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Abstract Focus on the implications of common perioperative drugs for mitochondrial quality control and their subsequent impact on the overall physiological condition has been increasing. This review discusses the effects of perioperative drugs, such as intravenous and inhaled anesthetics, analgesics, local anesthetics on mitochondrial quality and their underlying mechanisms. These drugs influence mitochondrial properties, including morphology, dynamics, energy metabolism, and protein expression, thereby affecting the clinical outcomes of patients undergoing surgery. Such effects can be either protective or detrimental and are contingent upon multiple variables such as the specific drug used, dosage, application timing, and the patient's overall health status. Recognizing the effects of these perioperative drugs on mitochondrial quality control is crucial to selecting safer anesthetic protocols, reducing postoperative complications, enhancing postoperative recovery, and gaining insights into the development of innovative treatment methodologies and optimization of perioperative care.

AbstractContext Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection.Objective To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality.Materials and methods A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an in vitro model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1’s safe dosage. Groups for each model were: in vivo—a control group, a CLP-induced sepsis group, and a CLP + NGR1 treatment group (30 mg/kg/d for 3 d); in vitro—a control group, a LPS-induced sepsis group, and a LPS + NGR1 treatment group (4 μM for 30 min). NGR1’s effects on survival, intestinal function, mitochondrial quality, and mitochondrial dynamic-related protein (Drp1) were evaluated.Results Sepsis resulted in approximately 60% mortality within 7 days post-CLP, with significant reductions in intestinal microvascular perfusion and increases in vascular leakage. Severe mitochondrial quality imbalance was observed in IMVECs. NGR1 (IC50 is 854.1 μM at 30 min) targeted Drp1, inhibiting mitochondrial translocation, preventing mitochondrial fragmentation and restoring IMVEC morphology and function, thus protecting against intestinal barrier dysfunction, vascular permeability, microcirculatory flow, and improving sepsis prognosis.Discussion and conclusions Drp1-mediated mitochondrial quality imbalance is a potential therapeutic target for sepsis. Small molecule natural drugs like NGR1 targeting Drp1 may offer new directions for organ protection following sepsis. Future research should focus on clinical trials to evaluate NGR1’s efficacy across various patient populations, potentially leading to novel treatments for sepsis.

Abstract Background Vitamin D deficiency, a common occurrence among pregnant women, is an emerging public health concern worldwide. According to research, prenatal vitamin D deficiency is associated with various complications. This study assessed the vitamin D status of pregnant women in Yanbian, Jilin Province, as well as the correlation and predictive value of their vitamin D levels in relation to gestational length (weeks) and fetal weight, aiming to provide a basis for clinical diagnosis and treatment. Methods We conducted a population-based retrospective study involving 510 pregnant women from August 2019 to October 2022. Blood samples were collected at 16–20 weeks of gestation for the detection of serum vitamin D levels. Statistical analyses were performed using SPSS 28.0 and R 4.1.0 software. Multifactorial logistic regression analysis was employed to establish whether each variable was a risk factor for deliveries at ≤ 38 gestational weeks and low fetal weight. These results were used to construct a risk prediction model, and the model’s predictive efficacy was evaluated. Results or differences with p

Abstract The high cost of medical care and its association with poverty have given rise to a growing concern for developing countries, but how insurance plans affect household income and alleviate poverty has been rarely discussed. This study aims to bridge this research gap by examining a medical insurance reform in China, a major program of the targeted poverty alleviation (TPA) strategy, which offers higher reimbursement rates and lower medical deductibles for low‐income households. We use an administrative data set on impoverished people in a Chinese county to examine how exogenous changes in the medical insurance system affect the income structure of low‐income households. We apply a two‐part model to a Difference‐in‐Differences framework, with households that received reimbursement of the insurance reform as the treatment group and others as the control group. Our results imply that the medical insurance reform could increase the overall household income diversity. The mechanism analysis suggests that the medical insurance reform improves the health conditions of patients and encourages caregivers to engage more in off‐farm work.

BackgroundCervical cancer is a leading cause of cancer-related deaths among women. However, in developing countries, the primary focus for cervical cancer prevention and control remains on the timely detection and treatment of precancerous lesions. This study aims to evaluate the accuracy of colposcopic diagnosis of cervical intraepithelial lesions and analyze the factors influencing its accuracy.MethodsThis study collected data from 512 eligible patients who visited the gynecology outpatient clinic of the Second Hospital of Jilin University from January 2022 to August 2023. The final diagnosis was based on the highest grade observed in both biopsy pathology and postoperative pathology. A self-controlled, retrospective analysis was conducted to evaluate the accuracy of colposcopic diagnosis. Univariate analysis was used to assess the impact of factors such as menopausal status, duration of menopause, high-risk human papillomavirus (HR-HPV) genotypes, and transformation zone (TZ) types on the accuracy of colposcopic diagnosis of cervical lesions.ResultThe overall colposcopy diagnostic concordance rate was 78.71%. The concordance rates between the premenopausal and postmenopausal groups differed significantly (χ2 = 75.450, p

With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbroke and evolved into multi-subvariants in China without clearly established virological characteristics. Here, we evaluated the virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). Compared to the normal BA.5 spike, the double-mutated DY.1.1 spike demonstrates efficient cleavage, reduced fusogenicity and higher hACE2 binding affinity. BA.5.2.48 demonstrated enhanced airborne transmission capacity than BA.2 in hamsters. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in Omicron-lethal H11-K18-hACE2 rodents. In both naïve and convalescent hamsters, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus regional outbreaking of BA.5.2.48 promotes the multidirectional evolution of its subvariants, gaining either enhanced pathogenicity or a fitness in upper airways which is associated with higher transmission.

