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Abstract Background Deep vein thrombosis (DVT) is a common and serious risk in elderly patients with knee osteoarthritis (OA), making preoperative detection crucial. Despite this, identifying OA patients at high risk for preoperative DVT and appropriately targeting them for venous ultrasound screening remains a challenge. There is limited research-based evidence on the risk factors for preoperative DVT in elderly patients with end-stage OA. We examined the incidence of and risk factors for preoperative DVT in elderly patients with end-stage OA scheduled for total knee arthroplasty. Methods We retrospectively analyzed the demographic data (age, sex, body mass index, current smoking, alcohol consumption, walking status, and Barthel index score), medical history, and laboratory test indices of 1411 patients with end-stage OA aged ≥ 60 years scheduled for total knee arthroplasty from January 2015 to December 2018. Risk factors for preoperative DVT were evaluated by univariate and multivariate logistic analyses. Receiver operating characteristic analysis was performed to determine optimal cut-off values. Results The incidence of preoperative DVT was 4.5% (63 of 1411 patients). Seven independent risk factors were correlated with preoperative DVT in the multivariate logistic regression: age (odds ratio [OR], 1.073; P = 0.002), D-dimer concentration (OR, 1.173; P = 0.003), hyperlipidemia (OR, 2.038; P = 0.045), atrial fibrillation (OR, 4.004; P = 0.033), chronic renal failure (OR, 6.732; P = 0.008), chronic obstructive pulmonary disease (COPD) (OR, 8.721; P = 0.001), and walking status (wheelchair) (OR, 2.697; P = 0.002). The optimal cut-off values for predicting preoperative DVT were 0.585 µg/mL for the D-dimer concentration (area under the curve [AUC], 0.769; P 0.585 µg/mL), high age (> 72.5 years), hyperlipidemia, atrial fibrillation, chronic renal failure, COPD, and walking status (wheelchair).

Abstract Background Ectoine as an amino acid derivative is widely applied in many fields, such as the food industry, cosmetic manufacturing, biologics, and therapeutic agent. Large-scale production of ectoine is mainly restricted by the cost of fermentation substrates (e.g., carbon sources) and sterilization. Results In this study, Halomonas cupida J9 was shown to be capable of synthesizing ectoine using xylose as the sole carbon source. A pathway was proposed in H. cupida J9 that synergistically utilizes both WBG xylose metabolism and EMP glucose metabolism for the synthesis of ectoine. Transcriptome analysis indicated that expression of ectoine biosynthesis module was enhanced under salt stress. Ectoine production by H. cupida J9 was enhanced by improving the expression of ectoine biosynthesis module, increasing the intracellular supply of the precursor oxaloacetate, and utilizing urea as the nitrogen source. The constructed J9U-P8EC achieved a record ectoine production of 4.12 g/L after 60 h of xylose fermentation. Finally, unsterile production of ectoine by J9U-P8EC from either a glucose-xylose mixture or corn straw hydrolysate was demonstrated, with an output of 8.55 g/L and 1.30 g/L of ectoine, respectively. Conclusions This study created a promising H. cupida J9-based cell factory for low-cost production of ectoine. Our results highlight the potential of J9U-P8EC to utilize lignocellulose-rich agriculture waste for open production of ectoine.

Abstract Background Dual-task training has been a popular intervention for individuals with balance impairments. However, the effects of dual-task training on chronic ankle instability (CAI) have not been comprehensively analyzed and reliable clinical evidence is scarce. The purpose of this systematic review and meta-analysis is to evaluate the effectiveness of dual-task training on postural stability and functional ability in individuals with CAI. Methods PubMed, Web of Science, EBSCO, Cochrane Library, Physiotherapy Evidence Database (PEDro), and China National Knowledge Infrastructure (CNKI) were researched from inception to November 2022. This study was conducted by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers assessed the studies for inclusion and extracted data. The Cochrane Risk of Bias list was used to assess the risk of bias in included studies. Mean differences (MD) with a 95% confidence interval (CI) were calculated with the RevMan 5.3 software. Results A total of 7 randomized controlled trials with 192 CAI met the inclusion criteria. The meta-analysis results showed that compared with the control group, dual-task training significantly improved the Y-balance test (MD = 1.60, 95% CI: −0.00 to 3.21, P = 0.050) and reduced COP-area (MD = − 0.94, 95% CI: −1.62 to − 0.26, P = 0.007) in individuals with CAI. However, there is no significant difference between dual-task training and the control group on COP-velocity (MD = − 0.26, 95% CI: −0.70 to 0.17, P = 0.240), hop test (MD = − 0.20, 95% CI: −0.66 to 0.26, P = 0.386) and BESS (MD = − 1.24, 95% CI: −2.95 to 0.48, P = 0.157) in individuals with CAI. Conclusion This meta-analysis showed that dual-task training may be effective in improving static and dynamic postural stability. However, more high-quality randomized controlled trials are needed to verify the short and long-term effectiveness of dual-task training on CAI.

