Hierarchically Periodic Macroporous Niobium Oxide Architecture for Enhanced Hydrogen Evolution.

The fabrication of periodic macroporous (PM) in Nb2O5 via morphological control is crucial for improving the photocatalytic hydrogen evolution efficiency. In this study, Nb2O5 with PM is synthesized using a straightforward colloidal crystal templating approach. This material features an open, interconnected macroporous architecture with nanoscale walls, high crystallinity, and substantial porosity. Extensive characterization reveals that this hierarchically structured Nb2O5 possesses abundant surface active sites and is capable of capturing light effectively, facilitating rapid mass transfer and diffusion of reactants and markedly suppressing the recombination of photoexcited charge carriers. Macroporous Nb2O5 exhibits superior water-splitting hydrogen evolution performance compared with its bulk and commercial counterparts, achieving a hydrogen production rate of 405 µmol g-1 h-1, surpassing that of bulk Nb2O5 (B-Nb2O5) and commercial Nb2O5 (C-Nb2O5) by factors of 5 and 33, respectively. This study proposes an innovative strategy for the design of hierarchically structured PM, thereby significantly advancing the hydrogen evolution potential of Nb2O5.

Copper is required for oncogenic BRAF signalling and tumorigenesis.

The BRAF kinase is mutated, typically Val 600→Glu (V600E), to induce an active oncogenic state in a large fraction of melanomas, thyroid cancers, hairy cell leukaemias and, to a smaller extent, a wide spectrum of other cancers. BRAF(V600E) phosphorylates and activates the MEK1 and MEK2 kinases, which in turn phosphorylate and activate the ERK1 and ERK2 kinases, stimulating the mitogen-activated protein kinase (MAPK) pathway to promote cancer. Targeting MEK1/2 is proving to be an important therapeutic strategy, given that a MEK1/2 inhibitor provides a survival advantage in metastatic melanoma, an effect that is increased when administered together with a BRAF(V600E) inhibitor. We previously found that copper (Cu) influx enhances MEK1 phosphorylation of ERK1/2 through a Cu-MEK1 interaction. Here we show decreasing the levels of CTR1 (Cu transporter 1), or mutations in MEK1 that disrupt Cu binding, decreased BRAF(V600E)-driven signalling and tumorigenesis in mice and human cell settings. Conversely, a MEK1-MEK5 chimaera that phosphorylated ERK1/2 independently of Cu or an active ERK2 restored the tumour growth of murine cells lacking Ctr1. Cu chelators used in the treatment of Wilson disease decreased tumour growth of human or murine cells transformed by BRAF(V600E) or engineered to be resistant to BRAF inhibition. Taken together, these results suggest that Cu-chelation therapy could be repurposed to treat cancers containing the BRAF(V600E) mutation.

Machine Learning for Prioritization of Thermostabilizing Mutations for G-Protein Coupled Receptors.

Although the three-dimensional structures of G-protein coupled receptors (GPCRs), the largest superfamily of drug targets, have enabled structure-based drug design, there are no structures available for 87% of GPCRs. This is due to the stiff challenge in purifying the inherently flexible GPCRs. Identifying thermostabilized mutant GPCRs via systematic alanine scanning mutations has been a successful strategy in stabilizing GPCRs, but it remains a daunting task for each GPCR. We developed a computational method that combines sequence-, structure-, and dynamics-based molecular properties of GPCRs that recapitulate GPCR stability, with four different machine learning methods to predict thermostable mutations ahead of experiments. This method has been trained on thermostability data for 1231 mutants, the largest publicly available data set. A blind prediction for thermostable mutations of the complement factor C5a receptor 1 retrieved 36% of the thermostable mutants in the top 50 prioritized mutants compared to 3% in the first 50 attempts using systematic alanine scanning.

[Relationship Between Urban Spatial Pattern and Thermal Environment Response in Summer: A Case Study of Hefei City].

