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Endophytes, prevalent in plants, mediate plant-insect interactions. Nevertheless, our understanding of the key members of endophyte communities involved in inhibiting or assisting EAB infestation remains limited. Employing ITS and 16S rRNA high-throughput sequencing, along with network analysis techniques, we conducted a comprehensive investigation into the reaction of endophytic fungi and bacteria within F. bungeana phloem by comparing EAB-infested and uninfected samples. Our findings reveal that EAB infestation significantly impacts the endophytic communities, altering both their diversity and overall structure. Interestingly, both endophytic fungi and bacteria exhibited distinct patterns in response to the infestation. For instance, in the EAB-infested phloem, the fungi abundance remained unchanged, but diversity decreased significantly. Conversely, bacterial abundance increased, without significant diversity changes. The fungi community structure altered significantly, which was not observed in bacteria. The bacterial composition in the infested phloem underwent significant changes, characterized by a substantial decrease in beneficial species abundance, whereas the fungal composition remained largely unaffected. In network analysis, the endophytes in infested phloem exhibited a modular topology, demonstrating greater complexity due to an augmented number of network nodes, elevated negative correlations, and a core genera shift compared to those observed in healthy phloem. Our findings increase understanding of plant-insect-microorganism relationships, crucial for pest control, considering endophytic roles in plant defense.
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BACKGROUND: Temporary stoma formation is common in Crohn's disease (CD), while stoma reversal is associated with postoperative morbidity. This study aimed to evaluate the postoperative outcomes of split stoma reversal, SSR (i.e., exteriorization of proximal and distal ends of the stoma through a small common opening) and end stoma closure, ESC (i.e., the proximal stump externalized, and distal end localized abdominally. METHODS: Patients with CD who underwent stoma reversal surgeries between January 2017 and December 2021 were included. Demographic, clinical, and postoperative data were collected and analyzed to evaluate outcomes of reversal surgery. RESULTS: A total of 255 patients who underwent stoma reversal surgeries met the inclusion criteria. SSR was superior to ESC in terms of operative time (80.0 vs. 120.0, p = 0.0004), intraoperative blood loss volume (20.0 vs. 100.0, p = 0.0002), incision length (3.0 vs. 15.0, p < 0.0001), surgical wound classification (0 vs. 8.3%, p = 0.04), postoperative hospital stay (7.0 vs. 9.0, p = 0.0007), hospital expense (45.6 vs. 54.2, p = 0.0003), and postoperative complications (23.8% vs. 44.3%, p = 0.0040). Although patients in the ESC group experienced more surgical recurrence than those in the SSR group (8.3% vs. 3.2%) during the follow-up, the Kaplan-Meier curve analysis revealed no statistical difference (p = 0.29). CONCLUSIONS: The split stoma can be recommended when stoma construction is indicated in patients with Crohn's disease.
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Doença de Crohn , Complicações Pós-Operatórias , Reoperação , Estomas Cirúrgicos , Humanos , Doença de Crohn/cirurgia , Feminino , Masculino , Adulto , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Estomas Cirúrgicos/efeitos adversos , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem , Tempo de Internação/estatística & dados numéricos , Duração da Cirurgia , Ileostomia/efeitos adversos , Ileostomia/métodosRESUMO
Prussian blue analogue (PBA)/metal-organic frameworks (MOFs) are multifunctional precursors for the synthesis of metal/metal compounds, carbon, and their derived composites (P/MDCs) in chemical, medical, energy, and other applications. P/MDCs combine the advantages of both the high specific surface area of PBA/MOF and the electronic conductivity of metal compound/carbon. Although the calcination under different atmospheres has been extensively studied, the transformation mechanism of PBA/MOF under hydrothermal conditions remains unclear. The qualitative preparation of P/MDCs in hydrothermal conditions remains a challenge. Here, we select PBA to construct a machine-learning model and measure its hydrothermal phase diagram. The architecture-activity relationship of substances among nine parameters was analyzed for the hydrothermal phase transformation of PBA. Excitingly, we established a universal qualitative model to accurately fabricate 31 PBA derivates. Additionally, we performed three-dimensional reconstructed transmission electron microscopy, X-ray absorption fine structure spectroscopy, ultraviolet photoelectron spectroscopy, in situ X-ray powder diffraction, and theoretical calculation to analyze the advantages of hydrothermal derivatives in the oxygen evolution reaction and clarify their reaction mechanisms. We uncover the unified principles of the hydrothermal phase transformation of PBA, and we expect to guide the design for a wide range of composites.
