum UA can be used as a practical and economic biomarker for risk stratification and the evaluation of PAH-specific drug treatment effects for patients with PAH-CHD.

Background: Idiopathic pulmonary arterial hypertension (PAH) is a potentially fatal pulmonary vascular disease with an extremely poor natural course. The limitations of current treatment and the unclear etiology and pathogenesis of idiopathic PAH require new targets and avenues of exploration involved in the pathogenesis of PAH. tRNA-derived small RNAs (tsRNAs), a new type of small non-coding RNAs, have a significant part in the progress of diverse diseases. However, the potential functions behind tsRNAs in idiopathic PAH remain unknown.Methods: Small RNA microarray was implemented on three pairs of plasma of idiopathic PAH patients and healthy controls to investigate and compare tsRNAs expression profiles. Validation samples were used for real-time polymerase chain reaction (Real-time PCR) to verify several dysregulated tsRNAs. Bioinformatic analysis was adopted to determine potential target genes and mechanisms of the validated tsRNAs in PAH.Results: Microarray detected 816 statistically significantly dysregulated tsRNAs, of which 243 tsRNAs were upregulated and 573 were downregulated in PAH. Eight validated tsRNAs in the results of Real-time PCR were concordant with the small RNA microarray: four upregulated (tRF3a-AspGTC-9, 5’tiRNA-31-GluCTC-16, i-tRF-31:54-Val-CAC-1 and tRF3b-TyrGTA-4) and four downregulated (5’tiRNA-33-LysTTT-4, i-tRF-8:32-Val-AAC-2, i-tRF-2:30-His-GTG-1, and i-tRF-15:31-Lys-CTT-1). The Gene Ontology analysis has shown that the verified tsRNAs are related to cellular macromolecule metabolic process, regulation of cellular process, and regulation of cellular metabolic process. It is disclosed that potential target genes of verified tsRNAs are widely involved in PAH pathways by Kyoto Encyclopedia of Genes and Genomes.Conclusion: This study investigated tsRNA profiles in idiopathic PAH and found that the dysregulated tsRNAs may become a novel type of biomarkers and possible targets for PAH.

Abstract Background Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves monocrotaline (MCT)-induced PAH and right heart failure; however, the underlying mechanism remains unknown. Here we speculate that ApoA5 has a protective effect in pulmonary vessels and aim to evaluate the mechanism. Methods ApoA5 is overexpressed in an MCT-induced PAH animal model and platelet-derived growth factor (PDGF)-BB-induced proliferating PASMCs. Lung vasculature remodeling was measured by immunostaining, and PASMC proliferation was determined by cell counting kit‐8 and 5‐ethynyl‐2'‐deoxyuridine5‐ethynyl‐2'‐deoxyuridine incorporation assays. Coimmunoprecipitation-mass spectrometry was used to investigate the probable mechanism. Next, its role and mechanism were further verified by knockdown studies. Results ApoA5 level was decreased in MCT-induced PAH lung as well as PASMCs. Overexpression of ApoA5 could help to inhibit the remodeling of pulmonary artery smooth muscle. ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. Conclusion ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism.

The amount of anodically dissolved charge of silver by linear sweep stripping voltammetry has been observed to be smaller than that of the potentiostatically deposited charge. The imbalance in the charge is opposite to the participation in the double-layer capacitance. This can be explained in terms of the negative capacitive current, which is caused by dipoles of generated redox charge (Ag+) with counterions (NO3−). Lower concentrations of counterions may suppress the capacitance to retain the equality of the charge. This prediction is examined in this work by the oxidation of silver film at various concentrations of NO3− by anodic stripping voltammetry. The capacitance decreased with a decrease in the salt concentrations less than 0.05 mol dm−3. Low concentrations of salts prevent loss of the anodic charge in electroanalysis. This dependence was related with the lifespan of generated silver nitrate dipoles and is described theoretically.

As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.

Learning engagement is an important predictor of academic success and a key indicator of educational quality. It has therefore attracted considerable research interest, with previous studies exploring how to enhance engagement via pedagogical approaches, strategies, and content, as well as through teacher-student interaction. However, the relationship between individual learners’ internal mechanisms and learning engagement has yet to be investigated in depth. Accordingly, the present study explored the direct effects of career calling on higher vocational nursing students’ learning engagement and the mediating roles of career adaptability and career commitment via a parallel mediation model. Data were collected from 388 nursing students at two higher vocational colleges in China and the hypotheses were tested using correlation and regression analyses. The results showed that career calling imparted a significant positive effect on the nursing students’ engagement in learning, with career adaptability and career commitment mediating this relationship. These findings highlight the importance of promoting learning engagement among nursing students and the need to carefully design instructional activities for the healthcare profession.