With the continuous expansion of cities, the land cover type of the region is transformed, a large number of natural landscapes are replaced by man-made landscapes, and the environmental temperature rises. The study of the response relationship between urban spatial pattern and thermal environment provides some guidance for improving the ecological environment and optimizing the urban spatial layout. Based on the Landsat 8 series remote sensing image data of Hefei City in 2020 and analysis platforms such as ENVI and ARCGIS, Pearson correlation and profile lines were used to reflect the correlation between the two. Then, the three spatial pattern components with the greatest correlation were selected to construct multiple regression functions to investigate the influence of urban spatial pattern on urban thermal environment and its mechanism of action. The results showed that:① the high temperature area of Hefei City increased significantly with the advance of time during 2013-2020. For different seasons, the urban heat island effect showed that summer>autumn>spring>winter. ② In the central urban area, the building occupancy, building height, imperviousness occupancy, and population density were significantly higher than those in the suburbs, whereas fractional vegetation coverage presented a higher suburban than urban area and mainly showed a point distribution in the urban area and an irregular distribution of water bodies. ③ The urban high-temperature zone was mainly distributed in various development zones in urban areas, whereas other places in urban areas were dominated by medium-high temperature and above-temperature zoning, and suburban areas were dominated by medium-low temperature. ④ The Pearson coefficients between the spatial pattern of each element and the thermal environment were positively correlated with the building occupancy (0.395), impervious surface occupancy (0.333), population density (0.481), and building height (0.188) and negatively correlated with fractional vegetation coverage (-0.577) and water occupancy (-0.384). The coefficients of the constructed multiple regression functions, including building occupancy, population density, and fractional vegetation coverage, were 8.372, 0.295, and -5.639 respectively, with a constant of 38.555. The results of this study can provide a reference basis for optimizing urban spatial layouts and improving urban living quality.

Research disciplinary interactions on scientific collaboration network in photocatalytic hydrogen evolution: Characteristics and dynamics.

Interdisciplinary scientific collaboration promotes the innovative development of scientific research. Photocatalytic hydrogen evolution (PHE) is a typical interdisciplinary subject. This study aims to explore the characteristics of discipline interaction and the temporal evolution in the field. Bibliometric analysis could be used to understand the stage of research in a particular subject. In this work, the publications on the topic in Web of Science (WoS) platform from 1999 to 2020 were selected. On the basis of social network theory, the characteristics of interdisciplinary were revealed from three perspectives. First, the disciplinary interaction network is constructed through disciplinary co-occurrence to detect the characteristics of interaction structure among different disciplines. Then the node centrality index is employed to explore the influence of disciplines in the interactive network by using network centrality analysis. Moreover, the dynamic of discipline interaction evolution is studied using blockmodeling analysis. In the field of PHE, the number of disciplines and the intensity of interaction among different subjects gradually increased in the past 20 years. Chemistry and Material Sciences are the core discipline, and they play an important role in the network. The whole network is divided into different discipline groups. The scale of the discipline group is becoming large, and the disciplinary interaction is becoming more complex. The obtained results are helpful for guiding scholars to carry out interdisciplinary interaction. The methods of detecting interdisciplinary interactive relationship could provide paths for interdisciplinary research in other fields.

Dynamic monitoring and analysis of factors influencing ecological environment quality in northern Anhui, China, based on the Google Earth Engine.

