Inhibition of TREM-1 alleviates neuroinflammation by modulating microglial polarization via SYK/p38MAPK signaling pathway after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI), as a major public health problem, is characterized by high incidence rate, disability rate, and mortality rate. Neuroinflammation plays a crucial role in the pathogenesis of TBI. Triggering receptor expressed on myeloid cells-1 (TREM-1) is recognized as an amplifier of the inflammation in diseases of the central nervous system (CNS). However, the function of TREM-1 remains unclear post-TBI. This study aimed to investigate the function of TREM-1 in neuroinflammation induced by TBI. METHODS: Brain water content (BWC), modified neurological severity score (mNSS), and Morris Water Maze (MWM) were measured to evaluate the effect of TREM-1 inhibition on nervous system function and outcome after TBI. TREM-1 expression in vivo was evaluated by Western blotting. The cellular localization of TREM-1 in the damaged region was observed via immunofluorescence staining. We also conducted Western blotting to examine expression of SYK, p-SYK and other downstream proteins. RESULTS: We found that inhibition of TREM-1 reduced brain edema, decreased mNSS and improved neurobehavioral outcomes after TBI. It was further determined that TREM-1 was expressed on microglia and modulated subtype transition of microglia. Inhibition of TREM-1 alleviated neuroinflammation, which was associated with SYK/p38MAPK signaling pathway. CONCLUSIONS: These findings suggest that TREM-1 can be a potential clinical therapeutic target for alleviating neuroinflammation after TBI.

Suppressing Structure Delamination for Enhanced Electrochemical Performance of Solid Oxide Cells.

Reversible solid oxide cells (rSOCs) have significant potential as efficient energy conversion and storage systems. Nevertheless, the practical application of their conventional air electrodes, such as La0.8Sr0.2MnO3-δ (LSM), Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF), and PrBa0.8Ca0.2Co2O5+δ (PBCC), remains unsatisfactory due to interface delamination during prolonged electrochemical operation. Using micro-focusing X-ray absorption spectroscopy (µ-XAS), a decrease (increase) in the co-valence state from the electrode surface to the electrode/electrolyte interface is observed, leading to the above delamination. Utilizing the one-pot method to incorporate an oxygen-vacancy-enriched CeO2 electrode into these air electrodes, the uniform distribution of the Co valence state is observed, alleviating the structural delamination. PBCC-CeO2 electrodes exhibited a degradation rate of 0.095 mV h-1 at 650 °C during a nearly 500-h test as compared with 0.907 mV h-1 observed during the 135-h test for PBCC. Additionally, a remarkable increase in electrolysis current density from 636 to 934 mA cm-2 under 1.3 V and a maximum power density from 912 to 989 mW cm-2 upon incorporating CeO2 into PBCC is also observed. BSCF-CeO2 and LSM-CeO2 also show enhanced electrochemical performance and prolonged stability as compared to BSCF and LSM. This work offers a strategy to mitigate the structural delamination of conventional electrodes to boost the performance of rSOCs.

Breaking the pH Limitation of Nanozymes: Mechanisms, Methods, and Applications.

Although nanozymes have drawn great attention over the past decade, the activities of peroxidase-like, oxidase-like, and catalase-like nanozymes are often pH dependent with elusive mechanism, which largely restricts their application. Therefore, a systematical discussion on the pH-related catalytic mechanisms of nanozymes together with the methods to overcome this limitation is in need. In this review, various nanozymes exhibiting pH-dependent catalytic activities are collected and the root causes for their pH dependence are comprehensively analyzed. Subsequently, regulatory concepts including catalytic environment reconstruction and direct catalytic activity improvement to break this pH restriction are summarized. Moreover, applications of pH-independent nanozymes in sensing, disease therapy, and pollutant degradation are overviewed. Finally, current challenges and future opportunities on the development of pH-independent nanozymes are suggested. It is anticipated that this review will promote the further design of pH-independent nanozymes and broaden their application range with higher efficiency.