Pakistan is one developing country and 70% of the population is depending on Agriculture and faces a lack of innovation in the agriculture sector overall. the main objectives of our study were to i) identify ethical practices (knowledge-sharing, trustworthiness in loan providing, loyalty in professionalism, responsibility of actions, and accountability) of the agriculture departments and institutions or government towards improving digital technology in the agriculture sector. ii) Quantify the user behavior in the digitalization of the agricultural system. iii) Identify the intervening role of user behavior in the relation to ethical practices and agricultural technology development. The study examined 490 users of farming technologies who work in the agriculture sector in two provinces of Pakistan. Using the Baron and Kenny framework, this research confirmed the prediction that user behavior mediated the relationship between ethical practices and agricultural technology in a four-step process. The main outcomes of the study have revealed a positive and significant impact of ethical practices on the development of the digitalization of the agricultural system. Specifically, the study indicated that “user behavior” significantly mediates the association between ethical practices and agricultural technology development. Furthermore, this study proposes that it is essential for Pakistan’s agriculture sector to nurture circumstances dedicated to better practices as it will not only attract more residents to agricultural growth but also help the agriculture sector achieve its eventual goal of increased productivity. Implications of this research study are deliberated and provide directions for future research in the area.

Abstract Background Researches indicated the process of Endothelial-Mesenchymal-Transition (EndMT) of vascular endothelial cells (ECs) was critically involved in the progression of tumor. ECs demonstrated functional and phenotypic heterogeneity when located under different microenvironments. The extracellular pH of tumor tissues was acidic compared to that of normal tissues. However, there was still unclear whether the acidic microenvironment affected the EndMT of vascular ECs. Methods Human Umbilical Vein Endothelial Cell (HUVECs) was cultured under the normal or acidic medium to evaluate the alteration of morphology, migration, permeability, and EndMT markers. Microarray assay was adopted to analyze the differential expression of miRNAs in the acidity-treated HUVECs. Gain- and loss- of function experiments were performed to evaluate the functional role of miRNA-548ac on acidity-induced EndMT of HUVECs. Luciferase reporter and Chromatin-immunoprecipitation assays were conducted to assess the downstream pathway of miRNA-548ac in acidity-induced EndMT of HUVECs. Results Our results showed that HUVECs demonstrated mesenchymal transition under acidic conditions with the increase of migration, permeability, and expression of α-SMA and Vimentin, but the expression of vascular endothelial cadherin (VE-cadherin) and CD31 were reduced. In addition, the acidity-treated HUVECs remarkably facilitated the transmigration of pancreatic cancer cells. The expression of miRNA-548ac was significantly decreased in the acidity-treated HUVECs. Moreover, overexpression of miR-548ac inhibited the EndMT of HUVECs and consequently impeded the transmigration of pancreatic cancer cells. The miR-548ac inhibited the expression of YB-1 by binding to the 3’UTR of its mRNA, and YB-1 promoted the translation of Snail which was a critical regulator of EndMT. What’s more, Snail transcriptionally inhibited the expression of miR-548ac through binding to the promoter of its host gene. Conclusions Our data implicated that the acidic microenvironment promoted the EndMT of HUVECs by the miR-548ac/YB-1/Snail axis, which could contribute to the metastasis of pancreatic cancer.

Variations of the double layer capacitances (DLCs) at a platinum electrode with concentrations and kinds of salts in aqueous solutions were examined in the context of facilitating orientation of solvent dipoles. With an increase in ionic concentrations, the DLCs increased by ca. a half and then kept constant at concentrations over 1 mol dm−3. This increase was classically explained in terms of the Gouy–Chapman (GC) equation combined with the Stern model. Unfortunately, measured DLCs were neither satisfied with the Stern model nor the GC theory. Our model suggests that salts destroy hydrogen bonds at the electrode–solution interface to orient water dipoles toward the external electric field. A degree of the orientation depends on the interaction energy between the salt ion and a water dipole. The statistical mechanic calculation allowed us to derive an equation for the DLC as a function of salt concentration and the interaction energy. The equation took the Langmuir-type in the relation with the concentration. The interaction energy was obtained for eight kinds of salts. The energy showed a linear relation with the interaction energy of ion–solvent for viscosity, called the B-coefficient.

