Antioxidative effect of Periplaneta americana extract on dextran sulfate sodium-induced ulcerative colitis through activation of the Nrf2 signal.

CONTEXT: Periplaneta americana L. (Blattariae) is used as a treatment for ulcerative colitis (UC) in Chinese traditional medicine. OBJECTIVE: To evaluate the antioxidative activity of P. americana whole body ethanol extract (PAE) on UC mice and whether glycine and proline could be used for quality control and identification of active PAE components. MATERIALS AND METHODS: NCM460 cells were pre-incubated in PAE, AA-L, AA-M, and AA-H (low, high and medium doses of proline and glycine), then treated with recombinant human TNF-α. The glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) levels were determined. UC mice were fed with water containing 2.5% dextran sulfate sodium (w/v) after pre-treatment with different doses of PAE once a day for 7 days. ELISA was used to detect the concentrations of inflammation-related factors. Colon tissues of mice were used to detect the activity of myeloperoxidase (MPO), GSH, MDA, and SOD. Histological changes were observed using H&E staining. The expression of target proteins was determined by western blotting. RESULTS: In vivo, PAE treatment reduced the DAI score more than in the model group, restoring the weight and colonic length. It also reduced the severity of colitis, and inflammatory and oxidative stress intensity. Additionally, western blotting showed that the Nrf2 pathway was activated by PAE. In vitro PAE significantly alleviated TNF-α-induced cell damage and oxidative stress, which is relevant to the activation of the Nrf2 pathway. CONCLUSIONS: PAE may relieve oxidative stress through the Nrf2 signaling pathway, and proline and glycine may be used as active components of its antioxidative stress activity.

Health policy response to mobility during the pandemic: Evaluating the effectiveness using location-based services big data.

As an emergent health policy response, the population mobility restriction policy was implemented to cope with the unprecedented pandemic that outbroke in early 2020, but its effectiveness showed vast disparities even within a single country. Using multisource data from Baidu mobility big data and the statistics of novel coronavirus disease in China, mobility restrictions (including restrictions on inflow-mobility, outflow-mobility, and intra-city mobility) were examined. It was found that the mobility restriction had contained the development of pandemic, but such effect would gradually recede over time. Moreover, there existed region-specific policy effectiveness. Specifically, outflow-mobility restrictions were ineffective in reducing death cases in population influx areas, and restrictions on inflow-mobility (or intra-city mobility) were ineffective in reducing confirmed cases (or death cases) in population outflow areas. It was concluded that the mobility restriction policy can be effective in epidemic prevention and control in spatial-temporal pattern. However, there was a remarkable disparity in policy effectiveness between different regions with different population mobility patterns.

Periplaneta americana extract ameliorates dextran sulfate sodium-induced ulcerative colitis via immunoregulatory and PI3K/AKT/NF-κB signaling pathways.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with a low cure rate. Periplaneta americana is a traditional American Cockroach and reportedly has potential therapeutic roles for UC treatment; however, its mechanisms remain unclear. To address this, we investigated the therapeutic effects and underlying molecular mechanisms of Ento-A, a Periplaneta americana extract, in a dextran sulfate sodium (DSS)-induced chronic and recurrent UC mouse model. Ento-A treatment decreased pro-inflammatory cytokine secretion, disease activity index (DAI), colon mucosa damage index (CMDI), histopathological scores (HS), and increased colon length. Additionally, Ento-A effectively increased interleukin-4 (IL-4), and forkhead transcription factor protein 3 (Foxp3) expression levels, while it abated interferon-γ (IFN-γ) and IL-17 levels in spleen lymphocytes. Conversely, in mesenteric lymph nodes, IL-4 and Foxp3 expression were decreased, while IFN-γ and IL-17 expression was increased. Furthermore, Ento-A blocked p-PI3K, p-AKT,*and p-NF-κB activation. In conclusion, Ento-A improved UC symptoms and exerted therapeutic effects by regulating immune responses and inhibiting PI3K/AKT/NF-κB signaling.

Wasp venom from Vespa magnifica acts as a neuroprotective agent to alleviate neuronal damage after stroke in rats.

