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Abstract Pathogenic germline mutations in the P-type copper-transporting ATPase (ATP7B) gene cause Wilson’s disease (WD), a hereditary disorder characterized by disrupted copper metabolism. The Arg778Leu (R778L) mutation in exon 8 is prevalent among individuals with WD in East Asia and is associated with more severe phenotypes. In this study, we generated a WD mouse model harboring R778L mutation (R778L mice) using CRISPR/Cas9. R778L mice exhibit a range of pathological characteristics resembling those of patients with WD and the same point mutations, including aberrant copper metabolism, pathological cellular injury, inflammation, and severe hepatic fibrosis. At 3–5 months of age, these mice started to display neurological deficits in motor coordination and cognitive dysfunction, accompanied by increased expression of inflammatory cytokines in the central nervous system. Microglia in the striatum and cortex exhibit significant activation, shorter processes, and decreased branch points. However, the Cu2+ levels in the brain tissue of R778L mice did not differ significantly from those of wild-type mice. Notably, inhibition of hepatic inflammation with PJ34 or siNfkb markedly alleviated the deficiencies in cognitive performance and improved locomotor activity in R778L mice. Thus, this study establishes a novel murine model to investigate the pathophysiology of WD, highlights the liver-brain crosstalk responsible for neurological manifestations in individuals with WD caused by the R778L point mutation, and demonstrates the potential of modulating liver inflammation as a therapeutic strategy for alleviating the neurological manifestations of WD.

Abstract The low ion transport is a major obstacle for low‐temperature (LT) sodium‐ion batteries (SIBs). Herein, a core‐shell structure of bismuth (Bi) nanospheres coated with carbon (Bi@C) is constructed by utilizing a novel Bi‐based complex (1,4,5,8‐naphthalenetetracarboxylic dianhydride as the ligand) as the precursor, which provides an effective template to fabricate Bi‐based anodes. At −40°C, the Bi@C anode achieves a high capacity, which is equivalent to 96% of that at 25°C, benefitting from the core‐shell nanostructured engineering and Na+‐ether‐solvent cointercalation process. The special Na+‐diglyme cointercalation behavior may effectively reduce the activation energy and accelerate the Na+ diffusion kinetics, enabling the excellent low‐temperature performance of the Bi@C electrode. As expected, the fabricated Na3V2(PO4)3//Bi@C full‐cell delivers impressive rechargeability in the ether‐based electrolyte at −40°C. Density functional theory calculations and electrochemical tests also reveal the fast reaction kinetic mechanism at LT, thanks to a much lower diffusion energy barrier (167 meV) and a lower reaction activation energy (32.2 kJ mol−1) of Bi@C anode in comparison with that of bulk Bi. This work provides a rational design of Bi‐based electrodes for rechargeable SIBs under extreme conditions.

Sepsis-induced myocardial dysfunction (SIMD) is a severe complication in sepsis, manifested as myocardial systolic dysfunction, which is associated with poor prognosis and higher mortality. Mitophagy, a self-protective mechanism maintaining cellular homeostasis, plays an indispensable role in cardioprotection. This study aimed to unveil the cardioprotective effects of Baricitinib on LPS-induced myocardial dysfunction and its effect on mitophagy. Herein, we demonstrated that LPS induced severe myocardial dysfunction and initiated mitophagy in septic mice hearts. Despite the initiation of mitophagy, a significant number of apoptotic cells and damaged mitochondria persisted in the myocardium, and myocardial energy metabolism remained impaired, indicating that the limited mitophagy was insufficient to mitigate LPS-induced damage. The JAK2-AKT-mTOR signaling pathway is activated in LPS-induced cardiomyocytes and in the hearts of septic mice. Baricitinib administration remarkably improved cardiac function, suppressed systemic inflammatory response, attenuated histopathological changes, inhibited cardiac cell apoptosis and alleviated myocardial damage in septic mice. Furthermore, Baricitinib treatment significantly enhanced PINK1-Parkin-mediated mitophagy, increased autophagosomes, decreased impaired mitochondria, and restored myocardial energy metabolism. Mechanically, the limited mitophagy in septic myocardium was associated with increased p-ULK1 (Ser757), which was regulated by p-mTOR. Baricitinib reduced p-ULK1 (Ser757) and enhanced mitophagy by inhibiting the JAK2-AKT-mTOR signaling pathway. Inhibition of mitophagy with Mdivi-1 reversed the cardiac protective and anti-inflammatory effects of Baricitinib in septic mice. These findings suggest that Baricitinib attenuates SIMD by enhancing mitophagy in cardiomyocytes via the JAK2-AKT-mTOR signaling pathway, providing a novel mechanistic and therapeutic insight into the SIMD.