Abstract Background Radiotherapy (RT) has been identified as a vital treatment for esophageal squamous cell carcinoma (ESCC), while the development of radioresistance remains a major obstacle in ESCC management. The aim of this study was to investigate the effect of NIMA-related kinase 2 (NEK2) on radioresistance in ESCC cells and to reveal potential molecular mechanisms. Methods Human esophageal epithelial cells (HEEC) and human ESCC cell lines were obtained from the Research Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Cell Counting Kit-8 (CCK-8) and flow cytometry assays were applied to assess the proliferation ability, cell cycle, apoptosis rates, and ROS production of ESCC cells. The colony-forming assay was used to estimate the effect of NEK2 on radiosensitivity. Autophagy was investigated by western blotting analysis, GFP-mRFP-LC3 fluorescence assay, and transmission electron microscopy (TEM). Results In the present study, our results showed that NEK2 was associated with radioresistance, cell cycle arrest, apoptosis, ROS production, and survival of ESCC. NEK2 knockdown could significantly inhibit growth while enhancing radiosensitivity and ROS production in ESCC cells. Interestingly, NEK2 knockdown inhibited ESCC cell autophagy and reduced autophagic flux, ultimately reversing NEK2-induced radioresistance. Mechanistically, NEK2 bound to and regulated the stability of tripartite motif-containing protein 21 (TRIM21). The accumulation of NEK2-induced light chain 3 beta 2 (LC3B II) can be reversed by the knockdown of TRIM21. Conclusion These results demonstrated that NEK2 activated autophagy through TRIM21, which may provide a promising therapeutic strategy for elucidating NEK2-mediated radioresistance in ESCC.

Abstract Self-efficacy or perceived ability refers to the confidence an individual has in their ability to successfully perform a specific task. Previous researchers have demonstrated the importance of self-efficacy beliefs and its impact on predicting students’ mathematics performances. Specifically, gender has been regarded as an important moderator variable in the prediction of achievement from measures of affect. To this end, using data from High School Longitudinal Study of 2009, this study utilized the multi-group analysis under the framework of structural equation modeling to examine gender differences in the reciprocal relationship between mathematics self-efficacy and mathematics achievement. The results showed that there were statistically significant differences between male students and female students in the reciprocal relationship between mathematics self-efficacy and mathematics achievement; the impact of prior mathematics achievement on later mathematics achievement was stronger than the impact of prior mathematics self-efficacy on later mathematics self-efficacy. Significance of these findings were discussed in this paper.

ABSTRACT: This study aims to investigate the effects of hesperidin (Hes), thymol (Thy), rosmarinic acid (RA) and their combined effect on broiler growth performance, intestinal barrier function, and cecal microbiota. A total of 240 newly hatched Arbor Acres broiler chicks were randomly divided into 5 treatments with 6 replicates of 8 chickens. The birds were fed a basal diet (Con group), a basal diet supplemented with 40 mg/kg Hes (Hes group), a basal diet supplemented with 40 mg/kg Thy (Thy group), a basal diet supplemented with 20 mg/kg RA (RA group), or a basal diet supplemented with 40 mg/kg Hes + 40 mg/kg Thy + 20 mg/kg RA (HTR group) for 42 d. The results indicated that dietary Hes and HTR supplementation enhanced average daily gain, final body weight, and eviscerated yield of broilers compared with the Con group (P < 0.05). Notably, the HTR treatment showed a decrease in abdominal fat yield and ratio of feed to weight gain (P < 0.05). HTR treatment increased ileal villus height, villus height/crypt depth, and number of goblet cells, decreased the crypt depth (P < 0.05), up-regulated the mRNA expression of tight junction proteins (ZO-1, Claudin-1, Occludin) and MUC2 (P < 0.05). Hes, Thy, RA, HTR treatment decreased the concentrations of pro-inflammatory factors (IL-8, IFN-γ and TNF-α), and down-regulated the mRNA expression of TLR4/MyD88/NF-κB (P < 0.05). Importantly, the supplementation of HTR increased the relative abundance of beneficial bacteria (Parabacteroides, Lachnosiraceae NK4A136 and Turicbacter) and significantly decreased the relative abundance of opportunistic pathogenic bacteria such as Colidextribacter (P < 0.05). Additionally, the concentrations of propionate and butyrate in the cecum were elevated in the HTR group (P < 0.05). These findings indicate that the diet supplemented with HTR improved the growth performance and intestinal barrier function in broilers by modulating the cecal microbiota and its metabolites.

Esketamine nasal spray (ESK-NS) is a new drug for treatment-resistant depression, and we aimed to detect and characterize the adverse events (AEs) of ESK-NS using the Food and Drug Administration (FDA) adverse event reporting system (FAERS) database between 2019 Q1 and 2023 Q4. Reporting odds ratio (ROR), proportional reporting ratio (PRR), and multi-item gamma Poisson shrinker (MGPS) were performed to detect risk signals from the FAERS data to identify potential ESK-NS–AEs associations. A total of 14,606 reports on AEs with ESK-NS as the primary suspected drug were analyzed. A total of 518 preferred terms signals and 25 system organ classes mainly concentrated in psychiatric disorders (33.20%), nervous system disorders (16.67%), general disorders and administration site conditions (14.21%), and others were obtained. Notably, dissociation (n = 1,093, ROR 2,257.80, PRR 899.64, EBGM 876.86) exhibited highest occurrence rates and signal intensity. Moreover, uncommon but significantly strong AEs signals, such as hand–eye coordination impaired, feeling guilty, and feelings of worthlessness, were observed. Additionally, dissociative disorder (n = 57, ROR 510.92, PRR 506.70, EBGM 386.60) and sedation (n = 688, ROR 172.68, PRR 155.53, and EBGM 142.05) both presented strong AE signals, and the former is not recorded in the Summary of Product Characteristics (SmPC). In clinical applications, close attention should be paid to the psychiatric disorders and nervous system disorders, especially dissociation. Meanwhile, clinical professionals should be alert for the occurrence of AEs signals not mentioned in the SmPC and take preventive measures to ensure the safety of clinical use.