CONTEXT: Acute ischaemic stroke (AIS) is a major cause of disability and death, which is a serious threat to human health and life. Wasp venom extracted from Vespa magnifica Smith (Vespidae) could treat major neurological disorders. OBJECTIVE: This study investigated the effects of wasp venom on AIS in rats. MATERIAL AND METHODS: We used a transient middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats (260-280 g, n = 8-15) with a sham operation group being treated as negative control. MCAO rats were treated with wasp venom (0.05, 0.2 and 0.6 mg/kg, i.p.) using intraperitoneal injection. After treatment 48 h, behavioural tests, cortical blood flow (CBF), TTC staining, H&E staining, Nissl staining, TUNEL assay, immunohistochemistry (IHC) and ELISA were employed to investigate neuroprotective effects of wasp venom. RESULTS: Compared with the MCAO group, wasp venom (0.6 mg/kg) improved neurological impairment, accelerated CBF recovery (205.6 ± 52.92 versus 216.7 ± 34.56), reduced infarct volume (337.1 ± 113.2 versus 140.7 ± 98.03) as well as BBB permeability as evidenced by changes in claudin-5 and AQP4. In addition, function recovery of stroke by wasp venom treatment was associated with a decrease in TNF-α, IL-1ß, IL-6 and inhibition activated microglia as well as apoptosis. Simultaneously, the wasp venom regulated the angiogenesis factors VEGF and b-FGF in the brain. CONCLUSIONS: Wasp venom exhibited a potential neuroprotective effect for AIS. In the future, we will focus on determining whether the observed actions were due to a single compound or the interaction of multiple components of the venom.

High uric acid induces liver fat accumulation via ROS/JNK/AP-1 signaling.

Uric acid is the end metabolite derived from the oxidation of purine compounds. Overwhelming evidence shows the vital interrelationship between hyperuricemia (HUA) and nonalcoholic fatty liver disease (NAFLD). However, the mechanisms for this association remain unclear. In this study, we established a urate oxidase-knockout (Uox-KO) mouse model by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology. To study the correlation between HUA and NAFLD, human HepG2 hepatoma cells were treated in culture medium with high level of uric acid. In vivo, the Uox-KO mice spontaneously developed hyperuricemia and aberrant lipid-metabolism, concomitant with abnormal hepatic fat accumulation. HUA activated c-Jun N-terminal kinase (JNK) in vivo and in vitro. Furthermore, inhibiting JNK activation by a JNK-specific inhibitor, SP600125, decreased fat accumulation and lipogenic gene expression induced by HUA. Overexpression of the lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase 1 was via activation of JNK, which was blocked by the JNK inhibitor SP600125. HUA activated AP-1 to upregulate lipogenic gene expression via JNK activation. In addition, HUA caused mitochondrial dysfunction and reactive oxygen species production. Pretreatment with the antioxidant N-acetyl-l-cysteine could ameliorate HUA-activated JNK and hepatic steatosis. These data suggest that ROS/JNK/AP-1 signaling plays an important role in HUA-mediated fat accumulation in liver.NEW & NOTEWORTHY Hyperuricemia and nonalcoholic fatty liver disease are global public health problems, which are strongly associated with metabolic syndrome. In this study, we demonstrate that uric acid induces hepatic fat accumulation via the ROS/JNK/AP-1 pathway. This study identifies a new mechanism of NAFLD pathogenesis and new potential therapeutic strategies for HUA-induced NAFLD.

Uric acid inhibits HMGB1-TLR4-NF-κB signaling to alleviate oxygen-glucose deprivation/reoxygenation injury of microglia.

