Antiviral efficacy of RAY1216 monotherapy and combination therapy with ritonavir in patients with COVID-19: a phase 2, single centre, randomised, double-blind, placebo-controlled trial.

Background: This study aimed to evaluate the efficacy and safety of RAY1216, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in adults with coronavirus disease 2019 (COVID-19). Methods: This phase 2, single centre, randomised, double-blind, placebo-controlled trial included hospitalised patients between August 14, 2022, and September 26, 2022, in Sanya Central Hospital (The Third People's Hospital of Hainan Province) in China with no severe symptoms if they had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for not more than 120 h (5 days) and a real-time quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) value of ≤30 for both the open reading frames 1 ab (ORF1ab) and nucleocapsid (N) genes within 72 h before randomisation. Half of the participants (n = 30) were randomly assigned (2:1) to receive either RAY1216 or a matched placebo three times a day (TID) for 5 days (15 doses in total), while the other half received RAY1216 plus ritonavir (RAY1216 plus RTV) or a matched placebo every 12 h for 5 days (10 doses in total). The primary endpoint was the time of viral clearance. Secondary outcomes included the changes of the SARS-CoV-2 RNA viral load, the positivity rate of the nucleic acid test, and the recovery time of clinical symptoms. A safety evaluation was performed to record and analyse all adverse events that occurred during and after drug administration as well as any cases in which dosing was halted because of these events. Clinicaltrials.gov identifier: ChiCTR2200062889. Findings: The viral shedding times in the RAY1216 and RAY1216 plus RTV groups were 166 h (95% confidence interval (CI): 140-252) and 155 h (95%CI: 131-203), respectively, which were 100 h (4.2 days) and 112 h (4.6 days) shorter than that of the placebo group, respectively (RAY1216 group vs. Placebo p = 0.0060, RAY1216 plus RTV group vs. Placebo p = 0.0001). At 24 h, 72 h, and 120 h after administration, the viral RNA loads in the RAY1216 and RAY1216 plus RTV groups were significantly less than those of the placebo groups. At 280 h (11.5 days) after administration, the nucleic acid test results in the RAY1216 and RAY1216 plus RTV groups were both negative. The common adverse events related to the investigational drugs were mild and self-limiting laboratory examination abnormalities. Interpretation: Our findings suggest that RAY1216 monotherapy and RAY1216 plus ritonavir both demonstrated significant antiviral activity and reduced the duration of COVID-19 while maintaining a satisfactory safety profile. Considering the limited clinical application of RTV, it is recommended to use RAY1216 alone to further verify its efficacy and safety. Funding: This study was sponsored by the Key Research and Development Program of China (2022YFC0868700).

Cellular and Molecular Roles of Immune Cells in the Gut-Brain Axis in Migraine.

Migraine is a complex and multi-system dysfunction. The realization of its pathophysiology and diagnosis is developing rapidly. Migraine has been linked to gastrointestinal disorders such as irritable bowel syndrome and celiac disease. There is also direct and indirect evidence for a relationship between migraine and the gut-brain axis, but the exact mechanism is not yet explained. Studies have shown that this interaction appears to be influenced by a variety of factors, such as inflammatory mediators, gut microbiota, neuropeptides, and serotonin pathways. Recent studies suggest that immune cells can be the potential tertiary structure between migraine and gut-brain axis. As the hot interdisciplinary subject, the relationship between immunology and gastrointestinal tract is now gradually clear. Inflammatory signals are involved in cellular and molecular responses that link central and peripheral systems. The gastrointestinal symptoms associated with migraine and experiments associated with antibiotics have shown that the intestinal microbiota is abnormal during the attacks. In this review, we focus on the mechanism of migraine and gut-brain axis, and summarize the tertiary structure between immune cells, neural network, and gastrointestinal tract.

Investigation of the potential ameliorative effects of DHA-enriched phosphatidylserine on bisphenol A-induced murine nephrotoxicity.

