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1.
Ecotoxicol Environ Saf ; 270: 115948, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38184976

RESUMO

The increasing production and prevalence of antimony (Sb)-related products raise concerns regarding its potential hazards to reproductive health. Upon environmental exposure, Sb reportedly induces testicular toxicity during spermatogenesis; moreover, it is known to affect various testicular cell populations, particularly germline stem cell populations. However, the cell-cell communication resulting from Sb exposure within the testicular niche remains poorly understood. To address this gap, herein we analyzed testicular single-cell RNA sequencing data from Sb-exposed Drosophila. Our findings revealed that the epidermal growth factor receptor (EGFR) and WNT signaling pathways were associated with the stem cell niche in Drosophila testes, which may disrupt the homeostasis of the testicular niche in Drosophila. Furthermore, we identified several ligand-receptor pairs, facilitating the elucidation of intercellular crosstalk involved in Sb-mediated reproductive toxicology. We employed scRNA-seq analysis and conducted functional verification to investigate the expression patterns of core downstream factors associated with EGFR and WNT signatures in the testes under the influence of Sb exposure. Altogether, our results shed light on the potential mechanisms of Sb exposure-mediated testicular cell-lineage communications.


Assuntos
Drosophila , Testículo , Masculino , Animais , Testículo/metabolismo , Drosophila/metabolismo , Antimônio/toxicidade , Antimônio/metabolismo , Comunicação Celular , Receptores ErbB/metabolismo , Análise de Sequência de RNA
2.
RSC Adv ; 13(20): 13592-13603, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37152574

RESUMO

In this study, a novel magnetic bio-adsorbent was synthesized by modifying cotton linter (CL) cellulose with deep eutectic solvents (DESs) and Fe3O4 magnetic nanoparticles. The adsorption capacity of CL, Fe3O4/CL, Fe3O4/CL-oxidation, and Fe3O4/CL-DES for Cu2+ was 11.0, 66.1, 85.7, and 93.1 mg g-1, respectively, under the optimal adsorption conditions of an initial pH value of 6.0, stirring rate of 300 rpm, and a temperature of 30 °C. The presence of Fe3O4 nanoparticles increased the proportion of hydroxyl groups and thus improved the ion-exchange ability of Cu2+. The dissolution of DES significantly decreased fiber crystallinity and increased the number of hydroxyl group (amorphous regions increased), thus improving the chelation reaction of Cu2+, which was favorable for surface adsorption. In addition, we used the Langmuir and Freundlich isothermal models to simulate the adsorption behavior of Fe3O4/CL-DES, and the results indicated that Cu2+ follows a Freundlich isotherm model of multilayer adsorption. The fitting of the adsorption kinetics model indicated that the adsorption process involves multiple adsorption mechanisms and can be described by a quasi-second-order model. These results provide a potential method for the preparation of high-efficiency adsorbents from low-value cotton linter, which has broad application prospects in wastewater treatment.

3.
Nano Lett ; 23(4): 1514-1521, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36730120

RESUMO

Excitons are quasi-particles composed of electron-hole pairs through Coulomb interaction. Due to the atomic-thin thickness, they are tightly bound in monolayer transition metal dichalcogenides (TMDs) and dominate their optical properties. The capability to manipulate the excitonic behavior can significantly influence the photon emission or carrier transport performance of TMD-based devices. However, on-demand and region-selective manipulation of the excitonic states in a reversible manner remains challenging so far. Herein, harnessing the coordinated effect of femtosecond-laser-driven atomic defect generation, interfacial electron transfer, and surface molecular desorption/adsorption, we develop an all-optical approach to manipulate the charge states of excitons in monolayer molybdenum disulfide (MoS2). Through steering the laser beam, we demonstrate reconfigurable optical encoding of the excitonic charge states (between neutral and negative states) on a single MoS2 flake. Our technique can be extended to other TMDs materials, which will guide the design of all-optical and reconfigurable TMD-based optoelectronic and nanophotonic devices.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36395270