Long Non-coding RNA Neat1, NLRP3 Inflammasome, and Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with high mortality. Inflammation plays a key role in the pathophysiology of AKI. Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of the inflammatory and immune response, but its role in AKI remains unclear. METHODS: We explored the role of lncRNA Neat1 in (1) a cross-sectional and a longitudinal cohort of AKI in human; (2) three murine models of septic and aseptic AKI and (3) cultured C1.1 mouse kidney tubular cells. RESULTS: In human, hospitalized patients with AKI (n=66) demonstrated significantly increased lncRNA Neat1 levels in urinary sediment cells and buffy coat versus control participants (n=152) from a primary care clinic; and among 6 kidney transplant recipients, Neat1 levels were highest immediately after transplant surgery followed by a prompt decline to normal levels in parallel with recovery of kidney function. In mice with AKI induced by sepsis (via LPS injection or cecal ligation and puncture) and renal ischemia-reperfusion, kidney tubular Neat1 was increased versus sham-operated mice. Knockdown of Neat1 in the kidney using short hairpin RNA preserved kidney function, suppressed overexpression of the AKI biomarker NGAL, leukocyte infiltration and both intrarenal and systemic inflammatory cytokines IL-6, CCL-2 and IL-1ß. In LPS-treated C1.1 cells, Neat1 was overexpressed via TLR4/NF-κB signaling, and translocated from the cell nucleus into the cytoplasm where it promoted activation of NLRP3 inflammasomes via binding with the scaffold protein Rack1. Silencing Neat1 ameliorated LPS-induced cell inflammation, whereas its overexpression upregulated IL-6 and CCL-2 expression even without LPS stimulation. CONCLUSIONS: Our findings demonstrate a pathogenic role of Neat1 induction in human and mice during AKI with alleviation of kidney injury in 3 experimental models of septic and aseptic AKI after knockdown of Neat1. LPS/TLR4-induced Neat1 overexpression in tubular epithelial cells increases the inflammatory response by binding with the scaffold protein, Rack1, to activate NLRP3 inflammasomes.

Unveiling the Structural Origins of Dynamic Diversity in Pd-Based Metallic Glasses.

The ß-relaxation is one of the major dynamic behaviors in metallic glasses (MGs) and exhibits diverse features. Despite decades of efforts, the understanding of its structural origin and contribution to the overall dynamics of MG systems is still unclear. Here two palladium-based Pd─Cu─P and Pd─Ni─P MGs are reported with distinct different ß-relaxation behaviors and reveal the structural origins for the difference using the advanced X-ray photon correlation spectroscopy and absorption fine structure techniques together with the first-principles calculations. The pronounced ß-relaxation and fast atomic dynamics in the Pd─Cu─P MG mainly come from the strong mobility of Cu atoms and their locally favored structures. In contrast, the motion of Ni atoms is constrained by P atoms in the Pd─Ni─P MG, leading to the weakened ß-relaxation peak and sluggish dynamics. The correlation of atomic dynamics with microscopic structures provides a way to understand the structural origins of different dynamic behaviors as well as the nature of aging in disordered materials.

Identification of novel biomarkers based on lipid metabolism-related molecular subtypes for moderately severe and severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an unpredictable and potentially fatal disorder. A derailed or unbalanced immune response may be the root of the disease's severe course. Disorders of lipid metabolism are highly correlated with the occurrence and severity of AP. We aimed to characterize the contribution and immunological characteristics of lipid metabolism-related genes (LMRGs) in non-mild acute pancreatitis (NMAP) and identify a robust subtype and biomarker for NMAP. METHODS: The expression mode of LMRGs and immune characteristics in NMAP were examined. Then LMRG-derived subtypes were identified using consensus clustering. The weighted gene co-expression network analysis (WGCNA) was utilized to determine hub genes and perform functional enrichment analyses. Multiple machine learning methods were used to build the diagnostic model for NMAP patients. To validate the predictive effectiveness, nomograms, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) were used. Using gene set variation analysis (GSVA) and single-cell analysis to study the biological roles of model genes. RESULTS: Dysregulated LMRGs and immunological responses were identified between NMAP and normal individuals. NMAP individuals were divided into two LMRG-related subtypes with significant differences in biological function. The cluster-specific genes are primarily engaged in the regulation of defense response, T cell activation, and positive regulation of cytokine production. Moreover, we constructed a two-gene prediction model with good performance. The expression of CARD16 and MSGT1 was significantly increased in NMAP samples and positively correlated with neutrophil and mast cell infiltration. GSVA results showed that they are mainly upregulated in the T cell receptor complex, immunoglobulin complex circulating, and some immune-related routes. Single-cell analysis indicated that CARD16 was mainly distributed in mixed immune cells and macrophages, and MGST1 was mainly distributed in exocrine glandular cells. CONCLUSIONS: This study presents a novel approach to categorizing NMAP into different clusters based on LMRGs and developing a reliable two-gene biomarker for NMAP.

