Integrating Artificial DNAzymes with Natural Enzymes on 2D MOF Hybrid Nanozymes for Enhanced Treatment of Bacteria-Infected Wounds.

Removal of invasive bacteria is critical for proper wound healing. This task is challenging because these bacteria can trigger intense oxidative stress and gradually develop antibiotic resistance. Here, the use of a multienzyme-integrated nanocatalytic platform is reported for efficient bacterial clearance and mitigation of inflammatory responses, constructed by physically adsorbing natural superoxide dismutase (SOD), in situ reduction of gold nanoparticles (Au NPs), and incorporation of a DNAzyme on 2D NiCoCu metal-organic frameworks (DNAzyme/SOD/Au@NiCoCu MOFs, termed DSAM), which can adapt to infected wounds. O2 and H2 O2 replenishment is achieved and alleviated the hypoxic microenvironment using the antioxidant properties of SOD. The H2 O2 produced during the reaction is decomposed by peroxidase (POD)-like activity enhanced by Au NPs and DNAzyme, releasing highly toxic hydroxyl radicals (•OH) to kill the bacteria. In addition, it possesses glutathione peroxidase (GPx)-like activity, which depletes GSH and prevents •OH loss. Systematic antimicrobial tests are performed against bacteria using this multienzyme-integrated nanoplatform. A dual-mode strategy involving natural enzyme-enhanced antioxidant capacity and artificial enzyme-enhanced •OH release to develop an efficient and novel enzyme-integrated therapeutic platform is integrated.

The Prognostic Significance of Nomogram-Based Pretreatment Inflammatory Indicators in Patients With Esophageal Squamous Cell Carcinoma Receiving Intensity-Modulated Radiotherapy.

BACKGROUND: At present, there is no objective prognostic index available for patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiotherapy (IMRT). This study is to develop a nomogram based on hematologic inflammatory indices for ESCC patients treated with IMRT. METHODS: 581 patients with ESCC receiving definitive IMRT were enrolled in our retrospective study. Of which, 434 patients with treatment-naïve ESCC in Fujian Cancer Hospital were defined as the training cohort. Additional 147 newly diagnosed ESCC patients were used as the validation cohort. Independent predictors of overall survival (OS) were employed to establish a nomogram model. The predictive ability was evaluated by time-dependent receiver operating characteristic curves, the concordance index (C-index), net reclassification index (NRI), and integrated discrimination improvement (IDI). Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram model. The entire series was divided into 3 risk subgroups stratified by the total nomogram scores. RESULTS: Clinical TNM staging, primary gross tumor volume, chemotherapy, neutrophil-to-lymphocyte ratio and platelet lymphocyte ratio were independent predictors of OS. Nomogram was developed incorporating these factors. Compared with the 8th American Joint Committee on Cancer (AJCC) staging, the C-index for 5-year OS (.627 and .629) and the AUC value of 5-year OS (.706 and .719) in the training and validation cohorts (respectively) were superior. Furthermore, the nomogram model presented higher NRI and IDI. DCA also demonstrated that the nomogram model provided greater clinical benefit. Finally, patients with <84.8, 84.8-151.4, and >151.4 points were categorized into low-risk, intermediate-risk, and high-risk groups. Their 5-year OS rates were 44.0%, 23.6%, and 8.9%, respectively. The C-index was .625, which was higher than the 8th AJCC staging. CONCLUSIONS: We have developed a nomogram model that enables risk-stratification of patients with ESCC receiving definitive IMRT. Our findings may serve as a reference for personalized treatment.

Different Dimensional Copper-Based Metal-Organic Frameworks with Enzyme-Mimetic Activity for Antibacterial Therapy.

Fighting against bacterial infection and accelerating wound healing remain important and challenging in infected wound care. Metal-organic frameworks (MOFs) have received much attention for their optimized and enhanced catalytic performance in different dimensions of these challenges. The size and morphology of nanomaterials are important in their physiochemical properties and thereby their biological functions. Enzyme-mimicking catalysts, based on MOFs of different dimensions, display varying degrees of peroxidase (POD)-like activity toward hydrogen peroxide (H2O2) decomposition into toxic hydroxyl radicals (•OH) for bacterial inhibition and accelerating wound healing. In this study, we investigated the two most studied representatives of copper-based MOFs (Cu-MOFs), three-dimensional (3D) HKUST-1 and two-dimensional (2D) Cu-TCPP, for antibacterial therapy. HKUST-1, with a uniform and octahedral 3D structure, showed higher POD-like activity, resulting in H2O2 decomposition for •OH generation rather than Cu-TCPP. Because of the efficient generation of toxic •OH, both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus could be eliminated under a lower concentration of H2O2. Animal experiments indicated that the as-prepared HKUST-1 effectively accelerated wound healing with good biocompatibility. These results reveal the multivariate dimensions of Cu-MOFs with high POD-like activity, providing good potential for further stimulation of specific bacterial binding therapies in the future.

Influence of age as a continuous variable on survival outcomes and treatment options in patients with upper thoracic esophageal carcinoma.

Background: This retrospective review of patients with upper thoracic esophageal squamous cell carcinoma (ESCC) analyzed the prognostic value of age, as a continuous variable, and offered insight into treatment options. Methods: 568 upper ESCC patients underwent radical therapy between 2004 and 2016. Age as a continuous variable was entered into the Cox regression model with penalized spline (P-spline) analysis to investigate a correlation between age and survival outcomes. Results: Before adjustment, P-spline regression revealed U-shaped survival curves. Sixty years was the optimal cut-off age for differences in overall and progression-free survival (OS, PFS). The cohort was divided into age groups ≤ 50, 51-69, and ≥ 70 years. Multivariate analyses showed no significant differences in either PFS or OS for patients aged ≤ 50 and 51-69 years. After adjusting for covariates, P-spline regression showed that the risk of mortality and disease progression increased with age, and ≥ 70 years was an unfavorable independent prognostic factor. For age ≥ 70 years, the OS and PFS associated with non-surgery was comparable to that of surgery. For patients younger, the OS and PFS of patients given surgery was significantly better than that of patients given non-surgery. Conclusion: Age was an independent prognostic factor for upper ESCC. Patients ≥ 70 years achieved no significant survival benefit from surgery, but for those younger than 70 years surgery was the preferred treatment option.

Ultrathin trimetallic metal-organic framework nanosheets for accelerating bacteria-infected wound healing.

Bacteria-infected wounds are commonly regarded as a hidden threat to human health that can create persistent infection and even bring about amputation or death. Two-dimensional metal-organic frameworks (2D MOFs) with biomimetic enzyme activity have been used to reduce the huge harm caused by antibiotic resistance due to their massive active sites and ultralarge specific surface area. However, their therapeutic efficiency is unsatisfactory because of their relatively low catalytic activity and poor productivity. In this paper, we presented a simple and mild one-pot solution phase method for the large-scale synthesis of NiCoCu-based MOF nanosheets. The NiCoCu nanosheets (denoted as (Ni2Co1)1-xCux) with controlled molar ratios have different morphologies and sizes. Specifically, the (Ni2Co1)0.5Cu0.5 nanosheets showed the best catalytic performance toward the reduction of H2O2 and H2O2 was efficiently catalyzed to generate toxic •OH in the presence of MOF nanosheets with peroxidase-like activity. (Ni2Co1)0.5Cu0.5 exhibited the best antibacterial activity against gram-positive Escherichia coli and methicillin-resistant Staphylococcus aureus bacteria. Animal wound healing experiments demonstrate that ultrathin trimetallic nanosheets can effectively contribute to wound healing with excellent biocompatibility. This study reveals the immense potential of ultrathin trimetallic MOF nanosheets for clinical antibacterial therapy for future pragmatic clinical applications.

Recent Advances in Nanozymes for Bacteria-Infected Wound Therapy.