Abstract Background Nanoinjection—the process of intracellular delivery using vertically configured nanostructures—is a physical route that efficiently negotiates the plasma membrane, with minimal perturbation and toxicity to the cells. Nanoinjection, as a physical membrane-disruption-mediated approach, overcomes challenges associated with conventional carrier-mediated approaches such as safety issues (with viral carriers), genotoxicity, limited packaging capacity, low levels of endosomal escape, and poor versatility for cell and cargo types. Yet, despite the implementation of nanoinjection tools and their assisted analogues in diverse cellular manipulations, there are still substantial challenges in harnessing these platforms to gain access into cell interiors with much greater precision without damaging the cell’s intricate structure. Here, we propose a non-viral, low-voltage, and reusable electroactive nanoinjection (ENI) platform based on vertically configured conductive nanotubes (NTs) that allows for rapid influx of targeted biomolecular cargos into the intracellular environment, and for successful gene silencing. The localization of electric fields at the tight interface between conductive NTs and the cell membrane drastically lowers the voltage required for cargo delivery into the cells, from kilovolts (for bulk electroporation) to only ≤ 10 V; this enhances the fine control over membrane disruption and mitigates the problem of high cell mortality experienced by conventional electroporation. Results Through both theoretical simulations and experiments, we demonstrate the capability of the ENI platform to locally perforate GPE-86 mouse fibroblast cells and efficiently inject a diverse range of membrane-impermeable biomolecules with efficacy of 62.5% (antibody), 55.5% (mRNA), and 51.8% (plasmid DNA), with minimal impact on cells’ viability post nanoscale-EP (> 90%). We also show gene silencing through the delivery of siRNA that targets TRIOBP, yielding gene knockdown efficiency of 41.3%. Conclusions We anticipate that our non-viral and low-voltage ENI platform is set to offer a new safe path to intracellular delivery with broader selection of cargo and cell types, and will open opportunities for advanced ex vivo cell engineering and gene silencing. Graphical abstract

Abstract Background Multiple host factors are involved in modulating type I interferon expression induced by viruses; however, the mechanism is not fully elucidated. Influenza A virus infection causes severe respiratory symptoms and triggers a series of signaling cascades and host innate immune responses, including interferon production. The co-IP/MS technology was used to screen several antiviral factors in the early stage. Among these factors, ariadne-1 homolog (ARIH1) caught our attention. Methods Western blot assay was performed to detect the level of proteins and software ImageJ was used to analyze the band intensities. Polymerase activity assay was conducted to evaluate the polymerase activity of influenza A virus. Tissue culture infective dose (TCID50) assay was performed to measure influenza A virus titers, and quantitative RT-PCR assay was applied to test the mRNA level of IFN-β, ISG56, and CXCL10. Luciferase reporter assay was used to confirm the target of ARIH1 in RIG-I signaling. Immunoprecipitation assay was performed to detect the interaction and the ubiquitination of the proteins. All data were analyzed by biostatistical methods and presented as means ± standard deviation from three independent experiments. Statistical significance was determined using two-tailed student’s t test. A P value of less than 0.05 was considered statistically significant, and a P value of less than 0.01 was considered highly significant (ns, P ≥ 0.05; *, P

