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In CRISPR/Cas9 genome editing, the tight and persistent target binding of Cas9 provides an opportunity for efficient genetic and epigenetic modification on genome. In particular, technologies based on catalytically dead Cas9 (dCas9) have been developed to enable genomic regulation and live imaging in a site-specific manner. While post-cleavage target residence of CRISPR/Cas9 could alter the pathway choice in repair of Cas9-induced DNA double strand breaks (DSBs), it is possible that dCas9 residing adjacent to a break may also determine the repair pathway for this DSB, providing an opportunity to control genome editing. Here, we found that loading dCas9 onto a DSB-adjacent site stimulated homology-directed repair (HDR) of this DSB by locally blocking recruitment of classical non-homologous end-joining (c-NHEJ) factors and suppressing c-NHEJ in mammalian cells. We further repurposed dCas9 proximal binding to increase HDR-mediated CRISPR genome editing by up to 4-fold while avoiding exacerbation of off-target effects. This dCas9-based local inhibitor provided a novel strategy of c-NHEJ inhibition in CRISPR genome editing in place of small molecule c-NHEJ inhibitors, which are often used to increase HDR-mediated genome editing but undesirably exacerbate off-target effects.
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Sistemas CRISPR-Cas , Roturas del ADN de Doble Cadena , Animales , Reparación del ADN por Unión de Extremidades , Reparación del ADN por Recombinación , Edición Génica/métodos , ADN/genética , Reparación del ADN , Mamíferos/genéticaRESUMEN
Potential health risks related to environmental endocrine disruptors (EEDs) have aroused research hotspots at the forefront of water treatment technologies. Herein, nitrogen-doped titanium dioxide/schwertmannite nanocomposites (N-TiO2/SCH) have been successfully developed as heterogeneous catalysts for the degradation of typical EEDs via photo-Fenton processes. Due to the sustainable Fe(III)/Fe(II) conversion induced by photoelectrons, as-prepared N-TiO2/SCH nanocomposites exhibit much enhanced efficiency for the degradation of bisphenol A (BPA; ca. 100% within 60 min under visible irradiation) in a wide pH range of 3.0-7.8, which is significantly higher than that of the pristine schwertmannite (ca. 74.5%) or N-TiO2 (ca. 10.8%). In this photo-Fenton system, the efficient degradation of BPA is mainly attributed to the oxidation by hydroxyl radical (â¢OH) and singlet oxygen (1O2). Moreover, the possible catalytic mechanisms and reaction pathway of BPA degradation are systematically investigated based on analytical and photoelectrochemical analyses. This work not only provides a feasible means for the development of novel heterogeneous photo-Fenton catalysts, but also lays a theoretical foundation for the potential application of mineral-based materials in wastewater treatment.
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Compuestos de Bencidrilo , Compuestos de Hierro , Nanocompuestos , Nitrógeno , Fenoles , Titanio , Contaminantes Químicos del Agua , Titanio/química , Compuestos de Bencidrilo/química , Fenoles/química , Nanocompuestos/química , Contaminantes Químicos del Agua/química , Nitrógeno/química , Catálisis , Hierro/química , Peróxido de Hidrógeno/química , Disruptores Endocrinos/química , Purificación del Agua/métodosRESUMEN
BACKGROUND: The impact of retirement on physical activity among older individuals remains ambiguous. This study aims to investigate the influence of retirement on physical activity and delineate the trajectories of physical activity changes during the retirement transition among elderly Chinese residents. Additionally, we endeavor to examine the factors that contribute to each trajectory. METHODS: This longitudinal cohort study used data from four surveys of the China Health and Retirement Longitudinal Study and included a sample of 428 individuals who underwent formal retirement and provided information on physical activity. We employed generalized estimating equation to explore the impact of the retirement transition on physical activity among Chinese older adults. Latent class growth analysis was used to identify distinct trajectories of physical activity, and binary logistic regression was performed to identify pre-retirement factors influencing changes in physical activity. RESULTS: Our findings indicate that retirement can lead to a decline in physical activity among older Chinese residents (OR = 0.85, 95%CI 0.75 ~ 0.97). We identified three distinct trajectories of physical activity during the retirement transition: Trajectory 1 - "sustained low level of physical activity" (7.94%); Trajectory 2 - "middle level of physical activity with gradual decline" (69.16%); Trajectory 3 - "sustained high level of physical activity with significant fluctuations" (22.90%). Furthermore, we discovered that individuals in the "middle level of physical activity and gradual decline" trajectory were more likely to have an annual income exceeding 40,000 yuan (OR = 9.69, 95%CI 1.12 ~ 83.63), reside in urban areas (OR = 2.27, 95%CI 1.14 ~ 4.52), and have a fondness for playing Mahjong (OR = 2.42, 95%CI 1.18 ~ 5.00) compared to those in the "sustained high level of physical activity with significant fluctuations" trajectory. Additionally, having an annual income exceeding 40,000 yuan (OR = 19.67, 95%CI 1.30 ~ 298.61) predicted membership in the "sustained low level of physical activity" trajectory when compared to the "sustained high level of physical activity with significant fluctuations" trajectory. CONCLUSION: Retirement represents a substantial milestone in the life course and is associated with notable alterations in physical activity patterns. Among older Chinese residents, the trajectories of physical activity during the retirement transition exhibit diverse paths and are influenced by pre-retirement factors, including annual income, residential location, and hobbies. The findings of this study have important implications for the formulation of policies aimed at promoting healthy aging among individuals approaching retirement age.
