Nanobodies as negative allosteric modulators for human calcium sensing receptor.

Human calcium sensing receptor (CaSR) senses calcium ion concentrations in vivo and is an important class of drug targets. Mutations in the receptor can lead to disorders of calcium homeostasis, including hypercalcemia and hypocalcemia. Here, 127 CaSR-targeted nanobodies were generated from camels, and four nanobodies with inhibitory function were further identified. Among these nanobodies, NB32 can effectively inhibit the mobilization of intracellular calcium ions (Ca2+i) and suppress the G12/13 and ERK1/2 signaling pathways downstream of CaSR. Moreover, it enhanced the inhibitory effect of the calcilytics as a negative allosteric modulator (NAM). We determined the structure of complex and found NB32 bound to LB2 (Ligand-binding 2) domain of CaSR to prevent the interaction of LB2 domains of two protomers to stabilize the inactive state of CaSR.

Tungsten-Iron-Ruthenium Ternary Alloy Immobilized into the Inner Nickel Foam for High-Current-Density Water Oxidation.

The pursuit of highly-active and stable catalysts in anodic oxygen evolution reaction (OER) is desirable for high-current-density water electrolysis toward industrial hydrogen production. Herein, a straightforward yet feasible method to prepare WFeRu ternary alloying catalyst on nickel foam is demonstrated, whereby the foreign W, Fe, and Ru metal atoms diffuse into the Ni foam resulting in the formation of inner immobilized ternary alloy. Thanks to the synergistic impact of foreign metal atoms and structural robustness of inner immobilized alloying catalyst, the well-designed WFeRu@NF self-standing anode exhibits superior OER activities. It only requires overpotentials of 245 and 346 mV to attain current densities of 20 and 500 mA cm-2, respectively. Moreover, the as-prepared ternary alloying catalyst also exhibits a long-term stability at a high-current-density of 500 mA cm-2 for over 45 h, evidencing the inner-immobilization strategy is promising for the development of highly active and stable metal-based catalysts for high-density-current water oxidation process.

Pt-functionalized Amorphous RuOx as Excellent Stability and High-activity Catalysts for Low Temperature MEMS Sensors.

The unsaturated coordination and abundant active sites endow amorphous metals with tremendous potential in improving metal oxide semiconductors' gas-sensing properties. However, the amorphous materials maintain the metastable status and easily transfer into the lower-active crystals during the gas-sensing process at high working temperatures, significantly limiting their further applications. Here, a bimetal amorphous PtRu catalyst is developed by accurately regulating the introduction of Pt species into amorphous RuOx supports to realize the highly active and stable H2 S gas-sensing detection. It is found that incorporation of low-concentration Pt species can effectively maintain the amorphous state of initial RuOx and delay the crystallization temperature as high as 100 °C. Further, ex situ XPS and in situ Raman spectroscopy analysis confirm that active Pt species can facilitate H2 S adsorption by strong Pt-S coordination and dissociate the sulfur species to the surrounding support, which contribute to the chemisorption and sensitization of H2 S. Meanwhile, electron transport at the interface between Pt, RuOx and ZnO further activates the reaction process at the surface of the gas-sensitive material. The final PtRu-modified ZnO (PtRu/ZnO) sensor enables the detection of H2 S in the ultra-low concentration range of 15-2000 ppb with remarkable stability.

Kinetics-Driven Dual Hydrogen Spillover Effects for Ultrasensitive Hydrogen Sensing.

