Efficient remediation of different concentrations of Cr-contaminated soils by nano zero-valent iron modified with carboxymethyl cellulose and biochar.

Nano zero-valent iron (nZVI) is widely used in soil remediation due to its high reactivity. However, the easy agglomeration, poor antioxidant ability and passivation layer of Fe-Cr coprecipitates of nZVI have limited its application scale in Cr-contaminated soil remediation, especially in high concentration of Cr-contaminated soil. Herein, we found that the carboxymethyl cellulose on nZVI particles could increase the zeta potential value of soil and change the phase of nZVI. Along with the presence of biochar, 97.0% and 96.6% Cr immobilization efficiency through CMC-nZVI/BC were respectively achieved in high and low concentrations of Cr-contaminated soils after 90-days remediation. In addition, the immobilization efficiency of Cr(VI) only decreased by 5.1% through CMC-nZVI/BC treatment after 10 weeks aging in air, attributing to the strong antioxidation ability. As for the surrounding Cr-contaminated groundwater, the Cr(VI) removal capacity of CMC-nZVI/BC was evaluated under different reaction conditions through column experiments and COMSOL Multiphysics. CMC-nZVI/BC could efficiently remove 85% of Cr(VI) in about 400 hr when the initial Cr(VI) concentration was 40 mg/L and the flow rate was 0.5 mL/min. This study demonstrates that uniformly dispersed CMC-nZVI/BC has an excellent remediation effect on different concentrations of Cr-contaminated soils.

Selectively T cell phosphorylation activation of azvudine in the thymus tissue with immune protection effect.

Thymus is the important immune organ, responsible for T cell development and differentiation. The lower circulating T counts have been observed in patients who died from COVID-19 compared with survivors. Azvudine, also known as FNC, is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 patients. In this study, single-cell transcriptome, proteomics, and parallel reaction monitoring (PRM) were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey thymus. The results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as FNC. Key enzymes involved in the FNC phosphorylation process, such as Dck, Cmpk1, and Nme2, were highly expressed in CD4+ T cells, CD8+ T cells, and DP (CD4+ CD8+) cells. Additionally, FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases, phosphoribosyl transferases, and deaminases, respectively. The robust phosphorylation capacity of the thymus for cytidine analogue drug FNC, and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection effect. This suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties, as an important factor during antiviral drug design.

Active components of Dengzhan Shengmai ameliorate cognitive impairment by facilitating hippocampal long-term potentiation via the NMDA receptor-mediated Ca2+/CaMKII pathway.

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Effect and mechanism of gomisin D on the isoproterenol induced myocardial injury in H9C2 cells and mice.

We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis. Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+. Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle. These results demonstrated that gomisin D had a significant effect on isoproterenol-induced myocardial injury by inhibiting oxidative stress, calcium overload and improving mitochondrial energy metabolism.

Cancer Differentiation Inducer Chlorogenic Acid Suppresses PD-L1 Expression and Boosts Antitumor Immunity of PD-1 Antibody.

As immune checkpoint inhibitors have shown good clinical efficacy, immune checkpoint blockade has become a vital strategy in cancer therapy. However, approximately only 12.5% patients experience benefits from immunotherapy. Herein, we identified the cancer differentiation inducer chlorogenic acid (CGA, now in the phase II clinical trial in China for glioma treatment) to be a small-molecular immune checkpoint inhibitor that boosted the antitumor effects of the anti-PD-1 antibody. CGA suppressed the expression of PD-L1 induced by interferon-γ in tumor cell culture through inhibition of the p-STAT1-IRF1 pathway and enhanced activity of activated T-cells. In two murine tumor xenografts, combination therapy of CGA with anti-PD-1 antibody decreased the expression of PD-L1 and IRF1 and increased the inhibitory effect of the anti-PD-1 antibody on tumor growth. Particularly, the activity of tumor infiltrated T cells was enhanced by CGA. CGA improved the gene expression of granzymes in tumor-infiltrated immune cells. In conclusion, through induction of differentiation, CGA appeared to suppress the expression of PD-L1 on cancer cells, effectively promoting infiltrated T cells in the tumor and boosting the antitumor effect of the anti-PD-1 antibody. Thus, CGA might serve as a promising agent to enhance anticancer immunotherapy if combined with anti-PD-1 antibodies.

