Structure and Defect Engineering of V3S4-xSex Quantum Dots Confined in a Nitrogen-Doped Carbon Framework for High-Performance Sodium-Ion Storage.

Constructing quantum dot-scale metal sulfides with defects and strongly coupled with carbon is significant for advanced sodium-ion batteries (SIBs). Herein, Se substituted V3S4 quantum dots with anionic defects confined in nitrogen-doped carbon matrix (V3S4-xSex/NC) are fabricated. Introducing element Se into V3S4 crystal expands the interlayer distance of V3S4, and triggers anionic defects, which can facilitate Na+ diffusions and act as active sites for Na+ storage. Meanwhile, the quantum dots tightly encapsulated by conductive carbon framework improve the stability and conductivity of the electrode. Theoretical calculations also unveil that the presence of Se enhances the conductivity and Na+ adsorption ability of V3S4-xSex. These properties contribute to the V3S4-xSex/NC with high specific capacity of 447 mAh g-1 at 0.2 A g-1, and prominent rate and cyclic performance with 504 mAh g-1 after 1000 cycles at 10 A g-1. The sodium-ion hybrid capacitors (SIHCs) with V3S4-xSex/NC anode and activated carbon cathode can achieve high energy/power density (maximum 144 Wh kg-1/5960 W kg-1), capacity retention ratio of 71% after 4000 cycles at 2 A g-1. This work not only synthesizes V3S4-xSex/NC, but also provides a promising opportunity for designing quantum dots and utilizing defects to improve the electrochemical properties.

Knowledge, attitudes and practices about research misconduct among medical residents in southwest China: a cross-sectional study.

BACKGROUND: With the emergence of numerous scientific outputs, growing attention is paid to research misconduct. This study aimed to investigate knowledge, attitudes and practices about research misconduct among medical residents in southwest China. METHODS: A cross-sectional study was conducted in southwest China from November 2022 through March 2023. The links to the questionnaire were sent to the directors of the teaching management department in 17 tertiary hospitals. Answers were collected and analyzed. Logistic regression analysis was performed to explore the factors associated with research misconduct among residents. RESULTS: 6200 residents were enrolled in the study, and 88.5% of participants attended a course on research integrity, but 53.7% of participants admitted to having committed at least one form of research misconduct. Having a postgraduate or above, publishing papers as the first author or corresponding author, attending a course on research integrity, lower self-reported knowledge on research integrity and lower perceived consequences for research misconduct were positively correlated to research misconduct. Serving as a primary investigator for a research project was negatively associated with research misconduct. Most residents (66.3%) agreed that the reason for research misconduct is that researchers lack research ability. CONCLUSIONS: The high self-reported rate of research misconduct among residents in southwest China underscores a universal necessity for enhancing research integrity courses in residency programs. The ineffectiveness of current training in China suggests a possible global need for reevaluating and improving educational approaches to foster research integrity. Addressing these challenges is imperative not only for the credibility of medical research and patient care in China but also for maintaining the highest ethical standards in medical education worldwide. Policymakers, educators, and healthcare leaders on a global scale should collaborate to establish comprehensive strategies that ensure the responsible conduct of research, ultimately safeguarding the integrity of medical advancements and promoting trust in scientific endeavors across borders.

Review of Mechanisms and Research Methods for Blunt Ballistic Head Injury.

Head injuries account for 15%-20% of all military injuries and pose a high risk of causing functional disability and fatality. Blunt ballistic impacts are one of the threats that can lead to severe head injuries. This review aims to examine the mechanisms and injury risk assessment associated with blunt ballistic head injury (BBHI). The review further discusses research methods and instrumentation used in BBHI studies, focusing on their limitations and challenges. Studies on the mechanisms of focal and diffuse brain injuries remain largely inconclusive and require further effort. Some studies have attempted to associate BBHIs with head mechanics, but more research is required to establish correlations between head mechanics and injury severity. Limited access to experimental models and a lack of instrumentation capable of measuring the mechanics of brain tissue in situ are potential reasons for the lack of understanding of injury mechanisms, injury correlations, and injury tolerance levels specific to this loading regime. Targeted research for understanding and assessing head injuries in blunt ballistic impacts is a necessary step in improving our ability to design protection systems to mitigate these injuries.

