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Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of suboptimal peak signal-to-baseline ratio (SBR) with limited resolution for reporting subtle calcium transients. We report herein the development of a suite of calcium sensors, designated NEMO, with fast kinetics and wide dynamic ranges (>100-fold). NEMO indicators report Ca2+ transients with peak SBRs around 20-fold larger than the top-of-the-range GCaMP6 series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared with GCaMP6s, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times larger in vivo, thereby outperforming most existing state-of-the-art GECIs. Given their high sensitivity and resolution to report intracellular Ca2+ signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca2+-modulated physiological processes in both mammals and plants.
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Cálcio , Neurônios , Animais , Cálcio/metabolismo , Neurônios/fisiologia , Sinalização do Cálcio/fisiologia , Indicadores e Reagentes , Mamíferos/metabolismoRESUMO
Rapid advances in genetics are linking mutations on genes to diseases at an exponential rate, yet characterizing the gene-mutation-cell-behavior relationships essential for precision medicine remains a daunting task. More than 350 mutations on small GTPase BRaf are associated with various tumors, and â¼40 mutations are associated with the neurodevelopmental disorder cardio-facio-cutaneous syndrome (CFC). We developed a fast cost-effective lentivirus-based rapid gene replacement method to interrogate the physiopathology of BRaf and â¼50 disease-linked BRaf mutants, including all CFC-linked mutants. Analysis of simultaneous multiple patch-clamp recordings from 6068 pairs of rat neurons with validation in additional mouse and human neurons and multiple learning tests from 1486 rats identified BRaf as the key missing signaling effector in the common synaptic NMDA-R-CaMKII-SynGap-Ras-BRaf-MEK-ERK transduction cascade. Moreover, the analysis creates the original big data unveiling three general features of BRaf signaling. This study establishes the first efficient procedure that permits large-scale functional analysis of human disease-linked mutations essential for precision medicine.
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Sistema de Sinalização das MAP Quinases/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Transmissão Sináptica/genética , Animais , Células Cultivadas , Doença/genética , Feminino , Técnicas de Transferência de Genes , Humanos , Lentivirus/genética , Masculino , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Ratos Sprague-Dawley , Técnicas de Cultura de TecidosRESUMO
The electrocatalytic production of hydrogen peroxide (H2O2) through the two-electron oxygen reduction reaction (2e- ORR) has garnered significant research attention in recent years due to its numerous appealing advantages, such as being eco-friendly and exhibiting high energy conversion efficiency. Metal-free carbon materials with specific catalytic sites have been recognized as potential electrocatalysts for 2e- ORR; however, the design of highly efficient catalysts with well-defined structures and long-term stability for large-scale H2O2 production remains unsatisfactory. In this study, three covalent organic frameworks (COFs) - imine-linked LZU-1, oxazole-linked LZU-190, and thiazole-linked LZU-190(S), are successfully synthesized to explore their catalytic activity in electrocatalytic H2O2 production. Among these, the carbon sites LZU-190(S) are predominantly activated by the introduced adjacent heteroatoms via electronic effects, resulting in much higher H2O2 selectivity compared to the oxazole and imine linkages. This work provides new insights into developing COFs-based electrocatalysts for efficient H2O2 generation.
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Amidino-based additives show great potential in high-performance perovskite solar cells (PSCs). However, the role of different functional groups in amidino-based additives have not been well elucidated. Herein, two multifunctional amidino additives 4-amidinobenzoic acid hydrochloride (ABAc) and 4-amidinobenzamide hydrochloride (ABAm) are employed to improve the film quality of formamidinium lead iodide (FAPbI3) perovskites. Compared with ABAc, the amide group imparts ABAm with larger dipole moment and thus stronger interactions with the perovskite components, i.e., the hydrogen bonds between N H and I- anion and coordination bonds between C = O and Pb2+ cation. It strengthens the passivation effect of iodine vacancy defect and slows down the crystallization process of α-FAPbI3, resulting in the significantly reduced non-radiative recombination, long carrier lifetime of 1.7 µs, uniformly large crystalline grains, and enhances hydrophobicity. Profiting from the improved film quality, the ABAm-treated PSC achieves a high efficiency of 24.60%, and maintains 93% of the initial efficiency after storage in ambient environment for 1200 hours. This work provides new insights for rational design of multifunctional additives regarding of defect passivation and crystallization control toward highly efficient and stable PSCs.