Abstract Flexibility has become increasingly important considering the intermittency of variable renewable energy in low-carbon energy systems. Electrified transportation exhibits great potential to provide flexibility. This article analyzed and compared the flexibility values of battery electric vehicles and fuel cell electric vehicles for planning and operating interdependent electricity and hydrogen supply chains while considering battery degradation costs. A cross-scale framework involving both macro-level and micro-level models was proposed to compute the profits of flexible EV refueling/charging with battery degradation considered. Here we show that the flexibility reduction after considering battery degradation is quantified by at least 4.7% of the minimum system cost and enlarged under fast charging and low-temperature scenarios. Our findings imply that energy policies and relevant management technologies are crucial to shaping the comparative flexibility advantage of the two transportation electrification pathways. The proposed cross-scale methodology has broad implications for the assessment of emerging energy technologies with complex dynamics.

Septic cardiomyopathy (SCM) is associated with an imbalance in mitochondrial quality and high mortality rates, with no effective treatment developed to date. Curcumin provides antioxidant, anti-inflammatory, cardiovascular, and mitochondrial protection. However, curcumin has not been confirmed to improve cardiac dysfunction in sepsis. We hypothesized that curcumin can reduce abnormal inflammatory responses by improving mitochondrial function as a novel mechanism to improve SCM. To explore this hypothesis, we used an in vivo male C57BL/6 mouse sepsis model and an in vitro model of lipopolysaccharide-stimulated HL-1 cells. The effects of curcumin on sepsis-induced cardiac dysfunction, inflammatory responses, and mitochondrial quality of cardiac cells were observed using quantitative polymerase chain reaction, western blotting, echocardiography, and transmission electron microscopy. Curcumin activated sirtuin 1 (SIRT1); increased expression of the mitochondrial biogenesis-related genes Pgc1α, Tfam, and Nrf2; reduced dynamin-related protein 1 translocation from the cytoplasm to mitochondria; and restored the mitochondrial morphology and function in cardiac cells. Accordingly, curcumin protected heart function after septic shock and alleviated the effects of SCM. SIRT1 knockdown reversed the protective effects of curcumin on mitochondria. Therefore, curcumin promotes mitochondrial biogenesis and inhibits mitochondrial fragmentation by activating SIRT1, thereby improving the mitochondrial quality and reducing oxidative stress in cardiomyocytes and sepsis-induced cardiac dysfunction. These findings provide new evidence supporting the use of curcumin to treat SCM.

Abstract Radiotherapy (RT) plays an important role in tumor therapy due to its noninvasiveness and wide adaptation. In recent years, radiation therapy has been discovered to induce an anti-tumor immune response, which arouses widespread concern among scientists and clinicians. In this review, we highlight recent advances in the applications of nano-biomaterials for radiotherapy-activated immunotherapy. We first discuss the combination of different radiosensitizing nano-biomaterials and immune checkpoint inhibitors to enhance tumor immune response and improve radiotherapy efficacy. Subsequently, various nano-biomaterials-enabled tumor oxygenation strategies are introduced to alleviate the hypoxic tumor environment and amplify the immunomodulatory effect. With the aid of nano-vaccines and adjuvants, radiotherapy refreshes the host's immune system. Additionally, ionizing radiation responsive nano-biomaterials raise innate immunity-mediated anti-tumor immunity. At last, we summarize the rapid development of immune modulatable nano-biomaterials and discuss the key challenge in the development of nano-biomaterials for tumor radio-immunotherapy. Understanding the nano-biomaterials-assisted radio-immunotherapy will maximize the benefits of clinical radiotherapy and immunotherapy and facilitate the development of new combinational therapy modality. Graphical Abstract

To ensure the safe production of mines, the intelligent trend of underground mining operations is gradually advancing. However, the operational environment of subterranean mining is intricate, making the conventional path-planning algorithm used by mining inspection robots frequently inadequate for real requirements. To safeguard the mining inspection robot, targeting the problem of low search efficiency and path redundancy in the path planning of the existing rapidly exploring random tree (RRT) algorithm in the narrow and complex unstructured environment, a path-planning algorithm combining improved RRT and a probabilistic road map (PRM) is proposed. Initially, the target area is efficiently searched according to the fan-shaped goal orientation strategy and the adaptive step size expansion strategy. Subsequently, the PRM algorithm and the improved RRT algorithm are combined to reduce the redundant points of the planning path. Ultimately, considering the kinematics of the vehicle, the path is optimized by the third-order Bessel curve. The experimental simulation results show that the proposed path-planning algorithm has a higher success rate, smoother path, and shorter path length than other algorithms in complex underground mining environments, which proves the effectiveness of the proposed algorithm.

Sepsis is a dysregulated response to infection that can result in life-threatening organ failure, and septic cardiomyopathy is a serious complication involving ferroptosis. Olaparib, a classic targeted drug used in oncology, has demonstrated potential protective effects against sepsis. However, the exact mechanisms underlying its action remain to be elucidated. In our study, we meticulously screened ferroptosis genes associated with sepsis, and conducted comprehensive functional enrichment analyses to delineate the relationship between ferroptosis and mitochondrial damage. Eight sepsis-characterized ferroptosis genes were identified in sepsis patients, including DPP4, LPIN1, PGD, HP, MAPK14, POR, GCLM, and SLC38A1, which were significantly correlated with mitochondrial quality imbalance. Utilizing DrugBank and molecular docking, we demonstrated a robust interaction of Olaparib with these genes. Lipopolysaccharide (LPS)-stimulated HL-1 cells and monocytes were used to establish an in vitro sepsis model. Additionally, an in vivo model was developed using mice subjected to cecal ligation and perforation (CLP). Intriguingly, low-dose Olaparib (5 mg/kg) effectively targeted and mitigated markers associated with ferroptosis, concurrently improving mitochondrial quality. This led to a marked enhancement in cardiac function and a significant increase in survival rates in septic mice (p

