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1.
Adv Sci (Weinh) ; : e2401578, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602433

RESUMO

The appearance of triboelectric nanogenerators (TENG) provides a promising energy technology for harvesting abundant water wave energy. Here, the design and fabrication of a swinging origami-structured TENG (SO-TENG) tailored specifically for water wave energy harvesting are presented. The design incorporates an oscillating structure weighted at the bottom, inducing reciprocating motion propelled by the inertia of passing water waves. This reciprocating motion efficiently converts mechanical into electrical energy through the origami structure. By employing origami as the monomer structure, the surface contact area between friction layers is enhanced, thereby optimizing output performance. the swinging structure, combined with the placement of heavy objects, enhances the folding and contact of the origami, allowing it to operate effectively in low-frequency water wave environments. This configuration exhibits robust power generation capabilities, making it suitable for powering small electronic devices in water wave environments. Furthermore, when applied to metal corrosion protection, the SO-TENG demonstrates notable efficacy. Compared to exposed Q235 carbon steel, Q235 carbon steel protected by SO-TENG exhibits a significant reduction in open-circuit potential drop, approximately 155 mV, indicative of superior anti-corrosion properties. It lays a solid foundation for water wave energy collection and self-powered metal corrosion protection in marine environments.

2.
J Am Chem Soc ; 146(13): 9444-9454, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38513075

RESUMO

The 3d transition metal-catalyzed enantioconvergent radical cross-coupling provides a powerful tool for chiral molecule synthesis. In the classic mechanism, the bond formation relies on the interaction between nucleophile-sequestered metal complexes and radicals, limiting the nucleophile scope to sterically uncongested ones. The coupling of sterically congested nucleophiles poses a significant challenge due to difficulties in transmetalation, restricting the reaction generality. Here, we describe a probable outer-sphere nucleophilic attack mechanism that circumvents the challenging transmetalation associated with sterically congested nucleophiles. This strategy enables a general copper-catalyzed enantioconvergent radical N-alkylation of aromatic amines with secondary/tertiary alkyl halides and exhibits catalyst-controlled stereoselectivity. It accommodates diverse aromatic amines, especially bulky secondary and primary ones to deliver value-added chiral amines (>110 examples). It is expected to inspire the coupling of more nucleophiles, particularly challenging sterically congested ones, and accelerate reaction generality.

3.
J Am Chem Soc ; 145(27): 14686-14696, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37392183

RESUMO

The enantioconvergent C(sp3)-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched N-alkyl (hetero)aromatic amines yet has remained unexplored due to the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed enantioconvergent radical C(sp3)-N cross-coupling of activated racemic alkyl halides with (hetero)aromatic amines under ambient conditions. The key to success is the judicious selection of appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties for the formation of a stable and rigid chelating Cu complex. Thus, this kind of ligand could not only enhance the reducing capability of a copper catalyst to provide an enantioconvergent radical pathway but also avoid the coordination with other coordinating heteroatoms, thereby overcoming catalyst poisoning and/or chiral ligand displacement. This protocol covers a wide range of coupling partners (89 examples for activated racemic secondary/tertiary alkyl bromides/chlorides and (hetero)aromatic amines) with high functional group compatibility. When allied with follow-up transformations, it provides a highly flexible platform to access synthetically useful enantioenriched amine building blocks.