Identification and immunological characterization of lipid metabolism-related molecular clusters in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is now the major contributor to chronic liver disease. Disorders of lipid metabolism are a major element in the emergence of NAFLD. This research intended to explore lipid metabolism-related clusters in NAFLD and establish a prediction biomarker. METHODS: The expression mode of lipid metabolism-related genes (LMRGs) and immune characteristics in NAFLD were examined. The "ConsensusClusterPlus" package was utilized to investigate the lipid metabolism-related subgroup. The WGCNA was utilized to determine hub genes and perform functional enrichment analysis. After that, a model was constructed by machine learning techniques. To validate the predictive effectiveness, receiver operating characteristic curves, nomograms, decision curve analysis (DCA), and test sets were used. Lastly, gene set variation analysis (GSVA) was utilized to investigate the biological role of biomarkers in NAFLD. RESULTS: Dysregulated LMRGs and immunological responses were identified between NAFLD and normal samples. Two LMRG-related clusters were identified in NAFLD. Immune infiltration analysis revealed that C2 had much more immune infiltration. GSVA also showed that these two subtypes have distinctly different biological features. Thirty cluster-specific genes were identified by two WGCNAs. Functional enrichment analysis indicated that cluster-specific genes are primarily engaged in adipogenesis, signalling by interleukins, and the JAK-STAT signalling pathway. Comparing several models, the random forest model exhibited good discrimination performance. Importantly, the final five-gene random forest model showed excellent predictive power in two test sets. In addition, the nomogram and DCA confirmed the precision of the model for NAFLD prediction. GSVA revealed that model genes were down-regulated in several immune and inflammatory-related routes. This suggests that these genes may inhibit the progression of NAFLD by inhibiting these pathways. CONCLUSIONS: This research thoroughly emphasized the complex relationship between LMRGs and NAFLD and established a five-gene biomarker to evaluate the risk of the lipid metabolism phenotype and the pathologic results of NAFLD.

Notoginsenoside R1 can inhibit the interaction between FGF1 and VEGFA to retard podocyte apoptosis.

BACKGROUND: Diabetic nephropathy (DN) is a chronic condition resulting from microangiopathy in a high-glucose environment. The evaluation of vascular injury in DN has primarily focused on active molecules of VEGF, namely VEGFA and VEGF2(F2R). Notoginsenoside R1 (NGR1), a traditional anti-inflammatory medication, exhibits vascular activity. Therefore, identifying classical drugs with vascular inflammatory protection for the treatment of DN is a valuable pursuit. METHODS: The "Limma" method was employed to analyze the glomerular transcriptome data, while the Spearman algorithm for Swiss target prediction was utilized to analyze the drug targets of NGR1. The molecular docking technique was employed to investigate the relationship between vascular active drug targets, and the COIP experiment was conducted to verify the interaction between fibroblast growth factor 1 (FGF1) and VEGFA in relation to NGR1 and drug targets. RESULTS: According to the Swiss target prediction, the LEU32(b) site of the Vascular Endothelial Growth Factor A (VEGFA) protein, as well as the Lys112(a), SER116(a), and HIS102(b) sites of the Fibroblast Growth Factor 1 (FGF1) protein, are potential binding sites for NGR1 through hydrogen bonding. Additionally, the Co-immunoprecipitation (COIP) results suggest that VEGFA and FGF1 proteins can interact with each other, and NGR1 can impede this interaction. Furthermore, NGR1 can suppress the expression of VEGFA and FGF1 in a high-glucose environment, thereby decelerating podocyte apoptosis. CONCLUSION: The inhibition of the interaction between FGF1 and VEGFA by NGR1 has been observed to decelerate podocyte apoptosis.

