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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38706323

RESUMO

In recent years, cyclic peptides have emerged as a promising therapeutic modality due to their diverse biological activities. Understanding the structures of these cyclic peptides and their complexes is crucial for unlocking invaluable insights about protein target-cyclic peptide interaction, which can facilitate the development of novel-related drugs. However, conducting experimental observations is time-consuming and expensive. Computer-aided drug design methods are not practical enough in real-world applications. To tackles this challenge, we introduce HighFold, an AlphaFold-derived model in this study. By integrating specific details about the head-to-tail circle and disulfide bridge structures, the HighFold model can accurately predict the structures of cyclic peptides and their complexes. Our model demonstrates superior predictive performance compared to other existing approaches, representing a significant advancement in structure-activity research. The HighFold model is openly accessible at https://github.com/hongliangduan/HighFold.


Assuntos
Dissulfetos , Peptídeos Cíclicos , Peptídeos Cíclicos/química , Dissulfetos/química , Software , Modelos Moleculares , Conformação Proteica , Algoritmos , Biologia Computacional/métodos
2.
Mol Ther ; 31(12): 3594-3612, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37838829

RESUMO

Osteoarthritis (OA) is the most common joint disease, but no disease-modifying drugs have been approved for OA treatment. Mitophagy participates in mitochondrial homeostasis regulation by selectively clearing dysfunctional mitochondria, which might contribute to cartilage degeneration in OA. Here, we provide evidence of impaired mitophagy in OA chondrocytes, which exacerbates chondrocyte degeneration. Among the several classic mitophagy-regulating pathways and receptors, we found that FUNDC1 plays a key role in preserving chondrocyte homeostasis by inducing mitophagy. FUNDC1 knockdown in vitro and knockout in vivo decreased mitophagy and exacerbated mitochondrial dysfunction, exacerbating chondrocyte degeneration and OA progression. FUNDC1 overexpression via intra-articular injection of adeno-associated virus alleviated cartilage degeneration in OA. Mechanistically, our study demonstrated that PFKP interacts with and dephosphorylates FUNDC1 to induce mitophagy in chondrocytes. Further analysis identified KD025 as a candidate drug for restoring chondrocyte mitophagy by increasing the FUNDC1-PFKP interaction and thus alleviating cartilage degeneration in mice with DMM-induced OA. Our study highlights the role of the FUNDC1-PFKP interaction in chondrocyte homeostasis via mitophagy induction and identifies KD025 as a promising agent for treating OA by increasing chondrocyte mitophagy.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Camundongos , Mitofagia , Cartilagem Articular/metabolismo , Apoptose , Osteoartrite/terapia , Osteoartrite/metabolismo , Condrócitos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo
3.
Opt Express ; 31(19): 31082-31091, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710636

RESUMO

Broadband supercontinuum laser sources in the mid-infrared region have attracted enormous interest and found significant applications in spectroscopy, imaging, sensing, defense, and security. Despite recent advances in mid-infrared supercontinuum laser sources using infrared fibers, the average power of those laser sources is limited to 10-watt-level, and further power scaling to over 50 W (or hundred-watt-level) remains a significant technological challenge. Here, we report an over 50 W all-fiber mid-infrared supercontinuum laser source with a spectral range from 1220 to 3740 nm, by using low loss (<0.1 dB/m) fluorotellurite fibers we developed as the nonlinear medium and a tilted fusion splicing method for reducing the reflection from the fluorotellurite-silica fiber joint. Furthermore, the scalability of all-fiber mid-infrared supercontinuum laser sources using fluorotellurite fibers is analyzed by considering thermal effects and optical damage, which verifies its potential of power scaling to hundred-watt-level. Our results pave the way for realizing all-fiber hundred-watt-level mid-infrared lasers for real applications.