Solid-State Construction of CuOx/Cu1.5Mn1.5O4 Nanocomposite with Abundant Surface CuOx Species and Oxygen Vacancies to Promote CO Oxidation Activity.

Carbon monoxide (CO) oxidation performance heavily depends on the surface-active species and the oxygen vacancies of nanocomposites. Herein, the CuOx/Cu1.5Mn1.5O4 were fabricated via solid-state strategy. It is manifested that the construction of CuOx/Cu1.5Mn1.5O4 nanocomposite can produce abundant surface CuOx species and a number of oxygen vacancies, resulting in substantially enhanced CO oxidation activity. The CO is completely converted to carbon dioxide (CO2) at 75 °C when CuOx/Cu1.5Mn1.5O4 nanocomposites were involved, which is higher than individual CuOx, MnOx, and Cu1.5Mn1.5O4. Density function theory (DFT) calculations suggest that CO and O2 are adsorbed on CuOx/Cu1.5Mn1.5O4 surface with relatively optimal adsorption energy, which is more beneficial for CO oxidation activity. This work presents an effective way to prepare heterogeneous metal oxides with promising application in catalysis.

Evaluation of the Kinematic Biofidelity and Inter-Test Repeatability of Global Accelerations and Brain Parenchyma Pressure for a Head-Brain Physical Model.

Head surrogates are widely used in biomechanical research and headgear assessment. They are designed to approximate the inertial and mechanical properties of the head and are instrumented to measure global head kinematics. Due to the recent interest in studying disruption to the brain, some head models include internal fluid layers and brain tissue, and instrumentation to measure head intracranial biomechanics. However, it is unknown whether such models exhibit realistic human responses. Therefore, this study aims to assess the biofidelity and repeatability of a head model, the Blast Injury Protection Evaluation Device (BIPED), that can measure both global head kinematics and intraparenchymal pressure (IPP) for application in blunt impact, a common loading scenario in civilian life. Drop tests were conducted with the BIPED and the widely used Hybrid III headform. BIPED measures were compared to the Hybrid III data and published cadaveric data, and the biofidelity level of the global linear acceleration was quantified using CORrelation and Analysis (CORA) ratings. The repeatability of the acceleration and IPP measurements in multiple impact scenarios was evaluated via the coefficient of variation (COV) of the magnitudes and pulse durations. BIPED acceleration peaks were generally not significantly different from cadaver and Hybrid III data. The CORA ratings for the BIPED and Hybrid III accelerations ranged from 0.50 to 0.61 and 0.51 to 0.77, respectively. The COVs of acceleration and IPP were generally below 10%. This study is an important step toward a biofidelic head surrogate measuring both global kinematics and IPP in blunt impact.

Neuroprotective effects of salidroside on ageing hippocampal neurons and naturally ageing mice via the PI3K/Akt/TERT pathway.

Studies have found that salidroside, isolated from Rhodiola rosea L, has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced ß-galactosidase (ß-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment.

A Novel Method for Pathway Identification Based on Attractor and Crosstalk in Polyarticular Juvenile Idiopathic Arthritis.

