In-Situ Characterization Techniques for Mechanism Studies of CO2 Hydrogenation.

The paramount concerns of global warming, fossil fuel depletion, and energy crises have prompted the need of hydrocarbons productions via CO2 conversion. In order to achieve global carbon neutrality, much attention needs to be diverted towards CO2 management. Catalytic hydrogenation of CO2 is an exciting opportunity to curb the increasing CO2 and produce value-added products. However, the comprehensive understanding of CO2 hydrogenation is still a matter of discussion due to its complex reaction mechanism and involvement of various species. This review comprehensively discusses three processes: reverse water gas shift (RWGS) reaction, modified Fischer Tropsch synthesis (MFTS), and methanol-mediated route (MeOH) for CO2 hydrogenation to hydrocarbons. It is also very important to understand the real-time evolvement of catalytic process and reaction intermediates by employing in-situ characterization techniques. Subsequently, in second part of this review, we provided a systematic analysis of advancements in in-situ techniques aimed to monitor the evolution of catalysts during CO2 reduction process. The section also highlights the key components of in-situ cells, their working principles, and applications in identifying reaction mechanisms for CO2 hydrogenation. Finally, by reviewing respective achievements in the field, we identify key gaps and present some future directions for CO2 hydrogenation and in-situ studies.

Twin Strep-Tag Modified CPT1A Mitochondrial Membrane Chromatography in Screening Lipid Metabolism Regulators.

Mitochondrial Membrane Chromatography (MMC) is a bioaffinity chromatography technique developed to study the interaction between target proteins embedded in the mitochondrial membrane and their ligand compounds. However, the MMC stationary phases (MMSP) prepared by chemical immobilization are prone to nonspecific binding in candidate agent screening inevitably. To address these challenges, Twin Strep-Tag/Strep Tactin was employed to establish a specific affinity system in the present study. We prepared a carnitine palmitoyltransferase 1A (CPT1A) MMSP by specifically linking Strep-tactin-modified silica gel with the Twin Strep-Tag on the CPT1A-oriented mitochondrial membrane. This Twin Strep-Tag/Strep Tactin modified CPT1A/MMC method exhibited remarkably better retention behavior, longer stationary phase lifespan, and higher screening specificity compared with previous MMC systems with glutaraldehyde immobilization. We adopted the CPT1A-specific MMC system in screening CPT1A ligands from traditional Chinese medicines, and successfully identified novel candidate ligands: ononin, isoliquiritigenin, and aloe-emodin, from Glycyrrhiza uralensis Fisch and Senna tora (L.) Roxb extracts. Biological assessments illustrated that the compounds screened promote CPT1A enzyme activity without affecting CPT1A protein expression, as well as effectively reduce the lipid droplets and triglyceride levels in the high fat induction HepG2 cells. The results suggest that we have developed an MMC system, which is promising for studying the bioaffinity of mitochondrial membrane proteins to candidate compounds. This system provides a platform for a key step in mitochondrial medicine discovery, especially for bioactive molecule screening from complex herbal extracts.

Unveiling the role of APOM gene in liver cancer: Investigating the impact of hsa-miR-4489/MUC1-mediated ferroptosis on the advancement of hepatocellular carcinoma cells.