RESUMO

Multiple studies have investigated the association of interleukin-6 (IL-6) gene polymorphisms and osteoarthritis (OA) risk, but failed to reach a consistent conclusion. Therefore, this study was designed to elucidate the association of IL-6 polymorphisms and OA by a meta-analysis approach. Literature retrieval was carried out on PubMed, EMBASE, Web of Science, CNKI, and Wanfang databases. The strength of association was appraised by odds ratios (ORs) and 95% confidence intervals (95%CIs) in five genetic models. The data were merged by using RevMan 5.3 software. Ten studies with 4944 cases and 4651 controls were analyzed. Overall, no significant association was identified between rs1800795 polymorphism and OA. Subgroup analysis by ethnicity and OA site also suggested rs1800795 polymorphism was not associated with OA. For rs1800796 polymorphism, G-allele and GG-genotype carriers appeared to have an increased risk to OA (G vs. C, OR = 1.66, 95%CI 1.30-1.96, P < 0.01; GG vs. CC, OR = 1.75, 95%CI 1.07-2.84, P = 0.03; GG vs. GC + CC, OR = 1.82, 95%CI 1.42-2.34, P < 0.01). Findings of this study indicate that the rs1800795 polymorphism is not correlated to OA susceptibility, regardless of ethnicity or OA site. However, rs1800796 polymorphism trends to be associated with susceptibility to OA.


Assuntos
Interleucina-6 , Osteoartrite , Humanos , Interleucina-6/genética , Predisposição Genética para Doença , Polimorfismo Genético , Osteoartrite/genética , Genótipo , Polimorfismo de Nucleotídeo Único
5.
Polymers (Basel) ; 14(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36559881

RESUMO

Cotton fiber is favored by people because of its good moisture absorption, heat preservation, soft feel, comfortable wearing and other excellent performance. In recent years, due to the destruction of the ozone layer, the intensity of ultraviolet radiation at ground level has increased. Cotton fiber will degrade under long time ultraviolet irradiation, which limits the outdoor application of cotton fiber. In this study, titanium dioxide (TiO2) particles were prepared on the surface of cotton fibers with the help of supercritical carbon dioxide (SCCO2) to improve the UV resistance of cotton fibers. The effects of SCCO2 treatment on the morphology, surface composition, thermal stability, photostability and mechanical properties of TiO2 were studied by Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, thermogravimetric analysis, UV-VIS spectroscopy, and single fiber test. The results showed that TiO2 particles were generated on the fiber surface, which reduced the photo-degradation rate of cotton fiber. This is because TiO2 can absorb UV rays and reduce the absorption of UV rays by the cotton fiber itself. The synthesis process of SCCO2 is simple and environmentally friendly, which provides a promising technology for the synthesis of metal nitrogen dioxide on natural plant fibers.

6.
BMC Surg ; 22(1): 394, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401260

RESUMO

BACKGROUND: This study aimed to assess the clinical efficacy of one-stage posterior surgery combined with anti-Brucella therapy in the treatment of lumbosacral brucellosis spondylitis (LBS). METHODS: From June 2010 to June 2020, the clinical and radiographic data of patients with LBS treated by one-stage posterior surgery combined with anti-Brucella therapy were retrospectively analyzed. The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and Oswestry Disability Index scores (ODI) were used to evaluate the clinical outcomes. Frankel's classification system was employed to access the initial and final neurologic function. Fusion of the bone grafting was classified by Bridwell's grading system. RESULTS: A total of 55 patients were included in this study with a mean postoperative follow-up time of 2.6 ± 0.8 years (range, 2 to 5). There were 40 males and 15 females with a mean age of 39.8 ± 14.7 years (range, 27 to 57). The Brucella agglutination test was ≥ 1:160 in all patients, but the blood culture was positive in 43 patients (78.1%). A statistical difference was observed in ESR, CRP, VAS, ODI, and JOA between preoperative and final follow-up (P < 0.05). Neurological function was significantly improved in 20 patients with preoperative neurological dysfunction after surgery. According to Bridwell's grading system, the fusion of bone grafting in 48 cases (87.2%) was defined as grade I, and grade II in 7 cases (12.7%). None of the infestation recurrences was observed. CONCLUSION: One-stage posterior surgery combined with anti-Brucella therapy was a practical method in the treatment of LBS with severe neurological compression and spinal sagittal imbalance.