Caffeic acid alleviates cerebral ischemic injury in rats by resisting ferroptosis via Nrf2 signaling pathway.

There are few effective and safe neuroprotective agents for the treatment of ischemic stroke currently. Caffeic acid is a phenolic acid that widely exists in a number of plant species. Previous studies show that caffeic acid ameliorates brain injury in rats after cerebral ischemia/reperfusion. In this study we explored the protective mechanisms of caffeic acid against oxidative stress and ferroptosis in permanent cerebral ischemia. Ischemia stroke was induced on rats by permanent middle cerebral artery occlusion (pMCAO). Caffeic acid (0.4, 2, 10 mg·kg-1·d-1, i.g.) was administered to the rats for 3 consecutive days before or after the surgery. We showed that either pre-pMCAO or post-pMCAO administration of caffeic acid (2 mg·kg-1·d-1) effectively reduced the infarct volume and improved neurological outcome. The therapeutic time window could last to 2 h after pMCAO. We found that caffeic acid administration significantly reduced oxidative damage as well as neuroinflammation, and enhanced antioxidant capacity in pMCAO rat brain. We further demonstrated that caffeic acid down-regulated TFR1 and ACSL4, and up-regulated glutathione production through Nrf2 signaling pathway to resist ferroptosis in pMCAO rat brain and in oxygen glucose deprivation/reoxygenation (OGD/R)-treated SK-N-SH cells in vitro. Application of ML385, an Nrf2 inhibitor, blocked the neuroprotective effects of caffeic acid in both in vivo and in vitro models, evidenced by excessive accumulation of iron ions and inactivation of the ferroptosis defense system. In conclusion, caffeic acid inhibits oxidative stress-mediated neuronal death in pMCAO rat brain by regulating ferroptosis via Nrf2 signaling pathway. Caffeic acid might serve as a potential treatment to relieve brain injury after cerebral ischemia. Caffeic acid significantly attenuated cerebral ischemic injury and resisted ferroptosis both in vivo and in vitro. The regulation of Nrf2 by caffeic acid initiated the transcription of downstream target genes, which were shown to be anti-inflammatory, antioxidative and antiferroptotic. The effects of caffeic acid on neuroinflammation and ferroptosis in cerebral ischemia were explored in a primary microglia-neuron coculture system. Caffeic acid played a role in reducing neuroinflammation and resisting ferroptosis through the Nrf2 signaling pathway, which further suggested that caffeic acid might be a potential therapeutic method for alleviating brain injury after cerebral ischemia.

A study on cholesterol-cholesteryl ester metabolic homeostasis and drug intervention in hyperlipidemic hamsters using UHPLC-MS/MS.

Hyperlipidemia is a global metabolic disorder characterized by dysregulation of lipid metabolism. This dysregulation is closely associated with the altered homeostasis of cholesterol-cholesteryl ester (CE) metabolism in systemic circulation, and some organs. Additionally, the relationship between oxidized cholesteryl ester (oxCE) and the disease has also gained attention. Currently, there is a lack of comprehensive research on the alterations in cholesterol-CE metabolism in the context of hyperlipidemia, as well as the characteristics of lipid-lowering agents in regulating this metabolic state. Therefore, 40 oxCEs were identified in the hamster liver sample, and novel ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) methods were established for simultaneous analysis of cholesterol, 57 CEs, and 40 oxCEs in the serum, liver, adipose tissue, and intestine of hyperlipidemic hamsters. This study investigated the metabolic alterations between cholesterol-CE/oxCE in hyperlipidemic hamsters and those treated with lipid-lowering agents, including the Niemann-Pick-C1 like-1 protein (NPC1L1) inhibitor ezetimibe and the acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor avasimibe. The study findings demonstrate metabolic disorders in cholesterol-CE/oxCE homeostasis in hyperlipidemic hamsters. Lipid-lowering agent therapy can improve the metabolic dysregulation caused by hyperlipidemia, with distinct characteristics: ezetimibe is more effective in reducing cholesterol, while avasimibe is more effective in reducing CEs/oxCEs. Eight potential biomarkers indicating the dysregulation of cholesterol-CE metabolism caused by hyperlipidemia and its improvement by lipid-lowering agents have been identified in the serum. This study offers new insights into the hyperlipidemia pathophysiology and the mechanisms of lipid-lowering agents from a novel perspective on cholesterol-CE/oxCE metabolic homeostasis.

