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The vast majority of tumor cells maintain the length of the telomeres through a telomerase-dependent maintenance mechanism, allowing for unlimited proliferation. TCAB1 is indispensable for the correct assembly of telomerase complexes and the delivery of telomerase to the telomere. Therefore, this study aimed to explore small molecules capable of interfering with the assembly of TCAB1 and the telomerase complex as novel efficient telomerase inhibitors. Through virtual screening, biological evaluation, and the confirmation of target engagement, the potential ligands of TCAB1 effectively inhibiting telomerase activity were discovered. Among them, compound 9 exhibited telomerase inhibitory activity at a two-digit nanomolar level (IC50 = 0.03 µM), which was dramatically enhanced in comparison with the previously reported telomerase inhibitors. This research, based on the blockage of telomerase assembly through disturbing TCAB1, provides a novel strategy and a potential target for telomerase inhibitor discovery.
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Purpose: To investigate the effect of intravenous infusion of lidocaine compared with ultrasound-guided transverse abdominal plane (TAP) block on the quality of postoperative recovery and analgesic effect in patients undergoing bariatric surgery. Patients and Methods: Ninety-nine ASA II-III patients scheduled for elective laparoscopic bariatric surgery were randomized into the lidocaine group (group L), transverse abdominal plane block group (group T), and control group (group C). Group L: a loading dose of 1.5 mg/kg lidocaine was given at induction, followed by 2 mg·kg-1·h-1 maintenance until the end of surgery. Group T: ultrasound-guided bilateral administration of 0.25% ropivacaine in the transverse abdominal plane was given after induction of general anesthesia. Group C: no additional treatment was performed. Quality of recovery-40 (QoR-40) was assessed at 24 h after surgery. Consumption of propofol and remifentanil, visual analog scale (VAS) pain scores at rest at 0, 6, 12, and 24 h postoperatively, time to return of intestinal function, use of remedial analgesics within 24 h after surgery, adverse reactions were recorded. Results: Compared with Group C, Group L and Group T had higher QoR-40 scores at 24 h postoperatively, and the difference was statistically significant (P=0.002 and P=0.003, respectively). However, there was no difference between Group L and Group T (P=0.128). In addition, compared with those of Group T and Group C, VAS scores at 12 h and 24 h postoperatively were lower in Group L (P <0.0166). Conclusion: Both intravenous infusion of lidocaine and ultrasound-guided TAP block provided good postoperative recovery and postoperative analgesia for patients with bariatric surgery, and intravenous infusion of lidocaine provided better analgesia at 12 h and 24 h postoperatively compared with TAP block.
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Cirugía Bariátrica , Laparoscopía , Bloqueo Nervioso , Músculos Abdominales/diagnóstico por imagen , Humanos , Infusiones Intravenosas , Lidocaína/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Ultrasonografía IntervencionalAsunto(s)
Cesárea/métodos , Hipotensión/prevención & control , Metaraminol/administración & dosificación , Adulto , Anestesia Epidural/métodos , Anestesia Obstétrica/métodos , Anestesia Raquidea/métodos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Hipotensión/etiología , Embarazo , Posición Supina , Vasoconstrictores/administración & dosificación , Adulto JovenRESUMEN
Tensile strength, warping degree, and surface roughness are important indicators to evaluate the quality of fused deposition modeling (FDM) parts, and their accurate and stable prediction is helpful to the development of FDM technology. Thus, a quality prediction method of FDM parts based on an optimized deep belief network was proposed. To determine the combination of process parameters that have the greatest influence on the quality of FDM parts, the correlation analysis method was used to screen the key quality factors that affect the quality of FDM parts. Then, we use 10-fold cross-validation and grid search (GS) to determine the optimal hyperparameter combination of the sparse constrained deep belief network (SDBN), propose an adaptive cuckoo search (ACS) algorithm to optimize the weights and biases of the SDBN, and complete the construction of prediction model based on the above work. The results show that compared with DBN, LSTM, RBFNN, and BPNN, the ACS-SDBN model designed in this article can map the complex nonlinear relationship between FDM part quality characteristics and process parameters more effectively, and the CV verification accuracy of the model can reach more than 95.92%. The prediction accuracy can reach more than 96.67%, and the model has higher accuracy and stability.
