IGFBP-rP1 is a potential therapeutic target in androgenic alopecia.

The available interventions for androgenic alopecia (AGA), the most common type of hair loss worldwide, remain limited. The insulin growth factor (IGF) system may play an important role in the pathogenesis of AGA. However, the exact role of IGF binding protein-related protein 1 (IGFBP-rP1) in hair growth and AGA has not been reported. In this study, we first found periodic variation in IGFBP-rP1 during the hair cycle transition in murine hair follicles (HFs). We further demonstrated that IGFBP-rP1 levels were lower in the serum and scalp HFs of individuals with AGA than in those of healthy controls. Subsequently, we verified that IGFBP-rP1 had no cytotoxicity to human outer root sheath cells (HORSCs) and that IGFBP-rP1 reversed the inhibitory effects of DHT on the migration of HORSCs in vitro. Finally, a DHT-induced AGA mouse model was created. The results revealed that the expression of IGFBP-rP1 in murine HFs was downregulated after DHT treatment and that subcutaneous injection of IGFBP-rP1 delayed catagen occurrence and prolonged the anagen phase of HFs in mice with DHT-induced AGA. The present work shows that IGFBP-rP1 is involved in hair cycle transition and exhibits great therapeutic potential for AGA.

Divergent Access to Chiral C2- and C3-Alkylated Pyrrolidines by Catalyst-Tuned Regio- and Enantioselective C(sp3)-C(sp3) Coupling.

Novel-substituted pyrrolidine derivatives are widely used in drugs and bioactive molecules. The efficient synthesis of these valuable skeletons, especially enantiopure derivatives, is still recognized as a key bottleneck to overcome in chemical synthesis. Herein, we report a highly efficient catalyst-tuned regio- and enantioselective hydroalkylation reaction for the divergent synthesis of chiral C2- and C3-alkylated pyrrolidines through desymmetrization of the readily available 3-pyrrolines. The catalytic system consists of CoBr2 with a modified bisoxazoline (BOX) ligand, which can achieve the asymmetric C(sp3)-C(sp3) coupling via the distal stereocontrol, providing a series of C3-alkylated pyrrolidines in high efficiency. Moreover, the nickel catalytic system allows the enantioselective hydroalkylation to synthesize the C2-alkylated pyrrolidines through the tandem alkene isomerization/hydroalkylation reaction. This divergent method uses readily available catalysts, chiral BOX ligands, and reagents, delivering enantioenriched 2-/3-alkyl substituted pyrrolidines with excellent regio- and enantioselectivity (up to 97% ee). We also demonstrate the compatibility of this transformation with complex substrates derived from a series of drugs and bioactive molecules in good efficiency, which offers a distinct entry to more functionalized chiral N-heterocycles.

Oxygen Reduction Activity of B←N-Containing Organic Molecule Affected by Asymmetric Regulation.

Organic molecular catalysts have received great attention as they have the merits of well-controlled molecular structures for the development of catalytic chemistry. Herein, the electronic distribution of active sites is regulated by asymmetrically introducing S-heterocycle on one side of the molecular core. As a result, the asymmetric as-PYT and as-BNT show higher oxygen reduction performance than their symmetric counterparts without (s-PY, s-PY2T) or with two S-heterocycle units (s-BN, s-BN2T). Density functional theory calculations reveal that the carbon atoms (site-12) at symmetric s-BN and s-BN2T are the catalytic active sites, while for asymmetric as-BNT, it has changed to amino-N atom (site-14). Due to the non-uniform charge distribution and increased dipole moment of as-BNT caused by asymmetric molecular configuration, the kinetics of catalytic reaction has changed significantly. The catalytically active sites of specific N atoms are further verified experimentally and theoretically by using sterically hindered phenyl groups. This work provides a simple but efficient method to design metal-free oxygen reduction electrocatalysts.

Longer Operating Time During Gastrectomy Has Adverse Effects on Short-Term Surgical Outcomes.