Assuntos
Brucella , Brucelose , Fusão Vertebral , Espondilite , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Desbridamento/métodos , Espondilite/cirurgia , Brucelose/complicações , Brucelose/tratamento farmacológico , Brucelose/cirurgia
7.
Front Chem ; 10: 961355, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991607

RESUMO

The rapid economic and societal development have led to unprecedented energy demand and consumption resulting in the harmful emission of pollutants. Hence, the conversion of greenhouse gases into valuable chemicals and fuels has become an urgent challenge for the scientific community. In recent decades, perovskite-type mixed oxide-based catalysts have attracted significant attention as efficient CO2 conversion catalysts due to the characteristics of both reversible oxygen storage capacity and stable structure compared to traditional oxide-supported catalysts. In this review, we hand over a comprehensive overview of the research for CO2 conversion by these emerging perovskite-type mixed oxide-based catalysts. Three main CO2 conversions, namely reverse water gas shift reaction, CO2 methanation, and CO2 reforming of methane have been introduced over perovskite-type mixed oxide-based catalysts and their reaction mechanisms. Different approaches for promoting activity and resisting carbon deposition have also been discussed, involving increased oxygen vacancies, enhanced dispersion of active metal, and fine-tuning strong metal-support interactions. Finally, the current challenges are mooted, and we have proposed future research prospects in this field to inspire more sensational breakthroughs in the material and environment fields.

8.
Materials (Basel) ; 15(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35408020

RESUMO

Cotton fibers with ultra-high purity cellulose are ideal raw materials for producing nanocellulose. However, the strong hydrogen bond and high crystallinity of cotton fibers affect the dissociation of cotton fibers to prepare nanocellulose. The structures of two kinds of cotton fibers (CM and XM) in different growth stages from 10 to 50 days post-anthesis (dpa) were studied by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). In the process of cotton fiber growth, the deposition rate of cellulose macromolecules firstly increased and then stabilized. Then, the surface morphology, the chemical composition, and the crystal structure of the nanocellulose prepared from cotton fibers with different growth stages by deep eutectic solvent, a green solvent, were characterized by Transmission Electron Microscope (TEM), scanning electron microscopy (SEM) analysis, XRD, and Thermo Gravimetry (TG). The growth time of cotton fibers affected the properties of prepared nanocellulose, and nanocellulose obtained from cotton fibers at about 30 dpa had less energy consumption, higher yield, and milder reaction conditions.

9.
Chem Soc Rev ; 51(10): 4000-4022, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35477783

RESUMO

Layered semiconductors, represented by transition metal dichalcogenides, have attached extensive attention due to their unique and tunable electrical and optical properties. In particular, lateral layered semiconductor multijunctions, including homojunctions, heterojunctions, hybrid junctions and superlattices, present a totally new degree of freedom in research on electronic devices beyond traditional materials and their structures, providing unique opportunities for the development of new structures and operation principle-based high performance devices. However, the advances in this field are limited by the precise synthesis of high-quality junctions and greatly hampered by ambiguous device performance limits. Herein, we review the recent key breakthroughs in the design, synthesis, electronic structure and property modulation of lateral semiconductor multijunctions and focus on their application-specific devices. Specifically, the synthesis methods based on different principles, such as chemical and external source-induced methods, are introduced stepwise for the controllable fabrication of semiconductor multijunctions as the basics of device application. Subsequently, their structure and property modulation are discussed, including control of their electronic structure, exciton dynamics and optical properties before the fabrication of lateral layered semiconductor multijunction devices. Precise property control will potentially result in outstanding device performances, including high-quality diodes and FETs, scalable logic and analog circuits, highly efficient optoelectronic devices, and unique electrochemical devices. Lastly, we focus on several of the most essential but unresolved debates in this field, such as the true advantages of few-layer vs. monolayer multijunctions, how sharp the interface should be for specific functional devices, and the superiority of lateral multijunctions over vertical multijunctions, highlighting the next-phase strategy to enhance the performance potential of lateral multijunction devices.