Osteoarthritis (OA) is a prevalent bone and joint disease characterized by degeneration. The dysregulation between chondrocyte synthesis and breakdown is a key factor in OA development. Targeting the degenerative changes in cartilage tissue degradation could be a potential treatment approach for OA. Previous research has established a strong link between autophagy and the regulation of chondrocyte functions. Activating autophagy has shown promise in mitigating cartilage tissue degeneration. Currently, osteoarthritis treatment primarily focuses on symptom management, as there is no definitive medication to stop disease progression. Previous studies have demonstrated that luteolin, a flavonoid present in Chinese herbal medicine, can activate autophagy and reduce the expression of MMP1 and ADAMTS-5. This study utilized an in vitro osteoarthritis model with chondrocytes stimulated by IL-1β, treated with varying concentrations of luteolin. Treatment with luteolin notably increased the levels of synthesis factors Aggrecan and Collagen II, while decreasing the levels of decomposition factors MMP-1 and ADAMTS-5. Moreover, inhibition of autophagy by Chloroquine reversed the imbalances in chondrocyte activities induced by IL-1β. In an in vivo model of knee osteoarthritis induced by medial meniscal instability (DMM), luteolin was administered as a therapeutic regimen. After 12 weeks, knee cartilage tissues from mice were analyzed. Immunofluorescence and immunohistochemical staining revealed a decrease in P62 expression and an increase in Beclin-1 in the cartilage tissues. Additionally, cartilage wear in the knee joints of mice was alleviated by safranin O and fast green staining. Our study findings underscore the significant role of luteolin in effectively rebalancing chondrocyte activities disrupted by IL-1β. Our results strongly indicate that luteolin has the potential to be developed as a novel therapeutic agent for the treatment of osteoarthritis, offering promising prospects for future drug development.

Lithium metal batteries are promising devices for the next-generation energy storage due to their ultrahigh theoretical specific capacity and extremely low electrochemical potential. Their inherent problem is the formation of lithium dendrites in cycling, which has induced safety concerns for almost half a century. After understanding the formation mechanism of branching structures, we propose to suppress lithium dendrites by adopting external magnetic fields to induce diffusion enhancement at the interface of the anode, thus attenuating concentration gradient there and reducing the driving force for the formation of dendritic structures. The diffusion coefficient of lithium ions is dependent on the strength of magnetic fields, confirming the effectiveness of magnetic fields in improving Li+ diffusion. After employing the magnetic field of 0.8 T, the concentration gradients at the growth front becomes nearly half of the control case, which leads to a dendrite-free lithium deposition up to the high current density of 10 mA cm−2. Both the Cu|LiCoO2 batteries and the symmetric Li|Li coin cells show a long-term stable cycling at high current densities under the assistance of magnetic field. This diffusion enhanced technique promises a facile and general approach to suppress dendritic structures in secondary batteries, which may help to develop quick charging strategies.

Vitamin A, a fat-soluble vitamin, is the basic substance required to maintain healthy vision and the main physiological functions of cattle. The results from previous studies regarding the effect of vitamin A on intramuscular fat varied. This meta-analysis aimed to generate a more comprehensive understanding of the relationship between vitamin A and intramuscular fat content and to provide potential clues for future research and commercial practice. Electronic databases such as MEDLINE and Ovid were systematically searched, and studies investigating the relationship between vitamin A and intramuscular fat content were included. Standardized mean differences (SMDs) in intramuscular fat percentage and intramuscular fat score, with their respective 95% confidence intervals (CIs), were calculated. The heterogeneity and publication bias were evaluated. A total of 152 articles were identified through searches of databases. Seven articles were confirmed for inclusion in this meta-analysis. The SMD of IMF percentage derived from the analysis was−0.78 (-2.68, 1.12) (Q = 246.84, p < 0.01). The SMD of the IMF score was 1.25 (-2.75, 5.25) (Q = 87.20, p < 0.01). Our meta-analysis indicates that the addition of vitamin A could decrease intramuscular fat in cattle steers.

In this paper, the spherical particles growth during lithium electrodeposition was investigated by directly solving the governing equations based on the Landau transformation method. The basic growth kinetic characteristics of a spherical particle during electrodeposition was studied. Predicted results show that the dynamic oscillation of the growth velocity occurs during the spherical particle growth. It was found from numerical simulations that applied electrical potential difference, electrolyte concentration, and diffusion coefficient are 3 main factors influencing the spherical growth and the existence of the dynamic oscillation state of the growth velocity during electrodeposition. The increase in both the applied electrical potential difference and the electrolyte concentration can lead to the increase of the growth velocity of the spherical particle, while the growth velocity is independent of the diffusion coefficient. Moreover, it was found that the wavelength and the amplitude of the dynamic oscillation of the growth velocity can be influenced by the applied electrical potential difference, the electrolyte concentration, and the diffusion coefficient. We determined that the dynamic competition between electrochemical reactions and ion transport in the electrodeposition is the reason for the existence of the oscillation of the growth velocity.