BACKGROUND Juvenile idiopathic arthritis (JIA) is one of the most common inflammatory disorders of unknown etiology. We introduced a novel method to identify dysregulated pathways associated with polyarticular JIA (pJIA). MATERIAL AND METHODS Gene expression profiling of 61 children with pJIA and 59 healthy controls were collected from E-GEOD-13849; 300 pathways were obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) database and 787,896 protein-protein interaction sets were gathered from the Retrieval of Interacting Genes. Attractor and crosstalk were designed to complement each other to increase the integrity of pathways assessment. Then, impact factor was used to assess the interactions inter-pathways, and RP-value was used to evaluate the comprehensive influential ability of attractors. RESULTS There were seven attractors with p<0.01 and 14 pathways with RP<0.01. Finally, two significantly dysfunctional pathways were found, which were related to pJIA progression: p53 signaling pathway (KEGG ID: 04115) and non-alcoholic fatty liver disease (NAFLD) (KEGG ID: 04932). CONCLUSIONS A novel approach that identified the dysregulated pathways in pJIA was constructed based on attractor and crosstalk. The new process is expected to be efficient in the upcoming era of medicine.

Insulin-like growth factor-1 prevents dorsal root ganglion neuronal tyrosine kinase receptor expression alterations induced by dideoxycytidine in vitro.

Dideoxycytidine (zalcitabine, ddC) produces neurotoxic effects. It is particularly important to understand the toxic effects of ddC on different subpopulations of dorsal root ganglion (DRG) neurons which express distinct tyrosine kinase receptor (Trk) and to find therapeutic factors for prevention and therapy for ddC-induced peripheral sensory neuropathy. Insulin-like growth factor-1 (IGF-1) has been shown to have neurotrophic effects on DRG sensory neurons. However, little is known about the effects of ddC on distinct Trk (TrkA, TrkB, and TrkC) expression in DRG neurons and the neuroprotective effects of IGF-1 on ddC-induced neurotoxicity. Here, we have tested the extent to which the expression of TrkA, TrkB, and TrkC receptors in primary cultured DRG neurons is affected by ddC in the presence or absence of IGF-1. In this experiment, we found that exposure of 5, 25, and 50 µmol/L ddC caused a dose-dependent decrease of the mRNA, protein, and the proportion of TrkA-, TrkB-, and TrkC-expressing neurons. IGF-1 (20 nmol/L) could partially reverse the decrease of TrkA and TrkB, but not TrkC, expression with ddC exposure. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 µmol/L) blocked the effects of IGF-1. These results suggested that the subpopulations of DRG neurons which express distinct TrkA, TrkB, and TrkC receptors were affected by ddC exposure. IGF-1 might relieve the ddC-induced toxicity of TrkA- and TrkB-, but not TrkC-expressing DRG neurons. These data offer new clues for a better understanding of the association of ddC with distinct Trk receptor expression and provide new evidence of the potential therapeutic role of IGF-1 on ddC-induced neurotoxicity.

Enhanced CO2 reduction with hydrophobic cationic-ionomer layer-modified zero-gap MEA in acidic electrolyte.

A hydrophobic cationic-ionomer layer of quaternary ammonium poly(N-methyl-piperidine-co-p-terphenyl) and PTFE is presented to enhance the CO2 electroreduction in a zero-gap membrane electrode assembly (MEA) electrolyzer under acidic and low alkali ion concentration conditions. The modified MEA achieved a maximum CO faradaic efficiency of 95.6% at 100 mA cm-2.

Effects of insulin-like growth factor-1 on neurochemical phenotypes of cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate.

Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. The neuropeptide- and neurofilament (NF)-immunoreactive (IR) neurons are two major phenotypical classes in DRG. Whether IGF-1 affects neurochemical phenotypes of DRG neurons remains unknown. In the present study, primary cultured DRG neurons were used to determine the effects of IGF-1 on neurochemical phenotypes of the neurons with excitotoxicity induced by glutamate (Glu). DRG neurons were dissociated and cultured for 48 hours and then exposed to IGF-1 (20 nmol/L), Glu (0.2 mmol/L), Glu (0.2 mmol/L) plus IGF-1 (20 nmol/L) for additional 24 hours. The DRG neurons were continuously exposed to culture media as control. After that, all above cultured DRG neurons were processed for detecting mRNA levels of calcitonin gene-related peptide (CGRP) and neurofilament-200 (NF-200) by real time-PCR analysis. CGRP and NF-200 expression in situ was determined by fluorescent labeling technique. The results showed that CGRP mRNA, but not NF-200 mRNA, increased after IGF-1 administration in the absence or presence of Glu. IGF-1 could increase the percentage of CGRP-expressing neurons, but not NF-200-expressing neurons, in the absence or presence of Glu. The ability of IGF-1 on CGRP expression may play a role in neurogenic inflammation or nociception.