The effect of chronic alcohol exposure on spatial memory and BDNF-TrkB- PLCγ1 signaling in the hippocampus of male and female mice.

Alcohol is a commonly used drug worldwide, and abuse of alcohol has become a serious public health problem. Alcohol consumption over time can cause cognitive deficits and memory impairment, which is thought to be associated with changes in the hippocampus. Given previously known effects of brain-derived neurotrophic factor (BDNF) in regulating synaptic plasticity and learning and memory, we investigated the effect of chronic alcohol consumption on spatial memory impairment in both sexes and changes in BDNF signaling in the hippocampus. After 4 weeks of intermittent access to 20% alcohol, memory impairment in both male and female mice was evaluated using the Morris water maze and the expression of BDNF, TrkB, phosphorylation of PLCγ1 (p-PLCγ1) and PLCγ1 in the hippocampus was examined using Western blot. As expected, females spent longer escape latencies during the training phase, and both sexes spent shorter time in the target quadrant. Furthermore, after 4 weeks 20% alcohol exposure, we found significantly decreased expression levels of BDNF in the hippocampus of female mice but increased levels in male mice. TrkB and PLCγ1 expression showed no significant change in the hippocampus of both sexes. These findings suggest that chronic alcohol exposure may induce spatial memory impairment in both sexes and opposite changes in expression of BDNF and p-PLCγ1 in the hippocampus of males and females.

In situ catalytic cells for x-ray absorption spectroscopy measurement.

In catalysis, determining the relationship between the dynamic electronic and atomic structure of the catalysts and the catalytic performance under actual reaction conditions is essential to gain a deeper understanding of the reaction mechanism since the structure evolution induced by the absorption of reactants and intermediates affects the reaction activity. Hard x-ray spectroscopy methods are considered powerful and indispensable tools for the accurate identification of local structural changes, for which the development of suitable in situ reaction cells is required. However, the rational design and development of spectroscopic cells is challenging because a balance between real rigorous reaction conditions and a good signal-to-noise ratio must be reached. Here, we summarize the in situ cells currently used in the monitoring of thermocatalysis, photocatalysis, and electrocatalysis processes, focusing especially on the cells utilized in the BL14W1-x-ray absorption fine structure beamline at the Shanghai Synchrotron Radiation Facility, and highlight recent endeavors on the acquisition of improved spectra under real reaction conditions. This review provides a full overview of the design of in situ cells, aiming to guide the further development of portable and promising cells. Finally, perspectives and crucial factors regarding in situ cells under industrial operating conditions are proposed.

Cooperative Rh-O5/Ni(Fe) Site for Efficient Biomass Upgrading Coupled with H2 Production.

Designing efficient and durable bifunctional catalysts for 5-hydroxymethylfurfural (HMF) oxidation reaction (HMFOR) and hydrogen evolution reaction (HER) is desirable for the co-production of biomass-upgraded chemicals and sustainable hydrogen, which is limited by the competitive adsorption of hydroxyl species (OHads) and HMF molecules. Here, we report a class of Rh-O5/Ni(Fe) atomic site on nanoporous mesh-type layered double hydroxides with atomic-scale cooperative adsorption centers for highly active and stable alkaline HMFOR and HER catalysis. A low cell voltage of 1.48 V is required to achieve 100 mA cm-2 in an integrated electrolysis system along with excellent stability (>100 h). Operando infrared and X-ray absorption spectroscopic probes unveil that HMF molecules are selectively adsorbed and activated over the single-atom Rh sites and oxidized by in situ-formed electrophilic OHads species on neighboring Ni sites. Theoretical studies further demonstrate that the strong d-d orbital coupling interactions between atomic-level Rh and surrounding Ni atoms in the special Rh-O5/Ni(Fe) structure can greatly facilitate surface electronic exchange-and-transfer capabilities with the adsorbates (OHads and HMF molecules) and intermediates for efficient HMFOR and HER. We also reveal that the Fe sites in Rh-O5/Ni(Fe) structure can promote the electrocatalytic stability of the catalyst. Our findings provide new insights into catalyst design for complex reactions involving competitive adsorptions of multiple intermediates.

