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1.
Osteoarthritis Cartilage ; 32(8): 921-937, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38719085

RESUMEN

OBJECTIVE: DNA damage-inducible transcript 3 (DDIT3), as a downstream transcription factor of endoplasmic reticulum stress, is reported to regulate chondrogenic differentiation under physiological and pathological state. However, the specific involvement of DDIT3 in the degradation of condylar cartilage of temporomandibular joint osteoarthritis (TMJOA) is unclarified. DESIGN: The expression patterns of DDIT3 in condylar cartilage from monosodium iodoacetate-induced TMJOA mice were examined to uncover the potential role of DDIT3 in TMJOA. The Ddit3 knockout (Ddit3-/-) mice and their wildtype littermates (Ddit3+/+) were used to clarify the effect of DDIT3 on cartilage degradation. Primary condylar chondrocytes and ATDC5 cells were applied to explore the mechanisms of DDIT3 on autophagy and extracellular matrix (ECM) degradation in chondrocytes. The autophagy inhibitor chloroquine (CQ) was used to determine the effect of DDIT3-inhibited autophagy in vivo. RESULTS: DDIT3 were highly expressed in condylar cartilage from TMJOA mice. Ddit3 knockout alleviated condylar cartilage degradation and subchondral bone loss, compared with their wildtype littermates. In vitro study demonstrated that DDIT3 exacerbated ECM degradation in chondrocytes induced by TNF-α through inhibiting autophagy. The intraperitoneal injection of CQ further confirmed that Ddit3 knockout alleviated cartilage degradation in TMJOA through activating autophagy in vivo. CONCLUSIONS: Our findings identified the crucial role of DDIT3-inhibited autophagy in condylar cartilage degradation during the development of TMJOA.


Asunto(s)
Autofagia , Cartílago Articular , Condrocitos , Ratones Noqueados , Osteoartritis , Factor de Transcripción CHOP , Animales , Factor de Transcripción CHOP/metabolismo , Factor de Transcripción CHOP/genética , Autofagia/fisiología , Cartílago Articular/metabolismo , Ratones , Osteoartritis/metabolismo , Osteoartritis/genética , Condrocitos/metabolismo , Trastornos de la Articulación Temporomandibular/metabolismo , Trastornos de la Articulación Temporomandibular/genética , Cóndilo Mandibular/metabolismo , Cóndilo Mandibular/patología , Proteínas de la Membrana , Factor 2 Relacionado con NF-E2 , Hemo-Oxigenasa 1
2.
J Chem Phys ; 160(16)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38656442

RESUMEN

A large open-circuit voltage (VOC) deficit is the major challenge hindering the efficiency improvement of Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. Cation substitution, or doping, is usually an effective strategy to achieve carrier regulation and improve efficiency. In this work, we developed a rare-earth element lanthanum (La) doped CZTSSe thin-film solar cell by directly introducing La3+ ions into the CZTS precursor solution. Such a proposed La doping approach could effectively enhance light harvesting, adjust the bandgap, and increase the electron diffusion length. Furthermore, appropriate concentrations of La doping can reduce harmful defect cluster. Benefiting from the La doping, the VOC significantly increases from 431 to 497 mV. Consequently, the power conversion efficiency is enhanced significantly from 6.54% (VOC = 431 mV, JSC = 25.50 mA/cm2, FF = 58.28%) for the reference cell to 10.21% (VOC = 497 mV, JSC = 35.20 mA/cm2, FF = 58.41%) for the optimized La-doped cell. This research provides a new direction for enhancing the performance of CZTSSe cells, offering promising prospects for the future of CZTSSe thin-film solar cells.

