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1.
Blood ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968151

RESUMO

We report on the antileukemic activity of homoharringtonine (HHT) in T-ALL. We showed that HHT inhibited NOTCH/MYC pathway and induced a significantly longer survival in T-ALL mouse and patient-derived xenograft models, therefore supporting HHT as a promising agent for T-ALL.

2.
Org Lett ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008563

RESUMO

We disclose the synthesis of 3-arylquinoxalin-2-ones from o-phenylenediamines and readily available arylacetates. The method harnesses the selective oxidative property of elemental sulfur in the presence of amine base catalyst and DMSO. The reactions are operationally simple and tolerate a wide range of functional groups.

3.
Heliyon ; 10(11): e31615, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38841460

RESUMO

Non-traditional security (NTS) threats have a vast and profound impact on many aspects of economic, political, social, and many other areas, especially supply chain finance (SCF), particularly in countries like Vietnam, which potentially affects the economic efficiency of businesses' supply chain financial, thereby affecting the general economy of the country and the world. In order to prevent and minimize the negative impacts caused by NTS threats to SCF, this study was conducted to identify NTS threats affecting SCF in Vietnam, at the same time calculate the weight of the impact level and find out the cause and effect relationship between them. Solution strategies are also proposed and ranked, thereby serving as a reference basis for relevant parties to choose appropriate response solutions. Due to the multi-criteria nature of NTS threats, the multiple criteria decision-making (MCDM) method is used in combination with the Z-number concept and Fuzzy set theory to approach the problem of certainty and increase the accuracy of study. The NTS threats are first identified through a literature review and then validated for suitability using the DELPHI technique (DELPHI). Suitable threats will be determined by relationship, weighted by Decision Making Trial And Evaluation Laboratory (DEMATEL) method. Proposed strategies are ranked using the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method. The results indicate that there are 19 NTS factors affecting SCF in Vietnam, and the global economic downturn, pandemic and health crisis, financial crisis and cybersecurity risk are the four root cause factors with the most decisive influence. Businesses and concerns need to prioritize addressing these four threats because they not only have a strong impact but also entail many other threats. The two strategies considered to be the most effective are a sustainable practice and a risk-hedging strategy. Businesses, governments, and stakeholders also should pay attention to the macroeconomic environment, technology, and environment and build sustainable businesses, regularly monitoring economic fluctuations and creating plans to prevent risks.

4.
Front Bioeng Biotechnol ; 12: 1398237, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827037

RESUMO

Accurate medical image segmentation is critical for disease quantification and treatment evaluation. While traditional U-Net architectures and their transformer-integrated variants excel in automated segmentation tasks. Existing models also struggle with parameter efficiency and computational complexity, often due to the extensive use of Transformers. However, they lack the ability to harness the image's intrinsic position and channel features. Research employing Dual Attention mechanisms of position and channel have not been specifically optimized for the high-detail demands of medical images. To address these issues, this study proposes a novel deep medical image segmentation framework, called DA-TransUNet, aiming to integrate the Transformer and dual attention block (DA-Block) into the traditional U-shaped architecture. Also, DA-TransUNet tailored for the high-detail requirements of medical images, optimizes the intermittent channels of Dual Attention (DA) and employs DA in each skip-connection to effectively filter out irrelevant information. This integration significantly enhances the model's capability to extract features, thereby improving the performance of medical image segmentation. DA-TransUNet is validated in medical image segmentation tasks, consistently outperforming state-of-the-art techniques across 5 datasets. In summary, DA-TransUNet has made significant strides in medical image segmentation, offering new insights into existing techniques. It strengthens model performance from the perspective of image features, thereby advancing the development of high-precision automated medical image diagnosis. The codes and parameters of our model will be publicly available at https://github.com/SUN-1024/DA-TransUnet.