Constrained C2 adsorbate orientation enables CO-to-acetate electroreduction.

The carbon dioxide and carbon monoxide electroreduction reactions, when powered using low-carbon electricity, offer pathways to the decarbonization of chemical manufacture1,2. Copper (Cu) is relied on today for carbon-carbon coupling, in which it produces mixtures of more than ten C2+ chemicals3-6: a long-standing challenge lies in achieving selectivity to a single principal C2+ product7-9. Acetate is one such C2 compound on the path to the large but fossil-derived acetic acid market. Here we pursued dispersing a low concentration of Cu atoms in a host metal to favour the stabilization of ketenes10-chemical intermediates that are bound in monodentate fashion to the electrocatalyst. We synthesize Cu-in-Ag dilute (about 1 atomic per cent of Cu) alloy materials that we find to be highly selective for acetate electrosynthesis from CO at high *CO coverage, implemented at 10 atm pressure. Operando X-ray absorption spectroscopy indicates in situ-generated Cu clusters consisting of <4 atoms as active sites. We report a 12:1 ratio, an order of magnitude increase compared to the best previous reports, in the selectivity for acetate relative to all other products observed from the carbon monoxide electroreduction reaction. Combining catalyst design and reactor engineering, we achieve a CO-to-acetate Faradaic efficiency of 91% and report a Faradaic efficiency of 85% with an 820-h operating time. High selectivity benefits energy efficiency and downstream separation across all carbon-based electrochemical transformations, highlighting the importance of maximizing the Faradaic efficiency towards a single C2+ product11.

A novel in situ sample environment setup for combined small angle x-ray scattering (SAXS), wide-angle x-ray scattering (WAXS), and Fourier transform infrared spectrometer (FTIR) simultaneous measurement.

Developing the synchrotron radiation experiment method based on combined technology offers more information on the formation mechanism of new materials and their physical and chemical properties. In this study, a new small-angle x-ray scattering/ wide-angle x-ray scattering/ Fourier-transform infrared spectroscopy (SAXS/WAXS/FTIR) combined setup was established. Using this combined SAXS/WAXS/FTIR setup, x-ray and FTIR signals can be obtained simultaneously from the same sample. The in situ sample cell was designed to couple two FTIR optical paths for the attenuated total reflection and transmission modes, which greatly saved the time of adjusting and aligning the external infrared light path when switching between the two modes with good accuracy. A transistor-transistor logic circuit was used to trigger the synchronous acquisition from the IR and x-ray detectors. A special sample stage is designed, allowing access by the IR and x-ray with temperature and pressure control. The newly developed, combined setup can be used to observe the evolution of the microstructure during the synthesis of composite materials in real-time at both the atomic and molecular levels. The crystallization of polyvinylidene fluoride (PVDF) at different temperatures was observed. The time-dependent experimental data demonstrated the success of the in situ SAXS, WAXS, and FTIR study of the structural evolution, which is feasible to track the dynamic processes.

Photocatalytic CO2 reduction using La-Ni bimetallic sites within a covalent organic framework.

The precise construction of photocatalysts with diatomic sites that simultaneously foster light absorption and catalytic activity is a formidable challenge, as both processes follow distinct pathways. Herein, an electrostatically driven self-assembly approach is used, where phenanthroline is used to synthesize bifunctional LaNi sites within covalent organic framework. The La and Ni site acts as optically and catalytically active center for photocarriers generation and highly selective CO2-to-CO reduction, respectively. Theory calculations and in-situ characterization reveal the directional charge transfer between La-Ni double-atomic sites, leading to decreased reaction energy barriers of *COOH intermediate and enhanced CO2-to-CO conversion. As a result, without any additional photosensitizers, a 15.2 times enhancement of the CO2 reduction rate (605.8 µmol·g-1·h-1) over that of a benchmark covalent organic framework colloid (39.9 µmol·g-1·h-1) and improved CO selectivity (98.2%) are achieved. This work presents a potential strategy for integrating optically and catalytically active centers to enhance photocatalytic CO2 reduction.