Monitoring the ecological environment quality is an important task that is often connected to achieving sustainable development. Timely and accurate monitoring can provide a scientific basis for regional land use planning and environmental protection. Based on the Google Earth Engine platform coupled with the greenness, humidity, heat, and dryness identified in remote sensing imagery, this paper constructed a remote sensing ecological index (RSEI) covering northern Anhui and quantitatively analyzed the characteristics of the spatiotemporal changes in the ecological environment quality from 2001 to 2020. Geodetector software was used to explore the mechanism driving the characteristics of spatial differentiation in the ecological environment quality. The main conclusions were as follows. First, the ecological environment quality in northern Anhui declined rapidly from 2001 to 2005, but the rate of decline slowed from 2005 to 2020 and a trend of improvement gradually emerged. The ecological environment quality of Huainan from 2001 to 2020 was better and more stable compared with other regional cities. Bengbu and Suzhou showed a trend of initially declining and then improving. Huaibei, Fuyang, and Bozhou demonstrated a trend of a fluctuating decline over time. Second, vegetation coverage was the main influencing factor of the RSEI, while rainfall was a secondary factor in northern Anhui from 2001 to 2020. Finally, interactions were observed between the factors, and the explanatory power of these factors increased significantly after the interaction. The most apparent interaction was between vegetation coverage and rainfall (q = 0.404). In addition, we found that vegetation abundance had a positive impact on ecological environment quality, while population density and urbanization had negative impacts, and the ecological environment quality of wetlands was the highest. Our research will provide a theoretical basis for environmental protection and support the high-quality development of northern Anhui.

Distribution of SOCD along different offshore distances in China's fresh-water lake-Chaohu under different habitats.

Carbon storage in wetland ecosystems is an important part of the carbon cycle of terrestrial ecosystems and provides important ecosystem services. Chaohu Wetland is a typical freshwater lake wetland in China. In this study, soil and plant samples were collected every 500 m through three sample lines of different vegetation habitats (estuarine banks, woodlands and shrub beaches) and different offshore distances, revealing the spatial distribution characteristics of soil organic carbon density (SOCD) in Chaohu wetland. The overall SOCD of Chaohu wetland was low, with different habitats ranking as Woodland > Estuary and riverside > Shrub and beach. SOCD of different offshore distances had no obvious law, and the SOCD decreased significantly with soil depth. The plant biomass was significantly higher at the woodland habitat than at other habitats. Most of soil nutrient indicators were the highest at the woodland habitat, while the estuary-riverside habitat had the highest N and P contents. Soil and plant nutrients at different offshore distances had no obvious change patterns. The contents of soil K, Ca, Mg, and N were significantly positively correlated with SOCD, but soil bulk density and pH were significantly negatively correlated with SOCD, and vegetation P content was significantly negatively correlated with SOCD. The spatial pattern of SOCD changes in this lake coastal wetland was determined by the combined effects of plant nutrients, biomass, and soil physical and chemical properties. Our results indicate Chaohu wetlands may have been experiencing serious degradation. The SOCD of Chaohu wetland is lower than that of other wetlands in China, which is mainly affected by human activities. Different offshore distances and habitat heterogeneity are the main factors affecting the soil carbon cycle of the wetland.

Acupuncture Reduces the Risk of Dysphagia in Stroke Patients: A Propensity Score-Matched Cohort Study.