Primary liver cancer has consistently exhibited a high prevalence and fatality rate, necessitating the investigation of associated diagnostic markers and inhibition mechanisms to effectively mitigate its impact. The significance of apolipoprotein M (ApoM) in impeding the progression of neoplastic ailments is progressively gaining recognition. However, a comprehensive understanding of its underlying mechanism in liver cancer advancement remains to be elucidated. Recent evidence indicates a potential association between ApoM and polyunsaturated fatty acids (PUFAs), with the peroxidation of phospholipids (PLs) containing PUFAs being recognized as a crucial element in the occurrence of ferroptosis. This prompts us to investigate the impact of the APOM gene on the progression of liver cancer through the ferroptosis pathway and elucidate its underlying mechanisms. The findings of this study indicate that the liver cancer cell model, which was genetically modified to overexpress the APOM gene, demonstrated a heightened ferroptosis effect. Moreover, the observed inhibition of the GSH (Glutathione) - GPX4 (Glutathione Peroxidase 4) regulatory axis suggests that the role of this axis in inhibiting ferroptosis is weakened. Through intersection screening and validation, we found that Mucin 1,cell surface associated (MUC1) can inhibit ferroptosis and is regulated by the APOM gene. Bioinformatics analysis and screening identified miR-4489 as a mediator between the two. Experimental results using the dual luciferase reporter gene confirmed that has-miR-4489 targets MUC1's 3'-UTR and inhibits its expression. In conclusion, this study provides evidence that the APOM gene induces a down-regulation in the expression of the ferroptosis-inhibiting gene MUC1, mediated by miR-4489, thereby impeding the advancement of liver cancer cells through the facilitation of ferroptosis.

Supporting Nano Catalysts for the Selective Hydrogenation of Biomass-derived Compounds.

The selective hydrogenation of biomass derivatives presents a promising pathway for the production of high-value chemicals and fuels, thereby reducing reliance on traditional petrochemical industries. Recent strides in catalyst nanostructure engineering, achieved through tailored support properties, have significantly enhanced the hydrogenation performance in biomass upgrading. A comprehensive understanding of biomass selective upgrading reactions and the current advancement in supported catalysts is crucial for guiding future processes in renewable biomass. This review aims to summarize the development of supported nanocatalysts for the selective hydrogenation of the US DOE's biomass platform compounds derivatives into valuable upgraded molecules. The discussion includes an exploration of the reaction mechanisms and conditions in catalytic transfer hydrogenation (CTH) and high-pressure hydrogenation. By thoroughly examining the tailoring of supports, such as metal oxide catalysts and porous materials, in nano-supported catalysts, we elucidate the promoting role of nanostructure engineering in biomass hydrogenation. This endeavor seeks to establish a robust theoretical foundation for the fabrication of highly efficient catalysts. Furthermore, the review proposes prospects in the field of biomass utilization and address application bottlenecks and industrial challenges associated with the large-scale utilization of biomass.

Understanding the effect of spatially separated Cu and acid sites in zeolite catalysts on oxidation of methane.

Unraveling the effect of spatially separated bifunctional sites on catalytic reactions is significant yet challenging. In this report, we investigate the role of spatial separation on the oxidation of methane in a series of Cu-exchanged aluminosilicate zeolites. Regulation of the bifunctional sites is done either through studying a physical mixture of Cu-exchanged zeolites and acidic zeolites or by systematically varying the Cu and acid density within a family of zeolite materials. We show that separated Cu and acid sites are beneficial for the formation of hydrocarbons while high-density Cu sites, which are closer together, facilitate the production of CO2. By contrast, a balance of the spatial separation of Cu and acid sites shows more favorable formation of methanol. This work will further guide approaches to methane oxidation to methanol and open an avenue for promoting hydrocarbon synthesis using methanol as an intermediate.

Screening of CPT1A-Targeting Lipid Metabolism Modulators Using Mitochondrial Membrane Chromatography.

Carnitine palmitoyltransferase 1A (CPT1A), which resides on the mitochondrial outer membrane, serves as the rate-limiting enzyme of fatty acid ß-oxidation. Identifying the compounds targeting CPT1A warrants a promising candidate for modulating lipid metabolism. In this study, we developed a CPT1A-overexpressed mitochondrial membrane chromatography (MMC) to screen the compounds with affinity for CPT1A. Cells overexpressing CPT1A were cultured, and subsequently, their mitochondrial membrane was isolated and immobilized on amino-silica gel cross-linked by glutaraldehyde. After packing the mitochondrial membrane column, retention components of MMC were performed with LC/MS, whose analytic peaks provided structural information on compounds that might interact with mitochondrial membrane proteins. With the newly developed MMC-LC/MS approach, several Chinese traditional medicine extracts, such as Scutellariae Radix and Polygoni Cuspidati Rhizoma et Radix (PCRR), were analyzed. Five noteworthy compounds, baicalin, baicalein, wogonoside, wogonin, and resveratrol, were identified as enhancers of CPT1A enzyme activity, with resveratrol being a new agonist for CPT1A. The study suggests that MMC serves as a reliable screening system for efficiently identifying modulators targeting CPT1A from complex extracts.