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Constructing quantum dot-scale metal sulfides with defects and strongly coupled with carbon is significant for advanced sodium-ion batteries (SIBs). Herein, Se substituted V3S4 quantum dots with anionic defects confined in nitrogen-doped carbon matrix (V3S4-xSex/NC) are fabricated. Introducing element Se into V3S4 crystal expands the interlayer distance of V3S4, and triggers anionic defects, which can facilitate Na+ diffusions and act as active sites for Na+ storage. Meanwhile, the quantum dots tightly encapsulated by conductive carbon framework improve the stability and conductivity of the electrode. Theoretical calculations also unveil that the presence of Se enhances the conductivity and Na+ adsorption ability of V3S4-xSex. These properties contribute to the V3S4-xSex/NC with high specific capacity of 447 mAh g-1 at 0.2 A g-1, and prominent rate and cyclic performance with 504 mAh g-1 after 1000 cycles at 10 A g-1. The sodium-ion hybrid capacitors (SIHCs) with V3S4-xSex/NC anode and activated carbon cathode can achieve high energy/power density (maximum 144 Wh kg-1/5960 W kg-1), capacity retention ratio of 71% after 4000 cycles at 2 A g-1. This work not only synthesizes V3S4-xSex/NC, but also provides a promising opportunity for designing quantum dots and utilizing defects to improve the electrochemical properties.
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Atractylodes chinensis is one of the most commonly used bulk herbs in East Asia; however, root rot can seriously affect its quality and yields. In contrast to chemical pesticides, biological control strategies are environmentally compatible and safe. For this study, 68 antagonistic bacterial strains were isolated from the rhizospheres of healthy Atractylodes chinensis. Strain SY42 exhibited the most potent fungicidal activities, with inhibition rates against F. oxysporum, F. solani, and F. redolens of 67.07 %, 63.40 % and 68.45 %, respectively. Through morphological observation and molecular characterization, strain SY42 was identified as Paenibacillus polymyxa. The volatile organic components (VOCs) produced by SY42 effectively inhibited the mycelial growth of pathogenic fungi through diffusion. SY42 significantly inhibited the germination of pathogenic fungal spores. Following co-culturing with SY42, the mycelium of the pathogenic fungus was deformed, folded, and even ruptured. SY42 could produce cellulases and proteases to degrade fungal cell walls. Pot experiments demonstrated the excellent biocontrol efficacy of SY42. This study revealed that P. polymyxa SY42 inhibited pathogenic fungi through multiple mechanisms, which verified its utility as a biocontrol agent for the control of A. chinensis root rot.
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Atractylodes , Fusarium , Paenibacillus polymyxa , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , MicélioRESUMO
Decellularized extracellular matrix hydrogel (ECM hydrogel), a natural material derived from normal tissue with unique biocompatibility properties, is widely used for tissue repair. However, there are still problems such as poor biological activity and insufficient antimicrobial property. To overcome these drawbacks, fibroblast growth factor 2 (FGF 2) containing exosome (exoFGF 2) was prepared to increase the biological activity. Furthermore, the antimicrobial capacity of ECM hydrogel was optimised by using copper ions as a ligand-bonded cross-linking agent. The decellularized extracellular matrix hydrogel, intricately cross-linked with copper ions through ligand bonds and loaded with FGF 2 containing exosome (exoFGF 2@ECM/Cu2+ hydrogel), has demonstrated exceptional biocompatibility and antimicrobial properties. In vitro, exoFGF 2@ECM/Cu2+ hydrogel effectively promoted cell proliferation, migration, antioxidant and inhibited bacterial growth. In vivo, the wound area of rat treated with exoFGF 2@ECM/Cu2+ hydrogels were significantly smaller than that of other groups at Day 5 (45.24% ± 3.15%), Day 10 (92.20% ± 2.31%) and Day 15 (95.22% ± 1.28%). Histological examination showed that exoFGF 2@ECM/Cu2+ hydrogels promoted angiogenesis and collagen deposition. Overall, this hydrogel has the potential to inhibit bacterial growth and effectively promote wound healing in a variety of clinical applications.
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Proliferação de Células , Exossomos , Matriz Extracelular , Fator 2 de Crescimento de Fibroblastos , Hidrogéis , Pele , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator 2 de Crescimento de Fibroblastos/química , Exossomos/química , Exossomos/metabolismo , Ratos , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Cicatrização/efeitos dos fármacos , Pele/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ratos Sprague-Dawley , Humanos , Cobre/química , Cobre/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Masculino , Camundongos , Movimento Celular/efeitos dos fármacos , Engenharia Tecidual/métodosRESUMO
The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.
