Photoresponsive Biomimetic Functions by Light-Driven Molecular Motors in Three Dimensionally Printed Liquid Crystal Elastomers.

Despite the fascinating developments in design and synthesis of artificial molecular machines operating at the nanoscales, translating molecular motion along multiple length scales and inducing mechanical motion of a three-dimensional macroscopic entity remains an important challenge. The key to addressing this amplification of motion relies on the effective organization of molecular machines in a well-defined environment. By taking advantage of long-range orientational order and hierarchical structures of liquid crystals and unidirectional rotation of light-driven molecular motors, we report here photoresponsive biomimetic functions of liquid crystal elastomers (LCEs) by the repetitive unidirectional rotation of molecular motors using 3D printing. Molecular motors were built in the main chain of liquid crystals oligomers to serve as photoactuators. The oligomers were then used as the ink, and liquid crystal elastomers with different morphologies were printed. The obtained LCEs are able to conduct multiple types of motions including bending, helical coiling, closing of petals, and flipping of wings of a butterfly upon UV illumination, which paves the way for future design of responsive materials with enhanced complex actuating functions.

Photo-responsive functional materials based on light-driven molecular motors.

In the past two decades, the research and development of light-triggered molecular machines have mainly focused on developing molecular devices at the nanoscale. A key scientific issue in the field is how to amplify the controlled motion of molecules at the nanoscale along multiple length scales, such as the mesoscopic or the macroscopic scale, or in a more practical perspective, how to convert molecular motion into changes of properties of a macroscopic material. Light-driven molecular motors are able to perform repetitive unidirectional rotation upon irradiation, which offers unique opportunities for responsive macroscopic systems. With several reviews that focus on the design, synthesis and operation of the motors at the nanoscale, photo-responsive macroscopic materials based on light-driven molecular motors have not been comprehensively summarized. In the present review, we first discuss the strategy of confining absolute molecular rotation into relative rotation by grafting motors on surfaces. Secondly, examples of self-assemble motors in supramolecular polymers with high internal order are illustrated. Moreover, we will focus on building of motors in a covalently linked system such as polymeric gels and polymeric liquid crystals to generate complex responsive functions. Finally, a perspective toward future developments and opportunities is given. This review helps us getting a more and more clear picture and understanding on how complex movement can be programmed in light-responsive systems and how man-made adaptive materials can be invented, which can serve as an important guideline for further design of complex and advanced responsive materials.

The characterization and analysis of the compound hemostatic cotton based on Ca2+/poly (vinyl alcohol)/soluble starch-fish skin collagen.

Accidental bleeding is an unavoidable problem in daily life. To avoid the risk of excessive blood loss, it is urgent to design a functional material that can quickly stop bleeding. In this study, an efficient wound dressing for hemostasis was investigated. Based on the characteristics that Ca2+ and fish skin collagen (FSC) could activate the coagulation mechanism, hemostatic cotton was prepared by solvent replacement method using CaCl2, FSC, soluble starch (SS), and polyvinyl alcohol (PVA) as raw materials. The cytotoxicity test showed the Ca2+PVA/FSC-SS hemostatic cottons had good biocompatibility. The activated partial thromboplastin time (APTT) of Ca2+PVA/FSC-SS(4) was 35.34 s, which was 22.07 s faster than that of PVA/FSC-SS, indicating Ca2+PVA/FSC-SS mediated the endogenous coagulation system. In vitro coagulation test, Ca2+PVA/FSC-SS(4) could stop bleeding rapidly within 39.60 ± 5.16 s, and the ability of wound healing was higher than commercial product (Celox). This study developed a rapid procoagulant and hemostatic material, which had a promising application in a variety of environments.

The changes of different restriction level adjustments on antibiotic use in China.

This quasi-experimental study aimed to investigate the changes in antibiotic use tailored by adjusting provincial antibiotic restriction lists in China using interrupted time-series analysis from 2013 to 2019. Antibiotic use was assessed as defined daily dose (DDD) per 1000 patients per day. Trends and level changes were analysed with segmented regression. The study identified 19 antibiotic formulations in four provinces with adjusted restriction levels (intervention group) and 110 formulations in the rest provinces without adjustments (comparison group). Antibiotics restriction level changed between two categories: (1) between 'highly-restricted' and 'restricted' and (2) between 'restricted' and 'non-restricted'. Analysis revealed distinct trend changes for antibiotics moving between 'highly-restricted' and 'restricted' (ß = 0.0211, P = 0.003) and 'restricted' to 'highly-restricted' (ß = -0.0039, P = 0.128) compared to the comparison group. After a 2-y adjustment period, when moving from 'restricted' to 'highly-restricted', absolute antibiotic utilisation significantly decreased (P < 0.001), with a relative decrease of 100.8% (P < 0.001) compared to the comparison group. Besides, individual antibiotics with higher consumption displayed greater responsiveness to adjustment. These findings underscore the changes in restriction level adjustments on antibiotics, highlighting antibiotic restriction list policies as crucial tools for antimicrobial stewardship.