Abstract Excessive mitochondrial fission following ischemia and hypoxia relies on the formation of contacts between the endoplasmic reticulum and mitochondria (ER‐Mito); however, the specific mechanisms behind this process remain unclear. Confocal microscopy and time course recording are used to investigate how ischemia and hypoxia affect the activation of dynamin‐related protein 1 (Drp1), a protein central to mitochondrial dynamics, ER‐Mito interactions, and the consequences of modifying the expression of Drp1, shroom (Shrm) 4, and inverted formin (INF) 2 on ER‐Mito contact establishment. Both Drp1 activation and ER‐Mito contact initiation cause excessive mitochondrial fission and dysfunction under ischemic‐hypoxic conditions. The activated form of Drp1 aids in ER‐Mito contact initiation by recruiting Shrm4 and promoting actin bundling between the ER and mitochondria. This process relies on the structural interplay between INF2 and scattered F‐actin on the ER. This study uncovers new roles of cytoplasmic Drp1, providing valuable insights for devising strategies to manage mitochondrial imbalances in the context of ischemic‐hypoxic injury.

Background High mortality rates are prevalent among patients with non-small-cell lung cancer (NSCLC), and effective therapeutic targets are key prognostic factors. Fascin actin-bundling protein 1 (FSCN1) promotes NSCLC; however, its role as an RNA-binding protein in NSCLC remains unexplored. Therefore, we aimed to explore FSCN1 expression and function in A549 cells. Method We screened for alternative-splicing events and differentially expressed genes (DEGs) after FSCN1 silence via RNA-sequencing (RNA-seq). FSCN1 immunoprecipitation followed by RNA-seq were used to identify target genes whose mRNA expression and pre-mRNA alternative-splicing levels might be influenced by FSCN1. Results Silencing FSCN1 in A549 cells affected malignant phenotypes; it inhibited proliferation, migration, and invasion, and promoted apoptosis. RNA-seq analysis revealed 2,851 DEGs and 3,057 alternatively spliced genes. Gene ontology-based functional enrichment analysis showed that downregulated DEGs and alternatively splicing genes were enriched for the cell-cycle. FSCN1 promoted the alternative splicing of cell-cycle-related mRNAs involved in tumorigenesis (i.e., BCCIP, DLGAP5, PRC1, RECQL5, WTAP, and SGO1). Combined analysis of FSCN1 RNA-binding targets and RNA-seq data suggested that FSCN1 might affect ACTG1, KRT7, and PDE3A expression by modulating the pre-mRNA alternative-splicing levels of NME4, NCOR2, and EEF1D, that were bound to long non-coding RNA transcripts (RNASNHG20, NEAT1, NSD2, and FTH1), which were highly abundant. Overall, extensive transcriptome analysis of gene alternative splicing and expression levels was performed in cells transfected with FSCN1 short-interfering RNA. Our data provide global insights into the regulatory mechanisms associated with the roles of FSCN1 and its target genes in lung cancer.

Dielectric elastomers (DEs) are widely used in soft actuators but existing DE actuators often require high driving electrical fields. Here the authors demonstrate that introducing cyanoethyl cellulose into plasticized PVC gel confers high dielectric permittivity and allows the fabrication of elastomer actuators with high permittivity and low viscoelasticity

Supercontinuum (SC) generation pumped by fiber lasers with short wavelengths below 2.0 μm is important since it can provide a compact light source for various applications. We review the progress of SC generation in various materials regarding the formation of the waveguides and point out the existing issues in the current investigations and possible solutions in the future.

Marine structures, such as cross-sea bridges, port constructions, and offshore drilling platforms, are not only subjected to sulfate erosion, but also to various dynamic loads. Analyzing the damage evolution process of concrete under sulfate erosion and impact loads is the key to improving the lifespan of concrete. In order to study the damage evolution process of eroded concrete under high strain rates, the energy dissipation characteristics, basic physics and mechanical properties, and micro-fracture mechanism of sulfate-eroded concrete at different sulfate concentrations (C=0, 3%, 6%, and 9%) under high strain rate ranging from 70/s to 85/s are systematically studied by using the split Hopkinson pressure bar (SHPB) test system, X-ray diffractometer and SEM scanning electron microscope. The research results indicate that an increase in sulfate concentration leads to a decrease in Ca(OH)2 content and an increase in Ettringite (AFt) content in concrete specimens; As the sulfate concentration increases, the dynamic peak strength and dynamic elastic modulus of concrete specimens gradually decrease, while the dynamic peak strain of concrete specimens gradually increases; The degree of macroscopic fragmentation in concrete specimens subjected to impact compression becomes increasingly severe with rising sulfate concentrations; As the sulfate concentration increases, the proportion of reflected energy and dissipated energy gradually increases, while that of transmitted energy gradually decreases, and the energy absorption capacity of the sample is significantly improved; The results of the SEM test shows that with the increase of sulfate concentration, a large amount of AFt is generated at the joint fissures and the interface of cement aggregates, the expansion of AFt and the crack development of concrete reduce the integrity and stability of concrete. This study holds significant guidance for the application of concrete in impact situations under a sulfate attack environment.