BACKGROUND: Gastric cancer continues to be one of the malignant tumor types with high morbidity and mortality worldwide. Although remarkable improvements have been made to combat gastric cancer, surgery is still the first choice of treatment for gastric cancer. METHODS: This was a single-center and retrospective study. A total of 110 patients who underwent radical gastrectomy with D2 lymph node dissection between 2014 and 2017 were included in this study, and all patients were treated by the same medical staff. Based on the median operating time, patients were grouped into a long-time group (>180 min) and a short-time group (≤180 min). Influences of operating time on outcomes of patients in the short-term and long-term groups were analyzed. RESULTS: The long-time group showed a higher incidence of postoperative complications compared with the short time group (P < 0.01) with a significant decrease in serum albumin and the prognostic nutritional index value. Moreover, a long operating time was often caused by the operating start time (P < 0.001), excision difficulty caused by lager tumor size (P < 0.001), worse tumor differentiation, and deeper tumor invasion (P < 0.05). However, length of operating time did not significantly influence overall survival of patients who underwent radical gastrectomy. CONCLUSIONS: The results suggested that operating time might be an indicator of the incidence of postoperative complication and that several important variables, such as prognostic nutritional index, serum albumin, operating start time, and excision time, could be intervened in the perioperative period to help patients gain a better outcome after gastrectomy.

The influence of aberrant expression of GLI1/p-S6K on colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Recent studies have reported that PI3K/AKT/mTOR pathway regulated the GLI1 expression level via SMO-independent pathway in a variety of tumor types. We detected the expression level of GLI1/p-S6K in CRC tissues. We found the expression of GLI1/p-S6K was apparently close with lymph node metastasis and TNM stage and patients with positive GLI1/p-S6K expression had shorter survival time and patients with both GLI1 and p-S6K positive expression had an even worse overall survival than those with single positive expression. Moreover, GLI1 and p-S6K expression was considered to be independent prognostic factors in CRC patient and the positive co-expression of GLI1/p-S6K had greater influence than single expression positive on the prognosis of postoperative patients with tumor size≥5 cm, well differentiation, positive lymph node metastasis, venous invasion, neural invasion and TNM III-IV. Meanwhile, the GLI1/p-S6K expression had impact on more clinicopathologic features in colon-side carcinoma than in rectum-side carcinoma and the mTOR/S6K/GLI1 axis played an important role in CRC especially in advanced stage. Hence, further studies are underway to explore the molecular mechanism between GLI1 and p-S6K in CRC, and in addition, it offers novel facilities for molecular targeting therapy for CRC.

Lowering Molecular Symmetry To Improve the Morphological Properties of the Hole-Transport Layer for Stable Perovskite Solar Cells.

Inspired by the structural feature of the classical hole-transport material (HTM), Spiro-OMeTAD, many analogues based on a highly symmetrical spiro-core were reported for perovskite solar cells (PSCs). However, these HTMs were prone to crystallize because of the high molecular symmetry, forming non-uniform films, unfavorable for the device stability and large-area processing. By lowering the symmetry of spiro-core, we report herein a novel spirobisindane-based HTM, Spiro-I, which could form amorphous films with high uniformity and morphological stability. Compared to the Spiro-OMeTAD-based PSCs, those containing Spiro-I exhibit similar efficiencies for small area but higher ones for large area (1 cm2 ), and especially much higher air stability (retaining 80 % of initial PCE after 2400 h storage without encapsulation). Moreover, the Spiro-I can be synthesized from a cheap starting material bisphenol A and used with a small amount for the device fabrication.

Hybridizing Shear-Stiffening Gel and Chemically-Strengthened Ultrathin Glass Sheets for Flexible Impact-Resistant Armor.

Traditional anti-impact armors and shields are normally made of stiff and hard materials and therefore deficient in flexibility. This greatly limits their applications in protecting objects with complex geometries or significant deformability. Flexible armors can be developed with the application of hard platelets and soft materials, but the lower rigidity of the flexible armors renders them incapable of providing sufficient resistance against impact attacks. To address the inherent conflict between flexibility and impact resistance in traditional armors, here, a composite is developed by hybridizing a shear-stiffening gel as the matrix and chemically-strengthened ultrathin glass sheets (CSGS) as the reinforcement. The resulting laminate, termed PCCL, exhibits both high flexibility and high impact resistance. Specifically, at low strain rates, the high ductility of the gel combined with the high flexural strength of the CSGS enables the PCCL to undergo considerable deformation; at high strain rates, on the other hand, the shear stiffening behavior of the gel matrix endows the PCCL with excellent impact resistance manifested by its high performance in energy absorption and high rigidity. With the combination of high flexibility and high impact resistance, the PCCL is demonstrated to be an ideal armor for protecting curved vulnerable objects from impact attacks.

