Novel Isoalantolactone-Based Derivatives as Potent NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.

The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized. Among them, compound 49 emerged as the optimal lead, displaying the most potent inhibitory efficacy on nigericin-induced IL-1ß release in THP-1 cells, with an IC50 value of 0.29 µM, approximately 27-fold more potent than that of IAL (IC50: 7.86 µM), and exhibiting higher metabolic stability. Importantly, 49 remarkably improved DSS-induced ulcerative colitis in vivo. Mechanistically, we demonstrated that 49 covalently bound to cysteine 279 in the NACHT domain of NLRP3, thereby inhibiting the assembly and activation of NLRP3 inflammasome. These results provided compelling evidence to further advance the development of more potent NLRP3 inhibitors based on this scaffold.

Exploring the Immunomodulatory Properties of Red Onion (Allium cepa L.) Skin: Isolation, Structural Elucidation, and Bioactivity Study of Novel Onion Chalcones Targeting the A2A Adenosine Receptor.

Onions are versatile and nutritious food widely used in various cuisines around the world. In our ongoing pursuit of bioactive substances with health benefits from red onion (Allium cepa L.) skin, a comprehensive chemical investigation was undertaken. Consequently, a total of 44 compounds, including three previously unidentified chalcones (1-3) were extracted from red onion skin. Of these isolates, chalcones 1-4 showed high affinity to A2A adenosine receptor (A2AAR), and chalcone 2 displayed the best binding affinity to A2AAR, with the IC50 value of 33.5 nM, good A2AAR selectivity against A1AR, A2BAR, and A3AR, and high potency in the cAMP functional assay (IC50 of 913.9 nM). Importantly, the IL-2 bioassay and the cell-mediated cytotoxicity assay demonstrated that chalcone 2 could boost T-cell activation. Furthermore, the binding mechanism of chalcone 2 with hA2AAR was elucidated by molecular docking. This work highlighted that the active chalcones in red onion might have the potential to be developed as A2AAR antagonists used in cancer immunotherapy.

High-speed information reconciliation with syndrome-based early termination for continuous-variable quantum key distribution.

Information reconciliation (IR) is an indispensable component in the post-processing stage of continuous-variable quantum key distribution (CV-QKD), which adopts error-correcting codes to address the asymmetry of secret keys. Currently, low-density parity-check (LDPC) decoding in IR is a post-processing bottleneck in high-speed CV-QKD systems since the upper bound on secret key rate is higher than the information throughput delivered by decoder. In this paper, we study the relationship between the syndrome variation pattern (SVP) in iterative decoding and reconciliation frame error rate. An early termination scheme based on SVP is proposed and applied to multidimensional reconciliation, which can increase information throughput by adaptively adjusting the iteration number of iterative decoding to real-time decoding status. Furthermore, we show that only the resulting syndrome of the highest-rate code part in Raptor-like LDPC codes needs to be calculated to verify whether the reconciliation is successful by studying the convergency of resulting syndrome, which can save a large fraction of computational resources for syndrome calculation. Simulation results show that information throughput of the proposed scheme can be improved by 617.1% compared to the existing scheme when the IR efficiency reaches 97.09%. The proposed scheme points out a new direction for breaking the post-processing bottleneck in high-speed CV-QKD systems.

The day-night differences in cognitive and anxiety-like behaviors of mice after chronic sleep restriction.

Animal behavioral tests are often conducted during the day. However, rodents are nocturnal animals and are primarily active at night. The aim of this study was to determine whether there are diurnal changes in cognitive and anxiety-like performance of mice following chronic sleep restriction (SR). We also investigated whether this phenotypic difference is related to the diurnal variation of glymphatic clearance of metabolic wastes. Mice received 9-day SR by the use of the modified rotating rod method, followed by the open field, elevated plus maze, and Y-maze tests conducted during the day and at night, respectively. Brain ß-amyloid (Aß) and tau protein levels, the polarity of aquaporin4 (AQP4), a functional marker of the glymphatic system, and glymphatic transport ability were also analyzed. SR mice exhibited cognitive impairment and anxiety-like behaviors during the day, but not at night. AQP4 polarity and glymphatic transport ability were higher during the day, with lower Aß1-42 , Aß1-40 , and P-Tau levels in the frontal cortex. These day-night differences were totally disrupted after SR. These results reveal the diurnal changes in behavioral performance after chronic SR, which may be related to circadian control of AQP4-mediated glymphatic clearance of toxic macromolecules from the brain.

