TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.

Two Acentric Zn-Based l-Tartrates with Moderate Second Harmonic Generation Responses and Large Birefringence.

The discovery of novel organic-inorganic hybrid nonlinear optical (NLO) crystal materials holds great potential in advancing laser science and technology as they offer a wide range of benefits including easy synthesis, structural versatility, and high hyperpolarizability. Herein, the integration of l-tartaric acid (L-C4H6O6) and ZnSO4 gave rise to two acentric Zn-based organic-inorganic hybrid crystals, namely, Zn2(H2O)2(C4H4O6)2·3H2O (Zn-LT) and Zn2(H2O)(C4H4O6)(C4H6O6)(SO4)·4H2O (Zn-LTS). They both feature layered structures constructed by [ZnO6] octahedron, l-C4H6O6/l-C4H4O62-, water molecule, or [SO4] tetrahedron. Interestingly, they possess moderate second-order NLO effects of 0.28 × KH2PO4 (Zn-LT) and 0.57 × KH2PO4 (Zn-LTS), large birefringence of 0.075 (Zn-LT) and 0.069 (Zn-LTS), suggesting that the introduction of [SO4] groups with intrinsically weak polarizability and weak optical anisotropy induces the enhancement of the NLO effect while without reducing birefringence much. In addition, both of them display UV cutoff edges near 210 nm, indicating their potential as NLO crystals applied in the UV and solar-blind region.

Cpd-A1 alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

Protein acetylation and related potential therapeutic strategies in kidney disease.

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.

Clinical application of COVID-19 vaccine in liver transplant recipients.

BACKGROUND: Solid organ transplant (SOT) activities, such as liver transplant, have been greatly influenced by the pandemic of coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Immunosuppressed individuals of liver transplant recipients (LTRs) tend to have a high risk of COVID-19 infection and related complications. Therefore, COVID-19 vaccination has been recommended to be administered as early as possible in LTRs. DATA SOURCES: The keywords "liver transplant", "SARS-CoV-2", and "vaccine" were used to retrieve articles published in PubMed. RESULTS: The antibody response following the 1st and 2nd doses of vaccination was disappointingly low, and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination. Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer, a proportion of patients remained unresponsive. Furthermore, recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs, including allograft rejection and liver injury. CONCLUSIONS: This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine, risk factors for poor serological response and adverse events after vaccination.

Performance Evaluation Method for Intelligent Computing Components for Space Applications.

The computational performance requirements of space payloads are constantly increasing, and the redevelopment of space-grade processors requires a significant amount of time and is costly. This study investigates performance evaluation benchmarks for processors designed for various application scenarios. It also constructs benchmark modules and typical space application benchmarks specifically tailored for the space domain. Furthermore, the study systematically evaluates and analyzes the performance of NVIDIA Jetson AGX Xavier platform and Loongson platforms to identify processors that are suitable for space missions. The experimental results of the evaluation demonstrate that Jetson AGX Xavier performs exceptionally well and consumes less power during dense computations. The Loongson platform can achieve 80% of Xavier's performance in certain parallel optimized computations, surpassing Xavier's performance at the expense of higher power consumption.

Regulated Ion/Electron-Conducting Interphase Enables Stable Zinc-Metal Anodes for Aqueous Zinc-Ions Batteries.

Metallic Zinc (Zn) is considered as a remarkably promising anode for aqueous Zn-ion batteries due to its high volumetric capacity and low redox potential. Unfortunately, dendritic growth and severe side reactions destabilizes the electrode/electrolyte interface, and ultimately reduce the electrochemical performance. Here, an artificial protective layer (APL) with a regulated ion and electron-conducting interphase is constructed on the Zn-metal anode to provide excellent interfacial stability in high-rate cycling. The superior ionic and moderate electronic conductivity of the APL derives from the co-embedding of MXene and Zn(CF3 SO3 )2 salts into the polyvinyl alcohol hydrogel, which enables a synergistic effect of local current density reduction during plating and ion transport acceleration during stripping for Zn anode. Furthermore, the high Young's modulus of the protective layer and dendrite-free deposition morphology during cycling suppresses hydrogen evolution reactions (2.5 mmol h-1 cm-2 ) and passivation. As a result, in symmetrical cell tests, the modified battery presents a stable life of over 2000 cycles at ultra-high current density of 20 mA cm-2 . This research presents a new insight into the formation and regulation of stable electrode-electrolyte interface for the Zn-metal anode.