CoH-catalyzed asymmetric remote hydroalkylation of heterocyclic alkenes: a rapid approach to chiral five-membered S- and O-heterocycles.

Saturated heterocycles, which incorporate S and O heteroatoms, serve as fundamental frameworks in a diverse array of natural products, bioactive compounds, and pharmaceuticals. Herein, we describe a unique cobalt-catalyzed approach integrated with a desymmetrization strategy, facilitating precise and enantioselective remote hydroalkylation of unactivated heterocyclic alkenes. This method delivers hydroalkylation products with high yields and excellent stereoselectivity, representing good efficiency in constructing alkyl chiral centers at remote C3-positions within five-membered S/O-heterocycles. Notably, the broad scope and good functional group tolerance of this asymmetric C(sp3)-C(sp3) coupling enhance its applicability.

Regio- and Enantioselective Hydromethylation of 3-Pyrrolines and Glycals Enabled by Cobalt Catalysis.

Enantioenriched 3-methylpyrrolidine, with its unique chiral nitrogen-containing core skeleton, exists widely in various functional molecules, including natural products, bioactive compounds, and pharmaceuticals. Traditional methods for synthesizing these valuable methyl-substituted heterocycles often involve enzymatic processes or complex procedures with chiral auxiliaries, limiting the substrate scope and efficiency. Efficient catalytic methylation, especially in an enantioselective manner, has been a long-standing challenge in chemical synthesis. Herein, we present a novel approach for the remote and stereoselective installation of a methyl group onto N-heterocycles, leveraging a CoH-catalyzed asymmetric hydromethylation strategy. By effectively combining a commercial cobalt precursor with a modified bisoxazoline (BOX) ligand, a variety of easily accessible 3-pyrrolines can be converted to valuable enantiopure 3-(isotopic labeling)methylpyrrolidine compounds with outstanding enantioselectivity. This efficient protocol streamlines the two-step synthesis of enantioenriched 3-methylpyrrolidine, which previously required up to five or six steps under harsh conditions or expensive starting materials.

Low-intensity exercise training improves systolic function of heart during metastatic melanoma-induced cachexia in mice.

Cardiac dysfunction frequently emerges in the initial stages of cancer cachexia, posing a significant complication of the disease. Physical fitness is commonly recommended in these early stages of cancer cachexia due to its beneficial impacts on various aspects of the condition, including cardiac dysfunction. However, the direct functional impacts of exercise on the heart during cancer cachexia largely remain unexplored. In this study, we induced cancer cachexia in mice using a metastatic B16F10 melanoma model. Concurrently, these mice underwent a low-intensity exercise regimen to investigate its potential role in cardiac function during cachexia. Our findings indicate that exercise training can help prevent metastatic melanoma-induced muscle loss without significant alterations to body and fat weight. Moreover, exercise improved the melanoma-induced decline in left ventricular ejection fraction and fractional shortening, while also mitigating the increase in high-sensitive cardiac troponin T levels caused by metastatic melanoma in mice. Transcriptome analysis revealed that exercise significantly reversed the transcriptional alterations in the heart induced by melanoma, which were primarily enriched in pathways related to heart contraction. These results suggest that exercise can improve systolic heart function and directly influence the transcriptome of the heart during metastatic melanoma-induced cachexia.

Catalytic reduction of nitrogen monoxide using iron-nickel oxygen carriers derived from electroplating sludge: Novel method for the collaborative emission decrease of polluting gases.

The valorization of electroplating sludge (ES) for high added value presents greater economic and environmental benefits than conventional treatment methods such as thermal processing, solidification, and landfill. Inspired by the mechanism of chemical looping combustion (CLC), this study developed a novel cost-effective method for denitrification by preparing FeNi-OCs from ES to achieve the synergistic reduction of CO and NO emissions. The phase structure, micromorphology, and valence state changes of the FeNi-OC catalyst during the CO-catalyzed reduction of NO and the pathway for catalytic denitrification using FeNi-OCs were analyzed. Results showed that CO could reduce FeNi-OCs to FeNi, and the reduced FeNi was subsequently oxidized back to FeNi-OCs by NO, a process analogous to CLC. During experiments, the simultaneous consumption of CO and NO gases was observed at 350 °C. This phenomenon was highly pronounced at 600 °C, where the CO and NO concentrations decreased from initial values of 8550 and 470 ppm, respectively, to 6719 and 0 ppm, respectively, with conversion rates of 21.41 % and 100 %, respectively. Hence, synergistic emission reduction was achieved. Further experiments also indicated that the addition of 1.5 % ES during iron ore sintering could substantially reduce the CO and NO concentrations in the sintering flue gas from 1268.32 and 244.81 ppm, respectively, to 974.51 and 161.11 ppm, respectively.