MESPool: Molecular Edge Shrinkage Pooling for hierarchical molecular representation learning and property prediction.

Identifying task-relevant structures is important for molecular property prediction. In a graph neural network (GNN), graph pooling can group nodes and hierarchically represent the molecular graph. However, previous pooling methods either drop out node information or lose the connection of the original graph; therefore, it is difficult to identify continuous subtructures. Importantly, they lacked interpretability on molecular graphs. To this end, we proposed a novel Molecular Edge Shrinkage Pooling (MESPool) method, which is based on edges (or chemical bonds). MESPool preserves crucial edges and shrinks others inside the functional groups and is able to search for key structures without breaking the original connection. We compared MESPool with various well-known pooling methods on different benchmarks and showed that MESPool outperforms the previous methods. Furthermore, we explained the rationality of MESPool on some datasets, including a COVID-19 drug dataset.

Enhanced Bioactivity of Enzyme/MOF Biocomposite via Host Framework Engineering.

This study reports the successful development of a sustainable synthesis protocol for a phase-pure metal azolate framework (MAF-6) and its application in enzyme immobilization. An esterase@MAF-6 biocomposite was synthesized, and its catalytic performance was compared with that of esterase@ZIF-8 and esterase@ZIF-90 in transesterification reactions. Esterase@MAF-6, with its large pore aperture, showed superior enzymatic performance compared to esterase@ZIF-8 and esterase@ZIF-90 in catalyzing transesterification reactions using both n-propanol and benzyl alcohol as reactants. The hydrophobic nature of the MAF-6 platform was shown to activate the immobilized esterase into its open-lid conformation, which exhibited a 1.5- and 4-times enzymatic activity as compared to free esterase in catalyzing transesterification reaction using n-propanol and benzyl alcohol, respectively. The present work offers insights into the potential of MAF-6 as a promising matrix for enzyme immobilization and highlights the need to explore MOF matrices with expanded pore apertures to broaden their practical applications in biocatalysis.

Atomic Layer Deposition of the Geometry Separated Lewis and Brønsted Acid Sites for Cascade Glucose Conversion.

Solid acid catalysts with bi-acidity are promising as workhouse catalysts in biorefining to produce high-quality chemicals and fuels. Herein, we report a new strategy to develop bi-acidic cascade catalysts by separating both acid sites in geometry via the atomic layer deposition (ALD) of Lewis acidic alumina on Brønsted acidic supports. Visualized by transmission electron microscopy and electron energy loss spectroscopy mapping, the ALD-deposited alumina forms a conformal alumina domain with a thickness of around 3 nm on the outermost surface of mesoporous silica-alumina. Solid state nuclear magnetic resonance investigation shows that the dominant Lewis acid sites distribute on the outermost surface, whereas intrinsic Brønsted acid sites locate inside the nanopores within the silica-rich substrate. In comparison to other bi-acidic solid catalyst counterparts, the special geometric distance of Lewis and Brønsted acid sites minimized the synergetic effect, leading to a cascade reaction environment. For cascade glucose conversion, the designed ALD catalyst showed a highly enhanced catalytic performance.

The role of lysosomal membrane proteins in autophagy and related diseases.