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Microdroplets are a class of soft matter that has been extensively employed for chemical, biochemical, and industrial applications. However, fabricating microdroplets with largely controllable contact-area shape and apparent contact angle, a key prerequisite for their applications, is still a challenge. Here, by engineering a type of surface with homocentric closed-loop microwalls/microchannels, we can achieve facile size, shape, and contact-angle tunability of microdroplets on the textured surfaces by design. More importantly, this class of surface topologies (with universal genus value = 1) allows us to reveal that the conventional Gibbs equation (widely used for assessing the edge effect on the apparent contact angle of macrodroplets) seems no longer applicable for water microdroplets or nanodroplets (evidenced by independent molecular dynamics simulations). Notably, for the flat surface with the intrinsic contact angle ~0°, we find that the critical contact angle on the microtextured counterparts (at edge angle 90°) can be as large as >130°, rather than 90° according to the Gibbs equation. Experiments show that the breakdown of the Gibbs equation occurs for microdroplets of different types of liquids including alcohol and hydrocarbon oils. Overall, the microtextured surface design and topological wetting states not only offer opportunities for diverse applications of microdroplets such as controllable chemical reactions and low-cost circuit fabrications but also provide testbeds for advancing the fundamental surface science of wetting beyond the Gibbs equation.
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Lane detection plays a pivotal role in the successful implementation of Advanced Driver Assistance Systems (ADASs), which are essential for detecting the road's lane markings and determining the vehicle's position, thereby influencing subsequent decision making. However, current deep learning-based lane detection methods encounter challenges. Firstly, the on-board hardware limitations necessitate an exceptionally fast prediction speed for the lane detection method. Secondly, improvements are required for effective lane detection in complex scenarios. This paper addresses these issues by enhancing the row-anchor-based lane detection method. The Transformer encoder-decoder structure is leveraged as the row classification enhances the model's capability to extract global features and detect lane lines in intricate environments. The Feature-aligned Pyramid Network (FaPN) structure serves as an auxiliary branch, complemented by a novel structural loss with expectation loss, further refining the method's accuracy. The experimental results demonstrate our method's commendable accuracy and real-time performance, achieving a rapid prediction speed of 129 FPS (the single prediction time of the model on RTX3080 is 15.72 ms) and a 96.16% accuracy on the Tusimple dataset-a 3.32% improvement compared to the baseline method.
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Clathrate hydrates reserved in the seabed are often dispersed in the pores of coarse-grained sediments; hence, their formation typically occurs under nanoconfinement. Herein, we show the first molecular dynamics (MD) simulation evidence of the spontaneous formation of two-dimensional (2D) clathrate hydrates on crystal surfaces without conventional nanoconfinement. The kinetic process of 2D clathrate formation is illustrated via simulated single-molecule deposition. 2D amorphous patterns are observed on various superhydrophilic face-centered cubic surfaces. Notably, the formation of 2D amorphous clathrate can occur over a wide range of temperatures, even at room temperature. The strong water-surface interaction, the characteristic properties of guest-gas molecules, and the underlying surface structure dictate the formation of 2D amorphous clathrates. Semiquantitative phase diagrams of 2D clathrates are constructed where representative patterns of 2D clathrates for characteristic gas molecules on prototypical Pd(111) and Pt(111) surfaces are confirmed by independent MD simulations. A tunable pattern of 2D amorphous clathrates is demonstrated by changing the lattice strain of the underlying substrate. Moreover, ab initio MD simulations confirm the stability of 2D amorphous clathrate. The underlining physical mechanism for 2D clathrate formation on superhydrophilic surfaces is elucidated, which offers deeper insight into the crucial role of water-surface interaction.
