23-Hydroxybetulinic acid attenuates 5-fluorouracil resistance of colorectal cancer by modulating M2 macrophage polarization via STAT6 signaling.

Macrophage polarization is closely associated with the inflammatory processes involved in the development and chemoresistance of colorectal cancer (CRC). M2 macrophages, the predominant subtype of tumor-associated macrophages (TAMs) in a wide variety of malignancies, have been demonstrated to promote the resistance of CRC to multiple chemotherapeutic drugs, such as 5-fluorouracil (5-FU). In our study, we investigated the potential of 23-Hydroxybetulinic Acid (23-HBA), a significant active component of Pulsatilla chinensis (P. chinensis), to inhibit the polarization of M2 macrophages induced by IL-4. Our results showed that 23-HBA reduced the expression of M2 specific marker CD206, while downregulating the mRNA levels of M2 related genes (CD206, Arg1, IL-10, and CCL2). Additionally, 23-HBA effectively attenuated the inhibitory effects of the conditioned medium from M2 macrophages on apoptosis in colorectal cancer SW480 cells. Mechanistically, 23-HBA prevented the phosphorylation and nuclear translocation of the STAT6 protein, resulting in the inhibition of IL-10 release in M2 macrophages. Moreover, it interfered with the activation of the IL-10/STAT3/Bcl-2 signaling pathway in SW480 cells, ultimately reducing M2 macrophage-induced resistance to 5-FU. Importantly, depleting STAT6 expression in macrophages abolished the suppressive effect of 23-HBA on M2 macrophage polarization, while also eliminating its ability to decrease M2 macrophage-induced 5-FU resistance in cancer cells. Furthermore, 23-HBA significantly diminished the proportion of M2 macrophages in the tumor tissues of colorectal cancer mice, simultaneously enhancing the anti-cancer efficacy of 5-FU. The findings presented in this study highlight the capacity of 23-HBA to inhibit M2 macrophage polarization, a process that contributes to reduced 5-FU resistance in colorectal cancer.

Edgeworthia gardneri (Wall.) Meisn. Ethanolic Extract Attenuates Endothelial Activation and Alleviates Cardiac Ischemia-Reperfusion Injury.

Endothelial pro-inflammatory activation is pivotal in cardiac ischemia-reperfusion (I/R) injury pathophysiology. The dried flower bud of Edgeworthia gardneri (Wall.) Meisn. (EG) is a commonly utilized traditional Tibetan medicine. However, its role in regulating endothelium activation and cardiac I/R injury has not been investigated. Herein, we showed that the administration of EG ethanolic extract exhibited a potent therapeutic efficacy in ameliorating cardiac endothelial inflammation (p < 0.05) and thereby protecting against myocardial I/R injury in rats (p < 0.001). In line with the in vivo findings, the EG extract suppressed endothelial pro-inflammatory activation in vitro by downregulating the expression of pro-inflammatory mediators (p < 0.05) and diminishing monocytes' firm adhesion to endothelial cells (ECs) (p < 0.01). Mechanistically, we showed that EG extract inhibited the nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways to attenuate EC-mediated inflammation (p < 0.05). Collectively, for the first time, this study demonstrated the therapeutic potential of EG ethanolic extract in alleviating I/R-induced inflammation and the resulting cardiac injury through its inhibitory role in regulating endothelium activation.

Inhibition of PTEN-induced kinase 1 autophosphorylation may assist in preventing epileptogenesis induced by pentylenetetrazol.