4.
Chemistry ; 29(28): e202300438, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-36843339

RESUMO

Responsive photonic crystals (RPCs) assembled by monodisperse colloidal particles have attracted enormous interest recently due to their tremendous applications in smart devices. Their structural colors can be determined by particle sizes. However, the lack of a reliable way to tune the sizes in situ limits their development. Herein, we present an efficient route to solve this problem through the fabrication of spherical polymeric particles with light-triggered reversible swelling behavior via surfactant-free reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization-induced self-assembly (PISA). Amphiphilic macro-RAFT agents containing azobenzene groups were synthesized and subsequently employed to mediate the polymerization of methyl methacrylate. Uniform submicron spheres were obtained by modulating solid contents and other parameters. Benefiting from the photoisomerization of azobenzene moieties, the particle sizes expanded and contracted upon alternative ultraviolet/visible-light irradiation accordingly. This strategy will be a supplement to the emulsion PISA and especially give aid to the progress of the RPC materials.

5.
Phys Chem Chem Phys ; 25(3): 1649-1658, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36541051

RESUMO

In this study, a capillary device based on the surface plasmon-enhanced Raman scattering effect was prepared by a simple and easy method. First, the capillary was treated with APTES solution. Due to the electrostatic effect, gold nanoparticles could be easily and tightly assembled in the capillary inner wall. On this basis, the effects of changing the concentration of APTES, the concentration of colloids and the soaking time of the capillary in the colloids on the assembly of gold nanoparticles on the inner wall of the capillary were studied, and the SERS enhancement effect under different conditions was analyzed, and the optimal solution was successfully found. At the same time, the reason why the capillary substrate shows better SERS performance than the traditional planar substrate is deeply discussed. Since the nanoparticles can be attached to the upper and lower surfaces of the inner wall of the capillary, the utilization rate of nanoparticles and laser is improved, thereby achieving higher enhancement. For the detection of the probe molecule rhodamine 6G, it was proved that the substrate has good uniformity and the lowest detection limit can reach 10-10 M. Finally, the real-life pesticide thiram and the food additive aspartame were tested, and the detection limits could reach 10-6 M and 0.25 g L-1. It is confirmed that the prepared capillary shows excellent SERS performance and can be used for rapid detection in various fields.


Assuntos
Nanopartículas Metálicas , Praguicidas , Ouro/química , Nanopartículas Metálicas/química , Tiram , Análise Espectral Raman/métodos , Coloides
6.
J Acoust Soc Am ; 154(3): 1770-1786, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37721403

RESUMO

Both dynamic variation of interaural time difference (ITD) and static spectral cues provide information for front-back discrimination and vertical localization. However, the contributions of the two cues are still unclear. The static spectral cue has conventionally been regarded as the dominant one. In the present work, psychoacoustic experiments were conducted to examine the contribution of dynamic ITD and static spectral cues to vertical localization in the median plane. By modifying the head-related transfer functions used in a dynamic virtual auditory display, binaural signals with conflicting dynamic ITD and spectral cues that were either static or dynamically modified according to instantaneous head position were created. The results indicated that the dynamic ITD and static spectral cues contribute to vertical localization at low and high frequencies, respectively. For full a bandwidth stimulus, conflicting dynamic ITD and static spectral cues usually result in two separated virtual sources at different elevations corresponding to the spatial information conveyed by the low- and high-frequency bands, respectively. In most cases, no fused localization occurs in the high-level cognition system. Therefore, dynamic ITD and static spectral cues contribute to vertical localization at different frequency ranges, and neither of them dominates vertical localization in the case of wideband stimuli.


Assuntos
Sinais (Psicologia) , Localização de Som , Cognição , Psicoacústica
7.
Int J Neurosci ; 133(3): 278-289, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33781148

