Anionic cardiolipin stabilizes the transmembrane region of hyaluronan synthase and promotes catalysis-relevant dynamics.

Hyaluronic acid (HA) is a glycosaminoglycan essential for cellular processes and finding increasingly applications in medicine, pharmaceuticals, and cosmetics. While membrane-integrated Class I hyaluronan synthase (HAS) catalyzes HA synthesis in most organisms, the molecular mechanisms by which HAS-lipid interactions impact HAS catalysis remain unclear. This study employed coarse-grained molecular dynamics simulation combined with dimensionality reduction to uncover the interplay between lipids and Streptococcus equisimilis HAS (SeHAS). A minimum of 67 % cardiolipin is necessary for HA synthesis, as determined through simulations using gradient-composed membranes. The anionic cardiolipin stabilizes the cationic transmembrane regions of SeHAS and thereby maintains its conformation. Moreover, the highly dynamic cardiolipin is required to modulate the catalysis-relevant motions in HAS and thus facilitate HA synthesis. These findings provide molecular insights essential not only for understanding the physiological functions of HAS, but also for the development of cell factories and enzyme catalysts for HA production.

Bone cement distribution may significantly affect the efficacy of percutaneous vertebroplasty in treating symptomatic Schmorl's nodes.

PURPOSE: Percutaneous vertebroplasty(PVP) has been widely used in treating symptomatic Schmorl's nodes(SNs). However, there were still some patients with poor pain relief. At present, there is a lack of research to analyze the reasons for poor efficacy. METHODS: Review the SNs patients treated with PVP in our hospital from November 2019 to June 2022, collect their baseline data. Reverse reconstruction software was used to calculate the filling rate of bone edema ring(Rf). NRS score was used to evaluate pain and ODI to evaluate function. The patients were divided into remission group(RG) and non remission group(n-RG) according to symptom. In addition, according to the Rf, they were divided into excellent, good and poor groups. Differences between groups were investigated. RESULTS: A total of 26 vertebrae were included in 24 patients. When grouped according to symptoms, patients in n-RG were older, and surgical segments were tend to locate in lower lumbar spine. The proportion of Poor distribution was significantly higher. When grouped according to the cement distribution, the preoperative NRS and ODI of the three groups were comparable, but the NRS and ODI of Poor group were significantly worse than the Excellent and Good groups postoperatively and at the last follow-up. CONCLUSIONS: The cement distribution may significantly affect the efficacy of PVP in treating symptomatic SNs. We suggest that the bone edema ring should be filled as fully as possible to ensure the efficacy. In addition, advanced age and low lumbar lesions are also adverse factors for clinical outcomes.

Risk factors for spinal subdural hematoma after minimally invasive transforaminal lumbar Interbody Fusion (MI-TLIF): a multivariate analysis.

BACKGROUND: Spinal subdural hematoma (SSH) is a rare cause of compression of the neutral elements of the spinal cord. However, little is known about the presentation of acute SSH after lumbar spine surgery. The reason for this may be that symptomatic SSH occurs rarely and is not given enough attention by spine surgeons. Currently, the decision to perform MRI postoperatively is more dependent on surgeon preference; therefore, no high-quality studies have been published. Our team reports our experience in the diagnosis and management of SSH after lumbar decompression and fusion surgery. METHODS: We retrospectively studied 215 patients who underwent routine MRI following minimal invasive transforaminal lumbar interbody fusion (MI-TLIF) between 2020-01-01 and 2022-06-30. The patients were divided into SSH group (17 cases) and non-SSH group (198 cases) according to the occurrence of SSH. Univariate analysis and multivariate logistic regression analysis were performed to identify relevant risk factors that increase the risk of SSH postoperatively. RESULTS: None of the patients presented with serious neurologic symptoms, such as lower extremity paralysis or cauda equina syndrome that required emergency hematoma debridement. SSH was found in 17 (7.9%) patients and non-SSH in 198 (92.1%). Factors affecting SSH were presence of hypertension, presence of diabetes and postoperative anticoagulant therapy. The significantly independent risk factor of postoperative SSH were diabetes (P = 0.008, OR: 6.988) and postoperative anticoagulant therapy (P = 0.003, OR: 8.808). CONCLUSIONS: SSH after MI-TLIF is not a rare condition, with generally no requirement of emergency evacuation. Comprehensive anti-symptomatic treatment could achieve satisfactory results. Diabetes mellitus and postoperative anticoagulant therapy are independent risk factors for SSH. Spine surgeons should hold applicability of the use of anticoagulants after lumbar surgery.

