Identification of the Acid-Sensitive Site Critical for Chloral Hydrate (CH) Activation of the Proton-Activated Chloride Channel.

The transmembrane protein TMEM206 was recently identified as the molecular basis of the extracellular proton-activated Cl- channel (PAC), which plays an essential role in neuronal death in ischemia-reperfusion. The PAC channel is activated by extracellular acid, but the proton-sensitive mechanism remains unclear, although different acid-sensitive pockets have been suggested based on the cryo-EM structure of the human PAC (hPAC) channel. In the present study, we firstly identified two acidic amino acid residues that removed the pH-dependent activation of the hPAC channel by neutralization all the conservative negative charged residues located in the extracellular domain of the hPAC channel and some positively charged residues at the hotspot combined with two-electrode voltage-clamp (TEVC) recording in the Xenopus oocytes system. Double-mutant cycle analysis and double cysteine mutant of these two residues proved that these two residues cooperatively form a proton-sensitive site. In addition, we found that chloral hydrate activates the hPAC channel depending on the normal pH sensitivity of the hPAC channel. Furthermore, the PAC channel knock-out (KO) male mice (C57BL/6J) resist chloral hydrate-induced sedation and hypnosis. Our study provides a molecular basis for understanding the proton-dependent activation mechanism of the hPAC channel and a novel drug target of chloral hydrate.SIGNIFICANCE STATEMENT Proton-activated Cl- channel (PAC) channels are widely distributed in the nervous system and play a vital pathophysiological role in ischemia and endosomal acidification. The main discovery of this paper is that we identified the proton activation mechanism of the human proton-activated chloride channel (hPAC). Intriguingly, we also found that anesthetic chloral hydrate can activate the hPAC channel in a pH-dependent manner. We found that the chloral hydrate activates the hPAC channel and needs the integrity of the pH-sensitive site. In addition, the PAC channel knock-out (KO) mice are resistant to chloral hydrate-induced anesthesia. The study on PAC channels' pH activation mechanism enables us to better understand PAC's biophysical mechanism and provides a novel target of chloral hydrate.

Identification of Sodium- and Chloride-Sensitive Sites in the Slack Channel.

The Slack channel (KCNT1, Slo2.2) is a sodium-activated and chloride-activated potassium channel that regulates heart rate and maintains the normal excitability of the nervous system. Despite intense interest in the sodium gating mechanism, a comprehensive investigation to identify the sodium-sensitive and chloride-sensitive sites has been missing. In the present study, we identified two potential sodium-binding sites in the C-terminal domain of the rat Slack channel by conducting electrophysical recordings and systematic mutagenesis of cytosolic acidic residues in the rat Slack channel C terminus. In particular, by taking advantage of the M335A mutant, which results in the opening of the Slack channel in the absence of cytosolic sodium, we found that among the 92 screened negatively charged amino acids, E373 mutants could completely remove sodium sensitivity of the Slack channel. In contrast, several other mutants showed dramatic decreases in sodium sensitivity but did not abolish it altogether. Furthermore, molecular dynamics (MD) simulations performed at the hundreds of nanoseconds timescale revealed one or two sodium ions at the E373 position or an acidic pocket composed of several negatively charged residues. Moreover, the MD simulations predicted possible chloride interaction sites. By screening predicted positively charged residues, we identified R379 as a chloride interaction site. Thus, we conclude that the E373 site and the D863/E865 pocket are two potential sodium-sensitive sites, while R379 is a chloride interaction site in the Slack channel.SIGNIFICANCE STATEMENT The research presented here identified two distinct sodium and one chloride interaction sites located in the intracellular C-terminal domain of the Slack (Slo2.2, KCNT1) channel. Identification of the sites responsible for the sodium and chloride activation of the Slack channel sets its gating property apart from other potassium channels in the BK channel family. This finding sets the stage for future functional and pharmacological studies of this channel.

APETALA2/ethylene-responsive factors in higher plant and their roles in regulation of plant stress response.

Plants, anchored throughout their life cycles, face a unique set of challenges from fluctuating environments and pathogenic assaults. Central to their adaptative mechanisms are transcription factors (TFs), particularly the AP2/ERF superfamily-one of the most extensive TF families unique to plants. This family plays instrumental roles in orchestrating diverse biological processes ranging from growth and development to secondary metabolism, and notably, responses to both biotic and abiotic stresses. Distinguished by the presence of the signature AP2 domain or its responsiveness to ethylene signals, the AP2/ERF superfamily has become a nexus of research focus, with increasing literature elucidating its multifaceted roles. This review provides a synoptic overview of the latest research advancements on the AP2/ERF family, spanning its taxonomy, structural nuances, prevalence in higher plants, transcriptional and post-transcriptional dynamics, and the intricate interplay in DNA-binding and target gene regulation. Special attention is accorded to the ethylene response factor B3 subgroup protein Pti5 and its role in stress response, with speculative insights into its functionalities and interaction matrix in tomatoes. The overarching goal is to pave the way for harnessing these TFs in the realms of plant genetic enhancement and novel germplasm development.

Curcumin relieves oxaliplatin-induced neuropathic pain via reducing inflammation and activating antioxidant response.

Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles in neuropathic pain development. Here, neuropathic pain mouse model was constructed by continuous intraperitoneal injection of OXA. OXA administration induced mechanical pain, spontaneous pain, thermal hyperalgesia and motor disability in mice. The spinal cord tissues of OXA mice exhibited the suppressed antioxidative response, the activated NLRP3 inflammasome mediated inflammatory responses, and the increased GSK-3ß activity. Next, we injected curcumin (CUR) intraperitoneally in OXA mice for seven consecutive days. CUR-treated mice showed increased mechanical pain thresholds, reduced number of spontaneous flinches, increased paw withdrawal latency, and restored latency to fall. While in the spinal cord, CUR treatment inhibited the NLRP3 inflammasome mediated inflammatory response, increased Nrf2/GPX4-mediated antioxidant responses, and decreased mitochondrial oxidative generation. Additionally, CUR combined with GSK-3ß through four covalent bonds and reduced GSK-3ß activity. In conclusion, our findings suggest that CUR treatment inhibits GSK-3ß activation, increases Nrf2 mediated antioxidant responses, inhibits oxidative damage and inflammatory reaction, and alleviates OXA-induced neuropathic pain.

The significance of serum SLC7A11 levels in the occurrence of vascular calcification in maintenance peritoneal dialysis patients.

AIM: This research aimed to explore the serum levels of solute carrier family 7 member 11 (SLC7A11) in patients with maintenance peritoneal dialysis (MPD) and its correlation with vascular calcification (VC) and clinical results. METHODS: This present prospective observational cohort study enrolled 189 patients with MPD who were undergoing regular peritoneal dialysis for over 3 months in our hospital from February 2020 to July 2022. The abdominal aortic calcification score was used to assess the VC condition of MPD patients. The serum SLC7A11, interleukin (IL)-6, IL-1ß and C-reactive protein levels were measured by enzyme-linked immunosorbent assay (ELISA). Demographic and clinical statistics were collected. All patients were followed up for 1 year and the overall survival time (OS) of all patients were recorded. All data used SPSS 18.0 for statistical analyses. RESULTS: Patients with moderate/severe calcification in MPD had a longer duration of dialysis, higher serum levels of phosphate (P) and calcium (Ca) and lower serum levels of SLC7A11. Spearman's analysis revealed a negative correlation between serum SLC7A11 levels and the levels of P, Ca and IL-1ß. Additionally, we observed an association between serum SLC7A11 levels and clinical prognosis as well as the extent of VC in MPD patients. Multivariate logistic regression analysis indicated that dialysis duration, SLC7A11, and P were risk factors for VC in MPD patients. CONCLUSION: The serum SLC7A11 levels decreased remarkably in MPD patients with moderate/severe calcification. This study may provide new targets and comprehensive approach to cardiovascular protection in patients with chronic kidney disease.

Identification and Validation of the Diagnostic Markers for Inflammatory Bowel Disease by Bioinformatics Analysis and Machine Learning.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which is mediated by the inappropriate immune responses. This study was aimed to identify novel diagnostic biomarkers for diagnosis of IBD and explore the relationship between the diagnostic biomarkers and infiltrated immune cells. GSE38713, GSE53306, and GSE75214 downloaded from the Gene Expression Omnibus (GEO) database were split into training and testing sets. Differentially expressed genes (DEGs) were screened using the "limma" package. Gene Ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed by clusterProfiler package. The LASSO regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were conducted to identify novel diagnostic biomarkers. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of the candidate biomarkers. The relationship of the candidate biomarkers and infiltrating immune cells in IBD were evaluated by CIBERSOTR. Quantitative Real-Time PCR (qRT-PCR) was applied to measure the expression level of the biomarkers in IBD. A total of 289 dysregulated genes were identified as DEGs in IBD. These DEGs were significantly enriched in chemokine signaling pathway and cytokine-cytokine receptor interaction. RHOU was identified as a critical diagnostic gene in IBD, which was confirmed using ROC curve and qRT-PCR assays. Immune cell infiltration analysis showed that RHOU was correlated with macrophages M2, dendritic cells resting, mast cells resting, T cells CD4 memory resting, macrophages M0, and mast cells activated. Our results imply that RHOU may be a potential diagnostic biomarker for IBD.

Discovery of an antitumor compound from xenorhabdus stockiae HN_xs01.

Xenorhabdus, known for its symbiotic relationship with Entomopathogenic nematodes (EPNs), belongs to the Enterobacteriaceae family. This dual-host symbiotic nematode exhibits pathogenic traits, rendering it a promising biocontrol agent against insects. Our prior investigations revealed that Xenorhabdus stockiae HN_xs01, isolated in our laboratory, demonstrates exceptional potential in halting bacterial growth and displaying anti-tumor activity. Subsequently, we separated and purified the supernatant of the HN_xs01 strain and obtained a new compound with significant inhibitory activity on tumor cells, which we named XNAE. Through LC-MS analysis, the mass-to-nucleus ratio of XNAE was determined to be 254.24. Our findings indicated that XNAE exerts a time- and dose-dependent inhibition on B16 and HeLa cells. After 24 h, its IC50 for B16 and HeLa cells was 30.178 µg/mL and 33.015 µg/mL, respectively. Electron microscopy revealed conspicuous damage to subcellular structures, notably mitochondria and the cytoskeleton, resulting in a notable reduction in cell numbers among treated tumor cells. Interestingly, while XNAE exerted a more pronounced inhibitory effect on B16 cells compared to HeLa cells, it showed no discernible impact on HUVEC cells. Treatment of B16 cells with XNAE induced early apoptosis and led to cell cycle arrest in the G2 phase, as evidenced by flow cytometry analysis. The impressive capability of X. stockiae HN_xs01 in synthesizing bioactive secondary metabolites promises to significantly expand the reservoir of natural products. Further exploration to identify the bioactivity of these compounds holds the potential to shed light on their roles in bacteria-host interaction. Overall, these outcomes underscore the promising potential of XNAE as a bioactive compound for tumor treatment.

The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus.

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.

Two types of peptides derived from the neurotoxin GsMTx4 inhibit a mechanosensitive potassium channel by modifying the mechanogate.

Atrial fibrillation is the most common sustained cardiac arrhythmia in humans. Current atrial fibrillation antiarrhythmic drugs have limited efficacy and carry the risk of ventricular proarrhythmia. GsMTx4, a mechanosensitive channel-selective inhibitor, has been shown to suppress arrhythmias through the inhibition of stretch-activated channels (SACs) in the heart. The cost of synthesizing this peptide is a major obstacle to clinical use. Here, we studied two types of short peptides derived from GsMTx4 for their effects on a stretch-activated big potassium channel (SAKcaC) from the heart. Type I, a 17-residue peptide (referred to as Pept 01), showed comparable efficacy, whereas type II (i.e., Pept 02), a 10-residue peptide, exerted even more potent inhibitory efficacy on SAKcaC compared with GsMTx4. We identified through mutagenesis important sequences required for peptide functions. In addition, molecular dynamics simulations revealed common structural features with a hydrophobic head followed by a positively charged protrusion that may be involved in peptide channel-lipid interactions. Furthermore, we suggest that these short peptides may inhibit SAKcaC through a specific modification to the mechanogate, as the inhibitory effects for both types of peptides were mostly abolished when tested with a mechano-insensitive channel variant (STREX-del) and a nonmechanosensitive big potassium (mouse Slo1) channel. These findings may offer an opportunity for the development of a new class of drugs in the treatment of cardiac arrhythmia generated by excitatory SACs in the heart.

Renewable Adsorbents for Selective Phosphorus Removal: Co(OH)2-Derived ZIF-67 on Anion Exchange Resin.

Metal organic framework (MOF)-based adsorbents are appealing for removing low-concentration phosphates with interfering ions in wastewater purification, a new strategy developed to maintain the good activity of metal sites. Here, ZIF-67 was immobilized onto the porous surface of anion exchange resin (D-201) with a high loading amount of 22.0 wt % by a modifiable Co(OH)2 template. We observed that the removal rate of low-concentration phosphate (2 mg P/L) by ZIF-67/D-201 nanocomposites was 98.6%, and more than 90% phosphate adsorption capacity was still maintained, with 5 times molar concentration of interfering ions in the solution. Moreover, after six times of regeneration by solvothermal reaction in the ligand solution, the structure of ZIF-67 was better preserved in D-201 with more than 90% phosphate removal rate. ZIF-67/D-201 could be employed effectively in fixed-bed adsorption runs. By the analysis of experiment and characterization, we found that during the adsorption-regeneration process of ZIF-67/D-201 for phosphate, reversible structural transformation of ZIF-67 and Co3(PO4)2 occurred in D-201. In general, the study reported a new method to develop MOF adsorbents for wastewater treatment.

Catalytic Oxidation Mechanism of Toluene over CexMn1-xO2: The Role of Oxygen Vacancies in Adsorption and Activation of Toluene.

Catalytic oxidation has been extensively studied as a promising technology for the removal of toluene from industrial waste gases and indoor air. However, the debate regarding the oxidation mechanism is far from resolved. CexMn1-xO2 catalysts with different mixing ratios are prepared by the sol-gel method and found to exhibit better catalytic activities for toluene oxidation than a single oxide. Characterizations and theoretical calculations reveal that the doped Mn increases the number of oxygen vacancies and the ability of oxygen vacancies to activate aromatic rings, which promotes the rate-determining step of toluene oxidation, i.e., ring-opening reactions. The oxidation products detected by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and Vocus proton transfer reaction mass spectrometry (Vocus-PTR-MS) show that the doped Mn significantly improves the ring-opening efficiency and subsequently yields more short-chain products, such as pyruvic acid and acetic acid. A comprehensive oxidation pathway of toluene is refined in this work.

Local-Scale Damming Impact on the Planktonic Bacterial and Eukaryotic Assemblages in the upper Yangtze River.

Dam construction and impoundment cause discontinuities in the natural biophysical gradients in rivers. These discontinuities may alter distinctive habitats and different microbial community assembly mechanisms upstream and downstream of dams, which reflect the potential impacts of damming on riverine aquatic ecosystems. In this study, we investigated the planktonic microbial assemblages of three large dams in the upper Yangtze River by using high-throughput sequencing. The results revealed that the alpha diversity indexes increased downstream of the dams. In addition, more eukaryotic ASVs solely occurred downstream of the dams, which indicated that a large proportion of eukaryotes appeared downstream of the dams. The nonmetric multidimensional scaling analysis indicated that there was no obvious geographic clustering of the planktonic microbial assemblages among the different locations or among the different dams. However, the dam barriers changed dam-related variables (maximum dam height and water level) and local environmental variables (water temperature, DOC, etc.) that could possibly affect the assembly of the planktonic microbial communities that are closest to the dams. A co-occurrence network analysis demonstrated that the keystone taxa of the planktonic bacteria and eukaryotes decreased downstream of the dams. In particular, the keystone taxa of the eukaryotes disappeared downstream of the dams. The robustness analysis indicated that the natural connectivity of the microbial networks decreased more rapidly upstream of the dams, and the downstream eukaryotic network was more stable. In conclusion, damming has a greater impact on planktonic eukaryotes than on bacteria in near-dam areas, and planktonic microbial assemblages were more susceptible to the environmental changes. Our study provides a better understanding of the ecological effects of river damming.

Correlation Analysis of Vascular Endothelial Growth Factor Level with Clinicopathological Features and Prognosis in Patients with Diabetic Nephropathy: A Biopsy-based Study.

Globally, Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases, which poses a great potential threat to the human body. Diabetic nephropathy (DN), a very common complication in T2DM, is also the main trigger for end-stage renal disease. A thorough understanding of the pathogenesis is the key as well as the breakthrough for future diagnosis and treatment of DN. This investigation aims to provide more in-depth and accurate guidance for future follow-up research by analyzing the role of vascular endothelial growth factor (VEGF) in the kidney tissue of DN patients. Seventy-nine patients with suspected DN who underwent renal needle biopsy in our hospital from January 2015 to June 2019 were selected as the research participants. After the biopsy, 36 cases were confirmed as DN, and the other 43 were T2DM with primary glomerulonephritis. Determination of VEGF mRNA and protein expression in renal tissue employed PCR and Western blot, and the connection between VEGF mRNA level and clinical pathology (such as renal function, inflammatory factors and pathological manifestations) was discussed. The disease recurrence in DN patients was recorded through the 3-year prognostic followed up, and the related influencing factors were analyzed. In kidney tissue, VEGF mRNA level and protein expression were notably higher in DN patients than in diabetic patients (P<0.05). Pearson correlation coefficient analysis identified that VEGF mRNA and protein had a positive connection with blood urea nitrogen (BUN), serum creatinine (Scr), 24-hour urine total protein (24hUTP) and C-reactive protein (CRP) (P<0.05). Among the various clinicopathological features of DN patients, age, BMI, sex, family history, smoking, drinking, exercise habits, clinical presentations and pathological changes had no significant relationship with VEGF level (P>0.05), but the course of the disease, fasting blood glucose (FBG), glycosylated hemoglobin (HBALC) and pathological stages of nephropathy had a close connection with VEGF level (P<0.05). Prognostic follow-up revealed that VEGF mRNA was noticeably higher in patients with recurrence than in those without (P<0.05). When VEGF mRNA >5.20 in kidney tissue, the sensitivity and specificity for predicting the 3-year recurrence were 85.71% and 84.00% respectively (P<0.05). Finally, Logistic regression analysis identified the independence of FBG, HBALC and VEGF levels as the influencing factors for the prognostic recurrence of DN (P<0.05).VEGF expression in kidney tissue of DN patients is closely linked to renal function and increases as the disease progresses, which is an independent risk factor associated with the prognostic recurrence of DN, with great potential significance for future DN diagnosis and treatment.

Enrichment of miR-17-5p enhances the protective effects of EPC-EXs on vascular and skeletal muscle injury in a diabetic hind limb ischemia model.

BACKGROUND/AIMS: Diabetes mellitus (DM) is highly susceptible to diabetic hind limb ischemia (DHI). MicroRNA (MiR)-17-5p is downregulated in DM and plays a key role in vascular protection. Endothelial progenitor cell (EPC)-released exosomes (EPC-EXs) contribute to vascular protection and ischemic tissue repair by transferring their contained miRs to target cells. Here, we investigated whether miR-17-5p-enriched EPC-EXs (EPC-EXsmiR-17-5p) had conspicuous effects on protecting vascular and skeletal muscle in DHI in vitro and in vivo. METHODS: EPCs transfected with scrambled control or miR-17-5p mimics were used to generate EPC-EXs and EPC-EXsmiR-17-5p. Db/db mice were subjected to hind limb ischemia. After the surgery, EPC-EXs and EPC-EXsmiR-17-5p were injected into the gastrocnemius muscle of the hind limb once every 7 days for 3 weeks. Blood flow, microvessel density, capillary angiogenesis, gastrocnemius muscle weight, structure integrity, and apoptosis in the hind limb were assessed. Vascular endothelial cells (ECs) and myoblast cells (C2C12 cells) were subjected to hypoxia plus high glucose (HG) and cocultured with EPC-EXs and EPC-EXsmiR-17-5p. A bioinformatics assay was used to analyze the potential target gene of miR-17-5p, the levels of SPRED1, PI3K, phosphorylated Akt, cleaved caspase-9 and cleaved caspase-3 were measured, and a PI3K inhibitor (LY294002) was used for pathway analysis. RESULTS: In the DHI mouse model, miR-17-5p was markedly decreased in hind limb vessels and muscle tissues, and infusion of EPC-EXsmiR-17-5p was more effective than EPC-EXs in increasing miR-17-5p levels, blood flow, microvessel density, and capillary angiogenesis, as well as in promoting muscle weight, force production and structural integrity while reducing apoptosis in gastrocnemius muscle. In Hypoxia plus HG-injured ECs and C2C12 cells, we found that EPC-EXsmiR-17-5p could deliver their carried miR-17-5p into target ECs and C2C12 cells and subsequently downregulate the target protein SPRED1 while increasing the levels of PI3K and phosphorylated Akt. EPC-EXsmiR-17-5p were more effective than EPC-EXs in decreasing apoptosis and necrosis while increasing viability, migration, and tube formation in Hypoxia plus HG-injured ECs and in decreasing apoptosis while increasing viability and myotube formation in C2C12 cells. These effects of EPC-EXsmiR-17-5p could be abolished by a PI3K inhibitor (LY294002). CONCLUSION: Our results suggest that miR-17-5p promotes the beneficial effects of EPC-EXs on DHI by protecting vascular ECs and muscle cell functions.

Electrocatalytic oxidation of gaseous toluene in an all-solid cell using a foam Ti/Sb-SnO2/ß-PbO2 anode.

Mineralization of benzene, toluene, and xylene (BTX) with high efficiency at room temperature is still a challenge for the purification of indoor air. In this work, a foam Ti/Sb-SnO2/ß-PbO2 anode catalyst was prepared for electrocatalytically oxidizing gaseous toluene in an all-solid cell at ambient temperature. The complex Ti/Sb-SnO2/ß-PbO2 anode, which was prepared by sequentially deposing Sb-SnO2 and ß-PbO2 on a foam Ti substrate, shows high electrocatalytic oxidation efficiency of toluene (80%) at 7 hr of reaction and high CO2 selectivity (94.9%) under an optimized condition, i.e., a cell voltage of 2.0 V, relative humidity of 60% and a flow rate of 100 mL/min. The better catalytic performance can be ascribed to the high production rate of ⋅OH radicals from discharging adsorbed water and the inhibition of oxygen evolution on the surface of foam Ti/Sb-SnO2/ß-PbO2 anode when compared with the foam Ti/Sb-SnO2 anode. Our results demonstrate that prepared complex electrodes can be potentially used for electrocatalytic removal of gaseous toluene at room temperature with a good performance.

Emodin alleviates arthritis pain through reducing spinal inflammation and oxidative stress.

Chronic pain is the predominant problem for rheumatoid arthritis patients, and negatively affects quality of life. Arthritis pain management remains largely inadequate, and developing new treatment strategies are urgently needed. Spinal inflammation and oxidative stress contribute to arthritis pain and represent ideal targets for the treatment of arthritis pain. In the present study, collagen-induced arthritis (CIA) mouse model was established by intradermally injection of type II collagen (CII) in complete Freund's adjuvant (CFA) solution, and exhibited as paw and ankle swelling, pain hypersensitivity and motor disability. In spinal cord, CIA inducement triggered spinal inflammatory reaction presenting with inflammatory cells infiltration, increased Interleukin-1ß (IL-1ß) expression, and up-regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase-1 levels, elevated spinal oxidative level presenting as decreased nuclear factor E2-related factor 2 (Nrf2) expression and Superoxide dismutase (SOD) activity. To explore potential therapeutic options for arthritis pain, emodin was intraperitoneally injected for 3 days on CIA mice. Emodin treatment statistically elevated mechanical pain sensitivity, suppressed spontaneous pain, recovered motor coordination, decreased spinal inflammation score and IL-1ß expression, increased spinal Nrf2 expression and SOD activity. Further, AutoDock data showed that emodin bind to Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) through two electrovalent bonds. And emodin treatment increased the phosphorylated AMPK at threonine 172. In summary, emodin treatment activates AMPK, suppresses NLRP3 inflammasome response, elevates antioxidant response, inhibits spinal inflammatory reaction and alleviates arthritis pain.

Damming river shapes distinct patterns and processes of planktonic bacterial and microeukaryotic communities.