SuperMap-Based Research on the Spread Situation and Visual Monitoring Platform of Major Health Events.

To present information on infectious diseases caused by viruses clearly and track the changes of data in real-time, data visualization can be used preferentially considering that it can identify problems behind data accurately. In this paper, based on the SuperMap Online platform and Tianditu, a national platform for common geospatial information services, a risk level map of infectious diseases distribution area is made by Web GIS and cartography. Meanwhile, the platform plays an important role in information collection, management, analysis, prevention and control, and release of measures when a major health event spreads. The method shows many advantages, such as various visualization means, ease to be published and shared, simple operation, and programming realization, which may be taken as technical references for solving the same type of visualization application problems. The research also facilitates the data visualization and monitoring of the spread of infectious diseases in major health events, and can effectively provide services for monitoring, decision-making, dispatching, and handling the spread of infectious diseases.

Conference report for the 10th China Bioanalysis Forum annual meeting.

The 10th China Bioanalysis Forum annual conference was held in Suzhou between 9 and 11 June 2023. This year a full range of bioanalytical topics were discussed such as new technology and bioanalytical approaches for biotherapeutics and biomarkers, particularly in the areas of gene and cell therapy. Another research area covered extensively at the conference was drug metabolism, including new drug metabolism and pharmacokinetic methods; absorption, distribution, metabolism and excretion of new modality drugs, recent regulatory guidance such as human mass balance study and preclinical study of antibody-drug conjugates and case studies of drug metabolism support to newly approved drugs.

Enhanced remediation of Cr(VI)-contaminated soil by modified zero-valent iron with oxalic acid on biochar.

Hexavalent chromium (Cr(VI)) is carcinogenic and widely presented in soil. In this study, modified zero-valent iron (ZVI) with oxalic acid on biochar (OA-ZVI/BC) was prepared using wet ball milling method for the remediation of Cr(VI)-contaminated soil. Microscopic characterizations showed that ZVI were distributed on the biochar uniformly and confirmed the enhanced interface interaction between biochar and ZVI by wet ball milling. Electrochemical analysis indicated the strong electron transfer ability and enhanced corrosion behavior of OA-ZVI/BC. Moreover, inhibitory efficiencies of Cr(VI) removal with the addition of 1,10-phenanthroline suggested abundant Fe2+ generation in OA-ZVI/BC, which might facilitate the reduction of Cr(VI) to Cr(III). Theory calculation further demonstrated the ZVI modified by oxalic acid was more susceptible to solid-solid interfacial reactions with Cr(VI), and more electrons were transferred to Cr(VI). When applied to Cr(VI)-contaminated soil, OA-ZVI/BC could passivate 96.7 % total Cr(VI) and maintained for 90 days. The toxicity characteristic leaching procedure (TCLP) and simple based extraction test (SBET) were used to evaluate the leaching toxicity and bioaccessibility of Cr(VI), respectively. The TCLP-Cr(VI) decreased to 0.11 mg·L-1 after OA-ZVI/BC treatment, much lower than that of soils with ZVI/BC and OA-ZVI remediation (1.5 mg·L-1 and 4.1 mg·L-1). The bioaccessibility of Cr(VI) reduced by 93.5 % after 3-month remediation. Sequential extraction showed that Cr fractions in the soil after OA-ZVI/BC remediation was converted from acetic acid-extractable (HOAc-extractable) to more stable forms (e.g., residual and oxidizable forms). Benefiting from the synergies of oxalic acid, biochar and wet ball milling, OA-ZVI/BC exhibited an excellent performance on the remediation of Cr(VI)-contaminated soil, whose mechanisms involved adsorption, reduction (Fe0/Fe2+, Fe2+/Fe3+) and co-precipitation. This study herein develops a promising ZVI technology in the remediation of heavy metal-contaminated soil.

CD300ld on neutrophils is required for tumour-driven immune suppression.