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In non-Hermitian systems, enhancing sensitivity under exceptional point (EP) conditions offers an ideal solution for reconciling the trade-off between sensitivity and size constraints in sensing applications. However, practical application is limited by undesired sensitivity to external fluctuations, noise, and errors in signal amplification synchronization. This paper presents a precisely controlled EP tracking and detection system (EPTDS) that achieves long-term rapid tracking and locking near the EP by constructing a second-order non-Hermitian optical sensing unit, employing an optical power adaptive control method, and utilizing a combinatorial demodulation-based dual-loop cascaded control (CDCC) technique to selectively suppress traditional noise at different frequencies. The system locking time is 10 ms, and in room temperature conditions, the output frequency error over 1 hour is reduced by more than 30 times compared to before locking. To assess its sensing capabilities, the EPTDS undergoes testing in a rotational experiment based on the Sagnac effect, with the output bias instability based on Allan deviation measured at 0.036 °/h. This is the best result for EP-enhanced angular rate sensing that we are aware of that has been reported. The EPTDS method can be extended to various sensing fields, providing a new path for transitioning non-Hermitian sensing from the laboratory to practical applications.
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By denaturing proteins and promoting the formation of multiprotein complexes, protein phosphorylation has important effects on the activity of protein functional molecules and cell signaling. The regulation of protein phosphorylation allows microbes to respond rapidly and reversibly to specific environmental stimuli or niches, which is closely related to the molecular mechanisms of bacterial drug resistance. Accurate prediction of phosphorylation sites (p-site) of prokaryotes can contribute to addressing bacterial resistance and providing new perspectives for developing novel antibacterial drugs. Most existing studies focus on human phosphorylation sites, while tools targeting phosphorylation site identification of prokaryotic proteins are still relatively scarce. This study designs a capsule network-based prediction technique for p-site in prokaryotes. To address the poor scalability and unreliability of dynamic routing processes in the output space of capsule networks, a more reliable way is introduced to learn the consistency between capsules. We incorporate a self-attention mechanism into the routing algorithm to capture the global information of the capsule, reducing the computational effort while enriching the representation capability of the capsule. Aiming at the weak robustness of the model, EcapsP improves the prediction accuracy and stability by introducing shortcuts and unconditional reconfiguration. In addition, the study compares and analyzes the prediction performance based on word vectors, physicochemical properties, and mixing characteristics in predicting serine (Ser/S), threonine (Thr/T), and tyrosine (Tyr/Y) p-site. The comprehensive experimental results show that the accuracy of the developed technique is close to 70% for the identification of the three phosphorylation sites in prokaryotes. Importantly, in side-by-side comparisons with other state-of-the-art predictors, our method improves the Matthews correlation coefficient (MCC) by approximately 7%. The results demonstrate the superiority of EcapsP in terms of high performance and reliability.
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Células Procarióticas , Proteínas , Humanos , Fosforilação , Reprodutibilidade dos Testes , Proteínas/metabolismo , Tirosina/metabolismoRESUMO
Objectives: To investigate the effect of combined balance and plyometric training on knee function and proprioception of elite badminton athletes. Methods: Sixteen elite male badminton players (age: 20.5 ± 1.1 years, height: 177.8 ± 5.1 cm, weight: 68.1 ± 7.2 kg, and training experience: 11.4 ± 1.4 years) volunteered to participate and were randomly assigned to a combined balance and plyometric training (CT) (n = 8) and plyometric (PT) group (n = 8). The CT group performed balance combined with plyometric training three times a week over 6 weeks (40 min of plyometrics and 20 min of balance training); while the PT group undertook only plyometric training for the same period (3-4 sets × 8-12 reps for each exercise). Both groups had the same technical training of badminton. Results: The knee function and proprioception were assessed at baseline and after the intervention by measuring the performance of single-legged hop tests (LSIO, LSIT, LSIC, LSIS), standing postural sway (COPAP, COPML), and LSI of dominant leg and non-dominant leg. The results showed that as compared to PT, CT induced significantly greater improvements in LSIT and LSIS (p < 0.001) and significant greater percent increase in NAP (p = 0.011). The changes in LSIO, LSIC, DAP, NAP, LSIAP, DML, NML, and LSIML induced by CT did not differ from that induced by PT (p > 0.213). Conclusion: In elite badminton players, intervention using CT holds great promise to augment the benefits for knee function compared to the intervention using PT only, and at the same time, with at least comparable benefits for proprioception. Future studies are needed to examine and confirm the results of this study.