5.
Plant Direct ; 8(5): e588, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38766509

RESUMO

Plants use chemistry to overcome diverse challenges. A particularly striking chemical trait that some plants possess is the ability to synthesize massive amounts of epicuticular wax that accumulates on the plant's surfaces as a white coating visible to the naked eye. The ability to synthesize basic wax molecules appears to be shared among virtually all land plants, and our knowledge of ubiquitous wax compound synthesis is reasonably advanced. However, the ability to synthesize thick layers of visible epicuticular crystals ("wax blooms") is restricted to specific lineages, and our knowledge of how wax blooms differ from ubiquitous wax layers is less developed. Here, we recruited the help of citizen scientists and middle school students to survey the wax bloom chemistry of 78 species spanning dicot, monocot, and gymnosperm lineages. Using gas chromatography-mass spectrometry, we found that the major wax classes reported from bulk wax mixtures can be present in wax bloom crystals, with fatty acids, fatty alcohols, and alkanes being present in many species' bloom crystals. In contrast, other compounds including aldehydes, ketones, secondary alcohols, and triterpenoids were present in only a few species' wax bloom crystals. By mapping the 78 wax bloom chemical profiles onto a phylogeny and using phylogenetic comparative analyses, we found that secondary alcohol and triterpenoid-rich wax blooms were present in lineage-specific patterns that would not be expected to arise by chance. That finding is consistent with reports that secondary alcohol biosynthesis enzymes are found only in certain lineages but was a surprise for triterpenoids, which are intracellular components in virtually all plant lineages. Thus, our data suggest that a lineage-specific mechanism other than biosynthesis exists that enables select species to generate triterpenoid-rich surface wax crystals. Overall, our study outlines a general mode in which research scientists can collaborate with citizen scientists as well as middle and high school classrooms not only to enhance data collection and generate testable hypotheses but also to directly involve classrooms in the scientific process and inspire future STEM workers.

6.
Clin Oral Investig ; 28(6): 307, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733524

RESUMO

PURPOSE: The factors related to pericoronitis severity are unclear, and this study aimed to address this knowledge gap. MATERIALS AND METHODS: In total, 113 patients with pericoronitis were included, and their demographic, clinical, and radiographic characteristics were recorded. The Patient-Clinician Pericoronitis Classification was used to score and categorize the severity of pericoronitis. Statistical analysis was conducted to examine the participants' characteristics, validity of the Patient-Clinician Pericoronitis Classification, and risk factors associated with the severity of pericoronitis. RESULTS: The demographic, clinical, and radiographic characteristics of males and females were similar, except for Winter's classification, pain, and intraoral swelling. The constructive validity of the Patient-Clinician Pericoronitis Classification was confirmed with three latent factors, including infection level, patient discomfort, and social interference. Ordinal logistic multivariate regression analysis revealed that upper respiratory tract infection was the sole risk factor associated with pericoronitis severity in males (odds ratio = 4.838). In females, pericoronitis on the right side (odds ratio = 2.486), distal radiolucency (odds ratio = 5.203), and menstruation (odds ratio = 3.416) were significant risk factors. CONCLUSION: This study demonstrated the constructive validity of the Patient-Clinician Pericoronitis Classification. Among females, pericoronitis in mandibular third molars on the right side with radiolucency in menstruating individuals was more severe. In males, upper respiratory tract infection was the sole risk factor associated with pericoronitis severity. CLINICAL RELEVANCE: Individuals with risk factors should be aware of severe pericoronitis in the coming future.


Assuntos
Dente Serotino , Pericoronite , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Fatores de Risco , Dente Serotino/diagnóstico por imagem , Pericoronite/complicações , Adulto , Adolescente , Mandíbula/diagnóstico por imagem
7.
Food Chem ; 454: 139792, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38810452