Enzyme immobilized on magnetic fluorescent bifunctional nanoparticles for α-glucosidase inhibitors virtual screening from Agrimonia pilosa Ledeb extracts accompanied with molecular modeling.

Agrimonia pilosa Ledeb (APL) is a significant source of inhibitors for α-glucosidase, which is an essential target enzyme for the treatment of type 2 diabetes, cancer and acquired immune deficiency syndrome. Ligand fishing is a suitable approach for the highly selective screening of bioactive substances in complex mixtures. Yet it is unable to conduct biomedical imaging screening, which is crucial for real-time identification. In this case, a bioanalytical platform combining magnetic fluorescent ligand fishing and in-situ imaging technique was established for the screening and identification of α-glucosidase inhibitors (AGIs) from APL crude extract, utilizing α-glucosidase coated CuInS2/ZnS-Fe3O4@SiO2 (AG-CIZSFS) nanocomposites as extracting material and fluorescent tracer. The AG-CIZSFS nanocomposites prepared through solvothermal and crosslinking methods displayed fast magnetic separation, excellent fluorescence performance and high enzyme activity. The tolerance of immobilized enzyme to temperature and pH was stronger than that of free enzyme. Prior to proof-of-concept with APL crude extract, a number essential parameters (glutaraldehyde concentration, immobilized time, enzyme amount, reaction solution pH, incubation temperature, incubation time, percentage of methanol in eluen, elution times and eluent volume) were optimized using an artificial test mixture. The fished ligands were identified by UPLC-MS/MS and their biological activities were preliminarily evaluated by real-time cellular morphological imaging of human colon carcinoma (HCT-116) cells based on confocal laser scanning microscope (CLSM). Their α-glucosidase inhibitory activities were further verified and studied by classical pNPG method and molecular docking. The isolated compounds exhibited significant α-glucosidase inhibitory activities with a IC50 value of 11.57 µg·mL-1. Six potential AGIs including tribuloside, ivorengenin A, tormentic acid, 1ß, 2ß, 3ß, 19α-Tetra hydroxyurs-12-en-28-oic acid, corosolic acid and pomolic acid were ultimately screened out and identified from APL crude extracts. The proposed approach, which combined highly specific screening with in-situ visual imaging, provided a powerful platform for discovering bioactive components from multi-component and multi-target traditional Chinese medicine (TCM).

Hsa-circ-0052001 promotes gastric cancer cell proliferation and invasion via the MAPK pathway.

BACKGROUND: Gastric cancer (GC) ranks fourth among the causes of death from malignant tumors in the world. Studies have implicated the dysregulation of circRNAs with GC. However, the relationship between hsa-circ-0052001 and GC is unclear. METHODS: In our current study, we assessed the expression levels of hsa-circ-0052001 in GC cells and tissues using quantitative real-time PCR (qPCR). The role of hsa-circ-0052001 expression on the proliferation and invasion of GC cells was assessed using in vitro experiments. The role of hsa-circ-0052001 on the proliferation of GC cells was also analyzed using in vivo models. The pathways downstream of hsa-circ-0052001 were identified using bioinformatics analyses, western blot (WB) assays, and qRT-PCR. RESULTS: We found that compared with normal gastric mucosa epithelial cells and adjacent paracancer tissues, hsa-circ-0052001 was overexpressed in GC cells and tissues. Also, the hsa-circ-0052001 level was linked to patient clinicopathological characteristics of GC. Cell proliferation and metastatic ability were inhibited in gastric cancer cells when hsa-circ-0052001 was knocked down in vitro and cancer growth in vivo. Mechanistically, hsa-circ-0052001 promoted the carcinogenesis of GC cells via the MAPK signal pathway. CONCLUSION: Hsa-circ-0052001 functions as a tumor gene in promoting the progression of GC through MAPK pathway, which has provided a promising target for patients with GC.

