Search

In preclinical studies, a new antituberculosis drug regimen markedly reduced the time required to achieve relapse-free cure. This study aimed to preliminarily evaluate the efficacy and safety of this four-month regimen, consisting of clofazimine, prothionamide, pyrazinamide and ethambutol, with a standard six-month regimen in patients with drug-susceptible tuberculosis. An open-label pilot randomized clinical trial was conducted among the patients with newly diagnosed bacteriologically-confirmed pulmonary tuberculosis. The primary efficacy end-point was sputum culture negative conversion. Totally, 93 patients were included in the modified intention-to-treat population. The rates of sputum culture conversion were 65.2% (30/46) and 87.2% (41/47) for short-course and standard regimen group, respectively. There was no difference on two-month culture conversion rates, time to culture conversion, nor early bactericidal activity (P > 0.05). However, patients on short-course regimen were observed with lower rates of radiological improvement or recovery and sustained treatment success, which was mainly attributed to higher percent of patients permanently changed assigned regimen (32.1% vs. 12.3%, P = 0.012). The main cause for it was drug-induced hepatitis (16/17). Although lowering the dose of prothionamide was approved, the alternative option of changing assigned regimen was chosen in this study. While in per-protocol population, sputum culture conversion rates were 87.0% (20/23) and 94.4% (34/36) for the respective groups. Overall, the short-course regimen appeared to have inferior efficacy and higher incidence of hepatitis but desired efficacy in per-protocol population. It provides the first proof-of-concept in humans of the capacity of the short-course approach to identify drug regimens that can shorten the treatment time for tuberculosis.

In this study, the total flavonoid composition and bioactivity of finger millet was analyzed. Eleusine coracana flavonoids (ECFs) were obtained through sequential 70% ethanol extraction, ethyl acetate extraction, and purification with D101 macroporous resin. The total flavonoid content was determined using the NaNO2-Al(NO3)3-NaOH colorimetric method, and the flavonoid composition using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vitro antioxidant activity of ECFs was evaluated using chemical assays, and the anti-aging activity using C. elegans as a model organism. The results demonstrated that the total flavonoid content of ECFs was 82.6%, with 16 major components being identified, including flavonoid glycosides and catechin. In vitro antioxidant tests showed that ECFs exhibited half-maximal inhibitory concentrations (IC50) of 45.34 and 22.75 μg/mL against 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radicals, respectively, with the IC50 against ABTS cation radicals being lower than that of the positive control vitamin E (29.25 μg/mL). At a concentration of 200 μg/mL, ECFs increased catalase activity in C. elegans by 53.98%, superoxide dismutase activity by 30.64%, and glutathione levels by 51.06%, while decreasing malondialdehyde (MDA) content by 11.82%. ECFs extended the lifespan of C. elegans by 17.86%, and improved its mobility compared to the control group, indicating improved vitality. ECFs had no significant effect on C. elegans fecundity suggesting no promoting effect on its reproductive function. Additionally, ECFs reduced the level of lipofuscin by 53.91%. These findings demonstrated that ECFs had significant antioxidant effects both in vitro and in vivo as well as remarkable anti-aging activity in C. elegans, which could provide a foundation for the functional application of finger millet.

In this paper, we study the control problem of auto-berthing marine surface vessels (MSVs) within a predefined, finite time in the restricted waters of a port, in the face of internal and external uncertain dynamics and actuator faults. We first use radial basis function neural networks to reconstruct the internal uncertainties of the system; then, using the minimum learning parameter method, we transform the weights of the neural networks, the external disturbances of the system, and the bias fault factors into an indirect single-parameter neural learning mode. We also apply a robust depth information adaptation technique to estimate the upper bound on the composite disturbances online. Dynamic surface control technology alleviates the burden of virtual control derivative calculations. Finite-time convergence of the system is guaranteed by a predetermined finite-time function based on a time-based generator (TBG). Based on these methods, we design a finite-time fault-tolerant auto-berthing control scheme based on TBG. The stability of the system is analysed based on Lyapunov stability theory. Finally, we verify the effectiveness of the proposed control scheme through simulation.