10.
Sci Rep ; 11(1): 20576, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663830

RESUMO

G-protein-coupled receptors (GPCRs) are a target for over 34% of current drugs. The calcium-sensing receptor (CaSR), a family C GPCR, regulates systemic calcium (Ca2+) homeostasis that is critical for many physiological, calciotropical, and noncalciotropical outcomes in multiple organs. However, the mechanisms by which extracellular Ca2+ (Ca2+ex) and the CaSR mediate networks of intracellular Ca2+-signaling and players involved throughout the life cycle of CaSR are largely unknown. Here we report the first CaSR protein-protein interactome with 94 novel putative and 8 previously published interactors using proteomics. Ca2+ex promotes enrichment of 66% of the identified CaSR interactors, pertaining to Ca2+ dynamics, endocytosis, degradation, trafficking, and primarily to protein processing in the endoplasmic reticulum (ER). These enhanced ER-related processes are governed by Ca2+ex-activated CaSR which directly modulates ER-Ca2+ (Ca2+ER), as monitored by a novel ER targeted Ca2+-sensor. Moreover, we validated the Ca2+ex dependent colocalizations and interactions of CaSR with ER-protein processing chaperone, 78-kDa glucose regulated protein (GRP78), and with trafficking-related protein. Live cell imaging results indicated that CaSR and vesicle-associated membrane protein-associated A (VAPA) are inter-dependent during Ca2+ex induced enhancement of near-cell membrane expression. This study significantly extends the repertoire of the CaSR interactome and reveals likely novel players and pathways of CaSR participating in Ca2+ER dynamics, agonist mediated ER-protein processing and surface expression.


Assuntos
Cálcio/metabolismo , Proteínas Sensoras de Cálcio Intracelular/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Animais , Células COS , Sinalização do Cálcio , Membrana Celular/metabolismo , Chlorocebus aethiops , Endocitose/fisiologia , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático/metabolismo , Células HEK293 , Humanos , Transporte Proteico , Proteínas de Transporte Vesicular/metabolismo
11.
Theranostics ; 11(19): 9331-9341, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646373

RESUMO

Rationale: Fibrosis is a pathologic condition of abnormal accumulation of collagen fibrils. Collagen is a major extracellular matrix (ECM) protein synthesized and secreted by myofibroblasts, composing mainly (Gly-X-Y)n triplet repeats with >30% Gly residue. During fibrosis progression, myofibroblasts must upregulate glycine metabolism to meet the high demands of amino acids for collagen synthesis. Method: Expression of PKM2 in myofibroblasts was analyzed in cultured fibroblasts and fibrosis disease tissues. Functional roles of PKM2 and PKM2 activator in biosynthesis of serine → glycine and production of collagen from glycolysis intermediates were assayed in cultured activated LX-2 and human primary lung fibroblast cells. Mouse models of Liver, lung, and pancreas fibrosis were employed to analyze treatment effects of PKM2 activator in organ tissue fibrosis. Results: We report here that myofibroblast differentiation upregulates pyruvate kinase M2 (PKM2) and promotes dimerization of PKM2. Dimer PKM2 slows the flow rate of glycolysis and channels glycolytic intermediates to de novo glycine synthesis, which facilitates collagen synthesis and secretion in myofibroblasts. Our results show that PKM2 activator that converts PKM2 dimer to tetramer, inhibits fibrosis progression in mouse models of liver, lung, and pancreatic fibrosis. Furthermore, metabolism alteration by dimer PKM2 increases NADPH production, which consequently protects myofibroblasts from apoptosis. Conclusion: Our study uncovers a novel role of PKM2 in tissue/organ fibrosis, suggesting a possible strategy for treatment of fibrotic diseases using PKM2 activator.