As a self-degrading and highly conserved survival mechanism, autophagy plays an important role in maintaining cell survival and recycling. The discovery of autophagy-related (ATG) genes has revolutionized our understanding of autophagy. Lysosomal membrane proteins (LMPs) are important executors of lysosomal function, and increasing evidence has demonstrated their role in the induction and regulation of autophagy. In addition, the functional dysregulation of the process mediated by LMPs at all stages of autophagy is closely related to neurodegenerative diseases and cancer. Here, we review the role of LMPs in autophagy, focusing on their roles in vesicle nucleation, vesicle elongation and completion, the fusion of autophagosomes and lysosomes, and degradation, as well as their broad association with related diseases.

Insight into the Evolution Track for the Metathesis of Alkenes within Hierarchical Zeolite-Based Catalysts.

The usage of hierarchical MFI zeolite enables a boost of the catalytic performance of Mo-based catalysts for the olefin-metathesis reaction. The harvest of active catalysts roots in a segmental evolution track between hierarchical zeolite and Al2 O3 slices for the fabrication of active sites. The working evolution track requires the indispensable engagements from intracrystalline mesoporous surface, Al2 O3 slices, and zeolitic Brønsted acid sites. The infilling of disaggregated Al2 O3 slices into the intracrystalline mesopores triggers the creation of localized intrazeolite-Al2 O3 interfaces, which enables the subsequent migration and trapping of surface molybdates into the micropores. The insulation of intrazeolite-Al2 O3 interface or shielding of zeolitic Brønsted acid sites leads to the break of the evolution track. Our findings disclose the hidden functionality of mesoporosity as intrazeolite interface boundary for the fabrication of active sites and supply a new strategy for the rational design of zeolite catalysts.

The functions of SID1 transmembrane family, member 2 (Sidt2).

The SID1 transmembrane family, member 2, namely, Sidt2, is a highly glycosylated multichannel lysosomal transmembrane protein, but its specific physiological function remains unknown. Lysosomal membrane proteins are very important for the executive functioning of lysosomes. As an important part of the lysosomal membrane, Sidt2 can maintain the normal morphology of lysosomes and help stabilize them from the acidic pH environment within. As a receptor/transporter, it binds and transports nucleic acids and mediates the uptake and degradation of RNA and DNA by the lysosome. During glucose metabolism, deletion of Sidt2 can cause an increase in fasting blood glucose and the impairment of grape tolerance, which is closely related to the secretion of insulin. During lipid metabolism, the loss of Sidt2 can cause hepatic steatosis and lipid metabolism disorders and can also play a role in signal regulation and transport. Here, we review the function of the lysosomal membrane protein Sidt2, and focus on its role in glucose and lipid metabolism, autophagy and nucleotide (DNA/RNA) transport.

Sidt2 is a key protein in the autophagy-lysosomal degradation pathway and is essential for the maintenance of kidney structure and filtration function.

The regulation and homeostasis of autophagy are essential for maintaining organ morphology and function. As a lysosomal membrane protein, the effect of Sidt2 on kidney structure and renal autophagy is still unknown. In this study, we found that the kidneys of Sidt2-/- mice showed changes in basement membrane thickening, foot process fusion, and mitochondrial swelling, suggesting that the structure of the kidney was damaged. Increased urine protein at 24 h indicated that the kidney function was also damaged. At the same time, the absence of Sidt2 caused a decrease in the number of acidic lysosomes, a decrease in acid hydrolase activity and expression in the lysosome, and an increase of pH in the lysosome, suggesting that lysosomal function was impaired after Sidt2 deletion. The accumulation of autophagolysosomes, increased LC3-II and P62 protein levels, and decreased P62 mRNA levels indicated that the absence of the Sidt2 gene caused abnormal autophagy pathway flow. Chloroquine experiment, immunofluorescence autophagosome, and lysosome fusion assay, and Ad-mcherry-GFP-LC3B further indicated that, after Sidt2 deletion, the production of autophagosomes did not increase, but the fusion of autophagosomes and lysosomes and the degradation of autophagolysosomes were impaired. When incubating Sidt2-/- cells with the autophagy activator rapamycin, we found that it could activate autophagy, which manifested as an increase in autophagosomes, but it could not improve autophagolysosome degradation. Meanwhile, it further illustrated that the Sidt2 gene plays an important role in the smooth progress of autophagolysosome processes. In summary, the absence of the Sidt2 gene caused impaired lysosome function and a decreased number of acidic lysosomes, leading to formation and degradation disorders of the autophagolysosomes, which eventually manifested as abnormal kidney structure and function. Sidt2 is essential in maintaining the normal function of the lysosomes and the physiological stability of the kidneys.