4.
Int J Med Inform ; 176: 105107, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37257235

RESUMO

BACKGROUND: The medical industry is one of the key industries for the application of artificial intelligence (AI). Although it is believed that the combination of CDSS and physicians could improve the medical service, there are still many concerns about the usage of CDSS. Based on these concerns, limited studies have answered the question that when a physician makes decision independently or with AI's help, will there be any differences in patients' satisfaction with the medical service? METHODS: This study uses the service fairness theory as a theoretical lens and employs three vignette experiments to address this research gap. There are totally 740 subjects recruited to participate into the three experiments. Group comparison methods and structural equation model are used to verify the hypotheses. RESULTS: The experimental results reveal that: (1) physicians using AI can reduce patients' service satisfaction (Mdifference=0.404,p=0.004); (2) the negative relationship between AI usage and service satisfaction can partially be mediated through distributive fairness and procedural fairness; (3) physicians actively informing their patients about the usage of AI can help mitigate the reduction in service satisfaction (Mdifference=0.400,p=0.003) and three types of fairness Mdifferencedistributive=0.307,p=0.042;Mdifferenceprocedural=0.483,p<0.001;Mdifferenceinteractional=0.253,p=0.027. CONCLUSION: This study investigates the effect of physicians using decision-making support AI on their patients' service satisfaction. These results contribute to the existing literature pertaining to AI and fairness theory, and also help in formulating some practical suggestions for medical staff and AI development companies.


Assuntos
Inteligência Artificial , Médicos , Humanos , Satisfação do Paciente , Tomada de Decisão Clínica , Satisfação Pessoal
5.
Front Surg ; 10: 1134934, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36925507

RESUMO

Purpose: A palatal fistula following the closure of palatal clefts remains a difficult clinical complication. Surgical treatment of fistulas is often complicated, with high recurrence rates. We present our results of fistula closure augmented with GTR, a resorbable membrane designed to promote guided tissue regeneration. Methods: We reviewed the records of 75 patients operated on between 2008 and 2022 for closure of the palatal fistula. The patients included 24 who underwent fistula closure augmented with GTR and 51 who underwent fistula closure with other techniques. We reviewed the age at surgery, sex, fistula location, and outcome. Operation success was defined as an asymptomatic patient with a healed fistula on clinical examination. Results: The overall fistula closure rate was 79.1% in the GTR group and 76.5% in the non-GTR group(p = 0.79). Discussion: The success rate of fistula closure in the GTR group is comparable to that in the non-GTR group in this study. An additional advantage is that this procedure does not require harvesting any autologous tissue and reduces tissue damage in the long term.

6.
Nature ; 618(7964): 294-300, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36940729

RESUMO

Chiral amines are commonly used in the pharmaceutical and agrochemical industries1. The strong demand for unnatural chiral amines has driven the development of catalytic asymmetric methods1,2. Although the N-alkylation of aliphatic amines with alkyl halides has been widely adopted for over 100 years, catalyst poisoning and unfettered reactivity have been preventing the development of a catalyst-controlled enantioselective version3-5. Here we report the use of chiral tridentate anionic ligands to enable the copper-catalysed chemoselective and enantioconvergent N-alkylation of aliphatic amines with α-carbonyl alkyl chlorides. This method can directly convert feedstock chemicals, including ammonia and pharmaceutically relevant amines, into unnatural chiral α-amino amides under mild and robust conditions. Excellent enantioselectivity and functional-group tolerance were observed. The power of the method is demonstrated in a number of complex settings, including late-stage functionalization and in the expedited synthesis of diverse amine drug molecules. The current method indicates that multidentate anionic ligands are a general solution for overcoming transition-metal-catalyst poisoning.


Assuntos
Alquilação , Aminas , Catálise , Cobre , Amidas/química , Aminas/química , Cobre/química , Ligantes , Preparações Farmacêuticas/química
7.
Oral Dis ; 29(8): 3493-3502, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36251469