Palladium (Pd)-modified metal oxide semiconductors (MOSs) gas sensors often exhibit unexpected hydrogen (H2 ) sensing activity through a spillover effect. However, sluggish kinetics over a limited Pd-MOS surface seriously restrict the sensing process. Here, a hollow Pd-NiO/SnO2 buffered nanocavity is engineered to kinetically drive the H2 spillover over dual yolk-shell surface for the ultrasensitive H2 sensing. This unique nanocavity is found and can induce more H2 absorption and markedly improve kinetical H2 ab/desorption rates. Meanwhile, the limited buffer-room allows the H2 molecules to adequately spillover in the inside-layer surface and thus realize dual H2 spillover effect. Ex situ XPS, in situ Raman, and density functional theory (DFT) analysis further confirm that the Pd species can effectively combine H2 to form Pd-H bonds and then dissociate the hydrogen species to NiO/SnO2 surface. The final Pd-NiO/SnO2 sensors exhibit an ultrasensitive response (0.1-1000 ppm H2 ) and low actual detection limit (100 ppb) at the operating temperature of 230 °C, which surpass that of most reported H2 sensors.

Preparation of MOF-derived ZnO/Co3O4 nanocages and their sensing performance toward H2S.

We report a type of micro-electro-mechanical system (MEMS) H2S gas sensors with excellent sensing performance at the ppb level (lowest detection limit is 5 ppb). The sensors were fabricated with ZnO/Co3O4 sensing materials derived from Zn/Co-MOFs by annealing at a suitable temperature of 500 °C. ZnO/Co3O4-500 exhibits the highest response when exposed to 10 ppb H2S gas at 120 °C, and the response/recovery times are 10 s/21 s. Moreover, it exhibits outstanding selectivity, long-term stability (retained 95% response after 45 days), and moisture resistance (only a minor fluctuation of 2% even at 90% RH). This can be ascribed to the fact that ZnO/Co3O4-500 has regular morphology, abundant oxygen vacancies (52.8%) and high specific surface area (96.5 m2 g-1). This work provides not only a high performance H2S MEMS gas sensor but also a systematic study of the effect of the annealing temperature on the sensing performance of ZnO/Co3O4 sensing materials derived from bimetal organic frameworks.

The effects of palliative care on patients with different classes heart function: A pilot study.

The aim of this study was to explore effects of palliative care (PC) on patients with different heart function. Patients with NYHA (New York Heart Association) class II, III, IV were divided into separate groups. The KCCQ (Kansas City Cardiomyopathy Questionnaire) and HADS (Hospital Anxiety and Depression Scale) scores were compared before and 3 months after PC intervention. After 3 months, compared with the control group, PC could further significantly improve the KCCQ, HADS-depression and -anxiety scores of patients in NYHA class IV (P < 0.05); PC could significantly improve the HADS-depression and -anxiety scores of patients with NYHA class III (P < 0.05), and had an improvement tendency on KCCQ score. The study revealed that PC can significantly improve anxiety and depression of patients with NYHA class III or IV, and significantly improve the quality of life of patients with NYHA class IV, but had no effects on patients with NYHA class II.

A Stress Self-Adaptive Structure to Suppress the Chemo-mechanical Degradation for High Rate and Ultralong Cycle Life Sodium Ion Batteries.

Transition-metal phosphides (TMPs) as typical conversion-type anode materials demonstrate extraordinary theoretical charge storage capacity for sodium ion batteries, but the unavoidable volume expansion and irreversible capacity loss upon cycling represent their long-standing limitations. Herein we report a stress self-adaptive structure with ultrafine FeP nanodots embedded in dense carbon microplates skeleton (FeP@CMS) via the spatial confinement of carbon quantum dots (CQDs). Such an architecture delivers a record high specific capacity (778 mAh g-1 at 0.05 A g-1 ) and ultra-long cycle stability (87.6 % capacity retention after 10 000 cycles at 20 A g-1 ), which outperform the state-of-the-art literature. We decode the fundamental reasons for this unprecedented performance, that such an architecture allows the spontaneous stress transfer from FeP nanodots to the surrounding carbon matrix, thus overcomes the intrinsic chemo-mechanical degradation of metal phosphides.

Highly Selective Chloromethanes Detection Based on Quartz Crystal Microbalance Gas Sensors with Ba-MOFs.

