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In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.
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Dendritos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos , Bulbo Olfatório , Olfato , Animais , Feminino , Masculino , Camundongos , Dendritos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Microtúbulos/metabolismo , Morfogênese/genética , Bulbo Olfatório/metabolismo , Olfato/fisiologiaRESUMO
Low-dimensional perovskites afford improved stability against moisture, heat, and ionic migration. However, the low dimensionality typically results in a wide bandgap and strong electron-phonon coupling, which is undesirable for optoelectronic applications. Herein, semiconducting A-site organic cation engineering by electron-acceptor bipyridine (bpy) cations (2,2'-bpy2+ and 4,4'-bpy2+) is employed to optimize band structure in low-dimensional perovskites. Benefiting from the merits of lower lowest unoccupied molecular orbital (LUMO) energy for 4,4'-bpy2+ cation, the corresponding (4,4'-bpy)PbI4 is endowed with a smaller bandgap (1.44 eV) than the (CH3NH3)PbI3 (1.57 eV) benchmark. Encouragingly, an intramolecular type II band alignment formation between inorganic Pb-I octahedron anions and bpy2+ cations favors photogenerated electron-hole pairs separation. In addition, a shortening distance between inorganic Pb-I octahedral chains in (4,4'-bpy)PbI4 single crystal (SC) can effectively promote carrier transfer. As a result, a self-powered photodetector based on (4,4'-bpy)PbI4 SC exhibits 131 folds higher on/off ratio (3807) than the counterpart of (2,2'-bpy)2Pb3I10 SC (29). The presented result provides an effective strategy for exporting novel organic cation-based low-dimensional perovskite SC for high-performance optoelectronic devices.
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Predicting the melting temperature of materials has always been a topic of great concern. This article proposes an alternative model for determining the melting temperature of materials based on the main idea of the Lindemann melting criterion combined with the first-principles calculations of density functional theory. To verify the accuracy of the melting model, this article selected typical ionic crystals of MgO and 10 alkali metal halides as the validation objects. The calculation results indicate that the melting temperature of the MgO crystals and I-VII compounds is in good agreement with the experimental results.
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OBJECTIVE: Fungal keratitis is a severe sight-threatening ocular infection, without effective treatment strategies available now. Calprotectin S100A8/A9 has recently attracted great attention as a critical alarmin modulating the innate immune response against microbial challenges. However, the unique role of S100A8/A9 in fungal keratitis is poorly understood. METHODS: Experimental fungal keratitis was established in wild-type and gene knockout (TLR4-/- and GSDMD-/-) mice by infecting mouse corneas with Candida albicans. The degree of mouse cornea injuries was evaluated by clinical scoring. To interrogate the molecular mechanism in vitro, macrophage RAW264.7 cell line was challenged with Candida albicans or recombinant S100A8/A9 protein. Label-free quantitative proteomics, quantitative real-time PCR, Western blotting, and immunohistochemistry were conducted in this research. RESULTS: Herein, we characterized the proteome of mouse corneas infected with Candida albicans and found that S100A8/A9 was robustly expressed at the early stage of the disease. S100A8/A9 significantly enhanced disease progression by promoting NLRP3 inflammasome activation and Caspase-1 maturation, accompanied by increased accumulation of macrophages in infected corneas. In response to Candida albicans infection, toll-like receptor 4 (TLR4) sensed extracellular S100A8/A9 and acted as a bridge between S100A8/A9 and NLRP3 inflammasome activation in mouse corneas. Furthermore, the deletion of TLR4 resulted in noticeable improvement in fungal keratitis. Remarkably, NLRP3/GSDMD-mediated macrophage pyroptosis in turn facilitates S100A8/A9 secretion during Candida albicans keratitis, thus forming a positive feedback cycle that amplifies the proinflammatory response in corneas. CONCLUSIONS: The present study is the first to reveal the critical roles of the alarmin S100A8/A9 in the immunopathology of Candida albicans keratitis, highlighting a promising approach for therapeutic intervention in the future.