Design and optimization of well spacing is a key indicator for evaluating the development effect of shale gas reservoirs. On the basis of theoretical understanding, and after the verification by analogy, numerical simulation, and economic evaluation, a complete workflow from inter-well interference simulation and dynamic data diagnosis to multi-well production simulation and well spacing optimization was formed. First, a pressure detection boundary propagation model is established to simulate the response degree of inter-well interference under different connected conditions. Second, inter-well interference is identified and diagnosed depending on the inter-well interference response behaviors and the interpretation of performance data from gas wells. Third, taking the geological interpretation and dynamic analysis results as basic parameters, a multi-well numerical model for volume fracturing in gas reservoirs is established to simulate the production performance of gas field, and then well spacing is optimized in combination with the net present value model. The application in the Ning 201 well block in the Changning National Shale Gas Demonstration Area has shown that a smaller well spacing can allow a premature inter-well interference and also the enhancement of recovery in the entire block. Given the current fracturing scale and parameter system, the well spacing of 300–400 m can be optimized to 260–320 m, that is, the number of wells per unit area increases by 20%–30%. As a result, the recovery percent of reserves in the block increase by about 10%. The net present value of the block rises, but the corresponding optimal well spacing does not change, with the production period.

Abstract Background Charcot‐Leyden crystals (CLCs) are recognized to be classic hallmarks of eosinophilic inflammation. Both protein and mRNA levels of CLC in nasal secretions and nasal brushing samples have been associated with nasal polyp recurrence. However, whether the crystalline CLC structures in nasal tissue could serve as an effective biomarker to predict polyp recurrence remains unclear. Methods A total of 110 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) completing the postoperative follow‐up over a period of 24 months were recruited. Hematoxylin and eosin staining was employed for CLCs identification. The predictive factors for polyp recurrence were determined by binary logistic regression analysis. Results Thirty three (30.00%) patients developed recurrence during a 24‐month postoperative follow‐up, in which 84.85% (28/33) patients had crystalline CLC structures. Logistic regression analysis showed that crystalline CLC structure in nasal tissues is predictive of polyp recurrence. Youden index demonstrated crystalline CLC structure higher than 1 per high power field can predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity. Conclusions The crystalline CLC structures in nasal tissues may serve as an easy‐counting and promising biomarker to predict CRSwNP recurrence.

Manure treatment with black soldier fly larvae (BSFL) and BSFL frass application in crop land is a sustainable strategy; however, whether residual antibiotic resistance genes (ARGs) and their transmission risk are related to the manure BSFL treatment process is still unknown. In this paper, the effect of BSFL addition density on residual tetracycline resistance genes (TRGs) and transmission from frass to pakchoi was determined. The results showed that BSFL frass can provide sufficient nutrients for growth, improve the economic value of pakchoi, and reduce the risk of transmission of TRGs in chicken manure regardless of BSFL density. The potential hosts of the TRGs we detected were found in BSFL frass (Oblitimonas and Tissierella), rhizosphere soil (Mortierella and Fermentimonas), and pakchoi endophytes (Roseomonas). The present study concluded that BSFL frass produced by adding 100 BSFL per 100 g of chicken manure has the advantages of high value and low risk. These findings will provide important strategic guidance for animal manure disposal and theoretical support for preventing the transmission of TRGs in BSFL applications.

The reasonable distribution of urban green space (UGS) is a topic that urban researchers have been exploring for a long time. Solving the imbalance between the supply and demand of UGS plays an important role in improving the health level of a city. This study examines the central urban area of Hefei as an example. We developed a modified Gaussian two-step floating catchment area method and used the path planning model of Gaode Map to evaluate the accessibility of UGS under different transportation modes and different time thresholds while integrating mobile phone signaling data. Additionally, a fine-scale analysis of the actual supply and demand relationship of UGS was conducted by integrating the accessibility evaluation results with the recreational situation of UGS to analyze the deviation of supply and demand to further discuss the spatial distribution equilibrium of UGS. The main conclusions are as follows. (1) The spatial distribution of UGSs in the central urban area of Hefei is uneven. Different time thresholds and different transportation modes have a significant impact on the UGS accessibility evaluation results. (2) With the increase in the time threshold or travel distance, the number of grids above the moderate accessibility level generally increases. The spatial distribution of the grids with moderate, high and highest accessibility level present different patterns of contiguous, clusters, and spots distribution. (3) After combining these results with the actual recreational situation of UGS, we found that the overall demand in the central urban area exceeds the supply at the 15-min threshold, while the overall supply exceeds the demand at the 30-min threshold. The grids with balanced supply and demand or more supply than demand have comprehensive parks with a moderate population density and strong road connectivity in the neighborhood. This study strengthens the data granularity and improves the accuracy of accessibility evaluation by integrating mobile phone signaling data with the path planning model of Gaode Map. Also, we evaluate the accessibility with multi-transport modes and different time thresholds, which can bring more practical guidance for optimizing the distribution of UGS.