The role of conformational dynamics in the activity of polymer-conjugated CalB in organic solvents.

Perennial interest in enzyme catalysis has been expanding its applicability from aqueous phases where enzymes are naturally evolved to organic solvents in which the majority of industrial chemical syntheses are carried out. Although conjugating an enzyme with a soluble polymer has been attempted to enhance enzyme activity in organic solvents, the underlying mechanism remains poorly understood in terms of the conformational dynamics and enzyme activity. Herein, we combine LF-NMR measurements and MD simulations to investigate the effects of polymer grafting on the conformational dynamics of CalB in organic solvents and the consequential impacts on the catalytic kinetics, using the lipase-catalyzed transesterification reaction as a model system. LF-NMR measurements confirm that conjugation with a soluble polymer improves the enzyme flexibility in organic solvents, leading to an increase in the catalytic efficiency of up to two orders of magnitude. MD simulations suggest that the conjugated enzyme samples a larger conformational space, compared to its native counterpart, validating the hypothesis that polymer motion enhances enzyme dynamics. These experimental and simulation results provide new insights for enhancing enzyme conformational dynamics and thereby catalytic kinetics in organic solvents.

The leucine-rich repeat receptor-like kinase OsERL plays a critical role in anther lobe formation in rice.

In Arabidopsis, ERECTA (ER) subfamily of leucine-rich repeat (LRR) receptor kinases (LRR-RKs) play important roles in cell division and cell elongation. However, the functions of OsER genes in rice are still very much unknown. In this study, sixty-seven TILLING and four gene-edited mutants were identified for one of the three OsERs, OsERL, and used for functional analyses. Results showed that mutations in OsERL led to striking defects in anther development. Compete male sterility and reduced numbers of anther lobes, more severe than knockout mutants, were observed in mutants with amino acid substitutions in the kinase domain. Among alleles with amino acid changes in LRRs, only one mutation in the 16th LRR showed evident phenotype, suggesting a role of the LRR in ligand sensing. OsERL is expressed in shoot apcies, internodes and anthers, and within the anther OsERL is expressed in sporophytic and tapetal cells. Cell biological analyses revealed that mutations in OsERL led to defected periclinal division in archesporial cells in anthers, suggesting a critical role of OsERL in rice anther development.

Dihydrotanshinone I inhibits ovarian cancer cell proliferation and migration by transcriptional repression of PIK3CA gene.

Dihydrotanshinone I (DHTS), extracted from Salvia miltiorrhiza, was found to be the most effective compound of tanshen extracts against cancer cells in our previous studies. However, the therapeutic benefits and underlying mechanisms of DHTS on ovarian cancer remain uncertain. In this study, we demonstrated the cytocidal effects of DHTS on chemosensitive ovarian cancer cells with or without platinum-based chemotherapy. DHTS was able to inhibit proliferation and migration of ovarian cancer cells in vitro and in vivo through modulation of the PI3K/AKT signalling pathways. Combinatorial treatment of DHTS and cisplatin exhibited enhanced DNA damage in ovarian cancer cells. Overall, these findings suggest that DHTS induces ovarian cancer cells death via induction of DNA damage and inhibits ovarian cancer cell proliferation and migration.

Needle-Guided Suture Technique for Lumbar Annular Fiber Closure in Microendoscopic Discectomy: A Technical Note and Case Series.

BACKGROUND Annular fiber closure techniques have been proven effective in reducing short-term recurrence after discectomy. However, annular fiber closure devices are expensive and still fail at a low rate. We present a novel suture method, needle-guided annular closure suture (NGACS) that does not require a special device and can be performed for annular fiber closure following microendoscopic discectomy. MATERIAL AND METHODS Twenty-five patients who underwent treatment with NGACS were reviewed by analysis of the medical records. The clinical outcomes were assessed and compared preoperatively and immediately, 1, 6, and 12 months postoperatively. The parameters included the Visual Analog Scale (VAS)-back and VAS-leg scores and the Oswestry Disability Index (ODI). Midsagittal T2WI images were obtained to evaluate lumbar disc degeneration using the Pfirrmann grade. Additional adverse events were also recorded and tracked. RESULTS The VAS-back and VAS-leg scores and the ODI were significantly different at each follow-up time point (P<0.001), and improvements in pain and disability were maintained well during the follow-up period. Lumbar disc reherniation or other serious adverse events were not observed in this series. There was no significant difference between the initial and final Pfirrmann grades (Z=-1.414, P=0.157). The preoperative average disc height was 9.94±1.97 mm, and the disc height at 12 months after surgery was 9.14±1.88 mm. The average decrease in disc height was 8.11±3.36%. CONCLUSIONS This study demonstrates the feasibility and superior clinical outcomes of the NGACS technique. This method can be a good substitution when annular fiber closure devices are not available. Moreover, this technique can be easily popularized due to its low cost and few restrictions.