Assuntos
Fibrose/metabolismo , Glicina/metabolismo , Piruvato Quinase/metabolismo , Animais , Apoptose , Diferenciação Celular , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Fibrose/fisiopatologia , Glicina/fisiologia , Glicólise/efeitos dos fármacos , Humanos , Fígado/patologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Miofibroblastos/metabolismo , Miofibroblastos/fisiologia , Pâncreas/patologia , Piruvato Quinase/fisiologia , Transdução de Sinais
12.
Angew Chem Int Ed Engl ; 60(43): 23289-23298, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34436811

RESUMO

Multi-scale calcium (Ca2+ ) dynamics, exhibiting wide-ranging temporal kinetics, constitutes a ubiquitous mode of signal transduction. We report a novel endoplasmic-reticulum (ER)-targeted Ca2+ indicator, R-CatchER, which showed superior kinetics in vitro (koff ≥2×103  s-1 , kon ≥7×106  M-1 s-1 ) and in multiple cell types. R-CatchER captured spatiotemporal ER Ca2+ dynamics in neurons and hotspots at dendritic branchpoints, enabled the first report of ER Ca2+ oscillations mediated by calcium sensing receptors (CaSRs), and revealed ER Ca2+ -based functional cooperativity of CaSR. We elucidate the mechanism of R-CatchER and propose a principle to rationally design genetically encoded Ca2+ indicators with a single Ca2+ -binding site and fast kinetics by tuning rapid fluorescent-protein dynamics and the electrostatic potential around the chromophore. The design principle is supported by the development of G-CatchER2, an upgrade of our previous (G-)CatchER with improved dynamic range. Our work may facilitate protein design, visualizing Ca2+ dynamics, and drug discovery.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Cálcio/análise , Retículo Endoplasmático/metabolismo , Proteínas Luminescentes/metabolismo , Animais , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Proteínas de Ligação ao Cálcio/química , Células HEK293 , Células HeLa , Humanos , Proteínas Luminescentes/química , Camundongos , Simulação de Dinâmica Molecular , Ligação Proteica , Engenharia de Proteínas , Espectrometria de Fluorescência
13.
iScience ; 24(3): 102129, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33665552

RESUMO

The precise spatiotemporal characteristics of subcellular calcium (Ca2+) transients are critical for the physiological processes. Here we report a green Ca2+ sensor called "G-CatchER+" using a protein design to report rapid local ER Ca2+ dynamics with significantly improved folding properties. G-CatchER+ exhibits a superior Ca2+ on rate to G-CEPIA1er and has a Ca2+-induced fluorescence lifetimes increase. G-CatchER+ also reports agonist/antagonist triggered Ca2+ dynamics in several cell types including primary neurons that are orchestrated by IP3Rs, RyRs, and SERCAs with an ability to differentiate expression. Upon localization to the lumen of the RyR channel (G-CatchER+-JP45), we report a rapid local Ca2+ release that is likely due to calsequestrin. Transgenic expression of G-CatchER+ in Drosophila muscle demonstrates its utility as an in vivo reporter of stimulus-evoked SR local Ca2+ dynamics. G-CatchER+ will be an invaluable tool to examine local ER/SR Ca2+ dynamics and facilitate drug development associated with ER dysfunction.

14.
Small ; 16(35): e2001435, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32755007

RESUMO

1D silicon-based nanomaterials, renowned for their unique chemical and physical properties, have enabled the development of numerous advanced materials and biomedical technologies. Their production often necessitates complex and expensive equipment, requires hazardous precursors and demanding experimental conditions, and involves lengthy processes. Herein, a flash solid-solid (FSS) process is presented for the synthesis of silicon oxide nanorods completed within seconds. The innovative features of this FSS process include its simplicity, speed, and exclusive use of solid precursors, comprising hydrogen-terminated silicon nanosheets and a metal nitrate catalyst. Advanced electron microscopy and X-ray spectroscopy analyses favor a solid-liquid-solid reaction pathway for the growth of the silicon oxide nanorods with vapor-liquid-solid characteristics.

