IL-22 signaling promotes sorafenib resistance in hepatocellular carcinoma via STAT3/CD155 signaling axis.

Introduction: Sorafenib is currently the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Nevertheless, sorafenib resistance remains a huge challenge in the clinic. Therefore, it is urgent to elucidate the mechanisms underlying sorafenib resistance for developing novel treatment strategies for advanced HCC. In this study, we aimed to investigate the role and mechanisms of interleukin-22 (IL-22) in sorafenib resistance in HCC. Methods: The in vitro experiments using HCC cell lines and in vivo studies with a nude mouse model were used. Calcium staining, chromatin immunoprecipitation, lactate dehydrogenase release and luciferase reporter assays were employed to explore the expression and roles of IL-22, STAT3 and CD155 in sorafenib resistance. Results: Our clinical results demonstrated a significant correlation between elevated IL-22 expression and poor prognosis in HCC. Analysis of transcriptomic data from the phase-3 STORM-trial (BIOSTORM) suggested that STAT3 signaling activation and natural killer (NK) cell infiltration may associate sorafenib responses. STAT3 signaling could be activated by IL-22 administration in HCC cells, and then enhanced sorafenib resistance in HCC cells by promoting cell proliferation and reducing apoptosis in vitro and in vivo. Further, we found IL-22/STAT3 axis can transcriptionally upregulate CD155 expression in HCC cells, which could significantly reduce NK cell-mediated HCC cell lysis in a co-culture system. Conclusions: Collectively, IL-22 could contribute to sorafenib resistance in HCC by activating STAT3/CD155 signaling axis to decrease the sensitivities of tumor cells to sorafenib-mediated direct cytotoxicity and NK cell-mediated lysis. These findings deepen the understanding of how sorafenib resistance develops in HCC in terms of IL-22/STAT3 signaling pathway, and provide potential targets to overcome sorafenib resistance in patients with advanced HCC.

Drug-Loaded Tumor-Derived Microparticles Elicit CD8+ T Cell-Mediated Anti-Tumor Response in Hepatocellular Carcinoma.

Background: Hepatocellular Carcinoma (HCC) poses significant challenges due to limited effective treatments and high recurrence rates. Immunotherapy, a promising approach, faces obstacles in HCC patients due to T-cell exhaustion and immunosuppression within the tumor microenvironment. Methods: Using doxorubicin-loaded tumor-derived microparticles (Dox-TMPs), the mice with H22 ascites model and subcutaneous tumors model were treated. Following the treatment, mice were re-challenged with H22 cells to compare the therapeutic effects and recurrence among different groups of mice, alongside examining the changes in the proportions of immune cells within the tumor microenvironment. Furthermore, Dox-TMPs were combined with anti-PD-1 to further validate their anti-tumor efficacy. In vitro studies using various liver cancer cell lines were conducted to verify the tumor-killing effects of Dox-TMPs. Additionally, CD8+ T cells from the abdominal cavity of tumor-free mice were co-cultured with H22 cells to confirm their specific tumor-killing abilities. Results: Dox-TMPs demonstrate effective anti-tumor effects both in vitro and in vivo. In vivo, their effectiveness primarily involves enhancing CD8+ T cell infiltration, alleviating T cell immunosuppression, and improving the immune microenvironment to combat tumors. When used in combination with anti-PD-1, their anti-tumor effects are further enhanced. Moreover, some mice treated with Dox-TMPs developed anti-tumor immunity, displaying a self-specific T-cell immune response upon re-challenged with tumor cells. This suggests that Dox-TMPs also have the potential to act as a long-term immune response against tumor recurrence, indicating their capability as a tumor vaccine. Conclusion: Dox-TMPs exhibit a dual role in liver cancer by regulating T cells within the tumor microenvironment, functioning both as an anti-tumor agent and a potential tumor vaccine.

Prognosis of LSPD versus TIPS for the treatment of esophagogastric variceal bleeding in cirrhosis.