RESUMO

PURPOSE OF THE STUDY: granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor existing in neutrophils, glial cells and neurons. Increasing researches discovered that G-CSF improved cell survival in neurodegenerative diseases by its anti-inflammatory effect. However, the effect of G-CSF in suppressing inflammation in Parkinson's disease (PD) remains unclear. Thus, the purpose of this study is to explored the anti-inflammatory effect of G-CSF in mouse model of PD. MATERIALS AND METHODS: G-CSF was administrated in the PD model induced by MPTP. Subsequently, the protein of tyrosine hydroxylase (TH), ionized calcium-binding adaptor molecule 1 (Iba-1) and the inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) in the midbrain were examined. In addition, the phosphorylated mitogen-activated protein kinases (MAPK) including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK in the midbrain were investigated. RESULTS: Compared with the MPTP group, the protein of TH in the midbrain was increased, while the Iba-1 and the inflammatory factors were decreased. In addition, the expression of phosphorylated JNK (p-JNK) in the midbrain of the MPTP + G-CSF group was decreased, while the phosphorylated ERK (p-ERK) levels were elevated. CONCLUSIONS: These findings emphasize that G-CSF inhibited the degradation of DA neurons. The protective effect is associated with the reduction of the inflammatory factors caused by the inhibition of the microglial activation. Moreover, G-CSF may decrease the inflammatory factors through the decrease of P-JNK and the increase of P-ERK.


Assuntos
Doença de Parkinson , Fator de Necrose Tumoral alfa , Camundongos , Animais , Doença de Parkinson/tratamento farmacológico , Interleucina-1beta , Neurônios Dopaminérgicos , Fator Estimulador de Colônias de Granulócitos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(3): 295-301, 2023 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-36946166

RESUMO

OBJECTIVES: To systematically evaluate the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) versus nasal intermittent positive pressure ventilation (NIPPV) as post-extubation respiratory support in preterm infants. METHODS: China National Knowledge Infrastructure, Wanfang Data, Chinese Journal Full-text Database, China Biology Medicine disc, PubMed, Web of Science, and the Cochrane Library were searched for articles on NHFOV and NIPPV as post-extubation respiratory support in preterm infants published up to August 31, 2022. RevMan 5.4 software and Stata 17.0 software were used for a Meta analysis to compare related indices between the NHFOV and NIPPV groups, including reintubation rate within 72 hours after extubation, partial pressure of carbon dioxide (PCO2) at 6-24 hours after switch to noninvasive assisted ventilation, and the incidence rates of bronchopulmonary dysplasia (BPD), air leak, nasal damage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). RESULTS: A total of 9 randomized controlled trials were included. The Meta analysis showed that compared with the NIPPV group, the NHFOV group had significantly lower reintubation rate within 72 hours after extubation (RR=0.67, 95%CI: 0.52-0.88, P=0.003) and PCO2 at 6-24 hours after switch to noninvasive assisted ventilation (MD=-4.12, 95%CI: -6.12 to -2.13, P<0.001). There was no significant difference between the two groups in the incidence rates of complications such as BPD, air leak, nasal damage, PVL, IVH, and ROP (P>0.05). CONCLUSIONS: Compared with NIPPV, NHFOV can effectively remove CO2 and reduce the risk of reintubation, without increasing the incidence of complications such as BPD, air leak, nasal damage, PVL, and IVH, and therefore, it can be used as a sequential respiratory support mode for preterm infants after extubation.


Assuntos
Displasia Broncopulmonar , Ventilação de Alta Frequência , Ventilação não Invasiva , Síndrome do Desconforto Respiratório do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Ventilação com Pressão Positiva Intermitente , Extubação , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Pressão Positiva Contínua nas Vias Aéreas
9.
J Chem Inf Model ; 62(19): 4579-4590, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36129104

RESUMO

In the face of low-resource reaction training samples, we construct a chemical platform for addressing small-scale reaction prediction problems. Using a self-supervised pretraining strategy called MAsked Sequence to Sequence (MASS), the Transformer model can absorb the chemical information of about 1 billion molecules and then fine-tune on a small-scale reaction prediction. To further strengthen the predictive performance of our model, we combine MASS with the reaction transfer learning strategy. Here, we show that the average improved accuracies of the Transformer model can reach 14.07, 24.26, 40.31, and 57.69% in predicting the Baeyer-Villiger, Heck, C-C bond formation, and functional group interconversion reaction data sets, respectively, marking an important step to low-resource reaction prediction.