In order to investigate the amelioration of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced nephrotoxicity, the murine nephrotoxicity model was established by intragastric administration of BPA (5 mg/kg/B.W.) for 6 weeks. The biochemical indices, hematoxylin-eosin (H&E) staining, kidney metabolomics, and related protein expression levels of SIRT1-AMPK pathway were then determined. Our results indicated that DHA-PS (100 mg/kg/B.W.) ameliorated the BPA-induced nephrotoxicity after 6 weeks of intragastric administration, primarily by decreasing the serum creatinine (CRE) and blood urea nitrogen (BUN), renal inflammatory cytokines and lipid levels, and increasing the antioxidant enzyme activities. In addition, the untargeted metabolomics of the kidney indicated that BPA perturbed the tryptophan metabolism, pyridine metabolism, and valine, leucine, and isoleucine biosynthesis, while DHA-PS administration significantly affected the glycerophospholipid metabolism, valine, leucine, and isoleucine biosynthesis to ameliorate the BPA-induced metabolic disorder. Moreover, DHA-PS administration could ameliorate the BPA-induced lipid disturbance by upregulating the expressions of AMPKα1, SIRT1, and PPARα while downregulating the expression of SREBP-1c through the SIRT1-AMPK pathway. This is the first time that the amelioration effects of DHA-PS on BPA-induced nephrotoxicity have been investigated from multiple perspectives, suggesting that DHA-PS might be a potential dietary supplement for reducing BPA-induced nephrotoxicity.

Clinical Analysis of the Frosch Approach in the Treatment of Posterolateral Tibial Plateau Fractures Combined with Lateral Tibial Plateau Fractures.

OBJECTIVE: The treatment of posterolateral tibial plateau fractures is difficult, and providing sufficient exposure and effective fixation is a challenge. There is great controversy regarding the surgical approach for posterolateral tibial plateau fractures. The purpose of the study was to investigate the clinical effects of open reduction and internal fixation using the Frosch approach for the treatment of posterolateral tibial plateau fractures combined with lateral tibial plateau fractures. METHODS: Data from 19 patients with posterolateral tibial plateau fractures combined with lateral tibial plateau fractures treated from May 2018 to January 2022 were retrospectively analyzed. There were nine men and 10 women, ranging in age from 22 to 62 years, with an average age of 45.6 years. All patients were treated using the Frosch approach. Under direct vision, the posterolateral and lateral fractures were reduced, and full bone grafting was performed. We reshaped the oblique "T" shaped plate for the distal radius and placed it on the posterolateral tibial plateau to fix the posterolateral fractures. The lateral inverted "L" shaped locking plate was placed on the lateral tibial plateau to fix the lateral tibial plateau fractures. Within 2 weeks after the operation, the patients were instructed to perform knee joint function exercises within 90°. At the last follow-up, the Rasmussen radiological criteria were used to evaluate the effectiveness of fracture reduction and fixation. And the knee joint function was evaluated using Rasmussen functional score. RESULTS: The operation time ranged from 100 to 180 min, with an average of 134.2 min; intraoperative blood loss ranged from 20 to 150 mL, with an average of 66.8 mL. The follow-up duration ranged from 14 to 58 months, with an average of 36.2 months. There were no complications, such as vascular or nerve injury or incision infection. Fracture healing was achieved in all patients, and the healing time ranged from 10 to 14 weeks, with an average of 11.2 weeks. During the follow-up period, there was no loosening or breakage of the internal fixation, varus or valgus deformity of the knee joint, re-collapse of the articular surface, or instability of the knee joint. At the last follow-up, the effectiveness of fracture reduction and fixation was excellent in 13 patients and good in six patients. And the knee joint function was excellent in 17 patients and good in two patients. CONCLUSION: The Frosch approach for open reduction and internal fixation in the treatment of posterolateral tibial plateau fractures combined with lateral tibial plateau fractures has a definite clinical benefit and is worthy of promotion and application.

Alveolar Bone Morphologic Predictors for Guided Bone Regeneration Outcome in Anterior Maxilla.

OBJECTIVES: This study aimed to explore the influence of alveolar bone morphologic variables on the outcome of guided bone regeneration (GBR) in the anterior maxilla region. METHODS: Twenty-eight patients who received single maxillary anterior tooth delayed implant placed simultaneously with GBR were recruited. Baseline data including age, gender, implant site, implant brand, and bone graft materials were recorded. The resorption rate of the grafted bone (RRGB), labial bone width at 0 mm, 2 mm, and 4 mm apical to the implant platform at Tn (LBW0Tn, LBW2Tn, LBW4Tn), implant angulation (IA), maximum bone graft thickness (MBGT), bone graft volume (BGV), and the initial bone morphologic variables bone concavity depth (BCD) and bone concavity angulation (BCA) were measured. The Pearson correlation analysis, analysis of variance (ANOVA), and optimal binning method were used to explore the potential predictors for GBR. RESULTS: Among 28 patients, the labial bone width of implant and bone graft volume decreased significantly when measured 6 months after surgery. The mean percentage of RRGB was 49.78%. RRGB was not correlated with gender, age, bone graft material, IA, MBGT, bone graft volume at T1, implant site, and implant brand (P > .05). BCD and BCA were each moderately correlated with RRGB (r = -0.872 [P < .001] and r = 0.686 [P < .001], respectively). A BCD ≥1.03 mm and a BCA <155.30° resulted in a significantly lower percentage of RRGB (P < .001). CONCLUSIONS: A significant grafted bone materials volume reduction was detected after GBR with collagen membrane and deproteinized bovine bone mineral (DBBM). The initial bone morphology can influence GBR outcome, and a bone concavity with a depth ≥1.03 mm and an angulation <155.30° led to a lower RRGB. BCD and BCA can be used as variables to predict the outcome of GBR.

Clinical Characteristics and Treatment of Listeria monocytogenes Infections in the Central Nervous System.

Purpose: Listeria monocytogenes infections are rare in the central nervous system (CNS) and frequently difficult-to-diagnose. Our goal is to assess CNS listeriosis patients' clinical characteristics, diagnosis, treatment, and prognosis. Patients and Methods: Patients with CNS listeriosis admitted to the Department of neurology, the first medical center of the Chinese PLA general hospital, were enrolled in this study from March 2018 to August 2022. Results: This study analyzed eight adults, including five males and three females. The average age of onset was (50.25 ± 11.52) years. The clinical manifestations included fever, headache, altered mental status, vomiting, seizures, neck rigidity, hemiplegia and cranial nerve palsies. Cerebrospinal fluid (CSF) tests revealed intracranial hypertension, elevated cell count and protein concentration, and decreased glucose levels. The positive rates of blood and CSF culture were 40% and 28.57%, respectively. All patients underwent CSF metagenomic next-generation sequencing (mNGS), with a 100% positive rate and the specific read number 12-20394. Magnetic resonance imaging (MRI) exhibited leptomeningitis, meningoencephalitis, and brain abscess, and no specific changes were discovered in two patients. All patients received antibiotic treatment, seven were cured, and one died. Conclusion: Monitoring the proportion of monocytes in blood and mNGS results of CSF can play a crucial role in diagnosing pathogens. Early and sufficient application of two to three sensitive antibiotics with a BBB permeability of 20-30% for at least 2-3 months can significantly improve CNS listeriosis prognosis.

Strontium alleviated the growth inhibition and toxicity caused by cadmium in rice seedlings.

Cadmium (Cd) contamination of rice is an urgent ecological and agricultural problem. Strontium (Sr) has been shown to promote plant growth. However, the effect of Sr on rice seedlings under Cd stress is currently unclear. In this work hydroponic experiments were used to assess the impact of Sr on rice seedling growth under Cd stress. The findings demonstrated that foliar application of 0.5 mg L-1 Sr had no discernible impact on the development of rice seedlings. However, Sr significantly alleviated growth inhibition and toxicity in rice seedlings when threatened by Cd. Compared with the Cd treatment (Cd, 2.5 mg L-1), the root length, shoot height, and whole plant length of rice seedlings in the Cd + Sr treatment (Cd, 2.5 mg L-1; Sr, 0.5 mg L-1) increased by 4.96 %, 12.47 % and 9.60 %, respectively. The content of Cd in rice decreased by 23.34 % (roots) and 5.79 % (shoots). Sr lessened the degree of membrane lipid peroxidation damage (lower MDA concentration) among the seedlings of rice under Cd stress by controlling the activities of antioxidant enzymes and GSH content. By changing the expression of antioxidant enzyme-encoding genes and downregulating the heavy metal transporter gene (OsNramp5), Sr reduced accumulation and the detrimental effects of Cd on rice seedlings. Our study provides a new solution to the problem of Cd contamination in rice, which may promote the safe production of rice and benefit human health.

Diagnostic value of high-frequency ultrasound (HFUS) in evaluation of subcutaneous lesions.

BACKGROUND: It is unknown whether high-frequency ultrasound (HFUS) can evaluate invisible subcutaneous lesions. We aimed to investigate the diagnostic value of HFUS in invisible subcutaneous lesions. METHOD: Patients with invisible subcutaneous lesions were prospectively recruited from two centres. Before undergoing biopsy or surgery, each lesion was independently evaluated by two clinicians. One provides a clinical diagnosis by only clinical examination and the other provides an integrated diagnosis by combining clinical examination and HFUS information. Diagnoses were classified as correct, wrong, and indeterminate. A total of 391 lesions from 355 patients were enrolled, including 225 epidermoid cysts, 77 lipomas, 25 pilomatrixomas, 21 haemangiomas, 19 dermatofibromas, 11 dermatofibrosarcoma protuberans (DFSP), 7 neurofibromas, and 6 leiomyomas. Using pathological results as the gold standard, diagnostic performance was compared. RESULTS: The number of correct diagnoses increased from 185 (47.3%) by clinical examination alone to 316 (80.8%) after the addition of HFUS (P < 0.05). Meanwhile, the indeterminate diagnosis rate decreased from 143 (36.6%) to 10 (2.6%). Using HFUS, the accuracy improved significantly for epidermoid cysts (59.6% vs. 86.7%), lipomas (50.6% vs. 94.8%), pilomatrixomas (0% vs. 48.0%), haemangiomas (23.8% vs. 57.1%), and DFSPs (0% vs. 81.8%) (all p < 0.05). However, HFUS did not significantly improve the diagnostic accuracy of dermatofibromas (15.8% vs. 21.1%, p > 0.999), neurofibromas (42.9% vs. 71.4%, p = 0.625), or leiomyomas (16.7% vs. 100%, p = 0.063). CONCLUSION: Combining HFUS and clinical examination can generally improve the diagnostic accuracy and decrease the indeterminacy of invisible subcutaneous lesions, especially epidermoid cysts, lipomas, pilomatrixomas, haemangiomas, and DFSPs. However, for some rare lesions, HFUS cannot provide useful information.

Characterization of N-Terminal Asparagine Deamidation and Clipping of a Monoclonal Antibody.

This study presents a novel degradation pathway of a human immunoglobulin G (IgG) molecule featuring a light chain N-terminal asparagine. We thoroughly characterize this pathway and investigate its charge profiles using cation exchange chromatography (CEX) and capillary isoelectric focusing (cIEF). Beyond the well-documented asparagine deamidation into isoaspartic acid, aspartic acid, and succinimide intermediate, a previously unreported clipping degradation pathway is uncovered. This newly identified clipped N-terminal IgG variant exhibits a delayed elution in CEX, categorized as a "basic variant", while retaining the same main peak isoelectric point (pI) in cIEF. The influence of temperature and pH on N-terminal asparagine stability is assessed across various stressed conditions. A notable correlation between deamidation percentage and clipped products is established, suggesting a potential hydrolytic chemical reaction underlying the clipping process. Furthermore, the impact of N-terminal asparagine modifications on potency is evaluated through ELISA binding assays, revealing minimal effects on binding affinity. Sequence alignment reveals homology to a human IgG with the germline gene from Immunoglobulin Lambda Variable 6-57 (IGLV6-57), which has implications for amyloid light-chain (AL) amyloidosis. This discovery of the N-terminal clipping degradation pathway contributes to our understanding of immunoglobulin light chain misfolding and amyloid fibril deposition under physiological conditions.

Long-Term Exposure to Microcystin-LR Induces Gastric Toxicity by Activating the Mitogen-Activated Protein Kinase Signaling Pathway.

Previous studies have primarily concentrated on the hepatotoxicity of MC-LR, whereas its gastric toxicity effects and mechanisms of long-term exposure under low dosage remain unknown. Herein, the gastric tissue from C57BL/6 mice fed with drinking water contaminated by low-dose MC-LR (including 1, 60, and 120 µg/L) was investigated. The results obtained showed that exposure to different concentrations of MC-LR resulted in significant shedding and necrosis of gastric epithelial cells in mice, and a down-regulation of tight junction markers, including ZO-1, Claudin1, and Occludin in the stomach, which might lead to increased permeability of the gastric mucosa. Moreover, the protein expression levels of p-RAF/RAF, p-ERK1/2/ERK1/2, Pink1, Parkin, and LC3-II/LC-3-I were increased in the gastric tissue of mice exposed to 120 µg/L of MC-LR, while the protein expression level of P62 was significantly decreased. Furthermore, we found that pro-inflammatory factors, including IL-6 and TNF-ɑ, were dramatically increased, while the anti-inflammatory factor IL-10 was significantly decreased in the gastric tissue of MC-LR-exposed mice. The activation of the MAPK signaling pathway and mitophagy might contribute to the development of gastric damage by promoting inflammation. We first reported that long-term exposure to MC-LR induced gastric toxicity by activating the MAPK signaling pathway, providing a new insight into the gastric toxic mechanisms caused by MC-LR.

Lactobacillus fermentum Alleviates the Colorectal Inflammation Induced by Low-Dose Sub-Chronic Microcystin-LR Exposure.

Microcystin-LR (MC-LR) contamination is a worldwide environmental problem that poses a grave threat to the water ecosystem and public health. Exposure to MC-LR has been associated with the development of intestinal injury, but there are no effective treatments for MC-LR-induced intestinal disease. Probiotics are "live microorganisms that are beneficial to the health of the host when administered in sufficient quantities". It has been demonstrated that probiotics can prevent or treat a variety of human diseases; however, their ability to mitigate MC-LR-induced intestinal harm has not yet been investigated. The objective of this study was to determine whether probiotics can mitigate MC-LR-induced intestinal toxicity and its underlying mechanisms. We first evaluated the pathological changes in colorectal tissues using an animal model with sub-chronic exposure to low-dose MC-LR, HE staining to assess colorectal histopathologic changes, qPCR to detect the expression levels of inflammatory factors in colorectal tissues, and WB to detect the alterations on CSF1R signaling pathway proteins in colorectal tissues. Microbial sequencing analysis and screening of fecal microorganisms differential to MC-LR treatment in mice. To investigate the role of microorganisms in MC-LR-induced colorectal injury, an in vitro model of MC-LR co-treatment with microorganisms was developed. Our findings demonstrated that MC-LR treatment induced an inflammatory response in mouse colorectal tissues, promoted the expression of inflammatory factors, activated the CSF1R signaling pathway, and significantly decreased the abundance of Lactobacillus. In a model of co-treatment with MC-LR and Lactobacillus fermentum (L. fermentum), it was discovered that L. fermentum substantially reduced the incidence of the colorectal inflammatory response induced by MC-LR and inhibited the protein expression of the CSF1R signaling pathway. This is the first study to suggest that L. fermentum inhibits the CSF1R signaling pathway to reduce the incidence of MC-LR-induced colorectal inflammation. This research may provide an excellent experimental foundation for the development of strategies for the prevention and treatment of intestinal diseases in MC-LR.

Solving the issue of increasing forming voltage during device miniaturization in hafnium oxide-based resistive access memory using high-k sidewall material.

An electrothermal coupling model of resistive random access memory (RRAM) was established based on the oxygen vacancy conduction mechanism. By resolving the partial differential equation for the coefficients, the variation process of the device resistance was simulated. In our studies, a device model was proposed which can accurately simulate the whole process of RRAM forming, reset, and set. Based on the established model, a new high dielectric constant (high-k) material (La2O3) is introduced as the sidewall material. The La2O3 sidewall material can concentrate the electric field and helps to speed up the formation of conductive filaments. The La2O3 sidewall can effectively reduce the forming voltage increase during the miniaturization process. Then, the influence of sidewall thermal conductivity on forming voltage is studied, and it is discovered that low thermal conductivity helps to reduce the model's forming voltage and increase the temperature concentration. These findings serve as a foundation for more studies on the choice of sidewall materials.

Toward Sub-Terahertz: Space-Time Coding Metasurface Transmitter for Wideband Wireless Communications.

A space-time coding metasurface (STCM) operating in the sub-terahertz band to construct new-architecture wireless communication systems is proposed. Specifically, a programmable STCM is designed with varactor-diode-tuned metasurface elements, enabling precise regulation of harmonic amplitudes and phases by adjusting the time delay and duty cycle of square-wave modulation signal loaded on the varactor diodes. Independent electromagnetic (EM) regulations in the space and time domains are achieved by STCM to realize flexible beam manipulations and information modulations. Based on these features, a sub-terahertz wireless communication link is constructed by employing STCM as a transmitter. Experimental results demonstrate that the STCM supports multiple modulation schemes including frequency-shift keying, phase-shift keying, and quadrature amplitude modulations in a wide frequency band. It is also shown that the STCM is capable of realizing wide-angle beam scanning in the range of ±45o , which offers an opportunity for user tracking during the communication. Thus, the STCM transmitter with high device density and low power consumption can provide low-complexity, low-cost, low-power, and low-heat solutions for building the next-generation wireless communication systems in the sub-terahertz frequency and even terahertz band.

Predictive value of reduced pulmonary arterial elasticity in acute pulmonary embolism for right ventricular dysfunction.

BACKGROUND: Computed tomography pulmonary angiography (CTPA) yields indices, such as the right ventricular/left ventricular (RV/LV) ratio > 1.0, which are commonly used for risk stratification of patients with acute pulmonary embolism (APE). Although pulmonary artery elasticity (PAE) has been previously described, its relationship with right ventricular dysfunction (RVD) has not been explored. Here, we investigated whether PAE, measured using CTPA, is associated with RVD. METHODS: Patients who underwent retrospective electrocardiogram-gated CTPA and had a definitive diagnosis of APE were included in the study. The subjects were classified into RVD and non-RVD groups according to the RVD on echocardiography. PAE, involving aortic distensibility (AD), aortic compliance (AC), and aortic stiffness (ASI), and right heart function indices were compared between the two groups, and their correlations were examined. Receiver operating characteristic (ROC) curves were generated to evaluate the specificity and sensitivity of the RVD prediction. RESULTS: Thirty-five patients with APE were enrolled in the study (RVD: 18, non-RVD: 17). The groups showed no significant differences in age, sex, number of patients receiving thrombolysis, and number of high-risk conditions (P > 0.05). Regarding PAE parameters, AD was significantly reduced in the RVD group compared to that in the non-RVD group (P < 0.05), whereas AC and ASI were not statistically different (P > 0.05). The ratio of the maximum cross-sectional area of PA and AA (PA/AAmax),the ratio of the minimum cross-sectional area of PA and AA(PA/AAmin), diameter of the coronary sinus, RV/LV diameter, RV/Lvarea, the ratio of the end-diastolic volume of right ventricular and left ventricular (RV/LVDV), the ratio of the end-systolic volume of right ventricular and left ventricular (RV/LVSV) were significantly greater in the RVD group than in the non-RVD group (P < 0.05). Correlation analysis of AD and right heart function parameters showed that AD was negatively correlated with PA/AAmax, PA/AAmin, RV/LV diameter, RV/LVDV, and PAE measured by ultrasound, with correlation coefficients ranging from - 0.336 to - 0.580 (P < 0.05). The ROC curves of AD and RV/LVdiameter to predict RVD had areas under the curve of 0.748 and 0.712, sensitivities of 82.35% and 70.59%, specificities of 66.67% and 72.22%, and cutoff values of 4.9433 and 1.1105, respectively. CONCLUSION: AD obtained by retrospective ECG-gated CTPA may be helpful in assessing RVD in patients with APE while accurately diagnosing APE. It contributes to timely diagnosis and treatment and improves the prognosis of patients with APE.

Comparison of supercritical fluid chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry for the stereoselective analysis of chlorfenvinphos and dimethylvinphos in tobacco.

This study used reversed-phase liquid chromatography-tandem mass spectrometry and supercritical fluid chromatography-tandem mass spectrometry for determination of the stereoisomers of chlorfenvinphos and dimethylvinphos in tobacco. Tobacco samples were extracted and purified with a modified quick, easy, cheap, effective, rugged, and safe technique using spherical carbon. The performance of both methodologies was comprehensively compared in terms of methods validation parameters (separation efficiency, linearity, selectivity, recovery, repeatability, sensitivity, matrix effect, etc.). Under optimized conditions, the calibration curves of the stereoisomers of chlorfenvinphos and dimethylvinphos in the range of 10-500 ng/mL showed excellent linearity with R2 ≥ 0.997 in both methods. The adequate recoveries of analytes from three different spiked tobaccos were obtained using reversed-phase liquid chromatography-tandem mass spectrometry (86.1-95.7%) as well as supercritical fluid chromatography-tandem mass spectrometry (86.5-94.0%). The relative standard deviations for spiked samples were all below 7.0%. Compared with supercritical fluid chromatography-tandem mass spectrometry, lower matrix effects and LODs can be obtained in reversed-phase liquid chromatography-tandem mass spectrometry.

UAV-WPT System Based on Novel Magnetic Structure and Model Predictive Control.

In this paper, a UAV-WPT based on a new orthogonal coupling structure is first designed. An offset weight method is proposed to optimize the design of the system resonance parameters to improve the power transmission efficiency in the offset state. The coupling mechanism's coupling ability and anti-offset performance are experimented with using Ansys software simulation. The system adopts LCC-S topology and proposes a secondary side constant current control strategy based on the model prediction control to ensure constant current output in the case of coupling coefficient deviation. Finally, an experimental platform is designed for experiments. The results show that the system can quickly realize 3A constant current output under the change of load and coupling coefficient, and at the same time, improve the working efficiency of the system.

Detection of Ferroptosis in Models of Brain Diseases.

Ferroptosis is a regulated form of non-apoptotic cell death driven by iron-dependent lipid peroxidation. In the past decade, ferroptosis has been reported to be involved in the pathological role in the central nervous system degenerative diseases (e.g., Alzheimer's disease, Huntington's disease, and Parkinson's disease), stroke, traumatic brain injury, and brain tumor. However, how to reliably detect and classify ferroptosis from other cell death in pathological conditions remains a great challenge, especially in primary brain cells and brain tissues. Here, we summarize the methods and protocols (such as real-time PCR, western blotting, immunofluorescence staining, lipid peroxidation assay kits and probe, immunofluorescence staining, GPX activity and glutathione depletion assay kits, iron detection, and TEM) used in the present study to detect and classify ferroptosis in the brain.

Epigenetically upregulating TROP2 and SLFN11 enhances therapeutic efficacy of TROP2 antibody drug conjugate sacitizumab govitecan.

TROP2 antibody drug conjugates (ADCs) are under active development. We seek to determine whether we can enhance activity of TROP2 ADCs by increasing TROP2 expression. In metaplastic breast cancers (MpBC), there is limited expression of TROP2, and downregulating transcription factor ZEB1 upregulates E-cad and TROP2, thus sensitizing cancers to TROP2 ADC sacituzumab govitecan (SG). Demethylating agent decitabine decreases DNA methyltransferase expression and TROP2 promoter methylation and subsequently increases TROP2 expression. Decitabine treatment as well as overexpression of TROP2 significantly enhance SG antitumor activity. Decitabine also increases SLFN11, a biomarker of topoisomerase 1 inhibitor (TOP1) sensitivity and is synergistic with SG which has a TOP1 payload, in TROP2-expressing SLFN11-low BC cells. In conclusion, TROP2 and SLFN11 expression can be epigenetically modulated and the combination of demethylating agent decitabine with TROP2 ADCs may represent a novel therapeutic approach for tumors with low TROP2 or SLFN11 expression.