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Candida albicans , Ceratite , Camundongos , Animais , Candida albicans/metabolismo , Inflamassomos/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Alarminas , Retroalimentação , Ceratite/genética , Ceratite/microbiologia , Imunidade Inata , Calgranulina A/genéticaRESUMO
An efficient palladium-catalyzed intermolecular selective C-H silylation of boronic acids is described. The combination of palladium catalyst with copper oxidant enables ortho-selective C-H silylation by employing hexamethyldisilane as the trimethylsilyl source, which relies on the control of NBE derivatives as a switch, thus providing straightforward access to divergent organosilicon compounds.
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Understanding and predicting the bond breaking mechanism of energetic materials before explosion initiation is one of the huge challenges in explosion science. By means of the mean square displacement of the atom from the equilibrium position and theoretical bond breaking tensile change of the chemical bond, we establish a new criterion to judge whether the chemical bond is broken. Further, α-RDX is used as the verification object to verify the accuracy of this model. We obtained an initial decomposition temperature of 434-513 K for α-RDX at 0 GPa, and the initial bond breaking type was N-NO2. Finally, based on this model, we discussed in detail the breaking of chemical bonds of solid nitromethane near the detonation pressure. We think that the high temperature and high pressure caused by the shock wave may break all the chemical bonds of nitromethane near the detonation pressure.
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The structural, electronic and vibrational properties of solid carbon dioxide phases (I, II, III, and IV) under high pressure are studied using first-principles calculations. The calculated structural parameters are in good agreement with the experimental values. The third-order Birch-Murnaghan equation of state is fitted, and the corresponding parameters are obtained. We obtained the phase boundary points of each phase and plotted the phase diagram of solid carbon dioxide. The influence of pressure on the band structure and density of states is studied. The vibrational properties of the four phases of carbon dioxide were studied in detail, and the infrared and Raman spectra of the four phases were obtained. It can be seen from the calculated spectrum that the number and frequency of vibration peaks are in good agreement with the experimental values. And, we also analyze the influence of pressure on the frequency of vibration mode.
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Due to the large distance or weak electronic conjugation between adjacent Bi-I octahedrons, the charge transport in the low-dimensional bismuth-based hybrid perovskites is impeded and thus hinders their future developments. In this work, A-site cation engineering by monoamine BZA (benzylamine) and diamine 3-AMP (3-(aminomethyl)pyridine) has been demonstrated as an efficient strategy to regulate the corresponding activation energy of ionic migration and carrier transport capacity. Given the higher polarity of 3-AMP than BZA, producing a more efficient dielectric screening effect, it gives rise to obtaining the small exciton binding energy (50â meV) and low defect states (3.53×109 â cm-3 ). The reduced distance of adjacent Bi-I octahedrons by the bilateral anchoring of the 3-AMP2+ diamine cation enhances both electronic conjugation and charge transport performance. Therefore, the photodetector for (3-AMP)BiI5 SC shows a 243-fold increase in on/off ratio compared with the (BZA)3 BiI6 SC.
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The partial substitution of chemical fertilizers with organic manure has positive effects on crop productivity and sustainable development. Nevertheless, few studies have focused on major grain crops. Herein, we report the short-term effects of the partial substitution of chemical fertilizers with organic manure on the physicochemical properties, microbial community, and enzyme activities in the rhizosphere soil of a maize (Zea mays L.) field. A decrease in soil bulk density, pH, and electrical conductivity, concomitant with an increase in soil urease, invertase, and alkaline phosphatase activities, and a high level of nutrients were observed in organic manure-treated soil. The influence of the organic substitution treatment on bacterial diversity was greater than that on fungal diversity, particularly on alpha diversity. Among dominant bacterial phyla, Actinobacteria abundance changed the most, with significantly increase under organic manure treatment. In turn, among fungi, only Ascomycota responded substantially to organic substitution. Binding spatial ordination analysis revealed that relative soil water content and soil organic carbon, and nitrate and total nitrogen contents had a stronger effect on bacteria and fungi, respectively, than any other soil physicochemical property. Additionally, the changes in bacterial and fungal communities influenced soil enzymatic activities. Moreover, partial least squares path model revealed that soil physicochemical properties indirectly affected soil enzymatic activities by their direct effects on microbial (both bacteria and fungi) community. Overall, our results indicate that the substitution of chemical fertilizers by organic manure changed the composition of the soil microbial community, and that the effects of the substitution were more significant on bacteria than on fungi.