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Ejercicio Físico , Jubilación , Humanos , Anciano , Estudios Longitudinales , Estudios de Cohortes , Encuestas y Cuestionarios , ChinaRESUMEN
Chiral boron/nitrogen doped multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters are promising for highly efficient and color-pure circularly polarized organic light-emitting diodes (CP-OLEDs). Herein, we report two pairs of MR-TADF materials (Czp-tBuCzB, Czp-POAB) based on planar chiral paracyclophane with photoluminescence quantum yields of up to 98 %. The enantiomers showed symmetric circularly polarized photoluminescence spectra with dissymmetry factors |gPL | of up to 1.6×10-3 in doped films. Meanwhile, the sky-blue CP-OLEDs with (R/S)-Czp-tBuCzB showed an external quantum efficiency of 32.1 % with the narrowest full-width at half-maximum of 24â nm among the reported CP-OLEDs, while the devices with (R/S)-Czp-POAB displayed the first nearly pure green CP electroluminescence with |gEL | factors at the 10-3 level. These results demonstrate the incorporation of planar chirality into MR-TADF emitter is a reliable strategy for constructing of efficient CP-OLEDs.
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Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, and it is a typical disease which can develop chronic pain. Our previous study has proved that endocannabinoid (2-AG)-CB1R-GABA-5-HT pathway is involved in electroacupuncture (EA) mediated inhibition of chronic pain. However, it is still unclear which among the 5-HT receptor subtype is involved in EA evoked 5-HT mediated inhibition of chronic pain in the dorsal spinal cord. 5-HT2A is a G protein-coupled receptor and it is involved in 5-HT descending pain modulation system. We found that EA treatment at frequency of 2 Hz +1 mA significantly increased the expression of 5-HT2A receptor in the dorsal spinal cord and intrathecal injection of 5-HT2A receptor antagonist or agonist reversed or mimicked the analgesic effect of EA in each case respectively. Intrathecal injection of a selective GABAA receptor antagonist Bicuculline also reversed the EA effect on pain hypersensitivity. Additionally, EA treatment reversed the reduced expression of GABAA receptor and KCC2 in the dorsal spinal cord of KOA mice. Furthermore, we demonstrated that intrathecal 5-HT2A receptor antagonist/agonist reversed or mimicked the effect of EA up-regulate of KCC2 expression, respectively. Similarly, intrathecal injection of PLC and PKC inhibitors prevented both anti-allodynic effect and up-regulation of KCC2 expression by EA treatment. Our data suggest that EA treatment up-regulated KCC2 expression through activating 5-HT2A-Gq-PLC-PKC pathway and enhanced the inhibitory function of GABAA receptor, thereby inhibiting chronic pain in a mouse model of KOA.