Redox-Responsive Lipidic Prodrug Nano-Delivery System Improves Antitumor Effect of Curcumin Derivative C210.

The poor bioavailability of curcumin and its derivatives limits their antitumor efficacy and clinical translation. Although curcumin derivative C210 has more potent antitumor activity than curcumin, it has a similar deficiency to curcumin. In order to improve its bioavailability and accordingly enhance its antitumor activity in vivo, we developed a redox-responsive lipidic prodrug nano-delivery system of C210. Briefly, we synthesized three conjugates of C210 and oleyl alcohol (OA) via different linkages containing single sulfur/disulfide/carbon bonds and prepared their nanoparticles using a nanoprecipitation method. The prodrugs required only a very small amount of DSPE-PEG2000 as a stabilizer to self-assemble in aqueous solution to form nanoparticles (NPs) with a high drug loading capacity (~50%). Among them, the prodrug (single sulfur bond) nanoparticles (C210-S-OA NPs) were the most sensitive to the intracellular redox level of cancer cells; therefore, they could rapidly release C210 in cancer cells and thus had the strongest cytotoxicity to cancer cells. Furthermore, C210-S-OA NPs exerted a dramatic improvement in its pharmacokinetic behavior; that is, the area under the curve (AUC), mean retention time and accumulation in tumor tissue were 10, 7 and 3 folds that of free C210, respectively. Thus, C210-S-OA NPs exhibited the strongest antitumor activity in vivo than C210 or other prodrug NPs in mouse models of breast cancer and liver cancer. The results demonstrated that the novel prodrug self-assembled redox-responsive nano-delivery platform was able to improve the bioavailability and antitumor activity of curcumin derivative C210, which provides a basis for further clinical applications of curcumin and its derivatives.

Nanoplastics impacts on Thiobacillus denitrificans: Effects of size and dissolved organic matter.

The widespread distribution of nanoplastics and dissolved organic matter (DOM) in sewage raises concerns about the potential impact of DOM on the bioavailability of nanoplastics. In this study, the effects of different sizes (100 nm and 350 nm) of polystyrene nanoplastics (PS-NPs, 50 mg/L) and combined with 10 mg/L or 50 mg/L DOMs (fulvic acid, humic acid and sodium alginate) on the growth and denitrification ability of Thiobacillus denitrificans were investigated. Results showed that 100 nm PS-NPs (50 mg/L) cause a longer delay in the nitrate reduction (3 days) of T. denitrificans than 350 nm PS-NPs (2 days). Furthermore, the presence of DOM exacerbated the adverse effect of 100 nm PS-NPs on denitrification, resulting in a delay of 1-4 days to complete denitrification. Fulvic acid (50 mg/L) and humic acid (50 mg/L) had the most significant adverse effect on increasing 100 nm PS-NPs (50 mg/L), causing a reduction of 20 mmol/L nitrate by T. denitrificans in nearly 7 days. It is noteworthy that the presence of DOM did not modify the adverse effect of 350 nm PS-NPs on denitrification. Further analysis of toxicity mechanism of PS-NPs revealed that they could induce reactive oxygen species (ROS) and suppressed denitrification gene expression. The results suggested that DOM may assist in the cellular internalization of PS-NPs by inhibiting PS-NPs aggregation, leading to the increased ROS levels and accelerated T. denitrificans death. This study highlights the potential risk of nanoplastics to autotrophic denitrifying bacteria in the presence of DOM and provides new insights for the treatment of nitrogen-containing wastewater by T. denitrificans.

Albumin-encapsulated HSP90-PROTAC BP3 nanoparticles not only retain protein degradation ability but also enhance the antitumour activity of BP3 in vivo.

