[Determination of individual components in finished motor gasoline by dual-channel three-column gas chromatography].

A method based on a dual-channel gas chromatograph equipped with three columns and three detectors was established for the determination of individual components in finished motor gasoline. The gasoline samples were separately introduced into the two injection ports of the chromatograph using two autosamplers. The components of the sample introduced into the first injection port (channel 1) were separated on a nonpolar PONA column (50 m×0.20 mm×0.5 µm) for gasoline analysis and detected by an flame ionization detector (FID). The components of the sample introduced into the second injection port (channel 2) were separated on another PONA column. Oxygenates (e.g., ethers and alcohols), other unconventional and prohibited additives that would co-elute with the hydrocarbons (e.g., methylal, dimethyl carbonate, sec-butyl acetate, and anilines), and some difficult-to-separate hydrocarbon pairs (e.g., 2,3,3-trimethylpentane and toluene) eluted from the PONA column and entered a DM-624 column (30 m×0.25 mm×1.4 µm) to achieve further separation according to the switch timetable using the Deans switch procedure and detected by an FID. The peak of 3-methylpentane, a common component in gasoline samples, also entered the DM-624 column by the Deans switch procedure for calculation purposes. The peak areas of target components on the PONA column in channel 1 were calculated using the peak areas on the DM-624 column as well as those of 3-methylpentane on both the DM-624 and PONA columns in channel 1 with a calibration factor between the two channels. The peak areas of co-eluted components were obtained by subtracting the calculated peak areas of the target components from those of the co-eluted peaks. The mass percentages of the individual components were calculated according to the normalization method using all peak areas on the PONA column in channel 1 with relative response factors. The mass percentages of the oxygenates, anilines, and individual hydrocarbons were determined, and the group-type distribution was calculated according to the carbon number. Separation and quantitation interferences between the additives and hydrocarbons were eliminated using this procedure. Twenty oxygenates and unconventional additives, each with a mass percentage of approximately 3%, were added to a real motor gasoline-92 sample and analyzed using the proposed method. The recoveries of the target components were between 90.1% and 118.2% with relative standard deviations (RSDs) between 0.2% and 5.1% (n=6). The analysis of a real ethanol-gasoline sample showed that the RSDs of contents of most components was less than 3% (n=6). Because the heart-cut of peaks using Deans switch technique requires the precise repeatability of retention times, the retention-time repeatability of components on the PONA column in channel 2 was investigated over an extended period of time after thousands of runs of real-sample analysis. The retention times of the same component in several randomly selected motor gasoline-92 samples varied from 0.01 to 0.03 min, indicating that the proper timetable for the Deans switch remained stable for two years. The precise repeatability of retention times was achieved owing to the high precision of the electric pneumatic control of the chromatograph and the stability of the column used. Real finished motor gasoline samples with different octane numbers (gasoline-92, gasoline-95, and ethanol gasoline-95) were analyzed using the developed method, and the results acquired were consistent with those of standard methods (GB/T 30519-2016, NB/SH/T 0663-2014, and SH/T 0693-2000). If some unconventional additives (such as methylal) were added to gasoline samples, the contents of these unconventional additives could also be detected, which means one run of the proposed method could provide results corresponding to three or four runs of different standard methods. The acquisition of information on the individual components of finished motor gasoline will assist in research on precise gasoline blending.

Switch to fixed-dose ainuovirine, lamivudine, and tenofovir DF versus elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV-1: the 48-week results of the SPRINT trial, a multi-centre, randomised, double-blind, active-controlled, phase 3, non-inferiority trial.

