A rechargeable coating with temporal-sequence antibacterial activity and soft tissue sealing.

Transcutaneous implants that penetrate through skin or mucosa are susceptible to bacteria invasion and lack proper soft tissue sealing. Traditional antibacterial strategies primarily focus on bacterial eradication, but excessive exposure to bactericidal agents can induce noticeable tissue damage. Herein, a rechargeable model (HPI-Ti) was constructed using perylene polyimide, an aqueous battery material, achieving temporal-sequence regulation of bacterial killing and soft tissue sealing. Charge storage within HPI-Ti is achieved after galvanostatic charge, and chemical discharge is initiated when immersed in physiological environments. During the early discharge stage, post-charging HPI-Ti demonstrates an antibacterial rate of 99.96 ± 0.01 % for 24 h, preventing biofilm formation. Contact-dependent violent electron transfer between bacteria and the material causes bacteria death. In the later discharge stage, the attenuated discharging status creates a gentler electron-transfer micro-environment for fibroblast proliferation. After discharge, the antibacterial activity can be reinstated by recharge against potential reinfection. The antibacterial efficacy and soft tissue compatibility were verified in vivo. These results demonstrate the potential of the charge-transfer-based model in reconciling antibacterial efficacy with tissue compatibility.

Metainterface Heterostructure Enhances Sonodynamic Therapy for Disrupting Secondary Biofilms.

Implant-related secondary infections are a challenging clinical problem. Sonodynamic therapy (SDT) strategies are promising for secondary biofilm infections by nonsurgical therapy. However, the inefficiency of SDT in existing acoustic sensitization systems limits its application. Therefore, we take inspiration from popular metamaterials and propose the design idea of a metainterface heterostructure to improve SDT efficiency. The metainterfacial heterostructure is defined as a periodic arrangement of heterointerface monoclonal cells that amplify the intrinsic properties of the heterointerface. Herein, we develop a TiO2/Ti2O3/vertical graphene metainterface heterostructure film on titanium implants. This metainterface heterostructure exhibits extraordinary sonodynamic and acoustic-to-thermal conversion effects under low-intensity ultrasound. The modulation mechanisms of the metainterface for electron accumulation and separation are revealed. The synergistic sonodynamic/mild sonothermal therapy disrupts biofilm infections (antibacterial rates: 99.99% for Staphylococcus aureus, 99.54% for Escherichia coli), and the osseointegration ability of implants is significantly improved in in vivo tests. Such a metainterface heterostructure film lays the foundation for the metainterface of manipulating electron transport to enhance the catalytic performance and holding promise for addressing secondary biofilm infections.

Construction of a nomogram model to predict technical difficulty in performing laparoscopic sphincter-preserving radical resection for rectal cancer.

BACKGROUND: Colorectal surgeons are well aware that performing surgery for rectal cancer becomes more challenging in obese patients with narrow and deep pelvic cavities. Therefore, it is essential for colorectal surgeons to have a comprehensive understanding of pelvic structure prior to surgery and anticipate potential surgical difficulties. AIM: To evaluate predictive parameters for technical challenges encountered during laparoscopic radical sphincter-preserving surgery for rectal cancer. METHODS: We retrospectively gathered data from 162 consecutive patients who underwent laparoscopic radical sphincter-preserving surgery for rectal cancer. Three-dimensional reconstruction of pelvic bone and soft tissue parameters was conducted using computed tomography (CT) scans. Operative difficulty was categorized as either high or low, and multivariate logistic regression analysis was employed to identify predictors of operative difficulty, ultimately creating a nomogram. RESULTS: Out of 162 patients, 21 (13.0%) were classified in the high surgical difficulty group, while 141 (87.0%) were in the low surgical difficulty group. Multivariate logistic regression analysis showed that the surgical approach using laparoscopic intersphincteric dissection, intraoperative preventive ostomy, and the sacrococcygeal distance were independent risk factors for highly difficult laparoscopic radical sphincter-sparing surgery for rectal cancer (P < 0.05). Conversely, the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance was identified as a protective factor (P < 0.05). A nomogram was subsequently constructed, demonstrating good predictive accuracy (C-index = 0.834). CONCLUSION: The surgical approach, intraoperative preventive ostomy, the sacrococcygeal distance, and the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance could help to predict the difficulty of laparoscopic radical sphincter-preserving surgery.