Mounting evidence has implicated inflammation in ischemia-reperfusion injury following acute ischemic stroke (AIS). Microglia remain the primary initiator and participant of brain inflammation. Emerging evidence has indicated that uric acid has promise for the treatment of AIS, but its explicit mechanisms remain elusive. Here, we observed that uric acid reduced the severity of cerebral infarction and attenuated the activation of microglia in the cerebral cortex in a mouse middle cerebral-artery occlusion/reperfusion model. Thus, we speculated that uric acid may play a role by directly interfering with the inflammatory response of microglia. First, we investigated whether the HMGB1-TLR4-NF-κB signaling plays a role in oxygen glucose deprivation and reperfusion (OGD/R) injury of BV2 cells. Inhibition of the signaling significantly reduced the release of the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1ß (IL1ß), and IL6 caused by OGD/R in BV2 cells. Second, uric acid weakened the decreased cell viability and lactate dehydrogenase release induced by OGD/R in BV2 cells. Finally, uric acid reduced the release of the proinflammatory cytokines TNF-α, IL1ß, and IL6 caused by OGD/R in BV2 cells by dampening HMGB1-TLR4-NF-κB signaling, which was reversed by probenecid treatment, an inhibitor of the uric acid channel. Hence, uric acid halted the release of inflammatory factors and the decreased cell viability induced by ODG/R via inhibiting the microglia HMGB1-TLR4-NF-κB signaling, thereby alleviating the damage to microglia. This may be part of the molecular mechanisms by which uric acid protects mice against the brain damage of middle cerebral-artery occlusion/reperfusion.

An Alkali Metal Ion-Exchanged Metal-Phosphate (C2H10N2) xNa1- x[Mn2(PO4)2] with High Proton Conductivity of 10-2 S·cm-1.

A two-dimensional layered inorganic-organic hybrid metal hydrogenophosphate (1) was treated with 0.1 M NaOH-ethanol solution, which resulted in a Na+-ion substitution product that exhibits excellent thermal and aqueous stability with 1, as well as much higher proton conductivity (σ = 10-2 S·cm-1) even at low temperature (283 K). This is because Na+ ions in aqueous solution make a more dense and extensive H-bonding network of water molecules, which enables protons to more easily transfer along the network.

A Two-Dimensional Inorganic-Organic Hybrid Solid of Manganese(II) Hydrogenophosphate Showing High Proton Conductivity at Room Temperature.

The inorganic-organic hybrid metal hydrogenophosphate with a formula of (C2H10N2)[Mn2(HPO4)3](H2O) (1) shows layered crystal structure. The inorganic anion layer is built from Mn3O13 cluster units, and the interlayer spaces are filled by the charge-compensated ethylenediammonium dications together with the lattice water molecules. The thermogravimetry, variable-temperature powder X-ray diffraction, and the proton conductance under anhydrous and moisture environments were investigated for 1, disclosing that 1 shows high thermal stability and high proton transport nature, and the proton conductivity reaches to 1.64 × 10(-3) S·cm(-1) under 99%RH even at 293 K. The high proton conductivity is related to the formation of denser H-bond networks in the lattice.

Recent advances in metal halide perovskite based photocatalysts for artificial photosynthesis and organic transformations.

Metal halide perovskites (MHP) emerged as highly promising materials for photocatalysis, offering significant advancements in the degradation of soluble and airborne pollutants, as well as the transformation of functional organic compounds. This comprehensive review focuses on recent developments in MHP-based photocatalysts, specifically examining two major categories: lead-based (such as CsPbBr3) and lead-free variants (e.g. Cs2AgBiX6, Cs3Bi2Br9 and others). While the review briefly discusses the contributions of MHPs to hydrogen (H2) production and carbon dioxide (CO2) reduction, the main emphasis is on the design principles that determine the effectiveness of perovskites in facilitating organic reactions and degrading hazardous chemicals through oxidative transformations. Furthermore, the review addresses the key factors that influence the catalytic efficiency of perovskites, including charge recombination, reaction mechanisms involving free radicals, hydroxyl ions, and other ions, as well as phase transformation and solvent compatibility. By offering a comprehensive overview, this review aims to serve as a guide for the design of MHP-based photocatalysis and shed light on the common challenges faced by the scientific community in the domain of organic transformations.