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Sinalização do Cálcio , Hibernação , Miócitos Cardíacos/metabolismo , Animais , Caveolinas/genética , Caveolinas/metabolismo , Células Cultivadas , Acoplamento Excitação-Contração , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Nucleares/sangue , Proteínas Nucleares/metabolismo , Sciuridae , Transativadores/sangue , Transativadores/metabolismoRESUMO
This study investigated the effects of different exercise interventions on cardiopulmonary function in male tobacco-dependent college students. Forty-five male tobacco-dependent college students were recruited as the tobacco-dependent (TB) group, and 45 non-tobacco-dependent college students were recruited as the control group. The TB group was randomly assigned to three subgroups: non-exercise (NE), high-intensity interval training (HIIT), and moderate-intensity continuous training (MICT). The HIIT and MICT groups underwent a 10-week exercise training, while the NE group received no intervention. Cardiac parameters, including maximal oxygen uptake (VO2max), heart rate max (HRmax), and heart rate reserve (HRR), and pulmonary indicators, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), vital capacity (VC), maximum ventilation volume (MVV), and peak expiratory flow (PEF) were investigated. The results showed that the TB group had significantly lower cardiopulmonary function than the control group. The degree of tobacco dependence was negatively correlated with VO2max, FVC, FEV1, FEV1/FVC, and MVV. Furthermore, both HIIT and MICT training improved cardiopulmonary function. HIIT training exhibited superior efficacy compared to MICT in improving HRmax, HRR, FVC, FEV1, FEV1/FVC, and PEF. In conclusion, tobacco dependence adversely affects cardiopulmonary function in male college students. Both HIIT and MICT effectively improved cardiopulmonary function, with HIIT showing superior efficacy.
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Radioisotope leaking from nuclear waste has become an intractable problem due to its gamma radiation and strong water solubility. In this work, a novel porous ZnFC-PA/PSF composite sphere was fabricated by immobilization of ferrocyanides modified zinc phytate into polysulfone (PSF) substrate for the treatment of Cs-contaminated water. The maximum adsorption capacity of ZnFC-PA/PSF was 305.38 mg/g, and the removal efficiency of Cs+ was reached 94.27% within 2 hr. The ZnFC-PA/PSF presented favorable stability with negligible dissolution loss of Zn2+ and Fe2+ (< 2%). The ZnFC-PA/PSF achieved high-selectivity towards Cs+ (Kd = 2.24×104 mL/g) even in actual geothermal water. The adsorption mechanism was inferred to be the ion-exchange between Cs+ and K+. What's more, ZnFC-PA/PSF worked well in the fixed-bed adsorption (E = 91.92%), indicating the application potential for the hazardous Cs+ removal from wastewater.
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Poluentes Químicos da Água , Adsorção , Poluentes Químicos da Água/química , Purificação da Água/métodos , Sulfonas/química , Polímeros/química , Porosidade , Césio/química , Eliminação de Resíduos Líquidos/métodos , Zinco/química , Águas Residuárias/químicaRESUMO
BACKGROUND: Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease, the leading cause of morbidity and mortality worldwide. At present, there is no effective therapy for reducing cardiac I/R injury. CaMKII (Ca2+/calmodulin-dependent kinase II) plays a pivotal role in the pathogenesis of severe heart conditions, including I/R injury. Pharmacological inhibition of CaMKII is an important strategy in the protection against myocardial damage and cardiac diseases. To date, there is no drug targeting CaMKII for the clinical therapy of heart disease. Furthermore, at present, there is no selective inhibitor of CaMKII-δ, the major CaMKII isoform in the heart. METHODS: A small-molecule kinase inhibitor library and a high-throughput screening system for the kinase activity assay of CaMKII-δ9 (the most abundant CaMKII-δ splice variant in human heart) were used to screen for CaMKII-δ inhibitors. Using cultured neonatal rat ventricular myocytes, human embryonic stem cell-derived cardiomyocytes, and in vivo mouse models, in conjunction with myocardial injury induced by I/R (or hypoxia/reoxygenation) and CaMKII-δ9 overexpression, we sought to investigate the protection of hesperadin against cardiomyocyte death and cardiac diseases. BALB/c nude mice with xenografted tumors of human cancer cells were used to evaluate the in vivo antitumor effect of hesperadin. RESULTS: Based on the small-molecule kinase inhibitor library and screening system, we found that hesperadin, an Aurora B kinase inhibitor with antitumor activity in vitro, directly bound to CaMKII-δ and specifically blocked its activation in an ATP-competitive manner. Hesperadin functionally ameliorated both I/R- and overexpressed CaMKII-δ9-induced cardiomyocyte death, myocardial damage, and heart failure in both rodents and human embryonic stem cell-derived cardiomyocytes. In addition, in an in vivo BALB/c nude mouse model with xenografted tumors of human cancer cells, hesperadin delayed tumor growth without inducing cardiomyocyte death or cardiac injury. CONCLUSIONS: Here, we identified hesperadin as a specific small-molecule inhibitor of CaMKII-δ with dual functions of cardioprotective and antitumor effects. These findings not only suggest that hesperadin is a promising leading compound for clinical therapy of cardiac I/R injury and heart failure, but also provide a strategy for the joint therapy of cancer and cardiovascular disease caused by anticancer treatment.