10.
Phys Chem Chem Phys ; 24(17): 10280-10291, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35437562

RESUMO

While state-of-art models can predict reactions through the transfer learning of thousands of samples with the same reaction types as those of the reactions to predict, how to prepare such models to predict "unseen" reactions remains an unanswered question. We aimed to study the Transformer model's ability to predict "unseen" reactions through "zero-shot reaction prediction (ZSRP)", a concept derived from zero-shot learning and zero-shot translation. We reproduced the human invention of the Chan-Lam coupling reaction where the inventor was inspired by the Suzuki reaction when improving Barton's bismuth arylation reaction. After being fine-tuned with samples from these two "existing" reactions, the USPTO-trained Transformer could predict "unseen" Chan-Lam coupling reactions with 55.7% top-1 accuracy. Our model could also mimic the later stage of the history of this reaction, where the initial case of this reaction was generalized to more reactants and reagents via "one-shot/few-shot reaction prediction (OSRP/FSRP)" approaches.


Assuntos
Invenções , Aprendizado de Máquina , Humanos
11.
Phys Chem Chem Phys ; 24(46): 28362-28370, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36385134

RESUMO

Induced circular dichroism (ICD) is widely used in miniature polarizers, molecular detection, and negative refractive index media. However, enhancing and the dynamic regulation of ICD signals of achiral nanostructures in the visible and near-infrared range remain the current challenges. Here, monolayer borophene (MB) with anisotropic conductance was incorporated into achiral nanostructures, which consisted of achiral dielectric elliptical hole arrays (DENAs) placed on a silver substrate. Two narrowband ICD signals for DENAs/MB were achieved in the near-infrared range under different circularly polarized lights. The distributions of the magnetic field of DENAs/MB could explain the two narrowband ICD signals originating from the coupling of surface plasmon polariton resonances along the x- and y directions. Not only could the ICD signals be tuned by the structural parameters of DENAs/MB, but they could also be actively tuned by the incident angles of the excitation light and the carrier concentration of MB. In addition, the sensitivity and the figure of merit of DENAs/MB could reach 302/RIU and 61.0. These results provide a concise method for the design of dynamically adjustable chiral devices based on borophene and promote its application in molecular recognition and chiral catalysis.

12.
BMC Public Health ; 22(1): 1493, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931976

RESUMO

BACKGROUND: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP. METHODS: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors. RESULTS: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors. CONCLUSION: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.


Assuntos
Dor Lombar , Doenças Profissionais , China/epidemiologia , Estudos Transversais , Humanos , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Doenças Profissionais/etiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários
13.
BMC Musculoskelet Disord ; 23(1): 952, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329459

RESUMO

BACKGROUND: Changes in modern industrial production practices can easily lead to shoulder work-related musculoskeletal disorders (WMSD). The current reports on shoulder WMSD are limited to some industries are less well studied, and the sample size is usually small. This study aimed to describe the prevalence and severity of shoulder WMSD in a large sample of Chinese workers from 15 industries, analyze the possible correlations with sociodemographic and work-related variables, and compare the differences between industries. METHODS: A cross-sectional study was conducted among a sample of 55,749 participants from 252 enterprises in 15 industries throughout China. A Chinese version of the musculoskeletal disease questionnaire was used to collect the demographic factors, shoulder symptoms in past 12 months, and work-related factors including posture-related factors, repetition, vibration, work organization, job control, and environmental factors as independent variables. Descriptive statistics were used, and the binary logistic regression analysis was performed to explore the association between shoulder WMSD and potential demographic and work-related factors. RESULTS: Nearly 35.5% of participants reported shoulder pain and discomfort in the previous 12 months. Biopharmaceutical manufacturing (56.2%), medical services (54.4%), and aviation services (50.1%) were the three industries with the highest prevalence of shoulder WMSD. The pain score of aviation services workers was the highest. The related factors for shoulder WMSD varied among the different industries. CONCLUSION: Our study found a relatively high prevalence of shoulder WMSD in China. There were large differences in the prevalence of shoulder WMSD among industries, and the related factors were particular to each industry. Such information is useful to help occupational health practitioners and policymakers conduct preventive programs to reduce shoulder disorders in these working populations.