BACKGROUND: This study aimed to compare postoperative complications in patients with esophagogastric variceal bleeding (EVB) who underwent laparoscopic splenectomy combined with pericardial devascularization (LSPD) versus transjugular intrahepatic portosystemic shunt (TIPS) procedures. METHODS: A retrospective collection of medical records was conducted from January 2014 to May 2020 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The study included patients from the departments of trauma surgery, interventional radiology, and general surgery who were diagnosed with EVB caused by portal hypertension and treated with LSPD or TIPS. Follow-up data were obtained to assess the occurrence of postoperative complications in both groups. RESULTS: A total of 201 patients were included in the study, with 104 cases in the LSPD group and 97 cases in the TIPS group. There was no significant difference in the 1-year and 3-year post-surgery survival rates between the TIPS and LSPD groups (P = 0.669, 0.066). The 3-year survival rate of Child-Pugh B patients in the LSPD group was higher than TIPS group (P = 0.041). The LSPD group also had a significantly higher rate of freedom from rebleeding at 3-year post-surgery compared to the TIPS group (P = 0.038). Stratified analysis showed no statistically significant difference in the rebleeding rate between the two groups. Furthermore, the LSPD group had a higher rate of freedom from overt hepatic encephalopathy at 1-year and 3-year post-surgery compared to the TIPS group (P = 0.007, < 0.001). The LSPD group also had a lower rate of severe complications at 3-year post-surgery compared to the TIPS group (P = 0.020). CONCLUSION: Compared to TIPS, LSPD does not increase the risk of mortality and rebleeding, while demonstrating fewer complications. In patients classified as Child-Pugh A and B, the use of LSPD for treating EVB is both safe and effective.

Magnetic soft microfiberbots for robotic embolization.

Cerebral aneurysms and brain tumors are leading life-threatening diseases worldwide. By deliberately occluding the target lesion to reduce the blood supply, embolization has been widely used clinically to treat cerebral aneurysms and brain tumors. Conventional embolization is usually performed by threading a catheter through blood vessels to the target lesion, which is often limited by the poor steerability of the catheter in complex neurovascular networks, especially in submillimeter regions. Here, we propose magnetic soft microfiberbots with high steerability, reliable maneuverability, and multimodal shape reconfigurability to perform robotic embolization in submillimeter regions via a remote, untethered, and magnetically controllable manner. Magnetic soft microfiberbots were fabricated by thermal drawing magnetic soft composite into microfibers, followed by magnetizing and molding procedures to endow a helical magnetic polarity. By controlling magnetic fields, magnetic soft microfiberbots exhibit reversible elongated/aggregated shape morphing and helical propulsion in flow conditions, allowing for controllable navigation through complex vasculature and robotic embolization in submillimeter regions. We performed in vitro embolization of aneurysm and tumor in neurovascular phantoms and in vivo embolization of a rabbit femoral artery model under real-time fluoroscopy. These studies demonstrate the potential clinical value of our work, paving the way for a robotic embolization scheme in robotic settings.

Laparoscopic Image-Based Critical Action Recognition and Anticipation With Explainable Features.

Surgical workflow analysis integrates perception, comprehension, and prediction of the surgical workflow, which helps real-time surgical support systems provide proper guidance and assistance for surgeons. This article promotes the idea of critical actions, which refer to the essential surgical actions that progress towards the fulfillment of the operation. Fine-grained workflow analysis involves recognizing current critical actions and previewing the moving tendency of instruments in the early stage of critical actions. Aiming at this, we propose a framework that incorporates operational experience to improve the robustness and interpretability of action recognition in in-vivo situations. High-dimensional images are mapped into an experience-based explainable feature space with low dimensions to achieve critical action recognition through a hierarchical classification structure. To forecast the instrument's motion tendency, we model the motion primitives in the polar coordinate system (PCS) to represent patterns of complex trajectories. Given the laparoscopy variance, the adaptive pattern recognition (APR) method, which adapts to uncertain trajectories by modifying model parameters, is designed to improve prediction accuracy. The in-vivo dataset validations show that our framework fulfilled the surgical awareness tasks with exceptional accuracy and real-time performance.

Facile synthesis of core-shell Co-MOF with hierarchical porosity for enhanced electrochemical detection of furaltadone in aquaculture water.