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Proyectos de InvestigaciónRESUMEN
BACKGROUND: Recently, human infertility incidence is increasing in obese women causing it to become an emerging global health challenge requiring improved treatment. There is extensive evidence that obesity caused female reproductive dysfunction is accompanied by an endocrinological influence. Besides, systemic and tissue-specific chronic inflammatory status are common characteristics of obesity. However, the underlying molecular mechanism is unclear linking obesity to infertility or subfertility. METHODS: To deal with this question, we created an obese mouse model through providing a high fat diet (HFD) and determined the fertility of the obese mice. The morphological alterations were evaluated in both the reproductive glands and tracts, such as uterus, ovary and oviduct. Furthermore, to explore the underlying mechanism of these functional changes, the expressions of pro-inflammatory cytokines as well as the activations of MAPK signaling and NF-κB signaling were detected in these reproductive tissues. RESULTS: The obese females were successful construction and displayed subfertility. They accumulated lipid droplets and developed morphological alterations in each of their reproductive organs including uterus, ovary and oviduct. These pathological changes accompanied increases in pro-inflammatory cytokine expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in all of these sites. Such effects also accompanied increases in nuclear factor kappa B (NF-kB) expression and mitogen-activated protein kinase (MAPK) signaling pathway stimulation based on uniform time dependent increases in the NF-κB (p-NF-κB), JNK (p-JNK), ERK1/2 (p-ERK) and p38 (p-p38) phosphorylation status. CONCLUSIONS: These HFD-induced increases in pro-inflammatory cytokine expression levels and NF-κB and MAPKs signaling pathway activation in reproductive organs support the notion that increases of adipocytes resident and inflammatory status are symptomatic of female fertility impairment in obese mice.
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Genitales Femeninos/patología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Obesidad/patología , Animales , Dieta Alta en Grasa , Femenino , Fertilidad/fisiología , Genitales Femeninos/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/metabolismo , Transducción de Señal/fisiologíaRESUMEN
STUDY OBJECTIVE: To investigate the effect of propofol-based total intravenous anesthesia (TIVA) or sevoflurane-based inhalation anesthesia on postoperative quality of recovery in patients undergoing total laparoscopic hysterectomy. DESIGN: A prospective randomized controlled trial. SETTING: An operating room, a postoperative recovery area, and a hospital ward. PATIENTS: A total of 102 female patients scheduled for elective total laparoscopic hysterectomy were randomly divided into two groups: the propofol group (group P) or sevoflurane group (group S). INTERVENTIONS: Anesthesia in group P was induced by propofol, fentanyl and rocuronium, and maintained by intravenous infusion of propofol and remifentanil. Anesthesia in group S was induced by a tidal volume inhalation technique with sevoflurane and rocuronium and maintained with sevoflurane and remifentanil. Patients in group P did not receive any volatile drugs. MEASUREMENTS: Quality of Recovery-40 (QoR-40), Pittsburgh Sleep Quality Index (PSQI) and Numerical Rating Scale (NRS) scores were assessed at 8, 24, 48, 72 h, 7 days and 30 days after surgery. Intraoperative hemodynamics, postoperative inflammatory indicators and adverse reactions were also recorded. MAIN RESULTS: The QoR-40 score and its 5 dimensions were similar in the two groups at each point in time (P > 0.05). Group S had less consumption of remifentanil (P < 0.001) but increased use of phenylephrine (P = 0.001) intraoperatively. PSQI scores were also comparable between groups at each point in time (P > 0.05). NRS scores at 72 h (P = 0.023) and 7 days (P = 0.017) after surgery, postoperative NLR (P = 0.024) and hs-CRP (P = 0.042), and the incidence of abdominal distension (P = 0.017) were significantly lower in group P than in group S. Multiple linear regression analyses demonstrated that duration of pneumoperitoneum and sleep quality were associated with postoperative recovery. CONCLUSIONS: The choice of intravenous or inhalation maintenance anesthesia did not affect overall postoperative recovery as measured by the QoR-40 in patients undergoing total laparoscopic hysterectomy. Reducing the duration of pneumoperitoneum and improving sleep quality were conducive to postoperative recovery.