The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy1,2. Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance2-4. Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo CRISPR-Cas9 screen in a tumour mouse model and identified CD300ld as a top candidate of tumour-favouring receptors. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumour-bearing. CD300ld knockout inhibits the development of multiple tumour types in a PMN-MDSC-dependent manner. CD300ld is required for the recruitment of PMN-MDSCs into tumours and their function to suppress T cell activation. CD300ld acts via the STAT3-S100A8/A9 axis, and knockout of Cd300ld reverses the tumour immune-suppressive microenvironment. CD300ld is upregulated in human cancers and shows an unfavourable correlation with patient survival. Blocking CD300ld activity inhibits tumour development and has synergistic effects with anti-PD1. Our study identifies CD300ld as a critical immune suppressor present on PMN-MDSCs, being required for tumour immune resistance and providing a potential target for cancer immunotherapy.

A feasible protocol to profile bile acids in dried blood spots from rats using a UHPLC-MS/MS method combining a surrogate matrix.

Dried blood spot (DBS) sampling is a promising method for microliter blood sample collection with the advantages of convenient transportation, storage and clinical operations. However, it is challenging to develop an analytical protocol to determine endogenous metabolites, such as bile acids (BAs) in DBSs, due to the low-blood-volume character of DBSs and the complex features of filter paper. Herein, we developed a method of fast ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) to profile and quantify BAs in DBSs. The pretreatment methods were optimized and a two-step solvent addition method, where a small amount of water was firstly added to moisten the DBS and then methanol was added, showed high extraction efficiency for multiple BAs in DBSs. The UHPLC-MS/MS conditions were optimized and 35BAs in different types could be profiled with good resolution and quantified with acceptable precision and accuracy. Preparation of a DBS surrogate matrix without endogenous BAs has been well developed using rat erythrocytes in BSA solution and showed good performance on both the signal suppression/enhancement percentage and parallelism assessment evaluation of three different stable-isotope-labeled (SIL) BAs. The established protocol was successfully applied to profile BAs in DBSs of intrahepatic cholestasis model and healthy control rats with good repeatability. To our knowledge, it is the first time that 35 BAs in DBSs could be well profiled and an appropriate DBS surrogate matrix has been developed. This protocol presents future-oriented applications of DBSs for relevant preclinical studies to profile BAs and probe biomarkers.

Scutellarin Rescued Mitochondrial Damage through Ameliorating Mitochondrial Glucose Oxidation via the Pdk-Pdc Axis.

Mitochondrial bioenergetic deficits and their resulting glucose hypometabolism are the key pathophysiological modulators that promote neurodegeneration. However, there are no specific potential molecules that have been identified to treat neurological diseases by regulating energy metabolism and repairing mitochondrial damage. Pyruvate dehydrogenase (PDH) complex (PDC), which can be phosphorylated by pyruvate dehydrogenase kinase (PDK), is the gate-keeping enzyme for mitochondrial glucose oxidation. In this study, a small-molecule scutellarin (SG) is discovered that can significantly alleviate the neuropathological changes in hippocampal CA1 of cerebral hypoperfusion model rats, rescued the morphological changes of abnormal mitochondria, and restored mitochondrial homeostasis. Mitochondrial proteomics, energy metabolism monitoring, and 13 C-metabolic flux analysis targeted SG activity on PDK2, thus regulating PDK-PDC-mediated glycolytic metabolism to TCA cycle during mitochondrial OXPHOS damage. The knockdown of PDK2 in the SK-N-SH cells validated that SG could rescue mitochondrial damage via the PDK-PDC axis, promote the MMP level and reduce the mitochondria-dependent apoptosis. Collectively, this study explored the novel therapeutic approach: the PDK-PDC axis for neurological injury and cognitive impairment and uncovered the effect of SG on mitochondrial protection via the PDK-PDC axis and mitochondrial glucose oxidation. The findings indicate that active components ameliorating mitochondrial bioenergetic deficits could be of significant value for neurological disease therapy.