Metal-organic frameworks (MOFs) exhibited huge application potential in electrochemical analysis field, how to facilely and effectively boost the electrochemical sensing activity of MOFs materials still face enormous challenges. In this work, core-shell Co-MOF (Co-TCA@ZIF-67) polyhedrons with hierarchical porosity was easily synthesized via simple chemical etching reaction by selecting thiocyanuric acid as the etching reagent. Benefiting from the introduction of mesopores and thiocyanuric acid/Co2+ complex on the surface of ZIF-67 frameworks, the property and functions of the pristine ZIF-67 was seriously tailored. Compared with the pristine ZIF-67, the as-resulted Co-TCA@ZIF-67 nanoparticles displayed greatly enhanced physical adsorption capacity and electrochemical reduction activity toward the antibiotic drug furaltadone. As a result, a novel furaltadone electrochemical sensor with high sensitivity was fabricated. The linear detection range was from 50 nM to 5 µM with sensitivity of 110.40 µA-1 µM-1 cm-2 and detection limit of 12 nM. This work demonstrated chemical etching strategy is truly a facile and effective way to modify the electrochemical sensing performance of MOFs-based materials, and we believed the chemically etched MOFs materials will play a stronger role in terms of food safety and environmental conservation.

A Simple Technique of Tunnel Constructing for Occluding Splenic Vessels During Laparoscopic Splenectomy in Patients with Cirrhosis.

Purpose: Dissecting and ligating the splenic artery is crucial for bleeding control during laparoscopic splenectomy (LS). However, for patients with portal hypertension from liver cirrhosis, it is difficult for identification and ligation because the splenic vessel is circuitous and dilated. The aim of this study was to describe a simple technique of constructing a tunnel behind the tail of the pancreas for occluding the splenic vessels during LS in patients with portal hypertension. Materials and Methods: The clinical data of 61 patients who underwent LS from April 2016 to January 2017 were retrospectively analyzed. In 27 patients, the tunnel construction (TC) behind the tail of the pancreas approach was performed owning to difficulty in dissecting and ligating the splenic artery (TC group), including 17 patients who received the TC method directly and 10 patients who received the TC method after trying to dissect the splenic artery. The remaining 34 patients underwent traditional ligating of the splenic artery (LA group). The peri- and postoperative outcomes of operative time, blood loss, conversion rate, postoperative oral diet intake, postoperative hospital stay, and postoperative complication rate of the two groups were analyzed. All the operations were completed by the same group of surgeons. Results: All 61 operations were successfully completed. Compared with patients in the LA group, patients in the TC group had less blood loss (120.37 ± 40.74 mL versus 162.65 ± 87.47 mL; t = -2.317, P = .024). There was no statistical difference of operative time, conversion rate, complication rate, postoperative hospital stays, and follow-up between the two groups. Conclusions: The technique of constructing a tunnel behind the tail of the pancreas for occluding the splenic vessels was effective and safe in those patients whose splenic artery was difficult to dissect and ligate.

Ultrasound-assisted synthesis of graphene@MXene hybrid: A novel and promising material for electrochemical sensing.

To date, multiple graphene@MXene hybrids have been reported via various synthesis approaches, but almost all the graphene@MXene hybrids inevitably used the reduced graphene oxide that prepared by chemical oxidation/reduction method, which generally involved the complex and dangerous operation procedure, and the highly toxic chemical reagent. How to prepare graphene@MXene hybrid through a simple, safe and eco-friendly synthetic route is highly desired. Compared with traditional synthesis technology, ultrasound synthesis strategy displays the merits of simplicity, low cost and environment protection. Herein, MXene (Ti3C2Tx) nanoflakes coupled with graphene nanosheets (graphene@MXene) were prepared in N-methylpyrrolidone (NMP) by simple ultrasound-assisted liquid-phase exfoliation method for the first time. Besides, the effect of types of solvent with different viscocity, sonication temperature and sonication duration time on the property of graphene@MXene hybrids were systematacially investigated. It is found the liquid-phase exfoliated graphene owned excellent electron transfer ability and the MXene (Ti3C2Tx) nanoflakes possessed outstanding adsorption property, the as-synthesized graphene@MXene hybrid exhibited significant signal synergistic enhancement effect toward the oxidation of hazardous veterinary drug residue compound (chlorpromazine) and food additives (rhodamine B). Based on this, a novel and sensitive electrochemical sensor was fabricated, the linear detection ranges were 5 nM to 0.5 µM for chlorpromazine with sensitivity of 1090 µA µM-1 cm-2, and 10 nM to 2.5 µM for rhodamine B with sensitivity of 440 and 102.14 µA µM-1 cm-2. Besides, the detection limits were evaluated to be as low as 1.25 nM and 2.45 nM for chlorpromazine and rhodamine B, respectively.

