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1.
Cell ; 187(9): 2129-2142.e17, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670071

RESUMO

Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.


Assuntos
Prosencéfalo , Animais , Prosencéfalo/metabolismo , Prosencéfalo/embriologia , Camundongos , Ratos , Blastocisto/metabolismo , Feminino , Sistemas CRISPR-Cas/genética , Transcriptoma , Organogênese , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Masculino , Camundongos Endogâmicos C57BL
2.
Org Biomol Chem ; 22(14): 2824-2834, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38511321

RESUMO

An efficient, diversity-oriented synthesis of indole-1,2-fused 1,4-benzodiazepines, tetrahydro-ß-carbolines, and 2,2'-bis(indolyl)methanes was established starting from tosyl-protected tryptamine. These diverse privileged skeletons were controllably constructed by adjusting different hydride donors and Brønsted acids. A variety of indole-1,2-fused 1,4-benzodiazepines were facilely accessed using benzaldehydes bearing cyclic amines as hydride donors via a cascade N-alkylation/dehydration/[1,5]-hydride transfer/Friedel-Crafts alkylation sequence. The reaction site could be switched when benzaldehydes bearing an alkoxy moiety as hydride donors were used for the generation of tetrahydro-ß-carbolines. On the other hand, the switchable synthesis of 2,2'-bis(indolyl)methanes could be achieved as well by applying p-TsOH·H2O as a catalyst. The reactions feature mild conditions, simple and practical operation, excellent efficiency and the use of EtOH as a green solvent. Using the concept of diversity-oriented, reagent-based synthesis, the inexpensive feedstock tryptamine was efficiently converted to three different types of privileged scaffolds, which facilitates rapid compound library synthesis for accelerating drug discovery.

3.
Molecules ; 29(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38474524

RESUMO

The Sc(OTf)3-catalyzed dearomative [5+1] annulations between readily available 3-aminophenols and O-alkyl ortho-oxybenzaldehydes were developed for synthesis of spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones. The "two-birds-with-one-stone" strategy was disclosed by the dearomatization of phenols and direct α-C(sp3)-H bond functionalization of oxygen through cascade condensation/[1,5]-hydride transfer/dearomative-cyclization process. In addition, the antifungal activity assay and derivatizations of products were conducted to further enrich the utility of the structure.

4.
BMC Nurs ; 23(1): 296, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684975

RESUMO

BACKGROUND: Intrahospital transport of critically ill patients is a common practice in intensive care units (ICUs), where patients' safety is constantly challenged in high-intensity and dynamic environments. While Intrahospital Transport Safety Scale (IHTSS) is widely used internationally to evaluate the intrahospital transport safety, it has not been introduced in China. OBJECTIVES: This study aimed to assess the reliability and validity of the Chinese version of the IHTSS scale among critical care nurses in China. METHODS: A cross-sectional study was conducted using a cluster sampling method. A total of 544 critical care nurses from 25 ICUs in 10 tertiary hospitals were recruited. We employed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to examine the questionnaire's underlying factor structure, ensuring construct validity. Additionally, internal consistency was assessed using Cronbach's alpha coefficient, test-retest reliability, and corrected item-total correlation. RESULTS: The Chinese version of the scale displayed robust psychometric properties, with a Cronbach's α coefficient of 0.976, a split-half reliability of 0.906, and a test-retest reliability of 0.856. EFA revealed a robust four-factor model that accounted for 75.970% of the variance, with the factor loadings of the items ranging from 0.433 to 0.951. CFA indicated a strong model fit, with a chi-square to degrees of freedom ratio (CMIN/DF) of 2.765, comparative fit index (CFI) of 0.943, incremental fit index (IFI) of 0.943, and goodness-of-fit index (GFI) of 0.845, supporting the efficacy of the four-factor model in assessing intrahospital transport safety for critically ill patients. CONCLUSION: The Chinese version of the IHTSS demonstrated favourable reliability and validity among critical care nurses in China, making it a suitable tool for measuring the level of intrahospital transport safety for critically ill patients.

5.
Org Biomol Chem ; 21(4): 700-714, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36601772

RESUMO

The use of alkyl amines and ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions represents a promising strategy that greatly enriches redox-neutral hydride transfer chemistry. This review summarizes the remarkable progress made in this field, and focuses on (1) alkyl amines as traceless hydride donors in cascade [1,5]-hydride transfer/elimination reactions and (2) alkyl ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions. The reaction mechanisms, features, scope, limitations, and synthetic applications are included, where appropriate. Importantly, its powerful ability in allene synthesis and the combination with [Re]-vinylidene and carbocation chemistries render this strategy attractive enough to inspire chemists to develop colorful reactions for building molecular complexity.