Land optimization is a necessary means to improve the land use efficiency and promote the sustainable use of land resources. How to fully consider the regional background conditions and scientifically and comprehensively achieve the sustainable and optimal utilization of land resources is a necessary means to promote the sustainable utilization of land resources, especially in semiarid sandy areas with fragile ecological environments. Therefore, based on the characteristics of a semiarid sandy area and by using existing research, with important water resources as the core, this study constructed an optimal land allocation method in a semiarid sandy area based on the soil moisture characteristics. By taking the Horqin Zuoyihou Banner in the semiarid sandy area of China as a typical case, we explored its soil moisture characteristics and influencing factors and put forward the distribution patterns and suggestions for optimal land use. The results show that it is effective to optimize the land space allocation in semiarid sandy areas based on the soil moisture characteristics, and the corresponding land use activities should be arranged according to the moisture conditions of each region, which is beneficial to achieve sustainable semiarid sandy land use. We hope that this study can provide valuable sustainable land optimization solutions for the efficient, sustainable use and protection of land resources in semiarid regions.

Cochlear nerve deficiency (CND) is often associated with variable outcomes of cochlear implantation (CI). We assessed previous investigations aiming to identify the main factors that determine CI outcomes, which would enable us to develop predictive models. Seventy patients with CND and normal cochlea who underwent CI surgery were retrospectively examined. First, using a data-driven approach, we collected demographic information, radiographic measurements, audiological findings, and audition and speech assessments. Next, CI outcomes were evaluated based on the scores obtained after 2 years of CI from the Categories of Auditory Performance index, Speech Intelligibility Rating, Infant/Toddler Meaningful Auditory Integration Scale or Meaningful Auditory Integration Scale, and Meaningful Use of Speech Scale. Then, we measured and averaged the audiological and radiographic characteristics of the patients to form feature vectors, adopting a multivariate feature selection method, called stability selection, to select the features that were consistent within a certain range of model parameters. Stability selection analysis identified two out of six characteristics, namely the vestibulocochlear nerve (VCN) area and the number of nerve bundles, which played an important role in predicting the hearing and speech rehabilitation results of CND patients. Finally, we used a parameter-optimized support vector machine (SVM) as a classifier to study the postoperative hearing and speech rehabilitation of the patients. For hearing rehabilitation, the accuracy rate was 71% for both the SVM classification and the area under the curve (AUC), whereas for speech rehabilitation, the accuracy rate for SVM classification and AUC was 93% and 94%, respectively. Our results identified that a greater number of nerve bundles and a larger VCN area were associated with better CI outcomes. The number of nerve bundles and VCN area can predict CI outcomes in patients with CND. These findings can help surgeons in selecting the side for CI and provide reasonable expectations for the outcomes of CI surgery.

Abstract Background The repair of critical-sized bone defects is always a challenging problem. Electromagnetic fields (EMFs), used as a physiotherapy for bone defects, have been suspected to cause potential hazards to human health due to the long-term exposure. To optimize the application of EMF while avoiding its adverse effects, a combination of EMF and tissue engineering techniques is critical. Furthermore, a deeper understanding of the mechanism of action of EMF will lead to better applications in the future. Methods In this research, bone marrow mesenchymal stem cells (BMSCs) seeded on 3D-printed scaffolds were treated with sinusoidal EMFs in vitro. Then, 5.5 mm critical-sized calvarial defects were created in rats, and the cell scaffolds were implanted into the defects. In addition, the molecular and cellular mechanisms by which EMFs regulate BMSCs were explored with various approaches to gain deeper insight into the effects of EMFs. Results The cell scaffolds treated with EMF successfully accelerated the repair of critical-sized calvarial defects. Further studies revealed that EMF could not directly induce the differentiation of BMSCs but improved the sensitivity of BMSCs to BMP signals by upregulating the quantity of specific BMP (bone morphogenetic protein) receptors. Once these receptors receive BMP signals from the surrounding milieu, a cascade of reactions is initiated to promote osteogenic differentiation via the BMP/Smad signalling pathway. Moreover, the cytokines secreted by BMSCs treated with EMF can better facilitate angiogenesis and osteoimmunomodulation which play fundamental roles in bone regeneration. Conclusion In summary, EMF can promote the osteogenic potential of BMSCs and enhance the paracrine function of BMSCs to facilitate bone regeneration. These findings highlight the profound impact of EMF on tissue engineering and provide a new strategy for the clinical treatment of bone defects.