E. globulus leaf EO exhibits anti-inflammatory effects by regulating GSDMD-mediated pyroptosis, thereby alleviating neurological impairment and neuroinflammation in experimental stroke mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aromatic and medicinal plants continue to be a major component of alternative and traditional medicine in the developing countries. Eucalyptus globulus (Labill.) is being employed to cultivation and production in China. However, few studies have reported the chemical composition and anti-inflammatory activity of Eucalyptus globulus (Labill.) leaf essential oil (E. globulus leaf EO) extracted from Eucalyptus globulus. AIM OF THE STUDY: This study aimed to assess the composition of E. globulus leaf EO and identify its bacteriostatic action as well as anti-inflammatory activity. Importantly, we evaluated the effect of E. globulus leaf EO on neurological impairment and neuroinflammation in experimental stroke mice. MATERIALS AND METHODS: Gas Chromatography-Mass Spectrometer (GC-MS) analyses was employed to evaluate the chemical components of E. globulus leaf EO, and the relative content of each component was determined by area normalization method. The antimicrobial activity of E. globulus leaf EO was determined by Oxford cup method and microbroth dilution assay. Cytotoxic activity of E. globulus leaf EO on THP-1 cells or BV2 cells in vitro was determined by CCK8 assay. In addition, the lipopolysaccharide (LPS)/ATP-induced inflammation model in THP-1 cells or BV2 cells were established, and the relative expression of TNF-α, IL-1ß, MCP-1and IL-6 were confirmed by RT-PCR. Furthermore, the expression of protein GSDMD, IL-lß, NLRP3 and NFκB signaling pathway were assessed by immunoblotting. In vivo,the experimental stroke model constructed by middle cerebral artery occlusion/reperfusion (MCAO/R) in mice was employed and subsequently treated with E. globulus leaf EO (50,100 mg/kg, subcutaneous injection) for 3 days to assess neurological impairment and neuroinflammation. Behavioral and neuronal damage were assessed using grip strength test, rod trarod test, and Nissl staining. Pro-inflammatory factors in serum or ischemic brain tissue was detected by ELISA kits. RESULTS: GC-MS analyses revealed that the major compound in E. globulus leaf EO was eudesmol (71.967%). E. globulus leaf EO has antimicrobial activity against Staphylococcus aureus (gram positive bacteria, MIC = 0.0625 mg/mL), Escherichia coli (gram negative bacteria, MIC = 1 mg/mL), and Candida albicans (MIC = 4 mg/mL). E. globulus leaf EO (0.5312, 1.0625, and 2.15 mg/mL) significantly decreased the expression of inflammation-related genes, including IL-1ß, TNF-α, MCP-1, and IL-6. Furthermore, reduced levels of TLR4, Myd88, phosphorylated NF-κB P65, and IκBα were found in the E. globulus leaf EO group for BV2 cells (1.025, and 2.125 mg/mL). In addition, the expression levels of GSDMD, NLRP3, IL-1ß and AIM2 were significantly decreased in the E. globulus leaf EO group when compared with the LPS -stimulated group, regulating GSDMD-mediated pyroptosis. In vivo, E. globulus leaf EO improved neurological functional deficits, inhibited excessive activation of microglia, and reduced the secretion of pro-inflammatory factors IL-1ß, TNF-α in the ischemic tissue and serum after MCAO/R. CONCLUSION: E. globulus leaf EO has strong antibacterial and anti-inflammatory activity, which has been implicated in blocking GSDMD-mediated pyroptosis. Moreover, E. globulus leaf EO could exert neuroprotective effect on cerebral ischemia-reperfusion injury.

Mastoparan M promotes functional recovery in stroke mice by activating autophagy and inhibiting ferroptosis.

Neuronal ferroptosis and autophagy are crucial in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Mastoparan M (Mast-M), extracted from the crude venom of Vespa magnifica (Smith), comprises 14 amino acid residues. Previous studies suggested that Mast-M reduces neuronal damage following global CIRI, but its protective mechanisms remain unclear. The present study examined the effect of Mast-M on middle cerebral artery occlusion/reperfusion (MCAO/R) induced neurological deficits using Grip, Rotarod, Longa test, and TTC staining, followed by treating the mice for three days with Mast-M (20, 40, and 80 µg/kg, subcutaneously). The results demonstrate that Mast-M promotes functional recovery in mice post-ischemic stroke, evidenced by improved neurological impairment, reduced infarct volume and neuronal damage. Meanwhile, the level of iron (Fe2+) and malonyldialdehyde was decreased in the ischemic hemisphere of MCAO/R mice at 24 hours or 48 hours by Mast-M (80 µg/kg) treatment, while the expression of NRF2, x-CT, GPX4, and LC3B protein was increased. Furthermore, these findings were validated in three models-oxygen-glucose deprivation/ reoxygenation, H2O2-induced peroxidation, and erastin-induced ferroptosis-in hippocampal neuron HT22 cells or primary neurons. These data suggested that Mast-M activates autophagy as well as inhibits ferroptosis. Finally, autophagy inhibitors were introduced to determine the relationship between the autophagy and ferroptosis, indicating that Mast-M alleviates ferroptosis by activating autophagy. Taken together, this study described that Mast-M alleviates cerebral infarction, neurologic impairment, and neuronal damage by activating autophagy and inhibiting ferroptosis, presenting a potential therapeutic approach for CIRI.

Ento-A alleviates DSS-induced experimental colitis in mice by remolding intestinal microbiota to regulate SCFAs metabolism and the Th17 signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by changes in the metabolism of short chain fatty acids (SCFAs), dysregulation of gut microbiota, and an imbalance of Treg/Th17. Herein, we explore the effects of the Ento-A (an alcohol extract of Periplaneta americana L.) on a mouse model of UC. First, a chronic and recurrent UC model was constructed in BALB/c mice by 2.2% DSS administration. UC mice were continuously treated for 14 days with Ento-A (50, 100, 200 mg/kg, i.g.) or a negative control. Ento-A alleviated many of the pathological changes observed in UC mice, such as body weight loss, disease activity index, changes in colon length, and colonic mucosal damage index. Ento-A also decreased levels of proinflammatory cytokines (IL-1ß, IL-6, IL-17A, and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-ß1) and repaired the intestinal mucosal barrier. Additionally, Ento-A regulated the proportions of Th17 cells, and Treg cells in mesenteric lymph nodes harvested from treated mice (as assessed by Flow cytometry), and the expression levels of IL-17A and Foxp3 in colon (as assessed by immunohistochemistry). 16 S rRNA gene sequencing revealed that Ento-A regulated gut microbiota. GC-MS analysis demonstrated that Ento-A also restored SCFAs content in the intestinal tract. Finally, transcriptomic analysis revealed that Ento-A regulated the IL-17 signaling pathway. In summary, Ento-A regulates the diversity and abundance of intestinal flora in UC mice, enhancing the secretion of SCFAs, subsequently regulating the IL-17 signaling pathway, and ultimately repairing the intestinal mucosal barrier.

Targeting TNF-α: The therapeutic potential of certolizumab pegol in the early period of cerebral ischemia reperfusion injury in mice.

The neuroinflammatory response triggered by cerebral ischemia-reperfusion injury (CIRI) is characterized by the upsurge of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, which promote leukocyte infiltration and subsequent accumulation in the ischemic zone. This accumulation further intensifies inflammation and aggravates ischemic damage. Certolizumab pegol (CZP), a monoclonal antibody targeting TNF-α, is widely used in treating various inflammatory diseases. This study explored the therapeutic potential of CZP in a mouse model of CIRI, induced by middle cerebral artery occlusion (MCAO), focusing on its influence on the microglial inflammatory response. In vitro analyses revealed that CZP markedly inhibits TNF-α-stimulated inflammation in primary microglia with an EC50 of 1.743 ng/mL. In vivo, MCAO mice treated with CZP (10 µg/mouse, i.p.) for 3 days showed reduced infarct volume, partially improved neurological function, and diminished blood-brain barrierdisruption. Additionally, CZP treatment curtailed microglial activation and the release of pro-inflammatory mediators in the early stages of stroke. It also favorably modulated microglial M1/M2 polarization, rebalanced Th17/Treg cells dynamics, and inhibited Caspase-8-mediated GSDMD cleavage, preventing microglial pyroptosis. Collectively, this study described that the treatment with CZP reversed damaging process caused by CIRI, offering a promising therapeutic strategy for the treatment of ischemic stroke.

Compound musk injection in the treatment of ischemic stroke: A network analysis of the mechanism of action.

BACKGROUND: Ischemic stroke (IS) is affected by a wide range of factors and has certain treatment limitations. Studies have reported that compound musk injection (CMI) is effective in the treatment of IS, however, its mechanism of action is still unclear. METHODS: The main active ingredients in CMI were retrieved from HERB, TCMSP and BATMAN databases, and the relevant targets were predicted by Swiss Target Prediction platform. MalaCards, OMIM, DrugBank, DisGeNET, Genecards and TTD databases were used to obtain the genes related to IS. The intersection of drugs and disease targets was used to construct protein-protein interaction networks, and gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. AutoDock Vina software was used for molecular docking, and cell experiments were conducted to verify the results. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of relative mRNA in cells. RESULTS: Network analysis and molecular docking results showed that the key targets of CMI in the treatment of IS were SRC, TP53, PIK3R1, MAPK3, PIK3CA, MAPK1, etc. KEGG pathway enrichment analysis mainly involved PI3K/Akt signaling pathway, Rap1 signaling pathway and MAPK signaling pathway. The molecular docking results all showed that the key ingredients were strong binding activity with the key targets. The quantitative RT-PCR results indicated that CMI may increase the expression of PIK3CA, MAPK3 mRNA and decrease the expression of SRC mRNA. CONCLUSIONS: CMI can treat IS by regulating pathways and targets related to inflammatory response and apoptosis in a multi-component manner.

High Uric Acid Promotes Atherosclerotic Plaque Instability by Apoptosis Targeted Autophagy.

AIMS: Acute rupture or erosion of unstable atherosclerotic plaques is a major cause of adverse consequences of atherosclerotic cardiovascular disease, often leading to myocardial infarction or stroke. High uric acid (HUA) is associated with the increasing risk of cardiovascular events and death. However, the mechanism by which HUA promotes atherosclerosis and whether HUA affects plaque stability are still unclear. METHODS: We constructed an atherosclerotic Apoe-/- mouse model with HUA. The progression of atherosclerosis and plaques was determined by Oil Red O staining, hematoxylin and eosin (H&E) staining, and Masson staining. TdT-mediated dUTP nick-end labeling assay and immunohistochemistry were used to observe the changes of apoptosis and autophagy in plaques, respectively. Then, we validated the in vivo results with RAW 264.7 cell line. RESULTS: HUA promoted atherosclerosis and exacerbated plaque vulnerability, including significantly increased macrophage infiltration, lipid accumulation, enlarged necrotic cores, and decreased collagen fibers. HUA increased cell apoptosis and inhibited autophagy in plaques. In vitro results showed that HUA decreased cell viability and increased cell apoptosis in foam cells macrophages treated with oxidized low-density lipoprotein. An activator of autophagy, rapamycin, can partially reverse the increasing apoptosis. CONCLUSION: HUA promoted atherosclerosis and exacerbated plaque vulnerability, and HUA facilitates foam cell apoptosis by inhibiting autophagy.

Kinetically Controlled Synthesis of Highly Emissive Au18SG14 Clusters and Their Phase Transfer: Tips and Tricks.

Glutathione (GSH) protected gold nanoclusters (Au n SG m NCs) have been attractive because of their novel properties such as enhanced luminescence and band gap tunability at their quantum confinement region (below ∼2 nm). Initial synthetic routes of mixed-size clusters and size-based separation techniques had latter evolved toward atomically precise nanoclusters via thermodynamic and kinetic control routes. One such exemplary synthesis taking the advantages of a kinetically controlled approach is producing highly red-emissive Au18SG14 NCs (where SG = thiolate of glutathione), thanks to the slow reduction kinetics provided by the mild reducing agent NaBH3CN. Despite the developments in the direct synthesis of Au18SG14, several meticulous reaction conditions still need to be understood for the highly adaptable synthesis of atomically pure NCs irrespective of the laboratory conditions. Herein, we have systematically studied a series of reaction steps involved in this kinetically controlled approach starting from the role of the antisolvent, formation of precursors to Au-SG thiolates, growth of Au-SG thiolates as a function of aging time, and exploring an optimal reaction temperature to optimize the desired nucleation under slow reduction kinetics. The crucial parameters derived in our studies guide the successful and large-scale production of Au18SG14 at any laboratory condition. Next, we investigated the effect of pH on the NCs to study the stability and the best suitable condition for the phase transfer of Au18SG14 clusters. The commonly implemented method of phase transfer at the basic conditions (pH > 9) is not successful in this case. However, we developed a feasible method for the phase transfer by diluting the aqueous NC solution to enhance the negative charges on the NCs' surface by increasing the degree of dissociation at the carboxylic acid group. It is interesting to note that after the phase transfer, the Au18SG14-TOA NCs in toluene as well as in other organic solvents exhibited enhanced luminescence quantum yields from 9 to 3 times and increased average photoluminescence lifetimes by 1.5-2.5 times, respectively.

A Meta-analysis of the Clinical Efficacy of the Head-of-Bed Elevation for Patients With Acquired Brain Injury.

ABSTRACT: BACKGROUND: Acquired brain injury is caused by traumatic or nontraumatic factors and causes changes in cognition. Several reviews have described the influence of the head-of-bed (HOB) elevation on clinical indexes such as intracranial pressure (ICP) and cerebral perfusion pressure (CPP). However, the conclusions were inconsistent. Therefore, we aimed to evaluate the effects of HOB elevation in the care of the patients with ABI. METHODS: Two researchers independently screened the literature and extracted data. We searched PubMed, EMBASE, the Cochrane Library, Web of Science, and the Chinese Biological Literature Database to collect eligible randomized controlled trials published after September 2021. Reporting quality and methodological quality of the included studies were assessed by using the Preferred Reporting Items for Systematic Reviews and Meta-analysis and the Cochrane risk-of-bias tool. RESULTS : Eight studies were included in the meta-analysis. The results showed that, compared with the flat position, HOB elevation of 30° or 45° can significantly reduce ICP (mean difference [MD], -2.40 mm Hg; 95% confidence interval [CI], -3.19 to -1.61; P < .00001). However, there were no statistical differences in CPP (MD, -1.09; 95% CI, -3.93 to 1.75; P = .45), degree of disability at 90 days (relative risk, 1.01; 95% CI, 0.94-1.08; P = .83), and mean arterial pressure (MD, -0.44; 95% CI, -10.27 to 9.93; P = .93). CONCLUSION: Head-of-bed elevation of 30° can reduce ICP and maintain CPP, and may be an effective noninvasive nursing practice for the prognosis and rehabilitation of ABI patients. Owing to the lack of high-quality, large-sample randomized controlled trials, more rigorous trials are needed to support this conclusion.

Mastoparan M Suppressed NLRP3 Inflammasome Activation by Inhibiting MAPK/NF-κB and Oxidative Stress in Gouty Arthritis.

Background: Gouty arthritis is characterized by the accumulation of monosodium urate crystals (MSU) in the synovial joints and surrounding tissues. Mastoparan M (Mast-M) is a biologically active peptide composed of 14 amino acids, extracted from wasp venom. This study aims to assess the impact of Mast-M on in vitro and in vivo gouty arthritis induced by lipolyaccharide (LPS) plus MSU crystal stimulation. Methods: PMA-differentiated THP-1 macrophages were pre-treated with Mast-M or left untreated, followed by stimulation with LPS and MSU crystals. Cell lysates were collected to assess the expression of the NLRP3 inflammasome, inflammatory signaling pathways, and oxidative stress. Furthermore, to evaluate the in vivo anti-inflammatory effect of Mast-M, an experimental acute gouty arthritis mouse model was established through intra-articular injection of MSU crystals. Results: Mast-M treatment demonstrated significant inhibition of the phosphorylation of MAPKs/NF-κB signaling pathways and reduction in oxidative stress expression in LPS and MSU-induced THP-1 macrophages. This resulted in the suppression of downstream NLRP3 inflammasome activation and IL-1ß release. In vivo, Mast-M effectively attenuated the inflammation induced by MSU in mice with gouty arthritis. Specifically, Mast-M reduced swelling in the paws, inhibited the infiltration of neutrophils and macrophages into periarticular tissue, and decreased the activation of the NLRP3 inflammasome and IL-1ß production. Conclusion: Mast-M significantly improves gouty arthritis, and its potential mechanism may be achieved by inhibiting the MAPK/NF-κB pathway and alleviating oxidative stress, thus suppressing the activation of NLRP3 inflammasomes.