6.
Org Biomol Chem ; 21(19): 4007-4012, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37128724

RESUMO

Herein, we disclose a chemoselective and diastereoselective synthesis of the medicinally significant 4-alkylidene-tetrahydroquinoline via a redox-neutral vinylogous cascade condensation/[1,7]-hydride transfer/6-endo-trig cyclization strategy, which features a novel product skeleton, high chemoselectivity and diastereoselectivity, facile introduction of 4-alkylidenyl motifs, employment of α,ß,γ,δ-unsaturated dicyanoalkenes as novel hydride acceptors, and green and metal-free conditions with water as the only by-product. Additionally, the versatility of α,α-dicyanoalkenes has been fully exploited as hydride acceptors and γ-exclusive nucleophiles consecutively for accessing novel heterocyclic skeletons.

7.
Environ Sci Technol ; 57(38): 14482-14492, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37699122

RESUMO

It is critical to discover a non-noble metal catalyst with high catalytic activity capable of replacing palladium in electrochemical reduction. In this work, a highly efficient single-atom Co-N/C catalyst was synthesized with metal-organic frameworks (MOFs) as a precursor for electrochemical dehalogenation. X-ray absorption spectroscopy (XAS) revealed that Co-N/C exhibited a Co-N4 configuration, which had more active sites and a faster charge-transfer rate and thus enabled the efficient removal of florfenicol (FLO) at a wide pH, achieving a rate constant 3.5 and 2.1 times that of N/C and commercial Pd/C, respectively. The defluorination and dechlorination efficiencies were 67.6 and 95.6%, respectively, with extremely low Co leaching (6 µg L-1), low energy consumption (22.7 kWh kg-1), and high turnover frequency (TOF) (0.0350 min-1), demonstrating excellent dehalogenation performance. Spiking experiments and density functional theory (DFT) verified that Co-N4 was the active site and had the lowest energy barrier for forming atomic hydrogen (H*) (ΔGH*). Capture experiments, electron paramagnetic resonance (EPR), electrochemical tests, and in situ Fourier transform infrared (FTIR) proved that H* and direct electron transfer were responsible for dehalogenation. Toxicity assessment indicated that FLO toxicity decreased significantly after dehalogenation. This work develops a non-noble metal catalyst with broad application prospects in electrocatalytic dehalogenation.


Assuntos
Cobalto , Paládio , Catálise , Espectroscopia de Ressonância de Spin Eletrônica
8.
Sensors (Basel) ; 23(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139687

RESUMO

The non-uniform reflectance characteristics of object surfaces and underwater environment disturbances during underwater laser measurements can have a great impact on laser stripe center extraction. Therefore, we propose a normalized grayscale gravity method to address this problem. First, we build an underwater structured light dataset for different illuminations, turbidity levels, and reflective surfaces of the underwater object and compare several state-of-the-art semantic segmentation models, including Deeplabv3, Deeplabv3plus, MobilenetV3, Pspnet, and FCNnet. Based on our comparison, we recommend PSPnet for the specific task of underwater structured light stripe segmentation. Second, in order to accurately extract the centerline of the extracted light stripe, the gray level values are normalized to eliminate the influence of noise and light stripe edge information on the centroids, and the weights of the cross-sectional extremes are increased to increase the function convergence for better robustness. Finally, the subpixel-structured light center points of the image are obtained by bilinear interpolation to improve the image resolution and extraction accuracy. The experimental results show that the proposed method can effectively eliminate noise interference while exhibiting good robustness and self-adaptability.

9.
Molecules ; 27(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36234975

RESUMO

The fast and reliable analysis of electrolytes such as K, Na, Ca in human blood serum has become an indispensable tool for diagnosing and preventing diseases. Laser-induced breakdown spectroscopy (LIBS) has been demonstrated as a powerful analytical technique on elements. To apply LIBS to the quantitative analysis of electrolyte elements in real time, a self-developed portable laser was used to measure blood serum samples supported by glass slides and filter paper in this work. The partial least squares regression (PLSR) method was employed for predicting the concentrations of K, Na, Ca from serum LIBS spectra. Great prediction accuracies with excellent linearity were obtained for the serum samples, both on glass slides and filter paper. For blood serum on glass slides, the prediction accuracies for K, Na, Ca were 1.45%, 0.61% and 3.80%. Moreover, for blood serum on filter paper, the corresponding prediction accuracies were 7.47%, 1.56% and 0.52%. The results show that LIBS using a portable laser with the assistance of PLSR can be used for accurate quantitative analysis of elements in blood serum in real time. This work reveals that the handheld LIBS instruments will be an excellent tool for real-time clinical practice.