Proteolysis-targeting chimaera (PROTAC) has received extensive attention in industry. However, there are still some limitations that hinder its further development. In a previous study, our group first demonstrated that the HSP90 degrader BP3 synthesised by the principle of PROTACs showed therapeutic potential for cancer. However, its application was hindered by its high molecular weight and water insolubility. Herein, we aimed to improve these properties of HSP90-PROTAC BP3 by encapsulating it into human serum albumin nanoparticles (BP3@HSA NPs). The results demonstrated that BP3@HSA NPs showed a uniform spherical shape with a size of 141.01 ± 1.07 nm and polydispersity index < 0.2; moreover, BP3@HSA NPs were more readily taken up by breast cancer cells and had a stronger inhibitory effect in vitro than free BP3. BP3@HSA NPs also demonstrated the ability to degrade HSP90. Mechanistically, the improved inhibitory effect of BP3@HSA NPs on breast cancer cells was related to its stronger ability to induce cell cycle arrest and apoptosis. Furthermore, BP3@HSA NPs improved PK properties and showed stronger tumour suppression in mice. Taken together, this study demonstrated that hydrophobic HSP90-PROTAC BP3 nanoparticles encapsulated by human serum albumin could improve the safety and antitumour efficacy of BP3.

Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis.

INTRODUCTION: Lipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated. OBJECTIVES: Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3). METHODS: Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting. RESULTS: Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect. CONCLUSIONS: All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.

Microbial reduction of schwertmannite by co-cultured iron- and sulfate-reducing bacteria.

Schwertmannite (Sch) is an iron-hydroxysulfate mineral commonly found in acid mine drainage contaminated environment. The transformation mechanism of Sch mediated by pure cultured iron-reducing bacteria (FeRB) or sulfate-reducing bacteria (SRB) has been studied. However, FeRB and SRB widely coexist in the environment, the mechanism of Sch transformation by the consortia of FeRB and SRB is still unclear. This study investigated the Sch reduction by co-cultured Shewanella oneidensis (FeRB) and Desulfosporosinus meridiei (SRB). The results showed that co-culture of FeRB and SRB could accelerate the reductive dissolution of Sch, but not synergistically, and there were two distinct phases in the reduction of Sch mediated by FeRB and SRB: an initial phase in which FeRB predominated and Fe3+ in Sch was reduced, accompanied with the release of SO42-, and the detected secondary minerals were mainly vivianite; the second phase in which SRB predominated and mediated the reduction of SO42-, producing minerals including mackinawite and siderite in addition to vivianite. Compared to pure culture, the abundance of FeRB and SRB in the consortia decreased, and more minerals aggregated inside and outside the cell; correspondingly, the transcription levels of genes (cymA, omcA, and mtrCBA) related to Fe3+ reduction in co-culture was down-regulated, while the transcription levels of SO42--reducing genes (sat, aprAB, dsr(C)) was generally up-regulated. These phenomena suggested that secondary minerals produced in co-culture limited but did not inhibit bacterial growth, and the presence of SRB was detrimental to dissimilatory Fe3+ reduction, while existed FeRB was in favor of dissimilatory SO42- reduction. SRB mediated SO42- reduction by up-regulating the expression of SO42- reduction-related genes when its abundance was limited, which may be a strategy to cope with external coercion. These findings allow for a better understanding of the process and mechanism of microbial mediated reduction of Sch in the environment.

DNA methylation: The epigenetic mechanism of Alzheimer's disease.

Nowadays, with the development of the social health care system, there is an increasing trend towards an aging society. The incidence of Alzheimer's disease (AD) is also on the rise. AD is a kind of neurodegenerative disease that can be found in any age group. For years, scientists have been committing to discovering the cause of AD. DNA methylation is one of the most common epigenetic mechanisms in mammals and plays a vital role in the pathogenesis of several diseases, including tumors. Studying chemical changes in the epigenome, or DNA methylation can help us understand the effects of our environment and life on diseases, such as smoking, depression, and menopause, which may affect people's chances of developing Alzheimer's or other diseases. Recent studies have identified some crucial genes like ANK1, RHBDF2, ABCA7, and BIN1, linking DNA methylation to AD. This review focuses on elucidating the relationship between DNA methylation and the pathogenesis of AD and provides an outlook on possible targeted therapeutic modalities.

A multi-center, randomized, double-blinded, parallel, placebo-controlled study to assess the efficacy and safety of Shenqisuxin granule in complex coronary artery disease after PCI: Study protocol.

