Tumor Microenvironment-Regulating Two-Photon Probe Based on Bimetallic Post-Coordinated MOF Facilitating the Dual-Modal and Deep Imaging-Guided Synergistic Therapies.

The intricate tumor microenvironment (TME) always brings about unsatisfactory therapeutic effects for treatments, although nanomedicines have been demonstrated to be highly beneficial for synergistic therapies to avoid the side effects caused by the complexity and heterogeneity of cancer. Developing nanotheranostics with the functionalities of both synergistic therapies and TME regulation is a good strategy but is still in its infancy. Herein, an "all-in-one" nanoplatform for integrated diagnosis and treatment, namely, Carrier@ICG@DOX@FA (CIDF), is constructed. Benefiting from the bimetallic coordination of Eu3+-HTHA (4,4,4-trifluoro-1-(9-hexylcarbazol-3-yl)-1,3-butanedione) and Fe3+ with the ligands in UiO-67, CIDF can simultaneously achieve two-photon fluorescence imaging, fluorescent lifetime imaging in deep tumors, and regulation of TME. Owing to its porosity, CIDF can encapsulate indocyanine green as photosensitizers and doxorubicin as chemotherapeutic agent, further realizing light-controlled drug release. Moreover, CIDF exhibited good biocompatibility and tumor targeting by coating with folic-acid-modified polymers. Both in vitro and in vivo experiments demonstrate the excellent therapeutic efficacy of CIDF through dual-modal-imaging-guided synergistic photothermal-, photodynamic-, and chemotherapy. CIDF provides a new paradigm for the construction of TME-regulated synergistic nanotheranostics and realizes the complete elimination of tumors without recurrence.

Assessing the Impact of Climate Change on Potential Distribution of Meconopsis punicea and Its Influence on Ecosystem Services Supply in the Southeastern Margin of Qinghai-Tibet Plateau.

Meconopsis punicea is an iconic ornamental and medicinal plant whose natural habitat has degraded under global climate change, posing a serious threat to the future survival of the species. Therefore, it is critical to analyze the influence of climate change on possible distribution of M. punicea for conservation and sustainable utilization of this species. In this study, we used MaxEnt ecological niche modeling to predict the potential distribution of M. punicea under current and future climate scenarios in the southeastern margin region of Qinghai-Tibet Plateau. Model projections under current climate show that 16.8% of the study area is suitable habitat for Meconopsis. However, future projections indicate a sharp decline in potential habitat for 2050 and 2070 climate change scenarios. Soil type was the most important environmental variable in determining the habitat suitability of M. punicea, with 27.75% contribution to model output. Temperature seasonality (16.41%), precipitation of warmest quarter (14.01%), and precipitation of wettest month (13.02%), precipitation seasonality (9.41%) and annual temperature range (9.24%) also made significant contributions to model output. The mean elevation of suitable habitat for distribution of M. punicea is also likely to shift upward in most future climate change scenarios. This study provides vital information for the protection and sustainable use of medicinal species like M. punicea in the context of global environmental change. Our findings can aid in developing rational, broad-scale adaptation strategies for conservation and management for ecosystem services, in light of future climate changes.

Hepatotoxicity evaluation of traditional Chinese medicines using a computational molecular model.

BACKGROUND: Liver injury caused by traditional Chinese medicines (TCMs) is reported from many countries around the world. TCM hepatotoxicity has attracted worldwide concerns. OBJECTIVE: This study aims to develop a more applicable and optimal tool to evaluate TCM hepatotoxicity. METHODS: A quantitative structure-activity relationship (QSAR) analysis was performed based on published data and U.S. Food and Drug Administration's Liver Toxicity Knowledge Base (LTKB). RESULTS: Eleven herbal ingredients with proven liver toxicity in the literature were added into the dataset besides chemicals from LTKB. The finally generated QSAR model yielded a sensitivity of 83.8%, a specificity of 70.1%, and an accuracy of 80.2%. Among the externally tested 20 ingredients from TCMs, 14 hepatotoxic ingredients were all accurately identified by the QSAR model derived from the dataset containing natural hepatotoxins. CONCLUSIONS: Adding natural hepatotoxins into the dataset makes the QSAR model more applicable for TCM hepatotoxicity assessment, which provides a right direction in the methodology study for TCM safety evaluation. The generated QSAR model has the practical value to prioritize the hepatotoxicity risk of TCM compounds. Furthermore, an open-access international specialized database on TCM hepatotoxicity should be quickly established.