Space-Time Block Coded Cooperative MIMO Systems.

The main objective of a Cooperative Multiple-Input Multiple-Output (CMIMO) system is to improve network throughput and network coverage and save energy. By grouping wireless devices as virtual multi-antenna nodes, it can thus simulate the functions of multi-antenna systems. A Space-Time Block Code (STBC) was proposed to utilize the spatial diversity of MIMO systems to improve the diversity gain and coding gain. In this paper, we proposed a cooperative strategy based on STBC and CMIMO, which is referred to as Space-Time Block Coded Cooperative Multiple-Input Multiple-Output (STBC-CMIMO) to inherit the advantages from both STBC and CMIMO. The theoretical performance analysis for the proposed STBC-CMIMO is presented. The performance advantages of the STBC-CMIMO are also shown by simulations. In the simulations, it is demonstrated that STBC-CMIMO can obtain significant performance compared with the existing CMIMO system.

High Efficiency Continuous-Variable Quantum Key Distribution Based on ATSC 3.0 LDPC Codes.

Due to the rapid development of quantum computing technology, encryption systems based on computational complexity are facing serious threats. Based on the fundamental theorem of quantum mechanics, continuous-variable quantum key distribution (CVQKD) has the property of physical absolute security and can effectively overcome the dependence of the current encryption system on the computational complexity. In this paper, we construct the spatially coupled (SC)-low-density parity-check (LDPC) codes and quasi-cyclic (QC)-LDPC codes by adopting the parity-check matrices of LDPC codes in the Advanced Television Systems Committee (ATSC) 3.0 standard as base matrices and introduce these codes for information reconciliation in the CVQKD system in order to improve the performance of reconciliation efficiency, and then make further improvements to final secret key rate and transmission distance. Simulation results show that the proposed LDPC codes can achieve reconciliation efficiency of higher than 0.96. Moreover, we can obtain a high final secret key rate and a long transmission distance through using our proposed LDPC codes for information reconciliation.

Cryptococcal pneumonia in a human immunodeficiency virus-negative patient: A case report.

BACKGROUND: Cases of cryptococcal pneumonia are frequently observed in patients with various innate or acquired immunodeficiencies, including organ transplant patients, cancer patients undergoing chemotherapy, patients with acquired immune deficiency syndrome, or patients on dialysis. Fluconazole is most often used to treat this condition when it is detected. CASE SUMMARY: In the present report, we describe the case of a 42-year-old human immunodeficiency virus-negative man with normal immune function who had cryptococcal pneumonia that was diagnosed after undergoing computed tomography-guided percutaneous lung puncture. We successfully treated this patient via administration of 200 mg voriconazole twice per day for 9 mo. CONCLUSION: This report provides evidence of the successful treatment of pulmonary cryptococcosis using voriconazole.

miR-146a promoted breast cancer proliferation and invasion by regulating NM23-H1.

The study aimed to investigate the regulatory effect of miR-146a in proliferation, invasion and migration of breast cancer and its possible mechanism via NM23-H1. The expression levels of miR-146a in breast cancer with different pathological classification were significantly increased, while the expression levels of NM23-H1 were significantly decreased, which were closely correlated. Double luciferase reporter gene was used to verify the target regulatory relationship between miR-146 and NM23-H1 on a human breast cancer cell line. miR-146a was closely related to the proliferation and metastasis of breast cancer. miR-146a also promoted the growth of breast cancer in vivo via targeting NM23-H1. In conclusion, miR-146 can promote the proliferation and invasion of breast cancer by targeting NM23-H1.

Secrecy Enhancing Scheme for Spatial Modulation Using Antenna Selection and Artificial Noise.

In this paper, we present a new secrecy-enhancing scheme for the spatial modulation (SM) system, by considering imperfect channel state information (CSI). In the proposed scheme, two antennas are activated at the same time. One of the activated antennas transmits information symbols along with artificial noise (AN) optimized under the imperfect CSI condition. On the other hand, the other activated antenna transmits another AN sequence. Because the AN are generated by exploiting the imperfect CSI of the legitimate channel, they can only be canceled at the legitimate receiver, while the passive eavesdropper will suffer from interference. We derive the secrecy rate of the proposed scheme in order to estimate the performance. The numerical results demonstrated in this paper verify that the proposed scheme can achieve a better secrecy rate compared to the conventional scheme at the same effective data rate.