A double layer capacitance (DLC) has mainly been brought about in the Helmholtz layer rather than in the diffuse layer, as was demonstrated with the invariance of DLC to salt concentration, c, less than 0.5 M (M = mol dm−3). The DLC measured here increased with concentrations of KCl and HCl solutions as high as 1 M at a platinum electrode by the ac impedance method. It was represented as a sum of the Helmholtz capacitance and the ionic one which had 0.7 power of the concentrations. The simple addition implies that the Helmholtz contribution and the ionic one should be represented by a parallel combination rather than a series one such as in the Stern model. The disagreement of the experimental values of the DLC with the Gouy–Chapman theory at high concentrations has been conventionally attributed to the effects of packing of ions over their sizes. In this paper, a model of avoiding the packing was introduced, in which ions were distributed in the direction normal to the electrode in the balance of electric motive force and the thermal energy, keeping the uniform distribution on a plane projected to the electrode. The energy balance was taken by using the grand canonical ensemble in statistical mechanics. The ionic contribution had a linear relation with the applied voltage rather than exponential dependence. When a series combination was applied to the Helmholtz capacitance and the ionic one under the condition of difference between the locally anionic DLC and the cationic one, we obtained approximately a parallel combination of the two capacitances because either the anionic or the cationic DLC works predominantly.

Methamphetamine (Meth) is a predominantly abused neurostimulant, and its abuse is often associated with multiple neurological symptoms. Olfaction, the sense of smell, is a highly neurotransmission-dependent physiological process; however, the effect of Meth on olfactory function and its underlying mechanisms remain largely unknown. This study aimed to explore the impact of Meth abuse on the olfactory system and the potential mechanisms. Chronic Meth abuse was induced by daily administration of Meth in male mice for 4 weeks, and we then systematically examined olfactory performance. Behavioral tests found that Meth-treated animals showed increased olfactory threshold, decreased olfactory sensitivity, reduced olfactory-dependent discrimination, and difficulty in seeking buried food. Notably, the increased deposition of α-synuclein (α-syn) in the olfactory bulb was detected. Adeno-associated virus (AAV)-mediated α-syn intervention therapy in the olfactory bulb significantly alleviated Meth-induced olfactory function impairment, and 8 weeks of aerobic exercise showed similar effects through the same principle of α-syn intervention. Notably, exercise-mediated reduction of α-syn inhibited abnormal firing activity and restored the inhibitory synaptic regulation of mitral cells in the olfactory bulb. These findings suggest the involvement of α-syn in the pathogenic mechanisms of Meth-induced olfactory dysfunction and shed light on the possible therapeutic applications of aerobic exercise in Meth-induced olfactory dysfunction.

ObjectTo investigate the long-term development of auditory and speech in patients with common cavity deformity (CCD) after cochlear implantation (CI) and its relationship to imaging characteristics.MethodsTwenty-three CCD patients and 59 age- and sex-matched CI children with normal inner ear structure were recruited. The auditory and speech development of these two groups were evaluated at 0, 1, 3, 6, 12, and 18 months after CI activation using four parent reports questionnaires [Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR), Meaningful Auditory Integration Scale/Infant-Toddler Meaningful Auditory Integration Scale (MAIS/ITMAIS), and Meaningful Use of Speech Scale (MUSS)]. Computed tomography-based 3-dimensional reconstruction of the surgical side of 18 CCD children was performed, the volume and surface area were calculated. Correlation analysis was performed on the imaging performance and post-operative outcomes.ResultsThe percentages of MAIS/IT-MAIS scores and CAP scores at different evaluation time points are significantly different (p < 0.05). When comparing SIR results across time points, significant growth was observed in most of the comparisons. In addition, significant differences (p < 0.05) are observed among the percentages of MUSS scores at different time points except the comparison between 0 and 1 month after CI activation. Patients in the CCD group had poorer auditory and speech performances at different stages after CI compared with those in the control group. According to the reconstruction of CCD patients, the volume ranged from 12.21 to 291.96 mm3; the surface area ranged from 27.81 to 284.7 mm2. When the lumen surface area was