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Dolor Crónico , Electroacupuntura , Osteoartritis de la Rodilla , Simportadores , Animales , Dolor Crónico/metabolismo , Dolor Crónico/terapia , Ratones , Osteoartritis de la Rodilla/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor de Serotonina 5-HT2A/metabolismo , Receptores de GABA-A/metabolismo , Serotonina/metabolismo , Médula Espinal/metabolismo , Simportadores/metabolismoRESUMEN
Herein, we report the structures of chiral-at-cage carborane derivatives bearing carbazole chromophores that emit circularly polarized luminescence (CPL) and aggregation-induced electrochemiluminescence (AIECL). By adjusting the substituent positions on the carborane derivatives, two chiral luminescent molecules, Cb1 and Cb2, with different properties were obtained. The photoluminescence dissymmetry factors |gPL | of both (R/S)-Cb1 and (R/S)-Cb2 enantiomers in neat films were as high as 6.24×10-3 and 7.38×10-3 , respectively. Cb1 showed a deep blue emission peak at 434â nm in n-pentane. Interestingly, distinct fluorescence and CPL spectra were observed in solvents of different polarities due to the twisted intramolecular charge transfer effect, suggesting its potential use in solvent recognition. Meanwhile, Cb2 exhibited good AIECL property, excellent ECL stability and could be used for determining dopamine concentrations, suggesting its potential applications in biology and diagnosis.
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Luminiscencia , Mediciones Luminiscentes , EstereoisomerismoRESUMEN
BACKGROUND: Infrahepatic inferior vena cava (IVC) clamping is considered to be an effective method to reduce central venous pressure (CVP) and intraoperative bleeding in liver resection. However, its efficacy and safety during laparoscopic hepatectomy (LH) remain unclear. We perform this retrospective study to evaluate its efficacy and safety during LH. METHODS: Consecutive patients scheduled for LH from September 2014 to August 2019 were retrospectively reviewed. The intraoperative parameters and postoperative outcomes were analyzed. RESULTS: All patients in the infrahepatic IVC clamping group were able to tolerate partial clamping of IVC. The CVP was significantly decreased after infrahepatic IVC clamping without hemodynamic instability (8.7 ± 1.4 cmH2O vs. 2.1 ± 1.3 cmH2O, P = 0.000). Infrahepatic IVC clamping did not significantly reduce total blood loss (287.3 ± 112.5 mL vs. 301.4 ± 127.6 mL, P = 0.133) and blood loss during parenchymal transection (273.2 ± 107.9 mL vs. 296.5 ± 118.1 mL, P = 0.618) compared with the non-clamping group. In subgroup analysis, total blood loss and blood loss during parenchymal transection were significantly reduced in patients with moderate to severe cirrhosis in the clamping group (363.6 ± 71.2 mL vs. 473.4 ± 95.6 mL, P = 0.021), (358.7 ± 70.9 mL vs. 466.9 ± 94.5 mL, P = 0.016), respectively. The complications and hospital stay were comparable. CONCLUSIONS: In conclusion, these data suggest that infrahepatic IVC clamping may be safe and effective.
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Pérdida de Sangre Quirúrgica , Hepatectomía , Laparoscopía , Pérdida de Sangre Quirúrgica/prevención & control , Presión Venosa Central , Constricción , Hepatectomía/efectos adversos , Humanos , Estudios Retrospectivos , Vena Cava Inferior/cirugíaRESUMEN
BACKGROUND: Preoperative diagnosis of peritoneal metastasis with gastric cancer remains challenging. This study explored the abnormal computed tomography (CT) signs of occult peritoneal metastasis (OPM) and evaluated it by region-to-region comparison using staging laparoscopy, from which a 4-point CT score system was developed. METHODS: Patients with advanced gastric cancer (stage cT ≥ 2M0) diagnosed by CT were enrolled in the study. Occult peritoneal metastasis detected during staging laparoscopy was compared with preoperative CT to investigate the presence of abnormal signs by a region-to-region comparison. A 4-point CT score system was developed to define the radiologic characteristics. Subsequently, the diagnostic efficacy of the CT score system was prospectively verified. RESULTS: In this study, 57 OPM regions were detected by staging laparoscopy in 33 of the 385 enrolled patients. The greater omentum was the most frequent site of OPM (38.60%, 22/57), which usually exhibited a smudge-like ground-glass opacity (S-GGO) (90.91%, 20/22) with a mean CT score of 2.14. The parietal and perihepatic peritoneum was the second most common site (22.81%, 13/57). A 4-point CT score system was developed based on the results. A cutoff CT score of 2 or higher was associated with a false-negative rate of 2% (2/99). This CT score system had a sensitivity of 87.5% and a specificity of 76.4% for an OPM-positive diagnosis (area under the curve, 0.848). The agreement between two radiologists on the assigned final score was 76.2% (kappa, 0.5). CONCLUSIONS: Patients with OPM mostly exhibited S-GGO on CT, which should be interpreted cautiously. The 4-point CT score system may improve the pretreatment evaluation of occult peritoneal metastasis, and staging laparoscopy might not be necessary for patients with a score lower than 2.