Background: We compared the efficacy and safety profiles of ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen. Methods: This study was a multi-centre, randomised, double-blind, active-controlled, non-inferiority trial recruiting PLWH from 10 clinical centres across China. Main inclusion criteria included age of 18-65 years (inclusive), and stably staying on an ARV regimen combining an NNRTI with a two-drug NRTI backbone for at least 12 months. Eligible participants must have maintained plasma HIV-1 ribonucleic acid (RNA) titre below 50 copies per mL confirmed on two successive tests at an interval of at least one month prior to randomisation. Participants were randomly assigned to receive ANV 150 mg plus lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate (TDF) 300 mg (ANV/3TC/TDF), or cobicistat (Cobi) 150 mg boosted EVG plus emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA titre at 50 copies per mL or above at week 48 using the US Food and Drug Administration snapshot algorithm, with a non-inferiority margin of 4 percentage points at a two-side 95% confidence level. This trial is active, but not recruiting, and is registered with Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100051605. Findings: Between October 2021 and February 2022, 923 patients were screened for eligibility, among whom 762 participants were randomized and had received at least one dose of ANV/3TC/TDF (n = 381) or EVG/Cobi/FTC/TAF (n = 381). At week 48, 7 (1.8%) participants on ANV/3TC/TDF and 6 (1.6%) participants on EVG/Cobi/FTC/TAF had plasma HIV-1 RNA titre at 50 copies per mL or above, including missing virological data within the time window (the Cochran-Mantel-Haenszel method, estimated treatment difference [ETD], 0.3%, 95% CI -1.6 to 2.1), establishing the non-inferiority of ANV/3TC/TDF to EVG/Cobi/FTC/TAF. The proportions of participants experiencing at least one treatment-emergent adverse events (AEs) were comparable between the two arms (97.6% versus 97.6%). A small proportion of participants discontinued study drug due to AEs (0.3% versus 0.3%). Serious AEs occurred in 11 (2.9%) participants on ANV/3TC/TDF and 9 (2.4%) participants on EVG/Cobi/FTC/TAF, respectively, none of which was considered related to study drug at the jurisdiction of the investigator. At week 48, participants on ANV/3TC/TDF showed a significantly less weight gain from baseline compared to those on EVG/Cobi/FTC/TAF (least square mean, 1.16 versus 2.05 kg, ETD -0.90 kg, 95% CI, -1.43 to -0.37). The changes in serum lipids from baseline also favoured ANV/3TC/TDF over EVG/Cobi/FTC/TAF. Interpretation: In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF. Funding: Jiangsu Aidea Pharmaceutical & the National "Thirteenth Five-year Period" Major Innovative Drugs Research and Development Key Project of the People's Republic of China Ministry of Science and Technology.

An overview of early genetic predictors of IgA deficiency.

INTRODUCTION: Inborn errors of immunity (IEIs) refer to a heterogeneous category of diseases with defects in the number and/or function of components of the immune system. Immunoglobulin A (IgA) deficiency is the most prevalent IEI characterized by low serum level of IgA and normal serum levels of IgG and/or IgM. Most of the individuals with IgA deficiency are asymptomatic and are only identified through routine laboratory tests. Others may experience a wide range of clinical features including mucosal infections, allergies, and malignancies as the most important features. IgA deficiency is a multi-complex disease, and the exact pathogenesis of it is still unknown. AREAS COVERED: This review compiles recent research on genetic and epigenetic factors that may contribute to the development of IgA deficiency. These factors include defects in B-cell development, IgA class switch recombination, synthesis, secretion, and the long-term survival of IgA switched memory B cells and plasma cells. EXPERT OPINION: A better and more comprehensive understanding of the cellular pathways involved in IgA deficiency could lead to personalized surveillance and potentially curative strategies for affected patients, especially those with severe symptoms.

Neuroelectrophysiological alteration associated with cognitive flexibility after 24 h sleep deprivation in adolescents.