Improving the blast resistance of the elite rice variety Kongyu-131 by updating the pi21 locus.

BACKGROUND: As an elite japonica rice variety, Kongyu-131 has been cultivated for over 20 years in the third accumulated temperature zone of Heilongjiang Province, China. However, the cultivated area of Kongyu-131 has decreased each year due to extensive outbreaks of rice blast. To achieve the goals of improving blast resistance and preserving other desirable traits in Kongyu-131, a genome-updating method similar to repairing a bug in a computer program was adopted in this study. A new allele of the broad-spectrum blast resistance gene pi21 in the upland rice variety GKGH was mined by genetic analysis and introgressed into the genome of Kongyu-131 to upgrade its blast resistance. RESULT: QTL analysis was performed with an F2 population derived from a cross between Kongyu-131 and GKGH, and a blast resistance QTL was detected near the pi21 locus. Parental Pi21 sequence alignment showed that the pi21 of the donor (GKGH) was a new allele. By 5 InDel or SNP markers designed based on the sequence within and around pi21, the introgressed chromosome segment was shortened to less than 634 kb to minimize linkage drag by screening recombinants in the target region. The RRPG was 99.92%, calculated according to 201 SNP markers evenly distributed on 12 chromosomes. Artificial inoculation at the seedling stage showed that the blast resistance of the new Kongyu-131 was improved significantly. Field experiments also indicated that the improved Kongyu-131 had enhanced field resistance to rice blast and grain-quality traits similar to those of the original Kongyu-131. CONCLUSIONS: It is feasible to improve resistance to rice blast and preserve other desirable traits by precisely improving the Pi21 locus of Kongyu-131. Linkage drag can be eliminated effectively via recombinant selection on both sides of the target gene.

Nanoparticles Penetrate into the Multicellular Spheroid-on-Chip: Effect of Surface Charge, Protein Corona, and Exterior Flow.

Nanoparticles (NPs) are widely studied as tumor targeted vehicles. The penetration of NPs into the tumor is considered as a major barrier for delivery of NPs into tumor cell and a big challenge to translate NPs from lab to the clinic. The objective of this study is to know how the surface charge of NPs, the protein corona surrounding the NPs, and the fluid flow around the tumor surface affect the penetration and accumulation of NPs into the tumor, through in vitro penetration study based on a spheroid-on-chip system. Surface decorated polystyrene (PS) NPs (100 nm) carrying positive and negative surface charge were loaded to the multicellular spheroids under static and flow conditions, in the presence or absence of serum proteins. NP penetration was investigated by confocal laser microscopy scanning followed with quantitative image analysis. The results reveal that negatively charged NPs are attached more on the spheroid surface and easier to penetrate into the spheroids. Protein corona, which is formed surrounding the NPs in the presence of serum protein, changes the surface properties of the NPs, weakens the NP-cell affinity, and, therefore, results in lower NP concentration on the spheroid surface but might facilitate deeper penetration. The exterior fluid flow enhances the interstitial flow into the spheroid, which benefits the penetration but also strips the NPs (especially the NPs with protein corona) on the spheroid surface, which decreases the penetration flux significantly. The maximal penetration was obtained by applying negatively charged NPs without protein corona under the flow condition. We hope the present study will help to understand the spatiotemporal performance of drug delivery NPs and inform the rational design of NPs with highly defined drug accumulation localized at a target site.

pH-Triggered Drug Release of Monodispersed P(St-co-DMAEMA) Nanoparticles: Effects of Swelling, Polymer Chain Flexibility and Drug-Polymer Interactions.