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Fertilizantes , Microbiota , Carbono , Fertilizantes/análise , Esterco , Nitrogênio , Rizosfera , Solo , Microbiologia do SoloRESUMO
AIMS: The instantaneous wave-free ratio (iFR) and whole-cycle Pd/Pa investigate coronary physiology during non-hyperaemic conditions. To test for unique physiologic properties of the wave-free period when making resting coronary pressure measurements, we compared post hoc a diastolic pressure ratio (dPR) and Pd/Pa against iFR for numerical similarity and test/retest repeatability. METHODS AND RESULTS: Eight hundred and ninety-three lesions from 833 subjects were included from the VERIFY 2 and CONTRAST studies. Diastolic pressure ratio and a linear transform of Pd/Pa were compared against iFR for diagnostic performance. Mean difference between dPR and iFR [Δ = -0.006 ± 0.011, r2 = 0.993, area under receiver operating characteristic (ROC) curve (AUC) = 0.997] mirrored the difference of two iFR measurements repeated immediately (Δ = <0.001 ± 0.004, r2 = 0.998, AUC = 1.00). Minor variations in the definition of dPR changed its value by <1-2% over a broad range of the cardiac cycle. A linear transform of Pd/Pa showed very good diagnostic performance (Δ = -0.012 ± 0.031, r2 = 0.927, AUC = 0.979). Post hoc iFR values were validated against real-time iFR values and matched almost exactly (average Δ = <0.001 ± 0.004, 99.6% within ±0.01). CONCLUSIONS: Our dPR offers numerical equivalency to iFR. Despite different technical approaches for identifying the relevant period of diastole, the agreement between dPR and iFR and the insensitivity of dPR to minor variations in its definition further confirm numerical equivalency among resting metrics.
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Pressão Sanguínea/fisiologia , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiologia , Infarto do Miocárdio/fisiopatologia , Descanso/fisiologia , Idoso , Algoritmos , Estudos de Casos e Controles , Cateterismo/métodos , Cateterismo/tendências , Doença da Artéria Coronariana/cirurgia , Eletrocardiografia/métodos , Feminino , Coração/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
A severe haze episode occurred in winter in the North China Plain (NCP), and the phenomenon of an explosive growth and sharp decline in PM2.5 (particulate matter with an aerodynamic diameter equal to or less than 2.5⯵m) concentration was observed. To study the systematic causes for this phenomenon, comprehensive observations were conducted in Beijing from November 26 to December 2, 2015; during this period, meteorological parameters, LIDAR data, and the chemical compositions of aerosols were determined. The haze episode was characterized by rapidly varying PM2.5 concentration, and the highest PM2.5 concentration reached 667⯵g/m3. During the haze episode, the NCP was dominated by a weak high-pressure system and continuously low PBL (planetary boundary layer) heights, which are unfavorable conditions for the diffusion of pollutants. The large increases in the concentrations of SNA (SO42-, NO3- and NH4+) during the haze implied that the formation of SNA was the largest contribution. Water vapor also played a vital role in the formation of haze by promoting the chemical transformation of secondary pollutants, which led to higher PM2.5 concentrations. The spatial distributions of PM2.5 in Beijing at different times and the backward trajectories of the air masses also indicated that pollutants from surrounding provinces in particular, contributed to the higher PM2.5 concentration.
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Material Particulado/análise , Tempo (Meteorologia) , China , CidadesRESUMO
Low-dimensional luminescent lead halide perovskites have attracted tremendous attention for their fascinating optoelectronic properties, while the toxicity of lead is still considered a drawback. Herein, we report a novel lead-free zero-dimensional (0D) indium-based perovskite (Cs2 InBr5 â H2 O) single crystal that is red-luminescent with a high photoluminescence quantum yield (PLQY) of 33 %. Experimental and computational studies reveal that the strong PL emission might originate from self-trapping excitons (STEs) that result from an excited-state structural deformation. More importantly, the inâ situ transformation between hydrated Cs2 InBr5 â H2 O and the dehydrated form is accompanied with a switchable dual emission, which enables it to act as a PL water-sensor in humidity detection or the detection of traces of water in organic solvents.