Abstract Background and objectives Frozen shoulder (FS) is characterized by pain and significant loss of active and passive shoulder motion. Strengthening exercises are among the standard exercises used for FS. Neuromuscular exercise (NME) effectively improved pain and the range of motion in shoulder. However, no prior research has looked into the effects of NME compared to strengthening exercises in FS rehabilitation. The aim of the present study was to evaluate the effects of NME compared to strengthening exercises on pain and active range of motion (AROM) in individuals with idiopathic frozen shoulder. Methods Forty individuals with idiopathic frozen shoulder were randomly assigned to either the experimental group (NME with regular physical therapy, n = 20) or the control group (strengthening exercises with regular physical therapy, n = 20). In both groups, the interventions were performed once a day, 5 days a week for 8 weeks. Pain scores on the visual analogue scale (VAS) and AROM of the shoulder were assessed at baseline and after the 8-week treatment. The primary analysis was the group × time interaction. Results Two-by-two mixed analysis of variance (ANOVA) revealed a significant group × time interaction for VAS (F = 29.67; p

Abstract Nanofabrication technologies have been recently applied to the development of engineered nano–bio interfaces for manipulating complex cellular processes. In particular, vertically configurated nanostructures such as nanoneedles (NNs) have been adopted for a variety of biological applications such as mechanotransduction, biosensing, and intracellular delivery. Despite their success in delivering a diverse range of biomolecules into cells, the mechanisms for NN-mediated cargo transport remain to be elucidated. Recent studies have suggested that cytoskeletal elements are involved in generating a tight and functional cell–NN interface that can influence cargo delivery. In this study, by inhibiting actin dynamics using two drugs—cytochalasin D (Cyto D) and jasplakinolide (Jas), we demonstrate that the actin cytoskeleton plays an important role in mRNA delivery mediated by silicon nanotubes (SiNTs). Specifically, actin inhibition 12 h before SiNT-cellular interfacing (pre-interface treatment) significantly dampens mRNA delivery (with efficiencies dropping to 17.2% for Cyto D and 33.1% for Jas) into mouse fibroblast GPE86 cells, compared to that of untreated controls (86.9%). However, actin inhibition initiated 2 h after the establishment of GPE86 cell–SiNT interface (post-interface treatment), has negligible impact on mRNA transfection, maintaining > 80% efficiency for both Cyto D and Jas treatment groups. The results contribute to understanding potential mechanisms involved in NN-mediated intracellular delivery, providing insights into strategic design of cell–nano interfacing under temporal control for improved effectiveness.

Abstract Background The immune checkpoint inhibitors (ICIs) combined with other therapeutic strategies have shown exciting results in various malignancies, and ICIs have now become the gold standard for current cancer treatment. In several preclinical and clinical investigations, ablation coupled with immunotherapy has proved to be quite effective. Our previous studies have shown that ablation coupled with ICI is a potential anti-cancer regimen for colorectal cancer liver metastases (CRLM). Furthermore, we have reported that following microwave ablation (MWA), the expression of LAG3 is up-regulated in tumor microenvironment (TME), indicating that LAG3 is implicated in the regulation of immunosuppressive immune response, and combination therapy of MWA and LAG3 blockade can serve as a promising therapeutic strategy against cancer. Methods The expression of LAG3 was investigated in this study utilizing a preclinical mouse model treated with MWA. Moreover, we monitored the tumor development and survival in mice to assess the anti-cancer effects of MWA alone or in combination with LAG3 blockade. Flow cytometry was also used to phenotype the tumor-infiltrating lymphocytes (TILs) and CD8+ T cell effector molecules. We finally analyzed the single-cell RNA sequencing (scRNA-seq) data of infiltrating CD45+ immune cells in the tumors from the MWA alone and MWA combined with LAG3 blockade groups. Results After MWA, the expression of LAG3 was up-regulated on sub-populations of TILs, and introducing LAG3 blockade to MWA postponed tumor development and extended survival in the MC38 tumor model. Flow cytometry and scRNA-seq revealed that LAG3 blockade in combination with MWA markedly boosted the proliferation and the function of CD8+ TILs, leading to altered myeloid cells in the TME. Conclusion Combination therapy of LAG3 blockade and MWA was a unique therapeutic regimen for some solid tumors, and such combination therapy might reprogram the TME to an anti-tumor manner.

