A layerlike MOF (MIL-124, orGa2(OH)4(C9O6H4)) has been prepared and chosen as a parent compound to encapsulate Eu(3+) cations by one uncoordinated carbonyl group in its pores. The Eu(3+)-incorporated ...sample (Eu(3+)@MIL-124) is fully characterized, which shows excellent luminescence and good fluorescence stability in water or other organic solvents. Subsequently, we choose Eu(3+)@MIL-124 as sensitive probe for sensing metal ions, anions, and organic small molecules because of its robust framework. Studying of the luminescence properties reveals that the complex Eu(3+)@MIL-124 was developed as a highly selective and sensitive probe for detection of Fe(3+) (detection limit, 0.28 μM) and Fe(2+) ions through fluorescence quenching of Eu(3+) and MOF over other metal ions. In connection to this, a probable sensing mechanism was also discussed in this paper. In addition, when Eu(3+)@MIL-124 was immersed in the different anions solutions and organic solvents, it also shows highly selective for Cr2O7(2-)(detection limit, 0.15 μM)and acetone. Remarkably, it is the first Eu-doped MOF to exhibit an excellent ability for the detection of Fe(3+) and Fe(2+) in an aqueous environment without any structural disintegration of the framework.
A novel copper‐catalyzed regiodivergent alkylboration of alkenes with bis(pinacolato)diboron and alkyl halides has been developed. The regioselectivity of the alkylboration was controlled by subtle ...differences in the ligand structure. The reaction thus enables the practical, regiodivergent synthesis of two different alkyl boronic esters with complex structures from a single alkene.
One way or another: The copper‐catalyzed regiodivergent alkylboration of alkenes with bis(pinacolato)diboron and alkyl halides is described. The regioselectivity of the carboboration can be controlled by fine‐tuning the ligand structure.
Metabolic diseases are serious threats to public health and related to gut microbiota. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are powerful regulators of gut microbiota, thus ...possessing prospects for preventing metabolic diseases. Therefore, the effects and mechanisms of PPSP on metabolic diseases targeting gut microbiota are worth discussing and clarifying. Generally, PPSP benefit metabolic diseases management, especially obesity and type 2 diabetes mellitus. The underlying gut microbial-related mechanisms are mainly the modulation of gut microbiota composition, regulation of gut microbial metabolites, and improvement of intestinal barrier function. Moreover, clinical trials showed the benefits of PPSP on patients with metabolic diseases, while the clinical strategies for gestational diabetes mellitus, optimal formula of synbiotics and health benefits of postbiotics need further study. This review fully summarizes the relationship between probiotics, prebiotics, synbiotics, postbiotics, and metabolic diseases, presents promising results and the one in dispute, and especially attention is paid to illustrates potential mechanisms and clinical effects, which could contribute to the next research and development of PPSP.
Recent events across many regions around the world have shown that short-term droughts (i.e., daily or weekly) with sudden occurrence can lead to huge losses to a wide array of environmental and ...societal sectors. However, the most commonly used drought indices can only identify drought at the monthly scale. Here, we introduced a daily scale drought index, that is, the standardized antecedent precipitation evapotranspiration index (SAPEI) that utilizes precipitation and potential evapotranspiration and also considers the effect of early water balance on dry/wet conditions on the current day. The robustness of SAPEI is first assessed through comparison with two typical monthly indices Palmer drought severity index (PDSI) and standardized precipitation evapotranspiration index (SPEI) and soil moisture, and then applied to tracking short-term droughts during 1961–2015 for the Pearl River basin in south China. It is demonstrated that SAPEI performs as well as SPEI/self-calibrating PDSI at the monthly scale but outperforms SPEI at the weekly scale. Moreover, SAPEI is capable of revealing daily drought conditions, fairly consistent with soil moisture changes. Results also show that many of the historical short-term droughts over the Pearl River basin have multiple peaks in terms of severity, affected area, and intensity. The daily scale SAPEI provides an effective way of exploring drought initiation, development, and decay, which could be conducive for decision-makers and stakeholders to make early and timely warnings.
Sunitinib resistance is a major challenge for advanced renal cell carcinoma (RCC). Understanding the underlying mechanisms and developing effective strategies against sunitinib resistance are highly ...desired in the clinic. Here we identified an lncRNA, named lncARSR (lncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response. Therefore, lncARSR may serve as a predictor and a potential therapeutic target for sunitinib resistance.
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•lncARSR promotes sunitinib resistance and predicts poor response of RCC patients•Intercellular transfer of lncARSR by exosomes disseminates sunitinib resistance•lncARSR acts as a ceRNA for miR-34 and miR-449 to promote AXL and c-MET expression•Targeting lncARSR or AXL/c-MET in sunitinib-resistant RCC restores drug sensitivity
Qu et al. identify lncARSR as a mediator of sunitinib resistance in renal cell carcinoma by acting as a competing endogenous RNA for miR-34 and miR-449, thereby increasing expression of their targets AXL and c-MET, and show that exosome-mediated transmission of lncARSR can confer resistance to sensitive cells.