Monodispersed pH-sensitive poly(styrene-co-N,N'-dimethylaminoethyl methacrylate) (P(St-co- DMAEMA)) nanoparticles (NPs) were synthesized by emulsion polymerization for use in potential applications in targeted drug delivery to the tumor microenvironment. pH-Sensitive volume swelling and drug release of the NPs with varied St/DMAEMA molar ratios, crosslinking degrees and model drug coumarin-6 loading were explored in vitro to elucidate the pH-sensitive drug release mechanisms. The swelling of the NPs, which accounts for the electrostatic repulsion of protonated tertiary amine groups under acidic conditions, reaches maximum at low pH, low crosslinking density and high DMAEMA content. The NPs undergo a pH-triggered drug release, and under the condition of pH 5 and pH 2, the average release rate during 24 h is 1.5-fold and 3-fold higher than that at physiological pH, respectively. The pH-triggered drug release is related to pH-sensitive swelling, polymer chain flexibility and drug-polymer interaction, and is significantly impacted by the St/DMAEMA molar ratio, degree of crosslinking and drug loading.

A novel series of indazole-/indole-based glucagon receptor antagonists.

A novel, potent series of glucagon receptor antagonists (GRAs) was discovered. These indazole- and indole-based compounds were designed on an earlier pyrazole-based GRA lead MK-0893. Structure-activity relationship (SAR) studies were focused on the C3 and C6 positions of the indazole core, as well as the benzylic position on the N-1 of indazole. Multiple potent GRAs were identified with excellent in vitro profiles and good pharmacokinetics in rat. Among them, GRA 16d was found to be orally active in blunting glucagon induced glucose excursion in an acute glucagon challenge model in glucagon receptor humanized (hGCGR) mice at 1, 3 and 10mg/kg (mpk), and significantly lowered acute glucose levels in hGCGR ob/ob mice at 3 mpk dose.

Effect of oxygen-containing functional groups on the micromechanical behavior of biodegradable plastics and their formation of microplastics during aging.

Biodegradable plastics (BPs) are more prone to generate harmful microplastics (MPs) in a short time, which have always been ignored. Oxygenated functional group formation is considered to be a key indicator for assessing microplastic formation, while it is difficult to characterize at a very early stage. The micromechanical properties of the aging plastic during the formation of the MPs are highly influenced by the evolution of oxygen-containing functional groups, however, their relationship has rarely been revealed. Herein, we compared changes in the physicochemical properties of BPs and non-degradable plastic bags during aging in artificial seawater, soil, and air. The results showed that the oxidation of plastics in the air was the most significant, with the most prominent oxidation in BPs. The accumulation of carbonyl groups leads to a significant increase in the micromechanical properties and surface brittleness of the plastic, further exacerbating the formation of MPs. It was also verified by the FTIR, 2D-COS, AFM, and Raman spectroscopy analyses. Furthermore, the increased adhesion and roughness caused by oxygen-containing functional groups suggest that the environmental risks of BPs cannot be ignored. Our findings suggest that the testing of micromechanical properties can predicate the formation of the MPs at an early stage.

Ex-vivo biomechanical evaluation of the application of a novel annulus closure device to closure of annulus fibrosus.

Objective: To investigate the technical feasibility of applying a simple suture guide device to close the annulus fibrosus (AF) of the intervertebral discs (IVD). Methods: 30 sheep functional discal units (FDUs) were obtained and subjected to mock discectomy. Mock sutures were performed using 3-0 non-absorbable sutures under a novel AF suture device following a suture procedure. The FDUs were compressed under axial loading at 1.8 mm/min and evaluated for Failure load (N). Results: The failure loads of the hand stitching group (Group H) and suture device stitching group (Group S) were significantly higher than those of the control group (Group C) (p = 0.033; p < 0.001). Conclusion: This study provides reasonable reasons to believe that the simple suture guide device described here is technically feasible for AF defect closure. It thus constitutes an encouraging proof of concept for the proposed device; however, it does not constitute a complete demonstration of the device's feasibility in the clinical setting considering that the annulus closure operation is performed ex vivo on functional spinal units, as opposed to within an environment that mimics the clinical setting. To this end, confirmatory experiments will be conducted such as more multiaxial or dynamic mechanical testing, and notably performing the surgery on sheep models instead of on ex vivo functional spinal units.

The current status and development trend of hydrogel application in spinal surgery.