Abstract Background The aim of this study was to identify potential indicators to predict the success of multimodal rehabilitation in chronic ankle instability (CAI) patients based on patient-reported outcomes. Methods Sixty patients with self-reported CAI participated. Their demographic information, injury history, and symptoms were recorded. Physical examinations and dynamic posture control tests were performed. The participants underwent sixteen 30-min treatment sessions of multimodal rehabilitation over 8 weeks. Fifty-one patients (85.0%) were available for follow-up after 8 weeks of the intervention. Treatment success was defined based on the participants’ perceived recovery using the global rating of change (GRC). Potential predictor variables were entered into a stepwise logistic regression model to identify variables for the prediction of treatment success. Results Forty of 51 participants (78.4%) were considered to have a successful outcome. Of the variables assessed, time since last sprain ≤ 8 months was a predictor of treatment success (p

Abstract Study design Retrospective case series. Objectives This study aimed to determine the prevalence and risk factors for orthostatic hypotension (OH) in adolescents undergoing posterior spinal fusion for spinal deformity correction. Methods The data of 282 consecutive adolescents who underwent posterior spinal fusion for spinal deformity correction in our center over 12 months were retrieved. Patient characteristics, including whether laminectomy or osteotomy was performed during the surgery, the occurrence of postoperative nausea and vomiting (PONV), perioperative hemoglobin albumin changes, perioperative blood transfusion, length of bed rest, willingness to ambulate, length of postoperative exercises of the lower limbs, and length of hospital stay, were collected and compared statistically between patients who did and did not develop postoperative OH. Results Of 282 patients, 197 (69.86%) developed OH postoperatively, and all cases completely resolved 5 days after the first out-of-bed exercises. Significant differences in the incidence of PONV, the willingness to ambulate and the length of postoperative exercises of the lower limbs were observed. The mean length of hospital stay of the patients with OH was longer than that of the patients without OH. Conclusion Our study suggests that temporary OH is a common manifestation following posterior spinal fusion for spinal deformity correction in adolescents. Postoperative OH may increase the length of hospital stay in these patients. Patients with PONV, who are not willing to ambulate and who perform postoperative lower limb exercises for a shorter time are more likely to have OH.

Abstract Background Damage to sensory input is an underlying pathology of chronic ankle instability (CAI). Therefore, it is necessary to evaluate the sensory function of patients with CAI. The present study quantitatively evaluated sensory nerve function in patients with CAI and healthy controls using current perception threshold (CPT) measurements, as well as the influence of sex, age, and body mass index (BMI) on CPT values and the relations between CPT frequencies. Methods Fifty-nine subjects with CAI and 30 healthy controls participated in this study. CPT values at the anterior talofibular ligament region were recorded on the injured and uninjured sides in CAI patients and on both sides in the healthy control group. Between group differences were compared. The influence of sex, age and BMI on CPT values was evaluated. Correlations between different frequencies were also studied. Results There were no significant differences in age, sex, height, weight or BMI between the CAI and healthy control groups. The CPT values did not show a significant difference by sex. The CPT values did not significantly correlate with age or BMI. Compared to the control group, the CAI group had significantly higher CPT values on the injured and uninjured sides under 250-Hz and 5-Hz electrical stimuli; the difference between the groups was significant (p

Abstract Background Schizophrenia is associated with widespread cognitive impairment. The MATRICS Consensus Cognitive Battery (MCCB) is most frequently used to assess cognitive function. However, the MCCB test is time consuming for the clinician. Virtual reality (VR) has emerged as an adjunctive tool to overcome this limitation and provides a new means to assess cognitive function. Methods The present study examined the validity and safety of using VR technology to assess cognitive function in Han Chinese patients with schizophrenia (SZs). The VR cognition training system (VRCTS) was used to simulate real-life supermarkets and assess cognitive function. Thirty-two SZs and 25 healthy controls (HCs) underwent VRCTS and MCCB assessments. An auxiliary diagnosis model was created based on the outcomes of the VRCTS to classify SZs and HCs by cognitive impairment. Results Significant differences in completion time between the SZs and HCs were detected using the VRCTS. SZs spent more time completing tasks than HCs. The outcome of VRCTS significantly correlated with the MCCB. The auxiliary diagnosis model had a sensitivity of 88.89% and a specificity of 88.89%. Conclusions These results support the use of VR technology in the assessment of cognitive impairment in Han Chinese schizophrenia patients. Trial registration China Clinical Trial Registry, ChiVTR1800016121. Registered 13 May 2018, http://www.chictr.org.cn/showproj.aspx?proj=27233