Spatially Confined PdHx Metallenes by Tensile Strained Atomic Ru Layers for Efficient Hydrogen Evolution.

Hydride metallenes show great potential for hydrogen-related catalytic applications due to favorable electronic structures modulated by interstitial hydrogen atoms and large active surface areas of metallenes. Metallene nanostructures generally have compressive strain relative to bulk, which can affect both the stability and the catalytic behavior of hydride metallenes but in general cannot be controlled. Here, we demonstrate highly stable PdHx metallenes with a tensile strained Ru surface layer and reveal the spatial confinement effect of the Ru skin by multiple spectroscopic characterizations and molecular dynamics simulations. These PdHx@Ru metallenes with a 4.5% expanded Ru outer layer exhibit outstanding alkaline hydrogen evolution reaction activity with a low overpotential of 30 mV at 10 mA cm-2 and robust stability with negligible activity decay after 10,000 cycles, which are superior to commercial Pt/C and most reported Ru-based electrocatalysts. Control experiments and first-principles calculations reveal that the tensile strained Ru outer layer lowers the energy barrier of H2O dissociation and provides a moderate hydrogen adsorption energy.

Tubulovascular protection from protease-activated receptor-1 depletion during AKI-to-CKD transition.

BACKGROUND: Thromboembolic events are prevalent in chronic kidney disease (CKD) patients due to increased thrombin generation leading to a hypercoagulable state. We previously demonstrated that inhibition of protease-activated receptor-1 (PAR-1) by vorapaxar reduces kidney fibrosis. METHODS: We used an animal model of unilateral ischemia-reperfusion injury-induced CKD to explore the tubulovascular crosstalk mechanisms of PAR-1 in acute kidney injury (AKI)-to-CKD transition. RESULTS: During the early phase of AKI, PAR-1-deficient mice exhibited reduced kidney inflammation, vascular injury, and preserved endothelial integrity and capillary permeability. During the transition phase to CKD, PAR-1 deficiency preserved kidney function and diminished tubulointerstitial fibrosis via downregulated transforming growth factor-ß/Smad signaling. Maladaptive repair in the microvasculature after AKI further exacerbated focal hypoxia with capillary rarefaction, which was rescued by stabilization of hypoxia-inducible factor and increased tubular vascular endothelial growth factor A in PAR-1-deficient mice. Chronic inflammation was also prevented with reduced kidney infiltration by both M1- and M2-polarized macrophages. In thrombin-induced human dermal microvascular endothelial cells (HDMECs), PAR-1 mediated vascular injury through activation of NF-κB and ERK MAPK pathways. Gene silencing of PAR-1 exerted microvascular protection via a tubulovascular crosstalk mechanism during hypoxia in HDMECs. Finally, pharmacologic blockade of PAR-1 with vorapaxar improved kidney morphology, promoted vascular regenerative capacity, and reduced inflammation and fibrosis depending on the time of initiation. CONCLUSIONS: Our findings elucidate a detrimental role of PAR-1 in vascular dysfunction and profibrotic responses upon tissue injury during AKI-to-CKD transition and provide an attractive therapeutic strategy for post-injury repair in AKI.

Significant differences in the electrochemical activity of black phosphorus anodes prepared under different atmospheres.

The effects of atmosphere and temperature on the electrochemical reversibility of black phosphorus (BP) anodes were investigated. BP anodes prepared in ambient air exhibited much-enhanced electrochemical activity due to the newly formed Cu3P phase. This work highlights the importance of maintaining intragranular electronic conduction for developing advanced BP-based anodes with high reversible capacities.

COx hydrogenation to methanol and other hydrocarbons under mild conditions with Mo3S4@ZSM-5.