PTEN-induced kinase 1 (PINK1) autophosphorylation-triggered mitophagy is the main mitophagic pathway in the nervous system. Moreover, multiple studies have confirmed that mitophagy is closely related to the occurrence and development of epilepsy. Therefore, we speculated that the PINK1 autophosphorylation may be involved in epileptogenesis by mediating mitophagic pathway. This study aimed to explore the contribution of activated PINK1 to epileptogenesis induced by pentylenetetrazol (PTZ) in Sprague‒Dawley rats. During PTZ-induced epileptogenesis, the levels of phosphorylated PINK1 were increased, accompanied by elevated mitophagy, mitochondria oxidative stress and neuronal damage. After microRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7) or overlapping with the m-AAA protease 1 homolog (OMA1), the levels of PINK1 phosphorylation, mitophagy, mitochondrial oxidative stress, neuronal injury were observed in the rats with induced epileptogenesis. Furthermore, inhibiting of the expression of TOM7, a positive regulator of PINK1 autophosphorylation, reversed the increase in PINK1 phosphorylation and alleviated mitophagy, neuronal injury, thereby preventing epileptogenesis. In contrast, reducing the levels of OMA1, a negative regulator of PINK1 autophosphorylation, led to increased phosphorylation of PINK1, accompanied by aggravated neuronal injury and ultimately, epileptogenesis. This study confirmed the contribution of activated PINK1 to PTZ-induced epileptogenesis and suggested that the inhibition of PINK1 autophosphorylation may assist in preventing epileptogenesis.

[Bletilla striata polysaccharide improves toxic and side effects induced by 5-FU: an untargeted metabolomics study].

This study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.

Case report: cerebral venous sinus thrombosis and pulmonary embolism as the initial presentation in a child with asymptomatic primary nephrotic syndrome.

Background: Cerebral venous sinus thrombosis (CVST) is rare, but potentially life-threatening. The clinical course definitely become more unpredictable and fatal in patients complicated by pulmonary embolism (PE). Nephrotic syndrome (NS) is an uncommon etiology of CVST. Concurrence of CVST and PE at the initial onset of NS is extremely unusual and rarely reported. Considering that edema might be absent in NS individuals, thromboembolic events probably become unrecognized, thereby causing a missed or delayed diagnosis and poor outcome. Herein, we described an extraordinary case of an adolescent boy presenting with both CVST and PE initially just within 5 days of disease onset, who was ultimately diagnosed with asymptomatic NS, aiming to emphasize a high index of suspicion of these diseases in patients with conditions of hypercoagulability. Case presentation: A 13-year-old male child presented acutely with dizziness, fever and dyspnea, with signs of shock but undetected edema. Initial laboratory investigations revealed hypoalbuminemia, typical images of pneumonia, and normal radiographic findings on non-enhanced computed tomography of head. Despite evidence of hypoalbuminemia and neurological symptoms, the child was still misdiagnosed as pneumonia. His dyspnea and period of headache deteriorated even if hemodynamic stability and undetected fever after initial therapy. The delayed urinalysis and 24-h urine examination both showed massive proteinuria. A computed tomography angiography of chest along with cranial magnetic resonance imaging/magnetic resonance venography were subsequently performed, consistent with the imaging features of PE and CVST, respectively. The diagnosis of asymptomatic primary NS complicated by PE and CVST was ultimately confirmed. The patient received corticosteroids and antithrombotic therapy with satisfactory results. Conclusion: A persistent clinical suspicion of CVST should be borne in mind in patients with a sudden, new or worsening headache, specifically among those with prothrombotic conditions. NS should always be considered in the differential diagnosis of risk factors for CVST, even in absence of edema. Since CVST and PE can be present simultaneously at extraordinary early-onset of NS, early radiological diagnosis is clinically substantial to proper management and satisfactory long-term outcomes.

[UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood].

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

SnS-SnO2 Heterostructures Anchored on GO as a High-Performance Anode for Sodium Ion Battery.