Three new metal-organic frameworks (MOFs), {(CH3NH3)3[Ba2(TTHA)(NO3)(H2O)2]}·2H2O (1), {(CH3NH3)4[Ba3(HTTHA)2(H2O)7]}·3H2O (2), and [Ba7(TTHA)2(NO3)2(H2O)10]·2H2O (3) (H6TTHA = 1,3,5-triazine-2,4,6-triamineh-exaacetic acid) have been synthesized and characterized. The sensing properties of 1-3 were explored with regard to volatile organic compounds (VOCs) by the quartz crystal microbalance (QCM) technique. The results indicated that 1 and 2 have a much higher selectivity and response to chloromethanes (CH2Cl2, CHCl3, and CCl4) compared with H2O, CH3OH, CH3CH2OH, CH3CN, (CH3)2CO, C6H6, C6H5CH3, C6H5CH2CH3, and C6H5Cl at room temperature. Furthermore, 1 and 2 sensing film also exhibits excellent reversibility and stability, and the response and recovery times are almost within 10 s. 3 displays a lower response and poor selectivity to the above VOCs. The significant difference may be caused by their different structural characteristics. The Ba2+ ions are all decacoordinated in 1 and 2, while Ba2+ ions have more open metal sites in 3. So, the high selectivity and response of 1 and 2 may be due to the exchange of coordination water molecules with chloromethanes and possible electrostatic effects between (CH3NH3)+ cations and chloromethanes containing more electronegative Cl atoms. DFT calculation results show that the bond energy of Ba-Cl and Ba-O is not much different, so chloromethanes at high concentrations may exchange coordination water to form weak Ba···Cl interactions and show higher response values. 3 has no obvious VOCs selectivity and higher response due to more open sites of Ba2+ ions and smaller pore size. This work develops a fast and effective method to detect chloromethanes, providing a new opportunity for designing QCM gas sensors coated with different MOF materials.

A retrospective analysis of clinical efficacy of ribavirin in adults hospitalized with severe COVID-19.

INTRODUCTION: Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. METHODS: A total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. RESULTS: 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63-1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. CONCLUSIONS: In hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.

Controllable preparation of ultrathin MXene nanosheets and their excellent QCM humidity sensing properties enhanced by fluoride doping.

A 2D ultrathin MXene nanosheet was prepared under controlled conditions and employed as a sensitive film to construct a QCM (quartz crystal microbalance) humidity sensor by a dip coating method. The MXene nanosheets were obtained by dislodging the element A from the MAX phase by a facile liquid phase etching method. The morphology and composition of the MXene nanosheets were characterized by means of a number of advanced instruments. It was found that the sample is an ultrathin graphene-like nanosheet. The sensing test results showed that the sensor has a 12.8 Hz/% RH sensitivity, 6 s and 2 s (@ 90%) response/recovery time, maximum humidity hysteresis of 1.16% RH, good stability, and selectivity. Finally, the enhanced humidity response mechanism of the MXene nanosheets was explored by density-functional theory (DFT) calculation and experimental verification. The DFT simulation together with comparison of fluoride-free sample revealed that F elements on the surface of the MXene nanosheets play a more important role in improving humidity responses than OH groups. The results present a new strategy to enhance humidity sensing performance of sensing materials by F- doping or decoration. Thus, the sensor has bright potential for humidity sensing.

Monodispersed gold nanoparticles entrapped in ordered mesoporous carbon/silica nanocomposites as xanthine oxidase mimic for electrochemical sensing of xanthine.

Monodispersed Au nanoparticles in ordered mesoporous carbon/silica (Au/OMCS) nanocomposites were prepared by the solvent evaporation induced self-assembly. Au/OMCS nanocomposites were characterized through XRD, BET, and TEM. The obtained nanocomposites exhibit uniform mesopores with the size of 18 ± 2 nm. And ultrafine Au nanoparticles with the size of 3~7 nm are well dispersed in the cavities. An ultrasensitive nanoenzyme sensor was fabricated based on a Au/OMCS-modified electrode. The Au/OMCS-modified electrode displays high xanthine oxidase-like catalytic activity evaluated through cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The DPV response currents are linearly dependent on concentrations of xanthine (Xa) in the range 0.10-20 µM, along with a high sensitivity of 6.84 µA µM-1 cm-2 and very low detection limit of 0.006 µM (S/N = 3) under the optimal working potential of 0.64 V vs. SCE. Interference experiments show that the nanoenzyme sensor has no obvious responses to most potentially interfering species at a potential of 0.64 V. The fabricated sensor has been applied to the determination of Xa in spiked urine samples with recoveries ranging from 98.26 to 101.4%. Graphical abstract.