RESUMO

OBJECTIVE: Our previous research have found that mesenchymal ß-catenin may be involved in palatal shelf (PS) elevation by regulating F-actin. Here, we further investigated the exact mechanism of ß-catenin/F-actin in the PS mesenchyme to regulate palatal reorientation. MATERIALS AND METHODS: (1) Firstly, Ctnnb1ex3f (ß-catenin) mice were conditionally overexpressed in the palatal mesenchyme by crossing with the Sox9-creERT2 mice (induced by Tamoxifen injections); (2) Subsequently, histology and immunohistochemistry were used to characterize the variations of PS morphology and expression of key molecules associated with developmental process; (3) Finally, experiments in vivo and ex vivo were employed to identify the critical mechanisms in ß-catenin silenced and overexpressed models. RESULTS: We found that the Sox9CreER; Ctnnb1ex3f mice exhibited failed palatal elevation and visible cleft palate, and overexpression of ß-catenin disturbed the F-actin responsible for cytoskeletal remodeling in palatal mesenchymal cells. qRT-PCR results showed mRNA levels of α-actinin4, a gene involved in F-actin cross-linking, were associated with knockdown or overexpression of ß-catenin in ex vivo, respectively. Experiments in vivo revealed that mesenchymal specific inactivation or overexpression of ß-catenin exhibited decreased or increased α-actinin-4 expression. CONCLUSIONS: Mesenchymal ß-catenin/F-actin plays an essential role in PS reorientation, which mediate α-actinin-4 to regulate F-actin cytoskeleton reorganization.


Assuntos
Actinas , beta Catenina , Camundongos , Animais , beta Catenina/metabolismo , Actinas/metabolismo , Actinina/genética , Actinina/metabolismo , Transdução de Sinais/genética , Citoesqueleto de Actina/metabolismo
8.
ISA Trans ; 136: 535-547, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36371261

RESUMO

Autonomous emergency braking (AEB) systems are able to control vehicles as needed to avoid vehicle rear-end collisions. However, these systems are ineffective in scenarios with laterally cut-in vehicles and rapidly-changing dangerous scenes. This paper proposes a novel collision-free emergency braking system (CFEBS) that can enable intelligent connected vehicles (CAVs) to plan and execute a more conservative safety trajectory for the braking process in dangerous scenes by considering the longitudinal and lateral motion intentions of the surrounding vehicles. An intention identification model for surrounding vehicles is proposed based on long-short term memory (LSTM) networks and conditional random fields (CRFs). By considering the surrounding vehicles as risk sources and quantifying the risk with the speed of the risk flow, a potential risk flow model is built to calculate the potential risk map (PRM) around the ego vehicle. The global safest trajectory is generated via the PRM using the discrete method. The output trajectory profile is regarded as the reference for a model predictive controller (MPC). Simulation results show that the proposed CFEBS can predict vehicle intention with 91.6% accuracy and control the ego vehicle to perform effective collision-free braking operations in emergency traffic environments.

9.
Adv Sci (Weinh) ; 9(35): e2203499, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36266926

RESUMO

Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have posed serious threats to humans and animals, which urgently calls for effective broad-spectrum antivirals. RNA-dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthesis and is an ideal pan-coronaviral therapeutic target. Herein, based on cryo-electron microscopy and biochemical approaches, gossypol (GOS) is identified from 881 natural products to directly block SARS-CoV-2 RdRp, thus inhibiting SARS-CoV-2 replication in both cellular and mouse infection models. GOS also acts as a potent inhibitor against the SARS-CoV-2 variant of concern (VOC) and exerts same inhibitory effects toward mutated RdRps of VOCs as the RdRp of the original SARS-CoV-2. Moreover, that the RdRp inhibitor GOS has broad-spectrum anti-coronavirus activity against alphacoronaviruses (porcine epidemic diarrhea virus and swine acute diarrhea syndrome coronavirus), betacoronaviruses (SARS-CoV-2), gammacoronaviruses (avian infectious bronchitis virus), and deltacoronaviruses (porcine deltacoronavirus) is showed. The findings demonstrate that GOS may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and other coronavirus outbreaks.


