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1.
Cancer Cell Int ; 24(1): 158, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711062

RESUMO

OBJECTIVE: Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1. Therefore, this study aimed to explore the effects of FKC on NPC proliferation, glycolysis, and angiogenesis by regulating HSP90B1 and the underlying molecular regulatory mechanisms. METHODS: HSP90B1 expression was analyzed in NPC tissues and its relationship with patient's prognosis was further identified. Afterward, the effects of HSP90B1 on proliferation, apoptosis, glycolysis, and angiogenesis in NPC were studied by loss-of-function assays. Next, the interaction of FKC, HSP90B1, and epidermal growth factor receptor (EGFR) was evaluated. Then, in vitro experiments were designed to analyze the effect of FKC treatment on NPC cells. Finally, in vivo experiments were allowed to investigate whether FKC treatment regulates proliferation, glycolysis, and angiogenesis of NPC cells by HSP90B1/EGFR pathway. RESULTS: HSP90B1 was highly expressed in NPC tissues and was identified as a poor prognostic factor in NPC. At the same time, knockdown of HSP90B1 can inhibit the proliferation of NPC cells, trigger apoptosis, and reduce glycolysis and angiogenesis. Mechanistically, FKC affects downstream EGFR phosphorylation by regulating HSP90B1, thereby regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. FKC treatment inhibited the proliferation, glycolysis, and angiogenesis of NPC cells, which was reversed by introducing overexpression of HSP90B1. In addition, FKC can affect NPC tumor growth and metastasis in vivo by regulating the HSP90B1/EGFR pathway. CONCLUSION: Collectively, FKC inhibits glucose metabolism and tumor angiogenesis in NPC by targeting the HSP90B1/EGFR/PI3K/Akt/mTOR signaling axis.

2.
Phys Rev Lett ; 133(5): 050401, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39159107

RESUMO

The nonequilibrium fluctuation relation is a cornerstone of quantum thermodynamics. It is widely believed that the system-bath heat exchange obeys the famous Jarzynski-Wójcik fluctuation theorem. However, this theorem is established in the Born-Markovian approximation under the weak-coupling condition. Via studying the energy exchange between a harmonic oscillator and its coupled bath in the non-Markovian dynamics, we establish a generalized quantum fluctuation theorem for energy exchange being valid for arbitrary coupling strength. The Jarzynski-Wójcik fluctuation theorem is recovered in the weak-coupling limit. We also find the average energy exchange exhibits rich nonequilibrium characteristics when different numbers of system-bath bound states are formed, which suggests a useful way to control the quantum heat. Deepening our understanding of the fluctuation relation in quantum thermodynamics, our result lays the foundation to design high-efficiency quantum heat engines.

3.
Phys Rev Lett ; 132(9): 090401, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489615

RESUMO

The quantum battery (QB) makes use of quantum effects to store and supply energy, which may outperform its classical counterpart. However, there are two challenges in this field. One is that the environment-induced decoherence causes the energy loss and aging of the QB, the other is that the decreasing of the charger-QB coupling strength with increasing their distance makes the charging of the QB become inefficient. Here, we propose a QB scheme to realize a remote charging via coupling the QB and the charger to a rectangular hollow metal waveguide. It is found that an ideal charging is realized as long as two bound states are formed in the energy spectrum of the total system consisting of the QB, the charger, and the electromagnetic environment in the waveguide. Using the constructive role of the decoherence, our QB is immune to the aging. Additionally, without resorting to the direct charger-QB interaction, our scheme works in a way of long-range and wireless-like charging. Effectively overcoming the two challenges, our result supplies an insightful guideline to the practical realization of the QB by reservoir engineering.

4.
Ecotoxicol Environ Saf ; 284: 116948, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39205355

RESUMO

Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (±5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin (Pinteraction=0.04) and deltamethrin (Pinteraction=0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98-1.56) and 0.91 (0.77-1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02-1.47) and 0.95 (0.78-1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03-7.07], Pinteraction=0.03 and 3.23 [95 % CI: 1.78-5.87], Pinteraction=0.05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin.