To investigate the clinical and imaging characteristics of computed tomography (CT) in novel coronavirus pneumonia (NCP) caused by SARS-CoV-2.
A retrospective analysis was performed on the imaging ...findings of patients confirmed with COVID-19 pneumonia who had chest CT scanning and treatment after disease onset. The clinical and imaging data were analyzed.
Fifty patients were enrolled, including mild type in nine, common in 28, severe in 10 and critically severe in the rest three. Mild patients (29 years) were significantly (P<0.03) younger than either common (44.5 years) or severe (54.7) and critically severe (65.7 years) patients, and common patients were also significantly (P<0.03) younger than severe and critically severe patients. Mild patients had low to moderate fever (<39.1 °C), 49 (98%) patients had normal or slightly reduced leukocyte count, 14 (28%) had decreased counts of lymphocytes, and 26 (52%) patients had increased C-reactive protein. Nine mild patients were negative in CT imaging. For all the other types of NCP, the lesion was in the right upper lobe in 30 cases, right middle lobe in 22, right lower lobe in 39, left upper lobe in 33 and left lower lobe in 36. The lesion was primarily located in the peripheral area under the pleura with possible extension towards the pulmonary hilum. Symmetrical lesions were seen in 26 cases and asymmetrical in 15. The density of lesion was mostly uneven with ground glass opacity as the primary presentation accompanied by partial consolidation and fibrosis.
CT imaging presentations of NCP are mostly patchy ground glass opacities in the peripheral areas under the pleura with partial consolidation which will be absorbed with formation of fibrotic stripes if improved. CT scanning provides important bases for early diagnosis and treatment of NCP.
Climate change and human activities are two major driving forces affecting the hydrologic cycle, which further influence the stationarity of the hydrologic regime. Hydrological drought is a ...substantial negative deviation from the normal hydrologic conditions affected by these two phenomena. In this study, we propose a framework for quantifying the effects of climate change and human activities on hydrological drought. First, trend analysis and change‐point test are performed to determine variations of hydrological variables. After that, the fixed runoff threshold level method (TLM) and the standardized runoff index (SRI) are used to verify whether the traditional assessment methods for hydrological drought are applicable in a changing environment. Finally, two improved drought assessment methods, the variable TLM and the SRI based on parameter transplantation are employed to quantify the impacts of climate change and human activities on hydrological drought based on the reconstructed natural runoff series obtained using the variable infiltration capacity hydrologic model. The results of a case study on the typical semiarid Laohahe basin in North China show that the stationarity of the hydrological processes in the basin is destroyed by human activities (an obvious change‐point for runoff series is identified in 1979). The traditional hydrological drought assessment methods can no longer be applied to the period of 1980–2015. In contrast, the proposed separation framework is able to quantify the contributions of climate change and human activities to hydrological drought during the above period. Their ranges of contributions to hydrological drought calculated by the variable TLM method are 20.6–41.2% and 58.8–79.4%, and the results determined by the SRI based on parameter transplantation method are 15.3–45.3% and 54.7–84.7%, respectively. It is concluded that human activities have a dominant effect on hydrological drought in the study region. The novelty of the study is twofold. First, the proposed method is demonstrated to be efficient in quantifying the effects of climate change and human activities on hydrological drought. Second, the findings of this study can be used for hydrological drought assessment and water resource management in water‐stressed regions under nonstationary conditions.
Age‐associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation ...leads to the redistribution of fat to the intra‐abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β‐oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro‐inflammatory cytokines. In turn, these muscle‐secreted cytokines may exacerbate adipose tissue atrophy, support chronic low‐grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full‐blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the ‘obesity paradox’, could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full‐blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.
Abstract
Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory ...diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.
By taking advantage of facile preparation and sensitive recognition capacity, the first example of a fluorescence system based on Eu(III) functionalized UiO(bpdc) (UMOFs) has been constructed for ...effective combination of ions recognition and logic computing. All the ions, including Hg2+, Ag+, and S2− in the system are water harmful, which can be recognized through affecting energy transfer or framework structure. By the self‐assembling, competing and connecting with each other, Eu(III)@UMOFs and the ions have achieved the implementation of Boolean logic network system connecting the elementary logic operations (NOR, INH, and IMP) and integrative logic operation (OR + INH), also obtaining computing keypad‐lock security system by sequential logic operation. To deal with uncertain information in the analog region of nonlinear response (fluorescence and concentration), soft computation through the formulation of fuzzy logic operation has been constructed. On the basis of Boolean logic and fuzzy logic, one intelligent molecular searcher can be realized by taking chemical events (Hg2+, Ag+, and S2−) as programmable words and chemical interactions as syntax. Considering the particularity of all the input ions, the approach is helpful in developing the advanced logic program based on Eu(III)@UMOFs for application in environmental monitoring.
By combining ion recognition and logic computing (Boolean and fuzzy), an intelligent molecular searcher for polluting ions (Hg2+, Ag+, and S2−) in water has been constructed based on fluorescence Eu(III) functionalized UiO(bpdc) system and the molecular searcher is helpful in developing the advanced logic program for application in environmental monitoring.
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