Abstract Background Lipid management is the first line of treatment for decreasing the incidence of cardiovascular events in patients with coronary heart disease (CHD), and a variety of indicators are used to evaluate lipid management. This work analyses the differences in LDL-C and apoB for lipid management evaluation, as well as explores the feasibility of skin cholesterol as a marker that can be measured non-invasively for lipid management. Methods The prospective study enrolled 121 patients who had been diagnosed with acute coronary syndrome (ACS) at the department of emergency medicine of the First Affiliated Hospital of the USTC from May 2020 to January 2021, and the patients were grouped into Group I (n=53) and Group II (n=68) according to whether they had comorbid hyperlipidemia and/or diabetes mellitus. All patients were administered 10 mg/day of rosuvastatin and observed for 12 weeks. Lipid management was assessed on the basis of LDL-C and apoB, and linear correlation models were employed to assess the relationship between changes in these well accepted markers to that of changes in skin cholesterol. Results Out of 121 patients with ACS, 53 patients (43.80 %) had combined hyperlipidemia and/or diabetes mellitus (Group I), while 68 patients (56.20 %) did not (Group II). Cardiovascular events occur at earlier ages in patients with CHD who are comorbid for hyperlipidemia and/or diabetes (P

Coupling the bi-functional mechanism with compressive lattice strain might be an effective way to boost the electrocatalysis of platinum (Pt)-based nanoparticles for methanol oxidation reaction (MOR). This strategy weakens the chemisorption of poisoning CO-like intermediates generated during MOR on the active Pt sites by lowering their d-band center. In this context, we herein report the synthesis of ternary copper-tungsten-platinum (CuWPt) nanoalloys with light doping of W element by simply co-reducing their precursors at elevated temperature. In this ternary alloy system, the presence of only small amount of W element not only weakens the chemisorption of CO-like intermediates by lowering the Pt d-band center through compressive lattice strain, but also cleans the active Pt sites by "hydrogen spillover effect", endowing the as-prepared CuWPt nanoalloys at an appropriate Cu/W/Pt ratio with good activity for MOR. In specific, the ternary CuWPt alloy nanoparticles at a Cu/W/Pt molar ratio of 21/4/75 show a specific activity of 2.5 mA·cm−2 and a mass activity of 2.11 A·mg−1 with a better durability, outperforming those ternary CuWPt alloy nanoparticles at other Cu/W/Pt ratios, binary CuPt alloys and commercial Pt/C catalyst as well as a large number of reported Pt-based electrocatalysts. In addition, a single direct methanol fuel cell (DMFC) assembled using ternary CuWPt nanoalloys as anodic catalysts shows a power density of 24.3 mW·cm−2 and an open-circle voltage of 0.6 V, also much higher than those of the single DMFC assembled from commercial Pt/C catalysts.

ObjectiveThe purpose of this study was to investigate attentional network functional characteristics in patients with cervical dystonia (CD).MethodsA total of 29 patients with CD and 26 healthy controls (HCs) were recruited. All subjects participated in the study and underwent the Attention Network Test (ANT), which evaluated the efficiencies of three independent attention networks (alerting, orienting, and executive control), as well as reaction time (RT) and accuracy.ResultsSignificant differences between CD patients (9.86 ± 27.95 ms) and HCs (33.62 ± 23.41 ms) were observed in the alerting network (t = −3.40, p

In this paper, the numerical method for a multiterm time-fractional reaction–diffusion equation with classical Robin boundary conditions is considered. The full discrete scheme is constructed with the L1-finite difference method, which entails using the L1 scheme on graded meshes for the temporal discretisation of each Caputo fractional derivative and using the finite difference method on uniform meshes for spatial discretisation. By dealing with the discretisation of Robin boundary conditions carefully, sharp error analysis at each time level is proven. Additionally, numerical results that can confirm the sharpness of the error estimates are presented.

Abstract Background Establishing a high-accuracy and non-invasive method is essential for evaluating cardiovascular disease. Skin cholesterol is a novel marker for assessing the risk of atherosclerosis and can be used as an independent risk factor of early assessment of atherosclerotic risk. Methods We propose a non-invasive skin cholesterol detection method based on absorption spectroscopy. Detection reagents specifically bind to skin cholesterol and react with indicator to produce colored products, the skin cholesterol content can be obtained through absorption spectrum information on colored products detected by non-invasive technology. Gas chromatography is used to measure cholesterol extracted from the skin to verify the accuracy and reliability of the non-invasive test method. A total of 342 subjects were divided into normal group (n = 115), disease group (n = 110) and risk group (n = 117). All subjects underwent non-invasive skin cholesterol test. The diagnostic accuracy of the measured value was analyzed by receiver-operating characteristic (ROC) curve. Results The proposed method is able to identify porcine skin containing gradient concentration of cholesterol. The values measured by non-invasive detection method were significantly correlated with gas chromatography measured results (r = 0.9074, n = 73, p