Assuntos
Lasers , Soro , Eletrólitos , Humanos , Análise dos Mínimos Quadrados , Análise Espectral/métodos
10.
Phys Rev Lett ; 126(25): 256401, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34241529

RESUMO

Impurity pinning has long been discussed to have a profound effect on the dynamics of an incommensurate charge density wave (CDW), which would otherwise slide through the lattice without resistance. Here, we visualize the impurity pinning evolution of the CDW in ZrTe_{3} using the variable temperature scanning tunneling microscopy. At low temperatures, we observe a quasi-1D incommensurate CDW modulation moderately correlated to the impurity positions, indicating a weak impurity pinning. As we raise the sample temperature, the CDW modulation gets progressively weakened and distorted, while the correlation with the impurities becomes stronger. Above the CDW transition temperature, short-range modulations persist with the phase almost all pinned by impurities. The evolution from weak to strong impurity pinning through the CDW transition can be understood as a result of losing phase rigidity.

11.
J Environ Manage ; 289: 112486, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831757

RESUMO

Climate change is a global issue threatening agricultural production and human survival. However, agriculture sector is a major source of global greenhouse gases (GHGs), especially CH4 and N2O. Crop residue returning (RR) is an efficient practice to sequestrate soil carbon and increase crop yields. However, the efficiency of RR to mitigate climate change and maintain food security will be affected by the response of GHG emissions at both per area-scale and per yield-scale. Therefore, a national meta-analysis was conducted using 309 comparisons from 44 publications to assess the responses of GHG emissions to RR in China's croplands. The results indicated that little response of GWP to RR was observed with conditions under lower nitrogen fertilizer input rates (0-120 kg ha-1), mulch retention, returning one time in double cropping systems, returning with half residue, weakly acidic soil (pH 5.5-6.5), initial SOC contents >20 g kg-1, or mean annual precipitation <1000 mm. In order to mitigate climate change and sustain food security, RR combined with paddy-upland rotation, nitrogen fertilizer input rates of 240-360 kg ha-1, and neutral soil (pH 6.5-7.5) could decrease GWP at per unit of crop yield, which ultimately leads to a lower effect on GHGI and a higher crop production efficiency. In-depth studies should be conducted in the future to explore the interactions between various factors influencing GHG emissions under RR conditions. Overall, optimizing the interactions with management and site-specific conditions, potential for regulating GHGs emissions of RR can be enhanced.


Assuntos
Gases de Efeito Estufa , Oryza , Agricultura , China , Produtos Agrícolas , Aquecimento Global , Efeito Estufa , Gases de Efeito Estufa/análise , Humanos , Metano/análise , Óxido Nitroso/análise , Solo
12.
J Neurosci ; 39(3): 456-471, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30459220

RESUMO

AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto ∼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRP→mPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger.SIGNIFICANCE STATEMENT In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRP→mPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.


Assuntos
Proteína Relacionada com Agouti/fisiologia , Comportamento Materno/fisiologia , Rede Nervosa/fisiologia , Comportamento de Nidação/fisiologia , Neurônios/fisiologia , Área Pré-Óptica/fisiologia , Proteína Relacionada com Agouti/genética , Animais , Temperatura Baixa , Feminino , Privação de Alimentos , Região Hipotalâmica Lateral/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Optogenética , Núcleo Hipotalâmico Paraventricular/fisiologia , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo
13.
Opt Express ; 28(18): 26041-26055, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32906881

RESUMO

Planar achromatic metalenses with a thickness of the order of wavelength have attracted much attention for their potential applications in ultra-compact optical devices. However, realizing single-layer achromatic metalenses across a wide bandwidth requires that the corresponding meta-atoms have complex cross-sections for correct phase profile and dispersion compensation. Herein, we introduce an effective Abbe number and use lens maker equations to design a dual-layer achromatic metalens in which we compensate the dispersion by using a plano-convex liked metalens combined with a plano-concave liked metalens. The stacked metalens are designed based on simple high refractive index dielectric cylindrical meta-atoms with different radii, which simplify the design and fabrication processes. We demonstrate that a dual-layer achromatic metalens has a small focal length difference across the visible wavelength range and an average focusing efficiency above 50%, which proves that the design method is promising for many potential applications in multi-functional flat optical devices.