Abstract Background Hypovolemic shock and septic challenge are two major causes of acute kidney injury (AKI) in the clinic setting. Src homology 2 domain-containing phosphatase 2 (SHP2) is one of the major protein phosphatase tyrosine phosphatase (PTPs), which play a significant role in maintaining immunological homeostasis by regulating many facets of immune cell signaling. In this study, we explored whether SHP2 signaling contributed to development of AKI sequential hemorrhage (Hem) and cecal ligation and puncture (CLP) and whether inactivation of SHP2 through administration of its selective inhibitor, phenylhydrazonopyrazolone sulfonate 1 (PHPS1), attenuated this injury. Methods Male C57BL/6 mice were subjected to Hem (a “priming” insult) followed by CLP or sham-Hem plus sham-CLP (S/S) as controls. Samples of blood and kidney were harvested at 24 h post CLP. The expression of neutrophil gelatinase-associated lipocalin (NGAL), high mobility group box 1 (HMGB1), caspase3 as well as SHP2:phospho-SHP2, extracellular-regulated kinase (Erk1/2): phospho-Erk1/2, and signal transducer and activator of transcription 3 (STAT3):phospho-STAT3 protein in kidney tissues were detected by Western blotting. The levels of creatinine (Cre) and blood urea nitrogen (BUN) in serum were measured according to the manufacturer’s instructions. Blood inflammatory cytokine/chemokine levels were detected by ELISA. Results We found that indices of kidney injury, including levels of BUN, Cre and NGAL as well as histopathologic changes, were significantly increased after Hem/CLP in comparison with that in the S/S group. Furthermore, Hem/CLP resulted in elevated serum levels of inflammatory cytokines/chemokines, and induced increased levels of HMGB1, SHP2:phospho-SHP2, Erk1/2:phospho-Erk1/2, and STAT3:phospho-STAT3 protein expression in the kidney. Treatment with PHPS1 markedly attenuated these Hem/CLP-induced changes. Conclusions In conclusion, our data indicate that SHP2 inhibition attenuates AKI induced by our double-hit/sequential insult model of Hem/CLP and that this protective action may be attributable to its ability to mitigate activation of the Erk1/2 and STAT3 signaling pathway. We believe this is a potentially important finding with clinical implications warranting further investigation.

Abstract Background This study was aimed to assess the coverage of two doses of measles vaccine and identify the determinants of the delayed vaccination. Methods A cluster survey among 1386 children aged 24–35 months was conducted. Characteristics on demographic and socio-economic and vaccination records was collected. The overall coverage was defined as the proportion of children receiving the first dose of measles vaccination and the second dose of measles vaccination by 24 months of age. The age-appropriate coverage was defined as the proportion of children receiving the measles vaccine doses within one month after its relevant due date. Timeliness was evaluated with the Kaplan-Meier analysis. Cox proportional hazard regression was adopted to identify determinants of the delayed vaccination. Results The overall coverage was 96.9% for the first dose of measles vaccine and 93.9% for the second dose of measles vaccine. The age-appropriate coverage of the first and the second dose of measles vaccine was 76.6 and 68.2%, respectively. Household having more than one child, non-local children were associated with the delayed vaccination for the first and the second dose of measles vaccine. Children delivered at home, younger mothers, low maternal education background, mothers with a fixed job, and low household income were associated with the delayed vaccination for the second dose of measles vaccine. Conclusions The coverage of measles vaccine had been improved for both the first and the second dose, while the timeliness still needed improvement. We suggested the policy-makers pay more attention to the reasons for non-vaccination and determinants of delayed vaccination when planning efforts to ensure the high age-appropriate coverage of measles vaccination.

Abstract Background We evaluated the effect of two Elaboration Likelihood Model (ELM)-based health educational interventions on varicella vaccine (VarV) vaccination among pregnant women in a province in the east China. Methods A prospective randomized controlled trial was conducted among 200 pregnant women with ≥12 gestation weeks to test two interventions, including a messaging video and a messaging booklet. The participants were randomly assigned into the control group, the video group or the booklet group. The VarV coverage at 12 and 24 months old was compared among the children of the three groups and relative risks (RRs) were calculated, by using the coverage of the control group as reference. The timeliness of VarV was also assessed. Furthermore, differences in the effects on the knowledge and attitude of VarV vaccination between the two interventions was evaluated. Results The VarV coverage of their children by 24 months of age was 86.4%, 76.1% and 56.7% for the video group, the booklet group and the control group, respectively. The relative risks (RRs) for the coverage of VarV at 24 months of age were 4.8 (95% CI: 2.06–11.3) for the video group and 2.4 (95% CI: 1.2–5.1) for the booklet group. The means of delays were 57.3 days in the video group, 76.9 days in the booklet group, and 100.6 days in the control group. The proportion of women who intended to vaccinate their children with VarV was higher in the video group than the booklet group (93.9% vs. 82.1%, p