Calibration of the stereo vision systems is a crucial step for precise 3D measurements. Restricted by the outdoors’ large field of view (FOV), the conventional method based on precise calibration boards is not suitable since the calibration process is time consuming and the calibration accuracy is not guaranteed. In this paper, we propose a calibration method for estimating the extrinsic parameters of the stereo vision system aided by an inclinometer and a range sensor. Through the parameters given by the sensors, the initial rotation angle of the extrinsic parameters and the translation vector are pre-established by solving a set of linear equations. The metric scale of the translation vector is determined by the baseline length provided by the range sensor or GNSS signals. Finally, the optimal extrinsic parameters of the stereo vision systems are obtained by nonlinear optimization of inverse depth parameterization. The most significant advantage of this method is that it enhances the capability of the stereo vision measurement in the outdoor environment, and can achieve fast and accurate calibration results. Both simulation and outdoor experiments have verified the feasibility and correctness of this method, and the relative error in the outdoor large FOV was less than 0.3%. It shows that this calibration method is a feasible solution for outdoor measurements with a large FOV and long working distance.

Abstract Wilson’s disease (WD) is an inherited disorder characterized by excessive accumulation of copper in the body, particularly in the liver and brain. In the central nervous system (CNS), extracellular copper accumulation triggers pathological microglial activation and subsequent neurotoxicity. Growing evidence suggests that levels of inflammatory cytokines are elevated in the brain of murine WD models. However, the mechanisms associated with copper deposition to neuroinflammation have not been completely elucidated. In this study, we investigated how the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to copper-mediated neuroinflammation in an animal model of WD. Elevated levels of interleukin-1β, interleukin-18, interleukin-6, and tumor necrosis factor-α were observed in the sera of WD patients and toxic milk (TX) mice. The protein levels of inflammasome adaptor molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), cleaved caspase-1, and interleukin-1β were upregulated in the brain regions of the TX mice. The NLRP3 inflammasome was activated in the TX mice brains. Furthermore, the activation of NLRP3 inflammasome was noted in primary microglia treated with CuCl2, accompanied by the increased levels of cleaved caspase-1, ASC, and interleukin-1β. Blocking NLRP3 inflammasome activation with siNlrp3 or MCC950 reduced interleukin-1β and interleukin-18 production, thereby effectively mitigating cognitive decline, locomotor behavior impairment, and neurodegeneration in TX mice. Overall, our study demonstrates the contribution of copper overload-mediated activation of NLRP3 inflammasome to progressive neuropathology in the CNS of a murine model of WD. Therefore, blockade of the NLRP3 inflammasome activation could be a potential therapeutic strategy for WD.

It is urgent for westward coal mine development to control surrounding rock of thick unconsolidated stratum, thin basement rock, and super high seam under geological conditions. Studying surrounding rock deformation control mechanism under special geological conditions in western regions is of practical guiding significance for the implementation of China’s energy strategy in western regions, with special mining geological conditions of the experimental mine as the background, deformation rule, failure characteristic, and stress distribution characteristic of surrounding rock in fully mechanized caving mining of thick unconsolidated stratum. By establishing the structural mechanics model of “sidestepped rock beam,” the stability criterion is determined. The horizontal displacement of surrounding rock in the middle of the working face is small, and the displacement at both ends is large. After the mining of the working face, an “O” ring appears on the main roof. The ring extends outward with the excavation, reaches the maximum at the initial weighting, and its displacement decreases from inside to outside. Finally, through theoretical analysis, experimental research, numerical calculation, and field observation, the thin bedrock and ultra-high coal seam are systematically analyzed, and its deformation and failure mechanism is revealed. Relevant research findings are successfully implemented on the scene and effectively ensured safety, high yield, and high efficiency of the mine.

As a major hidden danger of mine safety production, the impact resistance tendency of rock seriously restricts the safety and high yield of coal mine. At the same time, as one of the puzzles of rock mechanics, it has been perplexing many domestic and foreign scholars since the recorded rock burst in South Stafford coal mine in 1738. At present, this research is relatively weak; so, it is different for economic and social benefits. The study of the impact resistance law and the antishock measures of water-bearing rocks are extremely meaningful. In order to deeply explore the impact resistance law of rock with different water content and the antishock support measures after roadway excavation, based on the previous research results of the previous research, the impact tendency of different coal samples was firstly tested by coal uniaxial compression experiment, judging and then calculating the damage characteristics of rock with different water content according to the obtained data, as one of the judgment basis of the impact law of coal mine. Secondly, according to the experimental data, the energy evolution characteristics are calculated and analyzed with the graph. Finally, the impact tendency of the rock under different moisture conditions is obtained.