The cognitive neural mechanisms by which sleep deprivation affects cognitive flexibility are poorly understood. Therefore, the study investigated the neuroelectrophysiological basis of the effect of 24 h sleep deprivation on cognitive flexibility in adolescents. 72 participants (36 females, mean age ± SD=20.46 ± 2.385 years old) participated in the study and were randomly assigned to the sleep deprivation group and control group. They were instructed to complete a task switch paradigm, during which participants' behavioral and electroencephalographic data were recorded. Behaviorally, there were significant between-group differences in accuracy. The results of event-related potential showed that the P2, N2 and P3 components had significant group effects or interaction effects. At the time-frequency level, there were statistically significant differences between the delta and theta bands. These results suggested that 24 h sleep deprivation affected problem-solving effectiveness rather than efficiency, mainly because it systematically impaired cognitive processing associated with cognitive flexibility.

Shedding More than Weight: Metabolic and Bariatric Surgery and the Journey to Insulin Independence in Insulin-Treated Type 2 Diabetes.

BACKGROUND: Type 2 diabetes (T2D) imposes a significant health burden, necessitating lifelong pharmacological interventions, with insulin being one of the cornerstone therapies. However, these regimens are associated with health risks and psychological stressors. We aim to examine the rates of insulin-treated T2D remission as well as cessation or reduction in dosage of insulin therapy following metabolic and bariatric surgery (MBS). MATERIALS AND METHODS: A retrospective analysis of patients with a preoperative diagnosis of insulin-treated T2D who underwent primary laparoscopic sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) or biliopancreatic diversion with duodenal switch (BPD/DS) with a minimum of 3 and up to 5 years of follow-up. The average daily dose for each type of insulin, measured in units, was calculated at yearly intervals. RESULTS: Among 287 patients included, 201 (70%) underwent RYGB, 66 (23%) SG and 20 (7%) BPD/DS. Average follow-up period was 4.6 ± 0.7 years. At five years follow-up, mean total weight loss was highest in the BPD/DS subgroup at 37.5 ± 11.6%. Insulin usage decreased significantly from complete dependency at baseline to 36.2% just one year postoperatively, and the use of non-insulin antidiabetic drugs decreased from 79.4% initially to 26.1%. These results were sustained for the duration of the study. Subgroup analysis indicated that, five-years postoperatively, T2D remission was highest following BPD/DS (73.7%) compared to RYGB (43.2%) and SG (23.3%) (p< 0.001). CONCLUSIONS: MBS is a transformative approach for achieving significant remission in insulin-treated T2D and reducing insulin requirements. Our findings reinforce the efficacy of these surgical interventions, particularly highlighting the promising potential of procedures that bypass the proximal small intestine such as BPD/DS and RYGB.

A ligation-independent sequencing method reveals tRNA-derived RNAs with blocked 3' termini.

Despite the numerous sequencing methods available, the diversity in RNA size and chemical modification makes it difficult to capture all RNAs in a cell. We developed a method that combines quasi-random priming with template switching to construct sequencing libraries from RNA molecules of any length and with any type of 3' modifications, allowing for the sequencing of virtually all RNA species. Our ligation-independent detection of all types of RNA (LIDAR) is a simple, effective tool to identify and quantify all classes of coding and non-coding RNAs. With LIDAR, we comprehensively characterized the transcriptomes of mouse embryonic stem cells, neural progenitor cells, mouse tissues, and sperm. LIDAR detected a much larger variety of tRNA-derived RNAs (tDRs) compared with traditional ligation-dependent sequencing methods and uncovered tDRs with blocked 3' ends that had previously escaped detection. Therefore, LIDAR can capture all RNAs in a sample and uncover RNA species with potential regulatory functions.

Niclosamide modulates phenotypic switch and inflammatory responses in human pulmonary arterial smooth muscle cells.

Excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) represent key steps of pulmonary vascular remodeling, leading to the development of pulmonary arterial hypertension (PAH) and right ventricular failure. Niclosamide (NCL), an FDA-approved anthelmintic, has been shown to regulate cell proliferation, migration, invasion, and apoptosis through a variety of signaling pathways. However, its role on modulating the phenotypic switch and inflammatory responses in PASMCs remains unclear. In this study, cell proliferation assay showed that NCL inhibited PDGF-BB induced proliferation of human PASMCs in a dose-dependent manner. Western blot analysis further confirmed a notable reduction in the expression of cyclin D1 and PCNA proteins. Subsequently, flow cytometry analysis demonstrated that NCL induced an increased percentage of cells in the G1 phase while promoting apoptosis in PASMCs. Moreover, both scratch wound assay and transwell assay confirmed that NCL decreased PDGF-BB-induced migration of PASMCs. Mechanistically, western blot revealed that pretreatment of PASMCs with NCL markedly restored the protein levels of SMA, SM22, and calponin, while reducing phosphorylation of P38/STAT3 signaling in the presence of PDGF-BB. Interestingly, macrophages adhesion assay showed that NCL markedly reduced recruitment of Calcein-AM labeled RAW264.7 by TNFα-stimulated PASMCs. Western blot revealed that NCL suppressed TNFα-induced expression of both of VCAM-1 and ICAM-1 proteins. Furthermore, pretreatment of PASMCs with NCL significantly inhibited NLRP3 inflammasome activity through reducing NLRP3, AIM2, mature interleukin-1ß (IL-ß), and cleaved Caspase-1 proteins expression. Together, these results suggested versatile effects of NCL on controlling of proliferation, migration, and inflammatory responses in PASMCs through modulating different pathways, indicating that repurposing of NCL may emerge as a highly effective drug for PAH treatment.

Identification of antennal alternative splicing by combining genome and full-length transcriptome analysis in Bactrocera dorsalis.

Alternative splicing is an essential post-transcriptional regulatory mechanism that diversifies gene function by generating multiple protein isoforms from a single gene and act as a crucial role in insect environmental adaptation. Olfaction, a key sense for insect adaptation, relies heavily on the antennae, which are the primary olfactory organs expressing most of the olfactory genes. Despite the extensive annotation of olfactory genes within insect antennal tissues facilitated by high-throughput sequencing technology advancements, systematic analyses of alternative splicing are still relatively less. In this study, we focused on the oriental fruit fly (Bactrocera dorsalis), a significant pest of fruit crops. We performed a detailed analysis of alternative splicing in its antennae by utilizing the full-length transcriptome of its antennal tissue and the insect's genome. The results revealed 8600 non-redundant full-length transcripts identified in the oriental fruit fly antennal full-length transcriptome, spanning 4,145 gene loci. Over 40% of these loci exhibited multiple isoforms. Among these, 161 genes showed sex-biased isoform switching, involving seven different types of alternative splicing. Notably, events involving alternative transcription start sites (ATSS) and alternative transcription termination sites (ATTS) were the most common. Of all the genes undergoing ATSS and ATTS alternative splicing between male and female, 32 genes were alternatively spliced in protein coding regions, potentially affecting protein function. These genes were categorized based on the length of the sex-biased isoforms, with the highest difference in isoform fraction (dIF) associated with the ATSS type, including genes such as BdorABCA13, BdorCAT2, and BdorTSN3. Additionally, transcription factor binding sites for doublesex were identified upstream of both BdorABCA13 and BdorCAT2. Besides being expressed in the antennal tissues, BdorABCA13 and BdorCAT2 are also expressed in the mouthparts, legs, and genitalia of both female and male adults, suggesting their functional diversity. This study reveals alternative splicing events in the antennae of Bactrophora dorsalis from two aspects: odorant receptor genes and other types of genes expressed in the antennae. This study not only provides a research foundation for understanding the regulation of gene function by alternative splicing in the oriental fruit fly but also offers new insights for utilizing olfaction-based behavioral manipulation techniques to manage this pest.

Real-World First-Line Maintenance Niraparib Monotherapy Use Following Chemotherapy Plus Bevacizumab: The SW1TCH Study.