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Objective: The aim of this study is to explore and analyze the high risk factors and preventive measures of percutaneous nephrolithotomy under the guidance of B-ultrasound in the treatment of postoperative renal calculi. Methods: The clinical data of 220 patients with renal calculi admitted to our hospital from 2018 to October 2021 were retrospectively analyzed. All patients were treated with percutaneous nephrolithotomy n = 36) and nonbleeding group (n = 184), comparing the personal data, disease-related data, surgical operation related data of the two groups of patients, single factor and logistic multifactor regression analysis to explore the influence of B-guided percutaneous. Nephrolithotomy is a high-risk factor for postoperative bleeding in patients with kidney stones, and preventive measures are based on high-risk factors. Results: There was no significant difference in the proportion of patients with different genders, whether they had renal surgery, whether they had hypertension, and those with postoperative hepatic insufficiency in the hemorrhagic group and the nonbleeding group (p > 0.05). There was no significant difference in age and body mass index between the bleeding group and the nonbleeding group (p > 0.05). The proportion of patients with diabetes in the bleeding group was higher than that in the nonbleeding group, and the difference between the groups was statistically significant (p < 0.05). Compared with the nonbleeding group, the bleeding group had a higher proportion of patients with calculus diameter ≥2 cm. The proportion of patients with staghorn calculi in the bleeding group was higher than that in the nonbleeding group. The difference between the groups was statistically significant (p < 0.05). There was no significant difference in the proportion of patients with hemorrhage, single or multiple renal stones, and ureteral stones in the hemorrhage group compared with the nonbleeding group (p > 0.05). Compared with the nonbleeding group, the proportion of patients with bleeding in the first stage was higher, and the proportion of patients with operation time >90 min was higher. The difference between the groups was statistically significant (p < 0.05). There was no significant difference in the proportion of patients in the bleeding group compared with the nonbleeding group (p > 0.05). Using Logic multifactorial regression analysis, independent risk factors for bleeding after percutaneous nephrolithotomy under ultrasound-guided bovery include diabetes mellitus, stone diameter, staghorn kidney stones, surgical timing, and staging surgery (p < 0.05). Conclusion: The independent high-risk factors affecting bleeding after percutaneous nephrolithotomy guided by B-ultrasound include diabetes, stone diameter, staghorn type kidney stones, operation time, and staged surgery. According to this, effective preventive measures can effectively reduce the operation and the occurrence of postbleeding.
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The study aimed to investigate the effect of combined balance and plyometric training on dynamic balance and quickness performance of elite badminton athletes. Sixteen elite male badminton players volunteered to participate and were randomly assigned to a balance-plyometric group (PB: n = 8) and plyometric group (PT: n = 8). The PB group performed balance combined with plyometric training three times a week over 6 weeks (40 min of plyometrics and 20 min of balance training); while the PT group undertook only plyometric training for the same period (3-4 sets × 8-12 reps for each exercise). Both groups were given the same technical training (badminton techniques for 6 days a week). The dynamic stability and quick movement ability were assessed at baseline and after the intervention by measuring the performance of dynamic posture stability test (DPSI and COP), T-running test and hexagon jump test. The results showed that compared to PT, PB induced significantly greater improvements in F-DPSI, L-DPSI (p = 0.003, 0.025, respectively), F-COPAP, F-COPML, F-COPPL, L-COPPL (p = 0.024, 0.002, 0.029, 0.043, respectively), T-running test and hexagon jump test (p < 0.001). The change in L-DPSI, L-COPAP, L-COPML did not differ between PB and PT (p > 0.907). The findings suggest that combined training holds great promise of improving the dynamic balance and quickness performance in elite badminton athletes.