An operation in itself is a kind of trauma and may lead to immunosuppression followed by a bounce back. Not many studies exist that describe dynamics of the distribution of peripheral blood (PB) immune cells during the perioperative period. Considering this scarcity, we aggregated the data on the dynamics of immune cells in patients with digestive system resections during the perioperative period and the relationship with short- and long-term prognoses. By the systematic retrieval of documents, we collected perioperative period data on white blood cells (WBC), lymphocytes, neutrophil–lymphocyte ratio (NLR), CD4+ T cells, CD8+ T cells, helper T cells (Th), B cells, natural killer cells (NK), dendritic cells (DCs), regulatory T cells (Tregs), regulatory B cells (Bregs), and Myeloid derived suppressor cells (MDSC). The frequency and distribution of these immune cells and the relationship with the patient’s prognosis were summarized. A total of 1916 patients’ data were included. Compared with before surgery, WBC, lymphocytes, CD4+ cells, CD8+ T cells, MDSC, and NK cells decreased after surgery, and then returned to preoperative levels. After operation DCs increased, then gradually recovered to the preoperative level. No significant changes were found in B cell levels during the perioperative period. Compared with the preoperative time-point, Tregs and Bregs both increased postoperatively. Only high levels of the preoperative and/or postoperative NLR were found to be related to the patient’s prognosis. In summary, the surgery itself can cause changes in peripheral blood immune cells, which might change the immunogenicity. Therefore, the immunosuppression caused by the surgical trauma should be minimized. In oncological patients this might even influence long-term results.

Background: Abnormal nutritional status is frequently seen in patients with chronic diseases. To date, no study has investigated the detailed characteristics of abnormal nutritional status among Wilson's disease (WD) patients in the Chinese cohort. This study aimed to describe the nutritional status of WD patients, with a particular focus on the differences between patients with different phenotypes.Methods: The study subjects comprised 119 healthy controls, 129 inpatients (hepatic subtype, n = 34; neurological subtype, n = 95) who were being treated at the affiliated hospital of the Institute of Neurology, Anhui University of Chinese Medicine. All of the subjects were assessed for body composition by using bioelectrical impedance analysis. All WD patients received anthropometry, nutritional risk screening 2002 (NRS2002), and laboratory test (hemocyte and serum biomarkers) additionally.Results: Compared with healthy controls, the fat mass and rate of total body and trunk were significantly higher in WD patients (P < 0.001), the muscle and skeletal muscle mass of total body and trunk were significantly lower in WD patients (P < 0.001). Compared with hepatic subtype patients, the fat mass and rate of total body, trunk, and limbs were significantly lower in neurological subtype patients (P

Here we report a strategy to enhance the energy density of supercapacitors by increasing the utilization rate of the specific surface area (SSA) via wettability improvement. The nonporous gold (NPG) film is used as the electrodes and the ionic liquid [EMIM]BF4 is the electrolyte. When the electrode is coated by paraffin, an increase of the contact angle leads to a remarkable reduction of the specific capacitance. While when acetonitrile is added into the electrolyte, the contact angle is decreased and the utilization rate of SSA is improved, which results in an increase of the specific capacitance. The addition of isopropyl acetate into the electrolyte leads to a further increase of the specific capacitance. To generalize the role of the wettability in improving the energy density, a carbon-based electrode is evaluated in the solution of potassium hydroxide. An addition of propyl alcohol into the potassium hydroxide solution leads to an increase of the specific capacitance, as well as a long-term stability of the supercapacitor. The role of conductivity in this study is excluded by designing experiments. This paper highlights the significance of wettability in determining the specific capacitance, showing an alternative to improve the energy density of supercapacitors. Keywords: Supercapacitor, Energy density, Specific capacitance, Effective surface area, Wettability

Classic crystallization describes a burst nucleation followed by a layer-by-layer atom deposition. The non-classic crystallization refers to particle mediated crystallization process. Different crystallization routes lead to the formation of diverse structured materials. Here we report a rational synthesis of silver particles by selecting the crystallization routes. Silver particles were synthesized by a solution reduction approach. The crystallization routes were regulated by adding amino acids to stabilize silver ions which leads to the decrease of the reduction rate. Without amino acids, silver dendrites were largely formed. With the addition of amino acids, flower-like (low concentration of amino acids) and spherical silver (high concentration of amino acid) particles were synthesized. Three kinds of amino acids were tested and the similar results were obtained. The time-dependent characterization on the evolution of silver particles showed that silver dendrites were formed by the classic atom deposition while the other two morphologies were formed by the combination of classic and non-classic crystallization. The silver particles synthesized were evaluated for ethylene epoxidation and the dendritic particles demonstrated a high selectivity.