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Neoplasias Peritoneales/diagnóstico por imagen , Radiometría/métodos , Neoplasias Gástricas/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Humanos , Laparoscopía , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/secundario , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologíaRESUMEN
Click chemistry focuses on the development of highly selective reactions using simple precursors for the exquisite synthesis of molecules. Undisputedly, the CuI -catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most valuable examples of click chemistry, but it suffers from some limitations as it requires additional reducing agents and ligands as well as cytotoxic copper. Here, we demonstrate a novel strategy for the azide-alkyne cycloaddition reaction that involves a photoredox electron-transfer radical mechanism instead of the traditional metal-catalyzed coordination process. This newly developed photocatalyzed azide-alkyne cycloaddition reaction can be performed under mild conditions at room temperature in the presence of air and visible light and shows good functional group tolerance, excellent atom economy, high yields of up to 99 %, and absolute regioselectivity, affording a variety of 1,4-disubstituted 1,2,3-triazole derivatives, including bioactive molecules and pharmaceuticals. The use of a recyclable photocatalyst, solar energy, and water as solvent makes this photocatalytic system sustainable and environmentally friendly. Moreover, the azide-alkyne cycloaddition reaction could be photocatalyzed in the presence of a metal-free catalyst with excellent regioselectivity, which represents an important development for click chemistry and should find versatile applications in organic synthesis, chemical biology, and materials science.
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Monoclinic and hexagonal LaPO4 nanorods were prepared through hydrothermal method without the assistance of additives. The products were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED). Monoclinic and hexagonal LaPO4 nanorods can be achieved by adjusting the hydrothermal temperature and the pH value. The photocatalytic activity of monoclinic and hexagonal LaPO4 nanorods on rhodamine B (RB) and Congo red (CR) under UV irradiation was investigated, respectively. Interestingly, the monoclinic and hexagonal phase shows different photocatalytic performance for the photodegradation of the organic RB and CR dye.
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Phosphorylated histone H2AX, termed 'γH2AX', mediates the chromatin response to DNA double strand breaks (DSBs) in mammalian cells. H2AX deficiency increases the numbers of unrepaired DSBs and translocations, which are partly associated with defects in non-homologous end joining (NHEJ) and contributing to genomic instability in cancer. However, the role of γH2AX in NHEJ of general DSBs has yet to be clearly defined. Here, we showed that despite little effect on overall NHEJ efficiency, H2AX deficiency causes a surprising bias towards accurate NHEJ and shorter deletions in NHEJ products. By analyzing CRISPR/Cas9-induced NHEJ and by using a new reporter for mutagenic NHEJ, we found that γH2AX, along with its interacting protein MDC1, is required for efficient classical NHEJ (C-NHEJ) but with short deletions and insertions. Epistasis analysis revealed that ataxia telangiectasia mutated (ATM) and the chromatin remodeling complex Tip60/TRRAP/P400 are essential for this H2AX function. Taken together, these data suggest that a subset of DSBs may require γH2AX-mediated short-range nucleosome repositioning around the breaks to facilitate C-NHEJ with loss of a few extra nucleotides at NHEJ junctions. This may prevent outcomes such as non-repair and translocations, which are generally more destabilizing to genomes than short deletions and insertions from local NHEJ.