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To investigate the characteristics and the specific mechanism of continuous haze, comprehensive measurements were conducted from 15 October to 19 November in the Atmospheric Environment Monitoring Super-Station in Heshan of Guangdong province. Five haze episodes occurred in October and November 2014 in the Pearl River Delta (PRD) region. The meteorological parameters, gas data, chemical compositions, and optical parameters of the aerosols were obtained. Among these events, the second haze episode, with the highest concentration of PM2.5 of 187.51µg/m3, was the most severe. NO3- was always higher than SO42-, which indicated that motor vehicles played an important role in the haze, even though the oxidation rate from SO2 to SO42- was faster than that of NOX to NO3-. The difference between the hourly averages of Na+ and K+ during the haze episode and clean days was small, implying that straw combustion and sea salt had no significant effect on the occurrence of haze, and the backward trajectories of the air masses also conformed with this result. The air pollutants were difficult to disperse because of the significant decrease in the planetary boundary layer (PBL) height. Relative humidity played a crucial role in the formation of haze by leading to hygroscopic growth of the diameter of aerosols.
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Monitoramento Ambiental , Material Particulado/análise , Poluentes Atmosféricos , ChinaRESUMO
Isocorydine (ICD), an aporphine alkaloid, is widely distributed in nature. Its ability to target side population (SP) cells found in human hepatocellular carcinoma (HCC) makes it and its derivative 8-amino-isocorydine (NICD) promising chemotherapeutic agents for the treatment of HCC. To improve the anticancer activity of isocorydine derivatives, twenty derivatives of NICD were designed and synthesized through chemical structure modifications of the aromatic amino group at C-8. The anti-proliferative activities of all synthesized compounds against human hepatocellular (HepG2), cervical (HeLa), and gastric (MGC-803) cancer cell lines were evaluated using an MTT assay. The results showed that all the synthetic compounds had some tumor cell growth inhibitory activity. The compound COM33 (24) was the most active with IC50 values under 10⯵M (IC50 for HepG2â¯=â¯7.51⯵M; IC50 for HeLaâ¯=â¯6.32⯵M). FICD (12) and COM33 (24) were selected for further investigation of their in vitro and in vivo activities due to their relatively good antiproliferative properties. These two compounds significantly downregulated the expression of four key proteins (C-Myc, ß-Catenin, CylinD1, and Ki67) in HepG2 cells. The tumor inhibition rate of COM33 (24) in vivo was 73.8% after a dose 100â¯mg/kg via intraperitoneal injection and the combined inhibition rate of COM33 (24) (50â¯mg/kg) with sorafenib (50â¯mg/kg) was 66.5%. The results indicated that these isocorydine derivatives could potentially be used as targeted chemotherapy agents or could be further developed in combination with conventional chemotherapy drugs to target cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT), the main therapeutic targets in HCC.
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Antineoplásicos/farmacologia , Aporfinas/farmacologia , Desenho de Fármacos , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Aporfinas/síntese química , Aporfinas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Modelos Moleculares , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Relação Estrutura-AtividadeRESUMO
The rotationally resolved infrared spectra of (HCOOH)2, (HCOOD)2, and HCOOH-HCOOD complexes have been measured in 7.2 µm region by using a segmented rapid-scan distributed-feedback quantum cascade laser absorption spectrometer to probe a slit supersonic jet expansion. The observed spectra are assigned to the v21 (H-C/O-H in-plane bending) fundamental band of (HCOOH)2, the v15 (H-C/O-D in-plane bending) fundamental band of HCOOH-HCOOD, and the v20 (H-C-O in-plane bending) fundamental band of (HCOOD)2. Strong local perturbations caused by the rotation-tunneling coupling between two tunneling components are observed in (HCOOH)2. The v21 fundamental band of (HCOOH)2 and the previously measured v22 fundamental and v12 + v14 combination bands [K. G. Goroya et al., J. Chem. Phys. 140, 164311 (2014)] are analyzed together, yielding a more precise tunneling splitting in the ground state, 0.011 367(92) cm-1. The band-origin of the v21 band of (HCOOH)2 is 1371.776 74(8) cm-1, and the tunneling splitting decreases to 0.000 38(18) cm-1 upon the vibrational excitation. The vibrational energy is 1386.755 49(16) cm-1 for the v15 vibrational mode of HCOOH-HCOOD and 1391.084 39(17) cm-1 for the v20 vibrational mode of (HCOOD)2. No apparent spectral splittings are resolved for HCOOH-HCOOD and (HCOOD)2 under our experimental conditions. The tunneling splitting in the ground state of HCOOH-HCOOD is estimated to be 0.001 13 cm-1 from its average linewidth.