Advances in natural compound-based nanomedicine and the interaction with gut microbiota in ulcerative colitis therapy.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder of the large intestine. Previous studies have indicated that the gut microbiota plays an important role in the triggers, development, and treatment response of UC. Natural active molecules and their nanoformulations show huge potential for treating UC. The nanoparticles can regulate the gut microbiota and metabolites, whereas gut microbiota-mediated effects on nanomedicines can also bring additional therapeutic benefits. Therefore, this review aims to integrate current research on natural active molecule-based nanomedicines for UC therapy and their interaction with the gut microbiota. Here, this discussion focuses on the effects and functions of gut microbiota and metabolites in UC. The use of active molecules and the nanoformulation from natural compounds for UC therapy have been provided. The interactions between the gut microbiota and nanomedicines are derived from natural products and elucidate the possible biological mechanisms involved. Finally, the challenges and future directions for enhancing the therapeutic efficacy of nanomedicine in treating UC are proposed.

Novel Strategy to Rapidly Profile and Identify Oxidized Species of Polysorbate 80 Using Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry.

Polysorbate 80 (PS80) is widely used as an excipient in vaccines and biopharmaceuticals. The oxidized species of PS80 have raised concern because of their potential to compromise product stability and pose a clinical risk. Analytical methods to profile and identify the oxidized species are hard to develop owing to their complexity and low abundance. Herein, a novel strategy was demonstrated to comprehensively profile and identify the oxidized species of PS80 using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The characteristic fragmentation patterns of the oxidized species were obtained under the "all ions" scan mode. Then, 10 types of distinct fragments from oxidized oleates were identified and confirmed using two purified oxidized species (polyoxyethylene (POE) sorbitan mono-hydroxy oleate and POE mono-keto oleate) whose structures were elucidated via nuclear magnetic resonance. A total of 348 (32 types) oxidized species were profiled and identified in the oxidized PS80 samples, including 119 (10 types) species found for the first time to our knowledge. Mathematical models were established and validated based on the good logarithmic relation between the POE degree of polymerization and the relative retention time and used to rapidly discover and identify the oxidized species. A novel strategy was established to profile and identify the PS80 oxidized species based on their retention time, HRMS, and HRMS2 data of the detected peaks using an in-house dataset. Using this strategy, 104 (14 types) and 97 (13 types) oxidized species were identified for the first time in PS80 and its preparations, respectively.

Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases.

Metformin (MTF) and berberine (BBR) share several therapeutic benefits in treating metabolic-related disorders. However, as the two agents have very different chemical structure and bioavailability in oral route, the goal of this study is to learn their characteristics in treating metabolic disorders. The therapeutic efficacy of BBR and MTF was systemically investigated in the high fat diet feeding hamsters and/or ApoE(-/-) mice; in parallel, gut microbiota related mechanisms were studied for both agents. We discovered that, although both two drugs had almost identical effects on reducing fatty liver, inflammation and atherosclerosis, BBR appeared to be superior over MTF in alleviating hyperlipidemia and obesity, but MTF was more effective than BBR for the control of blood glucose. Association analysis revealed that the modulation of intestinal microenvironment played a crucial role in the pharmacodynamics of both drugs, in which their respective superiority on the regulation of gut microbiota composition and intestinal bile acids might contribute to their own merits on lowering glucose or lipids. This study shows that BBR may be a good alternative for MTF in treating diabetic patients, especially for those complicated with dyslipidemia and obesity.