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Roturas del ADN de Doble Cadena , Reparación del ADN por Unión de Extremidades , Histonas/fisiología , Proteínas Adaptadoras Transductoras de Señales , Animales , Proteínas de la Ataxia Telangiectasia Mutada/fisiología , Secuencia de Bases , Sistemas CRISPR-Cas , Proteínas de Ciclo Celular , Línea Celular , Proteína Quinasa Activada por ADN/fisiología , Proteínas de Unión al ADN/fisiología , Histonas/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Nucleótidos/análisis , Eliminación de SecuenciaRESUMEN
BACKGROUND: Postoperative pancreatic fistula (POPF) is a severe complication of the pancreaticoduodenectomy (PD). Recently, we introduced a method of suspender pancreaticojejunostomy (PJ) to the PD. In this study, we retrospectively analyzed various risk factors for complications after PD. We also introduced and assessed the suspender PJ to demonstrate its advantages. METHODS: Data from 335 patients with various periampullary lesions, who underwent the Whipple procedure (classic Whipple procedure or pylorus-preserving) PD by either traditional end-to-side invagination PJ or suspender PJ, were analyzed. The correlation between either perioperative or postoperative complications and corresponding PD approaches was evaluated by univariate analysis. RESULTS: A total of 147 patients received the traditional end-to-side invagination PJ, and 188 patients were given the suspender PJ. Overall, 51.9% patients had various complications after PD. The mortality rate was 2.4%. The POPF incidence in patients who received the suspender PJ was 5.3%, which was significantly lower than those who received the traditional end-to-side invagination PJ (18.4%) (Pâ¯<â¯0.001). Univariate analysis showed that PJ approach and the pancreas texture were significantly associated with the POPF incidence rate (Pâ¯<â¯0.01). POPF was a risk factor for both postoperative abdominal cavity infection (ORâ¯=â¯8.34, 95% CI: 3.99-17.42, Pâ¯<â¯0.001) and abdominal cavity hemorrhage (ORâ¯=â¯4.86, 95% CI: 1.92-12.33, Pâ¯=â¯0.001). CONCLUSIONS: Our study showed that the impact of the pancreas texture was a major risk factor for pancreatic leakage after a PD. The suspender PJ can be easily accomplished and widely applied and can effectively decrease the impact of the pancreas texture on pancreatic fistula after a PD and leads to a lower POPF incidence rate.
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Neoplasias del Sistema Digestivo/cirugía , Fístula Pancreática/cirugía , Pancreaticoduodenectomía/efectos adversos , Pancreatoyeyunostomía/métodos , Anciano , Distribución de Chi-Cuadrado , China/epidemiología , Neoplasias del Sistema Digestivo/mortalidad , Neoplasias del Sistema Digestivo/patología , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Fístula Pancreática/diagnóstico por imagen , Fístula Pancreática/etiología , Fístula Pancreática/mortalidad , Pancreaticoduodenectomía/mortalidad , Pancreatoyeyunostomía/efectos adversos , Pancreatoyeyunostomía/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIM: Voltage-gated sodium channels composed of a pore-forming α subunit and auxiliary ß subunits are responsible for the upstroke of the action potential in cardiac myocytes. The pore-forming subunit of the cardiac sodium channel Nav1.5, which is encoded by SCN5A, is the main ion channel that conducts the voltage-gated cardiac sodium current (INa) in cardiac cells. The current study sought to investigate the inhibitory effects of hesperetin on human cardiac Nav1.5 channels stably expressed in human embryonic kidney 293 (HEK 293) cells and on the voltage-gated cardiac sodium current (INa) in human atrial myocytes. METHODS: The effects of hesperetin on human cardiac Nav1.5 channels expressed in HEK 293 cells and on cardiac Na+ currents in human atrial myocytes were examined through whole-cell patch-clamp techniques. RESULTS: Nav1.5 currents were potently and reversibly suppressed in a concentration- and voltage-dependent manner by hesperetin, which exhibited an IC50 of 62.99 µmol/L. Hesperetin significantly and negatively shifted the voltage-dependent activation and inactivation curves. Hesperetin also markedly decelerated Nav1.5 current inactivation and slowed the recovery from Nav1.5 channel inactivation. The hesperetin-dependent blockage of Nav1.5 currents was frequency-dependent. Hesperetin also potently and reversibly inhibited Na+ current (INa) in human atrial myocytes, consistently with its effects on Nav1.5 currents in HEK 293 cells. CONCLUSION: Hesperetin is a potent inhibitor of INa in human atrial myocytes and Nav1.5 channels expressed in human embryonic kidney 293 cells. Hesperetin probably functions by blocking the open state and the inactivated state of these channels.