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Isocorydine and its analogs were extracted from Dicranostigma leptopodum and Stephania yunnanensis through the method of natural products chemistry. Its derivatives were prepared by chemical structure modifications from isocorydine. MTT method was used to study the inhibitory effect of those compounds on the growth of HepG2, HeLa and MGC-803 cancer cell lines in vitro. The results showed that isocorydine and its analogs all have the growth inhibition for those cancer cell lines. This paper investigated the structure-activity relationship of isocorydine and its derivatives with anticancer activity in the aspect of stereochemical structure, functional groups positions of the compounds and the electron density of aromatic rings based on the single crystal diffraction structure and the molecular docking of EGFR and isocorydine.
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Antineoplásicos/farmacologia , Aporfinas/farmacologia , Linhagem Celular Tumoral , Receptores ErbB , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
A surfactant-free solution methodology, simply using water as a solvent, has been developed for the straightforward synthesis of single-phase orthorhombic SnSe nanoplates in gram quantities. Individual nanoplates are composed of {100} surfaces with {011} edge facets. Hot-pressed nanostructured compacts (Eg ≈0.85â eV) exhibit excellent electrical conductivity and thermoelectric power factors (S(2) σ) at 550â K. S(2) σ values are 8-fold higher than equivalent materials prepared using citric acid as a structure-directing agent, and electrical properties are comparable to the best-performing, extrinsically doped p-type polycrystalline tin selenides. The method offers an energy-efficient, rapid route to p-type SnSe nanostructures.
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Damage to soft tissues in the human body has been investigated for applications in healthcare, sports, and biomedical engineering. This paper reviews and classifies damage models for soft tissues to summarize achievements, identify new directions, and facilitate finite element analysis. The main ideas of damage modeling methods are illustrated and interpreted. A few key issues related to damage models, such as experimental data curve-fitting, computational effort, connection between damage and fractures/cracks, damage model applications, and fracture/crack extension simulation, are discussed. Several new challenges in the field are identified and outlined. This review can be useful for developing more advanced damage models and extending damage modeling methods to a variety of soft tissues.
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In order to improve the anticancer activity of isocorydine (ICD), ten isocorydine derivatives were prepared through chemical structure modifications, and their in vitro and in vivo activities were experimentally investigated. 8-Amino-isocorydine (8) and 6a,7-dihydrogen-isocorydione (10) could inhibit the growth of human lung (A549), gastric (SGC7901) and liver (HepG2) cancer cell lines in vitro. Isocorydione (2) could inhibit the tumor growth of murine sarcoma S180-bearing mice, and 8-acetamino-isocorydine (11), a pro-drug of 8-amino-isocorydine (8), which is instable in water solution at room temperature, had a good inhibitory effect on murine hepatoma H22-induced tumors. The results suggested that the isocorydine structural modifications at C-8 could significantly improve the biological activity of this alkaloid, indicating its suitability as a lead compound in the development of an effective anticancer agent.
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Antineoplásicos Fitogênicos/química , Aporfinas/química , Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Alcaloides/administração & dosagem , Alcaloides/síntese química , Alcaloides/química , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/síntese química , Aporfinas/administração & dosagem , Aporfinas/síntese química , Células Hep G2 , Humanos , Camundongos , Neoplasias/patologiaRESUMO
Intermolecular annulation reactions of 1-naphthyl-1,3-indandiones with alkenes proceed efficiently in the presence of a copper catalyst to generate spirocarbocycle compounds. Various spirocyclic molecules bearing an all-carbon quaternary center could be obtained by this novel method with good yields, excellent regioselectivity, and good functional group tolerance. A radical mechanism is proposed based on the HRMS analysis results of control experiments.