Preparation of Reusable Porous Carbon Nanofibers from Oxidized Coal Liquefaction Residue for Efficient Adsorption in Water Treatment.

Porous carbon nanofibers are commonly used for adsorption processes owing to their high specific surface area and rich pore structure. However, the poor mechanical properties of polyacrylonitrile (PAN)-based porous carbon nanofibers have limited their applications. Herein, we introduced solid waste-derived oxidized coal liquefaction residue (OCLR) into PAN-based nanofibers to obtain activated reinforced porous carbon nanofibers (ARCNF) with enhanced mechanical properties and regeneration for efficient adsorption of organic dyes in wastewater. This study examined the effects of contact time, concentration, temperature, pH, and salinity on the adsorption capacity. The adsorption processes of the dyes in ARCNF are appropriately described by the pseudo-second-order kinetic model. The maximum adsorption capacity for malachite green (MG) on ARCNF is 2712.84 mg g-1 according to the fitted parameters of the Langmuir model. Adsorption thermodynamics indicated that the adsorptions of the five dyes are spontaneous and endothermic processes. In addition, ARCNF have good regenerative performance, and the adsorption capacity of MG is still higher than 76% after 5 adsorption-desorption cycles. Our prepared ARCNF can efficiently adsorb organic dyes in wastewater, reducing the pollution to the environment and providing a new idea for solid waste recycling and water treatment.

Management of typical VOCs in air with adsorbents: status and challenges.

The serious harm of volatile organic compounds (VOCs) to the ecological environment and human health has attracted widespread attention worldwide. With economic growth and accelerated industrialization, the anthropogenic emissions of VOCs have continued to increase. The most crucial aspect is to choose the appropriate adsorbent, which is very important for the VOCs removal. The search for environmentally friendly VOCs treatment technologies is urgent. The adsorption method is one of the most promising VOCs emission reduction technologies with the advantages of high cost-effectiveness, simple operation, and low energy consumption. One of the most critical aspects is the selection of the appropriate adsorbent, which is very important for the removal of VOCs. This work provides an overview of the sources and hazards of VOCs, focusing on recent research advances in VOCs adsorption materials and the key factors controlling the VOCs adsorption process. A summary of the key challenges and opportunities for each adsorbent is also provided. The adsorption capacity for VOCs is enhanced by an abundant specific surface area; the most efficient adsorption process is achieved when the pore size is slightly larger than the molecular diameter of VOCs; the increase in the number of chemical functional groups contributes to the increase in adsorption capacity. In addition, methods of activation and surface modification to improve the adsorption capacity for VOCs are discussed to guide the design of more advanced adsorbents.

Evaluating the Intracranial Pressure Biofidelity and Response Repeatability of a Physical Head-Brain Model in Frontal Impacts.