STAT3 rs4796793 contributes to lung cancer risk and clinical outcomes of platinum-based chemotherapy.

BACKGROUND: Signal transducer and activator of transcription (STAT) 3 plays a vital role in carcinogenesis and drug response. Platinum-based chemotherapy is the first-line treatment for lung cancer patients, especially those in advanced stages. In the present study, we investigated the association of STAT3 polymorphism rs4796793 with lung cancer susceptibility, platinum-based chemotherapy response, and toxicity. METHODS: A total of 498 lung cancer patients and 213 healthy controls were enrolled in the study. 467 of them received at least 2-cycle platinum-based chemotherapy. Unconditional logistical regression analysis was used to assess the associations. RESULTS: STAT3 rs4769793 G allele carriers had an increased susceptibility of lung cancer [additive model: adjusted OR (95% CI) 1.376 (1.058-1.789), P = 0.017; recessive model: adjusted OR (95% CI) 1.734 (1.007-2.985), P = 0.047]. Rs4769793 was not significantly associated with platinum-based chemotherapy response in lung cancer patients. STAT3 rs4796793 was associated with an increased risk of severe overall toxicity [additive model: adjusted OR (95% CI) 1.410 (1.076-1.850), P = 0.013; dominant model: adjusted OR (95% CI) 1.638 (1.091-2.459), P = 0.017], especially hematological toxicity [additive model: adjusted OR (95% CI) 1.352 (1.001-1.826), P = 0.049]. CONCLUSIONS: STAT3 rs4796793 may be considered as a potential candidate biomarker for the prediction of susceptibility and prognosis in Chinese lung cancer patients. However, well-designed studies with larger sample sizes are required to verify the results.

Light enhanced room temperature resistive NO2 sensor based on a gold-loaded organic-inorganic hybrid perovskite incorporating tin dioxide.

A material is described for sensing NO2 in the gas phase. It has an architecture of type Au/MASnI3/SnO2 (where MA stands for methylammonium cation) and was fabricated by first synthesizing Au/MASnI3 and then crystallizing SnO2 on the surface by calcination. The physical and NO2 sensing properties of the composite were examined at room temperature without and with UV (365 nm) illumination, and the NO2-sensing mechanism was studied. The characterization demonstrated the formation of a p-n heterojunction structure between p-MASnI3 and n-SnO2. The sensor, best operated at a voltage of 1.1 V at room temperature, displays superior NO2 sensing performance. Figures of merit include (a) high response (Rg/Ra = 240 for 5 ppm NO2; where Rg stands for the resistance of a sensor in test gas, and Ra stands for the resistance of a sensor in air), (b) fast recovery (about 12 s), (c) excellent selectivity compared to sensors based on the use of SnO2 or Au/SnO2 only, both at room temperature under UV illumination; (d) a low detection limit (55 ppb), and (e) a linear response between 0.5 and 10 ppm of NO2. The enhanced sensing performance is mainly attributed to the high light absorption capacity of MASnI3, the easy generation and transfer of photo-induced electrons from MASnI3 to the conduction band of SnO2, and the catalytic effect of gold nanoparticles. Graphical abstract Schematic of the energy band diagrams of the gold-functionalized MASnI3/SnO2 system after equilibrium with UV illumination, by which the enhanced sensing performance for NO2 can be explained.

Facile Chemical Bath Synthesis of SnS Nanosheets and Their Ethanol Sensing Properties.