The role of lysosomal membrane proteins in glucose and lipid metabolism.

Lysosomes have long been regarded as the "garbage dump" of the cell. More recently, however, researchers have revealed novel roles for lysosomal membranes in autophagy, ion transport, nutrition sensing, and membrane fusion and repair. With active research into lysosomal membrane proteins (LMP), increasing evidence has become available showing that LMPs are inextricably linked to glucose and lipid metabolism, and this relationship represents mutual influence and regulation. In this review, we summarize the roles of LMPs in relation to glucose and lipid metabolism, and describe their roles in glucose transport, glycolysis, cholesterol transport, and lipophagy. The role of transport proteins can be traced back to the original discoveries of GLUT8, NPC1, and NPC2, which were all found to have significant roles in the pathways involved in glucose and lipid metabolism. CLC-5 and SIDT2-knockout animals show serious phenotypic disorders of metabolism, and V-ATPase and LAMP-2 have been found to interact with proteins related to glucose and lipid metabolism. These findings all emphasize the critical role of LMPs in glycolipid metabolism and help to strengthen our understanding of the independent and close relationship between LMPs and glycolipid metabolism.

Engineering the Distinct Structure Interface of Subnano-alumina Domains on Silica for Acidic Amorphous Silica-Alumina toward Biorefining.

Amorphous silica-aluminas (ASAs) are important solid catalysts and supports for many industrially essential and sustainable processes, such as hydrocarbon transformation and biorefining. However, the wide distribution of acid strength on ASAs often results in undesired side reactions, lowering the product selectivity. Here we developed a strategy for the synthesis of a unique class of ASAs with unvarying strength of Brønsted acid sites (BAS) and Lewis acid sites (LAS) using double-flame-spray pyrolysis. Structural characterization using high-resolution transmission electron microscopy (TEM) and solid-state nuclear magnetic resonance (NMR) spectroscopy showed that the uniform acidity is due to a distinct nanostructure, characterized by a uniform interface of silica-alumina and homogeneously dispersed alumina domains. The BAS population density of as-prepared ASAs is up to 6 times higher than that obtained by classical methods. The BAS/LAS ratio, as well as the population densities of BAS and LAS of these ASAs, could be tuned in a broad range. In cyclohexanol dehydration, the uniform Brønsted acid strength provides a high selectivity to cyclohexene and a nearly linear correlation between acid site densities and cyclohexanol conversion. Moreover, the concerted action of these BAS and LAS leads to an excellent bifunctional Brønsted-Lewis acid catalyst for glucose dehydration, affording a superior 5-hydroxymethylfurfural yield.

CCL24 Protects Renal Function by Controlling Inflammation in Podocytes.

Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with chronic inflammation. We have examined the role of the inflammatory chemokine CCL24 in DN. We observed that serum levels of CCL24 were significantly elevated in patients with DN. Not only that, the expression of CCL24 was significantly increased in the kidneys of DN mice. The kidney of DN mice showed increased renal fibrosis and inflammation. We characterized an in vitro podocyte cell model with high glucose. Western blot analysis showed that expression of CCL24 was significantly increased under high-glucose conditions. Stimulation with high glucose (35 mmol/L) resulted in an increase in CCL24 expression in the first 48 hours but changed little after 72 hours. Moreover, with glucose stimulation, the level of podocyte fibrosis gradually increased, the expression of the proinflammatory cytokine IL-1ß was upregulated, and the expression of the glucose transporter GLUT4, involved in the insulin signal regulation pathway, also increased. It is suggested that CCL24 is involved in the pathogenesis of DN. In order to study the specific role of CCL24 in this process, we used the CRISPR-Cas9 technique to knock out CCL24 expression in podocytes. Compared with the control group, the podocyte inflammatory response induced by high glucose after CCL24 knockout was significantly increased. These results suggest that CCL24 plays a role in the development of early DN by exerting an anti-inflammatory effect, at least, in podocytes.

Formation and Location of Pt Single Sites Induced by Pentacoordinated Al Species on Amorphous Silica-Alumina.

Alumina and its mixed oxides are popular industrial supports for emerging supported metal catalysts. Pentacoordinated Al (AlV) species are identified as key surface sites for anchoring and stabilizing metal single-site catalysts; however, AlV is rare in conventional amorphous silica-alumina (ASA). Recently, we have developed AlV-enriched ASA, which was applied as a support for the synthesis of Pt single-site catalysts in this work. Each preparation stage and the interaction between Pt and surface Al species were explored by 1H and 27Al solid-state nuclear magnetic resonance spectroscopy, and the formation of the dominant Pt single sites on the surface of AlV-enriched ASA was confirmed by high-angle annular dark-field imaging scanning transmission electron microscopy and energy dispersive spectroscopy line scanning. On the surface of supports without a significant AlV population (Pt/Al2O3 and Pt/SiO2), mainly Pt nanoparticles were formed. This indicates that AlV contributes to the strong metal-support interaction to stabilize the Pt single sites on Pt/ASA, which was characterized by diffuse reflectance infrared Fourier transform spectroscopy combined with CO adsorption, X-ray photoelectron spectroscopy, and electron energy loss spectroscopy. Pt single sites supported on AlV-enriched ASA exhibit excellent chemoselectivity in the hydrogenation of C═O groups, affording 2-3-fold higher yields compared to those of Pt nanoparticles supported on Al2O3 and SiO2.

The lysosomal membrane protein Sidt2 is a vital regulator of mitochondrial quality control in skeletal muscle.

The role of Sidt2 in the process of glucose and lipid metabolism has been recently reported. However, whether Sidt2 is involved in the metabolic regulation in skeletal muscle remains unknown. In this study, for the first time, using skeletal muscle-selective Sidt2 knockout mice, we found that Sidt2 was vital for the quality control of mitochondria in mouse skeletal muscle. These mice showed significantly reduced muscle tolerance and structurally abnormal mitochondria. Deletion of the Sidt2 gene resulted in decreased expression of mitochondrial fusion protein 2 (Mfn2) and Dynamin-related protein 1 (Drp1), as well as peroxisome proliferator-activated receptor γ coactivator-1 (PGC1-α). In addition, the clearance of damaged mitochondria in skeletal muscle was inhibited upon Sidt2 deletion, which was caused by blockade of autophagy flow. Mechanistically, the fusion of autophagosomes and lysosomes was compromised in Sidt2 knockout skeletal muscle cells. In summary, the deletion of the Sidt2 gene not only interfered with the quality control of mitochondria, but also inhibited the clearance of mitochondria and caused the accumulation of a large number of damaged mitochondria, ultimately leading to the abnormal structure and function of skeletal muscle.

Efficacy of tripterygium glycosides combined with ARB on diabetic nephropathy: a meta-analysis.