Metal-Catalyst-Controlled Divergent Synthesis of γ-Butyrolactones via Intramolecular Coupling of Epoxides with Alcohols.

A metal-controlled divergent protocol for the synthesis of α- and ß-substituted γ-butyrolactones was developed through intramolecular coupling of epoxides with alcohols. This method provides an efficient and practicable way to afford γ-butyrolactones with good efficiency, excellent regioselectivity, and broad substrate scope.

Low-intensity exercise training increases systolic function of heart and MHCII low cardiac resident macrophages.

Physical activities have beneficial effects on cardiovascular health, although the specific mechanisms are largely unknown. Cardiac resident macrophages (cMacs) and the distribution of their subsets are critical regulators for maintaining cardiovascular health and cardiac functions in both steady and inflammatory states. Therefore, we investigated the subsets of cMacs in mice after low-intensity exercise training to elucidate the exercise-induced dynamic changes of cMacs and the benefits of exercise for the heart. The mice were subjected to treadmill running exercise five days per week for five weeks using a low-intensity exercise training protocol. Low-intensity exercise training resulted in a suppression of body weight gain in mice and a significant increase in the ejection fraction, a parameter that represents the systolic function of the heart. Low-intensity exercise training induced the alterations in the transcriptome of the heart, which are associated with muscle contraction and mitochondrial function. Furthermore, low-intensity exercise training did not alter the number of lymphocyte antigen 6 complex, locus C1 (Ly6c)- cMacs but instead remodeled the distributions of Ly6c- cMac subsets. We observed an increase in the percentage of major histocompatibility complex class II (MHCII)low cMacs and a decrease in the percentage of MHCIIhigh cMacs in the heart after low-intensity exercise training. Therefore, the benefits of exercise for cardiovascular fitness might be associated with the redistribution of cMac subsets and the enhancement of the ejection fraction.

San-wei-tan-xiang capsule attenuates atherosclerosis by increasing lysosomal activity in adipose tissue macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Dyslipidemia is the leading risk factor of atherosclerosis (AS). Adipose tissue macrophages (ATMs) can regulate postprandial cholesterol levels via uptake and hydrolyzation of lipids and regulation of macrophage cholesterol efflux (MCE). San-wei-tan-xiang (SWTX) capsule, a Traditional Chinese medicine, exerts clinical benefits in patients with atherosclerotic cardiovascular diseases. AIM OF THE STUDY: This work is aimed to evaluate the chemical ingredients and mechanisms of SWTX in anti-AS. MATERIALS AND METHODS: The chemical ingredients of SWTX identified by liquid chromatography coupled with tandem mass spectrometry were used for network pharmacological analysis. The atheroprotective function of SWTX was evaluated in ApoE-/- mice fed a cholesterol-enriched diet. RESULTS: The chemical ingredients identified in SWTX were predicated to be important for lipid metabolism and AS. Animals studies suggested that SWTX effectively attenuated the atherosclerotic plaque growth, elevated postprandial HDL cholesterol levels, elevated the proportion of Tim4 and CD36-expressed ATMs, and upregulated the uptake of lipid and lysosomal activity in ATMs. SWTX-induced elevation of postprandial HDL cholesterol levels was dependent on increased lysosomal activity, since chloroquine, an inhibitor of lysosomal function, blocked the effect of SWTX. Lastly, some predicated bioactive compounds in SWTX can elevate lysosomal activity in vitro. CONCLUSION: SWTX could attenuate atherosclerotic plaque formation by elevating lysosomal activity and enhancing MCE in ATMs.

Polycomb repressive complex 2 controls cardiac cell fate decision via interacting with RNA: Promiscuously or well-ordered.