The impact of landscape patterns on urban plant diversity has received significant attention; however, previous studies have primarily focused on two-dimensional (2D) patterns. Limited investigations have been conducted to explore the effects of three-dimensional (3D) landscape patterns on urban plant diversity. Spontaneous plants are ideal objects for studying the response of plant diversity to urban environments due to their independence from intentional human inputs. Buildings, as a crucial symbol of urbanization, exhibit strong 3D characteristics in urban landscapes. Green spaces, the most important source of plant propagules in cities, are closely related to spontaneous plant diversity in urban areas. Therefore, we examined how 2D/3D building and green space patterns influence urban spontaneous plant species richness and compared the responses between different categories (native and non-native). We surveyed spontaneous plants in the built-up areas of Shenzhen, a highly urbanized region situated along China’s southern coast. Our survey recorded 278 species belonging to 208 genera and 77 families. Results from boosted regression tree models (BRT) indicated significant correlations between spontaneous plant species richness and various metrics, including building coverage ratio (BCR), mean building height (MAH), green space coverage ratio (GCR), edge density of green spaces (ED_G), spatial congestion degree (SCD), and floor area ratio (FAR). These metrics exhibited complex nonlinear correlations with the species richness of spontaneous plants. Furthermore, native and non-native species richness responded differently to building and green space patterns; while native species richness was equally affected by green space and building patterns, non-native species richness was more strongly impacted by building patterns than green space ones. Our study quantified the nonlinear relationships between urban spontaneous plant species richness and 2D/3D green space and building patterns, demonstrating that optimizing green space and building patterns can be a practical approach for managing and promoting spontaneous plant diversity in highly urbanized areas.

Dyslipidemia due to renal insufficiency is a common complication in patients with chronic kidney diseases (CKD), and a major risk factor for the development of cardiovascular events. Atorvastatin (AT) is mainly used in the treatment of dyslipidemia in patients with CKD. However, response to the atorvastatin varies inter-individually in clinical applications. We examined the association between polymorphisms in genes involved in drug metabolism and transport, and plasma concentrations of atorvastatin and its metabolites (2-hydroxy atorvastatin (2-AT), 2-hydroxy atorvastatin lactone (2-ATL), 4-hydroxy atorvastatin (4-AT), 4-hydroxy atorvastatin lactone (4-ATL), atorvastatin lactone (ATL)) in kidney diseases patients. Genotypes were determined using TaqMan real time PCR in 212 CKD patients, treated with 20 mg of atorvastatin daily for 6 weeks. The steady state plasma concentrations of atorvastatin and its metabolites were quantified using ultraperformance liquid chromatography in combination with triple quadrupole mass spectrometry (UPLC−MS/MS). Univariate and multivariate analyses showed the variant in ABCC4 (rs3742106) was associated with decreased concentrations of AT and its metabolites (2-AT+2-ATL: β = -0.162, p = 0.028 in the dominant model; AT+2-AT+4-AT: β = -0.212, p = 0.028 in the genotype model), while patients carrying the variant allele ABCC4-rs868853 (β = 0.177, p = 0.011) or NR1I2-rs6785049 (β = 0.123, p = 0.044) had higher concentrations of 2-AT+2-ATL in plasma compared with homozygous wildtype carriers. Luciferase activity was enhanced in HepG2 cells harboring a construct expressing the rs3742106-T allele or the rs868853-G allele (p < 0.05 for each) compared with a construct expressing the rs3742106G or the rs868853-A allele. These findings suggest that two functional polymorphisms in the ABCC4 gene may affect transcriptional activity, thereby directly or indirectly affecting release of AT and its metabolites from hepatocytes into the circulation.

Abstract SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood–brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.

BackgroundUsing blood-derived circular RNAs (circRNAs) may be an efficient tool for noninvasive fluid biopsy in diagnosing non-small cell lung cancer (NSCLC). However, no relevant systemic meta-analysis has been conducted so far to support the diagnostic value of using blood-derived circRNAs in NSCLC clinically. The aim of this study is to clarify the issue through a meta-analysis.MethodsA systematic search strategy was used to search relevant literature in the databases of PubMed, Web of Science, and Cochrane Library from 2017 to 2022. The relationship between the diagnostic accuracy of circRNAs and NSCLC was analyzed. For the purpose of evaluating the quality of the literature, Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. Statistical analyses were assessed using Stata software (version 17.0) and META-DISC (version 1.4).ResultsThe meta-analysis included 1,093 patients with NSCLC and 959 controls. Results are as follows: pooled sensitivity, 0.78 (95% CI = 0.71–0.83, I2 = 71.86); pooled specificity, 0.76 (95% CI = 0.70–0.82, I2 = 70.12); pooled positive likelihood ratio (PLR), 3.3 (95% CI = 2.6–4.2, I2 = 37.56); pooled negative likelihood ratio (NLR), 0.29 (95% CI = 0.23–0.37, I2 = 64.67); diagnostic odds ratio (DOR), 11.42 (95% CI = 7.88–16.56, I2 = 99.05); area under the receiver operating characteristic curve (AUC), 0.84 (95% CI = 0.80–0.87). Based on the subgroup analysis, it appears that the heterogeneity is primarily caused by the NSCLC subgroup.ConclusioncircRNAs are highly useful diagnostic biomarkers for NSCLC in China. Further prospective studies on the diagnostic value of circRNAs should be conducted in multiple countries.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022323804.