Spinal diseases often result in compromised mobility and diminished quality of life due to the intricate anatomy surrounding the nervous system. Medication and surgical interventions remain the primary treatment methods for spinal conditions. However, currently available medications have limited efficacy in treating spinal surgical diseases and cannot achieve a complete cure. Furthermore, surgical intervention frequently results in inevitable alterations and impairments to the initial anatomical integrity of the spinal structure, accompanied by the consequential loss of certain physiological functionalities. Changes in spine surgery treatment concepts and modalities in the last decade have led to a deepening of minimally invasive treatment, with treatment strategies focusing more on repairing and reconstructing the patient's spine and preserving physiological functions. Therefore, developing novel and more efficient treatment strategies to reduce spinal lesions and iatrogenic injuries is essential. In recent years, significant advancements in biomedical research have led to the discovery that hydrogels possess excellent biocompatibility, biodegradability, and adjustable mechanical properties. The application of hydrogel-based biotechnology in spinal surgery has demonstrated remarkable therapeutic potential. This review presents the therapeutic strategies for spinal diseases based on hydrogel tissue engineering technology.

Enhancing therapeutic effects of murine cancer vaccine by reshaping gut microbiota with Lactobacillus rhamnosus GG and jujube powder.

Cancer vaccines have gained widespread attention in recent years as an emerging treatment for tumors. However, most therapeutic cancer vaccines have failed in phase III clinical trials due to faint clinical benefits. In this study, we funded that a specific synbiotic composing Lactobacillus rhamnosus GG (LGG) and jujube powder significantly enhanced the therapeutic effects of whole cells cancer vaccine in MC38 cancer cells bearing-mouse. The utilization of LGG increased the abundance of Muribaculaceae, which is conductive to an enhanced anti-tumor effect, but reduced microbial α-diversity. The use of jujube nursed probiotic microorganisms in Lachnospiaceae and enriched microbial diversity, as indicated by increased Shannon and Chao index. The reshaped gut microbiota by this synbiotic improved lipid metabolism conductive to intensified infiltration of CD8+ T cells in the tumor microenvironment and enhanced the potency of above-mentioned cancer vaccine. These encouraging findings are helpful for further efforts towards enhancing the therapeutic effects of cancer vaccines through nutritional intervention.

Recent advances in the repair of degenerative intervertebral disc for preclinical applications.

The intervertebral disc (IVD) is a load-bearing, avascular tissue that cushions pressure and increases flexibility in the spine. Under the influence of obesity, injury, and reduced nutrient supply, it develops pathological changes such as fibular annulus (AF) injury, disc herniation, and inflammation, eventually leading to intervertebral disc degeneration (IDD). Lower back pain (LBP) caused by IDD is a severe chronic disorder that severely affects patients' quality of life and has a substantial socioeconomic impact. Patients may consider surgical treatment after conservative treatment has failed. However, the broken AF cannot be repaired after surgery, and the incidence of re-protrusion and reoccurring pain is high, possibly leading to a degeneration of the adjacent vertebrae. Therefore, effective treatment strategies must be explored to repair and prevent IDD. This paper systematically reviews recent advances in repairing IVD, describes its advantages and shortcomings, and explores the future direction of repair technology.

Boosting HSA Vaccination with Jujube Powder Modulating Gut Microbiota Favorable for Arginine Metabolism.

Whereas vaccination is established as one of the most effective and available methods against seasonal flu and holds high potential for many infectious diseases, immune response may differ among individuals and regions. In this study we examined the effects of gut microbiota on vaccination with human serum albumin (HSA) as the model vaccine in C57BL/6J mice. We observed that a two-week antibiotic cocktail (ABX) treatment hampered HSA-specific IgG1 in serum, whereas fecal microbiota transplantation (FMT) restored the gut microbiota impaired by the ABX treatment and consequently increased the proportions of macrophages in the mesenteric lymph nodes (MLNs), plasma cells in the peripheral blood, and HSA-specific immunoglobulin G1 (IgG1) in the serum. A week of daily application of jujube powder (800 mg/kg) to ABX-treated mice achieved a significantly higher HSA-specific IgG1 concentration in the serum compared with the ABX treatment group. Of particular note was that the administration of the jujube powder did not increase the myeloid cells, indicating a different mechanism of vaccination compared with FMT. More interestingly, daily pre-administration of jujube powder (800 mg/kg) to healthy mice one week ahead of vaccination boosted their immune response, as evidenced by the proportion of macrophages in the MLNs, B cells in the spleen, plasma cells and memory B cells in the peripheral blood, and HSA-specific IgG1 concentration in the serum. The 16S rRNA sequencing of gut microbiota revealed that the administration of jujube powder increased the abundance of Coriobacteriaceae associated with the metabolism of amino acids. The Kyoto encyclopedia of genes and genomes (KEGG) analysis suggested the altered microbiota is more favorable for arginine and proline metabolism, which may promote macrophages in the MLNs. These results indicate a high potential for boosting vaccination by manipulating gut microbiota with natural products.

