Roles of soil minerals in the degradation of chlorpyrifos and its intermediate by microwave activated peroxymonosulfate.

Soil mineral is one of the important factors that affecting oxidant decomposition and pollutants degradation in soil remediation. In this study, the effects of iron minerals, manganese minerals and clay minerals on the degradation of chlorpyrifos (CPF) and its intermediate product 3,5,6-trichloro-2-pyridinol (TCP) by microwave (MW) activated peroxymonosulfate (PMS) were investigated. As a result, the addition of minerals had slight inhibitory effect on the degradation efficiency of CPF by MW/PMS, but the degradation efficiency of TCP was improved by the addition of some specific minerals, including ferrihydrite, birnessite, and random symbiotic mineral of pyrolusite and ramsdellite (Pyr-Ram). The stronger MW absorption ability of minerals is beneficial for PMS decomposition, but the MW absorption ability of minerals cannot be fully utilized because of the weaker MW radiation intensity under constant temperature conditions. Through electron spin resonance test, quenching experiment and electrochemical experiment, electron transfer, SO4- and OH, SO4- dominated TCP degradation by MW/PMS with the addition of birnessite, Pyr-Ram and ferrihydrite, respectively. Besides, the adsorption effect of ferrihydrite also enhanced the removal of TCP. The redox of Mn (III)/Mn (IV) or Fe (II)/Fe (III) in manganese/iron minerals participated in the generation of reactive species. In addition, the addition of minerals not only increased the variety of alkyl hydroxylation products of CPF, causing different degradation pathways from CPF to TCP, but also further degraded TCP to dechlorination or hydroxylation products. This study demonstrated the synergistic effect of minerals and MW for PMS activation, provided new insights for the effects of soil properties on soil remediation by MW activated PMS technology.

Heavy metals remediation through lactic acid bacteria: Current status and future prospects.

With the development of industrialization and urbanization, heavy metal (HM) pollution has become an urgent problem in many countries. The use of microorganisms to control HM pollution has attracted the attention of many scholars due to its advantages of mild conditions, low process cost, and no secondary pollution. In this context, this review aimed to compile recent advances on the potential of lactic acid bacteria (LAB) as HMs biosorbents. As a food-safe class of probiotic, LAB can not only be used for HM remediation in soil and wastewater, but most importantly, can be used for metal removal in food. The extracellular adsorption and intracellular accumulation are the main mechanisms of HM removal by LAB. Lactic acid (LA) fermentation is also one of the removal mechanisms, especially in the food industry. The pH, temperature, biomass, ion concentration and adsorption time are the essential parameters to be considered during the bioremediation. Although the LAB remediation is feasible in theory and lab-scale experiments, it is limited in practical applications due to its low efficiency. Therefore, the commonly used methods to improve the adsorption efficiency of LAB, including pretreatment and mixed-cultivation, are also summarized in this review. Finally, based on the review of literature, this paper presents the emerging strategies to overcome the low adsorption capacity of LAB. This review proposes the future investigations required for this field, and provides theoretical support for the practical application of LAB bioremediation of HMs.

Saccharide mapping as an extraordinary method on characterization and identification of plant and fungi polysaccharides: A review.

Saccharide mapping was a promising scheme to unveil the mystery of polysaccharide structure by analysis of the fragments generated from polysaccharide decomposition process. However, saccharide mapping was not widely applied in the polysaccharide analysis for lacking of systematic introduction. In this review, a detailed description of the establishment process of saccharide mapping, the pros and cons of downstream technologies, an overview of the application of saccharide mapping, and practical strategies were summarized. With the updating of the available downstream technologies, saccharide mapping had been expanding its scope of application to various kinds of polysaccharides. The process of saccharide mapping analysis included polysaccharides degradation and hydrolysates analysis, and the degradation process was no longer limited to acid hydrolysis. Some downstream technologies were convenient for rapid qualitative analysis, while others could achieve quantitative analysis. For the more detailed structure information could be provided by saccharide mapping, it was possible to improve the quality control of polysaccharides during preparation and application. This review filled the blank of basic information about saccharide mapping and was helpful for the establishment of a professional workflow for the saccharide mapping application to promote the deep study of polysaccharide structure.