BackgroundEpidemiological studies have reported various results regarding whether FOXO3A is related to various carcinomas. However, the prognostic significance of FOXO3A in upper tract urothelial carcinoma (UTUC) remains unclear. The purpose of this study was to validate the correlation between FOXO3A expression and oncological outcomes in UTUC.MethodsThe expression levels of FOXO3A in 107 UTUC patients were examined by immunohistochemistry (IHC). We examined the prognostic role of FOXO3A by using the Cox proportional hazard model.ResultsThe results indicated that FOXO3A expression was notably decreased in UTUC tissue compared with control tissue. Decreased expression of FOXO3A was also related to advanced pathologic stage (P = 0.026), lymph node metastasis (P = 0.040), lymphovascular invasion (P < 0.001), and adjuvant therapy (P = 0.048). In addition, UTUC patients with low FOXO3A expression had a significantly shorter survival time, including both overall survival (OS) [hazard ratio (HR) 2.382, P = 0.004] and recurrence-free survival (RFS) (HR 2.385, P = 0.004), than those with high expression. Multivariate analyses showed that FOXO3A was a significant predictor for OS (HR 2.145, P = 0.014) and RFS (HR 2.227, P = 0.010) in UTUC patients.ConclusionOur results indicate that FOXO3A may be involved in the recurrence of UTUC and that it has certain clinical value in the therapeutic targeting and prognostic evaluation of UTUC.

Background: Our previous study found that electroacupuncture (EA) can promote the recovery of neurological functions, reduce the volume of cerebral infarction, and protect the neurovascular unit in middle cerebral artery occlusion (MCAO) rats. Some studies have shown that ferroptosis is closely related to ischemic stroke; however, whether EA plays a protective role by regulating ferroptosis is unknown.Objective: We aimed to investigate the inhibitory effects of EA on ferroptosis in MCAO rats.Methods: We used 36 adult male Sprague–Dawley rats in this study. MCAO rats were established according to the Zea method and treated with EA at a continuous wave of 2/100 Hz and ~2–4 V for 30 min for 7 consecutive days. We analyzed the coordinated motor deficit and volume of cerebral infarction in vivo through 9.4-tesla magnetic resonance imaging. Then, the ischemic brain tissue was isolated and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron were determined. Western blotting and real-time quantitative PCR were performed to evaluate the expression of glutathione peroxidase 4 (GPX4), transferrin (Tf), transferrin receptor 1 (TfR1), and ferritin heavy chain 1 (FTH1). To confirm the results, we used a transmission electron microscope to observe the mitochondrial morphology.Results: EA intervention significantly decreased the oxidative stress level and inhibited ferroptosis. EA significantly improved coordinated motor deficit (P < 0.01) and decreased cerebral infarct volume (P < 0.01) in the EA + MCAO group, compared with the MCAO group. EA downregulated the level of MDA (P < 0.01) and total iron (P < 0.01) and upregulated the level of SOD (P < 0.01) and GSH (P < 0.01) in the EA + MCAO group, compared with the MCAO group. EA increased the levels of GPX4 and GPX4 mRNA (P < 0.01) and FTH1 and FTH1 mRNA (P < 0.05, P < 0.01), whereas it decreased the levels of Tf and Tf mRNA (P < 0.05, P < 0.01) and TfR1 and TfR1 mRNA (P < 0.01) in the EA + MCAO group, compared with the MCAO group. EA also promoted the recovery of mitochondrial morphology according to the mitochondrial classification system for the ischemic cerebral tissue.Conclusion: Our results indicate that EA can inhibit ferroptosis by regulating oxidative stress and iron-related proteins, thus conferring protection against MCAO in a rat model.

Studies have indicated that oxidative stress plays a crucial role in the development of Parkinson’s disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of antioxidant response elements (AREs), thus preventing oxidative stress. Thymoquinone (TQ) is the bioactive component of Nigella sativa, a medicinal plant that exhibits antioxidant and neuroprotective effects. In the present study we examined whether TQ alleviates in vivo and in vitro neurodegeneration induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by acting as an activator of the Nrf2/ARE cascade. We showed that TQ significantly reduced MPP+-mediated cell death and apoptosis. Moreover, TQ significantly elevated the nuclear translocation of Nrf2 and significantly increased the subsequent expression of antioxidative genes such as Heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1) and Glutathione-S-Transferase (GST). The application of siRNA to silence Nrf2 led to an abolishment in the protective effects of TQ. We also found that the intraperitoneal injection of TQ into a rodent model of PD ameliorated oxidative stress and effectively mitigated nigrostriatal dopaminergic degeneration by activating the Nrf2-ARE pathway. However, these effects were inhibited by the injection of a lentivirus wrapped Nrf2 siRNA (siNrf2). Collectively, these findings suggest that TQ alleviates progressive dopaminergic neuropathology by activating the Nrf2/ARE signaling cascade and by attenuating oxidative stress, thus demonstrating that TQ is a potential novel drug candidate for the treatment of PD.