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Desempenho Atlético , Exercício Pliométrico , Esportes com Raquete , Futebol , Teste de Esforço , Humanos , Masculino , Força Muscular , Exercício Pliométrico/métodosRESUMO
Trans/cis stereoisomers with multiple functionalities play an important role in chemistry and materials science. In this work, two pure stereoisomers (trans- and cis-TPE-2GA) of the tetraphenylethene (TPE) derivatives bi-substituted by a bio-resourced rigid triterpenoid and glycyrrhetinic acid (GA) were synthesized and characterized by 1D and 2D NMR, single crystal analysis, and HR-MS. Both trans- and cis-TPE-2GA are thermally stable even on heating at 160 °C for 30 min, whereas they can undergo trans-to-cis and cis-to-trans photoisomerization under similar UV illumination. The introduction of triterpenoid units endowed isomers with different aggregation-induced emission (AIE) and self-assembly properties and distinct crystallinity. Trans- and cis-TPE-2GA exhibit different evolution of the fluorescent intensity in water/acetone mixture with the increase in the water fraction, which are closely related to the different evolution of the aggregate morphology, from nanorods to nanospheres for trans-TPE-2GA, while from twisted ribbons, to nanotubes and nanospheres for cis-TPE-2GA. In the solid state, the mechano-chromic properties are shown by cis-TPE-2GA, while no mechano-chromic effect is observed for trans-TPE-2GA under the same grinding conditions because of their distinct crystallinity. Finally, theoretical calculation and photophysical study demonstrate that despite both isomers being assigned to the charge transfer state emission, cis-TPE-2GA has a slightly lower energy gap, a higher quantum yield, and a longer lifetime in comparison with trans-TPE-2GA, which explained their difference in the fluorescence and mechano-chromic properties. This work may improve the understanding of the TPE-based trans and cis stereoisomers, which will be beneficial in the design of novel TPE-based functional materials.
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Organic nitrogen (ON) compounds are key contents of particulate matter in the megacities of Asia. As a series of important ON, nitrated phenolic compounds (NPs) are of high concentration in the atmosphere, although their formation mechanism and role in particulate nucleation and growth are not fully understood. Herein, using a high level of quantum mechanical calculations, we explore the formation paths of NPs initiated by NO3· radicals, where some common atmospheric species, such as H2O, (H2O)2, NH3, and dimethylamine (DMA), can act as molecular catalysts. The kinetic study predicts that the formation rate of methyl nitrophenols with the assistance of DMA and (H2O)2 can reach â¼103 molecules·cm-3·s-1 in a polluted and humid atmosphere. The volatilities obtained from the empirical model show the formed NPs mainly belong to the intermediate and semivolatile organic compounds, which can participate in the growth process of aerosols rather than the early stage of cluster nucleation. Moreover, some NPs can be salified with atmospheric bases to further increase their contributions to the particulate formation.
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Atmosfera , Nitrocompostos , Aerossóis/análise , Ásia , Material ParticuladoRESUMO
Numerous field and laboratory studies have shown that amines, especially dimethylamine (DMA), are crucial to atmospheric particulate nucleation. However, the molecular mechanism by which amines lead to atmospheric particulate formation is still not fully understood. Herein, we show that DMA molecules can also promote the conversion of atmospheric SO2 to sulfate. Based on ab initio simulations, we find that in the presence of DMA, the originally endothermic and kinetically unfavourable hydrolysis reaction between gaseous SO2 and water vapour can become both exothermic and kinetically favourable. The resulting product, bisulfite NH2(CH3)2 +·HSO3 -, can be readily oxidized by ozone under ambient conditions. Kinetic analysis suggests that the hydrolysis rate of SO2 and DMA with water vapour becomes highly competitive with and comparable to the rate of the reaction between SO2 and OH·, especially under the conditions of heavily polluted air and high humidity. We also find that the oxidants NO2 and N2O5 (whose role in sulfate formation is still under debate) appear to play a much less significant role than ozone in the aqueous oxidation reaction of SO2. The newly identified oxidation mechanism of SO2 promoted by both DMA and O3 provides another important new source of sulfate formation in the atmosphere.
