Luminal fluid reabsorption plays a fundamental role in male fertility. We demonstrated that the ubiquitous GPCR signaling proteins Gq and β-arrestin-1 are essential for fluid reabsorption because ...they mediate coupling between an orphan receptor ADGRG2 (GPR64) and the ion channel CFTR. A reduction in protein level or deficiency of ADGRG2, Gq or β-arrestin-1 in a mouse model led to an imbalance in pH homeostasis in the efferent ductules due to decreased constitutive CFTR currents. Efferent ductule dysfunction was rescued by the specific activation of another GPCR, AGTR2. Further mechanistic analysis revealed that β-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, this specificity is critical for male fertility. Therefore, manipulation of the signaling components of the ADGRG2-Gq/β-arrestin-1/CFTR complex by small molecules may be an effective therapeutic strategy for male infertility.
Oxygen plays an essential role in the photodynamic therapy (PDT) of cancer. However, hypoxia inside tumors severely attenuates the therapeutic effect of PDT. To address this issue, a novel strategy ...is reported for cutting off the oxygen consumption pathway by using sub‐50 nm dual‐drug nanoparticles (NPs) to attenuate the hypoxia‐induced resistance to PDT and to enhance PDT efficiency. Specifically, dual‐drug NPs that encapsulate photosensitizer (PS) verteporfin (VER) and oxygen‐regulator atovaquone (ATO) with sub‐50 nm diameters can penetrate deep into the interior regions of tumors and effectively deliver dual‐drug into tumor tissues. Then, ATO released from NPs efficiently reduce in advance cellular oxygen consumption by inhibition of mitochondria respiratory chain and further heighten VER to generate greater amounts of 1O2 in hypoxic tumor. As a result, accompanied with the upregulated oxygen content in tumor cells and laser irradiation, the dual‐drug NPs exhibit powerful and overall antitumor PDT effects both in vitro and in vivo, and even tumor elimination. This study presents a potential appealing clinical strategy in photodynamic eradication of tumors.
A novel strategy for reducing oxygen consumption to attenuate the hypoxia‐induced resistance to photodynamic therapy (PDT) by using sub‐50 nm dual‐drug nanoparticles (ATO/VER NPs) is described. ATO has the ability of alleviating hypoxic regions and can eliminate tumors by enhancing PDT, which provides a valuable reference for research on targeted treatment of hypoxic tumor tissues.
Microcirculation dysfunction and organ injury after ischemia and reperfusion (I/R) result from a complex pathologic process consisting of multiple links, with metabolism impairment in the ischemia ...phase and oxidative stress in the reperfusion phase as initiators, and any treatment targeting a single link is insufficient to cope with this. Compound Chinese medicine (CCM) has been applied in clinics in China and some Asian nations for >2000years. Studies over the past decades revealed the protective and therapeutic effect of CCMs and major ingredients on I/R-induced microcirculatory dysfunction and tissue injury in the heart, brain, liver, intestine, and so on. CCM contains diverse bioactive components with potential for energy metabolism regulation; antioxidant effect; inhibiting inflammatory cytokines release; adhesion molecule expression in leukocyte, platelet, and vascular endothelial cells; and the protection of thrombosis, albumin leakage, and mast cell degranulation. This review covers the major works with respect to the effects and underlying mechanisms of CCM and its ingredients on microcirculatory dysfunction and organ injury after I/R, providing novel ideas for dealing with this threat.
Enormous research interest is devoted to fabricating three-dimensional graphene-based gels (3D GBGs) toward improved conversion of solar energy by virtue of the intrinsic properties of single ...graphene and 3D porous structure characteristics. Here, this concise minireview is primarily focused on the recent progress on applications of 3D GBGs, including aerogels and hydrogels, in photocatalytic degradation of pollutants from water and air, such as organic pollutants, heavy metal ions, bacteria and gaseous pollutants. In particular, the preponderances of 3D GBG photocatalysts for environmental pollutants degradation have been elaborated. Furthermore, in addition to discussing opportunities offered by 3D GBG composite photocatalysts, we also describe the existing problems and the future direction of 3D GBG materials in this burgeoning research area. It is hoped that this review could spur multidisciplinary research interest for advancing the rational utilization of 3D GBGs for practical applications in environmental remediation.