Headforms are widely used in head injury research and headgear assessment. Common headforms are limited to replicating global head kinematics, although intracranial responses are crucial to understanding brain injuries. This study aimed to evaluate the biofidelity of intracranial pressure (ICP) and the repeatability of head kinematics and ICP of an advanced headform subjected to frontal impacts. Pendulum impacts were performed on the headform using various impact velocities (1-5 m/s) and impactor surfaces (vinyl nitrile 600 foam, PCM746 urethane, and steel) to simulate a previous cadaveric experiment. Head linear accelerations and angular rates in three axes, cerebrospinal fluid ICP (CSFP), and intraparenchymal ICP (IPP) at the front, side, and back of the head were measured. The head kinematics, CSFP, and IPP demonstrated acceptable repeatability with coefficients of variation generally being less than 10%. The BIPED front CSFP peaks and back negative peaks were within the range of the scaled cadaver data (between the minimum and maximum values reported by Nahum et al.), while side CSFPs were 30.9-92.1% greater than the cadaver data. CORrelation and Analysis (CORA) ratings evaluating the closeness of two time histories demonstrated good biofidelity of the front CSFP (0.68-0.72), while the ratings for the side (0.44-0.70) and back CSFP (0.27-0.66) showed a large variation. The BIPED CSFP at each side was linearly related to head linear accelerations with coefficients of determination greater than 0.96. The slopes for the BIPED front and back CSFP-acceleration linear trendlines were not significantly different from cadaver data, whereas the slope for the side CSFP was significantly greater than cadaver data. This study informs future applications and improvements of a novel head surrogate.

Influence of surrogate scalp material and thickness on head impact responses: Toward a biofidelic head-brain physical model.

Advanced physical head models capable of replicating both global kinematics and intracranial mechanics of the human head are required for head injury research and safety gear assessment. These head surrogates require a complex design to accommodate realistic anatomical details. The scalp is a crucial head component, but its influence on the biomechanical response of such head surrogates remains unclear. This study aimed to evaluate the influence of surrogate scalp material and thickness on head accelerations and intraparenchymal pressures using an advanced physical head-brain model. Scalp pads made from four materials (Vytaflex20, Vytaflex40, Vytaflex50, PMC746) and each material with four thicknesses (2, 4, 6, and 8 mm) were evaluated. The head model attached to the scalp pad was dropped onto a rigid plate from two heights (5 and 19.5 cm) and at three head locations (front, right side, and back). While the selected materials' modulus exhibited a relatively minor effect on head accelerations and coup pressures, the effect of scalp thickness was shown to be major. Moreover, by decreasing the thickness of the head's original scalp by 2 mm and changing the original scalp material from Vytaflex 20 to Vytaflex 40 or Vytaflex 50, the head acceleration biofidelity ratings could improve by 30% and approached the considered rating (0.7) of good biofidelity. This study provides a potential direction for improving the biofidelity of a novel head model that might be a useful tool in head injury research and safety gear tests. This study also has implications for selecting appropriate surrogate scalps in the future design of physical and numerical head models.

Construction of oxygen vacancies and heterostructure in VO2-x/NC with enhanced reversible capacity, accelerated redox kinetics, and stable cycling life for sodium ion storage.

Developing anode materials with high reversible capacity, fast redox kinetics, and stable cycling life for Na+ storage remains a great challenge. Herein, the VO2 nanobelts with oxygen vacancies supported on nitrogen-doped carbon nanosheets (VO2-x/NC) were developed. Benefitting from the enhanced electrical conductivity, the accelerated kinetics, the increased active sites as well as the constructed 2D heterostructure, the VO2-x/NC delivered extraordinary Na+ storage performance in half/full battery. Theoretical calculations (DFT) demonstrated that oxygen vacancies could regulate the adsorption ability for Na+, enhance electronic conductivity, as well as achieve rapid and reversible Na+ adsorption/desorption. The VO2-x/NC exhibited high Na+ storage capacity of 270 mAh g-1 at 0.2 A g-1, and impressive cyclic stability with 258 mAh g-1 after 1800 cycles at 10 A g-1. The assembled sodium-ion hybrid capacitors (SIHCs) could achieve maximum energy density/power output of 122 Wh kg-1/9985 W kg-1, ultralong cycling life with 88.4% capacity retention after 25,000 cycles at 2 A g-1, and practical applications (55 LEDs could be actuated for 10 min), promising to be utilized in a practicable Na+ storage.

A Preliminary Step Towards a Physical Surrogate of the Human Calvarium to Model Fracture.