Insight on Cathodes Chemistry for Aqueous Zinc-Ion Batteries: From Reaction Mechanisms, Structural Engineering, and Modification Strategies.

By virtue of low cost, eco-friendliness, competitive gravimetric energy density, and intrinsic safety, more and more attention has increasingly focused on aqueous zinc ion batteries (AZIBs) as a promising alternative for scalable energy storage. However, plagued by a complex interfacial process, sluggish dynamics, lability of electrodes and electrolytes, insufficient energy density, and poor cycle life heavily restrict practical applications of AZIBs, indicating that profound understandings on cathode storage chemistry are necessarily needed. Hence, this paper comprehensively summarizes recent advance in cathodes with critical insight on the energy storage mechanism. Furthermore, the issues and challenges for high-performance cathodes are meticulously explored, presenting inspiring structural engineering and modification strategies. Finally, rational evaluations on representative cathodes are rendered, suggesting the potential development direction of AZIBs.

A Quasi-Randomized Controlled Trial of an Integrated Healthcare Model for Patients with Coronary Heart Disease.

Background: An increasing number of coronary heart disease (CHD) patients with an aging population are demanding available and effective out-of-hospital continuous healthcare services. However, great efforts still need to be made to promote out-of-hospital healthcare services for better CHD secondary prevention. This study aims to evaluate the effectiveness of a hospital-community-family (HCF)-based integrated healthcare model on treatment outcomes, treatment compliance, and quality of life (QoL) in CHD patients. Methods: A quasi-randomized controlled trial was conducted at the Department of Cardiology, a tertiary A-level hospital, Wuhan, China from January 2018 to January 2020 in accordance with the Consolidated Standards of Reporting Trials guidelines. CHD patients were enrolled from the hospital and quasi-randomly assigned to either HCF-based integrated healthcare model services or conventional healthcare services. The treatment outcomes and QoL were observed at the 12-month follow-up. Treatment compliance was observed at the 1-month and 12-month follow-ups. Results: A total of 364 CHD patients were quasi-randomly assigned to either integrated healthcare model services (n = 190) or conventional healthcare services (n = 174). Treatment outcomes including relapse and readmission rate (22.6% vs 41.9%; relative risk [RR] = 0.54; 95% confidence interval [CI], 0.40-0.74; p = 0.0031), the occurrence of major cardiovascular events (19.5% vs 45.4%; RR = 0.43; 95% CI, 0.30-0.59; p = 0.0023), complication rate (19.5% vs 35.0%; RR = 0.56; 95% CI, 0.39-0.79; p = 0.0042), and the control rate of CHD risk factors (p < 0.05, average p = 0.009) at the 12-month follow-up in the intervention group were better than those of the control group. There was no significant difference in treatment compliance at the 1-month follow-up between groups (p > 0.05, average p = 0.872). Treatment compliance at the 12-month follow-up in the intervention group, including correct medication, reasonable diet, adherence to exercise, emotional control, self-monitoring, and regular re-examination, was higher than that of the control group (p < 0.05, average p = 0.007). No difference was found in the compliance with smoking cessation and alcohol restriction at the 12-month follow-up between groups (p = 0.043). QoL at the 12-month follow-up in the intervention group was better than that of the control group (86.31 ± 9.39 vs 73.02 ± 10.70, p = 0.0048). Conclusions: The integrated healthcare model effectively improves treatment outcomes, long-term treatment compliance, and QoL of patients, and could be implemented as a feasible strategy for CHD secondary prevention.

Diagnostic Value of Procalcitonin and Interleukin-6 on Early Postoperative Pneumonia after Adult Cardiac Surgery: A Prospective Observational Study.