3.
J Chem Phys ; 160(15)2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38619459

RESUMEN

Integrating both electrical and light-modulated multi-type neuromorphic functions in a single synaptic memristive device holds the most potential for realizing next-generation neuromorphic systems, but is still challenging yet achievable. Herein, a simple bi-terminal optoelectronic synaptic memristor is newly proposed based on kesterite Cu2ZnSnS4, exhibiting stable nonvolatile resistive switching with excellent spatial uniformity and unique optoelectronic synaptic behaviors. The device demonstrates not only low switching voltage (-0.39 ± 0.08 V), concentrated Set/Reset voltage distribution (<0.08/0.15 V), and long retention time (>104 s) but also continuously modulable conductance by both electric (different width/interval/amplitude) and light (470-808 nm with different intensity) stimulus. These advantages make the device good electrically and optically simulated synaptic functions, including excitatory and inhibitory, paired-pulsed facilitation, short-/long-term plasticity, spike-timing-dependent plasticity, and "memory-forgetting" behavior. Significantly, decimal arithmetic calculation (addition, subtraction, and commutative law) is realized based on the linear conductance regulation, and high precision pattern recognition (>88%) is well achieved with an artificial neural network constructed by 5 × 5 × 4 memristor array. Predictably, such kesterite-based optoelectronic memristors can greatly open the possibility of realizing multi-functional neuromorphic systems.

4.
J Virol ; 96(2): e0164821, 2022 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-34730394

RESUMEN

Human parainfluenza virus 3 (HPIV3) belongs to the Paramyxoviridae, causing annual worldwide epidemics of respiratory diseases, especially in newborns and infants. The core components consist of just three viral proteins: nucleoprotein (N), phosphoprotein (P), and RNA polymerase (L), playing essential roles in replication and transcription of HPIV3 as well as other paramyxoviruses. Viral genome encapsidated by N is as a template and recognized by RNA-dependent RNA polymerase complex composed of L and P. The offspring RNA also needs to assemble with N to form nucleocapsids. The N is one of the most abundant viral proteins in infected cells and chaperoned in the RNA-free form (N0) by P before encapsidation. In this study, we presented the structure of unassembled HPIV3 N0 in complex with the N-terminal portion of the P, revealing the molecular details of the N0 and the conserved N0-P interaction. Combined with biological experiments, we showed that the P binds to the C-terminal domain of N0 mainly by hydrophobic interaction and maintains the unassembled conformation of N by interfering with the formation of N-RNA oligomers, which might be a target for drug development. Based on the complex structure, we developed a method to obtain the monomeric N0. Furthermore, we designed a P-derived fusion peptide with 10-fold higher affinity, which hijacked the N and interfered with the binding of the N to RNA significantly. Finally, we proposed a model of conformational transition of N from the unassembled state to the assembled state, which helped to further understand viral replication. IMPORTANCE Human parainfluenza virus 3 (HPIV3) causes annual epidemics of respiratory diseases, especially in newborns and infants. For the replication of HPIV3 and other paramyxoviruses, only three viral proteins are required: phosphoprotein (P), RNA polymerase (L), and nucleoprotein (N). Here, we report the crystal structure of the complex of N and its chaperone P. We describe in detail how P acts as a chaperone to maintain the unassembled conformation of N. Our analysis indicated that the interaction between P and N is conserved and mediated by hydrophobicity, which can be used as a target for drug development. We obtained a high-affinity P-derived peptide inhibitor, specifically targeted N, and greatly interfered with the binding of the N to RNA, thereby inhibiting viral encapsidation and replication. In summary, our results provide new insights into the paramyxovirus genome replication and nucleocapsid assembly and lay the basis for drug development.


Asunto(s)
Chaperonas Moleculares/química , Proteínas de la Nucleocápside/química , Virus de la Parainfluenza 3 Humana/química , Fosfoproteínas/química , Secuencia de Aminoácidos , Antivirales/química , Antivirales/metabolismo , Cristalografía por Rayos X , Interacciones Hidrofóbicas e Hidrofílicas , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Mutación , Proteínas de la Nucleocápside/genética , Proteínas de la Nucleocápside/metabolismo , Virus de la Parainfluenza 3 Humana/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Unión Proteica , Conformación Proteica , ARN Viral/metabolismo
5.
J Virol ; 96(3): e0171321, 2022 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-34787453

