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1.
Front Med (Lausanne) ; 9: 816973, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547209

RESUMO

Introduction: The staphylococcal enterotoxin C (SEC), a commercially available bio-product from Staphylococcus aureus (S. aureus), has been widely used to control MPE. Objectives: We designed and performed a new systematic review (SR) and meta-analysis to clarify the perfusion protocols with SEC, determine their clinical effectiveness and safety, and reveal the indication and optimum usage for achieving the desired responses. Methodology: All randomized controlled trials (RCTs) about SEC for MPE were collected from electronic databases (from inception until July 2021), and clustered into multiple logical topics. After evaluating their methodological quality, we pooled the data from each topic using the meta-analysis or descriptive analysis, and summarized the evidence quality using the grading of recommendation assessment, development, and evaluation (GRADE) approach. Results: All 114 studies were clustered into SEC perfusion alone or plus chemical agents. The SEC alone showed a better complete response (CR), a lower pleurodesis failure, and adverse drug reactions (ADRs), and a higher fever than cisplatin (DDP) alone. The SEC and chemical agents developed 10 perfusion protocols. Among them, only SEC and DDP perfusion showed a better CR, a lower failure, disease progression and ADRs, and a higher fever than DDP alone. The SEC (100-200 ng per time, one time a week for one to four times) with DDP (30-40 mg, or 50-60 mg each time) significantly improved clinical responses for patients with moderate to large volume, Karnofsky performance status (KPS) scores ≥40, ≥50, or ≥60, and anticipated survival time (AST) ≥2 or 3 months. Most results were moderate to low quality. Conclusion: Current pieces of evidence indicate that super-antigen SEC is a pleurodesis agent, which provides an attractive alternative to existing palliative modalities for patients with MPE. Among 10 protocols, the SEC and DDP perfusion is a most commonly used, which shows a significant improvement in clinical responses with low ADRs. These findings also provide a possible indication and optimal usage for SEC and DDP perfusion.

2.
Polymers (Basel) ; 14(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35566845

RESUMO

This research aimed to investigate the hybrid effects of carbon and polypropylene fibers on the stress-strain behavior of lightweight aggregate concrete (LWAC). The considered test variables were two fiber volume fractions of 0.2% and 0.4% and two water/binder ratios of 0.27 and 0.30. Eighteen groups of prisms fabricated with fiber-reinforced LWAC were tested under axial compressive load. Experimental studies were carried out to analyze the influence of different fiber combinations on the complete stress-strain behavior. It was found that the carbon-polypropylene hybrid fibers led to toughness enhancement that was numerically more significant than the sum of individual fibers, indicating a positive synergistic effect between them. Finally, a mathematical expression of the stress-strain curve accounting for the fiber combinations was developed. Compared with existing stress-strain models, the proposed model shows better accuracy in predicting the effect of carbon and polypropylene fibers in both single and hybrid forms on the stress-strain curve of LWAC.

3.
Front Microbiol ; 13: 802409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572636

RESUMO

Background: Host-microbiota crosstalk has been implicated in multiple host metabolic pathway axes that regulate intestinal barrier function. Although constitutive cytochrome P4501A1 (CYP1A1) expression perturbs the microbiome-derived autoregulatory loop following enteric infection, little is known about the role of host CYP1A1 in modulating gut microbiome-mediated signaling during methicillin-resistant Staphylococcus aureus (MRSA)-induced abdominal sepsis and its effects on intestinal barrier integrity. Methods: Abdominal sepsis was induced by the intraperitoneal injection of MRSA in mice. The effect of CYP1A1 deficiency on gut barrier integrity was investigated using RNA sequencing, microbiome analyses, and targeted metabolomics. The microbiota-produced metabolites were validated in patients with sepsis and persistent MRSA infection. Results: Mice lacking CYP1A1 exhibited an altered gut microbiome, a reduced metabolic shift from lysine to cadaverine in the caecal contents and antimicrobial molecule production (Retnlb, Gbp7, and Gbp3), and they were protected against gut barrier disruption when subjected to MRSA challenge. These beneficial effects were validated in aryl hydrocarbon receptor (AHR) knockout (KO) mice by cohousing with CYP1A1 KO mice and abrogated after supplementation with cadaverine or Enterococcus faecalis, the primary microbiota genus for cadaverine synthesis. Antibiotic-driven gut dysbacteriosis impaired the survival benefit and disrupted the intestinal barrier integrity in CYP1A1 KO mice after MRSA infection. Furthermore, increased cadaverine levels in feces and serum were detected in critically ill patients with gut leakiness during persistent MRSA infection, whereas cadaverine was not detected in healthy controls. Additionally, microbiota-derived cadaverine induced enterocyte junction disruption by activating the histamine H4 receptor/nuclear factor-κB/myosin light-chain kinase signaling pathway. Conclusion: This study revealed the unexpected function of host CYP1A1 in microbiota-mediated cadaverine metabolism, with crucial consequences for dysbacteriosis following MRSA-induced abdominal sepsis, indicating that inhibiting CYP1A1 or blocking cadaverine-histamine H4 receptor signaling could be a potential therapeutic target against abdominal sepsis. Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1800018646].

4.
Front Microbiol ; 13: 874536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572716

RESUMO

The microbial community performs vital functions in the intestinal system of animals. Modulation of the gut microbiota structure can indirectly or directly affect gut health and host metabolism. Aohan fine-wool sheep grow in semi-desert grasslands in China and show excellent stress tolerance. In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. We found that from the foregut to the hindgut, the dominant bacteria changed from Proteobacteria to Bacteroidetes. In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. Ruminococcaceae and Caldicoprobacteraceae were significantly abundant in hindgut, which can degrade cellulose polysaccharides in the large intestine and produce beneficial metabolites. Moreover, Coriobacteriaceae and Eggthellaceae are involved in flavonoid metabolism and polyphenol production. Interestingly, these unique bacteria have not been reported in Mongolian sheep or other sheep breeds. Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. Our results provide new insights into the role of gut microbiota in improving stress tolerance and gut health in sheep.

5.
Front Med (Lausanne) ; 9: 872831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572985

RESUMO

Background: Ulcerative colitis (UC) is characterized by refractory and recurrent mucosal inflammation, leading to a substantial healthcare burden. Diagnostic biomarkers predicting disease activity and treatment response remain elusive. To evaluate the application value of a novel neutrophil-based index (the neutrophil-to-albumin ratio, NAR) as a novel diagnostic biomarker in patients with UC and a predictive marker for disease activity and response to infliximab (IFX) therapy. Methods: Clinical characteristics and laboratory parameters of enrolled subjects (patients with UC and healthy controls) were retrieved from the electronic medical record database of our hospital. Serum cytokine and fecal calprotectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR). Results: We found that NAR, which had not yet been explored in UC, was significantly increased in patients with UC (n = 146) compared to that in controls (n = 133) (1.95 ± 0.41 vs. 1.41 ± 0.23, p < 0.0001). NAR showed a positive association with the disease activity and inflammatory load in patients with UC. Pre-treatment NAR was significantly lower in IFX responders than that in non-responders (2.18 ± 0.29 vs. 2.44 ± 0.21, p = 0.0118), showing a significant ability to discriminate initial responders from primary non-responders to IFX induction therapy (AUC = 0.7866, p = 0.0076). Moreover, pre-treatment NAR predicted postinduction serum IFX trough level. Conclusion: Our study provides evidences to utilize NAR in the diagnosis, activity monitoring, and IFX response prediction in patients with UC.

6.
Ying Yong Sheng Tai Xue Bao ; 33(4): 878-886, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35543037

RESUMO

Grasslands in Qilian Mountains plays an important role in maintaining the ecological security of western China. To understand soil physical and chemical properties and the distribution characteristics of vegetation, as well as their correlation in different types of grasslands in Qilian Mountains, we measured soil moisture, nutrient content, bulk density, particle composition, and vegetation characteristics in seven types of grassland in Qilian Mountains. The fractal dimension of soil particles, soil organic carbon, total nitrogen and total phosphorus storages in 0-40 cm soil layer, and plant diversity index were calculated. The results showed that there were significant differences in soil physical and chemical properties and vegetation characteristics among different grassland types. Compared with other types of grassland, alpine meadow had higher soil water, nutrient and clay content, but lower bulk density and sand content. Soil organic carbon, total nitrogen and total phosphorus storages in 0-40 cm layer ranged from 3084 to 45247, 164 to 2358 and 100 to 319 g·m-2, respectively, with high contents of organic carbon and total nitrogen and low content of total phosphorus. There was a significant positive correlation between soil total phosphorus storage and plant diversity index, indicating that soil total phosphorus content was the key factor affec-ting grassland plant diversity in Qilian Mountains. Compared with other grassland types, alpine meadow in Qilian Mountains had better vegetation status, soil moisture, and nutrient conditions.


Assuntos
Pradaria , Solo , Carbono/análise , China , Nitrogênio/análise , Fósforo , Plantas , Solo/química
7.
Org Lett ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35549279

RESUMO

This study describes a regioselective ortho,ortho'-diborylation of aromatic triazenes catalyzed by [Ir(OMe)(cod)]2 in near-quantitative yields without an additional ligand. Aromatic triazenes act as both substrates and ligands. The X-ray structures of 2a and 2p indicate that the monoborylation products could promote the occurrence of diborylation. The synthesized triazene-substituted diboronate esters could undergo a variety of transformations including directing group removal. One-pot sequential modification provides a short entry to densely functionalized arenes.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35490432

RESUMO

BACKGROUND: Aptamers, consist of single-stranded DNA or RNA, have secondary and tertiary structures which could bind specifically to target molecules. They are characterized by strong specificity, high affinity, low molecular weight and low immunogenicity, so current researchs focuses on their potential as a targeted drug carrier, a diagnostic probes for diseases, or as a direct therapeutic drug. OBJECTIVE: In this review, how to improve the success rate of adaptor screening and the optimization after screening are described. RESULTS: For aptamer screening, the efficient selection strategy is needed. In this article, by analyzing key aspects of SELEX such as initial library design, screening procedures, truncation and modification after screening, providing a comprehensive analysis of each step which might meet obstacles in SELEX. CONCLUSION: Aptamers, which possess the specificity and affinity with the target,can be serve as targeted drug carriers or biosensors for diagnosing disease. If the problems in the screening process in cell-SELEX technology, truncation and modification after screening be solved, it will have a broader prospect in application.

9.
Dev Comp Immunol ; 133: 104444, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35588580

RESUMO

The role of TANK-binding kinase 1 (TBK1) of humans and mice in innate immunity is well elucidated. Still, the molecular characterization and biological function of the TBK1 gene in herbivorous animals are less studied. Here, the open reading frame (ORF) of TBK1 of the cow and goat was firstly cloned and successfully expressed. The Phylogenetic tree analysis reveals that the TBK1 gene of goats and cows is similar to chicken and mute swans, respectively. Some evolutionary distances of the TBK1 gene were still present among different species. A slightly subcellular distribution difference was observed among full-length and truncated TBK1 of goats and cows. Dual-luciferase reporter assay has shown that the full-length TBK1 of goats and cows plays a vital role in the induction of IFN-ß production. The viral infection experiment showed that the over-expression of the full-length TBK1 gene of the cow and goat significantly suppresses intracellular viral replication of the Lumpy skin disease virus (LSDV) in infected cells. Our study showed that TBK1 in the cows and goats is a crucial immunoregulatory for IFN-ß production during viral infection, contributing to a better understanding of innate immunity in the herbivorous animal.

10.
J Hazard Mater ; 436: 129060, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35594679

RESUMO

A representative transition metal oxide (TMO), CoMn2O4 (CMO), is recognized as an effective peroxymonosulfate (PMS) activator with disadvantages like limited reactive sites and metal leakage. Herein, novel catalysts were synthesized by anchoring CMO on kaolinite (Kln) and halloysite (Hal) matrixes, two natural clay minerals with lamellar and tubular structures, for PMS activation in pharmaceutical degradation. Hal and Kln helped to control the crystallinity of CMO spontaneously with induce oxygen vacancies (OVs), which significantly enhanced the working efficiency. The reaction rate constants of Hal/CMO and Kln/CMO towards OFX degradation were nearly triple and twice that of bare CMO, respectively, with a 60% decrease in metal usage. The formation of OVs provided additional active sites for the reaction and accelerated the electron transfer. CMO/Hal and CMO/Kln exhibited better stability and durability than CMO, while CMO/Kln showed higher structural stability with lower metal leaching after 3 rounds of reaction. The higher crystallinity of CMO/Kln resulted in less OVs, but higher structural stability. The universal applicability of CMO/Hal and CMO/Kln were verified by using three other pharmaceuticals as probes. This work shed light on the modification of TMO catalysts by introducing clay mineral substrates for the efficient and ecofriendly remediation of pharmaceuticals in wastewater.

11.
Anal Methods ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608240

RESUMO

Background: plasma soluble growth stimulating gene protein 2 (sST2) is a new generation biomarker in heart failure (HF), which is an independent predictor of adverse outcomes of heart failure. Thus, the establishment of a rapid and sensitive method for detecting sST2 is urgently needed. Methods: lanthanide element Eu3+ coated fluorescent nanometer microspheres (Eu3+@FMN) can be used as markers to label monoclonal mouse anti-human sST2 antibody ST-01 (ST-01-Eu3+@FMN). When the immune sandwich complex formed between the monoclonal mouse anti-human sST2 antibody ST-02 and ST-01-Eu3+@FMN on the test band with the appearance of target object sST2, we can detect the fluorescence intensity of Eu3+ on the test band and the quality control band using a dry fluorescence analyzer. We calculated the T/C value (T/C = fluorescence intensity of the test band/fluorescence intensity of the quality control band), fitted to the calibration curve, and measured the concentration value of sST2 in the corresponding sample. Results: the best reaction time was 15 min after condition exploration, and the optimal sample volume was 80 µL. The detection sensitivity of the scheme was 2.14 ng mL-1. The calibration curve of the assay was y = 0.0113x + 0.0033, and the linear range was 5-200 ng mL-1. No cross reaction was found when the samples contained BNP, NT-proBNP, and galectin-3, indicating a good specificity. The precision was good with a relative deviation < 15%. The coefficient of variation of detection results of low-concentration samples and high-concentration samples was 4.20% and 3.30% respectively in the same batch of strip tests, so the intra-assay CV was set as <10%; when different batches of strips were used for testing, the coefficient of variation of detection results of low-concentration samples and high-concentration samples was 10.06% and 8.38% respectively, so the inter-assay CV was set as <15%. Stability test results showed that the relative deviation of test results at each time node was <15%, indicating good stability of the assay strips. The correlation coefficient between the ST-01-Eu3+@FMN based time-resolved fluorescence immunochromatography analysis and sST2 ELISA kit was 0.98. To confirm the usage of our proposed TRF-ICA for clinical samples, it was used to determine the concentration of sST2 in samples obtained from 34 patients with heart insufficiency, acute and chronic heart failure. As a result, we successfully detected a minimal concentration of 5.21 ng mL-1 and a maximum concentration of 184.26 ng mL-1 for sST2. Conclusion: this technique provides a rapid, simple and quantitative detection method for sST2 in clinics. It can help clinicians to predict the incidence of adverse events in patients with HF.

12.
Analyst ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35521826

RESUMO

RNA interference (RNAi) is currently under fast development, which brings improved crop quality and new activity against pests in agriculture, by producing RNAs to specifically inhibit gene expression. This technology, in turn, creates a pressing need for sensitive and specific analytical methods of exogenous RNA molecules in genetically modified (GM) crops for safety assessment and regulation of RNAi plants and their products. In this work, we developed a novel RNA electrochemical biosensor for the analysis of GM maize samples based on a polyA-DNA capturing probe containing three DNA segments: the central polyA segment combined onto a gold electrode surface with adjustable configuration and density, and two flanking DNA probes simultaneously captured the RNA targets through hybridization. Both the assembling and hybridization capability of our probe were demonstrated, and we systematically optimized the analytical conditions. Finally, the ultrasensitive detection of 10 fM RNA was realized without any amplification processes, and the specificity was verified by analyzing non-target maize samples. Our electrochemical biosensor provided a reliable and convenient measurement strategy for RNAi safety and quality assessment, and more importantly, our PAP (probe-polyA-probe) capturing probe exhibited an innovative design for the detection of large RNA molecules with complex secondary structures.

13.
Bioprocess Biosyst Eng ; 45(6): 1065-1074, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35511298

RESUMO

The formation of electroactive biofilm from activated sludge on electrode surface is a key step to construct a bio-electrochemical system, yet it is greatly limited by the poor affinity between the bacteria and the electrode interface. Herein, we report a new method to promote the formation of electroactive biofilm by regulating the extracellular polymeric substance (EPS) content in activated sludge with lysozyme. The investigation of the effect of lysozyme treatment on the content of extracellular polymers and the biofilm formation of electroactive bacteria suggests that lysozyme can improve the permeability of the positive bacterial cell membrane and thus increase the EPS content in the activated sludge. The characterizations of electrochemical activity, surface morphology and community structure of the anode biofilm indicate that increasing EPS content promotes the adhesion of the mixed bacteria in the activated sludge on the electrode and results in denser biofilms with better conductivities. The microbial fuel cell (MFC) inoculated with the sludge of high EPS content exhibits the power density up to 2.195 W/m2, much higher than that inoculated with the untreated sludge (1.545 W/m2). The strategy of adjusting EPS content in activated sludge with a biological enzyme can effectively enhance the ability of the bacterial community to form biofilms and exhibits great application potentials in the construction of high efficiency bio-electrochemical systems.

14.
Transl Lung Cancer Res ; 11(4): 509-522, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35529798

RESUMO

Background: In East Asia, the number of patients with adenocarcinoma, especially those presenting with ground-glass nodules (GGNs), is gradually increasing. Family aggregation of pulmonary GGNs is not uncommon; however, genetic predisposition in these patients remains poorly understood and identification of genes involved in the cause of these early-stage lung cancers might contribute to understanding of the underlying mechanisms and potential prevention strategies. Methods: Fifty patients with early-stage lung adenocarcinoma (LUAD) presenting as GGNs and a first-degree family history of lung cancer (FHLC) from 34 independent families were enrolled into this study. Germline mutations of these patients were analyzed with whole exome sequencing (WES) and compared with age- and sex-matched 39 patients with sporadic lung cancer and 689 local healthy people. We used a stepwise variant filtering strategy, gene-based burden testing, and enrichment analysis to investigate rare but potentially pathogenic heritable mutations. Somatic tumor mutations were analyzed to consolidate germline findings. Results: In total, 1,571 single nucleotide variants (SNVs) and 238 frameshifts with a minor allele frequency (MAF) <0.01, which were rare, recurrent, and potentially damaging candidates, were finally identified through the filtering in the GGN cohort. Pathway analysis showed the extracellular matrix to be the top dysregulated pathway. Gene-based burden testing of these highly disruptive risk-conferring heritable variants showed that MSH5 [odds ratio (OR), 9.28, 95% confidence interval (CI): 2.49-35.87], MMP9 (OR, 8.11, 95% CI: 2.22-28.43), and CYP2D6 (OR, 8.09, 95% CI: 2.68-24.92) were significantly enriched in our cohort (P<0.05). The number of rare damaging germline variants in non-smoking patients was significantly higher than that of smoking-affected patients (Spearman's ρ=-0.39, P=0.02). Conclusions: Heritable, potentially deleterious, and rare candidate variants of MSH5, MMP9 and CYP2D6 were significantly associated with early-stage LUAD presenting with GGNs. Nonsmoking patients likely have a higher genetic predisposition to this type of cancer than smoking-affected patients. These results have extended our understanding of the underlying mechanisms of early-stage LUAD.

15.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1831-1846, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35534253

RESUMO

In recent years, the MYB-related gene family has been found pivotal in plant growth and development. MYB-related gene family in Angelica dahurica var. formosana was systematically investigated based on "Chuanzhi No. 2" through transcriptome database search and bioinformatics and the temporal and spatial expression patterns were analyzed through real-time fluorescence-based quantitative polymerase chain reaction(PCR). The results showed that 122 MYB-related proteins family were identified, mainly including the unstable hydrophilic proteins with good thermal stability. Most of the proteins were located in nuclei. The majority of the proteins had the structures of random coil and α-helix. Five MYB-related proteins family of A. dahurica var. formosana had membrane-binding domains. The conserved domain analysis of MYB-related proteins family of A. dahurica var. formosana showed that the MYB domains of genes in five subgroups, similar to 2 R-, 3 R-, and 4 R-MYB proteins, contained three evenly distributed Trp(W) residues in the MYB repeat sequence. The phylogenetic analysis of MYB-related proteins family in A. dahurica var. formosana and Arabidopsis thaliana showed that the MYB-related members were unevenly distributed in five subgroups, and A. thaliana and A. dahurica var. formosana had almost the same number of genes in the CCA1-like subgroup. There were differences in the number, type, and distribution of motifs contained in 122 encoded proteins. Transcription factors with similar branches had similar domains and motifs. The expression pattern analysis showed that the transcription factors AdMYB53, AdMYB83, and AdMYB89 responded to hormones to varying degrees, and they were highly expressed in leaves and responded quickly in roots. This study lays a foundation for further investigating the function of MYB-related transcription factors of A. dahurica var. formosana and solving the corresponding biological problems such as bolting early.


Assuntos
Angelica , Gastrópodes , Angelica/química , Animais , Biologia Computacional , Filogenia , Folhas de Planta , Proteínas de Plantas/genética , Fatores de Transcrição/genética
16.
Cancer Discov ; : OF1-OF12, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543554

RESUMO

The efficacy and potential limitations of molecular residual disease (MRD) detection urgently need to be fully elucidated in a larger population of non-small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent definitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the population, only six patients (3.2%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 96.8%. Longitudinal undetectable MRD may define the patients who were cured. The peak risk of developing detectable MRD was approximately 18 months after landmark detection. Correspondingly, the positive predictive value of longitudinal detectable MRD was 89.1%, with a median lead time of 3.4 months. However, brain-only recurrence was less commonly detected by MRD (n = 1/5, 20%). Further subgroup analyses revealed that patients with undetectable MRD might not benefit from adjuvant therapy. Together, these results expound the value of MRD in NSCLC. SIGNIFICANCE: This study confirms the prognostic value of MRD detection in patients with NSCLC after definitive surgery, especially in those with longitudinal undetectable MRD, which might represent the potentially cured population regardless of stage and adjuvant therapy. Moreover, the risk of developing detectable MRD decreased stepwise after 18 months since landmark detection.

17.
Phytochemistry ; : 113221, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35605808

RESUMO

Metabolism of special endophytes and phytopathogens can be induced by the symbiotic interactions with the host. A phytopathogen Epicoccum sorghinum cultured in host mushroom Thelephora ganbajun medium exhibited different metabolites compared with that of ordinary medium. An unprecedented scaffold possessing the same substructure as perylenequinone mycotoxin, a first methyl rearrangement product of phytotoxin, epoxydon 6-methylsalicylate ester, three undescribed compounds, and an undescribed natural product were isolated from E. sorghinum cultured in T. ganbajun. Episorin A and epicosorin A were produced from E. sorghinum induced by culturing in host medium. Episorin A was the first example of perylenequinone analogue in the natural products. These induced compounds and other metabolites showed notable antibiosis against endogenous fungi, and insect existing in mushroom. Induced episorin A showed significant inhibitory effects on nitric oxide production in LPS-activated macrophages, and anti-acetylcholinesterase with the IC50 at 5.40 ±â€¯0.25 µM, and 4.32 µM, respectively, and cytotoxicity against HL-60, A-549, SMMC-7721, MCF-7 and SW480 with IC50 at 14.21 ±â€¯0.53, 17.93 ±â€¯0.22, 18.17 ±â€¯0.63, 28.36 ±â€¯0.43, and 18.20 ±â€¯1.03 µM.

18.
Chem Biodivers ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35580000

RESUMO

Five new bisabolane sesquiterpenes, a new polyketide, along with seven known compounds, were isolated from endophyte Schizophyllum commune associated with a famous medicinal and edible plant, Gastrodia elata . Most compounds 1 - 12 , and extract indicated antifeedant activities against silkworm with feeding deterrence index (FDI) of 21-85 %, at concentrations of 20 µg/cm 2 , 40 µg/cm 2 , respectively. Compound 6 indicated obvious insecticidal activity with fatality rate of 60%, at the concentration of 20 µg/cm 2 . Five bisabolane sesquiterpenes, two ergosterols, and a glyceride showed insecticidal synergism by combining with abamectin. Interesting, ergosterol peroxide ( 13 ) distributed widely in mushrooms and fungi, was found to have feeding attractant activities on insects and antifungal activity against entomopathogen Beauveria bassiana . The reciprocal relationship should be occurred between S. commune and pests for the fungus produced ergosterol peroxide to attract the pests propagating spore, and its anti-entomopathogen activity was also benefit for the health of insects.

19.
Zhongguo Fei Ai Za Zhi ; 25(5): 337-350, 2022 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-35599009

RESUMO

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations are the third most prevalent activating EGFR mutation in non-small cell lung cancer (NSCLC), accounting for 5%-12% of all EGFR mutations in NSCLC cases. Patients harboring EGFR exon 20 insertion mutations exhibit similar clinical characteristics except for worse prognosis as compared to those with 'classic' EGFR mutations. EGFR exon 20 insertion mutations are considered as a heterogeneous class of alterations that cause different conformational changes in EGFR. The majority of mutations (almost 90% of cases) is positioned in the loop that immediately follows the C-terminal of the C-helix, and the most widely reported subtype of insertion mutations is D770_N771>ASVDN(A767_V769dupASV) with frequency of 21%-28%. NSCLC patients with EGFR exon 20 insertion mutations show primary drug resistance to previously approved EGFR tyrosine kinase inhibitors and are generally insensitive to conventional chemotherapy and immunotherapy. The recently approved targeted drugs Amivantamab and Mobocertinib shift the treatment paradigm for NSCLC patients harboring EGFR exon 20 insertion mutations. There are also several new compounds targeting NSCLC EGFR exon 20 insertion mutations are in development. In this article, we provide a through overview on the treatment development in EGFR exon 20 insertion mutant NSCLC.
.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Biespecíficos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Éxons , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutagênese Insercional , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
20.
Neurobiol Learn Mem ; 192: 107625, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35504555

RESUMO

We aimed to explore whether modafinil mitigates the working memory decline induced by 36 h of acute total sleep deprivation (36-h TSD). Sixteen healthy male participants were enrolled in a randomized double-blind crossover control study involving three sleep-deprivation sessions. Participants were administered 400 mg of placebo, caffeine, or modafinil during these sessions. Behavior and EEG data were recorded while participants performed pronunciation-related working memory tasks. Behavioral indicators showed that, compared with placebo, modafinil improved the accuracy of pronunciation-related working memory tasks and reduced the response time. Compared with before sleep deprivation, the amplitudes of the event-related potentials (ERPs) increased in the N2 component and decreased in the P3 component after sleep deprivation in the placebo condition. In the caffeine condition, the amplitude of the P3 component decreased, the latency of the N2 component was prolonged, and the N2 amplitude remained unchanged. In the modafinil condition, the P3 latency was shortened, and no significant difference was found in the amplitude of the N2 or P3 ERPs; no significant difference was recorded in the N2 latency. Modafinil (400 mg) effectively ameliorated the decline in pronunciation-related working memory after 36-h TSD, suggesting that it may effectively counteract cognitive decline caused by acute sleep deprivation.

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