Assuntos
Diabetes Mellitus Tipo 2 , Interação Gene-Ambiente , Predisposição Genética para Doença , Células Secretoras de Insulina , Piretrinas , Diabetes Mellitus Tipo 2/genética , Piretrinas/sangue , Piretrinas/toxicidade , Humanos , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Masculino , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Estudos Prospectivos , Inseticidas/sangue , Inseticidas/toxicidade , Adulto , Nitrilas , China , Idoso , Fatores de Risco
5.
Mikrochim Acta ; 191(3): 156, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407632

RESUMO

A magnetic fluorescent molecularly imprinted sensor was successfully prepared and implemented to determine catechol (CT). Fe3O4 nanoparticles were synthesized by the solvothermal technique and mesoporous Fe3O4@SiO2@mSiO2 imprinted carriers were prepared by coating nonporous and mesoporous SiO2 shells on the surface of the Fe3O4 subsequently. The magnetic surface molecularly imprinted fluorescent sensor was created after the magnetic mesoporous carriers were modified with γ-methacryloxyl propyl trimethoxy silane to introduce double bonds on the surface of the carries and the polymerization was carried out in the presence of CT and fluorescent monomers. The magnetic mesoporous carriers were modified with γ-methacryloxyl propyl trimethoxy silane and double bonds were introduced on the surface of the carriers. After CT binding with the molecularly imprinted polymers (MIPs), the fluorescent intensity of the molecularly imprinted polymers (Ex = 400 nm, Em = 523 nm) increased significantly. The fluorescent intensity ratio (F/F0) of the sensor demonstrated a favorable linear correlation with the concentration of CT between 5 and 50 µM with a detection limit of 0.025 µM. Furthermore, the sensor was successfully applied to determine CT in actual samples with recoveries of 96.4-105% and relative standard deviations were lower than 3.5%. The results indicated that the research of our present work provided an efficient approach for swiftly and accurately determining organic pollutant in water.

6.
Phys Rev Lett ; 131(5): 050801, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37595225

RESUMO

Permitting a more precise measurement to physical quantities than the classical limit by using quantum resources, quantum metrology holds a promise in developing many revolutionary technologies. However, the noise-induced decoherence forces its superiority to disappear, which is called no-go theorem of noisy quantum metrology and constrains its application. We propose a scheme to overcome the no-go theorem by Floquet engineering. It is found that, by applying a periodic driving on the atoms of the Ramsey spectroscopy, the ultimate sensitivity to measure their frequency characterized by quantum Fisher information returns to the ideal t^{2} scaling with the encoding time whenever a Floquet bound state is formed by the system consisting of each driven atom and its local noise. Combining with the optimal control, this mechanism also allows us to retrieve the ideal Heisenberg-limit scaling with the atom number N. Our result gives an efficient way to avoid the no-go theorem of noisy quantum metrology and to realize high-precision measurements.

7.
Bioorg Chem ; 131: 106304, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36463590

RESUMO

Velvet antler is a traditional Chinese medicine with various pharmacological values, which is an important raw material for traditional Chinese medicinal wine. Nevertheless, the chemical compositions and bioactivities of velvet antler residue used for making medicinal wine are rarely reported, leading to a waste of resources. In this study, a velvet antler protein (VA-pro) was extracted from velvet antler residue by simulating the gastrointestinal digestion, and its composition, structural characteristics and in vivo anti-tumor activities were determined and investigated. VA-pro possessed high purity with a relatively low molecular weight as 22.589 kDa under HPLC, one- and two-dimensional electrophoresis, and it contained high contents of Pro, Gly, Glu and Ala. Besides, the secondary structure of VA-pro was dominated by ß-turn and ß-sheet, and VA-pro possessed similar protein sequence, isoelectric point and amino acid compositions to hypothetical protein G4228_020061. The in vivo results substantiated that VA-pro could improve the body weights and immune organ indices, increase the expressions of sera cytokines and regulate the distributions of T and B lymphocytes subsets in peripheral blood of S180 tumor-bearing mice. Furthermore, VA-pro could effectively inhibit solid S180 tumors growth by inducing S phase cell cycle arrest mediated through mitochondria. To summarize, our study provided theoretical support that VA-pro had the potential to be used as an immunopotentiator in immunocompromised or cancer-bearing hosts.