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Insuficiência Cardíaca , Traumatismo por Reperfusão Miocárdica , Neoplasias , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Insuficiência Cardíaca/patologia , Humanos , Indóis , Isquemia/metabolismo , Camundongos , Camundongos Nus , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Neoplasias/patologia , Ratos , SulfonamidasRESUMO
High and increasing production of separation of C8 aromatic isomers demands the development of purification methods that are efficient, scalable, and inexpensive, especially for p-xylene, PX, the largest volume C8 commodity. Herein, we report that 4-(1H-1,2,4-triazol-1-yl)-phenyl-1H-benzo[de]isoquinoline-1,3(2H)-dione (TPBD), a molecular compound that can be prepared and scaled up via solid-state synthesis, exhibits exceptional PX selectivity over each of the other C8 isomers, o-xylene (OX), m-xylene (MX), and ethylbenzene (EB). The apohost or α form of TPBD was found to exhibit conformational polymorphism in the solid state enabled by rotation of its triazole and benzene rings. TPBD-αI and TPBD-αII are nonporous polymorphs that transformed to the same PX inclusion compound, TPBD-PX, upon contact with liquid PX. TPBD enabled highly selective capture of PX, as established by competitive slurry experiments involving various molar ratios in binary, ternary, and quaternary mixtures of C8 aromatics. Binary selectivity values for PX as determined by 1H NMR spectroscopy and gas chromatography ranged from 22.4 to 108.4, setting new benchmarks for both PX/MX (70.3) and PX/EB (59.9) selectivity as well as close to benchmark selectivity for PX/OX (108.4). To our knowledge, TPBD is the first material of any class to exhibit such high across-the-board PX selectivity from quaternary mixtures of C8 aromatics under ambient conditions. Crystallographic and computational studies provide structural insight into the PX binding site in TPBD-PX, whereas thermal stability and capture kinetics were determined by variable-temperature powder X-ray diffraction and slurry tests, respectively. That TPBD offers benchmark PX selectivity and facile recyclability makes it a prototypal molecular compound for PX purification or capture under ambient conditions.
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Ultramicroporous materials can be highly effective at trace gas separations when they offer a high density of selective binding sites. Herein, we report that sql-NbOFFIVE-bpe-Cu, a new variant of a previously reported ultramicroporous square lattice, sql, topology material, sql-SIFSIX-bpe-Zn, can exist in two polymorphs. These polymorphs, sql-NbOFFIVE-bpe-Cu-AA (AA) and sql-NbOFFIVE-bpe-Cu-AB (AB), exhibit AAAA and ABAB packing of the sql layers, respectively. Whereas NbOFFIVE-bpe-Cu-AA (AA) is isostructural with sql-SIFSIX-bpe-Zn, each exhibiting intrinsic 1D channels, sql-NbOFFIVE-bpe-Cu-AB (AB) has two types of channels, the intrinsic channels and extrinsic channels between the sql networks. Gas and temperature induced transformations of the two polymorphs of sql-NbOFFIVE-bpe-Cu were investigated by pure gas sorption, single-crystal X-ray diffraction (SCXRD), variable temperature powder X-ray diffraction (VT-PXRD), and synchrotron PXRD. We observed that the extrinsic pore structure of AB resulted in properties with potential for selective C3H4/C3H6 separation. Subsequent dynamic gas breakthrough measurements revealed exceptional experimental C3H4/C3H6 selectivity (270) and a new benchmark for productivity (118 mmol g-1) of polymer grade C3H6 (purity >99.99%) from a 1:99 C3H4/C3H6 mixture. Structural analysis, gas sorption studies, and gas adsorption kinetics enabled us to determine that a binding "sweet spot" for C3H4 in the extrinsic pores is behind the benchmark separation performance. Density-functional theory (DFT) calculations and Canonical Monte Carlo (CMC) simulations provided further insight into the binding sites of C3H4 and C3H6 molecules within these two hybrid ultramicroporous materials, HUMs. These results highlight, to our knowledge for the first time, how pore engineering through the study of packing polymorphism in layered materials can dramatically change the separation performance of a physisorbent.