A surrogate model of the human calvarium can be used to assess skull-fracture-related head injuries without continuously requiring post-mortem human skulls. Skull simulants developed in the literature often require sophisticated manufacturing procedures and/or materials not always practical when factoring in time or expense considerations. This study's objective was to fabricate three exploratory surrogate models (1. pure epoxy prototype, 2. epoxy-chalk mix prototype, and 3. epoxy-chalk three-layered prototype) of the calvarium to mimic the calvarium's mechanical response at fracture using readily available and cost-effective materials, specifically epoxy and chalk. The surrogates and calvaria were subject to quasi-static and dynamic impact 4-point bending and their mechanical responses were compared statistically. Under quasi-static loading, all three surrogates showed a considerable number of differences in mechanical response variables to calvaria that was deemed significant (p < 0.05). Under dynamic impact loading, there was no sufficient evidence to reject that the average mechanical response variables were equal between the epoxy-chalk three-layered prototype and calvaria (p > 0.05). This included force and bending moment at fracture, tensile strain at fracture, tensile and compressive stress at fracture, tensile modulus, and tensile strain rate. Overall, our study illustrates two main remarks: (1) the three exploratory surrogate models are potential candidates for mimicking the mechanical response of the calvarium at fracture during impact loading and (2) employing epoxy and chalk, which are readily available and cost-effective has the potential to mimic the mechanical response of calvaria in impact loading.

Modulation of Ligand Fields in a Single-Atom Site by the Molten Salt Strategy for Enhanced Oxygen Bifunctional Activity for Zinc-Air Batteries.

Achieving full utilization of active sites and optimization of the electronic structure of metal centers is the key to improving the intrinsic activity of single-atom catalysts (SACs) but still remains a challenge to date. Herein, a versatile molten salt-assisted pyrolysis strategy was developed to construct ultrathin, porous carbon nanosheets supported Co SACs. Molten salts are capable of inducing the formation of a Co single-atom and porous graphene-like carbon, which facilitates full exposure of the active center and simultaneously endows the Co SACs with abundant defective Co-N4 configurations. The reported Co SACs deliver an excellent bifunctional activity and good stability for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Moreover, metal-air batteries (MABs) assembled with the Co SACs as air electrode also deliver excellent performance with high power densities of 160 mW·cm-2, large capacities of 760 mAh·g-1, and superior long-term charge/discharge stability, outperforming those of commercial Pt/C+RuO2. DFT theoretical calculation results show that the defects in the second coordination shell (CS) of Co SACs promote desorption of the OH* intermediate for the ORR and facilitate deprotonation of OH* for the OER, which can serve as the favorable active site for oxygen bifunctional catalysts. Our work provides an efficient strategy for the preparation of SACs with fully exposed active centers and optimized electronic structures.

Platinum-Dysprosium Alloys as Oxygen Electrodes in Alkaline Media: An Experimental and Theoretical Study.

Platinum-dysprosium (Pt-Dy) alloys prepared by the arc melting technique are assessed as potential electrodes for the oxygen reduction reaction (ORR) using voltammetry and chronoamperometry in alkaline media. A relatively small change (10 at.%) in the alloy composition brought a notable difference in the alloys' performance for the ORR. Pt40Dy60 electrode, i.e., the electrode with a lower amount of Pt, was identified to have a higher activity towards ORR as evidenced by lower overpotential and higher current densities under identical experimental conditions. Furthermore, DFT calculations point out the unique single-atom-like coordination and electronic structure of Pt atoms in the Pt40Dy60 surface as responsible for enhanced ORR activity compared to the alloy with a higher Pt content. Additionally, Pt-Dy alloys showed activity in the oxygen evolution reaction (OER), with the OER current density lower than that of pure Pt.

Efficacy and safety of Dengyinnaotong Capsule in patients with Cognitive impairment caused by cerebral Small Vessel Disease: study protocol of a multicenter, randomized, open-label, controlled trial (De-CSVD trial).

