Kill Two Birds with One Stone: Dual-Metal MOF-Nanozyme-Decorated Hydrogels with ROS-Scavenging, Oxygen-Generating, and Antibacterial Abilities for Accelerating Infected Diabetic Wound Healing.

Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)-crosslinked chitosan (CS)-based hydrogels decorated with the biomimetic metal-organic framework (MOF)-nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP-CS (MCGC), are prepared. With catalase (CAT)-like activity, these dual-metal MOF-nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management.

Applications of MRI in Schizophrenia: Current Progress in Establishing Clinical Utility.

Schizophrenia is a severe mental illness that significantly impacts the lives of affected individuals and with increasing mortality rates. Early detection and intervention are crucial for improving outcomes but the lack of validated biomarkers poses great challenges in such efforts. The use of magnetic resonance imaging (MRI) in schizophrenia enables the investigation of the disorder's etiological and neuropathological substrates in vivo. After decades of research, promising findings of MRI have been shown to aid in screening high-risk individuals and predicting illness onset, and predicting symptoms and treatment outcomes of schizophrenia. The integration of machine learning and deep learning techniques makes it possible to develop intelligent diagnostic and prognostic tools with extracted or selected imaging features. In this review, we aimed to provide an overview of current progress and prospects in establishing clinical utility of MRI in schizophrenia. We first provided an overview of MRI findings of brain abnormalities that might underpin the symptoms or treatment response process in schizophrenia patients. Then, we summarized the ongoing efforts in the computer-aided utility of MRI in schizophrenia and discussed the gap between MRI research findings and real-world applications. Finally, promising pathways to promote clinical translation were provided. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Circulating soluble CD36 as a novel biomarker for progression and prognosis of HBV-related liver diseases.

Background: Our previous study suggested CD36 may be a positive regulator of hepatitis B virus (HBV) replication in vitro. Therefore, the present study aimed to investigate whether circulating soluble CD36 (sCD36) could serve as a diagnostic and prognostic biomarker for HBV-related liver diseases based on the clinic collected data. Methods: A total of 282 subjects were divided into healthy controls (HC, n = 47), chronic hepatitis B (CHB, n = 68), HBV-related liver cirrhosis (HBV-LC, n = 167). Soluble CD36 in plasma was measured by ELISA, and monocyte or platelet CD36 expression was determined by flow cytometry. Results: There was a step-wise increase of sCD36 with the progression of chronic HBV infection, and it was the highest in the HBV- LC group with liver failure (1.50, IQR:1.04-2.00) as compared with HC (0.38, IQR:0.27-0.38), CHB (0.75, IQR:0.40-1.13), and HBV-LC without liver failure (1.02, IQR,0.61-1.35) group. Circulating sCD36 was not correlated with serum HBV DNA levels, but correlated with liver function parameters. Additionally, ROC analysis confirmed sCD36 could be used to predict liver failure for HBV-LC patients, which yielded an AUC of 0.775 with 71.0% sensitivity and 72.2% specificity. Multivariate logistic regression analysis revealed sCD36 is an independent risk factor in predicting liver failure. Moreover, plasma sCD36 in HBV-LC patients was significantly correlated with prognostic indices, including MELD, MELD-Na and CHILD-PUGH scores. On the other hand, CD36 expression on monocytes or platelets was positively correlated with plasma sCD36 levels, whereas they were not strongly associated with the disease severity. Conclusion: Circulating sCD36 could be used as a novel noninvasive biomarker for predicting liver failure and prognosis in chronic HBV infected patients.

Magnetic COFs as satisfied support for lipase immobilization and recovery to effectively achieve the production of biodiesel by great maintenance of enzyme activity.

BACKGROUND: Production of biodiesel from renewable sources such as inedible vegetable oils by enzymatic catalysis has been a hotspot but remains a challenge on the efficient use of an enzyme. COFs (Covalent Organic Frameworks) with large surface area and porosity can be applied as ideal support to avoid aggregation of lipase and methanol. However, the naturally low density limits its application. In this work, we reported a facile synthesis of core-shell magnetic COF composite (Fe3O4@COF-OMe) to immobilize RML (Rhizomucor miehei lipase), to achieve its utilization in biodiesel production. RESULT: This strategy gives extrinsic magnetic property, and the magnetic COFs is much heavier and could disperse in water medium well, facilitating the attachment with the enzyme. The resultant biocomposite exhibited an excellent capacity of RML due to its high surface area and fast response to the external magnetic field, as well as good chemical stability. The core-shell magnetic COF-OMe structure not only achieved highly efficient immobilization and recovery processes but also maintained the activity of lipase to a great extent. RML@Fe3O4@COF-OMe performed well in practical applications, while free lipase did not. The biocomposite successfully achieved the production of biodiesel from Jatropha curcas Oil with a yield of about 70% in the optimized conditions. CONCLUSION: Magnetic COFs (Fe3O4@COF-OMe) for RML immobilization greatly improved catalytic performance in template reaction and biodiesel preparation. The magneticity makes it easily recovered and separated from the system. This first successful attempt of COFs-based immobilized enzyme broadened the prospect of biodiesel production by COFs with some inspiration.