Kangfuxin alleviates ulcerative colitis in rats by inhibiting NF-κB p65 activation and regulating T lymphocyte subsets.

Objectives: Ulcerative colitis (UC) remains an enduring, idiopathic inflammatory bowel disease marked by persistent mucosal inflammation initiating from the rectum and extending in a proximal direction. An ethanol extract of Periplaneta americana L., namely Kangfuxin (KFX), has a significant historical presence in Traditional Chinese Medicine and has been broadly utilized in clinical practice for the treatment of injury. Here, we aimed to determine the effect of KFX on 2,4,6-trinitro'benzene sulfonic acid (TNBS)-induced UC in Sprague-Dawley rats. Materials and Methods: We established the UC model by TNBS/ethanol method. Then, the rats were subject to KFX (50, 100, 200 mg/kg/day) for 2 weeks by intragastric gavage. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), and histopathological score were evaluated. The colonic tissue interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), IL-10, transforming growth factor-1 (TGF-ß1), and epidermal growth factor (EGF) were determined by Elisa. To study T-lymphocyte subsets, flow cytometry was performed. In addition, the expression level of NF-κB p65 was evaluated by immunohistochemistry and western blot analysis. Results: Compared with the TNBS-triggered colitis rats, the treatment of rats with KFX significantly increased the body weight, and decreased DAI, CMDI, and histopathological score. Also, KFX elicited a reduction in the secretion of colonic pro-inflammatory cytokines, namely IL-1ß, IL-6, and TNF-α, concomitant with up-regulation of IL-10, TGF-ß1, and EGF levels. Upon KFX treatment, the CD3+CD4+/CD3+CD8+ ratio in the spleen decreased, while the CD3+CD8+ subset and the CD3+CD4+CD25+/CD3+CD4+ ratio demonstrated an increase. In addition, the expression of NF-κB p65 in the colon was decreased. Conclusion: KFX effectively suppresses TNBS-induced colitis by inhibiting the activation of NF-κB p65 and regulating the ratio of CD4+/CD8+.

The proton conduction behavior of two 1D open-framework metal phosphates with similar crystal structures and different hydrogen bond networks.

Two open-framework zinc phosphates [C3N2H12][Zn(HPO4)2] (1) and [C6N4H22]0.5[Zn(HPO4)2] (2) were synthesized via hydrothermal reaction and characterized by powder X-ray diffraction, thermogravimetric analysis and scanning electron microscopy. Both compounds have a similar crystal structure and macroscopic morphology. However, the difference in equilibrium cations, in which the propylene diamine is for 1 and the triethylenetetramine is for 2, results in a significant distinction in the dense hydrogen grid. The diprotonated propylene diamine molecule in 1 is more favorable for forming a hydrogen-bond network in three dimensions than in 2, in which the twisted triethylenetetramine forms a hydrogen bond grid with the inorganic framework only in two dimensions owing to its large steric effect. This distinction further leads to a disparity in the proton conductivity of both compounds. The proton conductivity of 1 can reach 1.00 × 10-3 S cm-1 under ambient conditions (303 K and 75% RH) and then increase to 1.11 × 10-2 S cm-1 at 333 K and 99% RH, which is the highest value among the open-framework metal phosphate proton conductors operated in the same conduction. In contrast, the proton conductivity of 2 is four orders of magnitude smaller than 1 at 303 K and 75% RH and two orders smaller than 1 at 333 K and 99% RH.