RESUMEN

Rift Valley fever virus (RVFV) belongs to the order Bunyavirales and is the type species of genus Phlebovirus, which accounts for over 50% of family Phenuiviridae species. RVFV is mosquito-borne and causes severe diseases in both humans and livestock, and consists of three segments (S, M, L) in the genome. The L segment encodes an RNA-dependent RNA polymerase (RdRp, L protein) that is responsible for facilitating the replication and transcription of the virus. It is essential for the virus and has multiple drug targets. Here, we established an expression system and purification procedures for full-length L protein, which is composed of an endonuclease domain, RdRp domain, and cap-binding domain. A cryo-EM L protein structure was reported at 3.6 Å resolution. In this first L protein structure of genus Phlebovirus, the priming loop of RVFV L protein is distinctly different from those of other L proteins and undergoes large movements related to its replication role. Structural and biochemical analyses indicate that a single template can induce initiation of RNA synthesis, which is notably enhanced by 5' viral RNA. These findings help advance our understanding of the mechanism of RNA synthesis and provide an important basis for developing antiviral inhibitors. IMPORTANCE The zoonosis RVF virus (RVFV) is one of the most serious arbovirus threats to both human and animal health. RNA-dependent RNA polymerase (RdRp) is a multifunctional enzyme catalyzing genome replication as well as viral transcription, so the RdRp is essential for studying the virus and has multiple drug targets. In our study, we report the structure of RVFV L protein at 3.6 Å resolution by cryo-EM. This is the first L protein structure of genus Phlebovirus. Strikingly, a single template can initiate RNA replication. The structure and assays provide a comprehensive and in-depth understanding of the catalytic and substrate recognition mechanism of RdRp.


Asunto(s)
Modelos Moleculares , Conformación Proteica , ARN Polimerasa Dependiente del ARN/química , Virus de la Fiebre del Valle del Rift/enzimología , Secuencias de Aminoácidos , Dominio Catalítico , Fenómenos Químicos , Secuencia Conservada , Microscopía por Crioelectrón , Dominios y Motivos de Interacción de Proteínas , ARN Polimerasa Dependiente del ARN/metabolismo , Proteínas Recombinantes de Fusión , Proteínas Virales/química
6.
Biotechnol Appl Biochem ; 70(1): 374-386, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35644907

RESUMEN

Gram-negative bacterium Escherichia coli has a tripartite cell envelope with a cytoplasmic membrane, a peptidoglycan layer, and an asymmetric outer membrane containing lipopolysaccharide in its outer leaflet. The biogenesis of peptidoglycan and lipopolysaccharide shares the same substrate UDP-GlcNAc. From UDP-GlcNAc, MurA catalyzes the first reaction for peptidoglycan biosynthesis, while LpxA catalyzes the first reaction for lipopolysaccharide biosynthesis. This study demonstrates that murA overexpression in E. coli MG1655 inhibited the cell growth and increased the cell length, whereas lpxA overexpression in MG1655 neither inhibited the cell growth nor increased the cell length. Further study showed that individual overexpression of the other eight genes encoding the enzymes to catalyze the initial reactions in the biosynthetic pathway of lipopolysaccharide did not inhibit the cell growth. When MG1655/pBad-lpxA, MG1655/pBad-lpxD, and MG1655/pBad-lpxH were transformed with pFW01-thrA*BC-rhtC that contains the key genes for L-threonine biosynthesis and transport, the L-threonine production was increased. The L-threonine production in MG1655/pFW01-thrA*BC-rhtC/pBad-lpxH increased 46.1% as compared to the control MG1655/pFW01-thrA*BC-rhtC/pBad.


Asunto(s)
Escherichia coli , Lípido A , Escherichia coli/metabolismo , Vías Biosintéticas/genética , Peptidoglicano/metabolismo , Lipopolisacáridos , Treonina , Uridina Difosfato/metabolismo
7.
J Chem Phys ; 159(11)2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37712793

RESUMEN

Optoelectronic memristors hold the most potential for realizing next-generation neuromorphic computation; however, memristive devices that can integrate excellent resistive switching and both electrical-/light-induced bio-synaptic behaviors are still challenging to develop. In this study, an artificial optoelectronic synapse is proposed and realized using a kesterite-based memristor with Cu2ZnSn(S,Se)4 (CZTSSe) as the switching material and Mo/Ag as the back/top electrode. Benefiting from unique electrical features and a bi-layered structure of CZTSSe, the memristor exhibits highly stable nonvolatile resistive switching with excellent spatial uniformity, concentrated Set/Reset voltage distribution (variation <0.08/0.02 V), high On/Off ratio (>104), and long retention time (>104 s). A possible mechanism of the switching behavior in such a device is proposed. Furthermore, these memristors successfully achieve essential bio-synaptic functions under both electrical and various visible light (470-655 nm) stimulations, including electrical-induced excitatory postsynaptic current, paired pulse facilitation, long-term potentiation, long-term depression, spike-timing-dependent plasticity, as well as light-stimulated short-/long-term plasticity and learning-forgetting-relearning process. As such, the proposed neotype kesterite-based memristor demonstrates significant potential in facilitating artificial optoelectronic synapses and enabling neuromorphic computation.