Mitochondria get caught in the crossfire of coronavirus disease 2019 (COVID-19) and antiviral immunity. The mitochondria-mediated antiviral immunity represents the host’s first line of defense against viral infection, and the mitochondria are important targets of COVID-19. However, the specific manifestations of mitochondrial damage in patients with COVID-19 have not been systematically clarified. This study comprehensively analyzed one single-cell RNA-sequencing dataset of lung tissue and two bulk RNA-sequencing datasets of blood from COVID-19 patients. We found significant changes in mitochondrion-related gene expression, mitochondrial functions, and related metabolic pathways in patients with COVID-19. SARS-CoV-2 first infected the host alveolar epithelial cells, which may have induced excessive mitochondrial fission, inhibited mitochondrial degradation, and destroyed the mitochondrial calcium uniporter (MCU). The type II alveolar epithelial cell count decreased and the transformation from type II to type I alveolar epithelial cells was blocked, which exacerbated viral immune escape and replication in COVID-19 patients. Subsequently, alveolar macrophages phagocytized the infected alveolar epithelial cells, which decreased mitochondrial respiratory capacity and activated the ROS–HIF1A pathway in macrophages, thereby aggravating the pro-inflammatory reaction in the lungs. Infected macrophages released large amounts of interferon into the blood, activating mitochondrial IFI27 expression and destroying energy metabolism in immune cells. The plasma differentiation of B cells and lung-blood interaction of regulatory T cells (Tregs) was exacerbated, resulting in a cytokine storm and excessive inflammation. Thus, our findings systematically explain immune escape and excessive inflammation seen during COVID-19 from the perspective of mitochondrial quality imbalance.

Abstract Inorganic perovskite quantum dots CsPbX3 (X = Cl, Br, and I) has recently received extensive attention as a new promising class of X‐ray scintillators. However, relatively low light yield (LY) of CsPbX3 and strong optical scattering of the thick opaque scintillator film restrict their practical applications for high‐resolution X‐ray microscopic imaging. Here, the Ce3+ ion doped CsPbBr3 nanocrystals (NCs) with enhanced LY and stability are obtained and then the ultrathin (30 µm) and transparent scintillator films with high density are prepared by a suction filtration method. The small amount Ce3+ dopant greatly enhances the LY of CsPbBr3 NCs (about 33 000 photons per MeV), which is much higher than that of bare CsPbBr3 NCs. Moreover, the scintillator films made by these NCs with high density realize a high spatial resolution of 862 nm thanks to its thin and transparent feature, which is so far a record resolution for perovskite scintillator‐based X‐ray microscopic imaging. This strategy not only provides a simple way to increase the resolution down to nanoscale but also extends the application of as‐prepared CsPbBr3 scintillator for high resolution X‐ray microscopic imaging.

Ionic conductive hydrogels with good conductivity and biocompatibility have become one of the research highlights in the field of wearable flexible sensors and supercapacitors. In this work, poly(methacrylic acid–methyl methacrylate)-reinforced poly(sodium acrylate–vinyl phosphonic acid) composite hydrogels (P(AAS-VPA)/PMMS) were designed and tested for strain sensor or supercapacitor applications. The results showed recoverability for 20 cycles of tension and compression experiments, an excellent breaking strain of 2079%, and ionic conductivity of 0.045 S·cm−1, demonstrating strong support for the application of the P(AAS-VPA)/PMMS hydrogel in strain sensors and supercapacitors. The composite hydrogel exhibited outstanding sensing and monitoring capability with high sensitivity (GF = 4.0). The supercapacitor based on the P(AAS-VPA)/PMMS composite hydrogel showed excellent capacitance performance (area capacitance 100.8 mF·cm−2 and energy density 8.96 μWh·cm−2) at ambient temperature and even −30 °C (25.3 mF·cm−2 and 2.25 μWh·cm−2). The hydrogel has stable electrochemical stability (1000 cycles, Coulomb efficiency > 97%) and exhibits electrochemical properties similar to those in the normal state under different deformations. The excellent results demonstrate the great potential of the P(AAS-VPA)/PMMS composite hydrogel in the field of strain sensors and flexible supercapacitors.

Abstract Background In China, general practitioners have limited ability to provide care for common chronic non-communicable diseases because they lack postgraduate training. In an attempt to improve general practitioners’ skills in this regard, the present authors previously launched the Chronic Non-Communicable Diseases Training Programme. The present study aims to evaluate the effectiveness of this programme. Methods Thirty-nine trainee general practitioners who participated in the programme underwent semi-structured interviews, which explored how they performed the training, what they achieved from the programme, and their suggestions for future programmes. The interview data were analysed using a thematic analysis approach. Results Under the guidance of supervisors, the thirty-nine trainee general practitioners completed the structured but individualised training plan, which comprised a four-day basic theory class, 3 months practising in a ward, and 6 months assisting in an outpatient clinic. They reported an improvement in their ability to provide care for chronic non-communicable diseases and perform two-way referral, as well as their communication with patients. They also reported that, since returning to their communities, they had become more confident, were building better relationships with their patients, and had changed their clinic behaviours from copying prescriptions to making medical decisions independently. Their principal suggestion for the training programme was to alter the order of the training, as they preferred to practice in the ward before assisting in the outpatient clinic. Conclusion The course comprised a learner-centred, practice- and apprenticeship-based, general-practitioner training programme. Given the participants’ progress and the beneficial effects of the programme reported in the interview data, it appears to be worthwhile to extend the General Practitioner Chronic Non-Communicable Diseases Training Programme.

Due to the abundant and promising biological activities of aromatic hydrazones, it is of great significance to study the biological activities of their metal complexes for the research and development of metal-based drugs. In this review, we focus on the metal complexes of polycyclic aromatic hydrazones, which still do not receive much attention, and summarize the studies related to their biological activities. Although the large number of metal complexes in phenylhydrazone prevent them all from being summarized, the significant value of polycyclic aromatic hydrocarbons themselves (such as naphthalene and anthracene) as pharmacophores are also considered. Therefore, the bioactivities of the metal complexes of naphthylhydrazone and anthrahydrazone are focused on, and the recent research progress on the metal complexes of anthrahydrazone by the authors is also included. In terms of biological activities, these complexes mainly show antibacterial and anticancer activities, along with less bioactivities. The present review demonstrates that the structural design and bioactivities of these complexes are fundamental, which also indicates a certain structure—activity relationship (SAR) in some substructural areas. However, a systematic and comprehensive conclusion of the SAR is still not available, which suggests that more attention should be paid to the bioactivities of the metal complexes of polycyclic aromatic hydrazones since their potential in structural design and biological activity remains to be explored. We hope that this review will attract more researchers to devote their interest and energy into this promising area.