Abstract Background Current strategies for craniofacial defect are faced with unmet outcome. Combining 3D-printing with safe, noninvasive magnetic therapy could be a promising breakthrough. Methods In this study, polylactic acid/hydroxyapatite (PLA/HA) composite scaffold was fabricated. After seeding rat bone marrow mesenchymal stem cells (BMSCs) on scaffolds, the effects of electromagnetic fields (EMF) on the proliferation and osteogenic differentiation capacity of BMSCs were investigated. Additionally, 6-mm critical-sized calvarial defect was created in rats. BMSC-laden scaffolds were implanted into the defects with or without EMF treatment. Results Our results showed that PLA/HA composite scaffolds exhibited uniform porous structure, high porosity (~ 70%), suitable compression strength (31.18 ± 4.86 MPa), modulus of elasticity (10.12 ± 1.24 GPa), and excellent cyto-compatibility. The proliferation and osteogenic differentiation capacity of BMSCs cultured on the scaffolds were enhanced with EMF treatment. Mechanistically, EMF exposure functioned partly by activating mitogen-activated protein kinase (MAPK) or MAPK-associated ERK and JNK pathways. In vivo, significantly higher new bone formation and vascularization were observed in groups involving scaffold, BMSCs, and EMF treatment, compared to scaffold alone. Furthermore, after 12 weeks of implanting, craniums in groups including scaffold, BMSCs, and EMF exposure showed the greatest biomechanical properties. Conclusion In conclusion, EMF treatment combined with 3D-printed scaffold has great potential applications in craniofacial regeneration.

Some plants produce toxic isothiocyanates that protect them against pathogens. Here, Chen et al. show that the plant pathogenic fungus Sclerotinia sclerotiorum converts isothiocyanates into non-toxic compounds via glutathione conjugation and, more effectively, via hydrolysis to amines using an isothiocyanate hydrolase.

Purpose: Owing to the characteristic anatomy, cochlear implantation (CI) for common cavity deformity (CCD) has resulted in varied outcomes and frequent facial and vestibular nerve stimulation. The current study analyzed the correlation among the distance between each electrode and cavity wall (abbreviation, D), programming parameters, and performances outcomes.Materials and Methods: The current, retrospective study included 25 patients (27 ears) with CCD underwent CI. The multiplanar volume reconstruction (MPVR) techniques were employed to reconstruct and evaluate the postoperative temporal bone CT. The D and maximum comfortable level (MCL) 6 months after CI, facial and vestibular nerve stimulation, and outcomes 1, 2, and 3 years after CI pertaining to the questionnaires were documented and analyzed.Results: The patients were divided into symptomatic (10, 37%) and asymptomatic (17, 63%) groups according to with or without facial and vestibular nerve stimulation. The MCL pertaining to the symptomatic group was significantly lower than asymptomatic group, but Categories of Auditory Performance (CAP) scores 1 year after surgery was better (p < 0.05). The subjects were divided into flat (12, 44.4%) and curved (15, 55.6%) groups based on the contour of MCL map. The MCL and D were lower and shorter in the curved group than the flat group, and CAP score 1 year after surgery and Speech Intelligibility Rating (SIR) 3 years after surgery were better (p < 0.05).Conclusion: Although abnormal reactions such as facial and vestibular nerve stimulation were observed to be more frequent, lower MCL and better outcomes were observed in relation to the shorter D.

Background: In a long-term event-driven trial, macitentan has demonstrated beneficial time to clinical worsening in patients with pulmonary arterial hypertension (PAH) and reduced PAH-related hospitalization rates compared with placebo. Macitentan is the most recently approved endothelin receptor antagonist (ERA) and is the first ERA that has shown efficacy for morbidity and mortality in PAH patients; therefore, patients and physicians may consider converting treatment from ambrisentan to macitentan. Our study evaluated the safety, efficacy, and quality of life in PAH patients transitioning from ambrisentan to macitentan.Methods: This was a real-world, prospective study with a 12-month follow-up. PAH patients who had received stable doses of ambrisentan for over 3 months, were within the World Health Organization Functional Class II/III, and 6-min walk distance ≥ of 250 m were enrolled. The study included a screening period, followed by a transition phase, after which patients entered the long-term follow-up. Clinical data and treatment satisfaction outcomes were collected to assess and monitor the safety and efficacy of the transition. The trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn; No. ChiCTR2000034898).Results: One hundred and fifty-seven enrolled PAH patients completed the transition. All criteria for continuous treatment transition were met by 145 patients (92.4%). Results showed improvements in exercise capacity, cardiac function, and hemodynamics compared with baseline. During the process, 4 patients discontinued macitentan due to adverse events. There was no statistical difference in the overall incidence of adverse events before and after the transition.Conclusion: Transition to macitentan from ambrisentan was successful and well-tolerated by PAH patients, and was associated with greater efficacy and satisfaction.