SnO2 is a theoretically excellent transformed anode material with high theoretical capacity for SIBs. However, SnO2 faces serious volume effect and high resistance, which greatly damages its electrochemical performance. Given that, the SnS-SnO2 heterostructures is constructed with special internal electric field, which is beneficial to promote the transfer ability of sodium ions. Besides, the graphene oxide (GO) modification is carried out to isolate the intrinsic materials from direct contact with electrolyte, and alleviate volume expansion of the anode, ultimately promote the electrochemical performance. Furthermore, the structure and the conductivity characteristics of SnS, SnO2 , SnS-SnO2 and SnS-SnO2 @ GO are simulated respectively by first principles and are compared with the correspondence experiment results to verify the accuracy of established models. Owing to the special p-n junction in SnS-SnO2 @GO heterostructures, the resistance of SnS-SnO2 @GO can be reduced to 36.23 Ω, much lower than that of SnO2 (Rct=341.9 Ω). Notably, the combination of GO has effectively alleviated the volume expansion of SnS-SnO2 @GO electrodes, and present excellent capacity higher than 384.7 mAh g-1 after 100 cycles. Thus, the efficient synthesis of SnS-SnO2 @GO heterostructure electrodes with excellent performance for sodium storage is expected to provide valuable direction for SIBs anode materials.

Anemoside A3 Inhibits Macrophage M2-Like Polarization to Prevent Triple-Negative Breast Cancer Metastasis.

Triple negative breast cancer (TNBC) exhibits the characteristics of strong metastatic ability and a high recurrence rate, and M2-type macrophages play an important role in this process. Previous research data suggested that Anemoside A3 (A3), a monomeric component of Pulsatilla Chinensis, could prevent and treat TNBC by converting M0 macrophages into M1 immunogen phenotypes. This study showed that A3 significantly restrained the lung metastases of 4 T1-Luc cells with bioluminescence imaging in vivo and Hematoxylin and Eosin (H&E) staining. Meanwhile, the percentage of M2-type macrophages (CD206+ labeled cells) in the lung tissues was evidently decreased through immunohistochemical assay. We further proved that A3 markedly prevented M2-type polarization induced by IL-4 in vitro, as illustrated by the down-regulated expression of the cell surface marker CD206 protein by FACS and Arg-1, and of the Fizz1 and Ym1 genes by RT-PCR in M2-type macrophages. Furthermore, the invasion and migration of 4 T1 cells, which was promoted by the conditioned medium from M2-type macrophages, could be suppressed by A3. Luminex assay demonstrated that A3 treatment resulted in a reduction of the levels of CCL2, VEGF, CCL7, and MMP-9 in conditioned medium. Additionally, the expression of phosphorylated-STAT3 protein was inhibited by A3, which resulted in the macrophage M2-type polarization arrest, while no significant difference in JAK2 phosphorylation was detected. SiRNA transfection experiments suggested that STAT3 might be the target of A3 inhibiting M2-type polarization of macrophages. In conclusion, these results indicate that A3 could attenuate the metastasis of TNBC by inhibiting the M2-type polarization of macrophages, which may be related to the STAT3 pathway.

Leaching NCM cathode materials of spent lithium-ion batteries with phosphate acid-based deep eutectic solvent.

Deep eutectic solvents (DESs) play an important role in efficient recovery of spent lithium-ion batteries (LIBs). In this study, we proposed an efficient and safe method by using a choline chloride-phenylphosphinic acid DES as a lixiviant for the leaching of LiNixCoyMnzO2 (NCM) cathode active materials of spent LIBs. The leaching conditions were optimized based on the leaching time, liquid-solid ratio, and leaching temperature. Under optimal experimental conditions, the leaching efficiencies of Li, Co, Ni, and Mn reached 97.7 %, 97.0 %, 96.4 %, and 93.0 %, respectively. The kinetics of the leaching process were well-fitted using the logarithmic law equation. The apparent activation energies for Li, Co, Ni, and Mn have been reported to be 60.3 kJ/mol, 78.9 kJ/mol, 99.3 kJ/mol, and 82.1 kJ/mol, respectively. UV-visible spectroscopy and Fourier transform infrared analysis revealed that the coordination configurations of Ni and Co in the leaching solution were octahedral and tetrahedral, respectively. In addition, the PO bond in phenylphosphinic acid was involved in coordination during leaching. This finding may provide an effective and safe approach for leaching valuable metals from spent LIBs.