Background: Post-stroke dysphagia (PSD) affects the quality of life in stroke patients, impairs their rehabilitation ability, and causes other complications following stroke. Currently, there is currently some understanding of PSD risk factors, but its protective factors remain largely unknown. Objective: To analyze the effects of acupuncture (AP) on dysphagia in stroke patients and explore its potential as a preventive therapy. Methods: Patients with a diagnosis of stroke from 2010 to 2019 were selected and followed until 2020, utilizing factors such as age, gender, stroke location, stroke type, and baseline comorbidity. To compare the incidence of dysphagia, equal numbers of stroke patients treated with and without AP (n = 1,809) were matched by 1:1 propensity scoring. The Cox proportional hazards model and Kaplan-Meier method were used to assess the risk of dysphagia as an outcome measure. Results: The stroke patients treated with AP had a lower risk of dysphagia after adjusting for age, gender, stroke location, stroke type, and baseline comorbidity [adjusted hazard ratio (AHR) = 0.43, 95% confidence interval = 0.37-0.49] compared with those in the non-AP cohort. AP also decreased the risk of PSD among different gender groups. The risk ratios were AHR = 0.45 and AHR = 0.33 for males and females, respectively. AP also reduced the risk for PSD among different age groups. The risk ratios were AHR = 0.20, AHR = 0.37, AHR = 0.41, and AHR = 0.45 for the 18-39, 40-59, 60-79, and >80 years-old groups. Regarding stroke types (ischemic, hemorrhagic, and mixed type), patients treated with AP had a lower risk (AHR = 0.47, 0.28 and 0.17, respectively). With respect to stroke location, the risk of PSD in AP-treated patients was decreased regardless of location: brain stem (AHR = 0.41), diencephalon (AHR = 0.13), or multiple lesions (AHR = 0.40), the risk of PSD in AP-treated patients was decreased. For all baseline comorbidities, AP attenuated the risk of dysphagia. The cumulative incidence of dysphagia was remarkably lower in the AP group than in the non-AP group (log-rank test, P = 0.000). Limitations: First, this was a single-center clinical retrospective study. Second, we did not classify the severity of stroke and dysphagia. Third, all data were extracted manually. Lastly, the sample size was relatively small. Thus, future studies with larger sample sizes are warranted to verify our findings. Conclusion: Acupuncture treatment attenuates the risk of dysphagia in stroke patients. Future research should increase the sample size and elaborate further on the details of the AP protocol.

Multiple sugar binding sites in alpha-glucosidase.

Twenty-five analogs of D-glucose were examined as reversible inhibitors of yeast alpha-glucosidase (EC 3.2.1.20). The K(i) values range from 0.38 mM for 6-deoxy-D-glucose (quinovose) to 1.0 M for D-lyxose at pH=6.3 (0.1 M NaCl, 25 degrees ). All the monosaccharides and the three disaccharides (maltose, isomaltose and alpha,alpha-trehalose) were found to be linear competitive inhibitors with respect to alpha-p-nitrophenyl glucoside (pNPG) hydrolysis. Multiple inhibition analysis reveals that there are at least three monosaccharide binding sites on the enzyme. One of these can be occupied by glucose [K(i)=1.8(+/-0.1) mM], one by D-galactose [K(i)=164(+/-11) mM] and one by D-mannose [K(i)=120(+/-9) mM]. The pH dependence for glucose binding closely follows that of V/K [pK(a1)=5.55(+/-0.15), pK(a2)=6.79(+/-0.15)], but the binding of mannose does not. Although the glucose subsite can be occupied simultaneously with the mannose or galactose subsites in the enzyme-product complex, no transglucosylation can be detected between pNPG and either mannose or galactose. This suggests that neither of these nonglucose subsites can be occupied in a productive manner in the covalent glucosyl-enzyme intermediate.

Solvent isotope effects on alpha-glucosidase.

The solvent kinetic isotope effects (SKIE) on the yeast alpha-glucosidase-catalyzed hydrolysis of p-nitrophenyl and methyl-d-glucopyranoside were measured at 25 degrees C. With p-nitrophenyl-D-glucopyranoside (pNPG), the dependence of k(cat)/K(m) on pH (pD) revealed an unusually large (for glycohydrolases) solvent isotope effect on the pL-independent second-order rate constant, (DOD)(k(cat)/K(m)), of 1.9 (+/-0.3). The two pK(a)s characterizing the pH profile were increased in D(2)O. The shift in pK(a2) of 0.6 units is typical of acids of comparable acidity (pK(a)=6.5), but the increase in pK(a1) (=5.7) of 0.1 unit in going from H(2)O to D(2)O is unusually small. The initial velocities show substrate inhibition (K(is)/K(m) approximately 200) with a small solvent isotope effect on the inhibition constant [(DOD)K(is)=1.1 (+/-0.2)]. The solvent equilibrium isotope effects on the K(is) for the competitive inhibitors D-glucose and alpha-methyl D-glucoside are somewhat higher [(DOD)K(i)=1.5 (+/-0.1)]. Methyl glucoside is much less reactive than pNPG, with k(cat) 230 times lower and k(cat)/K(m) 5 x 10(4) times lower. The solvent isotope effect on k(cat) for this substrate [=1.11 (+/-0. 02)] is lower than that for pNPG [=1.67 (+/-0.07)], consistent with more extensive proton transfer in the transition state for the deglucosylation step than for the glucosylation step.

GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function.

The beta2-adrenergic receptor (beta2AR) is a well-studied prototype for heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) that respond to diffusible hormones and neurotransmitters. To overcome the structural flexibility of the beta2AR and to facilitate its crystallization, we engineered a beta2AR fusion protein in which T4 lysozyme (T4L) replaces most of the third intracellular loop of the GPCR ("beta2AR-T4L") and showed that this protein retains near-native pharmacologic properties. Analysis of adrenergic receptor ligand-binding mutants within the context of the reported high-resolution structure of beta2AR-T4L provides insights into inverse-agonist binding and the structural changes required to accommodate catecholamine agonists. Amino acids known to regulate receptor function are linked through packing interactions and a network of hydrogen bonds, suggesting a conformational pathway from the ligand-binding pocket to regions that interact with G proteins.

A monoclonal antibody for G protein-coupled receptor crystallography.

G protein-coupled receptors (GPCRs) constitute the largest family of signaling proteins in mammals, mediating responses to hormones, neurotransmitters, and senses of sight, smell and taste. Mechanistic insight into GPCR signal transduction is limited by a paucity of high-resolution structural information. We describe the generation of a monoclonal antibody that recognizes the third intracellular loop (IL3) of the native human beta(2) adrenergic (beta(2)AR) receptor; this antibody was critical for acquiring diffraction-quality crystals.

Coupling ligand structure to specific conformational switches in the beta2-adrenoceptor.

G protein-coupled receptors (GPCRs) regulate a wide variety of physiological functions in response to structurally diverse ligands ranging from cations and small organic molecules to peptides and glycoproteins. For many GPCRs, structurally related ligands can have diverse efficacy profiles. To investigate the process of ligand binding and activation, we used fluorescence spectroscopy to study the ability of ligands having different efficacies to induce a specific conformational change in the human beta2-adrenoceptor (beta2-AR). The 'ionic lock' is a molecular switch found in rhodopsin-family GPCRs that has been proposed to link the cytoplasmic ends of transmembrane domains 3 and 6 in the inactive state. We found that most partial agonists were as effective as full agonists in disrupting the ionic lock. Our results show that disruption of this important molecular switch is necessary, but not sufficient, for full activation of the beta2-AR.

A fluorescent probe designed for studying protein conformational change.

The usefulness of fluorescence in studying protein motions derives from its sensitivity, kinetic resolution, and compatibility with both live cells and physiological assays. Recent advances in microscopy and membrane protein purification have permitted the observation of fluorescence changes that accompany the functional transitions of complex eukaryotic membrane proteins. These techniques rely on probes that can clearly report the environmental changes of specific residues, but most commonly available side-chain-reactive probes are not well suited for this purpose. Here, we introduce a red Cys-reactive probe, aminophenoxazone maleimide (APM), designed with improved chemical and spectral properties for reporting protein conformational change. APM is compact, uncharged, and has a short linker between probe and protein, all of which ensure that it can closely track the motions of the side chain to which it is attached. It undergoes large polarity-dependent changes in Stokes shift, as well as large bathochromic shifts in both excitation maximum (from 521 nm in toluene to 598 nm in water) and emission maximum (580 nm to 633 nm). These polarity-dependent spectral changes offer a potentially simple means of relating fluorescence to local structure and motion, although they are partially offset by some complicating factors in APM fluorescence. We find that, like a rhodamine maleimide, APM senses the conformational changes underlying voltage sensing in the Shaker potassium channel, and it is superior at a site that shows limited reactivity to the rhodamine. The spectral characteristics of APM can also report subtle differences between aqueous positions in purified preparations of the beta2 adrenergic receptor.