High-power distributed feedback laser diode arrays with narrow spectral width over a wide temperature range.

High-power semiconductor lasers with stabilized wavelengths are recognized as exemplary pumping sources for solid-state lasers. This study introduces distributed feedback (DFB) laser diode arrays designed to maintain an extensive temperature locking range. We report experimentally on high-power 808 nm DFB laser diode arrays. The first-order sinusoidal grating was fabricated using nanoimprint lithography, succeeded by inductively coupled plasma (ICP) dry etching and subsequent wet polishing. These 808 nm DFB laser diode arrays have demonstrated a measured output power of 134 W under a pulsed current of 150 A, with the heat sink temperature maintained at 25°C. The slope efficiency was determined to be 1.1 W/A. At a current of 150 A, the laser operated with a narrow spectral width over a wide temperature range, extending from -30 to 90°C, with a temperature drift coefficient of 0.0595 nm/K.

Risks for prolonged mechanical ventilation and reintubation after cervical malignant tumor surgery: a nested case-control study.

PURPOSE: Prolonged mechanical ventilation (PMV) and reintubation are among the most serious postoperative adverse events associated with malignant cervical tumors. In this study, we aimed to clarify the incidence, characteristics, and risk factors for PMV and reintubation in target patients. METHODS: This retrospective nested case-control study was performed between January 2014 and January 2020 at a large spinal tumor center in China. Univariate analysis was used to identify the possible risk factors associated with PMV and reintubation. Logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) with covariates of a probability < 0.05 in univariate analysis. RESULTS: From a cohort of 560 patients with primary malignant (n = 352) and metastatic (n = 208) cervical tumors, 27 patients required PMV and 20 patients underwent reintubation. The incidence rates of PMV and reintubation were 4.82% and 3.57%, respectively. Three variables (all p < 0.05) were independently associated with an increased risk of PMV: Karnofsky Performance Status < 50 compared to ≥ 80, operation duration ≥ 8 h compared to < 6 h, and C4 nerve root encased by the tumor. Longer operative duration and preoperative hypercapnia (all p < 0.05) were independent risk factors for postoperative reintubation, both of which led to longer length of stay (32.6 ± 30.8 vs. 10.7 ± 5.95 days, p < 0.001), with an in-hospital mortality of 17.0%. CONCLUSION: Our results demonstrate the risk factors for PMV or reintubation after surgery for malignant cervical tumors. Adequate assessment, early detection, and prevention are necessary for this high-risk population.

Efficient Trifluoromethylation of Halogenated Hydrocarbons Using Novel [(bpy)Cu(O2CCF2SO2F)2] Reagent.

This study introduces a novel trifluoromethylating reagent, [(bpy)Cu(O2CCF2SO2F)2], notable for not only its practical synthesis from cost-effective starting materials and scalability but also its nonhygroscopic nature. The reagent demonstrates high efficiency in facilitating trifluoromethylation reactions with various halogenated hydrocarbons, yielding products in good yields and exhibiting broad functional group compatibility. The development of [(bpy)Cu(O2CCF2SO2F)2] represents an advancement in the field of organic synthesis, potentially serving as a valuable addition to the arsenal of existing trifluoromethylating agents.

Mechanisms of gastrointestinal toxicity in neuromyelitis optica spectrum disorder patients treated with mycophenolate mofetil: insights from a mouse model and human study.

Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial ß-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The ß-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF. IMPORTANCE: Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

An innovative approach to improving lactic acid production from food waste using iron tailings.