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A source of missing sulfate production associated with high-level fine-particle pollution in the megacities of China is believed to stem from the oxidation of a notable fraction of sulfur dioxide (SO2) by nitrogen dioxide (NO2) in aqueous aerosol environments, suggesting that an unknown reaction pathway exists for aqueous sulfur oxidation. At weakly acidic aerosols, the dissolved SO2 mainly exists in the form of HSO3-, whereas at neutral aerosols, SO32- becomes the main form. Herein, by using both ab initio molecular metadynamics simulations and high-level quantum mechanical calculations, we show a hitherto unreported chemical mechanism for the formation of sulfate through the reaction between HSO3-/SO32- anions at the surface/in the interior of a water nanodroplet and gas-phase NO2 molecules. For weakly acidic aerosols, contrary to the conventional high-barrier electron-transfer pathway in the gas phase, HSO3- at the water nanodroplet surface can transfer an electron to NO2 with a low free-energy barrier of 4.7 kcal/mol through a water bridge. For neutral aerosols, the electron-transfer pathway between SO32- in the interior of the water nanodroplet and NO2 needs to overcome a lower free-energy barrier of 3.6 kcal/mol to form SO3-, with the assistance of the hydrogen-bonding network of water molecules. This new reaction pathway for the sulfate formation from HSO3-/SO32- via water nanodroplets and gaseous NO2 provides a new perspective on the growth of haze particles from pre-existing aqueous aerosols and suggests that new control strategies are needed to address haze pollution.
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We present a combined molecular dynamics (MD) and classical nucleation theory (CNT) approach to address many issues regarding the nucleation of inorganic aerosols. By taking parameters from MD simulations, we find the CNT predicts fairly reasonable free-energy profiles for the hygroscopic nucleation of aerosols. Moreover, we find that the ionization of sulfates can play a key role in stabilizing aqueous clusters and that both the size of the critical nucleus and the nucleation barrier can be significantly lowered by the H2SO4 and NH4HSO4, whereas the effect of NH3 on nucleation is negligible. NH4HSO4 provides stronger enhancement effect to aerosol formation than H2SO4. In view of the consistency between the theoretical prediction and experimental observation, the combination of MD simulation and CNT appears to be a valuable approach to gain deeper understanding of how aerosol nucleation is affected by different chemical species.
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BACKGROUND: Cordyceps cicadae, an entomogenous fungus has been used as a dietary therapeutic in traditional Chinese medicine for several millennia, in the form of powders and decoction. However, wild C. cicadae is notably scarce. To date, there is still a lack of comprehensive and deep studies on the biological characteristics, chemical profiles and antineoplastic mechanisms of C. cicadae, especially its spores. AIM OF THE STUDY: This study aimed to identify wild C. cicadae using rDNA-ITS sequences. Active constituents and volatile ingredients of C. cicadae sporoderm-broken spore powders (CCBSP) were elucidated using UPLC-ESI-Q-TOF-MS and GC-MS, respectively. The underlying anti-neoplastic mechanisms of CCBSP were further investigated in A549 lung carcinoma cells. RESULTS: Molecular phylogenetic analysis of nuclear rDNA sequences indicated that wild C. cicadae belonged to Paecilomyces cicadae. Eight primary compounds from CCBSP were identified by MS fragmentation ions including nucleosides, cordycepic acid, cordycepin, beauvericin and myriocin. In total, forty-nine volatile components representing 99.56% of CCBSP were clearly identified. CCBSP exhibited antiproliferative effects on A549 cells with IC50 value of 125.54 ± 2.71⯵g/ml, blocking the cell cycle in the G2/M phase. The nuclear morphology exhibited typical characteristics of apoptosis by Hoechst fluorescent stain. AnnexinV-FITC/PI staining revealed that the number of apoptotic cells increased after CCBSP treatment. Furthermore, immunofluorescence experiments indicated that CCBSP lowered the expressions of ß-catenin and N-cadherin, which was accompanied by repressed Wnt/ß-catenin signalling and activation of caspase-mediated apoptosis pathways. CONCLUSIONS: rDNA-ITS sequencing enabled molecular identification of wild C. cicadae. Importantly, these findings provide the first evidence regarding the full-scale bioactive components and antineoplastic properties of CCBSP. These data highlight the significance of C. cicadae as a potential antineoplastic agent.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Cordyceps/química , Filogenia , Esporos Fúngicos/química , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Caderinas/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , China , Cordyceps/genética , Cordyceps/fisiologia , Depsipeptídeos/análise , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Concentração Inibidora 50 , Medicina Tradicional Chinesa , Nucleosídeos/análise , beta Catenina/metabolismoRESUMO
Polypoidal choroidal vasculopathy (PCV) is a common subtype of wet age-related macular degeneration in Asian populations, whereas choroidal neovascularization is the typical subtype in Western populations. The cause of PCV is unknown. By comparing the phenotype of a PCV mouse model expressing protease high temperature requirement factor A1 (HTRA1) in retinal pigment epithelium with transgenic mice expressing the inactive HTRA1S328A, we showed that HTRA1-mediated degradation of elastin in choroidal vessels is critical for the development of PCV, which exhibited destructive extracellular matrix remodeling and vascular smooth muscle cell loss. Compared with weak PCV, severe PCV exhibited prominent immune complex deposition, complement activation, and infiltration of inflammatory cells, suggesting inflammation plays a key role in PCV progression. More important, we validated these findings in human PCV specimens. Intravitreal delivery of an HTRA1 inhibitor (DPMFKLboroV) was effective (36% lesion reduction; P = 0.009) in preventing PCV initiation but ineffective in treating existing lesions. Anti-inflammatory glucocorticoid was effective in preventing PCV progression but ineffective in preventing PCV initiation. These results suggest that PCV pathogenesis occurs through two stages. The initiation stage is mediated by proteolytic degradation of extracellular matrix proteins attributable to increased HTRA1 activity, whereas the progression stage is driven by inflammatory cascades. This study provides a basis for understanding the differences between PCV and choroidal neovascularization, and helps guide the design of effective therapies for PCV.