INTRODUCTION: Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab. METHODS: This retrospective observational study used data from a US-based nationwide database of deidentified, electronic health record-derived data. Patients diagnosed with OC during the study period (1 January 2011-30 November 2022, inclusive) were eligible if they received 1L chemotherapy plus bevacizumab treatment followed by 1LM niraparib monotherapy, initiated between 1 January 2017 (inclusive) and 2 September 2022. Patients were followed from index date (initiation of niraparib 1LM) until the first occurrence of death, end of follow-up, or end of study. Clinical outcomes were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Kaplan-Meier curves were used to estimate TTD, TTNT, and 95% confidence intervals (CIs). RESULTS: Among 93 patients selected, median age at index was 67 years (interquartile range [IQR] 60-72 years). Most patients had BRCA wild-type/homologous recombination (HR)-proficient or BRCA wild-type/HR unknown disease (75.3%). In all, 18 (19.4%) patients had HR-deficient disease. Five (5.4%) patients had unknown test results for both BRCA and HR deficiency status. Median follow-up time was 16.3 months (IQR 8.7-25.4 months), and median time from end of 1L therapy to 1LM initiation was 35.0 days (IQR 25.0-53.9 days). Median TTD was 9.3 months (95% CI 6.1-11.3 months). Median TTNT was 12.9 months (95% CI 11.5-19.0 months). CONCLUSIONS: This real-world study provided insights into switch maintenance with 1LM niraparib monotherapy, which may be a viable treatment option for patients with advanced OC.

Lorentz Force-Actuated Bidirectional Nanoelectromechanical Switch with an Ultralow Operation Voltage.

The high operating voltage of conventional nanoelectromechanical switches, typically tens of volts, is much higher than the driving voltage of the complementary metal oxide semiconductor integrated circuit (∼1 V). Though the operating voltage can be reduced by adopting a narrow air gap, down to several nanometers, this leads to formidable manufacturing challenges and occasionally irreversible switch failures due to the surface adhesive force. Here, we demonstrate a new nanowire-morphed nanoelectromechanical (NW-NEM) switch structure with ultralow operation voltages. In contrast to conventional nanoelectromechanical switches actuated by unidirectional electrostatic attraction, the NW-NEM switch is bidirectionally driven by Lorentz force to allow the use of a large air gap for excellent electrical isolation, while achieving a record-low driving voltage of <0.2 V. Furthermore, the introduction of the Lorentz force allows the NW-NEM switch to effectively overcome the adhesion force to recover to the turn-off state.

Mixing due to Solution Switch Limits the Performance of Electrosorption for Desalination.

Electrosorption (ES) is a research frontier in electrochemical separation, with proven potential applications in desalination, wastewater treatment, and selective resource extraction. However, due to the limited adsorption capacity of film electrodes, ES requires short circuiting or circuit reversal, accompanied by a solution switch between the feed solution and receiving solution, to sustain desalination over many charge-discharge cycles. In previously reported studies, solution switches have been commonly ignored to simplify experimental procedures, and their impacts on separation performance are thus not well understood. This study aims to provide a quantitative analysis of the impacts of mixing due to a solution switch on the performance of ES-based desalination. A numerical model of ES has been employed to evaluate the adverse effects of the solution switch on the desalination performance in three commonly used operation modes. The analysis reveals that the impacts of mixing due to solution-switch are more severe with a larger concentration difference between the desalinated water and the brine and provides insights into the effectiveness of increasing electrode loading or specific capacity in mitigating the detrimental impacts of mixing. Even with state-of-the-art systems, producing freshwater from seawater or even brackish water with medium-to-high salinity is practically challenging due to the presence of solution switch.

Spatiotemporal changes in Netrin/Dscam1 signaling dictate axonal projection direction in Drosophila small ventral lateral clock neurons.