15.
J Chem Phys ; 153(2): 024703, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32668920

RESUMO

Gamma-phase cesium lead tri-bromide perovskite nanocrystals (γ-CsPbBr3 NCs) possess potentially photo-catalytic degradation ability and long-term stability. However, their serious aggregation issue decreases their active surface area, and the recombination of photo-generated hole-electron pairs weakens their photo-catalytic property. Furthermore, these NCs can be easily absorbed on the surface of dyes [e.g., methylene blue (MB)] or dissolved in the dye solution during the photo-catalytic degradation process, thus reducing the amount of γ-CsPbBr3 NCs and their photo-catalytic degradation ability. Besides, the residual γ-CsPbBr3 NCs in the photo-catalytic degradation products also present the toxicity issue (containing Pb) and are hazardous to the ecological environment and human health. In the present study, we fabricated γ-CsPbBr3 NCs/polymethyl methacrylate electrospun nanofibrous membranes (γ-CsPbBr3 NCs/PMMA ENMs) by using electrospinning technology to solve the above problems. It is found that the synthesized γ-CsPbBr3 NCs/PMMA ENMs show a large surface area and the abundant functional groups on their surfaces, which are benefit for forming multiple kinds of chemical bonding effect between γ-CsPbBr3 NCs and PMMA ENMs. In addition, γ-CsPbBr3 NCs could disperse homogeneously in or on the surface of PMMA ENMs. These abundant chemical bonds and homogeneous distributions of γ-CsPbBr3 NCs on the surface of PMMA ENMs can significantly decrease the recombination of photo-generated hole-electron pairs and toxicity issue of γ-CsPbBr3 NCs during the photo-catalytic degradation process. Exhilaratingly, γ-CsPbBr3 NCs/PMMA ENMs could maintain a superior photo-catalytic degradation ability toward various dyes and reveal a high photo-catalytic degradation efficiency of 99.18% in 60 min for MB.

16.
Molecules ; 25(9)2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32375353

RESUMO

Calcium controls numerous biological processes by interacting with different classes of calcium binding proteins (CaBP's), with different affinities, metal selectivities, kinetics, and calcium dependent conformational changes. Due to the diverse coordination chemistry of calcium, and complexity associated with protein folding and binding cooperativity, the rational design of CaBP's was anticipated to present multiple challenges. In this paper we will first discuss applications of statistical analysis of calcium binding sites in proteins and subsequent development of algorithms to predict and identify calcium binding proteins. Next, we report efforts to identify key determinants for calcium binding affinity, cooperativity and calcium dependent conformational changes using grafting and protein design. Finally, we report recent advances in designing protein calcium sensors to capture calcium dynamics in various cellular environments.


Assuntos
Técnicas Biossensoriais , Proteínas de Ligação ao Cálcio/química , Cálcio/química , Animais , Sítios de Ligação , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Humanos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Engenharia de Proteínas , Dobramento de Proteína , Pesquisa
17.
Curr Opin Physiol ; 17: 269-277, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33709045

RESUMO

Calcaium sensing receptors (CaSRs) play a central role in regulating extracellular calcium (Ca2+) homeostasis and many (patho)physiological processes. This regulation is primarily orchestrated in response to extracellular stimuli via the extracellular domain (ECD). This paper first reviews the modeled structure of the CaSR ECD and the prediction and investigation of the Ca2+ and amino acid binding sites. Several recently solved X-ray structures are then compared to support a proposed CaSR activation model involving functional cooperativity. The review also discusses recent implications for drug development. These studies provide new insights into the molecular basis of diseases and the design of therapeutic agents that target CaSR and other family C G protein-coupled receptors (cGPCRs).

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