Introduction: In coronavirus disease 2019 (COVID-19), particularly in older people, dysregulated immune response and aberrant repair can result in varied severity secondary pulmonary fibrosis (PF). By detecting some indicators, the occurrence and prognosis of fibrosis can be measured, providing directions for COVID-19 treatment. Methods: The research study lasted for 3 months and involved 88 COVID-19 patients. According to the chest radiological examination, 47 (53.41%) individuals were found to have no PF, while 41 (46.59%) showed PF. Clinical data such as inflammation markers, imaging findings, blood gas analysis, and hospital stay length were collected. Results: With area under the curve values of 0.7413, 0.7741, and 0.7048, respectively, and the study of the receiver operating characteristic curve demonstrated that mucin 1 (MUC1), carcinoembryonic antigen (CEA), and CXC chemokine receptor 10 (CXCL10) could diagnose the presence of COVID-19 PF. To evaluate the possibility of PF following severe acute respiratory syndrome coronavirus-2 infection, we established particular values for MUC1, CEA, and CXCL10 (1.296 ng/ml, 4.315 ng/ml, and 32.77 ng/ml, respectively). The survival curve for hospital days indicated that the length of hospital stays positively correlated with these three factors (P < 0.01). Transforming growth factor-beta did not correlate significantly with the severity of COVID-19 or PF. Conclusion: The results of this study suggested that the MUC1, CEA, and CXCL10 can be employed to explore the severity of secondary PF in COVID-19.

Objective: To explore the hypolipidemic activity and toxic side effect of lansiumamide B (LB) from chicken-heart shaped wampee (Clausena lansium) seeds in C57BL/6J mice fed on a high-fat-diet (HFD) model. Methods: The no observed adverse effect level (NOAEL) of LB in mice was assessed by oral acute toxicity test. HFD-fed mice were intragastrically administered with LB at 1/100, 1/50 and 1/25 NOAEL for 4 weeks. To evaluate the lipid-lowering activity of LB, body mass, serum lipids, insulin resistance, and oxidative stress indicators were measured. Results: The NOAEL of LB was 2 g/kg mb. LB significantly reduced body mass in HFD-fed mice. Compared with the HFD model group, body mass decreased by 15.51% and Lee’s index declined by 3.25% in the high-dose LB group; the concentration of high-density lipid-cholesterol (HDL-C) increased by 38.04%, and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in the serum increased by 41.86%, 41.95%, and 105.50%, respectively. Conclusion: LB within the NOAEL range has significant lipid-lowering activity in mice without obvious toxicity.

The results of studies on a trajectory-tracking problem affected by false data injection attacks (FDIAs) and internal and external uncertainties are presented in this paper. In view of the FDIAs experienced by the system, we compensate for the serious navigation deviation caused by malicious attacks by designing an online approximator. Next, we study the internal and external uncertainties introduced by environmental factors, system parameter fluctuations, or sensor errors, and we design adaptive laws for these uncertainties to approximate their upper bounds. To further enhance the response velocity and stability of the system, we introduce finite-time technology to ensure that the unmanned underactuated surface vessels (USVs) reach the predetermined trajectory-tracking target within finite time. To further reduce the update frequency of the controller, we introduced event-triggered control (ETC) technology. This saves the system’s communication resources and optimizes the system. Through Lyapunov stability theory, a strict and complete stability analysis is provided for the control scheme. Finally, the effectiveness of the control scheme is verified using two sets of simulations.

Circular RNAs (circRNAs) are key regulators of cervical cancer (CC) progression. This study aimed to elucidate the role and mechanism of circ_0051428, a novel circRNA, in CC tumorigenesis. Quantitative real-time polymerase chain reaction and western blotting analyses confirmed that circ_0051428 and matrix metalloprotein-2 (MMP2) were overexpressed in CC, whereas the microRNA miR-885-3p was poorly expressed. After performing a series of in vitro and in vivo experiments, circ_0051428 knockdown was shown to repress CC cell invasion and proliferation in vitro, and hamper tumor formation in vivo. Dual-luciferase reporter and RNA-binding protein immunoprecipitation experiments verified that circ_0051428 interacts with miR-885-3p to regulate the target gene MMP2 of miR-885-3p in CC. In addition, miR-885-3p knockdown offset the anticancer effects of circ_0051428 or MMP2 knockdown on CC cell malignancy. Overall, this study revealed that circ_0051428 executes a tumor-promoting function in CC pathogenesis by modulating the miR-885-3p/MMP2 axis. Our findings provide a novel approach for CC treatment.