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Anestésicos por Inhalación , Laparoscopía , Éteres Metílicos , Propofol , Anestesia por Inhalación/efectos adversos , Anestesia Intravenosa/efectos adversos , Anestésicos por Inhalación/efectos adversos , Anestésicos Intravenosos/efectos adversos , Femenino , Humanos , Histerectomía/efectos adversos , Éteres Metílicos/efectos adversos , Propofol/efectos adversos , Estudios ProspectivosRESUMEN
BACKGROUND: The intraoperative 15° left-tilt position during cesarean delivery has more recently been questioned regarding its effect on fetal acid-base balance and is a frequent source of complaints by surgeons. We hypothesized that a 30° left-tilt position during surgical preparation could improve the acid-base balance of the fetus compared with the 15° left-tilt or supine position during surgical preparation. METHODS: Women undergoing elective cesarean delivery under combined spinal epidural anesthesia were randomized to a supine position, 15° left-lateral tilt position or 30° left-lateral tilt position; the position was changed to supine before the incision. Anesthetic management was standardized and included fluid loading with 10 mL/kg of normal saline followed by colloid loading. Hypotension (systolic blood pressure [SBP] reduction >20% baseline value or SBP <90 mm Hg) was treated with boluses of phenylephrine or ephedrine according to maternal heart rate. The primary outcome was umbilical arterial blood pH and the secondary outcomes included maternal SBP within 15 minutes after induction of anesthesia, the amount of vasoactive drug administered before end of the surgery, and the incidence of hypotension during cesarean delivery. RESULTS: Seventy-five patients were included. After testing by analysis of variance, there was no significant difference in the umbilical arterial pH among the 3 groups (supine group: 7.31 ± 0.03 vs 15° group: 7.30 ± 0.04 vs 30° group: 7.31 ± 0.02, P = .28). The 30° group required significantly less phenylephrine (P = .007) and ephedrine (P = .005) before the end of surgery than the supine group; however, the only benefit observed in the 15° group was that the mean SBP at 3 minutes after spinal injection was significantly improved compared with the supine group. CONCLUSIONS: Compared with the supine position, the 30° left-tilt position during surgical preparation did not significantly improve the fetal acid-base status, but it significantly reduced the use of phenylephrine and ephedrine and reduced the incidence of hypotension; however, these benefits were not observed in the 15° left-tilt group.
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Equilibrio Ácido-Base , Anestesia Epidural , Anestesia Obstétrica , Anestesia Raquidea , Cesárea , Feto/fisiología , Posicionamiento del Paciente , Adulto , Anestesia Epidural/efectos adversos , Anestesia Obstétrica/efectos adversos , Anestesia Raquidea/efectos adversos , Presión Sanguínea/efectos de los fármacos , Cesárea/efectos adversos , China , Procedimientos Quirúrgicos Electivos , Femenino , Sangre Fetal/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Hipotensión/tratamiento farmacológico , Hipotensión/etiología , Hipotensión/fisiopatología , Recién Nacido , Posicionamiento del Paciente/efectos adversos , Embarazo , Posición Supina , Factores de Tiempo , Resultado del Tratamiento , Vasoconstrictores/uso terapéuticoRESUMEN
Aggregation-induced emission (AIE) is a photophysical phenomenon correlated closely with the excited-state intramolecular motions. Although AIE has attracted increasing attention due to the significant applications in biomedical and optoelectronics, an in-depth understanding of the excited-state intramolecular motion has yet to be fully developed. Here we found the non-aromatic annulene derivative of cyclooctatetrathiophene shows typical AIE phenomenon in spite of its rotor-free structure. The underlying mechanism is investigated through photoluminescence spectra, time-resolved absorption spectra, theoretical calculations, circular dichroism as well as by pressure-dependent fluorescent spectra etc., which indicate that the aromaticity reversal from ground state to the excited state serves as a driving force for inducing the excited-state intramolecular vibration, leading to the AIE phenomenon. Therefore, aromaticity reversal is demonstrated as a reliable strategy to develop vibrational AIE systems. This work also provides a new viewpoint to understand the excited-state intramolecular motion behavior of lumiongens.
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BACKGROUND: This study investigated the effect of flight transport stress on beagles' routine blood indexes and biochemical parameters and evaluated the anti-stress effect of dangshen (Codonopsis pilosula). METHODS: We selected 12 beagles and divided them into two groups. One group was treated with dangshen decoction two hours before the flight, and the other group was untreated. Their routine blood indexes and clinical biochemical parameters were tested and analyzed before transport, after unloading and after adaptation for 1, 2, 3, 4, 5, and 6 days after administering dangshen. RESULTS: We found that flight transportation stress adversely influenced many of the beagles' routine blood indexes. These recovered during adaptation, with dangshen administration assisting recovery of most indexes. Flight transport stress also adversely influenced biochemical indexes in the beagles. Again these recovered during adaptation, and dangshen aided in the recovery. CONCLUSION: Thus, we found that flight transport adversely affected the beagles' blood indexes, and dangshen reversed the damage from transport stress.
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The unsymmetric dithieno[3,2-b:3',4'-d]thiophene (ts-DTT) was efficiently synthesized, and two novel heptathienoacenes with linear and bull's horn shapes were designed and prepared via different ring cyclization connection manners. All intermediates and aimed heptathienoacenes were fully characterized by (1)H NMR, (13)C NMR, and HRMS. Their UV-vis absorption behavior, fluorescence, and electrochemical properties are characterized. In addition, DFT quantum calculation was employed to further understand the electron distribution and the origin of the absorption bands.