Introduction: The Shenqisuxin granule (SQSX), a novel Chinese herbal formula, has the effect of preventing in-stent restenosis and improving angiogenesis. We intend to evaluate the efficacy and safety of SQSX to provide a possible therapeutic strategy for complex coronary artery disease (CCAD) after percutaneous coronary intervention (PCI). Methods/design: The study is a multi-center, randomized, double-blinded, parallel, placebo-controlled trial. A total of 120 participants will be randomized 1:1 into the intervention group and the control group. Based on standardized treatment, the intervention group and control group will receive SQSX and placebo for 2 months, respectively. The primary outcomes, metabolic equivalents (METS) and peak oxygen uptake (Peak VO2), and the secondary outcomes, including other indicators of cardiorespiratory fitness (CRF), the European Quality of Life Questionnaire (EQ-5D-5L), the Seattle Angina Scale (SAQ), etc., will be assessed at baseline and 2 months ± 3 days. In addition, the survey scales will also be tested at 1 month ± 3 days. Trimethylamine N-oxide (TMAO), high-sensitivity C-reactive protein (hs-CRP), and gut microbiota features will be assessed at baseline and 2 months ± 3 days to probe possible mechanism. The major adverse cardiac and cerebrovascular events (MACCE) and bleeding events will be monitored until the 12-month follow-up. Discussion: This study is launched to assess the efficacy and safety of SQSX in CCAD after PCI and probe the possible mechanism. Clinical trial registration: China Clinical Trial Registry, ChiCTR2200060979, Registered on June 14, 2022.

Trends of Fixed-Dose Combination Antibiotic Consumption in Hospitals in China: Analysis of Data from the Center for Antibacterial Surveillance, 2013-2019.

Background: Fixed-dose combination (FDC) antibiotics can be clinically inappropriate and are concerning with regards to antimicrobial resistance, with little usage data available in low- and middle-income countries. Methods: Based on retrospective data from the Center for Antibacterial Surveillance, we investigated the consumption of FDC antibiotics in hospital inpatient settings in China from 1 January 2013 to 31 December 2019. The metric for assessing antibiotic consumption was the number of daily defined doses per 100 bed days (DDD/100BDs). FDC antibiotics were classified according to their composition and the Access, Watch, Reserve (AWaRe) classification of the World Health Organization. Results: A total of 24 FDC antibiotics were identified, the consumption of which increased sharply from 8.5 DDD/100BDs in 2013 to 10.2 DDD/100BDs in 2019 (p < 0.05) despite the reduction in the total antibiotic consumption in these hospitals. The increase was mainly driven by FDC antibiotics in the Not Recommended group of the AWaRe classification, whose consumption accounted for 63.0% (6.4 DDD/100BDs) of the overall FDC antibiotic consumption in 2019, while the consumption of FDC antibiotics in the Access group only accounted for 13.5% (1.4 DDD/100BDs). Conclusion: FDC antibiotic consumption significantly increased during the study period and accounted for a substantial proportion of all systemic antibiotic usage in hospitals in China. FDC antibiotics in the Not Recommended group were most frequently consumed, which raises concerns about the appropriateness of FDC antibiotic use.

Efficacy and Safety of Shenqisuxin Granule for Non-ST-segment Elevation Acute Coronary Syndrome: Study Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial.

Introduction: The Chinese herbal compound formula, Shenqisuxin granule (SQSX), promotes neovascularization and prevents in-stent restenosis in modern pharmaceutical studies and is expected to provide an effective strategy for non-ST-segment elevation acute coronary syndrome (NSTEACS). Thus, this study aims to examine the efficacy and safety of SQSX for NSTEACS and initially reveal its mechanism. Methods/Design: The study is a randomized, double-blinded and placebo-controlled trial. A total of 66 participants will be randomly allocated to one of the following two groups. Participants in the SQSX group will receive conventional treatment plus SQSX, while the placebo group will receive conventional treatment plus placebo, both for 14 days. The primary outcome, hs-CRP, and secondary outcome the Seattle Angina Questionnaire (SAQ) will be assessed at baseline, 7 ± 3 days and 14 ± 3 days. At all visit windows, other indicators including creatine kinase (CK), creatine kinase-myocardial band (CK-MB), cardiac troponins I (cTnI), 12-lead electrocardiograph and the syndrome scores of Qi deficiency and blood stasis will be tested and metagenomic sequencing for intestinal flora will be performed. Echocardiography and safety assessment will be performed at baseline and 14 ± 3 days. Adverse events will be monitored during the trial. Discussion: The purpose of the study is to examine the efficacy and safety of SQSX to improve NSTEACS and initially reveal its mechanism. Trial Registration: China Clinical Trial Registry, ChiCTR2000029226. Registered on January 19, 2020.