8.
J Chem Phys ; 158(18)2023 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-37154283

RESUMEN

Memristive devices with both electrically and optically induced synaptic dynamic behaviors will be crucial to the accomplishment of brain-inspired neuromorphic computing systems, in which the resistive materials and device architectures are two of the most important cornerstones, but still under challenge. Herein, kuramite Cu3SnS4 is newly introduced into poly-methacrylate as the switching medium to construct memristive devices, and the expected high-performance bio-mimicry of diverse optoelectronic synaptic plasticity is demonstrated. In addition to the excellent basic performances, such as stable bipolar resistive switching with On/Off ratio of ∼486, Set/Reset voltage of ∼-0.88/+0.96 V, and good retention feature of up to 104 s, the new designs of memristors possess not only the multi-level controllable resistive-switching memory property but also the capability of mimicking optoelectronic synaptic plasticity, including electrically and visible/near-infrared light-induced excitatory postsynaptic currents, short-/long-term memory, spike-timing-dependent plasticity, long-term plasticity/depression, short-term plasticity, paired-pulse facilitation, and "learning-forgetting-learning" behavior as well. Predictably, as a new class of switching medium material, such proposed kuramite-based artificial optoelectronic synaptic device has great potential to be applied to construct neuromorphic architectures in simulating human brain functions.

9.
J Chem Phys ; 157(13): 134706, 2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36209009

RESUMEN

Concernin the crucial interfacial issues in multi-layered kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells, (NH4)2S treatment has been proven to be effective in eliminating surface secondary phases. While for the CZTSSe absorbers without impurity phases, what can the low-temperature (NH4)2S treatment do to the absorbers, thus to the device performance? Herein, the chloride-fabricated CZTSSe absorbers are surface treated with the (NH4)2S solution at room temperature, and its influence on the device performance is investigated in detail. Surprisingly, such treatment can make the absorbers' surface become nearly super-hydrophilicity, greatly decreasing the surface wetting angle from 63.1° ± 3.4° to 7.3° ± 0.6° after 50 min-treating, and thus lead to marked differences in the interfacial properties of the CdS/CZTSSe heterojunctions deposited in a chemical bath. Consequently, for the best-performing CZTSSe cells, combining the passivated interfacial defects, increased carrier concentration, reduced carrier recombination, and prolonged minority lifetime, the efficiency is improved from 6.54% to 9.88%, together with the 37 mV and 7.9% increase in VOC and FF, respectively. This study confirms the newfound results that the (NH4)2S treatment can effectively adjust the wettability of the absorbers to form high-quality heterojunctions to boost the device efficiency, which would be valuable for an in-depth understanding of the intrinsic mechanisms of interfacial processing.

10.
J Am Chem Soc ; 143(8): 3231-3237, 2021 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-33600169

RESUMEN

Long-term durability is critically important for the commercialization of perovskite solar cells (PSCs). The ionic character of the perovskite and the hydrophilicity of commonly used additives for the hole-transporting layer (HTL), such as lithium bis(trifluoromethanesulfonyl)imide (Li-TFSI) and tert-butylpyridine (tBP), render PSCs prone to moisture attack, compromising their long-term stability. Here we introduce a trifluoromethylation strategy to overcome this drawback and to boost the PSC's solar to electric power conversion efficiency (PCE). We employ 4-(trifluoromethyl)benzylammonium iodide (TFMBAI) as an amphiphilic modifier for interfacial defect mitigation and 4-(trifluoromethyl)pyridine (TFP) as an additive to enhance the HTL's hydrophobicity. Surface treatment of the triple-cation perovskite with TFMBAI largely suppressed the nonradiative charge carrier recombination, boosting the PCE from 20.9% to 23.9% and suppressing hysteresis, while adding TFP to the HTL enhanced the PCS's resistance to moisture while maintaining its high PCE. Taking advantage of the synergistic effects resulting from the combination of both fluoromethylated modifiers, we realize TFMBAI/TFP-based highly efficient PSCs with excellent operational stability and resistance to moisture, retaining over 96% of their initial efficiency after 500 h maximum power point tracking (MPPT) under simulated 1 sun irradiation and 97% of their initial efficiency after 1100 h of exposure under ambient conditions to a relative humidity of 60-70%.