People show a strong aversion to inequality and are willing to sacrifice their own interests to punish violations of fairness norms. Empirical research has found that group membership could influence the fairness judgment and norm enforcement of the individuals but has shown inconsistent findings and has not focused much on the potential moderators. Here, the two studies aimed to investigate whether victim sensitivity and proposal size moderate the impact of group membership on reactions to unfair proposals. In both studies, the participants with different victim sensitivity (low vs. high group) played the hypothetical (Study 1) and incentivized (Study 2) ultimatum game under the intragroup and intergroup condition and indicated their responses to the different proposals. Results showed that, regardless of the victim sensitivity, ingroup member is often given preferential and positive treatment. Low victim sensitive persons are more likely to accept unfair offers from the ingroup than the outgroup, while this effect was attenuated for those with high victim sensitivity, especially for highly ambiguous unfair offers (offer 6:4 in Study 1 and 8:2 in Study 2). Moreover, the ingroup favoritism score for ambiguous unfair offers was smaller for high compared with the victim sensitivity group. Taken together, the victim sensitivity, and proposal size could moderate the ingroup favoritism on responses to unfairness.

A new rhodium(III) complex of a 9-anthrahydrazone ligand ((Z)-2-(2-(Anthracen-9-ylmethylene)hydrazineyl)pyrimidine, 9-PMAH) is six-coordinated respectively by one bidentate ligand, one solvent DMSO, and three chlorides, to form a distorted octahedral coordination geometry. The ligand chelates to Rh(III) via the hydrazone N atom (N1) and pyrimidine N atom (N3), whereas DMSO coordinates to Rh(III) via the S atom. The three chloride ligands (Cl1, Cl2, and Cl3) are in a mer-configuration of the octahedron, with the DMSO cis- to the pyrimidine nitrogen. In solution, the complex may exist in the positively charged species, [RhIIICl2(DMSO)(9-PMAH)]+, but can be stable in this mode for no less than 48 h. It was suggested by the fluorescence spectroscopic analysis that the complex showed much higher intercalative binding ability with ct-DNA than the typical DNA intercalator, EtBr.

The current study research showed the nature and potential sources of the gaps in mathematics achievement between English language learners (ELLs) and non-English language learners (non-ELLs). The nature of achievement gap was examined using three DIF methodologies: including Mantel-Haenszel procedure, Rasch model, and Hierarchical Generalized Linear Model (HGLM). These were conducted at the item level in contrast to total test level. Results revealed that the three DIF approaches identified 10 common items. These 10 items demonstrated in favor of non-ELLs. Findings from this study will help educational researchers, administrators, and policymakers understand the nature of the achievement gap in mathematics at item level so that United States can be competitive in middle school mathematics education. This study also suggested that item writers and test developers should construct assessments where language is equally accessible for ELL students.

Abstract Intestinal epithelial stem cells (IESCs) are one of the most rapidly self‐renewing and proliferating adult stem cells. The IESCs reside at the bottom of intestinal and colonic crypts, giving rise to all intestinal epithelial lineages and maintaining intestinal epithelial replenishment. The technique of three‐dimensional culture based upon intestinal stem cell biology has been recently developed to study gastrointestinal development and disease pathogenesis. Here, we summarize the techniques used to isolate Lgr5‐positive IESCs to form the enteroids from intestine or colonoids from colon, and present the means to examine these organoid functions. This study will provide a simple and practical way for producing intestinal tissues in the laboratory.

Twinning is a critical deformation mode in Mg alloys. Understanding deformation twinning (DT) is essential to improving mechanical properties of Mg alloys. To address the experimentally observed conspicuous hardening effects in Mg-1.8Zn-0.2Ca alloys, interactions between the {10–12} twin boundaries (TBs) and solute clusters in Mg-Zn-Ca alloys were examined via molecular dynamics (MD) simulations. We find that the Zn/Ca-containing clusters show different hindering effects on TBs and an increment in the applied shear stress of 100 MPa is required to accomplish the interaction between the boundary and the cluster with Ca content > 50 at%. The cluster hardening effects on twinning are positively correlated to the Ca content and the size of the clusters in Mg-Zn-Ca alloys.

In order to improve the aqueous solubility and enhance the bioavailability of Hyperoside (Hyp), three inclusion complexes (ICs) of Hyp with 2-hydroxypropyl-β-cyclodextrin (2H-β-CD), β-cyclodextrin (β-CD), and methyl-β-cyclodextrin (M-β-CD) were prepared using the ultrasonic method. The characterization of the inclusion complexes (ICs) was achieved using Fourier-transform infrared spectroscopy (FTIR), scanning electronic microscopy (SEM), X-ray powder diffraction (XRPD), thin-layer chromatography (TLC), and 1H nuclear magnetic resonance (1H NMR). The effects of the ICs on the solubility and antioxidant activity of Hyp were investigated. A Job’s plot revealed that the Hyp formed ICs with three kinds of cyclodextrin (CD), all at a 1:1 stoichiometric ratio. The FTIR, SEM, XRPD, TLC, and 1H NMR results confirmed the formation of inclusion complexes. The water solubility of the IC of Hyp with 2-hydroxypropyl-β-cyclodextrin was enhanced 9-fold compared to the solubility of the original Hyp. The antioxidant activity tests showed that the inclusion complexes had higher antioxidant activities compared to free Hyp in vitro and the H2O2–RAW264.7 cell model. Therefore, encapsulation with CDs can not only improve Hyp’s water solubility but can also enhance its biological activity, which provides useful information for the potential application of complexation with Hyp in a clinical context.