Bioactive mineralized small intestinal submucosa acellular matrix/PMMA bone cement for vertebral bone regeneration.

Polymethylmethacrylate (PMMA) bone cement extensively utilized for the treatment of osteoporotic vertebral compression fractures due to its exceptional handleability and mechanical properties. Nevertheless, the clinical application of PMMA bone cement is restricted by its poor bioactivity and excessively high modulus of elasticity. Herein, mineralized small intestinal submucosa (mSIS) was incorporated into PMMA to prepare a partially degradable bone cement (mSIS-PMMA) that provided suitable compressive strength and reduced elastic modulus compared to pure PMMA. The ability of mSIS-PMMA bone cement to promote the attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells was shown through cellular experiments carried out in vitro, and an animal osteoporosis model validated its potential to improve osseointegration. Considering these benefits, mSIS-PMMA bone cement shows promising potential as an injectable biomaterial for orthopedic procedures that require bone augmentation.

Preparation and evaluation of paclitaxel-loaded nanoparticle incorporated with galactose-carrying polymer for hepatocyte targeted delivery.

OBJECTIVE: Paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles incorporated with galactose-carrying polymer poly(vinyl benzyllactonamide) (PVLA) were prepared to facilitate the hepatocyte cell targeted delivery of paclitaxel via ligand-receptor mediated endocytosis. The factors impacting nanoparticle properties, drug release and cellular uptake efficiency were evaluated in vitro. METHOD: Paclitaxel-loaded nanoparticles incorporated with PVLA were prepared by emulsion solvent evaporation method with polyvinyl alcohol (PVA) as co-emulsifier. The presence of PVLA on the particle surface was investigated through the change of ζ potential and surface hydrophobicity. Cellular uptake and cytotoxic activity, involving factors concerned with them, were evaluated by HepG2 cells in vitro. RESULTS: The presence of PVLA led to the increase of ζ potential, reduction of the particle surface hydrophobicity, slight promotion of paclitaxel encapsulation efficiency and more homogeneous particle size, but excessive PVLA accelerated the burst release. With enhanced attachment and cellular uptake efficiency, the PVLA incorporated nanoparticles exhibited significant cytotoxicity to HepG2 cells, and particles with higher PVLA-to-PLGA ratio, although had larger size and almost the same cellular uptake efficiency, performed much higher cytotoxic activity due to the larger drug capacity and faster release rate.

Sex-Biased Immune Responses to Antibiotics during Anti-PD-L1 Treatment in Mice with Colon Cancer.

Colitis is a frequently occurred side effect of immune checkpoint inhibitors (ICIs), which are increasingly used in cancer treatment, whereas antibiotics are widely used to treat colitis, their effectiveness in ICI-associated colitis remains controversial. In this study, we firstly assessed the effectiveness of several commonly used antibiotics and antibiotic cocktails in alleviating of dextran sulfate sodium- (DSS-) induced colitis. We observed that two narrow-spectrum antibiotics, neomycin and metronidazole, were more effective in alleviating colitis, as evidenced by the remission of loss of the body weight, enlargement of the spleen, shortening of the colon, secretion of proinflammatory cytokines, and histological score of the colon tissue. Moreover, these two antibiotics resulted in better relief of colitis symptoms in the MC38 tumor-bearing male mice receiving the anti-PD-L1 mAb (αPD-L1) treatment, compared to the females. In the meantime, an enhanced response to αPD-L1 efficiency against mice colon cancer was observed in the male mouse group upon the application of these two antibiotics. In contrast, both neomycin and metronidazole showed destructive effects on the antitumor efficiency of αPD-L1 in female mice, despite relief from colitis. We found that antibiotic treatment attenuated the increased infiltration of granulocytes and myeloid cells in colon tissue induced by DSS in female mice, while reducing the proportion of Th17 cells in male mice. These differences were further associated with the sex-biased differences in the gut microbiota. These findings indicated that sex-dependent alterations in the gut microbiota should be considered when applying antibiotics for the treatment of ICI-associated colitis.