Ototoxic hearing loss results from hair cell death via reactive oxygen species (ROS) overproduction and consequent apoptosis. We investigated the effects of vitamin C (VC) on neomycin-induced HEI-OC1 cell damage, as well as the mechanism of inhibition. HEI-OC1 cells were treated with neomycin or with vitamin C (VC). The results indicated that VC had a protective effect on neomycin-induced HEI-OC1 cell death. Mechanistically, VC decreased neomycin-induced ROS generation, suppressed cell death, and increased cell viability. VC inhibited neomycin-induced apoptosis, ameliorated neomycin reduced antiapoptotic Bcl-2 expression, and suppressed neomycin increased expression of proapoptotic Bax, caspase-3 cleavage and caspase-8. TUNEL labeling demonstrated that VC blocked neomycin-induced apoptosis. Further study revealed that the effect of VC on neomycin-induced hair cell death was through interference with JNK activation and p38 phosphorylation. These results indicate that VC via suppressed ROS generation, which inhibited cell death by counteracting apoptotic signaling induced by neomycin in cells. Hence, VC is a potential candidate for protection agent against neomycin-induced HEI-OC1 cell ototoxicity.

Abstract Background Restoration of massive bone defects remains a huge challenge for orthopedic surgeons. Insufficient vascularization and slow bone regeneration limited the application of tissue engineering in bone defect. The effect of electromagnetic field (EMF) on bone defect has been reported for many years. However, sinusoidal EMF (SEMF) combined with tissue engineering in bone regeneration remains poorly investigated. Methods In the present study, we investigated the effect of SEMF and vascular endothelial growth factor (VEGF) on osteogenic and vasculogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Furthermore, pretreated rBMSC- laden polycaprolactone-hydroxyapatite (PCL/HA) scaffold was constructed and implanted into the subcritical cranial defect of rats. The bone formation and vascularization were evaluated 4 and 12 weeks after implantation. Results It was shown that SEMF and VEGF could enhance the protein and mRNA expression levels of osteoblast- and endothelial cell-related markers, respectively. The combinatory effect of SEMF and VEGF slightly promoted the angiogenic differentiation of rBMSCs. The proteins of Wnt1, low-density lipoprotein receptor-related protein 6 (LRP-6), and β-catenin increased in all inducted groups, especially in SEMF + VEGF group. The results indicated that Wnt/β-catenin pathway might participate in the osteogenic and angiogenic differentiation of rBMSCs. Histological evaluation and reconstructed 3D graphs revealed that tissue-engineered constructs significantly promoted the new bone formation and angiogenesis compared to other groups. Conclusion The combinatory effect of SEMF and VEGF raised an efficient approach to enhance the osteogenesis and vascularization of tissue-engineered constructs, which provided a useful guide for regeneration of bone defects.

Generally, cochlear implants (CIs) are effective in helping patients improve their hearing performance; however, some patients have poor hearing performance owing to facial nerve stimulation (FNS), which is often associated with cochlear anomalies. We report a case with a normal cochlea and severe and persistent FNS owing to cochlear–facial dehiscence (CFD) that affected the CI outcomes. Preoperatively, a careful review of the computed tomography images before CI surgery is necessary not only for patients with otosclerosis and inner ear malformations but also for patients with normal cochlear structures because facial nerve anomalies could be present.