Assuntos
Doenças Musculoesqueléticas , Doenças Profissionais , Humanos , Estudos Transversais , Ombro , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/epidemiologia , Prevalência , Inquéritos e Questionários , China/epidemiologia , Fatores de Risco
14.
Surg Radiol Anat ; 44(1): 15-23, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34994830

RESUMO

PURPOSE: Human anatomy is a core course of basic medicine and the first professional course for medical students. Traditional teaching includes "teacher-centered" instruction, passive learning, and a lack of interaction between teachers and students as well as between students. The aim of this study was to develop a "student-centered" multielement fusion teaching mode to address the mentioned drawbacks. METHODS: A total of 141 clinical medical students from grades 2016 and 2017 of Chengde Medical University participated in this study. The students were randomly divided into four classes: two experimental classes and two control classes. The experimental classes experienced a "student-centered" multielement fusion teaching mode, while the control classes experienced a traditional teaching method. Formative assessments and questionnaires were used to assess the students' preferences and obtain feedback. Theoretical and experimental tests were carried out to detect the students' scores at the end of the semester. RESULTS: The results of the questionnaires demonstrated that 100% of the students agreed that the multielement teaching mode was better. In the experimental test, the students in the experimental group achieved a mean score of 16.50 ± 0.3203, which was significantly higher than that of the control group 12.65 ± 0.4731 (P < 0.01). In the theoretical test, the average score of the experimental group was 45.86 ± 0.6273 and that of the control group was 46.59 ± 0.6636; thus, there was no significant difference between the two groups (P > 0.05). CONCLUSION: The application of a "student-centered" multielement fusion teaching mode obtained strong approval from the students. This teaching mode not only improved students' interest in learning and increased the interaction between teachers and students as well as between students but also enhanced students' competence and will lay a solid foundation for their future careers.


Assuntos
Avaliação Educacional , Estudantes de Medicina , Humanos , Aprendizagem , Inquéritos e Questionários , Ensino , Universidades
15.
Acc Chem Res ; 52(9): 2506-2515, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31424904

RESUMO

As a new class of photocatalysts, plasmonic noble metal nanoparticles with the unique ability to harvest solar energy across the entire visible spectrum and produce effective energy conversion have been explored as a promising pathway for the energy crisis. The resonant excitation of surface plasmon resonance allows the nanoparticles to collect the energy of photons to form a highly enhanced electromagnetic field, and the energy stored in the plasmonic field can induce hot carriers in the metal. The hot electron-hole pairs ultimately dissipate by coupling to phonon modes of the metal nanoparticles, resulting in a higher lattice temperature. The plasmonic electromagnetic field, hot electrons, and heat can catalyze chemical reactions of reactants near the surface of the plasmonic metal nanoparticles. This Account summarizes recent theoretical and experimental advances on the excitation mechanisms and energy transfer pathways in the plasmonic catalysis on molecules. Especially, current advances on plasmon-driven crystal growth and transformation of nanomaterials are introduced. The efficiency of the chemical reaction can be dramatically increased by the plasmonic electromagnetic field because of its higher density of photons. Similar to traditional photocatalysis, energy overlap between the plasmonic field and the HOMO-LUMO gap of the reactant is needed to realize resonant energy transfer. For hot-carrier-driven catalysis, hot electrons generated by plasmon decay can be transferred to the reactant through the indirect electron transfer or direct electron excitation process. For this mechanism, the energy of hot electrons needs to overlap with the unoccupied orbitals of the reactant, and the particular chemical channel can be selectively enhanced by controlling the energy distribution of hot electrons. In addition, the local thermal effect following plasmon decay offers an opportunity to facilitate chemical reactions at room temperature. Importantly, surface plasmons can not only catalyze chemical reactions of molecules but also induce crystal growth and transformation of nanomaterials. As a new development in plasmonic catalysis, plasmon-driven crystal transformation reveals a more powerful aspect of the catalysis effect, which opens the new field of plasmonic catalysis. We believe that this Account will promote clear understanding of plasmonic catalysis on both molecules and materials and contribute to the design of highly tunable catalytic systems to realize crystal transformations that are essential to achieve efficient solar-to-chemical energy conversion.