In this study, the feasibility of promoting the lactic acid (LA) fermentation of food waste (FW) with iron tailings (ITs) addition was explored. The best LA yield was 0.91 g LA/g total sugar when 1 % ITs were added into the system. The mechanisms for promoting LA production were acidification alleviation effects and reduction equivalent supply of ITs. Furthermore, the addition of ITs promoted carbohydrate hydrolysis, and the carbohydrates digestibility reached 88.85 % in the 1 % ITs group. The ITs also affected the microbial communities, Lactococcus gradually replaced Streptococcus as the dominant genus, and results suggested that Lactococcus had a positive correlation with LA production and carbohydrate digestibility. Finally, the complex LAB in FW had significant effects on heavy metal removal from ITs, and the removal efficiency Cr, As, Pb, Cd, and Hg can reach 50.84 %, 26.72 %, 59.65 %, 49.75 % and 78.87 % in the 1 % ITs group, respectively.

Discovery of small molecule guanylyl cyclase B receptor positive allosteric modulators.

Myocardial fibrosis is a pathological hallmark of cardiovascular disease (CVD), and excessive fibrosis can lead to new-onset heart failure and increased mortality. Currently, pharmacological therapies for myocardial fibrosis are limited, highlighting the need for novel therapeutic approaches. The particulate guanylyl cyclase B (GC-B) receptor possesses beneficial antifibrotic actions through the binding of its natural ligand C-type natriuretic peptide (CNP) and the generation of the intracellular second messenger, cyclic guanosine 3',5'-monophosphate (cGMP). These actions include the suppression of fibroblast proliferation and reduction in collagen synthesis. With its abundant expression on fibroblasts, the GC-B receptor has emerged as a key molecular target for innovative CVD therapeutics. However, small molecules that can bind and potentiate the GC-B/cGMP pathway have yet to be discovered. From a cell-based high-throughput screening initiative of the NIH Molecular Libraries Small Molecule Repository and hit-to-lead evolution based on a series of structure-activity relationships, we report the successful discovery of MCUF-42, a GC-B-targeted small molecule that acts as a positive allosteric modulator (PAM). Studies herein support MCUF-42's ability to enhance the binding affinity between GC-B and CNP. Moreover, MCUF-42 potentiated cGMP levels induced by CNP in human cardiac fibroblasts (HCFs) and notably also enhanced the inhibitory effect of CNP on HCF proliferation. Together, our findings highlight that MCUF-42 is a small molecule that can modulate the GC-B/cGMP signaling pathway, potentially enhancing the antifibrotic actions of CNP. Thus, these data underscore the continued development of GC-B small molecule PAMs as a novel therapeutic strategy for targeting cardiac fibrosis and CVD.

Physician Transfer Versus Patient Transfer for Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Physician transfer is an alternate option to patient transfer for expedient performance of mechanical thrombectomy in patients with acute ischemic stroke. METHODS AND RESULTS: We conducted a systematic review to identify studies that evaluate the effect of physician transfer in patients with acute ischemic stroke who undergo mechanical thrombectomy. A search of PubMed, Scopus, and Web of Science was undertaken, and data were extracted. A statistical pooling with random-effects meta-analysis was performed to examine the odds of reduced time interval between stroke onset and recanalization, functional independence, death, and angiographic recanalization. A total of 12 studies (11 nonrandomized observational studies and 1 nonrandomized controlled trial) were included, with a total of 1894 patients. Physician transfer was associated with a significantly shorter time interval between stroke onset and recanalization with a pooled mean difference estimate of -62.08 (95% CI, -112.56 to -11.61]; P=0.016; 8 studies involving 1419 patients) with high between-study heterogeneity in the estimates (I2=90.6%). The odds for functional independence at 90 days were significantly higher (odds ratio, 1.29 [95% CI, 1.00-1.66]; P=0.046; 7 studies with 1222 patients) with physician transfer with low between-study heterogeneity (I2=0%). Physician transfer was not associated with higher odds of near-complete or complete angiographic recanalization (odds ratio, 1.18 [95% CI, 0.89-1.57; P=0.25; I2=2.8%; 11 studies with 1856 subjects). CONCLUSIONS: Physician transfer was associated with a significant reduction in the mean of time interval between symptom onset and recanalization and increased odds for functional independence at 90 days with physician transfer compared with patient transfer among patients who undergo mechanical thrombectomy.

Quantitative analysis of cement raw materials based on nanoparticle-enhanced laser-induced breakdown spectroscopy.

The nanoparticle-enhanced laser-induced breakdown spectroscopy (NELIBS) technique has attracted much attention because of its significant spectral enhancement as well as the reduction of spectral noise. More NELIBS studies have focused on the effect of nanoparticles on spectral intensity and the optimization of experiments. NELIBS has not been studied for the detection of cement raw material components and the repeatability of quantitative analysis. In this paper, the effect of NELIBS on the spectral quality as well as the repeatability of the quantitative analysis of cement raw materials is investigated. The effects of different AuNP sizes and volumes on LIBS brought about by pre-ablation were compared and modeled for quantitative analysis. The results showed that the signal-to-noise ratio (SNR) of NELIBS spectra after pre-ablation was improved from 2.72 to 7.81, and the relative standard deviations (RSDs) of CaO, SiO2, Al2O3, and Fe2O3 in cement raw materials were reduced by 47%, 30%, 31%, and 33%, respectively. In summary, this paper provides a comprehensive discussion and comparison of AuNPs versus LIBS for quantitative analysis of cement raw material components, and also provides a new solution for quantitative analysis of cement raw materials.

HMGA1 is a Prognostic Biomarker and Correlated with Glycolysis in Lung Adenocarcinoma.

Purpose: Lung cancer is one of the leading causes with high morbidity and mortality. High mobility group A1 (HMGA1) protein participates in the process of tumorigenesis. This study seeks to explore the specific role of HMGA1 in prognostic value based on The Cancer Genome Atlas (TCGA) database of Lung adenocarcinoma (LUAD) and glycolysis progression in LUAD cells. Patients and Methods: In this research, we compared HMGA1 mRNA expression between tumor tissues and normal samples and evaluated the correlations with clinical characteristics in LUAD patients based on the data of TCGA database. The survival outcome with overall survival (OS), disease-specific survival (DSS) and clinicopathologic characteristics associated were performed using the Kaplan-Meier method and Cox regression. In addition, gene-set enrichment analysis (GSEA) was carried out to explore the biological pathways that related to HMGA1. Cell experiments including cell proliferation assay and glycolysis proteins were performed with A549 and H1299 cells. Results: Our results revealed that HMGA1 mRNA expression was higher in LUAD tissues than in normal tissues. Increased HMGA1 expression in LUAD was associated with Gender (p<0.01), Pathologic stage I&II vs stage III&IV (p<0.001), T1&T2 vs T3&T4 stage (p<0.05), N0 vs N2 stage (p<0.01). Furthermore, multivariate analysis revealed that HMGA1 was an independent risk factor of OS and DSS for LUAD patients (p<0.05). HMGA1 were positively correlated with glycolysis gluconeogenesis pathway and glycolysis markers (HK2, GLUT1, PKM2, LDHA) based on GSEA and Gene Expression Profiling Interactive Analysis (GEPIA) database. At the cellular level, the results of qRT-PCR and western blot assays showed that si-HMGA1 markedly decreased the expression of glycolysis markers. HMGA1 promoted cell glycolysis progression via PI3K/AKT pathway transfected with HMGA1-plasmid and the treatment with 20 µM LY294002. Relevant animal experiments were also synchronously validated and si-HMGA1 groups down-regulated xenograft growth including the weights and size in tumor xenografts. Conclusions: In conclusion, our results suggested that HMGA1 was significantly correlated with poor survival for LUAD tissues and involved in the process of glycolysis in LUAD cells.

Brucellosis infection complicated with myelitis: a case report and literature review.

Brucellosis is a zoonotic disease caused by a Gram-negative coccus a facultative intracellular pathogen. Neurobrucellosis has an incidence rate of 3-7% among all patients with brucellosis, while spinal cord involvement is rare and carries a significant mortality risk. This report describes a case of brucellosis myelitis in a 55-year-old male patient who presented with recurrent paralysis, incontinence, and damage to the visual and auditory nerves. The diagnosis of neurobrucellosis involves a serum tube agglutination test, cerebrospinal fluid analysis, a physical examination of the nervous system, and a comprehensive review of the patient's medical history. The presence of brucellosis was confirmed in cerebrospinal fluid using MetaCAP™ sequencing. Treatment with a combination of rifampicin, doxycycline, ceftriaxone sodium, amikacin, compound brain peptide ganglioside, and dexamethasone resulted in significant improvement of the patient's clinical symptoms and a decrease in the brucellosis sequence count in cerebrospinal fluid. For the first time, MetaCAP™ sequencing has been used to treat pathogenic microbial nucleic acids, which could be a valuable tool for early diagnosis and treatment of neurobrucellosis.

Novel Acyl Thiourea-Based Hydrophobic Tagging Degraders Exert Potent Anti-Influenza Activity through Two Distinct Endonuclease Polymerase Acidic-Targeted Degradation Pathways.

The spread of the influenza virus has caused devastating pandemics and huge economic losses worldwide. Antiviral drugs with diverse action modes are urgently required to overcome the challenges of viral mutation and drug resistance, and targeted protein degradation strategies constitute excellent candidates for this purpose. Herein, the first degradation of the influenza virus polymerase acidic (PA) protein using small-molecule degraders developed by hydrophobic tagging (HyT) technology to effectively combat the influenza virus was reported. The SAR results revealed that compound 19b with Boc2-(L)-Lys demonstrated excellent inhibitory activity against A/WSN/33/H1N1 (EC50 = 0.015 µM) and amantadine-resistant strain (A/PR/8/H1N1), low cytotoxicity, high selectivity, substantial degradation ability, and good drug-like properties. Mechanistic studies demonstrated that the proteasome system and autophagic lysosome pathway were the potential drivers of these HyT degraders. Thus, this study provides a powerful tool for investigating the targeted degradation of influenza virus proteins and for antiviral drug development.

Research progress on the mechanism of acute hypertriglyceridemic pancreatitis.

ABSTRACT: The incidence rate of hypertriglyceridemia pancreatitis (HTGP) has experienced a notable increase in recent years, with eclipsing alcohol as the second leading cause of acute pancreatitis (AP). HTGP is often associated with more severe local and systemic complications. Recognized as a metabolic disorder hypertriglyceridemia (HTG), holds significant relevance in the pathogenesis of HTGP, yet its mechanisms are not fully understood. Both primary (genetic) and secondary (acquired) factors contribute to elevated triglyceride (TG) levels, which concurrently influence the progression of HTGP. This article presents a comprehensive review of the evolving research on HTGP pathogenesis, encompassing lipid synthesis and metabolism, calcium signal transduction, inflammatory mediators, endoplasmic reticulum stress, autophagy, mitochondrial injury by fatty acids, oxidative stress response, genetic factors, and gene mutations. By unraveling the intricate mechanisms underlying HTGP, this article aims to enhance physicians' understanding of the disease and facilitate the development of potential targeted pharmacological interventions for patients.

Rapid and sensitive visual detection of avian leukosis virus by reverse transcription loop-mediated isothermal amplification combined with a lateral flow immunochromatographic strip assay.

Considering that avian leukosis virus (ALV) infection has inflicted massive economic losses on the poultry breeding industry in most countries, its early diagnosis remains an important measure for timely treatment and control of the disease, for which a rapid and sensitive point-of-care test is required. We established a user-friendly, economical, and rapid visualization method for ALV amplification products based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) combined with an immunochromatographic strip in a lateral flow device (LFD). Using the ALVp27 gene as the target, five RT-LAMP primers and one fluorescein-isothiocyanate-labeled probe were designed. After 60 min of RT-LAMP amplification at 64 °C, the products could be visualized directly using the LFD. The detection limit of this assay for ALV detection was 102 RNA copies/µL, and the sensitivity was 100 times that of reverse transcription polymerase chain reaction (RT-PCR), showing high specificity and sensitivity. To verify the clinical practicality of this assay for detecting ALV, the gold standard RT-PCR method was used for comparison, and consistent results were obtained with both assays. Thus, the assay described here can be used for rapid detection of ALV in resource-limited environments.

Multiple Observer Adaptive Fusion for Uncertainty Estimation and Its Application to Wheel Velocity Systems.

Uncertainty estimation in real-world scenarios is challenged by complexities arising from peaking phenomena and measurement noises. This article introduces a novel scheme for practical uncertainty estimation to mitigate peaking dynamics and enhance overall dynamic behavior. A fusion estimation framework for lumped uncertainties using multiple extended state observers (ESOs) is constructed, and the low-frequency adaptive parameter learning technique is employed to approximate the optimal fusion. The adaptive fusion estimation not only attenuates transient peaks in uncertainty estimation but also attains fast convergence and high accuracy under the high-gain scheduling of ESOs. Furthermore, the robustness of uncertainty estimation against measurement noises is enhanced by cascading filters in the proposed adaptive fusion framework for multiple ESOs. Extensive theoretical analyses are executed to verify practical applicability in peak and noise rejection. Finally, simulations and experiments on the wheel velocity system of a mobile robot are conducted to test the validity and feasibility.

Photodynamic therapy upregulates expression of HIF-1α and PD-L1 in related pathways and its clinical relevance in non-small-cell lung cancer.

BACKGROUND: Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. METHODS: Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein-protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. RESULTS: Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. CONCLUSIONS: PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.

Difference of carrier dynamics in a semiconductor saturable absorber mirror with and without B+ ion-implantation.

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

In vitro pharmacokinetic behavior in lung of harringtonine, an antagonist of SARS-CoV-2 associated proteins: New insights of inhalation therapy for COVID-19.

BACKGROUND: Recent studies have shown that harringtonine (HT) could specifically bind with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and host cell transmembrane serine protease 2 (TMPRSS2) to block membrane fusion, which is an effective antagonist for SARS-CoV-2. PURPOSE: Our study focused on in-depth exploration of in vitro pharmacokinetic characteristics of HT in lung. METHODS: HPLC-fluorescence detection method was used to detect changes of HT content. Incubation systems of lung microsomes for phase I metabolism and UGT incubation systems for phase II metabolism were performed to elucidate metabolites and metabolic mechanisms of HT, and then the metabolic enzyme phenotypes for HT were clarified by chemical inhibition method and recombinant enzyme method. Through metabolomics, we comprehensively evaluated the physiological dynamic changes in SD rat and human lung microsomes, and revealed the relationship between metabolomics and pharmacological activity of HT. RESULTS: HPLC-fluorescence detection method showed strong specificity, high accuracy, and good stability for rapid quantification of HT. We confirmed that HT mainly underwent phase I metabolism, and the metabolites of HT in different species were all identified as 4'-demethyl HT, with metabolic pathway being hydrolysis reaction. CYP1A2 and CYP2E1 participated in HT metabolism, but as HT metabolism was not NADPH dependent, the esterase HCES1 in lung also played a role. The main KEGG pathways in SD rat and human lung microsomes were cortisol synthesis and secretion, steroid hormone biosynthesis and linoleic acid metabolism, respectively. The downregulated key biomarkers of 11-deoxycortisol, 21-deoxycortisol and 9(10)-EpOME suggested that HT could prevent immunosuppression and interfere with infection and replication of SARS-CoV-2. CONCLUSION: HT was mainly metabolized into 4'-demethyl HT through phase I reactions, which was mediated by CYP1A2, CYP2E1, and HCES1. The downregulation of 11-deoxycortisol, 21-deoxycortisol and 9(10)-EpOME were key ways of HT against SARS-CoV-2. Our study was of great significance for development and clinical application of HT in the treatment of COVID-19.