A comprehensive perspective on the disposition, metabolism, and pharmacokinetics of representative multi-components of Dengzhan Shengmai in rats with chronic cerebral hypoperfusion after oral administration.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan Shengmai capsule (DZSM), an evidence-based Chinese medicine comprising Erigeron breviscapus (Vaniot) Hand. -Mazz., Panax ginseng C.A.Mey., Ophiopogon japonicus (Thunb.) Ker Gawl., and Schisandra chinensis (Turcz.) Baill., exhibits an excellent efficacy in treating cardio- and cerebrovascular diseases. It contains caffeoyl compounds, flavonoids, saponins, and lignans as primary active components. However, so far, the characteristics of disposition, metabolism, and pharmacokinetics of its active components remain mostly unclear. AIM OF STUDY: To elucidate disposition, metabolism, and pharmacokinetics of representative components of DZSM in rats with chronic cerebral hypoperfusion (CCH) by integrating ex vivo and in situ approaches. MATERIALS AND METHODS: Exposure and distribution of absorbed prototypes and their metabolites were comprehensively investigated using sensitive LC-MS/MS and high-resolution LC-Q-TOF/MS. Pharmacokinetics of representative 16 components (12 prototypes and 4 metabolites) with different chemical categories, relatively high in vivo levels, wide tissue distribution, and reported neuroprotective activities were profiled. The ex vivo everted gut sac and in situ linked-rat models were adopted. RESULTS: Representative 12 prototypes including 6 caffeoyl compounds (CA, 5-CQA, 3-CQA, 4-CQA, 1,3-CQA, and 3,4-CQA), 1 flavonoid (Scu), 2 saponins (Rd and Rg2), and 3 lignans (SchA, SchB, and SolA) presented characteristic absorption, disposition, and pharmacokinetics profiles in CCH rats. The caffeoyl compounds and flavonoid were well absorbed, exhibited wide distribution, and underwent extensive intestinal metabolism, such as methylation, isomerization, and sulfoconjugation. For CA, 5-CQA, Scu, and 4 related metabolites, the enterohepatic circulation was observed and resulted in bimodal or multimodal pharmacokinetic profiles. Saponins showed relatively low systemic exposure and limited distribution. The PPD-type ginsenoside Rd exhibited longer elimination half-life and systemic circulation than the PPT-type ginsenoside Rg2. No enterohepatic circulation was observed regarding saponins, suggesting that the multimodal pharmacokinetic profile of Rd could be due to its multi-site intestinal absorption. Lignans presented a low in vivo exposure and broad distribution. They were mainly transformed into hydroxylated metabolites. Corresponding to its bimodal pharmacokinetic profile, one metabolite of lignans completed the enterohepatic cycle. CONCLUSION: The disposition, metabolism, and pharmacokinetic profiles of representative active components of DZSM were comprehensively characterized and elucidated.

Microbiota-derived short-chain fatty acids mediate the effects of dengzhan shengmai in ameliorating cerebral ischemia via the gut-brain axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan shengmai (DZSM) formula, composed of four herbal medicines (Erigeron breviscapus, Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus), is widely used in the recovery period of ischemic cerebrovascular diseases; however, the associated molecular mechanism remains unclear. AIM OF THE STUDY: The purpose of this study was to uncover the links between the microbiota-gut-brain axis and the efficacy of DZSM in ameliorating cerebral ischemic diseases. MATERIALS AND METHODS: The effects of DZSM on the gut microbiota community and bacteria-derived short-chain fatty acid (SCFA) production were evaluated in vivo using a rat model of cerebral ischemia and in vitro through the anaerobic incubation with fresh feces derived from model animals. Subsequently, the mechanism underlying the role of SCFAs in the DZSM-mediated treatment of cerebral ischemia was explored. RESULTS: We found that DZSM treatment significantly altered the composition of the gut microbiota and markedly enhanced SCFA production. The consequent increase in SCFA levels led to the upregulation of the expression of monocarboxylate transporters and facilitated the transportation of intestinal SCFAs into the brain, thereby inhibiting the apoptosis of neurocytes via the regulation of the PI3K/AKT/caspase-3 pathway. The increased intestinal SCFA levels also contributed to the repair of the 2VO-induced disruption of gut barrier integrity and inhibited the translocation of lipopolysaccharide from the intestine to the brain, thus attenuating neuroinflammation. Consequently, cerebral neuropathy and oxidative stress were significantly improved in 2VO model rats, leading to the amelioration of cerebral ischemia-induced cognitive dysfunction. Finally, fecal microbiota transplantation could reproduce the beneficial effects of DZSM on SCFA production and cerebral ischemia. CONCLUSIONS: Our findings suggested that SCFAs mediate the effects of DZSM in ameliorating cerebral ischemia via the gut microbiota-gut-brain axis.

Ball milling enhanced Cr(VI) removal of zero-valent iron biochar composites: Functional groups response and dominant reduction species.