Assuntos
Tratamento Farmacológico da COVID-19 , Infecções por Coronavirus , RNA-Polimerase RNA-Dependente de Coronavírus , Gossipol , SARS-CoV-2 , Animais , Humanos , Camundongos , COVID-19 , Microscopia Crioeletrônica , Gossipol/farmacologia , Gossipol/uso terapêutico , Pandemias , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Suínos , Tratamento Farmacológico da COVID-19/métodos , Infecções por Coronavirus/tratamento farmacológico , RNA-Polimerase RNA-Dependente de Coronavírus/antagonistas & inibidores
10.
Front Cardiovasc Med ; 9: 864173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620510

RESUMO

The physiological changes associated with aging deleteriously impact cardiovascular function and regulation and therefore increase the risk of developing cardiovascular disease. There is substantial evidence that changes in the autonomic nervous system and arterial stiffness play an important role in the development of cardiovascular disease during the aging process. Exercise is known to be effective in improving autonomic regulation and arterial vascular compliance, but differences in the type and intensity of exercise can have varying degrees of impact on vascular regulatory responses and autonomic function. There is still little evidence on whether there are differences in the response of exercise interventions to cardiovascular modulatory effects across the lifespan. In addition, acute interval exercise challenges can improve autonomic modulation, although the results of interval exercise on autonomic physiological parameters vary. Therefore, this narrative review focuses on evaluating the effects of acute interval exercise on blood pressure regulation and autonomic responses and also incorporates studies investigating different age groups to evaluate the effects of acute interval exercise on the autonomic nervous system. Herein we also summarize existing literature examining the acute cardiovascular responses to varied modes of interval exercise, as well as to further compare the benefits of interval exercise with other types of exercise on autonomic regulation and arterial stiffness. After reviewing the existing literature, it has been shown that with advancing age, changes in the autonomic nervous activity of interval exercise result in significant impacts on the cardiovascular system. We document that with advancing age, changes in the autonomic nerves lead to aging of the nervous system, thereby affecting the regulation of blood pressure. According to the limited literature, interval exercise is more effective in attenuating arterial stiffness than continuous exercise, but the difference in exercise benefits may depend on the training mode, intensity, duration of exercise, and the age of participants. Therefore, the benefits of interval exercise on autonomic and arterial stiffness improvement still warrant investigation, particularly the impact of age, in future research.

11.
J Med Virol ; 94(8): 3992-3997, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35474319

RESUMO

The SARS-CoV-2 vaccines have been widely used to build an immunologic barrier in the population against the COVID-19 pandemic. However, a newly emerging Omicron variant, including BA.1, BA.1.1, BA.2, and BA.3 sublineages, largely escaped the neutralization of existing neutralizing antibodies (nAbs), even those elicited by three doses of vaccines. Here, we used the Omicron BA.1 RBD as a fourth dose of vaccine to induce potent Omicron-specific nAbs and evaluated the broadly neutralizing activities against SARS-CoV-2 variants. The BA.1-based vaccine was indeed prone to induce a strain-specific antibody response substantially cross-reactive with BA.2 sublineage, and yet triggered broad neutralization against SARS-CoV-2 variants when it was used in the sequential immunization with WT and other variant vaccines. These results demonstrated that the booster of Omicron RBD vaccine could be a rational strategy to enhance the broadly nAb response.


Assuntos
COVID-19 , Vacinas Virais , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Pandemias , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-35349060

RESUMO

This paper presents an energy consumption evaluation method for electric vehicles under different cooling and heating conditions. First, using the actual driving test data of electric vehicles, the weight coefficient of the energy consumption value per 100 km of the electric vehicle undercooling, heating, and non-cooling heating is obtained by the least-square method in the comprehensive energy consumption value of the electric vehicle per 100 km throughout the year. Then, the above weight coefficients are combined with the test results of the bench test to obtain the comprehensive energy consumption per 100 km of the electric vehicle in the whole year. The relevant vehicles are tested, and the simulation and experimental results show that the obtained weight coefficients of the least-squares method can better reflect the real energy consumption of the entire vehicle, and the energy consumption of 100 km is an evaluation method for electric vehicles. A feasible evaluation method is proposed in this paper.

13.
Virol J ; 19(1): 2, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983583

RESUMO

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.


Assuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Camundongos , SARS-CoV-2/imunologia
14.
ACS Omega ; 7(51): 48250-48260, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36591184

RESUMO

Multiplex transient grating (MTG) spectroscopy was applied to lutein in ethanol to investigate the excitation-energy dependence of the excited-state dynamics and vibrational relaxation. The transient spectra obtained upon low (480 nm) and high-energy (380 nm) excitation both recorded a strong excited-state absorption (ESA) of S1 → S n as well as a broad band in the blue wavelength that was previously proposed as the S* state. By means of Gaussian decomposition and global fitting of the ESA band, a long-time component assigned to the triplet state was derived from the kinetic trace of 480 nm excitation. Moreover, the MTG signal with a resolution of 110 fs displayed the short-time quantum beat signal. In order to unveil the vibrational coherence in the excited-state decay, the linear and non-linear simulations of the steady spectrum and dynamic signals were presented in which at least three fundamental modes standing for C-C stretching (ν1), C=C stretching (ν2), and O-H valence vibrations (ν3) were considered to analyze the experimental signals. It was identified that the vibrational coherence between ν1 and ν3 or ν2 and ν3 was responsible for quantum beat that may be associated with the triplet state. We concluded that upon low- or high-energy excitation into the S2 state, the photo-isomerization of the molecule and structural recovery on the time-scale of vibrational cooling are the key factors to form a mixed conformation in the hot-S1 state that is the precursor of a long life-time triplet.

15.
ISA Trans ; 120: 1-17, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33757645

RESUMO

Exploring the drift maneuver could extend the dynamic control envelope and application range of autonomous vehicles. This paper presents a novel autonomous drift controller for a distributed drive electric vehicle, whose configuration provides more possibilities for drift. In the upper-level controller, a control channel recombination method transforms the over-actuated system into a standard square system, which is compatible with the proposed fuzzy-integral sliding-mode controller considering the input coupling and uncertain disturbance of the system to bring the vehicle into a marginally stable condition. The operation of the lower-level controller considers the dynamic characteristics of actuators and tires, and distributes the "virtual control input" among each physical actuator. This controller's performance with fast response and strong robustness was proved through the bench test.

16.
Front Surg ; 9: 1080955, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684272

RESUMO

Purpose: The study aims to compare the velopharyngeal morphology of hard and soft cleft palate (HSCP) patients after Furlow and Sommerlad palatoplasty. Patients and methods: A total of 51 patients (20 cases in Furlow palatoplasty group, 16 cases in Sommerlad palatoplasty group and 15 normal children in the control group) were included in our study. Velopharyngeal function and speech outcomes of patients with HSCP who had either Furlow palatoplasty or Sommerlad palatoplasty for cleft palate repair were evaluated by perceptual speech assessment (PSA), lateral cephalometric radiographs and nasopharyngoscopy. To assess velopharyngeal morphology of patients treated with two techqiques, we analyzed measurements such as velar length, pharyngeal depth, and the Adequate ratio (the ratio of velar length to pharyngeal depth). Furthermore, skeletal landmarks including cranial base, cervical vertebrae, posterior nasal spine which were defined as the pharyngeal triangle were measured. Finally, the position of the point U relative to the pharyngeal triangle were compared. Results: Velopharyngeal closure (VPC) rate in Furlow palatoplasty group accounted for 90%, while that in Sommerlad palatoplasty group was 81.3%. PSA of the former group was significantly better than that of the latter group (P < 0.05). Velar length, pharyngeal depth and the Adequate ratio (1.37 ± 0.14 vs. 1.41 ± 0.15) were comparable between the Furlow group and control group (P > 0.05), while Sommerlad group had a shorter velar length, deeper pharyngeal depth and a smaller Adequate ratio (1.20 ± 0.18) compared to the above two groups (P < 0.05). Furhermore, the point U of Sommerlad group in the pharyngeal triangle was higher than that of the other two groups. Conclusions: In the treatment modality of patients with HSCP, both Furlow palatoplasty and Sommerlad palatoplasty seem to be effective. Furlow palatoplasty appears to have velopharyngeal morphology similar to normal control group., while Sommerlad group shows a shorter velar length, deeper pharyngeal depth and a smaller Adequate ratio.