Tin(II) monosulfide (SnS) nanosheets were synthesized using SnCl4•5H2O and S powders as raw materials in the presence of H2O via a facile chemical bath method. Orthorhombic phase SnS nanosheets with a thickness of ~100 nm and lateral dimensions of 2~10 µm were obtained by controlling the synthesis parameters. The formation of a SnO2 intermediate is key to the valence reduction of Sn ions (from IV to II) and the formation of SnS. The gas sensors fabricated from SnS nanosheets exhibited an excellent response of 14.86 to 100 ppm ethanol vapor when operating at 160 °C, as well as fast response and recovery times of 23 s and 26 s, respectively. The sensors showed excellent selectivity for the detection of ethanol over acetone, methanol, and ammonia gases, which indicates the SnS nanosheets are promising for high-performance ethanol gas sensing applications.

A 3D Calcium Spirobifluorene Metal-Organic Framework: Single-Crystal-to-Single-Crystal Transformation and Toluene Detection by a Quartz Crystal Microbalance Sensor.

A new 3D metal-organic framework Ca-SBF based on a zigzag-shaped tetranuclear calcium oxocluster and 9,9'-spirobi[9H-fluorene]-2,2',7,7'-tetracarboxylic acid was obtained and exhibited flu topology. Ca-SBF underwent a single-crystal-to-single-crystal transformation to form Ca-SBF-1 with a slight structure shrinkage. Activated Ca-SBF showed permanent porosity and CO2 adsorption properties. A Ca-SBF-modified quartz crystal microbalance sensor demonstrated selective response to toluene vapor.

Formation of n-n type heterojunction-based tin organic-inorganic hybrid perovskite composites and their functions in the photocatalytic field.

MASnI3/TiO2 composites (MA represents CH3NH3+) are prepared via a solvothermal method and characterized by various techniques. The results indicate that n-n type heterojunction structures and different ohmic contact interfaces are formed for the composites with different contents of MASnI3 and TiO2 before and after calcination, resulting in different optical and photocatalytic performances. Generally speaking, n-n type heterojunctions play roles in photocatalytic applications through two different mechanisms: the heterojunction mechanism and the Z-type mechanism. The calcined composites with better ohmic contact interfaces mainly follow the Z-type mechanism, which can promote direct radiative recombination of photogenerated carriers. As a result, higher luminous intensities and interface recombination instead of bulk recombination between electrons and holes can be achieved, which improves the photoluminescence and photocatalytic activities of the materials. Moreover, the n-n type heterojunction structure avoids p-type defect states to some degree, which averts the hydrolysis and oxidation of MASnI3 in atmosphere and enhances the long-term stability of the MASnI3/TiO2 composites.

A Case Study on the Influence of Substitutes on Interlayer Stacking of 2D Covalent Organic Frameworks.

Interlayer stacking of 2D covalent organic frameworks (COFs) plays a crucial role in determining not only the geometry of channels inside COFs but also the mobility of carrier transport between COF layers. However, though topological structures of 2D COFs monolayers can be precisely predicted through the structures of building blocks, factors affecting their interlayer stacking remain poorly understood. In this work, a truxene-based building block on which six methyl groups are introduced was designed. The condensation of it with 1,4-diaminobenzene or benzidine afforded 2D COFs with the methyl groups extending out-of-plane of the layers. A significant influence of the methyl groups on interlayer stacking of the COFs was revealed by the adoption of inclined packing of monolayers, which has never been experimentally observed before. This unprecedented stacking manner was confirmed by powder X-ray diffraction analysis, pore-size distribution analysis, and TEM investigation.

Facile synthesis and characterization of a SnO2-modified LiNi0.5Mn1.5O4 high-voltage cathode material with superior electrochemical performance for lithium ion batteries.