Zero-valent iron biochar composites (ZVI/BC) have been widely used to remove Cr(VI) from water. However, the application of ZVI/BC prepared by the carbothermal reduction was limited by the non-uniform dispersion of ZVI on the biochar surface. In this work, ball milling technique was introduced to modify ZVI/BC. Results showed that after ball milling, the maximum Langmuir adsorption capacity for Cr(VI) was 117.7 mg g-1 (298 K) which was 2.08 times higher than ZVI/BC. The initial adsorption rate of the Elovich model increased from 4.57 × 102 mg g-1 min-1 to 3.74 × 109 mg g-1 min-1 after ball milling. Dispersibility of ZVI on biochar surface and contact between ZVI and biochar were improved by the ball milling, thus accelerating the electron transfer. Besides, ball milling increased the content of oxygen-containing functional groups in biochar, contributing to the chemisorption of Cr(VI). The response sequence of oxygen-containing functional groups was analyzed by two-dimensional correlation spectroscopy, indicating that Cr(VI) preferentially complexed with phenolic -OH. Shielding experiments showed that Fe (0) was the dominant reducing species with a contribution of 73.4%, followed by surface-bound Fe(II) (21.3%) and dissolved Fe2+ (5.24%). Density functional theory calculations demonstrated that ball milled ZVI/BC improved the adsorption affinity and electron transfer flux towards Cr(VI) by introducing phenolic -OH and Fe (0). Combining all the textural characterization, the Cr(VI) removal mechanism of the ball milled ZVI/BC could be proposed as adsorption, reduction, and precipitation. Eventually, stable Cr-Fe oxides (FeOCr2O3 and Cr1·3Fe0·7O3) were formed. This work not only provides a simple method to modify ZVI/BC to remove Cr(VI) in water efficiently and rapidly, but also improves the mechanistic insight into the Cr(VI) removal by iron-carbon composites via the response sequence of functional group analysis and the quantitative analysis of reducing species.

Unraveling the mechanism of ethyl acetate extract from Prismatomeris connata Y. Z. Ruan root in treating pulmonary fibrosis: insights from bioinformatics, network pharmacology, and experimental validation.

Introduction: Pulmonary fibrosis is a terminal lung disease characterized by fibroblast proliferation, extracellular matrix accumulation, inflammatory damage, and tissue structure destruction. The pathogenesis of this disease, particularly idiopathic pulmonary fibrosis (IPF), remains unknown. Macrophages play major roles in organ fibrosis diseases, including pulmonary fibrosis. The phenotype and polarization of macrophages are closely associated with pulmonary fibrosis. A new direction in research on anti-pulmonary fibrosis is focused on developing drugs that maintain the stability of the pulmonary microenvironment. Methods: We obtained gene sequencing data and clinical information for patients with IPF from the GEO datasets GSE110147, GSE15197, GSE24988, GSE31934, GSE32537, GSE35145, GSE53845, GSE49072, GSE70864, and GSE90010. We performed GO, KEGG enrichment analysis and GSEA analysis, and conducted weighted gene co-expression network analysis. In addition, we performed proteomic analysis of mouse lung tissue. To verify the results of bioinformatics analysis and proteomic analysis, mice were induced by intratracheal instillation of bleomycin (BLM), and gavaged for 14 days after modeling. Respiratory function of mice in different groups was measured. Lung tissues were retained for histopathological examination, Western Blot and real-time quantitative PCR, etc. In addition, lipopolysaccharide, interferon-γ and interleukin-4 were used to induce RAW264.7 cells for 12h in vitro to establish macrophage inflammation and polarization model. At the same time, HG2 intervention was given. The phenotype transformation and cytokine secretion of macrophages were investigated by Western Blot, RT-qPCR and flow cytometry, etc. Results: Through bioinformatics analysis and experiments involving bleomycin-induced pulmonary fibrosis in mice, we confirmed the importance of macrophage polarization in IPF. The analysis revealed that macrophage polarization in IPF involves a change in the phenotypic spectrum. Furthermore, experiments demonstrated high expression of M2-type macrophage-associated biomarkers and inducible nitric oxide synthase, thus indicating an imbalance in M1/M2 polarization of pulmonary macrophages in mice with pulmonary fibrosis. Discussion: Our investigation revealed that the ethyl acetate extract (HG2) obtained from the roots of Prismatomeris connata Y. Z. Ruan exhibits therapeutic efficacy against bleomycin-induced pulmonary fibrosis. HG2 modulates macrophage polarization, alterations in the TGF-ß/Smad pathway, and downstream protein expression in the context of pulmonary fibrosis. On the basis of our findings, we believe that HG2 has potential as a novel traditional Chinese medicine component for treating pulmonary fibrosis.