14.
Org Biomol Chem ; 18(22): 4267-4271, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32441733

RESUMO

The hydrogen-bonding-assisted construction of tetrahydroquinolines decorated with structurally diverse 3,3'-difunctional groups has been realized via a hydride transfer-involved three-step cascade reaction in the presence of morpholine. This protocol solves the limitation of acyclic 1,3-dicarbonyl compounds by one-pot synthesis of tetrahydroquinolines, featuring operational simplicity, broadly applicable substrates, and metal- and acid-free conditions with EtOH as a hydrogen-bonding donor.

15.
Org Biomol Chem ; 18(5): 895-904, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31915775

RESUMO

Structurally diverse amino acids and their ester derivatives were conveniently N,N'-dialkylated via a TFE-promoted cascade condensation/[1,5]-hydride transfer/cyclization for straightforward construction of pharmeutically significant tetrahydroquinazolines incorporating various amino acids, which featured broad substrate scope, the use of TFE as a sole solvent, additive-free and mild conditions.

16.
Environ Sci Technol ; 54(9): 5608-5618, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32083475

RESUMO

The traditional cook stove is a major contributor to combustion-derived soot particles, which contain various chemical species that may cause a significant impact to human health and ecosystems. However, properties and toxicity associated with environmentally persistent free radicals (EPFRs) in such emissions are not well known. This paper investigated the characteristics and cytotoxicity of soot-associated EPFRs discharged from Chinese household stoves. Our results showed that the concentrations of EPFRs were related to fuel types, and they were higher in wood-burning soot (8.9-10.5 × 1016 spins/g) than in coal-burning soot (3.9-9.7 × 1016 spins/g). Meanwhile, EPFR concentrations in soot decreased with an increase of coal maturity. The soot EPFRs, especially reactive fractions, readily induced the generation of reactive oxygen species (ROS). Potential health effects of soot EPFRs were also examined using normal human bronchial epithelial cell line 16HBE as a model. Soot particles were internalized by 16HBE cells inducing cytotoxicity. The main toxicity inducers were identified to be reactive EPFR species, which generated ROS inside human cells. Our findings provided valuable insights into potential contributions of soot EPFRs associated with different types of fuel to health problems. This information will support regulations to end or limit current stove usage in numerous households.


Assuntos
Poluentes Atmosféricos/análise , Fuligem , Carvão Mineral/análise , Ecossistema , Radicais Livres/análise , Humanos , Material Particulado/análise , Madeira/química
17.
J Org Chem ; 84(4): 1833-1844, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30608677

RESUMO

The aromatization-driven redox-neutral cascade [1,5]-hydride transfer/spirocyclization and cascade [1,5]-hydride transfer/hydrolysis from para-quinone methide in HFIP were developed. These protocols enabled the synthesis of azaspirocyclohexadienones and ortho-benzylated anilines in good to high yields under mild conditions, featuring room temperature, additive-free, and good functional group tolerance.

18.
J Org Chem ; 84(7): 3990-3999, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30777425

RESUMO

The oxindole-embedded ortho-quinone methides were employed as reactive intermediates in formal [4 + 2] annulation with 1,3-dicarbonyls, providing an efficient access to spiro[chromen-4,3'-oxindole] scaffolds via a cascade conjugate addition/ketalization/dehydration process. This protocol featured metal-free conditions, wide substrate scope, and excellent yields.

19.
J Org Chem ; 84(5): 2779-2785, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30676022

RESUMO

An organocatalytic C(sp3)-H functionalization of 5-methyl-2,3-dihydrofuran derivatives with trifluoropyruvates was achieved via a sequential exo-tautomerization/carbonyl-ene process, providing the biologically important CF3-substituted 2,3-dihydrofurans in high yields. This method featured mild metal-free conditions, good chemoselectivity, and easy scalability.

20.
J Org Chem ; 84(13): 8440-8448, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31135154

RESUMO

The scandium-catalyzed redox-neutral cascade [1,5]-hydride transfer/cyclization between C4-amine-substituted isatins and 1,3-dicarbonyl compounds has been developed. This protocol enabled the synthesis of tricyclic [3,4]-fused oxindoles in good to high yields and excellent diastereoselectivities, featuring high atom- and step economy as well as good functional group tolerance.

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