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•3D graphene-based gels (3D GBGs) possess more active sites.•Porous structure of 3D GBGs promotes the photogenerated electrons transfer.•3D framework provides an ideal support for the active components.•Applications of 3D GBGs in photocatalytic environmental remediation are overviewed.
A financial computable general equilibrium model is established to quantitatively calculate the systematic effects of a green credit policy. The punitive high-interest rate is applied to the ...energy-intensive industries as the green credit policy. This study is focused on the following industries: paper, chemical, cement, and iron and steel. Short-, medium- and long-term scenarios are used to conduct experiments representing the green credit policy. Then, a scenario is simulated wherein a green security policy and the green credit policy are carried out simultaneously. Finally, effects of the green credit policy, a differential electricity price policy, and a raised production tax policy towards the energy-intensive industries are compared. The results show that the green credit policy is effective in suppressing the investments in energy-intensive industries, and it is comparatively less effective in adjusting the industrial production structure. The green security policy helps the green credit policy to reduce the total financing of the target industries, but it brings more negative impacts on the economy. Although the policies of differential electricity prices and raising production taxes support the output structural adjustments, their negative effects are much larger than those of the green credit policy.
•This paper analyses green credit policy aimed at energy-intensive industries.•A financial computable general equilibrium model is applied in the paper.•Green credit policy is effective in suppressing the investments of energy-intensive industries.•Green security policy helps to reduce the total financing of energy-intensive industries.•Two other energy policies have much larger negative impacts than the green credit policy.
A pulsed muon facility (the so‐called EMuS) at the China Spallation Neutron Source (CSNS) has been studied since 2007. It aims for multidisciplinary applications but with a focus on those based on ...muon spin rotation/relaxation/resonance techniques. As a standalone facility, EMuS will take about 5% or 25 kW of the total beam power (500 kW) from the CSNS‐II accelerator complex. Two schemes have been designed: the baseline scheme is based on an inner conical target in graphite and superconducting solenoids for the capture and transport of pions and muons; the simplified scheme is based on a conventional thick target and room‐temperature magnets for transport. With the former, multiple kinds of muon beams can be provided, from surface muons, decay muons, negative muons, to low‐energy muons. Mainly surface muons are available with the simplified scheme. With a number of novel design concepts such as forward capture of pions/muons from a target station based on superconducting solenoids and triple spatial beam splitting of a muon beam, the design aspects of EMuS are presented here. The wide application potential and the R&D progress are also included.
At the Experimental Muon Source at the China Spallation Neutron Source, a novel target station design is adopted to produce high‐intensity and different muon beam types. A conical graphite target is installed inside a series of superconducting solenoids. With a tapered magnetic field and forward collection, surface muons, decay muons, and high‐momentum muons can be provided in the downstream beamline.
This systematic review and meta-analysis was conducted to compare the safety and efficacy of 2019 novel coronavirus disease (COVID-19) vaccines according to vaccine platform and severe acute ...respiratory syndrome coronavirus 2 (SARS-COV-2) infection severity. Articles published between 24 January 2020 and 30 May 2021 were retrieved via a PubMed and EMBASE search. A total of 12 reports on phase-3 clinical trials and observational studies of COVID-19 vaccines were included in the review. In terms of vaccine safety, mRNA vaccines showed more relevance to serious adverse events than viral vector and inactivated vaccines, but no solid evidence indicated that COVID-19 vaccines directly caused serious adverse events. Serious metabolic, musculoskeletal, immune-system, and renal disorders were more common among inactivated vaccine recipients, and serious gastrointestinal complications and infections were more common among viral vector and inactivated vaccine recipients. The occurrence of serious vessel disorders was more frequent in mRNA vaccines. In terms of efficacy, two mRNA vaccine doses conferred a lesser risk of SARS-COV-2 infection (odds ratio: 0.05; 95% confidence interval: 0.02–0.13) than did vaccination with viral vector and inactivated vaccines. All vaccines protected more against symptomatic than asymptomatic cases (risk ratio, 0.11 vs. 0.34), but reduced the risk of severe SARS-COV-2 infection. The COVID-19 vaccines assessed in this study are sufficiently safe and effective. The results indicate that two mRNA vaccine doses prevent SARS-COV-2 infection most effectively, but further research is needed due to the high degree of heterogeneity among studies in this sample. Interventions should be implemented continuously to reduce the risks of infection after one vaccine dose and asymptomatic infection.