Quantitative imaging of natural products in fine brain regions using desorption electrospray ionization mass spectrometry imaging (DESI-MSI): Uncaria alkaloids as a case study.

Uncaria species (Rubiaceae) are used as traditional Chinese medicines (TCMs) to treat central nervous system (CNS) diseases, and monoterpene indole alkaloids are the main bioactive constituents. Localization and quantification of CNS drugs in fine brain regions are important to provide insights into their pharmacodynamics, for which quantitative mass spectrometry imaging (MSI) has emerged as a powerful technique. A systematic study of the quantitative imaging of seven Uncaria alkaloids in rat brains using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was presented. The distribution of the alkaloids in thirteen brain regions was quantified successfully using the calibration curves generated by a modified on-tissue approach. The distribution trend of different Uncaria alkaloids in the rat brain was listed as monoterpene indole alkaloids > monoterpene oxindole alkaloids, R-configuration epimers > S-configuration epimers. Particularly, Uncaria alkaloids were detected directly in the pineal gland for the first time and their enrichment phenomenon in this region had an instructive significance in future pharmacodynamic studies.

Efficacy of the lumbar sympathetic ganglion block in lower limb pain and its application prospects during the perioperative period.

The sympathetic nervous system is involved in the physiological pathogenesis of many different types of chronic pain. Sympathetic blocks can interrupt the reflex control system by intercepting the noxious afferent fibers accompanying autonomic nerves, resulting in changes in peripheral or central sensory processing. A lumbar sympathetic ganglion block (LSGB), as a treatment method, refers to the injection of nerve blockers into the corresponding lumbar sympathetic nerve segments, usually requiring imaging assistance (CT, X-ray, ultrasound) to guide. At present, LSGB has been widely used in the clinical treatment of lower limb pain, such as neuropathic pain, lower limb ischemic pain, and so on. Its mechanism of action may be through inhibiting sympathetic nerve activity and dilating blood vessels, thereby alleviating pain and inhibiting stress response. However, there are few reports of LSGB during the perioperative period, especially in postoperative pain and gastrointestinal function. Therefore, by studying the literature about LSGB-related studies, this article reviews the anatomy of the lumbar sympathetic nerve (LSN), with its clinical application and possible mechanism. We reviewed the analgesic effect of LSGB in patients with lower limb pain and postoperative pain and the potential application prospects in the recovery of gastrointestinal function, finally providing a reference for its clinical application.

Development and assessment of a mental health preliminary screening questionnaire for cancer patients.

BACKGROUND: The mental health of cancer patients is attracting increasing attention. Thus, an efficient mental health preliminary screening questionnaire (MHPSQ) for cancer patients is required. This study sought to develop an MHPSQ, test its reliability and validity, and administer it among cancer patients. METHODS: A literature review and interviews with 8 patients were conducted to determine the questionnaire item pool, and experts were consulted to confirm the first draft. Next, 150 cancer patients were selected for the project analysis and validity assessment to develop the final document; 400 patients were then selected for the reliability and validity tests. After which, 1,000 patients were assessed using the Self-Rating Anxiety Scale, Self-Rating Depression Scale (SDS), and MHPSQ, and the completion times for each scale were evaluated. Finally, the specificity and sensitivity of the MHPSQ were then determined. RESULTS: Four factors (i.e., mood, sleep, social function, and interpersonal relationships) were ultimately retained as MHPSQ items. MHPSQ's Cronbach's α and test-retest reliability were 0.76 and 0.92, respectively. The time required to complete the MHPSQ was 83.90±19.00 s. Its sensitivity and specificity were 92.4% and 98.5%, respectively. CONCLUSIONS: The MHPSQ has good reliability and validity. Comprising only 4 items, it is easy to operate and effectively identifies patients with psychological abnormalities.

Restoring perturbed oxylipins with Danqi Tongmai Tablet attenuates acute myocardial infarction.