Background: Mechanical ventilation (MV) often leads to ventilation-induced diaphragm dysfunction (VIDD). Although the development of this disorder had been linked to oxidative stress, mitochondrial energy deficiency, autophagy activation, and apoptosis in the diaphragm, it remains unclear whether the activation of mitophagy can induce VIDD. With our research, our endeavor is to uncover whether PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy affects the MV-caused diaphragmatic dysfunction Methods: Sprague-Dawley rats were subjected to MV treatment for 6 h (MV-6h), 12 h (MV-12h), or 24 h (MV-24h). Post MV, the diaphragm muscle compound action potential (CMAP) and cross-sectional areas (CSAs) of the diaphragm of these rats were measured. The levels of proteins of interest were examined to assess muscle health, mitochondrial dynamics, and mitophagy in the diaphragm. The co-localization of PINK1 with the mitochondrial protein marker tom20 was examined, as well as transmission electron microscopy analysis to detect changes in diaphragm mitochondrial ultrastructure. Results: MV-12h and MV-24h treatments resulted in a decrease in CSA of diaphragm and CMAP amplitude. In addition, the expressions of F-box (MFAbx), muscle-specific ring finger 1 (MURF1), PINK1, and p62 were elevated in rats treated with MV for 12 h and 24 h, while mfn2 expression was reduced. Rats following MV-24h treatment displayed an increase in mitochondrial dynamic protein (Drp1) and Parkin expression and microtubule-associated protein 1 light chain 3/1 (LC3II/I) ratio. Moreover, decreased SOD and GSH activity and membrane potential were observed after MV-12h and MV-24h treatment, while H 2 O 2 activity increased after MV-24h treatment. In addition, a strong co-localization between PINK1 and tom20 was identified. Conclusion: These results reveal that MV leads to various changes in mitochondrial dynamics and significantly increases the mitophagy levels, which subsequently cause the variation in diaphragmatic function and muscle atrophy, indicating that mitophagy could be one of the possible mechanisms by which MV induces diaphragmatic dysfunction. The reviews of this paper are available via the supplemental material section.

Abstract Sialic acid (Sia), the acylated derivative of the nine-carbon sugar neuraminic acid, is a terminal component of the oligosaccharide chains of many glycoproteins and glycolipids. In light of its important biological and pathological functions, the relationship between Sia and coronary artery disease (CAD) has been drawing great attentions recently. Large-scale epidemiological surveys have uncovered a positive correlation between plasma total Sia and CAD risk. Further research demonstrated that N-Acetyl-Neuraminic Acid, acting as a signaling molecule, triggered myocardial injury via activation of Rho/ROCK-JNK/ERK signaling pathway both in vitro and in vivo. Moreover, there were some evidences showing that the aberrant sialylation of low-density lipoprotein, low-density lipoprotein receptor and blood cells was involved in the pathological process of atherosclerosis. Significantly, the Sia regulates immune response by binding to sialic acid-binding immunoglobulin-like lectin (Siglecs). The Sia-Siglecs axis is involved in the immune inflammation of atherosclerosis. The generation of Sia and sialylation of glycoconjugate both depend on many enzymes, such as sialidase, sialyltransferase and trans-sialidase. Abnormal activation or level of these enzymes associated with atherosclerosis, and inhibitors of them might be new CAD treatments. In this review, we focus on summarizing current understanding of Sia metabolism and of its relevance to atherosclerosis.

Background Previous studies have investigated the association of ambient air pollution with blood pressure (BP) in children and adolescents, however, the results are not consistent. We conducted a systematic review and meta‐analysis to assess the relationship between short‐term and long‐term ambient air pollutant exposure with BP values among children and adolescents. Methods and Results We searched PubMed, Web of Science, and Embase before September 6, 2020. Two reviewers independently searched and selected studies, extracted data, and assessed study quality. The studies were divided into groups by composition of air pollutants (NO2, particulate matter (PM) with diameter ≤10 μm or ≤2.5 μm) and length of exposure. The beta regression coefficients (β) and their 95% CIs were calculated to evaluate the strength of the effect with each 10 μg/m3 increase in air pollutants. Out of 36 650 articles, 14 articles were included in this meta‐analysis. The meta‐analysis showed short‐term exposure to PM with diameter ≤10 μm (β=0.267; 95% CI, 0.033‒0.501) was significantly associated with elevated systolic BP values. In addition, long‐term exposure to PM with diameter ≤2.5 μm (β=1.809; 95% CI, 0.962‒2.655), PM with diameter ≤10 μm (β=0.526; 95% CI, 0.095‒0.958), and NO2 (β=0.754; 95% CI, 0.541‒0.968) were associated with systolic BP values and long‐term exposure to PM with diameter ≤2.5 μm (β=0.931; 95% CI, 0.157‒1.705), and PM with diameter ≤10 μm (β=0.378; 95% CI, 0.022‒0.735) was associated with diastolic BP. Conclusions Our study indicates that both short‐term and long‐term exposure to some ambient air pollutants may increase BP values among children and adolescents.