Genomic characterization and pathogenicity analysis of a porcine deltacoronavirus strain isolated in western China.

Porcine deltacoronavirus (PDCoV) is an enteric virus that was first identified in 2012. Although PDCoV has been detected worldwide, there is little information about its circulation in western China. In this study, fecal samples were collected from piglets with watery diarrhea in western China between 2015 and 2018 for the detection of PDCoV. The positive rate was 29.9%. A PDCoV strain (CHN/CQ/BN23/2016, BN23) was isolated and selected for further investigation. Phylogenetic analysis showed that this strain formed an individual cluster between the early Chinese lineage and the Chinese lineage. RDP4 and SimPlot analysis demonstrated that strain BN23 is a recombinant of Thailand/S5015L/2015 and CHN-AH-2004. The pathogenicity of BN23 was evaluated in 3-day-old piglets. Challenged piglets developed serious clinical signs and died at 3 days post-inoculation. Our data show that PDCoV is prevalent in western China and that strain BN23 is highly pathogenic to newborn piglets. Therefore, more attention should be paid to emerging PDCoV strains in western China.

Anti-Seizure and Neuronal Protective Effects of Irisin in Kainic Acid-Induced Chronic Epilepsy Model with Spontaneous Seizures.

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.

Attenuated succinate accumulation relieves neuronal injury induced by hypoxia in neonatal mice.

Hypoxia causes neonatal neuronal damage. However, the underlying mechanism remains unclear. This study aimed to explore the changes in succinate levels and identify the mechanisms underlying their contribution to hypoxia-induced damage in newborn mice. The neonatal C57BL/6J mouse hypoxia model was used in our study. We evaluated the levels of succinate, iron, reactive oxygen species (ROS), and mitochondrial ROS, and assessed mitophagy, neuronal damage, and learning and memory function, after hypoxia treatment. The neonatal mice showed increased succinate levels in the early hypoxia stage, followed by increased levels of oxidative stress, iron stress, neuronal damage, and cognitive deficits. Succinate levels were significantly reduced following treatment with inhibitors of succinate dehydrogenase (SDH), purine nucleotide cycle (PNC), and malate/aspartate shuttle (MAS), with the corresponding attenuation of oxidative stress, iron stress, neuronal damage, and cognitive impairment. Reversal catalysis of SDH through fumarate from the PNC and MAS pathways might be involved in hypoxia-induced succinate accumulation. Succinate accumulation in the early period after hypoxia may crucially contribute to oxidative and iron stress. Relieving succinate accumulation at the early hypoxia stage could prevent neuronal damage and cognitive impairment in neonatal hypoxia.

[Molecular mechanism of Dalbergia cochinchinensis heartwood in regulation of energy metabolism to treat myocardial ischemia based on network pharmacology and experimental validation].