11.
Antimicrob Agents Chemother ; 65(10): e0034121, 2021 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-34310209

RESUMEN

Gram-negative bacteria are intrinsically resistant to antibiotics due to the presence of the cell envelope, but the mechanisms of this resistance are still not fully understood. In this study, a series of mutants that lack one or more major components associated with the cell envelope were constructed from Escherichia coli K-12 W3110. WJW02 can only synthesize Kdo2-lipid A, which lacks the core oligosaccharide portion of lipopolysaccharide (LPS). WJW04, WJW07, and WJW08 were constructed from WJW02 by deleting the gene clusters relevant to the biosynthesis of exopolysaccharide, flagella, and fimbriae, respectively. WJW09, WJW010, and WJW011 cells cannot synthesize exopolysaccharide (EPS), flagella, and fimbria, respectively. Compared to the wild type (W3110), mutants WJW02, WJW04, WJW07, and WJW08 cells showed decreased resistance to more than 10 different antibacterial drugs, but the mutants WJW09, WJW010, and WJW011 did not. This indicates that the core oligosaccharide portion of lipopolysaccharide plays an important role in multiple antibiotic resistance in E. coli and that the first heptose in the core oligosaccharide portion is critical. Furthermore, the removal of the core oligosaccharide of LPS leads to influences on cell wall morphology, cell phenotypes, porins, efflux systems, and response behaviors to antibiotic stimulation. The results demonstrate the important role of lipopolysaccharide in the antibiotic resistance of Gram-negative bacteria.


Asunto(s)
Escherichia coli K12 , Escherichia coli , Farmacorresistencia Microbiana , Escherichia coli/genética , Escherichia coli K12/genética , Lipopolisacáridos , Oligosacáridos
12.
BMC Geriatr ; 21(1): 565, 2021 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-34663218

RESUMEN

BACKGROUND: Due to the increasingly ageing society and the shortage of nursing human resources in China, the imbalance between the home care needs of older patients and the inadequate supply of nursing services is increasing. Based on this medical situation, China is implementing internet-based home care (with the nurses who provide this care called online nurses or sharing nurses) based on the concept of the sharing economy, internet technology and knowledge from the home care experience in other countries. Internet-based home care follows an online application/offline service model. Patients place orders through an app, nurses grab orders instantly, and managers dispatch orders through a web platform based on various factors such as nurses' qualifications, professionalism and distance from the patient. In this way, home care is provided for patients with limited mobility, such as older or disabled patients, patients in rehabilitation and terminal patients. Only by fully understanding the barriers to accessing internet-based home care can we provide quality nursing services to older patients and achieve the sustainable development of internet-based home care. OBJECTIVE: The goal of this study was to use qualitative methods to explore barriers to accessing internet-based home care for older patients. METHODS: Based on Levesque's access to health care framework, semi-structured personal interviews were conducted with 19 older patients in a descriptive qualitative study using directed content analysis. RESULTS: We identified four barriers to accessing internet-based home care for older patients: barriers to perceiving, seeking, paying for, and engaging in internet-based home care. Specific barriers included traditional perceptions, barriers to internet use, high payment costs, uneven quality of services, and concerns about privacy and patient safety. CONCLUSIONS: Internet-based home care brings new risks and challenges. In order to enable older patients to better enjoy it, it is necessary to strengthen publicity, optimize the network application process, improve the health insurance system, formulate unified nursing service standards, and address safety risks.


Asunto(s)
Servicios de Atención de Salud a Domicilio , China , Humanos , Internet , Conocimiento , Investigación Cualitativa
13.
BMC Cancer ; 20(1): 900, 2020 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-32962642

RESUMEN

BACKGROUNDS: The association of neutrophil-lymphocyte ratio (NLR) and CD34 expression level with PSA level, Gleason score, and clinical stage was investigated in patients with prostate cancer. The correlation between NLR and CD34 expression was also investigated to provide evidence supporting the use of NLR for predicting the prognosis of prostate cancer patients. METHODS: Clinical data of 75 patients diagnosed with prostate cancer by prostate aspiration biopsy were retrospectively analyzed. The correlation between NLR, CD34 expression, and clinicopathological characteristics was analyzed using the χ2 test and one-way analysis of variance. The correlation between NLR and CD34 was determined using the Pearson coefficient. Disease free survival was estimated by Kaplan-Meier analysis. RESULTS: Both NLR and CD34 expression were significantly positively correlated with PSA, Gleason score, and clinical stage (P < 0.05 both). Patients in the NLRHigh/CD34High group were characterized by high PSA level and Gleason score and late clinical stage. NLR was positively correlated with CD34 expression (r = 0.529, P < 0.001). CONCLUSIONS: Pretreatment NLR was a valuable marker of prognosis in prostate cancer. NLR is positively correlated with CD34 expression.


Asunto(s)
Antígenos CD34/biosíntesis , Linfocitos/patología , Neutrófilos/patología , Neoplasias de la Próstata/sangre , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/sangre , Antígenos CD34/inmunología , Humanos , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Neoplasias de la Próstata/inmunología , Estudios Retrospectivos
14.
Org Biomol Chem ; 18(19): 3754-3760, 2020 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-32368777

RESUMEN

Five new dimethylmethylene-bridged triphenylamine (DTPA) derivatives 4a-e bearing peripheral cross-linkable vinyl and trifluorovinyl groups were synthesized. The chemical structure of these compounds was characterized by 1H NMR, 13C NMR and HRMS. Their optical properties were studied by UV/Vis spectroscopy and fluorescence spectroscopy. Based on these studies, blue-coloured fluorescence and high fluorescence quantum yields were obtained for 4a-e. The electrochemical properties of these compounds were studied by cyclic voltammetry and the results were further elucidated by DFT calculations. Furthermore, the thermotropic properties of the new DTPAs were investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Compounds 4a-d exhibit high thermal stability and thermal cross-linkable properties. These results provide an effective strategy for the design and synthesis of thermally stable and cross-linkable DTPA derivatives with tunable optical and electrochemical properties.

15.
J Environ Sci Health B ; 55(3): 230-238, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31679438

RESUMEN

Ciprofloxacin (CPFX) and enrofloxacin (ENFX), two of the most widely used fluoroquinolones (FQs), pose a great threat to humans and the ecosystem. In this study, the toxic mechanisms between the two FQs and trypsin were evaluated by means of multiple spectroscopic methods, as well as molecular docking. During the fluorescence investigations, both FQs quenched the intrinsic fluorescence of trypsin effectively, which was due to the formation of moderately strong complexes (mainly through van der Waals forces and hydrogen bonds). The binding of two FQs not only caused the conformational and micro-environmental changes of trypsin, but also changed its molecular activity; shown by the UV-Visible absorption spectroscopy, synchronous fluorescence spectroscopy, and functional tests. The established methods in this work can help to comprehensively understand the transport of FQs in the human body.


Asunto(s)
Ciprofloxacina/química , Ciprofloxacina/toxicidad , Enrofloxacina/química , Enrofloxacina/toxicidad , Tripsina/química , Dicroismo Circular , Enlace de Hidrógeno , Simulación del Acoplamiento Molecular , Conformación Proteica , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta
16.
J Am Chem Soc ; 141(3): 1217-1221, 2019 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-30623652

RESUMEN

We report an ambimodal trispericyclic transition state leading to [6+4]-, [4+6]-, and [8+2]-cycloadducts in the reactions of 8,8-disubstituted heptafulvenes with 6,6-dimethylfulvene. The potential energy surfaces for these reactions were explored with ωB97X-D density functional theory. Quasi-classical direct molecular dynamics simulations gave information on the ratios of products expected in these reactions.