The intermolecular H‐bonding density heavily influences the gelation and rheological behavior of hydrogen‐bonded supramolecular polymer hydrogels, thus offering a delicate pathway to tailor their ...physicochemical properties for meeting a specific biomedical application. Herein, one methylene spacer between two amides in the side chain of N‐acryloyl glycinamide (NAGA) is introduced to generate a variant monomer, N‐acryloyl alaninamide (NAAA). Polymerization of NAAA in aqueous solution affords an unprecedented ultrasoft and highly swollen supramolecular polymer hydrogel due to weakened H‐bonds caused by an extra methylene spacer, which is verified by variable‐temperature Fourier transform infrared (FTIR) spectroscopy and simulation calculation. Intriguingly, poly(N‐acryloyl alaninamide) (PNAAA) hydrogel can be tuned to form a transient network with a self‐fused and excellent antifouling capability that results from the weakened dual amide H‐bonding interactions and enhanced water‐amide H‐bonding interactions. This self‐fused PNAAA hydrogel can completely inhibit postoperative abdominal adhesion and recurrent adhesion after adhesiolysis in vivo. This transient hydrogel network allows for its disintegration and excretion from the body. The molecular mechanism studies reveal the signal pathway of PNAAA hydrogel in inhibiting inflammatory response and regulating fibrinolytic system balance. This self‐fused, antifouling ultrasoft supramolecular hydrogel is promising as a barrier biomaterial for completely preventing postoperative tissue adhesion.
One more methylene makes a difference: introducing one extra methylene between two amides in the side chain of poly(N‐acryloyl alaninamide) weakens the H‐bonding interaction, resulting in an ultrasoft and highly swollen supramolecular polymer hydrogel that can be tuned to form a transient network with a self‐fused and antifouling ability, which is harnessed to completely prevent postoperative tissue adhesion.
It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of ...WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all ana-lyzed WRKY proteins recognize the TrGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcrip-tion factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biologi- cal processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.
Enhanced electrochemiluminescence (ECL) aims to promote higher sensitivity and obtain better detection limit. The core–shell nanostructures, owing to unique surface plasmon resonance (SPR) enabling ...distance‐dependent strong localized electromagnetic field, have attracted rising attention in enhanced ECL research and application. However, the present structures usually with porous shell involve electrocatalytic activity from the metal core and adsorption effect from the shell, which interfere with practical SPR enhancement contribution to ECL signal. Herein, to exclude the interference and unveil exact SPR‐enhanced effect, shell‐isolated nanoparticles (SHINs) whose shell gets thicker and becomes pinhole‐free are developed by modifying pH value and particles concentration. Furthermore, allowing for the distribution of hotspots and stronger enhancement, excitation intensity and ECL reaction layer thickness are mainly investigated, and several types of SHINs‐enhanced ECL platforms are prepared to fabricate distinct hotspot distribution via electrostatic attraction (submonolayer) and a layer‐by‐layer deposition method (monolayer). Consequently, the strongest enhancement up to ≈250‐fold is achieved by monolayer SHINs with 10 nm shell, and the platform is applied in a “turn‐off” mode sensing for dopamine. The platform provides new guidelines to shell preparation, interface engineering and hotspots fabrication for superior ECL enhancement and analytical application with high performance.
Shell‐isolated nanoparticles (SHINs) with pinhole‐free silica shell can exclude the interference from electrocatalytic activity and adsorption effect, allowing for exact SPR‐enhanced effect. Moreover, several types of SHINs‐enhanced ECL platforms are established to investigate the distribution of hotspots, expecting for stronger enhancement. Consequently, the strongest ECL enhancement up to ≈250‐fold is achieved, and the platform applies in sensing for dopamine.
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