BACKGROUND: Cerebral small vessel disease (CSVD) is a common syndrome in the older population, with a prevalence ranging from 5% in subjects aged 50 years to almost 100% in those aged 90 years and older. It is regarded to be a major cause of vascular cognitive impairment. Existing prevention and treatment approaches have not yet shown ideal clinical outcomes. Dengyinnaotong Capsule has shown great potential for improving cognitive function. This trial (De-CSVD trial) is designed to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive function in patients with CSVD . METHODS: This multicenter, randomized, open-label, controlled trial is planned to recruit at least 270 patients with mild cognitive impairment related to CSVD in 25 centers in China. Recruitment started on 10 May 2021 and is foreseen to end on 31 December 2022. The final follow-up of participants will be completed by the end of March 2023. Participants will be randomized in a ratio of 1:1 to the experimental group (routine basic treatment plus Dengyinnaotong Capsule) or the control group (routine basic treatment). The primary outcome is the change in the Montreal Cognitive Assessment score from baseline to week 12. Secondary outcomes are changes in Shape Trail Test, Activities of Daily Living, Geriatric Depression Scale, and Dizziness Handicap Inventory score from baseline to week 12, new vascular events, and the changes in serum level of homocysteine, high-sensitivity C-reactive protein, and D-dimer from baseline to week 4 and 12, respectively. The exploratory outcome is the changes in the Tinetti performance-oriented mobility assessment score from baseline to week 12. Safety assessment is performed by monitoring vital signs, general biochemical examinations, 12-lead electrocardiogram examinations, and incidence of cardiovascular and cerebrovascular ischemia or bleeding events. Visits will be performed at week 0 (baseline, pre-randomization), week 4, and week 12 in the treatment period (post-randomization). DISCUSSION: This trial is the first to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive impairment in patients with CSVD. The findings of this study might provide convincing evidence regarding the efficacy of Dengyinnaotong Capsule in patients with mild cognitive impairment related to CSVD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045831. Registered on 25 April 2021.

Neuregulin-1ß prevents Ca(2+) overloading and apoptosis through PI3K/Akt activation in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate.

Neuregulin (NRG) plays an important role on the genesis and differentiation of neurons in the dorsal root ganglion (DRG). Whether NRG-1ß regulates Ca(2+) homeostasis and apoptosis of cultured DRG neurons with excitotoxicity induced by Glu remains unknown. In this study, primary cultured DRG neurons were used to determine the effects of NRG-1ß on Ca(2+) overload and apoptosis of DRG sensory neurons with excitotoxicity induced by Glu. The primary cultured DRG neurons at 48 h of culture age were then exposed to Glu (0.2 mmol/l), Glu (0.2 mmol/l) plus NRG-1ß (20 nmol/l), or Glu (0.2 mmol/l) plus NRG-1ß (20 nmol/l) and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 µmol/l) for additional 12 h. After that, intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated DRG neurons using the fluorescent Ca(2+) indicator fluo-3 was measured by confocal laser scanning microscope. Apoptotic neurons were monitored by Hoechst 33342 staining. Expression of caspase-3, procaspase-3, and pAkt was detected by Western blot assay. Administration of 0.2 mmol/l Glu evoked an increase in [Ca(2+)](i), confirming the excitatory effect of Glu. Compared with the control group, apoptotic (condensed and fragmented nuclei) neurons were observed in Glu-treated cells after Hoechst 33342 staining. The increase caspase-3 of and decrease of procaspase-3 expression levels after administration of 0.2 mmol/l Glu suggested the apoptotic effects of Glu. These effects could be inhibited by the presence of NRG-1ß. The effects of NRG-1ß could be blocked by PI3K inhibitor LY294002. These results implicated that NRG-1ß could prevents Ca(2+) overload and apoptosis by activating PI3K/Akt pathway of primary cultured DRG neurons with excitotoxicity induced by Glu.