The hydrogenation of CO2 or CO to single organic product has received widespread attentions. Here we show a highly efficient and selective catalyst, Mo3S4@ions-ZSM-5, with molybdenum sulfide clusters ([Mo3S4]n+) confined in zeolitic cages of ZSM-5 molecular sieve for the reactions. Using continuous fixed bed reactor, for CO2 hydrogenation to methanol, the catalyst Mo3S4@NaZSM-5 shows methanol selectivity larger than 98% at 10.2% of carbon dioxide conversion at 180 °C and maintains the catalytic performance without any degeneration during continuous reaction of 1000 h. For CO hydrogenation, the catalyst Mo3S4@HZSM-5 exhibits a selectivity to C2 and C3 hydrocarbons stably larger than 98% in organics at 260 °C. The structure of the catalysts and the mechanism of COx hydrogenation over the catalysts are fully characterized experimentally and theorectically. Based on the results, we envision that the Mo3S4@ions-ZSM-5 catalysts display the importance of active clusters surrounded by permeable materials as mesocatalysts for discovery of new reactions.

Identification of Markers for Diagnosis and Treatment of Diabetic Kidney Disease Based on the Ferroptosis and Immune.

Background: In advanced diabetic kidney disease (DKD), iron metabolism and immune dysregulation are abnormal, but the correlation is not clear. Therefore, we aim to explore the potential mechanism of ferroptosis-related genes in DKD and their relationship with immune inflammatory response and to identify new diagnostic biomarkers to help treat and diagnose DKD. Methods: Download data from gene expression omnibus (GEO) database and FerrDb database, and construct random forest tree (RF) and support vector machine (SVM) model to screen hub ferroptosis genes (DE-FRGs). We used consistent unsupervised consensus clustering to cluster DKD samples, and enrichment analysis was performed by Gene Set Variation Analysis (GSVA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) and then assessed immune cell infiltration abundance using the single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms. Ferroptosis scoring system was established based on the Boruta algorithm, and then, core compounds were screened, and binding sites were predicted by Coremine Medical database. Results: We finally established a 7-gene signature (DUSP1, PRDX6, PEBP1, ZFP36, GABARAPL1, TSC22D3, and RGS4) that exhibited good stability across different datasets. Consistent clustering analysis divided the DKD samples into two ferroptosis modification patterns. Meanwhile, autophagy and peroxisome pathways and immune-related pathways can participate in the regulation of ferroptosis modification patterns. The abundance of immune cell infiltration differs significantly across patterns. Further, molecular docking results showed that the core compound could bind to the protein encoded by the core gene. Conclusions: Our findings suggest that ferroptosis modification plays a crucial role in the diversity and complexity of the DKD immune microenvironment, and the ferroptosis score system can be used to effectively verify the relationship between ferroptosis and immune cell infiltration in DKD patients. Kaempferol and quercetin may be potential drugs to improve the immune and inflammatory mechanisms of DKD by affecting ferroptosis.

Relevance of the pyroptosis-related inflammasome drug targets in the Chuanxiong to improve diabetic nephropathy.

BACKGROUND: A chronic inflammatory disease caused by disturbances in metabolism, diabetic nephropathy (DN) is a chronic inflammatory disease. Pyroptosis is a novel form of programmed cell death in many inflammation-related diseases, including DN. Therefore, pyroptosis could be a promising target for DN therapy. METHODS: To get the components and pharmacodynamic targets of Chuanxiong, we identified by searching TCMID, TCMSP, ETCM and HERB databases. Then, from the Molecular Signatures Database (MSigDB) and Gene Ontology (GO) database, pyroptosis genes were collected. Identification of critical genes in DN by bioinformatics analysis and then using the ConsensusClusterPlus package to divide the express data of diff genes into some subgroups with different levels of pyroptosis; the WGCNA machine algorithm was used to simulate the mechanism Chuanxiong improving DN. RESULTS: In this study, we found DHCR24, ANXA1, HMOX1, CDH13, ALDH1A1, LTF, CHI3L1, CACNB2, and MTHFD2 interacted with the diff genes of DN. We used GSE96804 as a validation set to evaluate the changes of APIP, CASP6, CHMP2B, CYCS, DPP8, and TP53 in four different cell proapoptotic states. WGCNA analysis showed that DHCR24, CHI3L1, and CACNB2 had significant changes in different cell proapoptotic levels. In the experimental stage, we also confirmed that the active ingredients of Chuanxiong could improve the inflammatory state and the levels of pyroptosis under high glucose. CONCLUSION: The improvement of DN by Chuanxiong is related to the change of pyroptosis.