BACKGROUND: Postoperative pneumonia (PP) is the most common primary infection after cardiac surgery, increasing the hospitalization expense and causing the consumption of healthcare resources. This study aimed to investigate the diagnostic value of procalcitonin (PCT) and interleukin-6 (IL-6) on early postoperative pneumonia after adult cardiac surgery. METHODS: In this prospective observational study, patients with pneumonia and age- and sex-matched cases in our center from October 10, 2020 to January 31, 2021 were included. Patients diagnosed with pneumonia in this study needed meet both clinical and microbiological diagnostic criteria. Blood samples were collected in all patients from postoperative day (POD) 1 to postoperative day 5 to detect PCT, IL-6, white blood cell count, and C-reactive protein. The diagnostic performance of different biomarkers was evaluated by the receiver operating characteristic curves and the area under the curves. RESULTS: Our study enrolled 272 patients, including 24 patients with postoperative pneumonia and 248 age- and sex-matched cases. From POD1 to POD5, the absolute value of PCT and PCT variations showed diagnostic significance for pneumonia (P < .05); the diagnostic value of the absolute value of IL-6 and IL-6 variations was not satisfying. White blood cell count showed no differences; C-reactive protein had no diagnostic value before POD4. Multivariable logistic regression showed that PCT variation and IL-6 variation from POD3 to POD1 were the strongest risk factors for postoperative pneumonia [OR:12.50, 95% CI: (3.40-45.5); OR:13.71, 95% CI: (1.11-168.47)]. According to the above results, we defined the PL Index. PL Index showed the best diagnostic value among those biomarkers in POD3 [AUC: 0.90, 95% CI: (0.79-0.95)]. Multivariable logistic regression showed PL Index POD3 has significant correlation with postoperative pneumonia [OR:1.23, 95% CI: (1.11-1.37), P = .041]. CONCLUSIONS: PCT variation and IL-6 were more accurate than C-reactive protein and white blood cell count to predict early postoperative pneumonia, but the diagnostic properties of PCT could not be observed during the first three postoperative days due to the inflammatory process. By combining the variations of PCT and IL-6, we defined the PL Index, which shows the best diagnostic ability on early postoperative pneumonia after adult cardiac surgery.

Cobalt Selenide Hollow Polyhedron Encapsulated in Graphene for High-Performance Lithium/Sodium Storage.

Owing to the high specific capacities, high electrochemical activity, and various electronic properties, transition metal selenides are considered as promising anodes for lithium- and sodium-ion storage. However, poor electronic conductivity and huge volume expansion during cycling are still responsible for their restricted electrochemical performance. Herein, CoSe hollow polyhedron anchoring onto graphene (CoSe/G) is synthesized by self-assembly and subsequent selenization. In CoSe/G composites, the CoSe nanoparticles, obtained by in situ selenization of metal-organic frameworks (MOFs) in high temperature, are distributed among graphene sheets, realizing N element doping, developing robust heterostructures with a chemical bond. The unique architecture ensures the cohesion of the structure and endorses the reaction kinetics for metal ions, identified by in situ and ex situ testing techniques, and kinetics analysis. Thus, the CoSe/G anodes achieve excellent cycling performance (1259 mAh g-1 at 0.1 A g-1 after 300 cycles for lithium storage; 214 mAh g-1 at 2 A g-1 after 600 cycles for sodium storage) and rate capability (732 mAh g-1 at 5 A g-1 for lithium storage; 290 mAh g-1 at 5 A g-1 for sodium storage). The improved electrochemical performance for alkali-ion storage provides new insights for the construction of MOFs derivatives toward high-performance storage devices.

Preliminary single-center experience of Helicobacter pylori eradication among the liver transplant recipients.