DNA is subject to a range of endogenous and exogenous insults that can impair DNA replication and lead to DNA double-strand breaks (DSBs). The repair capacity of cancer cells mediates their radiosensitivity, but the roles of miR-1587 during radiation resistance are poorly characterized. In this study, we explored whether miR-1587 regulates the growth and radiosensitivity of colorectal cancer (CRC) cells through its ability to regulate DNA Ligase4 (LIG4). We found that CRC cells in which miR-1587 was overexpressed inhibited cell growth and promoted apoptosis through increasing DSBs and promoting cell cycle arrest. We found that overexpression of miR-1587 significantly inhibited LIG4 messenger RNA and protein expression and further revealed the ability of miR-1587 to directly bind to the LIG4-3′-untranslated region through dual-luciferase reporter assays. More notably, miR-1587 mimics increased the radiosensitivity of CRC cells. Taken together, we show that miR-1587 overexpression enhances the formation of DSBs, arrests CRC cell growth, and enhances the radiosensivity of CRC cells through the direct repression of LIG4 expression. These results reveal novel roles for miR-1587 during DNA damage repair and the radiosensivity of CRC cells. This highlights miR-1587 as a novel therapeutic target for CRC.

DNA damage repair and G2/M arrest are the key factors regulating the survival of cancer cells exposed to radiation. Recent studies have shown that long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes, including DNA repair, cell cycle regulation, differentiation, and epigenetic regulation. However, the knowledge about the genome scale of lncRNAs and their potential biological functions in tumor cells exposed to radiation are still unclear. In this study, we used LncRNA + mRNA Human Gene Expression Microarray V4.0 to profile lncRNA and messenger RNA (mRNA) from HeLa, MCF-7, and A549 cells after irradiation with 4 Gy of γ-radiation. We identified 230, 227, and 274 differentially expressed lncRNAs and 150, 214, and 274 differentially expressed mRNAs in HeLa, MCF-7, and A549 cells, respectively, among which there are 14 common differentially expressed lncRNAs and 22 common differentially expressed mRNAs in all of the 3 cell lines. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these differentially expressed mRNAs were mainly associated with cell cycle. Further, we also predicted the target genes and functions of these differentially expressed lncRNAs. Our study on lncRNAs has greatly expanded the field of gene research in the relationship of radiation, cell cycle, and DNA damage.

We examined the application of six different resins with the aim of selecting a macroporous resin suitable for purifying Acanthopanax senticosus total flavonoids (ASTFs) from Acanthopanax senticosus crude extract (EAS) by comparing their adsorption/desorption capacities, which led to the selection of HPD-600. Research on the adsorption mechanism showed that the adsorption process had pseudo-second-order kinetics and fit the Freundlich adsorption model. Moreover, the analysis of thermodynamic parameters indicated that the adsorption process is spontaneous and endothermic. The optimal conditions for purification of ASTFs were determined as sample pH of 3, 60% ethanol concentration, and 3 BV·h−1 flow rate, for both adsorption and desorption, using volumes of 2.5 and 4 BV, respectively. The application of macroporous resin HPD-600 to enrich ASTFs resulted in an increase in the purity of total flavonoids, from 28.79% to 50.57%. Additionally, the antioxidant capacity of ASTFs was higher than that of EAS, but both were lower than that of L-ascorbic acid. The changes in ASTFs compositions were determined using ultra-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS), with the results illustrating that the levels of seven major flavonoids of ASTFs were increased compared to that in the crude extract.

The interior sound quality (SQ) of pure electric vehicles (PEVs) has become an important consideration for users purchasing vehicles. At present, it is insufficient to take the sound pressure level as the interior acoustics design index of PEVs. Transfer path analysis (TPA) and transfer path synthesis (TPS) that take the SQ of interior noise as the improvement target remains in the preliminary exploration stage. In this paper, objective psychoacoustic parameters of SQ were taken as evaluation indexes of interior PEV noise. A virtual interior SQ synthesis model was designed on the basis of TPA and TPS, which combines experimentation and simulation. The SQ synthesis model demonstrates each noise component contribution in a PEV by new SQ separation technology. First, the interior noise transfer path and noise source of the PEV were determined in a synthesis analysis method of the interior PEV noise. Second, on the basis of the composition mechanism of interior noise and the basic principle of TPA, the excitation signal and transfer function of each interior noise path in the PEV were tested. On the basis of TPS, the interior SQ synthesis model of PEV was then established. Finally, the accuracy of the prediction model was verified in simulation and experimental comparison studies on the psychoacoustic objective parameters of SQ. The SQ objective parameter value of each transfer path was quantified by using contribution analysis. The results are expected to improve the comfort of the interior acoustic environment and enhance the competitiveness of vehicle products. They also provide an effective reference and new ideas for the development of interior SQ in PEVs.

The meso-structure mineral composition and fracture mechanism of uniaxial compressed mudstone samples at high temperature were analyzed by XRD and scanning electron microscopy. The effect of temperature on mudstone composition and fracture mechanism were studied from a meso-structural perspective, and the relationship between meso-structure and macro-mechanical characteristics at high temperature was revealed. The findings demonstrated that the fluctuation in diffraction intensity of kaolinite in the mudstone caused the fluctuation in its mechanical properties. The overall structure underwent a phase change around 600 °C, which led to the sudden change in the mechanical properties of mudstone samples. When the temperature reached 600 °C, the crystalline state worsened and kaolinite disappeared; however, some illite was produced, indicating that the chemical reaction of the structure and sudden drop of bearing capacity of the mudstone. Mudstone fracturing at high temperature involves mainly intergranular and transgranular fractures, which are typical in micro-brittle tensile failure. Considering the macro-fracture characteristics of mudstone, the results suggested that macro-fracture under external force corresponds to the meso-fracture. Keywords: Mudstone, Mineral composition, SEM, Meso-fracture, Macro-fracture