Axon projection is a spatial- and temporal-specific process in which the growth cone receives environmental signals guiding axons to their final destination. However, the mechanisms underlying changes in axonal projection direction without well-defined landmarks remain elusive. Here, we present evidence showcasing the dynamic nature of axonal projections in Drosophila's small ventral lateral clock neurons (s-LNvs). Our findings reveal that these axons undergo an initial vertical projection in the early larval stage, followed by a subsequent transition to a horizontal projection in the early-to-mid third instar larvae. The vertical projection of s-LNv axons correlates with mushroom body calyx expansion, while the s-LNv-expressed Down syndrome cell adhesion molecule (Dscam1) interacts with Netrins to regulate the horizontal projection. During a specific temporal window, locally newborn dorsal clock neurons secrete Netrins, facilitating the transition of axonal projection direction in s-LNvs. Our study establishes a compelling in vivo model to probe the mechanisms of axonal projection direction switching in the absence of clear landmarks. These findings underscore the significance of dynamic local microenvironments in the complementary regulation of axonal projection direction transitions.

Human-Induced Pluripotent Stem Cell (iPSC)-Derived GABAergic Neuron Differentiation in Bipolar Disorder.

Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABAA channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1. Using multi-electrode array (MEA) analysis, we observed that BP neurons exhibit increased firing, network bursting and decreased synchrony compared to C. Understanding GABA signaling in differentiation may identify novel approaches and new targets for treatment of neuropsychiatric disorders such as BP.

Rapid, Multiplexed, and Enzyme-Free Nucleic Acid Detection Using Programmable Aptamer-Based RNA Switches.

Rapid, simple, and low-cost diagnostic technologies are crucial tools for combatting infectious disease. We describe a class of aptamer-based RNA switches or aptaswitches that recognize target nucleic acid molecules and initiate folding of a reporter aptamer. Aptaswitches can detect virtually any sequence and provide an intense fluorescent readout without intervening enzymes, generating signals in as little as 5 minutes and enabling detection by eye with minimal equipment. Aptaswitches can be used to regulate folding of seven fluorogenic aptamers, providing a general means of controlling aptamers and an array of multiplexable reporter colors. Coupling isothermal amplification reactions with aptaswitches, we reach sensitivities down to 1 RNA copy/µL in one-pot reactions. Application of multiplexed all-in-one reactions against RNA from clinical saliva samples yields an overall accuracy of 96.67% for detection of SARS-CoV-2 in 30 minutes. Aptaswitches are thus versatile tools for nucleic acid detection that are readily integrated into rapid diagnostic assays.

Age Three: Milestone in the Development of Cognitive Flexibility.

Although the cognitive flexibility (CF) of preschool children has been extensively studied, the development of CF in children around three years old is unclear. This study aimed to investigate the CF of three-year-olds in a stepwise rule-induction task (sRIT) comprising nine steps in which children are encouraged to switch attention to a new rule and then implicitly inhibit the old one. A pair of boxes was displayed at each step, and children aged 2.5 to 3.5 years were asked to select the target. When children learned a rule (e.g., the shape rule), they were encouraged to switch rules through negative feedback. The results showed that most children (81.10%) passed at least one of the two sets of the sRIT, and children over the age of three years performed better than those under three years. Additionally, a positive correlation existed between rule switching and rule generalization, whereby the old rule was implicitly inhibited. These findings indicate that age three might be a milestone in the development of CF, and inhibitory control might play a vital role in rule switching.

Quercetin Attenuates KLF4-Mediated Phenotypic Switch of VSMCs to Macrophage-like Cells in Atherosclerosis: A Critical Role for the JAK2/STAT3 Pathway.