Sequential invasive-noninvasive mechanical ventilation weaning strategy for patients after tracheostomy.

BACKGROUND: Because the continuity and integrity of the trachea are likely damaged to some extent after tracheostomy, the implementation of sequential ventilation has certain difficulties, and sequential invasive-noninvasive ventilation on patients after tracheostomy is less common in practice. The present study aimed to investigate the feasibility of invasive-noninvasive sequential weaning strategy in patients after tracheostomy. METHODS: Fifty patients including 24 patients with withdrawal of mechanical ventilation (conventional group) and 26 patients with sequential invasive-noninvasive weaning by directly plugging of tracheostomy (sequential group) were analyzed retrospectively after appearance of pulmonary infection control (PIC) window. The analysis of arterial blood gases, ventilator-associated pneumonia (VAP) incidence, the total duration of mechanical ventilation, the success rate of weaning and total cost of hospitalization were compared between the two groups. RESULTS: Arterial blood gas analysis showed that the sequential weaning group was better than the conventional weaning group 1 and 24 hours after invasive ventilation. The VAP incidence was lowered, the duration of mechanical ventilation shortened, the success rate of weaning increased, and the total cost of hospitalization decreased. CONCLUSION: Sequential invasive-noninvasive ventilator weaning is feasible in patients after tracheostomy.

Rapid hydrolysis of phosphate ester promoted by Ce(IV) conjugating with a ß-cyclodextrin monomer and dimer.

Two N-donor ligands (L(1) and L(2)) derived from a ß-cyclodextrin (ßCD) monomer and dimer were employed to mediate the hydrolytic activity and stability of the Ce(IV) ion in aqueous solution. Complexes Ce(IV)-L(1) and Ce(IV)-L(2) were prepared in situ and characterized by means of UV-vis and NMR measurements. Ce(IV)-L(1) catalyzed the hydrolysis of a DNA model, bis(4-nitrophenyl)phosphate (BNPP) with k(cat) = 5.2 × 10(-3) s(-1) (half-life t(1/2) ≈ 2 minutes) under mild conditions, which represented an approximate 130 million-fold acceleration with respect to the spontaneous hydrolysis of BNPP. The dinuclear species, [Ce(2)L(1)(2)(OH)(5)](3+), contributed splendidly to the catalytic efficiency which echoed the active species postulation of [Ce(2)(OH)(7)](+) in the literature. Ce(IV)-L(2) exhibited efficient binding with BNPP giving 1/K(M) = 2.1 × 10(5) M(-1) which exceeded other Ce(IV) species, e.g. [Ce(4)(OH)(15)](+), by 2 orders of magnitude, which highlighted the hydrophobicity effect of ßCDs. Such a highly binding affinity leads to the second-order rate constant, k(cat)/K(M) = 2.3 × 10(2) M(-1) s(-1), which probably ranks as the highest in the non-enzymatic cleavage of BNPP under similar conditions. Additionally, Ce(IV)-L(2) showed favorable tolerance to basic aqua owing to the bulky protection of double ßCD pendants.

[Study on the epidemiology and risk factors on dysphagia after ischemic stroke in Chengdu City, China].

OBJECTIVE: To study the incidence and the risk factors of dysphagia after ischemic stroke in Chengdu City, China. METHODS: Review was made with unified questionnaire on dysphagia after ischemic stroke in 563 patients from four hospitals, from January to December 2005. Over 20 risk factors related to dysphagia after ischemic stroke were analyzed by logistic regression. RESULTS: The total incidence of dysphagia after ischemic stroke was 13.3% in Chengdu. Data from logistic regression analysis indicated that gender, morbidity frequency, basal nuclei, periventricular lesion, hypertension, pneumonia, hyperlipemia, cervical spondylosisi, internal carotid artherosclerosis were closely related to dysphagia after ischemic stroke,with OR values as 0.416, 0.489, 0.327, 0.454, 2.187, 2.146, 0.352, 0.242 and 0.273 respectively. CONCLUSION: The total incidence was lower than literature published from home and abroad. Gender, morbidity frequency, basal nuclei, periventricular lesion, hypertension, pneumonia, hyperlipemia, cervical spondylosisi and internal carotid artherosclerosis seemed to be risk factors to dysphagia after ischemic stroke.