A thin-layer-SnO2 modified LiNi0.5Mn1.5O4@SnO2 material is synthesized via a facile synthetic approach. It is physically and electrochemically characterized as a high-voltage lithium ion battery cathode and compared to the pristine LiNi0.5Mn1.5O4 material prepared under similar conditions. The two materials are proved to be crystals of a well-defined disordered spinel phase with the morphology of aggregates of micron/submicron polyhedral particles. The Mn3+ ions and the inactive NixLiyO phase in the LiNi0.5Mn1.5O4@SnO2 is less than those in the LiNi0.5Mn1.5O4 due to incorporation of a very small amount of Sn2+ into the spinel structure upon high-temperature calcination of the precursor. Besides, the mean particle size of the LiNi0.5Mn1.5O4@SnO2 is obviously smaller than that of the LiNi0.5Mn1.5O4. The LiNi0.5Mn1.5O4@SnO2 demonstrates much superior electrochemical performance over the LiNi0.5Mn1.5O4 in terms of specific capacity, rate capability and cyclability. For example, the discharge capacities at current rates of 0.2C, 2C and 20C are 145.4, 139.9 and 112.2 mA h g-1, respectively. A capacity retention rate of ca. 75% is obtained after 500 cycles at 2C rate. The improved electrochemical performance is attributed to the positive effect of the surface protective SnO2 coating layer as well as the structural and morphological modifications of the spinel.

Weakened negative effect of Au/TiO2 photocatalytic activity by CdS quantum dots deposited under UV-vis light illumination at different intensity ratios.

Herein, we demonstrate experimentally the coexistence of photocatalytic dual opposite roles of Au nanoparticles in a UV-vis light irradiated Au/TiO2 system. We have investigated that the photocatalytic performance curves of Au/TiO2 and CdS/Au/TiO2 for degradation of methylene blue (MB) all present a V-shape with different radiation power ratios. However, through the comparison of photocatalytic activities of Au/TiO2 and CdS/Au/TiO2 by statistics and mathematical simulation, we propose qualitatively that the deposition of CdS used as a photosensitizer could extend the Au/TiO2 light absorption range and weaken the negative effect of Au/TiO2. Compared with Au/TiO2, it is proven indirectly that the photo-excited electrons of CdS/Au/TiO2 transfer from CdS to Au, and then to TiO2. Furthermore, we discuss the photocatalytic dual opposite roles of Au nanoparticles between CdS and TiO2, the positive effect includes localized surface plasmon resonance (LSPR) and Schottky barrier (SB), and the negative effect is that Au nanoparticles can be used as a new charge-carrier recombination center. In addition, we have analyzed that the dual opposite relationship of Au/TiO2 under the irradiation of mixed-light could be regulated by changing the intensity ratio of visible to UV light as well.

Pt35Cu65 nanoarchitecture: a highly durable and effective electrocatalyst towards methanol oxidation.

Aiming at electro-catalytic performance enhancement and reduction of catalyst cost, PtxCu1-x (Pt35Cu65, Pt53Cu47, and Pt68Cu32) nanoarchitecture samples with controllable atomic composition, similar morphology and particle-size have been prepared by using a one-pot chemical route. The as-prepared PtxCu1-x nanoarchitectures are confirmed as consisting of the integration of initial small alloy nanoparticles (NPs), resulting in an interconnected nanoporous structure. The electrochemical experiments indicate that these PtxCu1-x nanocatalysts exhibit atomic composition dependent catalytic activity, although the surfaces of all the catalysts were characterized to be featured with a Pt enrichment structure. With optimal atomic composition, the Pt35Cu65 catalyst possesses enhanced electro-catalytic activities towards methanol oxidation in comparison with other PtxCu1-x samples and pure Pt catalyst with similar morphology. Furthermore, the integrated Pt35Cu65 nanoarchitecture displays good durability during the long term electrochemical scanning through as many as 1500 cycles. The comparable catalytic performance of Pt35Cu65 catalyst could be attributed to the interconnected initial small NPs, formation of open porous structure, durable nanoarchitecture, and synergetic effect of the alloyed atoms. The structural evolution from metastable small alloy NPs to integrated stable nanoarchitectures may provide new opportunities to design and prepare novel composite materials with durable structure and effective catalytic properties.