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Hesperidina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Bloqueadores de los Canales de Sodio/farmacología , Anciano , Células HEK293 , Humanos , Persona de Mediana Edad , Miocitos Cardíacos/metabolismoRESUMEN
Cellular response to DNA double-strand breaks (DSBs), the most deleterious type of DNA damage, is highly influenced by higher-order chromatin structure in eukaryotic cells. Compared with euchromatin, the compacted structure of heterochromatin not only protects heterochromatic DNA from damage, but also adds an extra layer of control over the response to DSBs occurring in heterochromatin. One key step in this response is the decondensation of heterochromatin structure. This decondensation process facilitates the DNA damage signaling and promotes proper heterochromatic DSB repair, thus helping to prevent instability of heterochromatic regions of genomes. This review will focus on the functions of the ataxia telangiectasia mutated (ATM) signaling cascade involving ATM, heterochromatin protein 1 (HP1), Krüppel-associated box (KRAB)-associated protein-1 (KAP-1), tat-interacting protein 60 (Tip60), and many other protein factors in DSB-induced decondensation of heterochromatin and subsequent repair of heterochromatic DSBs. As some subsets of DSBs may be repaired in heterochromatin independently of the ATM signaling, a possible repair model is also proposed for ATM-independent repair of these heterochromatic DSBs.
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Daño del ADN , Heterocromatina/fisiología , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Reparación del ADN , Transducción de SeñalRESUMEN
AIM: Neferine is an isoquinoline alkaloid isolated from seed embryos of Nelumbo nucifera (Gaertn), which has a variety of biological activities. In this study we examined the effects of neferine on Kv4.3 channels, a major contributor to the transient outward current (I(to)) in rabbit heart, and on ex vivo electrophysiology of rabbit hearts. METHODS: Whole-cell Kv4.3 currents were recorded in HEK293 cells expressing human cardiac Kv4.3 channels using patch-clamp technique. Arterially perfused wedges of rabbit left ventricles (LV) were prepared, and transmembrane action potentials were simultaneously recorded from epicardial (Epi) and endocardial (Endo) sites with floating microelectrodes together with transmural electrocardiography (ECG). RESULTS: Neferine (0.1-100 µmol/L) dose-dependently and reversibly inhibited Kv4.3 currents (the IC50 value was 8.437 µmol/L, and the maximal inhibition at 100 µmol/L was 44.12%). Neferine (10 µmol/L) caused a positive shift of the steady-state activation curve of Kv4.3 currents, and a negative shift of the steady-state inactivation curve. Furthermore, neferine (10 µmol/L) accelerated the inactivation but not the activation of Kv4.3 currents, and markedly slowed the recovery of Kv4.3 currents from inactivation. Neferine-induced blocking of Kv4.3 currents was frequency-dependent. In arterially perfused wedges of rabbit LV, neferine (1, 3, and 10 µmol/L) dose-dependently prolonged the QT intervals and action potential durations (APD) at both Epi and Endo sites, and caused dramatic increase of APD10 at Epi sites. CONCLUSION: Neferine inhibits Kv4.3 channels likely by blocking the open state and inactivating state channels, which contributes to neferine-induced dramatic increase of APD10 at Epi sites of rabbit heart.
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Bencilisoquinolinas/farmacología , Medicamentos Herbarios Chinos/farmacología , Corazón/efectos de los fármacos , Canales de Potasio Shal/metabolismo , Potenciales de Acción/efectos de los fármacos , Animales , Células HEK293 , Corazón/fisiología , Humanos , Masculino , Técnicas de Placa-Clamp , ConejosRESUMEN
Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function.
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Diagnóstico por Imagen/métodos , Grafito , Nanopartículas , Neoplasias/diagnóstico , Neoplasias/terapia , Óxidos , Animales , Línea Celular , Supervivencia Celular , Terapia Combinada , Humanos , Luciferasas/metabolismo , Polietilenglicoles/síntesis química , Polietilenglicoles/química , Polietileneimina/análogos & derivados , Polietileneimina/síntesis química , Polietileneimina/química , Espectrometría de Fluorescencia , Espectroscopía Infrarroja por Transformada de Fourier , TermogravimetríaRESUMEN
A six-residue facial cyclopeptide was designed with the following sequence: c-[D-Leu-L-Lys-D-Ala-L-Lys-D-Leu-L-Gln] (CP). Extensive hydrogen bonding between the cyclopeptide backbones mainly regulated CP to self-assemble into single-walled nanotubes. Simultaneously, the hydrophobic interaction among facial hydrophobic side chains of CP was introduced to stabilize the hydrogen bonding, resulting in the formation of the thick-walled nanotubes with high lengthdiameter ratios.