Salvianolic acids have a special synergic effect on panax notoginsenosides in acute myocardial infarction (AMI) and have been developed into a new drug as Danqi Tongmai Tablet (DQTT). To explore candidate targets and mechanisms of DQTT on AMI, a network pharmacology-based analysis was performed on absorbed prototype compounds of DQTT in rat plasma. Target prediction from network analysis indicated that the arachidonic acid pathway might contribute to the therapeutic effects of DQTT on AMI, and the regulatory effects on cyclooxygenase (COX) and lipoxygenase (LOX) were validated using an oxygen-glucose deprivation/reoxygenation model established on H9c2 cardiomyocytes. To further explore the action mechanisms of DQTT, 38 oxylipins were quantitatively analyzed among high, medium, and low doses of DQTT using a rat AMI model with an ultra high performance liquid chromatograph coupled with a triple quadrupole mass spectrometry (UHPLC-QqQ/MS) detection system. As attenuation was observed in AMI with DQTT treatment, the perturbed arachidonic acid metabolome was partly restored in a dose-dependent fashion with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. Cytokine array analysis also supported the anti-inflammatory effects of DQTT, as significant down-regulation of pro-inflammatory cytokines was observed. The analysis of ischemic heart tissues demonstrated that COX and LOX, the inflammation-induced catalytic enzymes of arachidonic acid metabolism, were inhibited on both gene expression and protein level. These results confirmed that DQTT could restore the arachidonic acid metabolome to maintain an anti-inflammatory profile against the ischemic tissue injury and support that DQTT can be a promising medicinal therapy against AMI.

Ni3S2 Nanocomposite Structures Doped with Zn and Co as Long-Lifetime, High-Energy-Density, and Binder-Free Cathodes in Flexible Aqueous Nickel-Zinc Batteries.

Flexible rechargeable Zn//Ni batteries are attractive owing to their high energy density, good safety, inexpensive cost, and simple manufacturing process. However, the effects of metal doping on the properties of Ni3S2 cathodes in Zn/Ni batteries are not well understood. Herein, a binder-free Ni3S2 electrode is doped with Zn and Co and the nanocomposite structures are prepared on nickel foam (named ZCNS/NF) by a simple two-step hydrothermal technique. The ZCNS/NF//Zn battery delivers excellent electrochemical performance such as a working voltage window can be as high as 2.05 V, a capacity of 2.3 mAh cm-2 at 12 mA cm-2, and 82% retention going through 2000 cycles at 20 mA cm-2. The battery has a maximum output area energy density of 1.8 mWh cm-2 (462 Wh kg-1) and a power density of 36.8 mW cm-2 (9.2 kW kg-1). In addition, the flexible battery remains operational while being bent at a large angle and even punctured. The high performance and robustness of the composite cathode suggest that the design principle and materials have large commercial potential in Ni//Zn batteries.

Fast determination of 16 circulating neurotransmitters and their metabolites in plasma samples of spontaneously hypertensive rats intervened with five different Uncaria.

This study aimed to establish a sensitive, reproducible, and rapid liquid chromatography method with tandem mass spectrometry detection to perform simultaneous quantitative analysis of 16 neurotransmitters and their metabolites in rat plasma, including levodopa, dopamine, norepinephrine, epinephrine, L-tryptophan, kynurenic acid, serotonin, melatonin, choline, acetylcholine, histamine, phenylethylamine, as well as excitatory (L-glutamic acid and L-aspartic acid) and inhibitory (γ-aminobutyric acid and L-glycine) neurotransmitters. These analytes were measured by ultra-high performance chromatography coupled with triple quadrupole mass spectrometry using a hydrophilic interaction chromatographic column (ethylene-bridged hybrid amide column). The internal standards of stable isotope labeling were used to improve the reliability of the results. Our method provided high linearity for all neurotransmitters (for all coefficients measured > 0.99), with inter- and intra-day accuracy from -14.82% to 17.49% and precision was between 0.89% and 17.70%. The method was subsequently verified in an animal study, where the intervention of five different Uncarias, the traditional Chinese medicine with hypotensive effects, was applied to the spontaneously hypertensive rats (SHRs). SHRs showed dysregulated plasma kynurenic acid, acetylcholine, and norepinephrine levels, and these neuroactive analytes were significantly restored by Uncaria treatment compared with the model group (SHR group). Compared with captopril, included as a positive control for its hypotensive effect, Uncaria had more effects on perturbing the levels of plasma neurotransmitters, which might indicate Uncaria's potential in treating symptoms related to the nervous system. These results suggested that the changes in the neurotransmitters and their metabolites in plasma may be related to the pathogenesis of hypertension. It also provided valuable information about the action mechanisms of Uncaria on its hypotensive effects.