Assuntos
Chifres de Veado , Neoplasias , Camundongos , Animais , Chifres de Veado/química , Chifres de Veado/metabolismo , Peso Molecular , Proteínas/metabolismo , Aminoácidos/metabolismo , Neoplasias/metabolismo
8.
Environ Res ; 228: 115743, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37001846

RESUMO

BACKGROUND: Previous epidemiological studies indicated that the association between polychlorinated biphenyls (PCB) and type 2 diabetes mellitus (T2DM) was inconclusive. OBJECTIVE: We investigated the association between PCBs exposure and incident T2DM in a nested case-control study, and further explored the relationship between PCBs and 5-year fasting blood glucose (FBG) changes. METHODS: Baseline concentrations of seven indicator-PCB (PCB-28, 52, 101, 118, 138, 153, 180) were measured in 1006 pairs of incident T2DM cases and matched controls nested within the Dongfeng-Tongji cohort. Conditional logistic regression models and pre-adjusted residuals method were used to assess the associations between PCBs and incident T2DM. We further computed beta coefficients (ßs) of 5-year FBG changes using multivariable generalized linear regression. RESULTS: Non-dioxin-like PCBs (NDL-PCBs) were significantly associated with higher T2DM incidence after adjustment for all covariates. Significant differences were observed for extreme quartiles comparisons (Q4 vs. Q1) of PCBs except PCB-138, and the incidence of T2DM were 1- to 3-fold higher among those in the highest versus lowest PCBs quartiles. Serum NDL-PCBs were positively associated with changes in FBG (P for overall association ≤0.01). Additionally, triglycerides mediated the associations between PCBs and T2DM incidence. CONCLUSION: Our findings showed positive associations of NDL-PCBs with incident T2DM and 5-year FBG changes. PCBs increased incident T2DM via lipid metabolic pathways.


Assuntos
Diabetes Mellitus Tipo 2 , Dioxinas , Poluentes Ambientais , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Humanos , Bifenilos Policlorados/análise , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Estudos de Casos e Controles , Poluentes Ambientais/toxicidade
9.
Can J Microbiol ; 69(4): 158-169, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36669152

RESUMO

This study explored the effects of Lactiplantibacillus plantarum (previously Lactobacillus plantarum) BW2013 on mucosal integrity and gut microbiota of mice with dextran sulfate sodium (DSS)-induced colitis. The results show that the clinical symptoms in DSS-modelled ulcerative colitis (UC) were improved by L. plantarum BW2013 via decreasing disease activity index scores and suppressing inflammatory cell infiltration. Furthermore, L. plantarum BW2013 decreased the levels of diamine oxidase activity, myeloperoxidase, and D-lactic acid. The mRNA expression of ZO-1, occludin, and claudin-1 was upregulated by L. plantarum BW2013, which also increased IL-10 and reduced TNF-α, IL-1ß, and IL-6 in the colon. 16S rDNA sequencing showed that L. plantarum BW2013 enhanced α-diversity. L. plantarum BW2013 upregulated significantly the abundance of unidentfied Lachnospiraceae, Lactococcus, Rikenella, Lactobacillus, and Odoribacter, which had an inhibitory effect on inflammation and a protective effect on the integrity of the mucosa. These results demonstrate that L. plantarum BW2013 alleviates DSS-modelled UC by protecting mucosal integrity and ameliorating the composition of gut microbiota.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Camundongos , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Mucosa Intestinal/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
10.
Ecotoxicol Environ Saf ; 265: 115493, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37729699

RESUMO

Prospective epidemiological evidence was lacking on the association of phthalates (PAEs) exposure with incident type 2 diabetes mellitus (T2DM) risk. In present nested case-control study, we identified 1006 T2DM cases and matched 1006 controls based on Dongfeng-Tongji cohort study, and 6 PAEs were detected in baseline serum. The conditional logistic regression model, Bayesian kernel machine regression (BKMR) model and Quantile-based g-computation were applied to evaluate the associations of determined PAEs, either as individuals or as a mixture, with incident T2DM risk. Subgroup analysis was conducted to identify the potential sensitive population of PAEs effects on T2DM. After multiple adjustment, no statistically significant association was observed between single or mixture of PAEs and incident T2DM risk in the whole population. However, serum levels of Di-n-butyl phthalate (DnBP) [OR= 2.06; 95% CI: (1.11-3.96)], Σdibutyl phthalate (ΣDBP) [OR= 1.96; 95% CI: (1.06-3.76)], and Σlow-molecular- weight phthalate (ΣLMW) [OR= 2.27; 95% CI: (1.17-4.57)] were significantly associated with T2DM in current drinker group. Moreover, significant potential interactions were observed among Di-iso-butyl phthalate (DiBP), DnBP, Butyl-benzyl phthalate (BBP), ΣDBP, and ΣLMW with drinking status on T2DM risk (P for interaction = 0.036, 0.005, 0.049. 0.010, and 0.005). We did not find significant associations between serum PAEs levels and T2DM in the whole population. However, current alcohol drinkers expose to higher levels of DnBP, ΣDBP, and ΣLMW had higher risk of T2DM.

11.
Chem Biodivers ; 20(11): e202300998, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37755070

RESUMO

Based on the research strategy of "drug repurposing", a series of derivatives and marketed drugs that containing salicylic acid skeleton were tested for their antibacterial activities against phytopathogens. Salicylic acid can not only regulate some important growth metabolism of plants, but also induce plant disease resistance. The bioassay results showed that the salicylamides exhibited excellent antibacterial activity. Especially, oxyclozanide showed the best antibacterial effect against Xanthomonas oryzae, Xanthomonas axonopodis pv. citri and Pectobacterium atroseptica with MICs of 0.78, 3.12 and 12.5 µg.mL-1, respectively. In vivo experiments with rice bacterial leaf blight had further demonstrated that oxyclozanide exhibited stronger antibacterial activity than the commercial bactericide, thiodiazole copper. Oxyclozanide could induce plant defense responses through the determination of salicylic acid content and the activities of defense-related enzymes including CAT, POD, and SOD in rice. The preliminarily antibacterial mechanism study indicated that oxyclozanide exhibited the antibacterial activity by disrupting cell integrity and reducing bacterial pathogenicity. Additionally, oxyclozanide could induce plant defense responses through the determination of salicylic acid content.


Assuntos
Oryza , Xanthomonas , Salicilamidas/farmacologia , Reposicionamento de Medicamentos , Oxiclozanida/farmacologia , Antibacterianos/farmacologia , Oryza/microbiologia , Testes de Sensibilidade Microbiana , Ácido Salicílico/farmacologia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , Oxidiazóis/farmacologia
12.
Chem Biodivers ; 20(5): e202300230, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36951446

RESUMO

Natural QPAs have anti-cancer property. The prodrugs of QPAs synthesized in our work with significantly improved solubility showed significantly stronger activity in animal experiments. Nevertheless, the mechanism of action of QPAs for treating cancers remains poorly understood. Here, a chemoproteomic study reveals that QPAs non-covalently and multivalently bind to PES1 in CRC cells, which impinges on the direct interaction between hTERT and hTR in the assembly of the telomerase complex, downregulates telomerase activity, and so promotes the aging process of CRC cells. This study is beneficial for us to conduct extensively the pharmaceutical chemistry research of QPAs.


Assuntos
Alcaloides de Berberina , Telomerase , Animais , Telomerase/metabolismo , RNA/química
13.
Chem Biodivers ; 20(6): e202300570, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37194166

RESUMO

Twenty-two quaternary 8-dichloromethylprotoberberine alkaloids were synthesized from unmodified quaternary protoberberine alkaloids (QPAs) to improve their physical and chemical properties and to obtain selectively anticancer derivatives. The synthesized derivatives showed more appropriate octanol/water partition coefficients by up to values 3-4 compared to unmodified QPA substrates. In addition, these compounds exhibited significant antiproliferative activity against colorectal cancer cells and lower toxicity on normal cells, resulting in more significant selectivity indices than unmodified QPA compounds in vitro. The IC50 values of antiproliferative activity of quaternary 8-dichloromethyl-pseudoberberine 4-chlorobenzenesulfonate and quaternary 8-dichloromethyl-pseudopalmatine methanesulfonate against colorectal cancer cells are 0.31 µM and 0.41 µM, respectively, significantly stronger than those of other compounds and positive control 5-fluorouracil. These findings suggest that 8-dichloromethylation can be used as one of the modification strategies to guide the structural modification and subsequent investigation of anticancer drugs for CRC based on QPAs.


Assuntos
Alcaloides , Antineoplásicos , Neoplasias Colorretais , Humanos , Alcaloides/farmacologia , Alcaloides/química , Linhagem Celular , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Estrutura Molecular
14.
Mikrochim Acta ; 190(4): 161, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36976361

RESUMO

A sensitive molecularly imprinted ratiometric fluorescence sensor was constructed for the first time to visually detect tetrabromobisphenol A (TBBPA). The blue fluorescent carbon quantum dots (CQDs) were coated with SiO2 through the reverse microemulsion method to obtain a stable internal reference signal CQDs@SiO2. The ratiometric fluorescence sensor was finally prepared using red fluorescent CdTe QDs as the response signal in the presence of CQDs@SiO2. When the molecularly imprinted polymers were combined with TBBPA, the fluorescence of CdTe QDs (Ex = 365 nm, Em = 665 nm) was rapidly quenched, while that of CQDs (Ex = 365 nm, Em = 441 nm) remained stable, resulting in a noticeable fluorescence color change. Moreover, the fluorescence intensity ratio (I665/I441)0/(I665/I441) of the sensor showed a linear response to TBBPA in the concentration range 0.1 to 10 µM with a low detection limit of 3.8 nM. The prepared sensor was successfully applied to detect TBBPA in water samples. The recoveries were in the range 98.2-103%, with relative standard deviations lower than 2.5%. Furthermore, a fluorescent test strip for visual monitoring of TBBPA was constructed to streamline the procedure. The excellent results demonstrate that the prepared test strip has a broad prospect for the offline detection of pollutants.

15.
Sensors (Basel) ; 23(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36772752

RESUMO

Frequency lock-in-induced deadband phenomena are major problems of ring laser gyroscopes (RLGs), which deteriorate linear responses to changes in the applied rotation rate. In this work, the frequency lock-in phenomenon occurring in the RLG was successfully investigated by compensating for the Sagnac effect through frequency analysis using a newly defined error function. Integrative and generalized viewpoints from the analyzed results provide new possibilities for relevant performance improvements of optical gyroscopes, as well as a deeper understanding of locked states in principle aspects.

16.
Yi Chuan ; 45(4): 354-363, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37077168

RESUMO

Drosophila is a crucial biological experimental teaching material extensively utilized in experimental teaching. In this experimental teaching, each student typically needs to manually identify hundreds of fruit flies and record multiple of each fly. This task involves substantial workload, and the classification standards can be inconsistent. To address this issue, we introduce a deep convolutional neural network that classifies the traits of every fruit fly, using a two-stage consisting of an object detector and a trait classifier. We propose a keypoint-assisted classification model with tailored training session for the trait classification task and significantly enhanced the model interpretability. Additionally, we've enhanced the RandAugment method to better fit the features of our task. The model is trained with progressive learning and adaptive regularization under limited computational resources. The final classification model, which utilizes MobileNetV3 as backbone, achieves an accuracy of 97.5%, 97.5% and 98% for the eyes, wings, gender tasks, respectively. After optimization, the model is highly lightweight, classifying 600 fruit fly traits from raw images in 10 seconds and having a size less than 5 MB. It can be easily deployed on any android device. The development of this system is conducive to promoting the experimental teaching, such as verifying genetic laws with Drosophila as the research object. It can also be used for scientific research involving a large number of Drosophila classifications, statistics and analyses.


Assuntos
Drosophila , Redes Neurais de Computação , Animais , Drosophila/genética , Computadores , Tecnologia
17.
Eur J Clin Microbiol Infect Dis ; 41(8): 1127-1132, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35882723

RESUMO

Recurrence of tuberculosis (TB) is still a key issue in the control of tuberculosis. The presence of nontuberculous mycobacteria (NTM) complicates the diagnosis of recurrent TB due to similarity in clinical presentation. Herein, we have used molecular genotyping methods to identify mycobacteria species, and analyzed the characteristics of patients with transition between MTB and NTM. Eighty-nine patients with recurrent tuberculosis over the past 12 years were included in our analysis. We found that 9 patients had NTM infections during the study period. Six patients were infected with different mycobacterial strains, half of which were transformed from NTM to MTB, and the other half from MTB to NTM. In addition, the other 3 patients were infected with the same NTM species. Further WGS analysis showed that only one patient had a relapse and the remaining two were classified as reinfection. In conclusion, our results demonstrate that a proportion of previously diagnosed recurrent TB cases are attributed to the transition between MTB and NTM, highlighting the significance of species identification prior to initiation of treatment. The recurrence of mycobacterial diseases is majorly noted within 1 year after treatment completion.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium tuberculosis , Tuberculose , Humanos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium tuberculosis/genética , Micobactérias não Tuberculosas/genética , Tuberculose/microbiologia
18.
Org Biomol Chem ; 20(3): 658-666, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-34951439

RESUMO

The first total synthesis of (S)-(+)-ovigerine, (S)-(+)-N-formylovigerine, and (6aS,6a'S)-(+)-ovigeridimerine of aporphine alkaloids with a benzo[d][1,3]dioxole structure feature was established. The strategy was based upon the well-known Pd-catalyzed arylation to set the aporphine framework, and Noyori asymmetric hydrogenation followed by diastereoselective resolution to achieve excellent enantioselectivity. By slightly modifying the total synthetic route and strategically combining it with a aza-Michael addition, Bischler-Napieralski reaction and N-arylation, this methodology was also applied to the total syntheses of benzo[d][1,3]dioxole-type benzylisoquinoline alkaloids of coptisines and dibenzopyrrocolines, including two impatiens, tetrahydrocoptisine, and quaternary coptisine bromide of coptisines and two dibenzopyrrocoline analogues, with the syntheses of all of these target compounds being efficient. Among the nine synthesized compounds, the total syntheses of the three aporphines and the two impatiens, all with ee values of greater than 99%, were reported for the first time. This work also represents the first unification of synthetic routes for the total synthesis of benzo[d][1,3]dioxole-type aporphines, coptisines, and dibenzopyrrocolines.

19.
Eur J Epidemiol ; 37(9): 959-970, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36031647

RESUMO

Pyrethroid insecticides have been extensively used worldwide, but few studies explored the prospective association between pyrethroid exposure and incident type 2 diabetes (T2D). We conducted a nested case-control study of 2012 paired cases and controls, and measured eight pyrethroid insecticides in the baseline sera. We used conditional logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals, and constructed multiple-pollutant models to investigate the association of pyrethroid mixture with incident T2D risk. The median concentrations (detection rates) were 3.53 µg/L (92.45%), 0.52 µg/L (99.80%), 1.16 µg/L (90.61%) and 1.43 µg/L (99.95%) for permethrin, cypermethrin, fenvalerate, and deltamethrin, respectively. Compared to participants with serum fenvalerate levels in the first quartile, the multivariable-adjusted ORs of incident T2D were 1.20 (95% CI 0.86-1.67), 1.41 (0.97-2.05), and 2.29 (1.27-4.11) for the second, third and fourth quartile (P trend = 0.01). Spline analysis further confirmed the positive association between serum fenvalerate levels and incident T2D risk (P for overall association = 0.006). Furthermore, mixture models revealed a positive association of pyrethroid mixture with incident T2D risk, with serum fenvalerate ranked as the top contributor (proportion of relative contribution: > 70%). We found that high concentrations of serum pyrethroid insecticides were significantly associated with an increased risk of incident T2D. The elevated risk was largely explained by fenvalerate. Further investigations are urgently needed to confirm our findings and elucidate the underlying mechanisms, given the widespread use of pyrethroids and the global pandemic of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Poluentes Ambientais , Inseticidas , Piretrinas , Humanos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Eletrólitos , Inseticidas/efeitos adversos , Nitrilas , Permetrina , Piretrinas/efeitos adversos
20.
Chem Biodivers ; 19(12): e202200635, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36282907

RESUMO

In general, Bletilla striata polysaccharides were mostly water-soluble. However, the structural property, immunomodulatory effects and antitumor activities of alcohol-soluble Bletilla striata polysaccharide were rarely reported. In this study, an alcohol-soluble Bletilla striata polysaccharide was firstly extracted, investigated the structural property and evaluated the antitumor activity in vivo and in vitro. Results showed that BSAP was a low molecular weight polysaccharide (2.29×104  Da) and consisted of glucose, xylose and mannose (molar ratio: 2.39 : 1.00 : 0.21). Animal experiments results suggested that BSAP could effectively inhibit the expansion of H22 solid tumors, protect thymus and spleen, improve macrophages, lymphocytes and NK cells activities and enhance lymphocyte subsets proportion, presenting a better immunological enhancement effect in vivo. Additionally, the results of cell experiments showed that BSAP had obvious antitumor effect in vitro, including inhibiting the proliferation of H22 cells and inducing the apoptosis of tumor cells. These results would provide theoretical basis and new ideas for the further development and utilization of BSAP in the biomedical field.


Assuntos
Orchidaceae , Polissacarídeos , Animais , Etanol , Glucose , Linfócitos , Orchidaceae/química , Extratos Vegetais/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos
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