OBJECTIVE: To investigate the prevalence of Helicobacter pylori infection among orthotopic liver transplant (LT) recipients and explore the efficacy and safety of H. pylori eradication therapy. METHODS: Liver transplant recipients receiving regular follow-up in our center were assessed by 13C-urea breath test between February 2018 and July 2020. A group of healthy tested patients were selected as control group at a rate of 1:3. All LT recipients with H. pylori were recommended to receive eradication therapy with bismuth-containing quadruple therapy (BQT), which included esomeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + bismuth 220 mg, twice daily for 14 days. RESULTS: The prevalence of H. pylori infection among the LT recipients was 19.6% (30/153), which was significantly lower than the control group (30/153 [19.6%] vs. 200/459 [43.6%], p < 0.001). In LT recipients who received transplantation at <1 year, 1-3 years, and >3 years, the prevalence of H. pylori infection was 10.6% (5/47), 17.5% (10/57), and 30.6% (15/49), respectively, which increased with the time after transplantation (p = 0.04). With BQT, the eradication rate of H. pylori was 91.3% (21/23). During the process of eradication, the blood trough concentration of immunosuppressants increased from 1.7 to 3.6 times, and reducing the dose of the drugs to one-third of what they were before the eradication therapy could avoid excessively elevated concentration of immunosuppressants. Adverse effects occurred in 55.2% (11/23), of the LT recipients and 21.0% (42/200) of the control group (p < 0.01), which was probably caused by the increased blood concentration of immunosuppressants. Normal liver function was observed, while transient abnormal kidney function was occurred in one recipient. CONCLUSION: The prevalence of H. pylori infection was 19.6% among the LT recipients, which increased with the postoperative time. With BQT, H. pylori eradication was safe and effective in LT recipients.

Chronic atrophic gastritis and Helicobacter pylori infection status in liver transplant recipients.

AIM: To investigate the abnormalities of the upper gastrointestinal tract in liver transplant (LT) recipients, especially the prevalence of Helicobacter pylori infection and the incidence of chronic atrophic gastritis (CAG), and to explore the efficacy and safety of H pylori eradication treatment. METHODS: Endoscopic screening was performed prospectively on LT recipients who received regular follow-up in our center. A group of healthy subjects with same age and sex was selected as a control group at a ratio of 1:3 with propensity score matching. All H pylori-positive recipients received Bismuth-containing quadruple therapy (esomeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + bismuth 220 mg, all of the medicines were applied twice daily, for 14 days). RESULT: The prevalence of H pylori infection was significantly lower in LT group than control group [12/102 (11.8%) vs 98/306 (32.0%), P < .001], whereas the prevalence of CAG was similar between the two groups [48/102 (47.1%) vs 138/306 (45.1%), P = .731]. Meanwhile, the incidence of reflux esophagitis [18/102 (17.6%) vs 31/306 (10.1%), P = .043] and bile regurgitation [19/102 (18.6%) vs 30/306 (9.8%), P = .018] were higher in LT group. No correlation between the incidence of upper gastroduodenal abnormalities and postoperative time after liver transplantation was found. The success rate of H pylori eradication therapy was 100% (10/10). The blood concentration of immunosuppressants was 1.7-3.6 times above baseline values during H pylori eradication therapy; however, no severe adverse effects were observed during the proceed with dose adjustments of the immunosuppressants. CONCLUSION: Although the prevalence of H pylori infection was lower in LT recipients than in control subjects, the prevalence of CAG was like that of the general population. H pylori eradication therapy was safe and effective after liver transplantation in our preliminary study.

[Research advances of Zaoren Anshen prescription preparations].

Zaoren Anshen prescription preparations(ZRASs), which are prepared from three traditional Chinese herb medicines, namely fried Zizyphi Spinosae Semen, Salvia Miltiorrhizae Radix et Rhizoma and vinegar-processed Schisandrae Chinensis Fructus, are a series of proprietary Chinese medicines for the treatment of insomnia, amnesia and dizzy in clinic. In recent years, pharmacodynamic effect, chemical constituents and quality control of ZRASs had been extensively studied for the purpose of ensuring their safety, efficacy and stability, and a great progress had been made. However, there is no review of the research advance of ZRASs up to date. The present review summarized the research advance of ZRASs in quality control standards, chemical constituents, pharmacodynamic effects, and chemical analysis for the first time, with the aim to provide a reference for further studies on the effective constituents and quality control of ZRASs.

BMAL1 Disrupted Intrinsic Diurnal Oscillation in Rat Cerebrovascular Contractility of Simulated Microgravity Rats by Altering Circadian Regulation of miR-103/CaV1.2 Signal Pathway.

The functional and structural adaptations in cerebral arteries could be one of the fundamental causes in the occurrence of orthostatic intolerance after space flight. In addition, emerging studies have found that many cardiovascular functions exhibit circadian rhythm. Several lines of evidence suggest that space flight might increase an astronaut's cardiovascular risks by disrupting circadian rhythm. However, it remains unknown whether microgravity disrupts the diurnal variation in vascular contractility and whether microgravity impacts on circadian clock system. Sprague-Dawley rats were subjected to 28-day hindlimb-unweighting to simulate the effects of microgravity on vasculature. Cerebrovascular contractility was estimated by investigating vasoconstrictor responsiveness and myogenic tone. The circadian regulation of CaV1.2 channel was determined by recording whole-cell currents, evaluating protein and mRNA expressions. Then the candidate miRNA in relation with Ca2+ signal was screened. Lastly, the underlying pathway involved in circadian regulation of cerebrovascular contractility was determined. The major findings of this study are: (1) The clock gene BMAL1 could induce the expression of miR-103, and in turn modulate the circadian regulation of CaV1.2 channel in rat cerebral arteries at post-transcriptional level; and (2) simulated microgravity disrupted intrinsic diurnal oscillation in rat cerebrovascular contractility by altering circadian regulation of BMAL1/miR-103/CaV1.2 signal pathway.

Mechanisms for therapeutic effect of bulleyaconitine A on chronic pain.

Bulleyaconitine A, a diterpenoid alkaloid isolated from Aconitum bulleyanum plants, has been used for the treatment of chronic pain in China since 1985. Clinical studies show that the oral administration of bulleyaconitine A is effective for treating different kinds of chronic pain, including back pain, joint pain, and neuropathic pain with minimal side effect in human patients. The experimental studies have revealed that bulleyaconitine A at therapeutic doses potently inhibits the peripheral sensitization and central sensitization that underlie chronic pain and has no effect on acute pain. Bulleyaconitine A preferably blocks tetrodotoxin-sensitive voltage-gated sodium channels in dorsal root ganglion neurons by inhibition of protein kinase C, and the effect is around 600 times more potent in neuropathic animals than in naïve ones. Bulleyaconitine A at 5 nM inhibits the hypersensitivity of dorsal root ganglion neurons in neuropathic rats but has no effect on excitability of dorsal root ganglion neurons in sham group. Bulleyaconitine A inhibits long-term potentiation at C-fiber synapses in spinal dorsal horn, a synaptic model of pathological pain, preferably in neuropathic pain rats over naïve rats. The following mechanisms may underlie the selective effect of bulleyaconitine A on chronic pain. (1) In neuropathic conditions, protein kinase C and voltage-gated sodium channels in dorsal root ganglion neurons are upregulated, which enhances bulleyaconitine A's effect. (2) Bulleyaconitine A use-dependently blocks voltage-gated sodium channels and therefore inhibits the ectopic discharges that are important for neuropathic pain. (3) Bulleyaconitine A is shown to inhibit neuropathic pain by the modulation of spinal microglia, which are involved in the chronic pain but not in acute (nociceptive) pain. Moreover, bulleyaconitine A facilitates the anesthetic effect of morphine and inhibits morphine tolerance in rats. Together, bulleyaconitine A is able to inhibit chronic pain by targeting at multiple molecules. Further clinical and experimental studies are needed for evaluating the efficacy of bulleyaconitine A in different forms of chronic pain in patients and for exploring the underlying mechanisms.

Bulleyaconitine A attenuates hyperexcitability of dorsal root ganglion neurons induced by spared nerve injury: The role of preferably blocking Nav1.7 and Nav1.3 channels.