Abstract Background Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. Design, setting, and subjects Blood and bronchial alveolar lavage fluid (BAL) from humans (n = 10–13) with ARDS and controls (n = 5–10) as well as a murine model of ARDS (n = 5–6) with controls (n = 6–7) were studied. Methods ARDS was induced in mice by hemorrhagic shock (day 1) followed by poly-microbial sepsis (day 2). Samples were then collected on the third day after the animals were euthanized. Ex vivo experiments used splenocytes from animals with ARDS cultured with and without soluble programmed death receptor-1 (sPD-1). Results Levels of sPD-1 are increased in both the serum (11,429.3 pg/mL(SD 2133.3) vs. 8061.4(SD 4187.8), p = 0.036) and bronchial alveolar lavage (BAL) fluid (6,311.1 pg/mL(SD 3758.0) vs. 90.7 pg/mL(SD 202.8), p = 0.002) of humans with ARDS. Similar results are seen in the serum (9396.1 pg/mL(SD 1546.0) vs. 3464.5 pg/mL(SD 2511.8), p = 0.001) and BAL fluid (2891.7 pg/mL(SD 868.1) vs. 1385.9 pg/mL(SD 927.8), p = 0.012) of mice. sPD-1 levels in murine blood (AUC = 1(1–1), p = 0.006), murine BAL fluid (AUC = 0.905(0.717–1.093), p = 0.015), and human BAL (AUC = 1(1–1), p = 0.001) fluid predicted ARDS. To assess the importance of sPD-1 in ARDS, ex vivo experiments were undertaken. BAL fluid from mice with ARDS dampens the TNF-α production compared to cells cultured with BAL lacking sPD-1 (2.7 pg/mL(SD 3.8) vs. 52.38 pg/mL(SD 25.1), p = 0.002). Conclusions This suggests sPD-1 is elevated in critical illness and may represent a potential biomarker for ARDS. In addition, sPD-1 has an anti-inflammatory mechanism in conditions of marked stress and aids in the resolution of severe inflammation. sPD-1 could be used to not only diagnose ARDS, but may be a potential therapy.

Abstract Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, the co-inhibitory molecule programmed death-ligand1 (PD-L1) has been shown to be involved in the regulation of intestinal immune tolerance and/or inflammation. Our previous studies showed that PD-L1 gene deficiency reduced sepsis-induced intestinal injury morphologically. However, it is not known how PD-L1 expression impacts intestinal barrier dysfunction during sepsis. Here we tested the hypothesis that PD-L1 expressed on intestinal epithelial cells (IECs) has a role in sepsis-induced intestinal barrier dysfunction. To address this, C57BL/6 or PD-L1 gene knockout mice were subjected to experimental sepsis and PD-L1 expression, intestinal permeability and tissue cytokine levels were assessed. Subsequently, septic or nonseptic colonic samples (assigned by pathology report) were immunohistochemically stained for PD-L1 in a blinded fashion. Finally, human Caco2 cells were used for in vitro studies. The results demonstrated that PD-L1 was constitutively expressed and sepsis significantly upregulates PD-L1 in IECs from C57BL/6 mice. Concurrently, we observed increased PD-L1 expression in colon tissue samples from septic patients. PD-L1 gene deficiency reduced ileal permeability and tissue levels of IL-6, TNF-α and MCP-1, and prevented ileal tight junction protein loss compared with WT after sepsis. Comparatively, while Caco2 cell monolayers also responded to inflammatory cytokine stimulation with elevated PD-L1 expression, increased monolayer permeability and altered/decreased monolayer tight junction protein morphology/expression, these changes were reversed by PD-L1 blocking antibody. Together these data indicate that ligation of PD-L1 plays a novel role in mediating the pathophysiology of sepsis-induced intestinal barrier dysfunction.