Dalbergia cochinchinensis(DC) is chemically similar to the valuable and scarce Chinese herb Dalbergiae Odoriferae Lignum, and both of them belong to the Dalbergia Leguminosae. DC is used for treating cardiovascular diseases and cancer. However, its potent active ingredient groups and molecular mechanisms in anti-myocardial ischemia are not fully clarified. In this study, the active ingredient groups, targets, and signaling pathways of DC heartwood for the treatment of myocardial ischemia were screened out based on network pharmacology and molecular docking technology, and the effects were verified by the rat model of acute myocardial ischemia induced by isoprenaline(ISO). The molecular mechanism of DC heartwood was elucidated based on the target of multi-ingredient and multi-target pathways. The crossing targets of DC heartwood for the treatment of myocardial ischemia were identified through the screening of active ingredients in DC heartwood and the prediction of targets. The Kyoto Encyclopedia of Genomes(KEGG) pathway enrichment and Gene Ontology(GO) functional annotation were performed. AutoDock was used to bind the active ingredient groups to the pathway targets. Finally, the molecular mechanism of myocardial ischemia treatment by DC heartwood extracts in the treatment of myocardial ischemia was revealed through the rat model of ISO-induced acute myocardial ischemia by performing electrocardiogram(ECG), hemodynamic, cardiac enzymes, hematoxylin-eosin(HE) staining, high-energy phosphate compounds, reverse transcription polymerase chain reaction(RT-PCR), and Western blot pharmacodynamic experiments, based on the multi-ingredient and multi-target action of active ingredient groups and pathway targets. The network pharmacology showed that the 18 ingredients of DC heartwood corresponded to 510 targets, 629 myocardial ischemia-related targets, and 101 cross-targets. GO and KEGG enrichment analyses showed that DC heartwood was involved in the hypoxic response, vasoconstriction, and nitric oxide biosynthesis, and had effects on the molecular functions of hemoglobin binding, protein binding, and adenosine triphosphate(ATP) binding. It regulated the signaling pathways such as hypoxia-inducible factor 1(HIF-1), vascular endothelial growth factor(VEGF), and phosphatidylinositol-3-kinase/protein kinase B(PI3 K/AKT) to act on myocardial ischemia. Experimental studies showed that DC heartwood slowed down the heart rate and ST segment change(ΔST), and increased systolic blood pressure(SBP), diastolic blood pressure(DBP), and mean arterial pressure(MBP) in rats with ISO-induced acute myocardial ischemia. It also reduced plasma lactate dehydrogenase(LDH), creatine kinase isoenzyme MB(CK-MB), and glutamate transaminase(AST) levels, relieved myocardial fiber disorders and inflammatory cell infiltration, and increased ATP and cellular energy(EC) levels. DC heartwood increased the mRNA expressions of calmodulin-dependent protein kinase kinase(CAMKK) in the myocardial tissue, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3), mammalian target of rapamycin(mTOR), PI3 K, VEGF, endothelial nitric oxide synthase(eNOS), HIF-1α in the myocardial tissue. It decreased the mRNA expression of pyruvate dehydrogenase(PDH), and increased the protein expressions of PFKFB3, VEGFA, and eNOS. Molecular docking showed that liquiritigenin, stigmasterol, isodalbergin, latifolin, 4-methoxydalbergione, dibutyl terephthalate, 2,4-dihydroxy-5-methoxybenzophenone in DC heartwood produced bio-binding activities with epidermal growth factor receptor(EGFR), HIF-1α, CAMKK, PI3 K, mTOR, and PDH, respectively. Therefore, the active ingredient groups of DC heartwood act on the HIF-1 signaling pathway, regulate cardiomyocyte energy metabolism, and increase ATP energy charge in a multi-ingredient and multi-target manner, improving cardiac function and histopathological changes to protect rats with acute myocardial ischemia induced by ISO.

Neuroprotective Effects of Exogenous Irisin in Kainic Acid-Induced Status Epilepticus.

Elevated reactive oxygen species (ROS) level is considered a crucial causative factor for neuronal damage in epilepsy. Irisin has been reported to ameliorate mitochondrial dysfunction and to reduce ROS levels; therefore, in this study, the effect of exogenous irisin on neuronal injury was evaluated in rats with kainic acid (KA)-induced status epilepticus (SE). Our results showed that exogenous irisin treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), and reduced the levels of neuronal injury and mitochondrial oxidative stress. Additionally, an inhibitor of UCP2 (genipin) was administered to investigate the underlying mechanism of irisin-induced neuroprotection; in rats treated with genipin, the neuroprotective effects of irisin on KA-induced SE were found to be partially reversed. Our findings confirmed the neuroprotective effects of exogenous irisin and provide evidence that these effects may be mediated via the BDNF/UCP2 pathway, thus providing valuable insights that may aid the development of exogenous irisin treatment as a potential therapeutic strategy against neuronal injury in epilepsy.