The objective of this study was to elucidate the protective role of quercetin in atherosclerosis by examining its effect on the phenotypic switch of vascular smooth muscle cells (VSMCs) to macrophage-like cells and the underlying regulatory pathways. Aorta tissues from apolipoprotein E-deficient (ApoE KO) mice fed a high-fat diet (HFD), treated with or without 100 mg/kg/day quercetin, were analyzed for histopathological changes and molecular mechanisms. Quercetin was found to decrease the size of atherosclerotic lesions and mitigate lipid accumulation induced by HFD. Fluorescence co-localization analysis revealed a higher presence of macrophage-like vascular smooth muscle cells (VSMCs) co-localizing with phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 3 (p-STAT3), and Krüppel-like factor 4 (KLF4) in regions of foam cell aggregation within aortic plaques. However, this co-localization was reduced following treatment with quercetin. Quercetin treatment effectively inhibited the KLF4-mediated phenotypic switch in oxidized low-density lipoprotein (ox-LDL)-loaded mouse aortic vascular smooth muscle cells (MOVAS), as indicated by decreased expressions of KLF4, LGALS3, CD68, and F4/80, increased expression of alpha smooth muscle actin (α-SMA), reduced intracellular fluorescence Dil-ox-LDL uptake, and decreased lipid accumulation. In contrast, APTO-253, a KLF4 activator, was found to reverse the effects of quercetin. Furthermore, AG490, a JAK2 inhibitor, effectively counteracted the ox-LDL-induced JAK2/STAT3 pathway-dependent switch to a macrophage-like phenotype and lipid accumulation in MOVAS cells. These effects were significantly mitigated by quercetin but exacerbated by coumermycin A1, a JAK2 activator. Our research illustrates that quercetin inhibits the KLF4-mediated phenotypic switch of VSMCs to macrophage-like cells and reduces atherosclerosis by suppressing the JAK2/STAT3 pathway.

A Metamaterials-Based Absorber Used for Switch Applications with Dynamically Variable Bandwidth in Terahertz Regime.

A broadband absorber based on metamaterials of graphene and vanadium dioxide (VO2) is proposed and investigated in the terahertz (THz) regime, which can be used for switch applications with a dynamically variable bandwidth by electrically and thermally controlling the Fermi energy level of graphene and the conductivity of VO2, respectively. The proposed absorber turns 'on' from 1.5 to 5.4 THz, with the modulation depth reaching 97.1% and the absorptance exceeding 90% when the Fermi energy levels of graphene are set as 0.7 eV, and VO2 is in the metallic phase. On the contrary, the absorptance is close to zero and the absorber turns 'off' with the Fermi energy level setting at 0 eV and VO2 in the insulating phase. Furthermore, other four broadband absorption modes can be achieved utilizing the active materials graphene and VO2. The proposed terahertz absorber may benefit the areas of broadband switch, cloaking objects, THz communications and other applications.

A model-based brain switch via periodic motor imagery modulation for asynchronous brain-computer interfaces.

Objective.Brain switches provide a tangible solution to asynchronized brain-computer interface, which decodes user intention without a pre-programmed structure. However, most brain switches based on electroencephalography signals have high false positive rates (FPRs), resulting in less practicality. This research aims to improve the operating mode and usability of the brain switch.Approach.Here, we propose a novel virtual physical model-based brain switch that leverages periodic active modulation. An optimization problem of minimizing the triggering time subject to a required FPR is formulated, numerical and analytical approximate solutions are obtained based on the model.Main results.Our motor imagery (MI)-based brain switch can reach 0.8FP/h FPR with a median triggering time of 58 s. We evaluated the proposed brain switch during online device control, and their average FPRs substantially outperformed the conventional brain switches in the literature. We further improved the proposed brain switch with the Common Spatial Pattern (CSP) and optimization method. An average FPR of 0.3 FPs/h was obtained for the MI-CSP-based brain switch, and the average triggering time improved to 21.6 s.Significance.This study provides a new approach that could significantly reduce the brain switch's FPR to less than 1 Fps/h, which was less than 10% of the FPR (decreasing by more than a magnitude of order) by other endogenous methods, and the reaction time was comparable to the state-of-the-art approaches. This represents a significant advancement over the current non-invasive asynchronous BCI and will open widespread avenues for translating BCI towards clinical applications.