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Nanotubos/química , Péptidos Cíclicos/química , Nanotubos/ultraestructura , Polimerizacion , Conformación ProteicaRESUMEN
OBJECTIVE: To compare the effect of patient-controlled intravenous analgesia(PCIA) and superior inguinal ligament iliac fascia block combined with PCIA after hip replacement in the elderly. METHODS: Total of 82 elderly patients were treated with hip arthroplasty from June 2019 to June 2021 and randomly divided into observation group and control group. There were 42 patients in control group, including 18 males and 24 females, aged from 60 to 78 years old with an average of (70.43±3.67) years old, 28 femoral neck fractures and 14 femoral head necrosis, who received PCIA. The study group consisted of 42 cases, including 20 males and 22 females, aged from 61 to 76 years old with an average of (69.68±3.74) years old, 25 femoral neck fractures and 17 femoral head necrosis, who received superior inguinal ligament iliac fascia block combined with PCIA. Pain visual analogue scale (VAS) and Ramesay sedation scores at 2 h, 6 h, 12 h, 24 h and 48 h after operation were evaluated. In addition, the follow-up results of the total consumption of sufentanil and the total number of PCIA compressions at 48 hours after operation, the first time of landing after surgery, the time of hospital stay, the incidence of adverse reactions, the satisfaction with analgesia of two groups were observed. RESULTS: All patients were followed up for 9 to 24 months with an average of(13.85±2.67) months. There was no significant difference in operation time and intraoperative bleeding between two groups (P>0.05). There was no difference in VAS between two groups at 2 hours after operation (P>0.05), and the VAS of the study group at 6 h, 12 h, 24 h and 48 h after operation were lower than those of the control group(P<0.05). The Ramesay sedation scores of the study group at 2 h, 6 h and 12 h after operation were higher than those of the control group(P<0.05), and there were no differences in Ramesay score between two groups at 24 h and 48 h after operation (P>0.05). The consumption of sufentanil in the study group within 48 hours after operation was lower than that in the control group (P<0.05), and PCIA compression times were lower than those in the control group(P<0.05), and the time of first landing was earlier than that in the control group(P<0.05). There was no significant difference in hospital stay, adverse reaction rate, complications between two groups (P>0.05). The satisfaction of analgesia in the study group was higher than that in the control group (P<0.05). CONCLUSION: Superior iliac fascia block of inguinal ligament combined with PCIA has significant analgesic and sedative effects after hip arthroplasty in the elderly. It can reduce the amount of sufentanil used and the total number of PCIA compressions, which is conducive to the early activity of patients out of bed, improve the satisfaction of analgesia.
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Analgesia Controlada por el Paciente , Artroplastia de Reemplazo de Cadera , Bloqueo Nervioso , Dolor Postoperatorio , Humanos , Masculino , Artroplastia de Reemplazo de Cadera/métodos , Femenino , Anciano , Analgesia Controlada por el Paciente/métodos , Bloqueo Nervioso/métodos , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Fascia , Ligamentos/cirugíaRESUMEN
A new species, Astragalusliuaiminii Z. Z. Yang & Q. R. Liu (Fabaceae), is described and illustrated from Xinjiang Province, China. The new species is close to A.wenquanensis S. B. Ho, but differs from the latter by leaves having a single leaflet (vs. 3-5 leaflets), and inflorescences with 1-2 flowers (vs. inflorescences with 5-7 flowers). It is also similar to A.monophyllus Maxim in leaf shape, but differs by its calyx expanding to become saccate and totally enveloping the pod (vs. calyx tubular, and ruptured by pod after flowering).
RESUMEN
The use of microbial inoculant is a promising strategy to improve plant health, but their efficiency often faces challenges due to difficulties in successful microbial colonization in soil environments. To this end, the application of biostimulation products derived from microbes is expected to resolve these barriers via direct interactions with plants or soil pathogens. However, their effectiveness and mechanisms for promoting plant growth and disease resistance remain elusive. In this study, we showed that root irrigation with the extracts of Streptomyces ahygroscopicus strain 769 (S769) solid fermentation products significantly reduced watermelon Fusarium wilt disease incidence by 30% and increased the plant biomass by 150% at a fruiting stage in a continuous cropping field. S769 treatment led to substantial changes in both bacterial and fungal community compositions, and induced a highly interconnected microbial association network in the rhizosphere. The root transcriptome analysis further suggested that S769 treatment significantly improved the expression of the MAPK signalling pathway, plant hormone signal transduction and plant-pathogen interactions, particular those genes related to PR-1 and ethylene, as well as genes associated with auxin production and reception. Together, our study provides mechanistic and empirical evidences for the biostimulation products benefiting plant health through coordinating plant and rhizosphere microbiome interaction.