Traditional Chinese medicine for the treatment of influenza: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To justify the clinical use of Traditional Chinese Medicine (TCM) in the treatment of influenza. METHODS: MEDLINE, EMBASE, Chinese Biomedical Literature Database, China National Knowledgeln-frastructure Database, China Science and Technology Journal Database, Wanfang Database and the Cochrane Database of Systematic Reviews were searched from the date of inception until January 1, 2013, for the literature on treatment of influenza with TCM. RESULTS: A total of 7 randomized controlled trials were identified and reviewed. Of these trials, 2 compared a (modified) prescription of TCM with oseltacmivir and 5 compared a patent traditional Chinese drug with oseltamivir. Based on the Meta-analysis, compared to oseltamivir, the (modified) prescription had similar effect in defervescence [WMD = 5.66, 95% CI (- 32.02, 43.35), P = 0.77] and viral sheddingWMD = - 6.21, 95% CI (- 84.19, 71.76), P = 0.88], and the patent traditional Chinese drug also had similar effect in viral shedding [WMD = - 0.24, 95% CI (- 4.79, 4.31), P = 0.92] but more effective in defervescence [WMD = - 4.65, 95%CI (- 8.91, - 0.38),P = 0.03]. CONCLUSION: TCM has potential positive effects in the treatment of influenza.

Acute liver failure associated with traditional Chinese medicine: report of 30 cases from seven tertiary hospitals in China*.

OBJECTIVES: Up to now, limited cases with acute liver failure caused by traditional Chinese medicine have been reported, and thus this topic has been scarcely discussed. This study aims to report such cases from China. DESIGN: A retrospective study. SETTING: Clinical investigation among seven tertiary hospitals in different areas of China. PATIENTS: From January 2007 to December 2012, patients with acute liver failure induced by traditional Chinese medicinal herbs were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 30 patients were finally identified, including six men and 24 women. The average age was 39.7 years. The median period from initial symptoms to the development of hepatic encephalopathy was 13 days. Nine patients (30%) had accepted herbal therapies due to their skin disorders before the onset of acute liver failure. Eighteen patients (60%) eventually died, 10 of whom died of heavy bleeding. No patients received liver transplantation. CONCLUSIONS: The model of safety monitoring for traditional Chinese materia medica should be established. For those critically ill patients with herb-induced acute liver failure, coagulopathy is a vital problem in critical care. Additionally, the rate of liver transplantation for acute liver failure in China needs to be improved.

Causes and outcomes of acute liver failure in China.

OBJECTIVES: No extensive investigation has been performed and thus no representative data are available regarding acute liver failure (ALF) in China. This study aims to investigate the causes and outcomes of ALF in China and establish a prognostic model. METHODS: Patients diagnosed as ALF in seven hospitals in different areas of China from January 2007 to December 2012 were retrospectively selected. RESULTS: Of the 177 patients included in this study, 112 (63.28%) eventually died. The common causes of ALF were drug toxicity (43.50%), indeterminate etiology (29.38%) and acute viral hepatitis (11.30%). Additionally, traditional Chinese herbs predominated in the causes of drug-induced ALF (30/77). No patients in this study received liver transplantation. In the established model for predicting death in ALF, four variables were finally selected out, including age (P=0.01), the entry hepatic encephalopathy grade (P=0.04), international normalized ratio (P<0.01) and arterial blood ammonia (P=0.02). Using a threshold value of 0.5683, this model had a sensitivity of 95.24% and a specificity of 91.30%. CONCLUSIONS: Traditional Chinese medicine was a major cause of ALF in China. The spontaneous mortality of ALF was high, whereas the rate of liver transplantation was significantly low. The established prognostic model of ALF had superior sensitivity and specificity.