The neuroprotective effect and possible therapeutic application of xenon in neurological diseases.

Xenon is an inert gas with stable chemical properties which is used as an anesthetic. Recent in vitro and in vivo findings indicate that xenon also elicits an excellent neuroprotective effect in subanesthetic concentrations. The mechanisms underlying this primarily involve the attenuation of excitotoxicity and the inhibition of N-methyl-d-aspartic acid (NMDA) receptors and NMDA receptor-related effects, such as antioxidative effects, reduced activation of microglia, and Ca2+ -dependent mechanisms, as well as the interaction with certain ion channels and glial cells. Based on this strong neuroprotective role, a large number of experimental and clinical studies have confirmed the significant therapeutic effect of xenon in the treatment of neurological diseases. This review summarizes the reported neuroprotective mechanisms of xenon and discusses its possible therapeutic application in the treatment of various neurological diseases.

Succinate accumulation contributes to oxidative stress and iron accumulation in pentylenetetrazol-induced epileptogenesis and kainic acid-induced seizure.

This study explored the role of succinate accumulation in the oxidative stress and iron accumulation in both pentylenetetrazol (PTZ)-induced epileptogenesis and kainic acid (KA)-induced status epilepticus (SE). The levels of succinate, oxidative stress, iron content, iron-related protein expression, and the severity of neuronal injury and seizures were measured in both models. We found that increased concentrations of succinate were associated with increased levels of oxidative stress, iron content, iron regulator protein, and iron importer divalent metal transporter 1, as well as decreased levels of iron exporter ferropotin 1. Aggravated neuronal injury was observed in the hippocampi and cortices of both models. The cell-permeable molecule dimethyl malonate (DM), a competitive inhibitor of succinate dehydrogenase (SDH), significantly attenuated succinate accumulation, reduced the oxidative stress and iron levels, and mitigated the severity of the seizures and neuronal injury. Our results thus indicate that the accumulation of succinate due to the reverse catalysis of SDH may exacerbate oxidative stress and thus induce iron accumulation and neuronal injury in both models. Targeting succinate accumulation may achieve neuroprotective and anti-seizure effects.

Study on the Optimization of Cu-Zn-Sn-O to Prepare Cu2ZnSnS4 Thin Film via a Nano Ink Coating Method.

To reduce the formation of the impurity phase, a buffer volume can be used to expands and smooths the surface of Cu2ZnSnS4(CZTS) thin film. In this study, a Cu-Zn-Sn-O(CZTO) precursor was synthesized through the process of coprecipitation-calcination-ball milling-spin coating. The influence of pH, temperature, and PVP on the constituent of hydroxides was investigated in the process of coprecipitation. Cu-Zn-Sn-O with appropriate compositions could be obtained by regulating the temperature and preservation time of the calcination stage. After ball milling to form a nano ink, and then spin coating, SEM images proved the generation of CZTO precursors, which effectively promoted the formation of Cu2ZnSnS4 thin films. Finally, the phase, microstructure, chemical composition, and optical properties of the Cu2ZnSnS4 thin films prepared by sulfurized annealing CZTO precursors were characterized by EDX, XRD, Raman, FESEM, Hall effect, and UV methods. The prepared CZTS thin film demonstrated a band gap of 1.30 eV, which was suitable for improving the performance of CZTS thin film solar cells.

Using Cu-Zn-Sn-O Precursor to Optimize CZTSSe Thin Films Fabricated by Se Doping With CZTS Thin Films.