With the increase of buried depth, the content of gas increases gradually. The gas in the mining process will lead to gas gush and other dynamic disasters, or even coal and gas gushing in front of the working face. Therefore, the study on the permeability distribution of coal and the surrounding rock is the core work of coal and gas mining at the same time. To study the mechanical behaviors and seepage characteristics of coal mass during unloading is to prepare for coal and gas mining in the future, which can not only ensure the safety of operators to the maximum extent but also increase the mining rate as much as possible. Based on the stress-strain curve and seepage curve, the brittleness index and seepage characteristics of coal are analyzed. The greater the brittleness index is, the more likely the coal mass is to produce cracks, and then to form large cracks, or even fracture. Through the study of brittleness index and seepage characteristics of coal mass, the mechanical behavior of coal mass can be easily obtained, so as to guide the mining of coal mass.

The deformation control of the surrounding rock during gob-side entry driving along deeply fully mechanized caving island working face is one of the main bottlenecks affecting the successful and efficient production in modern mining. The prior ordinary fully mechanized caving theories have been difficult in ensuring the safe and efficient mining along island working face during gob-side entry driving under the complex conditions in the west. Therefore, it is of great theoretical and practical significance to carry out the research on the deformation mechanism and control of the surrounding rock during gob-side entry driving along deeply fully mechanized caving island working face. This paper, by means of experimental research, theoretical analysis, numerical calculation, and field industrial test, systemically researched the deformation characteristics of the surrounding rock and the law of strata behaviors during gob-side entry driving along deeply fully mechanized caving island working face.

In the current study, we used 9.4-tesla magnetic resonance imaging (9.4T MRI) and inductively coupled plasma mass spectrometry (ICP-MS) to investigate the distribution of copper in the brain samples of a murine model of Wilson’s disease (WD) following penicillamine (PCA) treatment. We also evaluated if the distribution of copper in the brain samples of mice was correlated with behavioral symptoms. Results from the behavioral experiments showed that 7 days of PCA treatment decreased the total distance traveled in the open field and the number of rearing and climbing instances among the toxic milk (TX) mice as compared with model group. We also observed that the open arm ratio in the elevated plus-maze (EPM) was reduced, escape latency in the Barnes maze test was increased, and avoidance in the open field was enhanced in TX mice following 14 days of PCA treatment as compared with those in untreated TX mice. We found that PCA treatment for 21–28 days improved the cognitive abilities, exploratory behavior, and movement behavior of TX mice. The PCA-treated mice also exhibited varying degrees of magnetic susceptibilities in the cortex, corpus striatum, hippocampus, and amygdaloid nucleus across the treatment period. Low copper concentrations were found in all of the analyzed brain regions of PCA-treated mice after 21–28 days as compared with the model group (P < 0.05). However, copper concentrations were increased in the primary motor cortex and cerebellum at 7 days post-PCA treatment as compared with those in the model group (P < 0.05). After 14 days of PCA treatment, the copper concentrations in the sensorimotor cortex, corpus striatum, hippocampus, and amygdaloid nucleus were higher than those detected without treatment. The results from a Pearson’s correlation analysis revealed that there was a significant (P < 0.05) correlation between copper concentrations and magnetic susceptibility in all of the brain regions that were analyzed. Therefore, our results indicate that copper concentration and magnetic susceptibility are associated with alterations in mood-related behavior, recognition memory, and movement behaviors in TX mice that are treated with PCA. The redistribution of copper in the TX mouse brain during PCA treatment may aggravate changes in behavioral performance.

Rational synthesis of materials is a long-term challenging issue due to the poor understanding on the formation mechanism of material structure and the limited capability in controlling nanoscale crystallization. The emergent in situ electron microscope provides an insight to this issue. By employing an in situ scanning electron microscope, silver crystallization is investigated in real time, in which a reversible crystallization is observed. To disclose this reversible crystallization, the radicals generated by the irradiation of electron beam are calculated. It is found that the concentrations of radicals are spatiotemporally variable in the liquid cell due to the diffusion and reaction of radicals. The fluctuation of the reductive hydrated electrons and the oxidative hydroxyl radicals in the cell leads to the alternative dominance of the reduction and oxidation reactions. The reduction leads to the growth of silver crystals while the oxidation leads to their dissolution, which results in the reversible silver crystallization. A regulation of radical distribution by electron dose rates leads to the formation of diverse silver structures, confirming the dominant role of local chemical concentration in the structure evolution of materials.

With the deployment of China’s energy strategy in the western regions, complex geological mining conditions such as thin bedrock and ultrathick seams in western China have caused a series of problems such as serious deformation of the surrounding rock at the ends of the working face and the increase in the lead abutment pressure of the roadways; the research on end roof deformation in the resource exploitation in western China has become one of the great demands of the industry. Based on the failure characteristics of rock mass, relying on the actual mining geological conditions of a coal mine in Inner Mongolia, the failure characteristics of the overlying rock strata under the influence of mining were simulated and analyzed using similar material simulation experiment, which intuitively reproduced the failure and deformation processes of the immediate roof, main roof, and key strata and revealed the mechanical mechanism of the directional weakening of the end roof. It is of great significance for the stability control of the surrounding rock at the end of the fully mechanized caving face in the thin bedrocks and ultrathick seams, reducing the abutment pressure of gate roadway and controlling the spontaneous combustion of residual coal in the goaf.

Treating weak saturated soil foundation by drainage powder jetting pile foundation can not only increase the bearing capacity of the foundation but also accelerate the drainage and consolidation process of the foundation. Having been commonly used in engineering, the plum blossom pile layout scheme is based on the foundation axisymmetric consolidation model (the powder jetting pile is the model center and the drainage board is located at the outer boundary of the model). It adopts reasonable boundary conditions and foundation seepage conditions and the method of pile-soil composite modulus and obtains the expression of the average excess pore water pressure of the composite foundation of the instantaneous loading of the drainage powder jetting pile under the simplified model. Therefore, the average consolidation degree of the foundation is acquired. The expression of the average consolidation degree can comprehensively reflect factors such as pile-soil modulus ratio, displacement ratio, drain spacing ratio, and those which affect the consolidation process of the foundation. The obtained analytical solution is of certain practical application significance for the consolidation settlement calculation of such engineering.

Disorder of the sympathetic nervous system (SNS) is closely related to the pathogenesis of various autoimmune diseases (ADs). Catecholamine triggered beta2-adrenergic receptor (β2-AR) signaling is important in creating a bidirectional response in the progression of ADs due to factors including diverse expression patterns, single nucleotide polymorphisms (SNPs), biased signals, and desensitization of β2-AR, as well as different subtypes of Gα binding to β2-AR. In this review, we summarize the actions of β2-AR signaling in regulating the functions of immunocytes and in the pathogenesis of ADs, and the application of β2-AR agonists or antagonists in treating major types of ADs is also discussed. We suggest that restoring the immune balance via a soft regulation of the expression or activation of β2-AR is one of the promising therapeutic strategies for systematic ADs.

In crystallization, nanoparticle aggregation often leads to the formation of orderly structures, even single crystals. Why can nanoparticles form orderly structures and what is the mechanism dominating their orderly aggregation? These questions raise interesting research problems, but the occurrences that could answer them often fail to be directly observed, since the interaction among particles is invisible. Here, we report an attempt to discover the interaction and aggregation of building blocks through a computer simulation, focusing on the shape effect of building blocks on the aggregation. Four types of silver building blocks were selected, each consisting of (100) and (111) facets, but the ratio of these two facets was different. It was found that the area of facets played an important role in selecting the aggregation mode. The facets with a large area and high energy had a high possibility of aggregation. In addition, the effects of solvent viscosity and temperature were also investigated. High viscosity and low temperature enhanced the orderliness of aggregation. This paper reports a detailed view of the aggregation process of silver nanoparticles, which is expected to be helpful in understanding the structure evolution of materials in nonclassical crystallization.

Solvents are widely used in crystallization, but their effects on the shape development of crystals are under debate. Here, we report a view on how solvents play their role by considering the viscosity of solvents. We synthesize silver particles in a mixture of alcohol and water. The viscosity of the solvent is changed by varying the volume ratio of alcohol in water. With the variation of viscosity, diverse morphologies of silver particles are synthesized. Small cubic crystals are formed at low viscosity, while hierarchical flower-like particles are formed at high viscosity. Two alcohols are employed, namely ethanol and propanol. No matter which alcohol is employed, the results are similar. Due to the limitation of mass transfer at high viscosity, the particles synthesized in such solvent are smaller and stabilized by the solvent. When the solution containing these particles are dropped onto metal substrates, these tiny particles firstly aggregate, which is followed by classic crystallization, forming flower-like hierarchical structures. These findings show the importance of the viscosity of solvents in shaping particles, which is underestimated previously.

Wilson's disease (WD) is typically affected by attention, which is one of the cognitive domains. The Attention Network Test (ANT) was developed to measure the functioning of the following three individual attentional networks: orienting, alerting, and executive control. The ANT has been used in a variety of neuropsychiatric conditions; however, it has not been used in WD. The aim of this study was to investigate the attentional function of WD patients, and 35 patients with early and moderate neurological WD, as well as 35 gender-, age-, and education-matched healthy controls performed the ANT. Remarkable differences between the patients and healthy controls were observed in the alerting network (p = 0.007) in contrast the differences in the orienting (p = 0.729) and executive control (p = 0.888) networks of visual attention. The mean reaction time in the ANT was significantly longer in the WD patients than in the controls (p