Background Oral administration of Bulleyaconitine A, an extracted diterpenoid alkaloid from Aconitum bulleyanum plants, is effective for treating chronic pain in rats and in human patients, but the underlying mechanisms are poorly understood. Results As the hyperexcitability of dorsal root ganglion neurons resulting from the upregulation of voltage-gated sodium (Nav) channels has been proved critical for development of chronic pain, we tested the effects of Bulleyaconitine A on Nav channels in rat spared nerve injury model of neuropathic pain. We found that Bulleyaconitine A at 5 nM increased the threshold of action potentials and reduced the firing rate of dorsal root ganglion neurons in spared nerve injury rats but not in sham rats. Bulleyaconitine A preferably blocked tetrodotoxin-sensitive Nav channels over tetrodotoxin-resistant ones in dorsal root ganglion neurons of spared nerve injury rats. Bulleyaconitine A was more potent for blocking Nav1.3 and Nav1.7 than Nav1.8 in cell lines. The half maximal inhibitory concentration (IC50) values for resting Nav1.3, Nav1.7, and Nav1.8 were 995.6 ± 139.1 nM, 125.7 ± 18.6 nM, and 151.2 ± 15.4 µM, respectively, which were much higher than those for inactivated Nav1.3 (20.3 ± 3.4 pM), Nav1.7 (132.9 ± 25.5 pM), and Nav1.8 (18.0 ± 2.5 µM). The most profound use-dependent blocking effect of Bulleyaconitine A was observed on Nav1.7, less on Nav1.3, and least on Nav1.8 at IC50 concentrations. Bulleyaconitine A facilitated the inactivation of Nav channels in each subtype. Conclusions Preferably blocking tetrodotoxin-sensitive Nav1.7 and Nav1.3 in dorsal root ganglion neurons may contribute to Bulleyaconitine A's antineuropathic pain effect.

A Chemical Precipitation Method Preparing Hollow-Core-Shell Heterostructures Based on the Prussian Blue Analogs as Cathode for Sodium-Ion Batteries.

Prussian blue and its analogs are regarded as the promising cathodes for sodium-ion batteries (SIBs). Recently, various special structures are constructed to improve the electrochemical properties of these materials. In this study, a novel architecture of Prussian blue analogs with large cavity and multilayer shells is investigated as cathode material for SIBs. Because the hollow structure can relieve volume expansion and core-shell heterostructure can optimize interfacial properties, the complex structure materials exhibited a highly initial capacity of 123 mA h g-1 and a long cycle life. After 600 cycles, the reversible capacity of the electrode still maintains at 102 mA h g-1 without significant voltage decay, indicating a superior structure stability and sodium storage kinetics. Even at high current density of 3200 mA g-1 , the electrode still delivers a considerable capacity above 52 mA h g-1 . According to the electrochemical analysis and ex-situ measurements, it can be inferred that the enhanced apparent diffusion coefficient and improved insertion/extraction performance of electrode have been obtained by building this new morphology.

Upregulation of N-type calcium channels in the soma of uninjured dorsal root ganglion neurons contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury.

N-type voltage-gated calcium (Cav2.2) channels are expressed in the central terminals of dorsal root ganglion (DRG) neurons, and are critical for neurotransmitter release. Cav2.2 channels are also expressed in the soma of DRG neurons, where their function remains largely unknown. Here, we showed that Cav2.2 was upregulated in the soma of uninjured L4 DRG neurons, but downregulated in those of injured L5 DRG neurons following L5 spinal nerve ligation (L5-SNL). Local application of specific Cav2.2 blockers (ω-conotoxin GVIA, 1-100 µM or ZC88, 10-1000 µM) onto L4 and 6 DRGs on the operated side, but not the contralateral side, dose-dependently reversed mechanical allodynia induced by L5-SNL. Patch clamp recordings revealed that both ω-conotoxin GVIA (1 µM) and ZC88 (10 µM) depressed hyperexcitability in L4 but not in L5 DRG neurons of L5-SNL rats. Consistent with this, knockdown of Cav2.2 in L4 DRG neurons with AAV-Cav2.2 shRNA substantially prevented L5-SNL-induced mechanical allodynia and hyperexcitability of L4 DRG neurons. Furthermore, in L5-SNL rats, interleukin-1 beta (IL-1ß) and IL-10 were upregulated in L4 DRGs and L5 DRGs, respectively. Intrathecal injection of IL-1ß induced mechanical allodynia and Cav2.2 upregulation in bilateral L4-6 DRGs of naïve rats, whereas injection of IL-10 substantially prevented mechanical allodynia and Cav2.2 upregulation in L4 DRGs in L5-SNL rats. Finally, in cultured DRG neurons, Cav2.2 was dose-dependently upregulated by IL-1ß and downregulated by IL-10. These data indicate that the upregulation of Cav2.2 in uninjured DRG neurons via IL-1ß over-production contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury.