Photoinduced Dynamic Ligation in Metal-Organic Frameworks.

Metal organic frameworks (MOFs), a class of porous crystalline materials consisting of metal-based nodes and organic linkers, have emerged as a promising platform for photocatalysis due to their ultrahigh functional surface area, customizable topologies, and tunable energetics. While interesting photochemistry has been reported, the related photoinduced structural dynamics of MOFs remains unclear. The consensus is that the coordination bonds between MOF nodes and linkers are considered static during photoexcitation, while the open-metal sites on the nodes are taken as the key active sites for catalysis. In this work, through a complementary time-resolved visible and infrared (IR) spectroscopic investigation, along with computational studies, we report for the first time light-induced structural bond dissociation (COO-M) and reformation in an iron-oxo framework, MIL-101(Fe). The probed excited state displayed ligand-to-metal charge transfer (LMCT) characteristics and exhibited a ca. 30 µs lifetime. The incredibly long excited-state lifetime led us to probe potential structural rearrangements that facilitated charge separation in MIL-101(Fe). By probing the vibrational fingerprints of the carboxylate linker upon LMCT photoexcitation, we observed the reversible transition of the carboxylate-Fe bond from a bidentate bridging mode to a monodentate mode, indicating the partial dissociation of the carboxylate ligand. Importantly, the bidentate configuration is recovered on the same time scale of the excited state lifetimes as probed via visible transient absorption spectroscopy. The elucidated photoinduced configurational dynamics provides a foundation for an in-depth understanding of MOF-based photocatalytic mechanisms.

Construction and validation of an angiogenesis-related scoring model to predict prognosis, tumor immune microenvironment and therapeutic response in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with high morbidity and mortality. Identifying an effective marker for predicting the prognosis and therapeutic response is extremely meaningful. Angiogenesis-related genes (ARGs) play important roles in the tumor progression and immune-suppressive microenvironment formation. Methods: The differential expressed ARGs associated with the prognosis of HCC were identified in the TCGA dataset. Univariate Cox and least absolute shrinkage selection operator (LASSO) regression were applied to construct a ARGs Scoring model. The prognostic value of the ARGs Scoring model was assessed by Cox regression, Kaplan-Meier (KM) and ROC curve analyses. Then the model was further validated in an external dataset, ICGC dataset. The patients were split into two groups based on the ARGs Score and the clinical features were compared. TIMER, CIBERSORT and xCell algorithms were utilized to analyze the correlation between the ARGs Score and tumor immune microenvironment (TIME). Furthermore, we analyzed the efficacy of the model in predicting the therapeutic response for immunotherapy, targeted therapy and TACE treatment in different cohorts. Results: A total of 97 differential expressed ARGs were identified relating to the prognosis of HCC patients from the TCGA dataset. Then the ARGs Scoring model based on a 9-gene signature was constructed using the Cox and LASSO regression analyses. Higher ARGs Score had a poor clinical outcome and was considered to be an independent prognostic predictor for HCC in the multivariate Cox analysis. The ARGs Score was related to the enrichment of various immune cells, such as CD4+ T cells, Treg, macrophage, neutrophil and dendritic cells, exhibiting a more immunosuppressive phenotype. Higher ARGs Score was correlated with higher expression of immune checkpoint genes and poor response to immunotherapy. Furthermore, higher ARGs Score indicated poor therapeutic response in the sorafenib and TACE treatment cohorts, individually. Conclusions: The ARGs Scoring model exhibited robust predictive value for the prognosis and TIME for HCC patients. Higher ARGs Score indicated poor therapeutic response of the immunotherapy, sorafenib and TACE treatment. The ARGs Scoring model could be used as a biomarker to help physicians to develop more individualized treatment for HCC patients.

Efficacy of Combined Management with Nonsteroidal Anti-inflammatory Drugs for Prevention of Pancreatitis After Endoscopic Retrograde Cholangiography: a Bayesian Network Meta-analysis.

OBJECTIVES: To systematically evaluate the clinical efficacy of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) alone or in combination with other agents for preventing pancreatitis after endoscopic retrograde cholangiopanography. METHODS: We carried out a literature search of random controlled trials (RCTs) on preventing post-operative pancreatitis by administration of the anti-inflammatory drugs, indomethacin and diclofenac, following endoscopic retrograde cholangiopancreatography (ERCP). The databases searched for relevant publications up to July 7, 2021, included PubMed, Cochrane Library, and Embase. We screened the literature according to inclusion criteria and analyzed the extracted data. The overall population and high-risk patient groups were analyzed, with the main outcome being the incidence of PEP. RESULTS: The search identified 32 RCTs that included 15019 patients with post-ERCP pancreatitis and 9 different interventions. The results of the overall population network meta-analysis showed that NSAIDs alone, high-dose NSAIDs, and a combination of NSAIDs significantly reduced the incidence of PEP compared with placebo. However, compared with placebo, there was no statistically significant difference between the two interventions (NSAIDs + standard hydration and high-dose NSAIDs). In addition, NSAIDs + sublingual nitrates were associated with a lower incidence of PEP compared to that observed with NSAIDs alone. Probability ranking results showed that NSAIDs + sublingual nitrate had the best effect, followed by NSAIDs + standard hydration, NSAIDs + melatonin, NSAIDs + aggressive hydration, NSAIDs + somatostatin, NSAIDs alone, NSAIDs + epinephrine, high-dose NSAIDs, and placebo. In the high-risk subgroup, the results of the network meta-analysis showed that NSAIDs alone, high-dose NSAIDs, and a combination of NSAIDs showed no statistically significant difference in their ability to reduce the incidence of PEP compared with placebo. Probability ranking results showed that NSAIDs + hydration had the best effect, followed by NSAIDs + sublingual nitroglycerin and NSAIDs + aggressive hydration. CONCLUSION: Of the nine interventions, NSAIDs + sublingual nitrates had considerably better efficacy than the other drugs for reducing the incidence of PEP in the overall population. In high-risk patients, NSAIDs + standard hydration may be the best preventive treatment; however, more randomized, controlled trials are needed to validate our results. TRIAL REGISTRATION: Name of the registry: PROSPERO-International prospective register of systematic reviews. Unique identifying number or registration ID: CRD42021282205.