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Serina Peptidase 1 de Requerimento de Alta Temperatura A/metabolismo , Degeneração Macular/patologia , Degeneração Macular Exsudativa/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Feminino , Humanos , Inflamação/patologia , Degeneração Macular/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteólise , Degeneração Macular Exsudativa/metabolismoRESUMO
Isaria cicadae is an entomogenous fungus that has been used as a traditional Chinese medicinal materials to treat different diseases, including cancer. However, Isaria cicadae conidia for inhibitory activity against breast cancer cells growth are still not systematically studied. The present aim was to elucidate the phytochemical composition of Isaria cicadae conidia and to explore relevant anti-cancer potential in gynaecological carcinoma MCF-7 and Hela cells. Isaria cicadae conidia were identified by UPLC-ESI-Q-TOF-MS: high performance liquid chromatography-electrospray/quadrupole time of flight tandem mass spectrometry technology. Eight main compounds were identified which are nucleosides, cordycepic acid, cordycepin, beauvericin and myriocin by MS fragmentation ions. The nuclear morphology indicated the typical characteristics of apoptosis by Hoechst staining. Annexin V/PI staining revealed that the number of apoptotic cells was increased by Isaria cicadae conidia treatment. Furthermore, Isaria cicadae conidia also induced the caspase-mediated mitochondrial apoptosis pathway. The findings suggest that the full-scale active ingredients highlight the significance of Isaria cicadae conidia as potential anti-cancer agent in China.
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It is a deeply engrained notion that the visual pigment rhodopsin signals light as a monomer, even though many G protein-coupled receptors are now known to exist and function as dimers. Nonetheless, recent studies (albeit all in vitro) have suggested that rhodopsin and its chromophore-free apoprotein, R-opsin, may indeed exist as a homodimer in rod disk membranes. Given the overwhelmingly strong historical context, the crucial remaining question, therefore, is whether pigment dimerization truly exists naturally and what function this dimerization may serve. We addressed this question in vivo with a unique mouse line (S-opsin(+)Lrat(-/-)) expressing, transgenically, short-wavelength-sensitive cone opsin (S-opsin) in rods and also lacking chromophore to exploit the fact that cone opsins, but not R-opsin, require chromophore for proper folding and trafficking to the photoreceptor's outer segment. In R-opsin's absence, S-opsin in these transgenic rods without chromophore was mislocalized; in R-opsin's presence, however, S-opsin trafficked normally to the rod outer segment and produced functional S-pigment upon subsequent chromophore restoration. Introducing a competing R-opsin transmembrane helix H1 or helix H8 peptide, but not helix H4 or helix H5 peptide, into these transgenic rods caused mislocalization of R-opsin and S-opsin to the perinuclear endoplasmic reticulum. Importantly, a similar peptide-competition effect was observed even in WT rods. Our work provides convincing evidence for visual pigment dimerization in vivo under physiological conditions and for its role in pigment maturation and targeting. Our work raises new questions regarding a potential mechanistic role of dimerization in rhodopsin signaling.