The purpose of this meta-analysis was to evaluate the beneficial and adverse effects of tripterygium glycosides (TGs) combined with angiotensin II receptor blocker (ARB) on diabetic nephropathy (DN). We searched for randomized controlled trials (RCTs) in PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Biomedical Literature Database, China Science and Technology Journal Database up to June 2017. Weighted mean difference (WMD) and standardized mean difference (SMD) were used for continuous variables and all variables were expressed by 95% confidence interval (CI). Twenty-three studies with 1810 DN patients were included in this meta-analysis. TG combined with ARB statistically significantly improved 24-h urinary total protein (24-h UTP) (SMD = -1.46; 95% CI = -1.84 to -1.09; P<0.00001), urinary albumin excretion rate (UAER) (SMD = -6.9; 95% CI = -9.65 to -4.14, P<0.00001), serum creatinine (SCr) (WMD = -7.65.14; 95% CI = -12.99 to -2.31; P=0.005) and albumin (Alb) (WMD = 5.7; 95% CI = 4.44 to 6.96; P<0.00001) more than did ARB alone. TG combined with ARB statistically significantly affected the level of serum glutamic pyruvic transaminase (SGPT) (WMD = 1.08; 95% CI = 0.04 to 2.12, P=0.04) more than did ARB alone. Compared with ARB alone, TG combined with ARB showed no significant difference in improving blood urea nitrogen (BUN) and hemoglobin A1c (HbA1c). Minor side effects from the combined treatment were observed and mainly focused on the abnormal liver function. TG combined with ARB offers a novel concept in treating DN, more high-quality RCTs are needed for better understanding and applying the combined treatment in DN.

Effect of sidt2 Gene on Cell Insulin Resistance and Its Molecular Mechanism.

BACKGROUND: Sidt2 (SID1 transmembrane family, member 2) is a multiple transmembrane lysosomal membrane protein newly discovered in our previous study. In the previous study, we used gene targeting technique to make a mouse model of sidt2 gene knockout (sidt2-/-). It was found that sidt2-/- mice showed elevated fasting blood glucose and impaired glucose tolerance, showing a disorder of glucose metabolism, suggesting that sidt2 may be closely related to insulin resistance. We used 3T3-L1 adipocytes, C2-C12 myoblasts, and HEPA1-6 hepatoma cells as subjects to observe the effects of sidt2 on insulin-stimulated glucose uptake and the abovementioned insulin signal transduction pathways, and then to explore the effect of sidt2 on peripheral tissue insulin resistance and its possible molecular mechanism. METHODS: (1) Lentiviruses with sidt2 gene knockout and puromycin resistance were constructed by Crispr/cas9 vector and transfected into 3T3-L1 adipocytes, C2-C12 myoblasts, and HEPA1-6 hepatoma cells to construct sidt2 knockout cell line model. (2) Glucose uptake of 3T3-L1 adipocytes, C2-C12 myoblasts, and HEPA1-6 hepatoma cells stimulated by insulin was detected by glucose detection kit, and the results were analyzed. (3) Sidt2 knockout group and control group of 3T3-L1 adipocytes, C2-C12 myoblast, and HEPA1-6 hepatoma cells were cultured according to the routine method. The total proteins of the above cells were extracted, and the expression of PAKT (thr308), PI3-K, and PIRS-1 (ser307) in the IRS-1 signaling pathway of the three groups was detected by western blot technique. RESULTS: (1) The sidt2 elimination models of 3T3-L1 adipocytes, C2-C12 myoblasts, and HEPA1-6 hepatoma cells were successfully constructed. (2) It was found that the glucose uptake of cells in the sidt2 knockout group was lower than that in normal group under insulin stimulation through the detection of glucose concentration in the cell culture medium. (3) It was found that the expression of PAKT (thr308) and PI3-K protein decreased and the expression of PIRS-1 (ser307) protein increased in sidt2-/- group compared to the control group. CONCLUSIONS: sidt2 knockout can reduce glucose uptake in peripheral tissue under insulin stimulation, which may lead to peripheral tissue insulin resistance by affecting the IRS-1 signal pathway.