17.
Ann Transl Med ; 10(24): 1332, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36660634

RESUMO

Background: Palatogenesis is a highly regulated and coordinated developmental process that is coordinated by multiple transcription factors and signaling pathways. Our previous studies identified that defective palatal shelf reorientation due to aberrant mesenchymal ß-catenin signaling is associated with Filamentous actin (F-actin) dysregulation. Herein, the underlying mechanism of mesenchymal ß-catenin in regulating F-actin cytoskeleton reorganization is further investigated. Methods: Firstly, ß-catenin silenced and overexpressed mouse embryonic palatal mesenchymal (MEPM) cells were established by adenovirus-mediated transduction. Subsequently, we compared transcriptomes of negative control (NC) group, ß-catenin knockdown (KD) group, or ß-catenin overexpression group respectively using RNA-sequencing (RNA-seq), and differentially expressed genes (DEGs) screened were further identified by quantitative real-time polymerase chain reaction (qRT-PCR). Finally, in vivo experiments further verified the expression change of critical molecules. Results: We discovered 184 and 522 DEGs in the knockdown and overexpression groups compared to the NC group, respectively (adjusted P<0.05; |fold change| >2.0). Among these, 106 DEGs were altered in both groups. Gene Ontology (GO) enrichment analysis relating to biological functions identified cytokine-cytokine receptor interaction, and positive modulation of cellular migration. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment assessment indicated that these DEGs were chiefly linked by the regulation of signaling receptor activity and chemokine signaling pathways. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the similar expression trend of serum amyloid A3 (Saa3) and CXC-chemokine ligand 5 (Cxcl5) possibly involved in cytoskeletal rearrangement with RNA-seq data. Experiments in vivo displayed that no significant expression change of Saa3 and Cxcl5 was observed in ß-catenin knockout and overexpressed mouse models. Conclusions: Our study provides an expression landscape of DEGs in ß-catenin silenced and overexpressed MEPM cells, which emphasizes the important role of processes such as chemotactic factor and cell migration. Our data gain deeper insight into genes associated with F-actin reorganization that is regulated by ß-catenin either directly or by another route, which will contribute to further investigation of the exact mechanism of mesenchymal ß-catenin/F-actin in palatal shelf reorientation.

18.
ACS Cent Sci ; 7(6): 954-962, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34235256

RESUMO

Sesquiterpenes are a rich source of covalent inhibitors with a long history in traditional medicine and include several important therapeutics and tool compounds. Herein, we report the total synthesis of 16 sesquiterpene lactones via a build/couple/pair strategy, including goyasensolide. Using an alkyne-tagged cellular probe and proteomics analysis, we discovered that goyazensolide selectively targets the oncoprotein importin-5 (IPO5) for covalent engagement. We further demonstrate that goyazensolide inhibits the translocation of RASAL-2, a cargo of IPO5, into the nucleus and perturbs the binding between IPO5 and two specific viral nuclear localization sequences.

20.
Int J Oral Sci ; 13(1): 17, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039957

RESUMO

Normal mammalian secondary palate development undergoes a series of processes, including palatal shelf (PS) growth, elevation, adhesion and fusion, and palatal bone formation. It has been estimated that more than 90% of isolated cleft palate is caused by defects associated with the elevation process. However, because of the rapidly completed elevation process, the entire process of elevation will never be easy to clarify. In this article, we present a novel method for three-dimensional (3D) reconstruction of thick tissue blocks from two-dimensional (2D) histological sections. We established multiplanar sections of the palate and tongue in coronal and sagittal directions, and further performed 3D reconstruction to observe the morphological interaction and connection between the two components prior to and during elevation. The method completes an imaging system for simultaneous morphological analysis of thick tissue samples using both synthetic and real data. The new method will provide a comprehensive picture of reorientation morphology and gene expression pattern during the palatal elevation process.


Assuntos
Fissura Palatina , Imageamento Tridimensional , Animais , Palato , Língua
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