The epigenetic landscape determines cell fate during heart development. Polycomb repressive complex 2 (PRC2) mediates histone methyltransferase activity during cardiac cell differentiation. The PRC2 complex contains the proteins embryonic ectoderm development (EED), suppressor of zeste (SUZ12), the chromatin assembly factor 1 (CAF1) histone-binding proteins RBBP4 and RBBP7, and the histone methyltransferase called enhancer of zeste (EZH2 or EZH1), which incorporates the Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain. Cardiac PRC2-deficient mice display lethal congenital heart malformations. The dynamic process of cardiac cell fate decisions is controlled by PRC2 and the PRC2-mediated epigenetic landscape. Although specific individual long noncoding RNAs (lncRNAs) including Braveheart were widely reported to regulate the recruitments of PRC2 to their specific targets, a promiscuous RNA binding profile by PRC2 was also identified to play an essential role in cardiac cell fate decision. In this review, we focus on RNA-mediated PRC2 recruitment machinery in the process of cardiac cell fate decisions. The roles of individual lncRNAs which recruit PRC2, as well as promiscuous RNA binding by PRC2 in heart development are summarized. Since the binding priority of RNAs with different primary and secondary structures differs in its affinity to PRC2, the competitive relationship between individual lncRNAs binding and promiscuous RNA binding by PRC2 may be important for understanding the machinery by which biding of individual lncRNA and promiscuous RNA by PRC2 coordinately control the well-ordered dynamic cardiac cell lineage differentiation process.

Therapeutic targeting of mechanical stretch-induced FAK/ERK signaling by fisetin in hypertrophic scars.

Hypertrophic scarring is a complex fibrotic disease with few treatment options. Mechanical stress has been proven to be crucial for hypertrophic scar (HS) formation. Here, we showed that the flavonoid small molecule fisetin, could dramatically ameliorate HS formation in a mechanical stretch-induced mouse model. In addition, in vitro and in vivo studies demonstrated that fisetin inhibited the stretch-induced profibrotic effects by suppressing the proliferation, activation, and collagen production of fibroblasts. Mechanistically, we revealed that fisetin obviously downregulated mechanical stretch-induced the phosphorylation of FAK and ERK, and reduced nuclear localization of ERK. This bioactivity of fisetin may result from its selective binding to the catalytic region of FAK, which was suggested by the molecular docking study and kinase binding assay. Taken together, these findings suggest that fisetin is a promising agent for the treatment of hypertrophic scars and other excessive fibrotic diseases.

Nickel-catalyzed cross-coupling of epoxides with aryltriflates: rapid and regioselective construction of aryl ketones.

Aryl ketones are one of the most important classes of organic compounds, and widely present in various pharmacological compounds, biologically active molecules and functional materials. Presented herein is a facile synthetic method for the construction of ketones via Ni-catalyzed cross coupling of epoxides with aryltriflates. A range of easily accessible epoxides can be highly regioselectively converted to the corresponding aryl ketones with good yields in a redox neutral fashion.

Roux-en-Y reconstruction alleviates radical gastrectomy-induced colitis via down-regulation of the butyrate/NLRP3 signaling pathway.

BACKGROUND: Different methods for digestive tract reconstruction have a complex impact on the nutritional status of gastric cancer (GC) patients after radical gastrectomy. Previous studies reported that Roux-en-Y (R-Y) reconstruction resulted in obvious weight reduction and improvement in type 2 diabetes in obese patients. We investigated the relationship between R-Y reconstruction, gut microbiota, and the NLRP3 inflammasome in GC patients with poor basic nutrition. METHODS: Changes in the gut microbiota after radical gastrectomy accomplished by different methods of digestive tract reconstruction were investigated via fecal microbiota transplantation. The underlying mechanisms were also explored by analyzing the role of the microbiota, butyrate, and the NLRP3 inflammasome in the colon tissues of colitis model mice and GC patients after radical gastrectomy. FINDINGS: R-Y reconstruction effectively relieved intestinal inflammation and facilitated nutrient absorption. 16S rRNA analysis revealed that gavage transplantation with the fecal microbiota of R-Y reconstruction patients could reverse dysbacteriosis triggered by radical gastrectomy and elevate the relative abundance of some short-chain fatty acid (SCFA)-producing bacteria. Subsequently, butyrate negatively regulated the NLRP3-mediated inflammatory signaling pathway to inhibit the activation of macrophages and the secretion of pro-inflammatory mediators such as caspase-1 and interleukin (IL)-1ß, decreasing the level of intestinal inflammation and promoting nutrient absorption. INTERPRETATION: R-Y reconstruction induced colonization with SCFA-producing bacteria to alleviate radical gastrectomy-induced colitis by down-regulating the NLRP3 signaling pathway. This can be a new strategy and theoretical basis for the management of the postoperative nutritional status of GC patients. FUNDING: This work was supported by the National Nature Science Foundation of China (81974375), the BoXi cultivation program (BXQN202130), and the Project of Youth Foundation in Science and Education of the Department of Public Health of Suzhou (KJXW2018001).