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BACKGROUND: This study aimed to develop a novel predictive nomogram to identify specific stage IB non-small cell lung cancer (NSCLC) populations who could benefit from adjuvant chemotherapy (ACT). METHOD: Stage IB NSCLC patients were included in the Surveillance, Epidemiology, and End Results (SEER) database and divided into the ACT and non-ACT groups. Then the methods of Kaplan-Meier analysis, propensity score matching (PSM), Least absolute shrink and selection operator (LASSO) regression, and multivariate logistic regression analyses were implemented. Finally, the predictive nomogram was constructed and validated. RESULTS: 9055 stage IB NSCLC patients were enrolled from the SEER database while 47 patients from Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University were identified as the external validation cohort. Of these patients, 1334 cases underwent ACT while the other 7721 patients didn't receive ACT. After PSM, the patients in the ACT group presented longer median overall survival (100 vs 82 months, P < .001). Among the ACT group, 482 (49.6%) patients achieving more prolonged overall survival than 82 months were regarded as the beneficiary population. Then the LASSO regression and multivariate logistic regression analyses were implemented. Finally, 8 predictors were selected for model construction, including age, gender, marital status, laterality, pathology, tumor size, regional nodes examined, and tumor size. The predictive nomogram demonstrated good discrimination in the training cohort (AUC = .781), internal validation cohort (AUC = .772), and external validation cohort (AUC = .851). And calibration curves indicated ideal consistency between the predicted and observed probabilities. Decision curve analysis presented a clinically useful model. CONCLUSION: The practical nomogram could guide treatment decision-making and select optimal ACT candidates among stage IB NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante , Neoplasias Pulmonares/tratamento farmacológico , NomogramasRESUMO
BACKGROUND: Echocardiography plays an important role in the diagnosis of heart disease. Sometimes, however, it may also provide misdiagnosis information. CASE PRESENTATION: We report a rare case of a misdiagnosis of primary mitral valvular tumor with severe regurgitation by preoperative echocardiography. During the surgery, the true lesion was found to be mitral valve leaflet prolapse due to degenerative mitral valve disease. CONCLUSION: For individual patient, the best clinical decision not only needs the extensive application of echocardiography, but also needs the combination of clinical symptoms and more auxiliary examination.
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Insuficiência da Valva Mitral , Prolapso da Valva Mitral , Neoplasias , Humanos , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , EcocardiografiaRESUMO
BACKGROUND: Due to the widespread application of bioprosthetic valve in the treatment of mitral valve disease in recent years, the incidence of valve failure has increased significantly, which is facing the need of reoperation. For high-risk patients, transcatheter mitral valve-in-valve placement is increasingly being used as an alternative to surgical reoperation. CASE PRESENTATION: Here we report the successful transapical transcatheter mitral valve-in-valve implantations of J-Valves in 3 patients with high risk of mitral bioprostheses failure. All patients were discharged successfully, and the follow-up results were good 30 days after operation without major complication. CONCLUSIONS: For high-risk patients, transcatheter implantation of the J-valve is a feasible solution for the treatment of degenerated mitral bioprostheses.