PET imaging of hepatocellular carcinoma by targeting tumor-associated endothelium using [68Ga]Ga-PSMA-617.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant tumor associated with high morbidity and mortality rates. In many non-prostate solid tumors such as HCC, prostate-specific membrane antigens (PSMA) are overexpressed in tumor-associated endothelial cells. Therefore, the aim of this study was to evaluate the performance of [68Ga]Ga-PSMA-617 PET imaging on HCC with different animal models, including cell line-derived xenografts (CDX) and patient-derived xenografts (PDX), and to explore its mechanisms of function. METHODS: [68Ga]Ga-PSMA-617 was prepared. The expression level of PSMA in two human hepatocellular cancer cells (HepG2 and HuH-7) was evaluated, and the cellular uptakes of [68Ga]Ga-PSMA-617 were assayed. HepG2 and HuH-7 subcutaneous xenograft models, HepG2 orthotopic xenograft models, and four different groups of PDX models were prepared. Preclinical pharmacokinetics and performance of [68Ga]Ga-PSMA-617 were evaluated in different types of HCC xenografts models using small animal PET and biodistribution studies. RESULTS: Low PSMA expression level of HepG2 and HuH-7 cells was observed, and the cellular uptake and blocking study confirmed the non-specificity of the PSMA-targeted probe binding to HepG2 and HuH-7 cells. In the subcutaneous xenograft models, the tumor uptakes at 0.5 h were 0.76 ± 0.12%ID/g (HepG2 tumors) and 0.78 ± 0.08%ID/g (HuH-7 tumors), respectively, which were significantly higher than those of the blocking groups (0.23 ± 0.04%ID/g and 0.20 ± 0.04%ID/g, respectively). In the orthotopic xenograft models, PET images clearly displayed the tumor locations based on the preferential accumulation of [68Ga]Ga-PSMA-617 in tumor tissue versus normal liver tissue, suggesting the possibility of using [68Ga]Ga-PSMA-617 PET imaging to detect primary HCC lesions in deep tissue. In the four different groups of HCC PDX models, PET imaging with [68Ga]Ga-PSMA-617 provided clear tumor uptakes with prominent tumor-to-background contrast, further demonstrating its potential for the clinical imaging of PSMA-positive HCC lesions. The staining of tumor tissue sections with CD31- and PSMA-specific antibodies visualized the tumor-associated blood vessels and PSMA expression on endothelial cells in subcutaneous, orthotopic tissues, and PDX tissues, confirming the imaging with [68Ga]Ga-PSMA-617 might be mediated by targeting tumor associated endothelium. CONCLUSION: In this study, in vivo PET on different types of HCC xenograft models illustrated high uptake within tumors, which confirmed that [68Ga]Ga-PSMA-617 PET may be a promising imaging modality for HCC by targeting tumor associated endothelium.

Chinese expert consensus on conversion therapy for hepatocellular carcinoma (2021 edition).

Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma (HCC) have resulted in improved response rates. This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection, a 'conversion therapy' strategy. However, conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed. Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice. Evidence review: Many research centers in China have accumulated significant experience implementing HCC conversion therapy. Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC; however, there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields. In order to summarize and learn from past experience and review current challenges, the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma (2021 Edition) was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice. Sixteen consensus statements on the implementation of conversion therapy for HCC were developed. The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.

Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting.

Photodynamic therapy (PDT) has emerged as a promising locoregional therapy of hepatocellular carcinoma (HCC). The utilization of luminogens with aggregation-induced emission (AIE) characteristics provides a new opportunity to design functional photosensitizers (PS). PSs targeting the critical organelles that are susceptible to reactive oxygen species damage is a promising strategy to enhance the effectiveness of PDT. In this paper, a new PS, 1-[2-hydroxyethyl]-4-[4-(1,2,2-triphenylvinyl)styryl]pyridinium bromide (TPE-Py-OH) of tetraphenylethylene derivative with AIE feature was designed and synthesized for PDT. The TPE-Py-OH can not only simultaneously target lipid droplets and mitochondria, but also stay in cells for a long period (more than 7 days). Taking advantage of the long retention ability of TPE-Py-OH in tumor, the PDT effect of TPE-Py-OH can be activated through multiple irradiations after one injection, which provides a specific multiple light-activated PDT effect. We believe that this AIE-active PS will be promising for the tracking and photodynamic ablation of HCC with sustained effectiveness.

Auxiliary Liver Graft Can Be Protected From HBV Infection in HBsAg Positive Blood Circulation.

Auxiliary grafts have a high risk of Hepatitis B virus (HBV) infection in patients with chronic HBV-related diseases. Hepatitis B virus-related auxiliary partial orthotopic liver transplantation (APOLT) cases were reviewed to show the results of current methods to block native-to-graft HBV transmission. Three patients received APOLT for HBV-related liver cirrhosis and a recurrent upper gastrointestinal hemorrhage between April 2015 and January 2017 by the liver transplant team of Beijing Friendship Hospital affiliated with Capital Medical University. All three patients were positive for HBV surface antigen (HBsAg) and had a negative HBV DNA test result before transplantation. After auxiliary transplantations, HBsAg was found to be positive in two patients and negative in one patient. To avoid graft infection of HBV, entecavir-based therapy was employed and the remnant native livers of the recipients were removed 51-878 days after liver transplantation. Then, serum conversions of HBsAg were found in all three cases. For the first time, this case series shows the possibility of blocking the transmission of HBV from a native liver to a graft in auxiliary transplantation by entecavir-based therapy. Among the cases, a left lobe graft was successfully implanted as a replacement of the right lobe of the recipient, which is also discussed.

In-situ synthesis of ultrasmall Au nanoparticles on bimetallic metal-organic framework with enhanced electrochemical activity for estrone sensing.

In this work, ultrasmall Au nanoparticles decorated bimetallic metal-organic framework (US Au NPs@AuZn-MOF) hybrids were facilely prepared by a sequential ion exchange and in-situ chemical reduction strategy. Numerous of Au nanoparticles with size less than 5 nm was homogeneously dispersed on the surface of the whole bimetallic AuZn-MOF polyhedrons. The integration of ultrasmall Au nanoparticles greatly enhanced the electron transfer capacity and electrochemical active surface area of the metal-organic framework host. Compared with the pristine Zn-MOF, bimetallic AuZn-MOF, the as-synthesized US Au NPs@AuZn-MOF hybrids exhibited remarkably promoted electrochemical activity toward the oxidation and sensing of endocrine-disrupting chemical (EDC) estrone. As a result, a highly sensitive electrochemical sensing platform was developed for the detection of estrone in the range of 0.05 µM-5 µM with limit of detection of 12.3 nM (S/N = 3) and sensitivity of 101.3 µA-1 µM-1 cm-2. Considering the structural diversity of MOFs and superior property of ultrasmall Au nanoparticles, the strategy proposed here may open a new avenue for the design and synthesis of other high-activity nanomaterials for electrochemical sensing or other challenging fields.

Phytic acid functionalized ZIF-67 decorated graphene nanosheets with remarkably boosted electrochemical sensing performance.

Recently, metal-organic frameworks (MOFs) display great application potential in the field of electrochemical catalysis and sensing due to its extraordinary properties. Herein, Co-based MOFs (ZIF-67) decorated graphene nanosheets (GS) heterogeneous hybrids (ZIF-67@GS) with sandwich-like morphology is first prepared by a facile in situ synthesis method. The electrochemical activity of ZIF-67 polyhedrons is effectively enhanced for the introduction of the high conductivity of graphene nanosheets. Subsequently, phytic acid functionalized ZIF-67 with unique core-shell structure decorated GS (PA-ZIF-67@GS) is prepared through the chemical etching effect of phytic acid. Surprisingly, the exposure level of metal active sites, electrochemical active surface area, electron transfer kinetic of the chemically etched ZIF-67@GS are further significantly boosted. Benefiting from the greatly modified interface property, the as-obtained PA-ZIF-67@GS hybrids exhibit excellent electrocatalytic activity toward the oxidation of glucose, and an ultrasensitive nonenzymatic electrochemical sensing platform is then developed. It is believed that this work may provide effective guidance for optimizing the electrochemical catalytic and sensing performance of other series of MOFs.

CRISPR/Cas9-mediated knockout of NSD1 suppresses the hepatocellular carcinoma development via the NSD1/H3/Wnt10b signaling pathway.

BACKGROUND: The NSD family of histone lysine methyltransferases have emerged as important biomarkers that participate in a variety of malignancies. Recent evidence has indicated that somatic dysregulation of the nuclear receptor binding SET domain-containing protein 1 (NSD1) is associated with the tumorigenesis in HCC, suggesting that NSD1 may serve as a prognostic target for this malignant tumor. However, its mechanism in human hepatocellular carcinoma (HCC), the major primary malignant tumor in the human liver, remains unclear. Hence, we investigated how NSD1 regulated HCC progression via regulation of the Wnt/ß-catenin signaling pathway. METHODS: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis was performed to identify the expression of NSD1 in HCC cells and clinically obtained tissues. The relationship between NSD1 expression and prognosis was analyzed by Kaplan-Meier survival curve. Further, a NSD1 knockout cell line was constructed by CRISPR/Cas9 genomic editing system, which was investigated in a battery of assays such as HCC cell proliferation, migration and invasion, followed by the investigation into NSD1 regulation on histone H3, Wnt10b and Wnt/ß-catenin signaling pathway via ChIP. Finally, a nude mouse xenograft model was conducted in order to assess tumorigenesis affected by NSD1 knockout in vivo. RESULTS: NSD1 was overexpressed in HCC tissues and cell lines in association with poor prognosis. Knockout of NSD1 inhibited the proliferation, migration and invasion abilities of HCC cells. CRISPR/Cas9-mediated knockout of NSD1 promoted methylation of H3K27me3 and reduced methylation of H3K36me2, which inhibited Wnt10b expression. The results thereby indicated an inactivation of the Wnt/ß-catenin signaling pathway suppressed cell proliferation, migration and invasion in HCC. Moreover, these in vitro findings were reproduced in vivo on tumor xenograft in nude mice. CONCLUSION: In conclusion, the study provides evidence that CRISPR/Cas9-mediated NSD1 knockout suppresses HCC cell proliferation and migration via the NSD1/H3/Wnt10b signaling pathway, suggesting that NSD1, H3 and Wnt10b may serve as potential targets for HCC.

Ultrasmall HKUST-1 nanoparticles decorated graphite nanosheets for highly sensitive electrochemical sensing of DNA damage biomarker 8-hydroxy-2'-deoxyguanosine.

Herein, graphite nanosheets (GN) were first prepared through simple liquid-phase exfoliation of graphite powder in N, N-dimethylacetamide (DMAC). After then, ultrasmall Cu-based metal organic frame (HKUST-1) nanoparticles (less than 5 nm) were in-situ anchored on the surface of graphite nanosheets with high degree of dispersion. Due to the intrinsic structural advantages of the as-synthesized HKUST-1 nanoparticles decorated graphite nanosheets (HKUST-1/GN) hybrids, including superior electron transfer ability and the greatly enhanced adsorption property, HKUST-1/GN shows excellent electrochemical sensing performance toward DNA damage biomarker 8-hydroxy-2'-deoxyguanosine with fast detection speed (∼240 s), wide linear window (10 nM-1 µM), high sensitivity (346857 µA mM-1 cm-2), low detection limit (∼2.5 nM), and good reproducibility. As a result, a highly sensitive electrochemical sensing platform for the detection of DNA damage biomarker 8-hydroxy-2'-deoxyguanosine was fabricated basing the as-prepared HKUST-1/GN hybrids. What is more, the developed electrochemical method was successfully used for the detection of real samples and exhibited satisfied result.

DNA methylation biomarkers for hepatocellular carcinoma.

BACKGROUND: Aberrant methylation of DNA is a key driver of hepatocellular carcinoma (HCC). In this study, we sought to integrate four cohorts profile datasets to identify such abnormally methylated genes and pathways associated with HCC. METHODS: To this end, we downloaded microarray datasets examining gene expression (GSE84402, GSE46408) and gene methylation (GSE73003, GSE57956) from the GEO database. Abnormally methylated differentially expressed genes (DEGs) were sorted and pathways were analyzed. The String database was then used to perform enrichment and functional analysis of identified pathways and genes. Cytoscape software was used to create a protein-protein interaction network, and MCODE was used for module analysis. Finally, overall survival analysis of hub genes was performed by the OncoLnc online tool. RESULTS: In total, we identified 19 hypomethylated highly expressed genes and 14 hypermethylated lowly expressed genes at the screening step, and finally found six mostly changed hub genes including MAD2L1, CDC20, CCNB1, CCND1, AR and ESR1. Pathway analysis showed that aberrantly methylated-DEGs mainly associated with the cell cycle process, p53 signaling, and MAPK signaling in HCC. After validation in TCGA database, the methylation and expression status of hub genes was significantly altered and same with our results. Patients with high expression of MAD2L1, CDC20 and CCNB1 and low expression of CCND1, AR, and ESR1 was associated with shorter overall survival. CONCLUSIONS: Taken together, we have identified novel aberrantly methylated genes and pathways linked to HCC, potentially offering novel insights into the molecular mechanisms governing HCC progression and serving as novel biomarkers for precision diagnosis and disease treatment.

Morphology-dependent electrochemical sensing performance of metal (Ni, Co, Zn)-organic frameworks.

To clarify the morphology effect of metal-organic frameworks (MOFs) on their electrochemistry as well as to explore their electrochemical applications, three MOFs with metal centers of nickel, cobalt, and zinc are synthesized. The used organic ligand is only 1,3,5-benzenetricarboxylic acid. Characterizations using Fourier Transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and electrochemical techniques reveal that these MOFs possess similar bonding properties, crystalline structures and phase purity, but various morphology and electrochemical activities, including their own redox behavior, electrochemical response toward redox probes and analytes in solutions. As a case study of analytes, voltammetry of Ponceau 4R is investigated on three MOFs. Its sensitive and selective monitoring is further achieved on nickel MOFs with a linear range from 0.5 to 150 nM and a detection limit of 80 pM. Therefore, the morphology of MOFs determines electrochemistry of MOFs and their electrochemical sensing applications.

Reduced graphene oxide-ZnO nanocomposite based electrochemical sensor for sensitive and selective monitoring of 8-hydroxy-2'-deoxyguanosine.

Developing reliable and feasible electrochemical sensors for the detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) is important because the urinary level of 8-OHdG is related to cancer disease. Moreover, the co-existed uric acid (UA) as an interference severe affects the sensitive detection of 8-OHdG. Herein, sensitive monitoring of 8-OHdG was conducted using a nanocomposite of reduced graphene oxide (rGO) and ZnO nanoparticles (ZnO@rGO) as the sensing material. This nanocomposite was prepared via in-situ reduction of GO with Zn powders. Compared with those obtained on the unmodified glassy carbon electrode (GCE) and GO modified GCE (GO/GCE) the oxidation signals of 8-OHdG are significantly enhanced on the ZnO@rGO nanocomposite coated GCE (ZnO@rGO/GCE). Moreover, uricase has been employed successfully to eliminate the interferences of UA. A large amount of UA did not affect the oxidation signals of trace level of 8-OHdG. The linear range for the detection of 8-OHdG using ZnO@rGO/GCE was from 5.0 to 5000.0 nM. The detection limit was 1.25 nM calculated from a three-signal-to-noise ratio. The developed monitoring system is sensitive and selective for the determination of 8-OHdG and thus useful in practical applications, such as for the monitoring of 8-OHdG in the clinic urine samples.

S-Adenosylmethionine attenuates bile duct early warm ischemia reperfusion injury after rat liver transplantation.

Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 µmol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (P < .05). Simultaneously, SAM effectively improved the survival of the transplant recipients. Furthermore, the H2O2 and malondialdehyde (MDA) of the IRI group were much higher compared to the SAM group (P < .05). The GSH/GSSG ratio in the SAM group was significantly increased by SAM treatment compared to the IRI group (P < .05). SAM administration significantly inhibited macrophage infiltration in liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (P < .05). The number of apoptotic biliary epithelial cells and caspase-3-positive cells in IRI rat livers were much higher compared to those in SAM-treated rats at 24 h after liver transplantation (P < .05). These data suggested that SAM protected bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α.