Bacterial-infected wounds are a serious threat to public health. Bacterial invasion can easily delay the wound healing process and even cause more serious damage. Therefore, effective new methods or drugs are needed to treat wounds. Nanozyme is an artificial enzyme that mimics the activity of a natural enzyme, and a substitute for natural enzymes by mimicking the coordination environment of the catalytic site. Due to the numerous excellent properties of nanozymes, the generation of drug-resistant bacteria can be avoided while treating bacterial infection wounds by catalyzing the sterilization mechanism of generating reactive oxygen species (ROS). Notably, there are still some defects in the nanozyme antibacterial agents, and the design direction is to realize the multifunctionalization and intelligence of a single system. In this review, we first discuss the pathophysiology of bacteria infected wound healing, the formation of bacterial infection wounds, and the strategies for treating bacterially infected wounds. In addition, the antibacterial advantages and mechanism of nanozymes for bacteria-infected wounds are also described. Importantly, a series of nanomaterials based on nanozyme synthesis for the treatment of infected wounds are emphasized. Finally, the challenges and prospects of nanozymes for treating bacterial infection wounds are proposed for future research in this field.

Subcutaneous Peripheral Nerve Stimulation for Treatment of Acute/Subacute Herpes Zoster-related Trigeminal Neuralgia: A Retrospective Research.

OBJECTIVES: The purpose of this study was to observe the effect of subcutaneous stimulation of the peripheral nerve on acute or subacute zoster occurring in trigeminal nerve branches, and to evaluate the preventive effect of prior temporary implant of a peripheral stimulation electrode in the acute or subacute phase of herpes zoster (HZ) (from 30 to 90 d after zoster onset) before postherpetic neuralgia (PHN) presents. METHODS AND MATERIALS: A total of 26 patients' medical records were analyzed. All of patients had received temporary subcutaneous peripheral nerve stimulation (PNS). The clinical efficacy of treatment was evaluated on a visual analog scale (VAS), and dosages of pain medication were recorded before and at 1 to 6 months after the temporary stimulation. The rate of PHN was reevaluated at a 6 months follow-up. RESULTS: There was a significant decrease in VAS values after PNS. Medication doses decreased significantly after TPNS. The rate of clinically meaningful PHN (VAS >3) dropped below 4%. DISCUSSION: This study revealed that PNS is an effective treatment for trigeminal herpetic neuralgia following acute or subacute HZ. As a extend neuromodulation method, subcutaneous peripheral nerve-field stimulation might be a useful option to reduce the progression of neuropathic changes caused by persistent transmission of pain signals in the trigeminal nerve branches after the acute or subacute phase of HZ.

2D/3D Copper-Based Metal-Organic Frameworks for Electrochemical Detection of Hydrogen Peroxide.

Metal-organic frameworks (MOFs) have been extensively used as modified materials of electrochemical sensors in the food industry and agricultural system. In this work, two kinds of copper-based MOFs (Cu-MOFs) with a two dimensional (2D) sheet-like structure and three dimensional (3D) octahedral structure for H2O2 detection were synthesized and compared. The synthesized 2D and 3D Cu-MOFs were modified on the glassy carbon electrode to fabricate electrochemical sensors, respectively. The sensor with 3D Cu-MOF modification (HKUST-1/GCE) presented better electrocatalytic performance than the 2D Cu-MOF modified sensor in H2O2 reduction. Under optimal conditions, the prepared sensor displayed two wide linear ranges of 2 µM-3 mM and 3-25 mM and a low detection limit of 0.68 µM. In addition, the 3D Cu-MOF sensor exhibited good selectivity and stability. Furthermore, the prepared HKUST-1/GCE was used for the detection of H2O2 in milk samples with a high recovery rate, indicating great potential and applicability for the detection of substances in food samples. This work provides a convenient, practical, and low-cost route for analysis and extends the application range of MOFs in the food industry, agricultural and environmental systems, and even in the medical field.