16.
Molecules ; 25(10)2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32438572

RESUMO

Effective computational prediction of complex or novel molecule syntheses can greatly help organic and medicinal chemistry. Retrosynthetic analysis is a method employed by chemists to predict synthetic routes to target compounds. The target compounds are incrementally converted into simpler compounds until the starting compounds are commercially available. However, predictions based on small chemical datasets often result in low accuracy due to an insufficient number of samples. To address this limitation, we introduced transfer learning to retrosynthetic analysis. Transfer learning is a machine learning approach that trains a model on one task and then applies the model to a related but different task; this approach can be used to solve the limitation of few data. The unclassified USPTO-380K large dataset was first applied to models for pretraining so that they gain a basic theoretical knowledge of chemistry, such as the chirality of compounds, reaction types and the SMILES form of chemical structure of compounds. The USPTO-380K and the USPTO-50K (which was also used by Liu et al.) were originally derived from Lowe's patent mining work. Liu et al. further processed these data and divided the reaction examples into 10 categories, but we did not. Subsequently, the acquired skills were transferred to be used on the classified USPTO-50K small dataset for continuous training and retrosynthetic reaction tests, and the pretrained accuracy data were simultaneously compared with the accuracy of results from models without pretraining. The transfer learning concept was combined with the sequence-to-sequence (seq2seq) or Transformer model for prediction and verification. The seq2seq and Transformer models, both of which are based on an encoder-decoder architecture, were originally constructed for language translation missions. The two algorithms translate SMILES form of structures of reactants to SMILES form of products, also taking into account other relevant chemical information (chirality, reaction types and conditions). The results demonstrated that the accuracy of the retrosynthetic analysis by the seq2seq and Transformer models after pretraining was significantly improved. The top-1 accuracy (which is the accuracy rate of the first prediction matching the actual result) of the Transformer-transfer-learning model increased from 52.4% to 60.7% with greatly improved prediction power. The model's top-20 prediction accuracy (which is the accuracy rate of the top 20 categories containing actual results) was 88.9%, which represents fairly good prediction in retrosynthetic analysis. In summary, this study proves that transferring learning between models working with different chemical datasets is feasible. The introduction of transfer learning to a model significantly improved prediction accuracy and, especially, assisted in small dataset based reaction prediction and retrosynthetic analysis.


Assuntos
Inteligência Artificial , Técnicas de Química Sintética , Química Computacional/tendências , Aprendizado de Máquina , Algoritmos , Química Farmacêutica/tendências , Conjuntos de Dados como Assunto , Humanos
17.
Molecules ; 25(18)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916920

RESUMO

Y6 is a new type of non-fullerene acceptor, which has led to power conversion efficiencies of single-junction polymer solar cells over 17% when combined with a careful choice of polymeric donors. However, the excited state characteristics of Y6, which is closely correlated with its opto-electronic applications, are not clear yet. In this work, we studied the excited state properties of the Y6 solution and Y6 film, by using steady-state and time-resolved spectroscopies as well as time-dependent density functional theory (TD-DFT) calculations. UV-Vis absorption and fluorescence simulation, natural transition orbitals (NTOs) and hole-electron distribution analysis of Y6 solution were performed for understanding the excitation properties of Y6 by using TD-DFT calculations. The lifetimes of the lowest singlet excited state in Y6 solution and film were estimated to be 0.98 and 0.8 ns, respectively. Combining the exciton lifetime and photoluminescence (PL) quantum yield, the intrinsic radiative decay lifetimes of Y6 in the solution and film were estimated, which were 1.3 and 10.5 ns for the Y6 solution and film, respectively. Long exciton lifetime (~0.8 ns) and intrinsic radiative decay lifetime (~10.5 ns) of Y6 film enable Y6 to be a good acceptor material for the application of polymer solar cells.