Planktonic bacterial and microeukaryotic communities play important roles in biogeochemical cycles, but their biogeographic patterns and community assembly processes in large damming rivers still remain unclear. In this study, 16S rRNA and 18S rRNA coding genes were used for sample sequencing analysis of planktonic bacterial and microeukaryotic communities in the upper Yangtze River. The upper Yangtze River was divided into dam-affected zones and river zones based on the influence of dams. The results showed that there were significant differences in the bacterial and microeukaryotic communities between the two zones and that dams significantly reduced the α-diversity of the bacterial communities. Co-occurrence network analysis indicated that networks in the river zone were denser than those in the dam-affected zone. The relationships among species in bacterial networks were more complex than those in microeukaryotic networks. Dispersal limitation and ecological drift were the main processes influencing planktonic bacterial and microeukaryotic communities in the dam-affected zone respectively, whereas the role of deterministic processes increased in the river zone. Anthropogenic activities and hydraulic conditions affected suspended sediment and controlled microbial diversity in the river zone. These results suggest that dams impact planktonic bacteria more strongly than planktonic microeukaryotes, indicating that the distribution patterns and processes of the bacterial and microeukaryotic communities in large rivers are significantly different.

Cyanidin-3-O-glucoside impacts fecal discharge of polystyrene microplastics in mice: Potential role of microbiota-derived metabolites.

Microplastic particles degraded from plastic litters are recognized as a global environmental pollutant, which can be transferred and enriched via the food chain to impact ecosystems and human health. A balanced gut microbiota contributes to human health through host-gut interactions, environmentally-driven factors such as microplastic exposure would disturb the gut bacteria and affect its functionality. Dietary compounds can remodel the compositions of gut microbes, and interact with bacteria exerting profound effects on host physiology. This study explored the effects of bayberry-derived anthocyanin cyanidin-3-O-glucoside (C3G) and microplastic polystyrene (PS) on the gut microbiome in C57BL/6 mice, especially the alterations in gut bacteria and its metabolites. Using 16S rRNA high-throughput sequencing, variations in gut bacterial composition and enrichment of functional pathways were found upon PS and C3G administration. Meanwhile, the differential metabolites and metabolic pathways were identified by metabolomic analysis. Importantly, colonic and fecal PS levels were found to be strongly correlated with key microbiota-derived metabolites, which are associated with xenobiotic metabolism via regulation of xenobiotics-metabolizing enzymes and transporters. These results may offer new insights regarding the protective effects of C3G against xenobiotic PS exposure and the roles of gut bacterial metabolites.

Serum Fat-Soluble Vitamin Levels of 6,082 Minors in Zhuzhou City.

Objective: To explore the nutritional status of serum fat-soluble vitamins such as vitamin A, 25-hydroxyvitamin D, and vitamin E of minors in the Zhuzhou area to provide a scientific basis for clinical guidance to supplement fat-soluble vitamins reasonably. Method: A total of 6,082 minors who underwent physical examination from January 2017 to February 2019 in the Children's Health Department of Zhuzhou Hospital affiliated with XiangYa School of Medicine of Central South University were selected as the subjects to measure the levels of serum fat-soluble vitamins A, D, and E. Results: (1) Their average levels of serum vitamin A, 25-hydroxyvitamin D, and vitamin E were (0.34 ± 0.08) mg/mL, (34.65 ± 10.24) ng/mL, and (10.11 ± 2.65) mg/mL, respectively. (2) Serum vitamin E showed a gender difference (P < 0.001). (3) The average levels of serum 25-hydroxyvitamin D and vitamin E in infancy, early childhood, preschool age, school age, and adolescence decreased gradually (P < 0.05). In contrast, the average level of serum vitamin A ranged between 0.32 mg/mL and 0.37 mg/mL. (4) The age was negatively correlated with serum 25-hydroxyvitamin D (r = -0.517, P < 0.001) and weakly negatively correlated with vitamin E (r = -0.366, P < 0.001), but weakly positively correlated with vitamin A (r = 0.269, P < 0.001). Conclusion: Minors from infancy to adolescence in Zhuzhou should strengthen their supplementation of fat-soluble vitamins.

Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways.

Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1ß, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-ß1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway.