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In this paper, a simple sensing method based on a silicon oxide microcavity optomechanical oscillator (OMO) is proposed and demonstrated for the detection of acoustic signals. Firstly, the resonance damping was reduced by improving the optical quality factor (Qo) and increasing the sphere-to-neck ratio. After optimizing the process, a microsphere OMO was fabricated, which has an ultra-high mechanical quality factor (6.8 × 106) and greater sphere-to-neck ratio (â¼11:1), based on which ultra-narrow linewidth phonon laser (â¼1â Hz) is constructed. Secondly, by changing the refractive index of the coupling interval, the low-frequency acoustic pressure signal is efficiently coupled into the microcavity OMO to construct a high-resolution acoustic sensor. This sensing mechanism can not only measure the acoustic pressure, but also use the sideband signal in the modulation mechanism to measure the frequency of acoustic signals (15â Hzâ¼16 kHz), the sensitivity is 10.3 kHz/Pa, the minimum detectable pressure is 1.1â mPa, and noise-limited minimum detectable pressure is 28.8 µPa/Hz1/2. It is the highest detection resolution compared with the same type of low-frequency acoustic signal detection currently reported. This OMO-based acoustic sensing detection method opens up a new path for future miniaturized, ultra-high-precision, and cost-effective acoustic sensing.
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Pattern recognition receptors (PRRs) play a critical role in the innate immune response, and toll-like receptor 7 (TLR7) is an important member of PRRs. Although several TLR7 agonists are available, most of them are being tested clinically, with only one available on the market. Thus, it is imperative to develop new TLR7 agonists. In this study, we designed and synthesized three kinds of quinazoline derivatives and five kinds of pyrrolo[3,2-d]pyrimidine derivatives targeting TLR7. The antiviral efficacy of these compounds was evaluated in vitro and in vivo. Our findings indicated that four kinds of compounds showed exceptional antiviral activity. Furthermore, molecular docking studies confirmed that compound 11 successfully positioned itself in the pocket of the TLR7 guanosine loading site with a binding energy of -4.45 kcal mol-1. These results suggested that these compounds might be potential antiviral agents.
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Quinazolinas , Receptor Toll-Like 7 , Receptor Toll-Like 7/agonistas , Receptor Toll-Like 7/metabolismo , Quinazolinas/química , Simulación del Acoplamiento Molecular , Adyuvantes Inmunológicos , Antivirales/farmacología , Pirimidinas/químicaRESUMEN
Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.
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Regeneración Ósea , Diferenciación Celular , Osteogénesis , Animales , Ratones , Ingeniería de Tejidos/métodos , Células Madre Mesenquimatosas/citología , HumanosRESUMEN
Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.
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Hepatic ischemia-reperfusion injury (HIRI) is a relatively common complication of liver resection and transplantation that is intimately connected to oxidative stress. The superoxide anion radical (O2â¢-), as the first reactive oxygen species produced by organisms, is an important marker of HIRI. The endoplasmic reticulum (ER) is an essential site for O2â¢- production, especially ER oxidative stress, which is closely linked to HIRI. Thus, dynamic variations in ER O2â¢- may accurately indicate the HIRI extent. However, there is still a lack of tools for the dynamic reversible detection of ER O2â¢-. Therefore, we designed and prepared an ER-targeted fluorescent reversible probe DPC for real-time tracing of O2â¢- fluctuations. We successfully observed a marked increase in ER O2â¢- levels in HIRI mice. A potential NADPH oxidase 4-ER O2â¢--SERCA2b-caspase 4 signaling pathway in HIRI mice was also revealed. Attractively, DPC was successfully used for precise fluorescent navigation and excision of HIRI sites.
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Daño por Reperfusión , Superóxidos , Ratones , Animales , Superóxidos/metabolismo , Hígado/diagnóstico por imagen , Hígado/metabolismo , Daño por Reperfusión/diagnóstico por imagen , Daño por Reperfusión/metabolismo , Retículo Endoplásmico/metabolismo , Imagen ÓpticaRESUMEN
Tectonic extrusion bypassing the eastern Himalayan syntaxis results in a significant increase in regional stress instability and the associated frequent occurrence of earthquakes in southern Yunnan, China. However, the stress field, and the relationship between the focal mechanism of earthquakes and stress evolution in southern Yunnan, remain enigmatic. In this paper, using a modified grid point test method, we calculated the focal mechanism of ML ≥ 2.5 earthquakes in southern Yunnan (22-25° N, 100-104° E) from January 2009 to June 2023. Utilizing the solutions of historical earthquake focal mechanisms, we obtained the present-day regional tectonic stress field in southern Yunnan via inversion. The results indicate complex and diverse seismic focal mechanisms, and the main types of earthquakes are strike-slip events, followed by normal fault and reverse fault events. The orientations of the maximum and minimum principal stress axes rotate in a clockwise direction from northeast to southwest. The internal stress orientation distribution of the rhombic Sichuan-Yunnan block in the study area is consistent, and the block boundary zone is the site where stress deflection occurs, and the regional tectonic stress field is influenced by the interaction among different blocks. The distribution of R-value in the Lamping-Simao block gradually increases from north to south, indicating that the compressive stress required for material transport becomes relatively small. Combined with the geological and tectonic background of the study area, our results suggest that the speed of block movement gradually decreases from north to south; the distribution of R-value in the South China block is significantly smaller than that of the interior of the Sichuan-Yunnan rhombus, and the proportion of compressive stresses is larger, indicating a stronger extrusion in this region, which may be related to the fact that the Sichuan-Yunnan rhombus is strongly resisted by the South China block in the east.
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Hepatocellular carcinoma (HCC) is the most common type of liver malignancy with high incidence and poor prognosis. Transmembrane protein 147 (TMEM147) has been implicated in the development of colon cancer. However, the role of TMEM147 in HCC remains unclear. In this study, data of 371 HCC tissues, 50 adjacent nontumor tissues, and 110 normal liver tissues were retrieved from the TCGA and GTEx databases. TMEM147 expression was found to be increased in HCC tissues. High expression of TMEM147 was related to poor prognosis, and TMEM147 was confirmed to be an independent prognostic factor for HCC patients. A receiver operating characteristics (ROC) analysis was performed and showed that the diagnostic efficacy of TMEM147 was significantly higher than that of AFP (0.908 versus 0.746, p < 0.001). Furthermore, TMEM147 promoted tumor immune infiltration, and macrophages were the immune cells that predominantly expressed TMEM147 in HCC. Further analysis revealed that TMEM147 mainly impacted the ribosome pathway, and CTCF, MLLT1, TGIF2, ZNF146, and ZNF580 were predicted to be the upstream transcription factors for TMEM147 in HCC. These results suggest that TMEM147 serves as a promising biomarker for diagnosis and prognosis and may potentially become a therapeutic target for HCC.
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It was aimed at the therapeutic value of loop electrosurgical excision procedure (LEEP) under propofol intravenous anesthesia combined with nano-silver gel in chronic cervicitis. 100 patients with chronic cervicitis were selected and randomly divided into the control group with 50 cases (LEEP under intravenous anesthesia with fentanyl) and the experimental group with the other 50 cases (LEEP under propofol intravenous anesthesia combined with the nano-silver gel). It was suggested from the results that the mean arterial pressure (MAP) and heart rate (HR) (76.88±5.65mmHg, 75.45±5.06beats/min) of patients in the experimental group at T1 time were better than those of the control group (83.76±5.43mmHg, 68.31±5.28beats/min). Visual analogue scale (VAS) (1.85±0.73 points), onset time of anesthesia (0.56±0.21min), time to open eyes (2.45±1.38min) and time of consciousness recovery (5.22±1.42min) were all lower than those of the control group (2.83±0.79 points, 0.93±0.25min, 4.33±1.45min, and 7.15±1.34min, respectively). The incidence of adverse reactions, the effective rate of treatment, the time of wound healing, and the incidence of complications (6%, 94%, 23.83±2.05 days, and 6%, respectively) were all better than those of the control group (24%, 70%, 29.25±2.16 days, and 6%) (P<0.05). All in all, intravenous anesthesia with propofol was beneficial to perform LEEP better, and the combination of LEEP combined with nano-silver gel had an important value in the treatment of chronic cervicitis and was worthy of clinical promotion.
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Propofol , Cervicitis Uterina , Anestesia Intravenosa , Anestésicos Intravenosos , Electrocirugia , Femenino , Humanos , Propofol/uso terapéuticoRESUMEN
Lipopeptides are important non-ribosomal peptide synthetases (NRPSs) products with broad therapeutic potential in biotechnology and biopharmaceutical applications. Fatty acyl modifications in N-terminal of lipopeptides have attracted wide interest in the engineering processes of altered fatty acyl selectivity. In this study, we focused on the starter condensation domain of antibiotic A54145 (lptC1) and its indiscriminate selectivity of fatty acyl substrates, which results in multi-component products. Using in silico analysis, five site-directed mutations at protein-protein interface were identified with altered activity and selectivity towards wild type lptC1. The variants Y149W and A330T exhibited changed substrate selectivity to prefer longer branched chain fatty acyl substrate, while T16A and A350D showed improved selectivity for shorter linear chain fatty acyl substrates. Subsequently, molecular dynamics (MD) simulations were performed to analyze the impact of these residues on the changes of catalytic activity and conformation. Through in silico analysis, the altered binding free energy were coincident with the corresponding activity performance of the variants, and surface forces indicated that other factors or processes may influence the activity and selectivity. Moreover, the MD results revealed even altered active center conformations, implying the importance of these interface residues affected on distant active center thus reflected to catalysis activity. Based on the biochemistry and computational results, our work provides detailed insights from molecular and dynamics aspects into the role of C1's interface residues during complex NRPS biosynthesis machinery, prompting further rational engineering for lipopeptide catalysis.
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Ácidos Grasos/metabolismo , Análisis Mutacional de ADN , Ácidos Grasos/química , Lipoproteínas/biosíntesis , Lipoproteínas/química , Lipoproteínas/genética , Simulación de Dinámica Molecular , Mutagénesis Sitio-Dirigida , Unión Proteica , Especificidad por SustratoRESUMEN
The original pattern recognition and classification of crop diseases needs to collect a large amount of data in the field and send them next to a computer server through the network for recognition and classification. This method usually takes a long time, is expensive, and is difficult to carry out for timely monitoring of crop diseases, causing delays to diagnosis and treatment. With the emergence of edge computing, one can attempt to deploy the pattern recognition algorithm to the farmland environment and monitor the growth of crops promptly. However, due to the limited resources of the edge device, the original deep recognition model is challenging to apply. Due to this, in this article, a recognition model based on a depthwise separable convolutional neural network (DSCNN) is proposed, which operation particularities include a significant reduction in the number of parameters and the amount of computation, making the proposed design well suited for the edge. To show its effectiveness, simulation results are compared with the main convolution neural network (CNN) models LeNet and Visual Geometry Group Network (VGGNet) and show that, based on high recognition accuracy, the recognition time of the proposed model is reduced by 80.9% and 94.4%, respectively. Given its fast recognition speed and high recognition accuracy, the model is suitable for the real-time monitoring and recognition of crop diseases by provisioning remote embedded equipment and deploying the proposed model using edge computing.
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Algoritmos , Redes Neurales de la Computación , Simulación por ComputadorRESUMEN
OBJECTIVES: To determine the effect of NF-κB on cell proliferation and apoptosis, we investigate the expression of inflammation and apoptosis-related factors in the bovine mammary epithelial cell line, MAC-T. RESULTS: MAC-T cells were cultured in vitro and MTT and LDH assays used to determine the effects of lipopolysaccharide (LPS) on proliferation and cytotoxicity respectively. RT-PCR and western blotting were used to evaluate the effect of LPS and NF-κB inhibition [pyrrolidine dithiocarbamate (PDTC) treatment] on the expression of inflammation and apoptosis-related factors. LPS significantly inhibited MAC-T cell proliferation in a dose- and time-dependent manner. Furthermore, LPS promoted apoptosis while the NF-кB inhibitor PDTC attenuated this effect. After LPS treatment, the NF-кB signaling pathway was activated, and the expression of inflammation and apoptosis-related factors increased. When PDTC blocked NF-кB signaling, the expression of inflammation and apoptosis-related factors were decreased in MAC-T cells. CONCLUSIONS: LPS activates the TLR4/NF-κB signaling pathway, inhibits proliferation and promotes apoptosis in MAC-T cells. NF-кB inhibition attenuates MAC-T cell apoptosis and TLR4/NF-κB signaling pathway. NF-кB inhibitor alleviating MAC-T cell apoptosis is presumably modulated by NF-кB.
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Células Epiteliales/citología , Lipopolisacáridos/farmacología , FN-kappa B/genética , FN-kappa B/metabolismo , Pirrolidinas/farmacología , Tiocarbamatos/farmacología , Acidosis/genética , Acidosis/metabolismo , Acidosis/patología , Animales , Apoptosis/efectos de los fármacos , Bovinos , Enfermedades de los Bovinos/genética , Enfermedades de los Bovinos/metabolismo , Enfermedades de los Bovinos/patología , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacosRESUMEN
BACKGROUND AND AIM: Previous studies have revealed significantly increased levels of plasma and mucosal homocysteine (Hcy) in patients with Crohn's disease (CD); however, whether Hcy is involved in intestinal fibrosis of CD remains unclear. This study aimed to investigate the effects of Hcy on intestinal fibrosis in TNBS/ethanol-induced colitis and to elucidate its potential mechanisms. METHODS: Sprague-Dawley rats were divided into 4 groups: normal control, normal + Hcy injection, TNBS model and TNBS model + Hcy injection. Hyperhomocysteinemia was induced by subcutaneous injection of Hcy. DAI, CMDI and HI were calculated to evaluate the severity of colitis. Masson trichrome staining was performed to assess the severity of fibrosis. The plasma and mucosal levels of Hcy were measured by HPLC-FD. The levels of IL-1ß, IL-6, TNF-α, TGF-ß1, CTGF, MMP-2,9 and collagen I, III in the colon were determined by ELISA, and the mRNA expressions of TGF-ß1, MMP-2,9 and TIMP-1 were detected by RT-PCR. RESULTS: Hcy was found to increase the scores of DAI, CMDI and HI; levels of IL-1ß, Il-6, TNF-α, TGF-ß1, CTGF, MMP-2,9 and collagen I, III; and mRNA expressions of TGF-ß1, MMP-2,9 and TIMP-1 in colonic tissue of rats with TNBS/ethanol-induced colitis. CONCLUSIONS: Hcy promotes intestinal fibrosis in rats with TNBS/ethanol-induced colitis, the underlying mechanisms of which may be attributed to its effects of increasing inflammatory damage, promoting the expression of profibrogenic cytokines and influencing MMPs/TIMPs balance.
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Colitis/inducido químicamente , Colon/patología , Homocisteína , Hiperhomocisteinemia/inducido químicamente , Ácido Trinitrobencenosulfónico , Animales , Colitis/sangre , Colitis/patología , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Colon/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Etanol , Fibrosis , Homocisteína/sangre , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/patología , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratas Sprague-DawleyRESUMEN
First-principles calculations based on density functional theory have been performed to explore the stable configurations, electronic structures, and vibrational spectra of neutral and charged silicon monoxide clusters (SiO)n((0,±)) (n = 2-7), which could be used as precursors in the synthesis of silicon nanowires. Our theoretical calculations provide new results on characteristic electron affinity, ionization potential, and vibrational spectroscopy, guiding future experiments in the synthesis of high-quality silicon nanowires. Specifically, as the number of SiO units n increases, IR spectra of (SiO)n(±) and Raman spectra of (SiO)n(-) show an evident blue shift, and Raman spectra of (SiO)n demonstrate a red shift. Moreover, most of the neutral silicon monoxide clusters have strong IR intensities and weak Raman activities, while most of the anionic counterparts have relatively weak IR intensities and strong Raman activities. Some other energetically competitive isomers of some (SiO)n((0,±)) species were also studied for comparison.
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ATP-binding cassette (ABC) transporters, acting as cellular "pumps," facilitate solute translocation through membranes via ATP hydrolysis. Their overexpression is closely tied to multidrug resistance (MDR), a major obstacle in chemotherapy and neurological disorder treatment, hampering drug accumulation and delivery. Extensive research has delved into the intricate interplay between ABC transporter structure, function, and potential inhibition for MDR reversal. Cryo-electron microscopy has been instrumental in unveiling structural details of various MDR-causing ABC transporters, encompassing ABCB1, ABCC1, and ABCG2, as well as the recently revealed ABCC3 and ABCC4 structures. The newly obtained structural insight has deepened our understanding of substrate and drug binding, translocation mechanisms, and inhibitor interactions. Given the growing body of structural information available for human MDR transporters and their associated mechanisms, we believe it is timely to compile a comprehensive review of these transporters and compare their functional mechanisms in the context of multidrug resistance. Therefore, this review primarily focuses on the structural aspects of clinically significant human ABC transporters linked to MDR, with the aim of providing valuable insights to enhance the effectiveness of MDR reversal strategies in clinical therapies.
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Transportadoras de Casetes de Unión a ATP , Antineoplásicos , Humanos , Transportadoras de Casetes de Unión a ATP/metabolismo , Microscopía por Crioelectrón , Resistencia a Múltiples Medicamentos , Adenosina Trifosfato , Resistencia a Antineoplásicos , Antineoplásicos/farmacología , Línea Celular TumoralRESUMEN
In this study, we investigated the effects of salinity on elemental sulfur-driven autotrophic denitrification (SAD) efficiency, and microbial communities. The results revealed that when the salinity was ≤6 g/L, the nitrate removal efficiency in SAD increased with the increasing salinity reaching 95.53% at 6 g/L salinity. Above this salt concentration, the performance of SAD gradually decreased, and the nitrate removal efficiency decreased to 33.63% at 25 g/L salinity. Approximately 5 mg/L of the hazardous nitrite was detectable at 15 g/L salinity, but decreased at 25 g/L salinity, accompanied by the generation of ammonium. When the salinity was ≥15 g/L, the abundance of the salt-tolerant microorganisms, Thiobacillus and Sulfurimonas, increased, while that of other microbial species decreased. This study provides support for the practical application of elemental sulfur-driven autotrophic denitrification in saline nitrate wastewater.
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This paper presents a detailed theoretical understanding of the noncovalent interactions between antibiotics tetracycline and conjugated microporous polymer (CMP), which is important to understand the recent experimental finding of efficient removal of antibiotics by CMP materials. We show that the co-work of π-π and H-π interactions determines the final equilibrium structures, when a tetracycline molecule spontaneously adsorbs to the surface or within the pores of the CMP network at physisorption distances. The binding energies for tetracycline/CMP systems are calculated to be -0.31 â¼ -1.15 eV, demonstrating the reliability of the adsorption. The electronic structures of CMP nanostructures remain basically undamaged upon the tetracycline adsorption. The replacement of benzothiadiazole unit with S and N heteroatoms to the phenyl moiety in the linker effectively enhanced the molecular polarity of CMP molecule and increases the interaction area between tetracycline and CMP network, consequently enhancing the average binding energies notably. Our calculations provide useful theoretical guidance for design of novel carbon-based porous adsorbents with good adsorption performance to remove residual tetracycline and other antibiotics in water.
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Antibacterianos , Tetraciclina , Adsorción , Reproducibilidad de los Resultados , Antibacterianos/química , Tetraciclina/química , Polímeros/químicaRESUMEN
Since COVID-19, people have suffered tremendous impacts in all aspects of their lives and work, with subtle changes in their environment preferences. The rural areas, with their natural green space, low density, and leisurely habitat, have played an important role after the pandemic and are widely favored by people. Research on rural environments after COVID-19 has received much attention. In the wake of the pandemic, people's needs for the environment have changed not only in terms of physical space, but also in terms of psychological needs. To address the issue of adaptability and resiliency of the future tourism development of the rural areas, this study takes the real subjective feelings of rural visitors as the evaluation standard, and takes the rural gastronomic tourism environment as the research object. We analyzed a sample of 14,373 images and 324,676 comments in Chinese posted by 3484 visitors on social media to explore whether and how people's preferences for rural environments have changed since the pandemic. Findings revealed significant differences in preference for the rural gastronomic tourism environment factors before and after the pandemic. There is variability in environment preferences depending on different gender, environment flexibility and the region. From the perspective of the rural gastronomic tourism environment, the research results provide suggestions for rural planning and rural tourism sustainability, and provide feasible paths for sustainable development and conservation of rural landscapes oriented to human needs, to enhance the resilience and sustainability of rural environments in the future.
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Aqueous Zn metal batteries are promising candidates for large-scale energy storage due to their intrinsic advantages. However, Zn tends to deposit irregularly and forms dendrites driven by the uneven space electric field distribution near the Zn-electrolyte interphase. Herein it is demonstrated that trace addition of Co single atom anchored carbon (denoted as CoSA/C) in the electrolyte regulates the microspace electric field at the Zn-electrolyte interphase and unifies Zn deposition. Through preferential adsorption of CoSA/C on the Zn surface, the atomically dispersed Co-N3 with strong charge polarization effect can redistribute the local space electric field and regulate ion flux. Moreover, the dynamic adsorption/desorption of CoSA/C upon plating/stripping offers sustainable long-term regulation. Therefore, Zn||Zn symmetric cells with CoSA/C electrolyte additive deliver stable cycling up to 1600 h (corresponding to a cumulative plated capacity of 8 Ah cm-2 ) at a high current density of 10 mA cm-2 , demonstrating the sustainable feature of microspace electric field regulation at high current density and capacity.
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Maxillary protrusion combined with mandibular retraction is a highly prevalent but extremely complex maxillofacial deformity that can have a serious negative impact on patients' facial aesthetics and mental health. The traditional orthodontic treatment strategy often involves extracting 4 first premolars and conventional fixed techniques, combined with mini-implant screws, to retract the anterior teeth and improve facial protrusion. In recent years, an invisible orthodontic technique, without brackets, has become increasingly popular. However, while an invisible aligner has been used in some cases with reasonable results, there remain significant challenges in achieving a perfect outcome. This case report presents an adolescent patient with bimaxillary protrusion and mandibular retrognathia. Based on the characteristics of the invisible aligners and the growth characteristics of the adolescent's teeth and jawbone, we designed precise three-dimensional tooth movement and corresponding resistance/over-correction for each tooth, while utilizing the patient's jawbone growth potential to promote rapid development of the mandible, accurately and efficiently correcting bimaxillary protrusion and skeletal mandibular retrognathia. The patient's facial aesthetics, especially the lateral morphology, have been greatly improved, and various aesthetic indicators have also shown significant changes, and to the patient's great benefit, invasive mini-implant screws were not used during the treatment. This case highlights the advantages of using invisible aligners in adolescent maxillary protrusion combined with mandibular retraction patients. Furthermore, comprehensive and accurate design combined with good application of growth potential can also enable invisible orthodontic technology to achieve perfect treatment effects in tooth extractions, providing clinical guidance for orthodontists.
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Mandíbula , Humanos , Adolescente , Mandíbula/cirugía , Femenino , Técnicas de Movimiento Dental/métodos , Retrognatismo/cirugía , Retrognatismo/terapia , Retrognatismo/diagnóstico por imagen , Maxilar/cirugía , MasculinoRESUMEN
Daptomycin, a lipopeptide comprising an N-decanoyl fatty acyl chain and a peptide core, is used clinically as an antimicrobial agent. The start condensation domain (dptC1) is an enzyme that catalyzes the lipoinitiation step of the daptomycin synthesis. In this study, we integrated enzymology, protein engineering, and computer simulation to study the substrate selectivity of the start condensation domain (dptC1) and to screen mutants with improved activity for decanoyl loading. Through molecular docking and computer simulation, the fatty acyl substrate channel and the protein-protein interaction interface of dptC1 are analyzed. Key residues at the protein-protein interface between dptC1 and the acyl carrier were mutated, and a single-point mutant showed more than three-folds improved catalytic efficiency of the target n-decanoyl substrate in comparing with the wild type. Moreover, molecular dynamics simulations suggested that mutants with increased catalytic activity may correlated with a more "open" and contracted substrate binding channel. Our work provides a new perspective for the elucidation of lipopeptide natural products biosynthesis, and also provides new resources to enrich its diversity and optimize the production of important components.