Assuntos
Fotoquímica/métodos , Polímeros/química , Semicondutores , Espectrofotometria/métodos , Clorofórmio , Eletrônica , Elétrons , Fulerenos/química , Cinética , Luminescência , Modelos Moleculares , Distribuição Normal , Óptica e Fotônica , Teoria Quântica , Energia Solar , Espectrometria de Fluorescência
18.
J Cell Biochem ; 120(8): 12775-12784, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30854734

RESUMO

There is increasing evidence regarding the pivotal roles of microRNAs (miRNAs) and histone deacetylases (HDACs) in the development of osteoarthritis (OA). This study aimed to determine whether miR-193b-5p regulates HDAC7 expression directly to affect cartilage degeneration. Expression levels of miR-193b-5p, HDAC7, matrix metalloproteinase 3 (MMP3), and MMP13 were determined in normal and OA cartilage and primary human chondrocytes (PHCs) stimulated with interleukin-1ß (IL-1ß). PHCs were transfected with a miR-193b-5p mimic or inhibitor to verify whether miR-193b-5p influences the expression of HDAC7 and MMPs. A luciferase reporter assay was performed to demonstrate the binding between miR-193b-5p and the 3'-untranslated region (UTR) of HDAC7. Expression of miR-193b-5p was reduced in IL-1ß-stimulated PHCs and in OA cartilage compared to that in normal cartilage. Luciferase reporter assay exhibited the repressed activity of the reporter construct containing the 3'UTR of HDAC7. Both miR-193b-5p overexpression and HDAC7 inhibition decreased the expression of MMP3 and MMP13, whereas the inhibition of miR-193b-5p enhanced HDAC7, MMP3, and MMP13 expression. miR-193b-5p downregulates HDAC7 directly and, as a result, inhibits MMP3 and MMP13 expression, which suggests that miR-193b-5p has a protective role in OA.


Assuntos
Condrócitos/citologia , Histona Desacetilases/genética , Interleucina-1beta/efeitos adversos , MicroRNAs/genética , Osteoartrite/genética , Regiões 3' não Traduzidas , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Feminino , Humanos , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Osteoartrite/metabolismo , Cultura Primária de Células
19.
Small ; 15(34): e1901286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240871

RESUMO

Single crystal nanomaterials are very important for the fundamental investigation and application of luminescence. However, a very critical growth condition or high temperature treatment is always required for their preparation. Here, an easy and rapid in situ achievement of a single crystal luminescent material is realized by taking advantage of plasmon-induced thermal and catalysis effects. With the assistance of localized surface plasmon resonance of Au nanoparticles, polycrystalline NaYF4 transforms to single crystal Y2 O3 in tens of milliseconds, resulting in remarkable improvement of luminescence emission. It is important to point out that the single crystal transformation is also achieved even at a very low temperature, which is impossible with conventional approaches. Such a convenient and efficient plasmon assisted scheme provides a new technology for the rapid achievement of single crystal materials and extends the application of surface plasmon to a much broader field.

20.
Pharmazie ; 74(3): 150-153, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30961680

RESUMO

AK-968 is a small molecular weight compound. In this study, we evaluated its anti-tumor effects on human multiple myeloma (MM) cells. Our results demonstrated that AK-968 markedly inhibited proliferation of MM cell lines in a dose-and time-dependent manner. Additionally, our flow cytometry data showed that MM cell apoptosis was significantly induced by AK-968. As expected, caspase-3 cleavage and alternation of mitochondrial membrane potential (MMP) in the MM cells treated by AK-968 was detected or quantified by Western Blot or Flow cytometry technique, respectively. In conclusion, our results suggested that AK-968 may act as a potential drug to treat human multiple myeloma.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Triazóis/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Bibliotecas de Moléculas Pequenas/farmacologia
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