17.
J Cell Physiol ; 233(9): 6758-6766, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29226968

RESUMEN

Dishevelled 2 (Dvl-2), a key mediator of the wnt/ß-catenin signaling pathway, plays critical roles in osteoblasts differentiation in hyperlipidemia environment. In our previous study, we observed a strong correlation between increased dvl2 expression and decreased new bone formation around implants in a rat hyperlipidemia implant surgery model. However, transcriptional regulation of Dvl2 by microRNAs in this process remains unknown. In the current study, we searched in online database and identified four significantly up-regulated miRNAs, miR-21-5p, miR-29c-3p, miR-138-5p, and miR-351-5p that could potentially regulate Dvl2. Using Western blot and dual-luciferase assays, we confirmed that miR29c-3p suppresses Dvl2 expression by binding to its 3'-UTR. Our results suggest a novel transcriptional regulation mechanism of Dvl2 by miR-29c-3p in osteoblasts differentiation of BMSCs.


Asunto(s)
Células de la Médula Ósea/fisiología , Diferenciación Celular/genética , Proteínas Dishevelled/genética , Hiperlipidemias/genética , MicroARNs/genética , Osteoblastos/fisiología , Regiones no Traducidas 3'/genética , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Regulación de la Expresión Génica/genética , Hiperlipidemias/patología , Masculino , Células Madre Mesenquimatosas/fisiología , Osteogénesis/genética , Ratas , Ratas Wistar , Transcripción Genética/genética , Regulación hacia Arriba/genética
18.
J Am Chem Soc ; 140(8): 3061-3067, 2018 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-29419295

RESUMEN

Ambimodal reactions involve a single transition state leading to multiple products. In such reactions, transition state theory gives no information about the ratio of products that are formed, and molecular dynamics must be performed to predict this ratio. Understanding the relationship between the transition structure and the product ratio is a long-standing problem in molecular dynamics. We have studied 15 ambimodal pericyclic reactions and investigated the relationship between the TS bond lengths in the saddle points and the product ratios from trajectory simulations. A linear correlation, ln(B:A) = -9.4(Bond 3 - Bond 2), is found with R2 = 0.92, where A and B refer to the products formed upon formation of bonds 2 and 3, respectively. The correlation shows that the ratio of products formed after the bifurcation is related to the partial bond lengths, and corresponding bond orders, in the transition state.

19.
Anal Chem ; 88(5): 2929-36, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26857643

RESUMEN

A library of 32 polystyrene copolymer latexes, with diameters ranging between 53 and 387 nm, was used to develop and demonstrate a high-throughput assay using a 96-well microplate platform to measure critical coagulation concentrations, a measure of colloidal stability. The most robust assay involved an automated centrifugation-decantation step to remove latex aggregates before absorbance measurements, eliminating aggregate interference with optical measurements made through the base of the multiwell plates. For smaller nanoparticles (diameter <150 nm), the centrifugation-decantation step was not required as the interference was less than with larger particles. Parallel measurements with a ChemiDoc MP plate scanner gave indications of aggregation; however, the results were less sensitive than the absorbance measurements.

20.
J Integr Plant Biol ; 57(11): 943-53, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26282053

RESUMEN

Genome information from model species such as rice can assist in the cloning of genes in a complex genome, such as maize. Here, we identified a maize ortholog of rice GS5 that contributes to kernel development in maize. The genome-wide association analysis of the expression levels of ZmGS5, and 15 of its 26 paralogs, identified a trans-regulator on chromosome 7, which was a BAK1-like gene. This gene that we named as ZmBAK1-7 could regulate the expression of ZmGS5 and three of the paralogs. Candidate-gene association analyses revealed that these five genes were associated with maize kernel development-related traits. Linkage analyses also detected that ZmGS5 and ZmBAK1-7 co-localized with mapped QTLs. A transgenic analysis of ZmGS5 in Arabidopsis thaliana L. showed a significant increase in seed weight and cell number, suggesting that ZmGS5 may have a conserved function among different plant species that affects seed development.


Asunto(s)
Frutas/crecimiento & desarrollo , Oryza/genética , Proteínas de Plantas/genética , Zea mays/genética , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Oryza/crecimiento & desarrollo , Plantas Modificadas Genéticamente , Zea mays/crecimiento & desarrollo
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