Development of a quantitative segmentation model to assess the effect of comorbidity on patients with COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has brought a global disaster. Quantitative lesions may provide the radiological evidence of the severity of pneumonia and further to assess the effect of comorbidity on patients with COVID-19. METHODS: 294 patients with COVID-19 were enrolled from February, 24, 2020 to June, 1, 2020 from six centers. Multi-task Unet network was used to segment the whole lung and lesions from chest CT images. This deep learning method was pre-trained in 650 CT images (550 in primary dataset and 100 in test dataset) with COVID-19 or community-acquired pneumonia and Dice coefficients in test dataset were calculated. 50 CT scans of 50 patients (15 with comorbidity and 35 without comorbidity) were random selected to mark lesions manually. The results will be compared with the automatic segmentation model. Eight quantitative parameters were calculated based on the segmentation results to evaluate the effect of comorbidity on patients with COVID-19. RESULTS: Quantitative segmentation model was proved to be effective and accurate with all Dice coefficients more than 0.85 and all accuracies more than 0.95. Of the 294 patients, 52 (17.7%) patients were reported having at least one comorbidity; 14 (4.8%) having more than one comorbidity. Patients with any comorbidity were older (P < 0.001), had longer incubation period (P < 0.001), were more likely to have abnormal laboratory findings (P < 0.05), and be in severity status (P < 0.001). More lesions (including larger volume of lesion, consolidation, and ground-glass opacity) were shown in patients with any comorbidity than patients without comorbidity (all P < 0.001). More lesions were found on CT images in patients with more comorbidities. The median volumes of lesion, consolidation, and ground-glass opacity in diabetes mellitus group were largest among the groups with single comorbidity that had the incidence rate of top three. CONCLUSIONS: Multi-task Unet network can make quantitative CT analysis of lesions to assess the effect of comorbidity on patients with COVID-19, further to provide the radiological evidence of the severity of pneumonia. More lesions (including GGO and consolidation) were found in CT images of cases with comorbidity. The more comorbidities patients have, the more lesions CT images show.

Negative short-term impact of intraoperative biliary lavage in patients with hepatolithiasis.

AIM: To evaluate short-term outcomes following intraoperative biliary lavage for hepatolithiasis. METHODS: A total of 932 patients who were admitted to the West China Medical Center of Sichuan University between January 2010 and January 2014 and underwent bile duct exploration and lithotomy were retrospectively included in our study. The patients were divided into the lavage group and the control group. Related pre-, intra-, and postoperative factors were recorded, analyzed, and compared between the two groups in order to verify the effects of biliary lavage on the short-term outcome of patients with hepatolithiasis. RESULTS: Amongst the patients who were included, 678 patients with hepatolithiasis were included in the lavage group, and the other 254 patients were enrolled in the control group. Data analyses revealed that preoperative baseline and related intraoperative variables were not significantly different. However, patients who underwent intraoperative biliary lavage had prolonged postoperative hospital stays (6.67 d vs 7.82 d, P = 0.024), higher hospitalization fees (RMB 28437.1 vs RMB 32264.2, P = 0.043), higher positive rates of bacterial cultures from blood (13.3% vs 25.8%, P = 0.001) and bile (23.6% vs 40.7%, P = 0.001) samples, and increased usage of advanced antibiotics (26.3% vs 38.2%, P = 0.001). In addition, in the lavage group, more patients had fever (> 37.5 °C, 81.4% vs 91.1%, P = 0.001) and hyperthermia (> 38.5°C, 39.7% vs 54.9%, P = 0.001), and higher white blood cell counts within 7 d after the operation compared to the control group. CONCLUSION: Intraoperative biliary lavage might increase the risk of postoperative infection, while not significantly increasing gallstone removal rate.