Sec1 regulates intestinal mucosal immunity in a mouse model of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a common immune-mediated condition with its molecular pathogenesis remaining to be fully elucidated. This study aimed to deepen our understanding of the role of FUT2 in human IBD, by studying a new surrogate gene Sec1, a neighboring gene of Fut2 and Fut1 that co-encodes the α 1,2 fucosyltransferase in mice. CRISPR/Cas9 was used to prepare Sec1 knockout (Sec1-/-) mice. IBD was induced in mice using 3% w/v dextran sulphate sodium. Small interfering RNA (siRNA) was employed to silence Sec1 in murine colon cancer cell lines CT26.WT and CMT93. IBD-related symptoms, colonic immune responses, proliferation and apoptosis of colon epithelial cells were assessed respectively to determine the role of Sec1 in mouse IBD. Impact of Sec1 on the expression of death receptor 5 (DR5) and other apoptosis-associated proteins were determined. Sec1 knockout was found to be associated with deterioration of IBD in mice and elevated immune responses in the colonic mucosa. Silencing Sec1 in CT26.WT and CMT93 cells led to greater secretion of inflammatory cytokines IL-1ß, IL-6 and TNF-α. Cell counting kit 8 (CCK8) assay, flow cytometry and TUNEL detection suggested that Sec1 expression promoted the proliferation of colon epithelial cells, inhibited cell apoptosis, reduced cell arrest in G0/G1 phase and facilitated repair of inflammatory injury. Over-expression of DR5 and several apoptosis-related effector proteins was noticed in Sec1-/- mice and Sec1-silenced CT26.WT and CMT93 cells, supporting a suppressive role of Sec1 in cell apoptosis. Our results depicted important regulatory roles of Sec1 in mouse IBD, further reflecting the importance of FUT2 in the pathogenesis of human IBD.

Weighted gene coexpression network analysis and machine learning reveal oncogenome associated microbiome plays an important role in tumor immunity and prognosis in pan-cancer.

BACKGROUND: For many years, the role of the microbiome in tumor progression, particularly the tumor microbiome, was largely overlooked. The connection between the tumor microbiome and the tumor genome still requires further investigation. METHODS: The TCGA microbiome and genome data were obtained from Haziza et al.'s article and UCSC Xena database, respectively. Separate WGCNA networks were constructed for the tumor microbiome and genomic data after filtering the datasets. Correlation analysis between the microbial and mRNA modules was conducted to identify oncogenome associated microbiome module (OAM) modules, with three microbial modules selected for each tumor type. Reactome analysis was used to enrich biological processes. Machine learning techniques were implemented to explore the tumor type-specific enrichment and prognostic value of OAM, as well as the ability of the tumor microbiome to differentiate TP53 mutations. RESULTS: We constructed a total of 182 tumor microbiome and 570 mRNA WGCNA modules. Our results show that there is a correlation between tumor microbiome and tumor genome. Gene enrichment analysis results suggest that the genes in the mRNA module with the highest correlation with the tumor microbiome group are mainly enriched in infection, transcriptional regulation by TP53 and antigen presentation. The correlation analysis of OAM with CD8+ T cells or TAM1 cells suggests the existence of many microbiota that may be involved in tumor immune suppression or promotion, such as Williamsia in breast cancer, Biostraticola in stomach cancer, Megasphaera in cervical cancer and Lottiidibacillus in ovarian cancer. In addition, the results show that the microbiome-genome prognostic model has good predictive value for short-term prognosis. The analysis of tumor TP53 mutations shows that tumor microbiota has a certain ability to distinguish TP53 mutations, with an AUROC value of 0.755. The tumor microbiota with high importance scores are Corallococcus, Bacillus and Saezia. Finally, we identified a potential anti-cancer microbiota, Tissierella, which has been shown to be associated with improved prognosis in tumors including breast cancer, lung adenocarcinoma and gastric cancer. CONCLUSION: There is an association between the tumor microbiome and the tumor genome, and the existence of this association is not accidental and could change the landscape of tumor research.

Atomic Layer Deposition of Tantalum Oxide Films on 3D-Printed Ti6Al4V Scaffolds with Enhanced Osteogenic Property for Orthopedic Implants.

There is an evident advantage in personalized customization of orthopedic implants by 3D-printed titanium (Ti) and its alloys. However, 3D-printed Ti alloys have a rough surface structure caused by adhesion powders and a relatively bioinert surface. Therefore, surface modification techniques are needed to improve the biocompatibility of 3D-printed Ti alloy implants. In the present study, porous Ti6Al4V scaffolds were manufactured by a selective laser melting 3D printer, followed by sandblasting and acid-etching treatment and atomic layer deposition (ALD) of tantalum oxide films. SEM morphology and surface roughness tests confirmed that the unmelted powders adhered on the scaffolds were removed by sandblasting and acid-etching. Accordingly, the porosity of the scaffold increased by about 7%. Benefiting from the self-limitation and three-dimensional conformance of ALD, uniform tantalum oxide films were formed on the inner and outer surfaces of the scaffolds. Zeta potential decreased by 19.5 mV after depositing tantalum oxide films. The in vitro results showed that the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells on modified Ti6Al4V scaffolds were significantly enhanced, which may be ascribed to surface structure optimization and the compatibility of tantalum oxide. This study provides a strategy to improve the cytocompatibility and osteogenic differentiation of porous Ti6Al4V scaffolds for orthopedic implants.

Intratumour microbiome of pancreatic cancer.

Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates. Both normal and tumour tissues of the pancreas were previously considered sterile. In recent years, with the development of technologies for high-throughput sequencing, a variety of studies have revealed that pancreatic cancer tissues contain small amounts of bacteria and fungi. The intratumour microbiome is being revealed as an influential contributor to carcinogenesis. The intratumour microbiome has been identified as a crucial factor for pancreatic cancer progression, diagnosis, and treatment, chemotherapy resistance, and immune response. A better understanding of the biology of the intratumour microbiome of pancreatic cancer contributes to the establishment of better early cancer screening and treatment strategies. This review focuses on the possible origins of the intratumour microbiome in pancreatic cancer, the intratumour localization, the interaction with the tumour microenvironment, and strategies for improving the outcome of pancreatic cancer treatment. Thus, this review offers new perspectives for improving the prognosis of pancreatic cancer.

Immuno-oncology-microbiome axis of gastrointestinal malignancy.

Research on the relationship between the microbiome and cancer has been controversial for centuries. Recent works have discovered that the intratumor microbiome is an important component of the tumor microenvironment (TME). Intratumor bacteria, the most studied intratumor microbiome, are mainly localized in tumor cells and immune cells. As the largest bacterial reservoir in human body, the gut microbiome may be one of the sources of the intratumor microbiome in gastrointestinal malignancies. An increasing number of studies have shown that the gut and intratumor microbiome play an important role in regulating the immune tone of tumors. Moreover, it has been recently proposed that the gut and intratumor microbiome can influence tumor progression by modulating host metabolism and the immune and immune tone of the TME, which is defined as the immuno-oncology-microbiome (IOM) axis. The proposal of the IOM axis provides a new target for the tumor microbiome and tumor immunity. This review aims to reveal the mechanism and progress of the gut and intratumor microbiome in gastrointestinal malignancies such as esophageal cancer, gastric cancer, liver cancer, colorectal cancer and pancreatic cancer by exploring the IOM axis. Providing new insights into the research related to gastrointestinal malignancies.

Diagnostic performance of MRI using extracellular contrast agents versus gadoxetic acid for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND & AIMS: Magnetic resonance imaging (MRI) is the first-line tool for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with chronic liver diseases. We performed a meta-analysis to compare the performance of MRI using extracellular contrast agents (ECA-MRI) with that using gadoxetic acid (EOB-MRI) for diagnosing HCC. METHODS: We searched multiple databases for studies comparing the diagnostic performance of ECA-MRI with that of EOB-MRI in patients with suspected HCC until 31 May 2020. The bivariate random-effects model was used to pool the performance and further subgroup analysis was performed. RESULTS: Eight studies were included evaluating a total of 1002 patients. ECA-MRI revealed significantly higher per-lesion sensitivity in the diagnosis of HCC than EOB-MRI did (0.76 vs 0.63, P = .002). For modified EOB-MRI (mEOB-MRI) using extended washout to the transitional phase (TP) or hepatobiliary phase (HBP), the sensitivity increased compared with that of EOB-MRI using restrictive washout in the portal venous phase (PVP) (0.74 vs 0.63, P = .07). No significant difference among the specificities of ECA-MRI, EOB-MRI, and mEOB-MRI (0.96, 0.98, and 0.93, respectively) was found. The sensitivity for lesions < 20 mm was significantly lower than that for lesions ≥ 20mm (0.66 vs 0.87, P = .01) only for ECA-MRI, which achieved higher sensitivity in Asian patients or with a 3.0 T scanner. CONCLUSIONS: ECA-MRI outperforms EOB-MRI in per-lesion sensitivity for diagnosing HCC, whereas mEOB-MRI shows a trend towards improved sensitivity compared with EOB-MRI with slightly decreased specificity. Registration: Prospero CRD42020189680.

Characterization and cytocompatibility of hierarchical porous TiO2 coatings incorporated with calcium and strontium by one-step micro-arc oxidation.

Calcium (Ca) and strontium (Sr) are beneficial for bone reconstruction. This study incorporated Ca and Sr into the TiO2 coatings by one-step micro-arc oxidation (MAO) treatment with CaO and SrO added in tetraborate electrolytes. The structure, composition, hydrophilicity, ion release, and cytocompatibility of the coatings were studied. The coatings combine layered micron-scale pores in various sizes and nano-scaled pores, forming a hierarchical structure. This hierarchical structure is highly porous and super-hydrophilic. The coatings are composed of Ti, O, and B, as well as Ca or Sr. Ca and Sr mainly distribute in the outer layer of the coatings and exist in the forms of carbonates and oxides. The formation of the coatings was discussed. Ca and Sr incorporated into the coatings are readily released into aqueous solutions. The homogeneous surface structure of the coatings leads to an excellent and approximating performance in hydrophilicity, as well as the adhesion and spreading of the human bone marrow-derived mesenchymal stem cells (hBMSCs). The simultaneous incorporation of Ca and Sr incorporation exhibits superior facilitation in the proliferation of hBMSCs compared with single Ca or Sr incorporation. This study shows a promising method to incorporate bioactive elements into the MAO coatings on titanium surfaces.