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Bioprótese , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Resultado do Tratamento , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/métodos , Falha de Prótese , Desenho de PróteseRESUMO
Simultaneous dysregulation of multiple microRNAs (miRs) affects various pathological pathways related to cardiac failure. In addition to being potential cardiac disease-specific markers, miR-23b/27b/24-1 were reported to be responsible for conferring cardiac pathophysiological processes. In this study, we identified a conserved guanine-rich RNA motif within the miR-23b/27b/24-1 cluster that can form an RNA G-quadruplex (rG4) in vitro and in cells. Disruption of this intragenic rG4 significantly increased the production of all three miRs. Conversely, a G4-binding ligand tetrandrine (TET) stabilized the rG4 and suppressed miRs production in human and rodent cardiomyocytes. Our further study showed that the rG4 prevented Drosha-DGCR8 binding and processing of the pri-miR, suppressing the biogenesis of all three miRs. Moreover, CRISPR/Cas9-mediated G4 deletion in the rat genome aberrantly elevated all three miRs in the heart in vivo, leading to cardiac contractile dysfunction. Importantly, loss of the G4 resulted in reduced targets for the aforementioned miRs critical for normal heart function and defects in the L-type Ca2+ channel-ryanodine receptor (LCC-RyR) coupling in cardiomyocytes. Our results reveal a novel mechanism for G4-dependent regulation of miR biogenesis, which is essential for maintaining normal heart function.
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Quadruplex G , MicroRNAs/química , MicroRNAs/metabolismo , Contração Miocárdica/genética , Miócitos Cardíacos/metabolismo , Animais , Benzilisoquinolinas/farmacologia , Sistemas CRISPR-Cas , Células Cultivadas , Quadruplex G/efeitos dos fármacos , Regulação da Expressão Gênica , Miocárdio/metabolismo , Miócitos Cardíacos/fisiologia , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/metabolismo , Ratos , Ratos Sprague-Dawley , Ribonuclease III/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismoRESUMO
A general and adaptable method is proposed to reliably extract quantitative information from smartphone images of microfluidic sensors. By analyzing and processing the color information of selected standard substances, the influence of light conditions, device differences, and human factors could be significantly reduced. Machine learning and multivariate fitting methods were proved to be effective for chroma correction, and a key element was the training of sample size and the fitting form, respectively. A custom APP was developed and validated using a high-sensitivity chromium ion quantification paper chip. The average chroma deviations under different conditions were reduced by more than 75% in RGB color space, and the concentration test error was reduced by more than half compared with the commonly used method. The proposed approach could be a beneficial supplement to existing and potential colorimetry-based detection methods.
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We report that linker ligand substitution involving just one atom induces a shape-memory effect in a flexible coordination network. Specifically, whereas SIFSIX-23-Cu, [Cu(SiF6 )(L)2 ]n , (L=1,4-bis(1-imidazolyl)benzene, SiF6 2- =SIFSIX) has been previously reported to exhibit reversible switching between closed and open phases, the activated phase of SIFSIX-23-CuN , [Cu(SiF6 )(LN )2 ]n (LN =2,5-bis(1-imidazolyl)pyridine), transformed to a kinetically stable porous phase with strong affinity for CO2 . As-synthesized SIFSIX-23-CuN , α, transformed to less open, γ, and closed, ß, phases during activation. ß did not adsorb N2 (77â K), rather it reverted to α induced by CO2 at 195, 273 and 298â K. CO2 desorption resulted in α', a shape-memory phase which subsequently exhibited type-I isotherms for N2 (77â K) and CO2 as well as strong performance for separation of CO2 /N2 (15/85) at 298â K and 1â bar driven by strong binding (Qst =45-51â kJ/mol) and excellent CO2 /N2 selectivity (up to 700). Interestingly, α' reverted to ß after re-solvation/desolvation. Molecular simulations and density functional theory (DFT) calculations provide insight into the properties of SIFSIX-23-CuN .
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Photovoltaic technology with low weight, high specific power in cold environments, and compatibility with flexible fabrication is highly desired for near-space vehicles and polar region applications. Herein, we demonstrate efficient low-temperature flexible perovskite solar cells by improving the interfacial contact between electron-transport layer (ETL) and perovskite layer. We find that the adsorbed oxygen active sites and oxygen vacancies of flexible tin oxide (SnO2 ) ETL layer can be effectively decreased by incorporating a trace amount of titanium tetrachloride (TiCl4 ). The effective defects elimination at the interfacial increases the electron mobility of flexible SnO2 layer, regulates band alignment at the perovskite/SnO2 interface, induces larger perovskite crystal growth, and improves charge collection efficiency in a complete solar cell. Correspondingly, the improved interfacial contact transforms into high-performance solar cells under one-sun illumination (AM 1.5G) with efficiencies up to 23.7 % at 218â K, which might open up a new era of application of this emerging flexible photovoltaic technology to low-temperature environments such as near-space and polar regions.