The copper-zinc-tin oxide (CZTO) precursor was synthesized to avoid sudden volume expansion from CZTO precursor to Cu2ZnSnS4 (CZTS) thin films and smooth CZTSSe thin-film surfaces without pinholes. The CZTO precursor was prepared by coprecipitation and ball milling to form nanoink of CZTO. Based on the CZTO precursor, the CZTS thin film was fabricated and then selenized to make pinhole-free and flat Cu2ZnSn(S,Se)4(CZTSSe) thin films. The results show that the CZTO precursor greatly contributed to elevating the homologous surface characteristics and crystallinity of CZTSSe thin films by controlling selenium temperature, selenium time, and selenium source temperature. Finally, the conversion efficiency of the CZTSSe thin-film solar cell fabricated from the CZTO precursor was 4.11%, with an open-circuit voltage (Voc) of 623 mV, a short circuit current density (Jsc) of 16.02 mA cm-2, and a fill factor (FF) of 41.2%.

Effects of Eucommia ulmoides extract against renal injury caused by long-term high purine diets in rats.

Diets of overloaded purine-rich foods for a long time are one of the important reasons to cause renal lesions. Eucommia ulmoides is one of the traditional Chinese medicine herbs, which has been used to recover functions of the kidney. However, its mechanism remains unclear. The aim of this study was to explore the effects and protective mechanism of Eucommia ulmoides extract on renal injury caused by long-term high purine diets in rats. SD rats underwent an intragastric adenine (200 mg kg-1 d-1) administration for 9 weeks and were treated for 15 weeks. The results demonstrated that Eucommia ulmoides extract significantly reduced serum Cre and BUN levels in rats. H&E and Masson's trichrome stains showed notable lowering of the infiltration of inflammatory cells, the formation of fibrous tissues and collagen fibers, and improvement in the pathological morphology of kidneys. It also suppressed the protein and mRNA expressions of TGF-ß1 and α-SMA and enhanced E-cadherin expression. Meanwhile, Eucommia ulmoides extract prominently inhibited the mRNA expression of Col I, Col III, Col IV, TIMP-1, and TIMP-2 and promoted expressions of MMP-1, MMP-2 and MMP-9. Through our study, it is the first time to prove that Eucommia ulmoides extract could ameliorate renal interstitial fibrosis and may involve in the regulation of the extracellular matrix (ECM) degradation enzyme (MMPs/TIMPs) system, promotion of the expression of E-cadherin, and suppression of expressions of TGF-ß1 and α-SMA. The results provide a significant implication for the utilization of Eunomia Ulmoides extract as functional foods to enhance renal functions and improve renal injury caused by high purine diets.

Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway.

Macrophages polarized to different phenotypes critically contribute to colitis development by coordinating inflammatory and anti-inflammatory processes. Herein, targeting the balance between the pro-inflammatory M1 and the anti-inflammatory M2 macrophage phenotypes can be a novel therapeutic approach for colitis. In the present study, we firstly demonstrated that tiliroside possessed the ability to alleviate the clinical symptoms of colitis as evidenced by decreased disease activity index (DAI) scores, longer colon length, reduced myeloperoxidase (MPO) activity, and improvement of colonic pathological damage in vivo. Furthermore, we showed that tiliroside modulated the balance between M1 and M2 macrophages toward a more anti-inflammatory status in colonic lamina propria but has little effect on the T cell population and epithelial barrier function in colitis mice. The macrophage depletion study further showed the protective effect of tiliroside was macrophage dependent in vivo. Mechanistically, our study demonstrated that tiliroside regulated cellular metabolism by inhibiting aerobic glycolysis in LPS and IFNγ stimulated macrophages. At the molecular level, tiliroside facilitated the proteasomal degradation of HIF-1α and downregulated mRNA expressions of HIF-1α dependent glycolytic enzymes in macrophages. Collectively, our data highlight the aberrant M1/M2 macrophage polarization in the initiation and development of ulcerative colitis and put forth the stage for considering tiliroside as a metabolic regulator in reprogramming macrophage polarization, which may serve as a promising therapeutic approach for treatment of inflammation-associated and metabolic disorders.