Microenvironment-triggered cascade metal-polyphenolic nanozyme for ROS/NO synergistic hyperglycemic wound healing.

Wound infection of hyperglycemic patient often has extended healing period and increased probability due to the high glucose level. However, achieving precise and safe therapy of the hyperglycemic wound with specific wound microenvironment (WME) remains a major challenge. Herein, a WME-activated smart L-Arg/GOx@TA-Fe (LGTF) nanozymatic system composed of generally recognized as safe (GRAS) compound is engineered. The nanozymatic system combining metal-polyphenol nanozyme (tannic acid-Fe3+, TA-Fe) and natural enzyme (glucose oxidase, GOx) can consume the high-concentration glucose, generating reactive oxygen species (ROS) and nitric oxide (NO) in situ to synergistically disinfect hyperglycemia wound. In addition, glucose consumption and gluconic acid generation can lower glucose level to promote wound healing and reduce the pH of WME to enhance the catalytic activities of the LGTF nanozymatic system. Thereby, low-dose LGTF can perform remarkable synergistic disinfection and healing effect towards hyperglycemic wound. The superior biosafety, high catalytic antibacterial and beneficial WME regulating capacity demonstrate this benign GRAS nanozymatic system is a promising therapeutic agent for hyperglycemic wound.

The association of hypophysitis with immune checkpoint inhibitors use: Gaining insight through the FDA pharmacovigilance database.

The use of immune checkpoint inhibitor (ICI) marked a revolutionary change in cancer treatment and opened new avenues for cancer therapy, but ICI can also trigger immune-related adverse events (irAEs). Here, we investigated the publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insight into the possible association between immune checkpoint inhibitors and hypophysitis. Data on adverse events (AEs) due to hypophysitisfor nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected from the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, and the signals for hypophysitis associated with the four drugs were examined using the reporting odds ratio (ROR) method. The number of reported hypophysitis events ≥ 3 and the lower limit of the 95% confidence interval (CI) of the ROR > 1 were considered positive for hypophysitis signals. A total of 1252 AE reports of hypophysitis associated with nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected, including 419, 149, 643, and 41 cases, respectively. The RORs of hypophysitis were 289.58 (95% CI 258.49-324.40), 171.74 (95% CI 144.91-203.54), 2248.57 (95% CI 2025.31-2496.45), and 97.29 (95% CI 71.28-132.79), respectively. All four drugs were statistically correlated with the target AE, with the correlation being, in descending order, ipilimumab, nivolumab, pembrolizumab, and atezolizumab. Nivolumab, pembrolizumab, ipilimumab, and atezolizumab have all been associated with hypophysitis, which can negatively impact quality of life, and early recognition and management of immune checkpoint inhibitor-related hypophysitis is critical.

Effect of root exudates on the release, surface property, colloidal stability, and phytotoxicity of dissolved black carbon.

In this study, the release of dissolved black carbon (DBC) from bulk-BC, its surface properties, colloidal stability, and oxidative stress to rice seedlings in the presence and absence of rice root exudates were compared. The bulk-BCs were prepared at 550 °C and derived from wood chips and pig manure, respectively. The release of DBC from bulk-BC was significantly enhanced (20.19-23.63%) by the introduction of root exudates, where low molecular weight organic acids played a dominating role in the dissociation of DBC from carbon skeleton. The surface properties of DBC were greatly modified by root exudates including decreases in the surface area (18.13%) and mineral contents (43.90-69.57%). The O-containing groups and graphitization were also enhanced by 11.46% and 18.65%, respectively. Meanwhile, the presence of root exudates not only reduced the colloidal stability of DBC but also lowered the intensity of free radicals (19.44-22.22%) in DBC. Consequently, the oxidative stress of DBC to rice seedlings was significantly (p < 0.05) alleviated, evidenced by reduced antioxidative enzyme activities (5.67-29.25%) and soluble protein content (15.75-46.79%) in rice plants. These results indicate that the interaction between DBC and root exudates could remarkably modify the surface properties and reactivity of DBC, which has profound implications for understanding the behavior and functions of DBC in the environment.

Comparison of Modified Above-Knee and Conventional Surgery with the Stripping of the Great Saphenous Vein of Varicose Veins of the Lower Extremities: A Retrospective Study.

OBJECTIVE: To compare the clinical effects of modified above-knee and conventional surgery with the stripping of the great saphenous vein of varicose veins of the lower extremities. METHODS: Clinical data of patients with a varicose vein of the lower extremity from May 2016 to May 2018 were collected. A retrospective study was conducted on the patients receiving modified above-knee and conventional surgery with the great saphenous vein stripping. The baseline characteristics and long-term follow-up data were compared between the groups. RESULTS: There were no significant differences in baseline characteristics between the two groups (P > 0.05). The surgeries were successfully performed by the same group of surgeons under local anesthesia and neuraxial anesthesia. The hospital stay, operation time, intraoperative blood loss, total length, and number of incisions in the above-knee group were comparable to those in the conventional surgery group (P > 0.05). The incidence of saphenous nerve injury and subcutaneous hematoma in the above-knee group was lower than that in the conventional surgery group (P < 0.05). There were no significant differences in recurrent varicose vein incidences (P > 0.05). After surgery, the venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire (CIVIQ-14) scores of both groups were higher than those before operation (P < 0.05). There was no significant difference in VCSS score or CIVIQ-14 scores between the two groups postoperation (P > 0.05). At 24 months after surgery, the above-knee group (71.8%) and conventional surgery group (73.2%) resulted in changes of at least two CEAP-C clinical classes lower than baseline, respectively. CONCLUSION: The modified above-knee technique can ensure clinical outcomes, reduce intraoperative blood loss and complication incidences, and shorten the operative time. This gives evidence that the modified above-knee technique is worthy of clinical application.

Dextran-stabilized Fe-Mn bimetallic oxidase-like nanozyme for total antioxidant capacity assay of fruit and vegetable food.

The total antioxidant capacity (TAC) has become increasingly vital for evaluating antioxidant food quality in the field of healthcare. Herein, a convenient and sensitive method for TAC assay was proposed based on the absorbance difference of reaction systems between various antioxidants existed in food and Dex-FeMnzyme/oxTMB. Under the optimum condition, the limit of detection (LOD) of the colorimetric sensor was 1.17 µM with the linear concentration range from 1 µM to 30 µM. The analysis results demonstrated the excellent feasibility of practical application in fruit and vegetable food, which offered a new avenue for the establishment of colorimetric biosensors.

Photochemical Transformation and Catalytic Activity of Dissolved Black Nitrogen Released from Environmental Black Carbon.

Biomass combustion results in the formation and wide distribution of black carbon (BC) in soils, wherein the dissolved fractions are among the most active components. Although the presence of dissolved black nitrogen (DBN) in BC has been identified, its environmental behavior and implication are not understood. This study investigated the photochemical transformation and catalytic activity of DBN under simulated solar irradiation. DBN is more easily transformed than dissolved BC due to its photoactive heteroaromatic N structure, and the half-life of DBN produced at 500 °C (8.6 h) is two times shorter than that of the dissolved BC counterpart (23 h). Meanwhile, solar irradiation is favorable for the homoaggregation of DBN. During irradiation, DBN generates not only reactive oxygen species (e.g., 1O2, O2-, and •OH) but also reactive nitrogen species (mainly •ON), which account for its higher photocatalytic degradation of bisphenol A than dissolved BC. These findings shed new light on the impact of heteroatoms on the phototransformation and activity of BC as well as cycling of N in terrestrial systems.

Suppression of microRNA-141 suppressed p53 to protect against neural apoptosis in epilepsy by SIRT1 expression.

We investigated that microRNA (miRNA)-141 protects against epilepsy-induced apoptosis and its reaction mechanism. The serum expression of miRNA-141 in epilepsy model mice and control volunteer was measured by quantitative reverse-transcription polymerase chain reaction. We found that miRNA-141 serum expression was upregulated in patients with epilepsy. Overexpression of miRNA-141 induced nerve cell apoptosis, suppressed proliferation, promoted caspase-3/9, Bax and p53 protein expression, and reduced silent information regulator 1 (SIRT1) protein expression in vitro model. In addition, the downexpression miRNA-141 using si-miRNA-141 reduced nerve cell apoptosis and increased proliferation, suppressed caspase-3/9, Bax and p53 protein expression, induced SIRT1 protein expression. SIRT1 inhibitor (nicotinamide) decreased SIRT1, reduced the effects of miRNA-141 on nerve cell apoptosis in vitro model of epilepsy through SIRT1/p53. SIRT1 agonist also reduced the effects of miRNA-141 overexpression on nerve cell apoptosis in vitro model of epilepsy through SIRT1/p53. Our preliminary findings indicate that anti-miRNA-141 protects against epilepsy-induced apoptosis via SIRT1/p53 expression.

Comparative Epidemiological Investigation of Alzheimer's Disease and Colorectal Cancer: The Possible Role of Gastrointestinal Conditions in the Pathogenesis of AD.

Alzheimer's disease (AD) is a neurodegenerative disorder that affects approximately 35 million people worldwide, and diet has been reported to influence the prevalence/incidence of AD. Colorectal cancer is among the most common cancers in Western populations, and the correlation between constipation and the occurrence of colorectal cancer has been identified in a number of studies, which show that a Westernized diet is a mutual risk factor. Constipation is a growing health problem, particularly in middle-aged and older adults. As the most common gastrointestinal disorder in adults, constipation affects 2-20% of the world population, and it is associated with several diseases, such as diabetes, Parkinson's disease, and others. Comparing the epidemiological data on colorectal cancer and AD, we find that colorectal cancer and AD have similar epidemiologic feature, which is both disease correlate with high prevalence of constipation. Therefore, we hypothesized that constipation may influence Alzheimer's disease in a similar way that it contributes to colorectal cancer. This review aimed to systemically elucidate the evidence that constipation contributes to Alzheimer's disease progression.