RESUMO

Terpenes in essential oils (EOs) have recently received significant attention due to their potential to improve brain and whole-body health. A deeper understanding of the terpene composition of edible EOs is important for fully exploring their possible applications. In our study, we employed a comprehensive study using four different methods to analyze EO samples, including GC-MS with solid phase microextraction (SPME), liquid injection (LI), derivatization to trimethylsilyl ethers (TMSE), and LC-MS. Our findings revealed that relying on a single analytical method may be insufficient for detecting all terpenes in EOs. Despite identifying a total of 156 terpenes in the samples, only 58 were detectable across all 4 methods. To obtain a more accurate terpene profile of EOs, we advocate for the combined use of LI-GC and TMSE-GC. The terpenes detected by these two methods are complementary, enabling the detection of all terpenes with high VIP in the samples.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis , Microextração em Fase Sólida , Terpenos , Óleos Voláteis/química , Terpenos/análise , Terpenos/química , Microextração em Fase Sólida/métodos , Cromatografia Líquida/métodos , Óleos de Plantas/química
8.
Medicine (Baltimore) ; 103(18): e37997, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701272

RESUMO

Very few studies worldwide have assessed the estimated glomerular filtration rate (eGFR) using serum cystatin C (ScysC) in comparison to the gold standard measured glomerular filtration rate (mGFR) with a gamma camera technique using 99m-Technetium-Diethylene Triaminepentoacetic Acid (99mTc-DTPA). To determine the eGFR formula with the most accurate estimate of glomerular filtration rate when compared with mGFR in a healthy population in Vietnam. We conducted a cross-sectional descriptive study of more than 100 adults without hypertension. The study subjects were examined for general characteristics and blood biochemistry tests to assess eGFR, and the glomerular filtration rate was measured using 99mTc-DTPA with the Gates technique to record mGFR. The estimated values of the eGFR formula were evaluated and compared with the actual mGFR using 99mTechnetium-DTPA. Serum creatinine (Scr) concentration showed a significant difference between males and females: 0.9 ±â€…0.1 versus 0.8 ±â€…0.1 (P < .001), while ScysC concentration did not show this difference. The mGFR in the age groups < 40, 40 to 59, and ≥ 60: 105.0 ±â€…9.9, 94.8 ±â€…8.6, and 93.4 ±â€…10.6, respectively (P < .001). The eGFR-CKD-EPI-cystatin C 2012 formula showed the highest positive correlation with mGFR (ΔGFR = -1.6, R = 0.68, P < .001). eGFR calculated using cystatin C does not require sex adjustment, whereas, for creatinine, sex adjustment is necessary. The eGFR-CKD-Epi-CysC formula showed the lowest difference and a strong correlation with mGFR.


Assuntos
Creatinina , Cistatina C , Taxa de Filtração Glomerular , Humanos , Cistatina C/sangue , Feminino , Masculino , Creatinina/sangue , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Vietnã , Pentetato de Tecnécio Tc 99m , Idoso , Biomarcadores/sangue , Compostos Radiofarmacêuticos , População do Sudeste Asiático
9.
Lancet Microbe ; 5(6): e570-e580, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734030

RESUMO

BACKGROUND: Bacterial diversity could contribute to the diversity of tuberculosis infection and treatment outcomes observed clinically, but the biological basis of this association is poorly understood. The aim of this study was to identify associations between phenogenomic variation in Mycobacterium tuberculosis and tuberculosis clinical features. METHODS: We developed a high-throughput platform to define phenotype-genotype relationships in M tuberculosis clinical isolates, which we tested on a set of 158 drug-sensitive M tuberculosis strains sampled from a large tuberculosis clinical study in Ho Chi Minh City, Viet Nam. We tagged the strains with unique genetic barcodes in multiplicate, allowing us to pool the strains for in-vitro competitive fitness assays across 16 host-relevant antibiotic and metabolic conditions. Relative fitness was quantified by deep sequencing, enumerating output barcode read counts relative to input normalised values. We performed a genome-wide association study to identify phylogenetically linked and monogenic mutations associated with the in-vitro fitness phenotypes. These genetic determinants were further associated with relevant clinical outcomes (cavitary disease and treatment failure) by calculating odds ratios (ORs) with binomial logistic regressions. We also assessed the population-level transmission of strains associated with cavitary disease and treatment failure using terminal branch length analysis of the phylogenetic data. FINDINGS: M tuberculosis clinical strains had diverse growth characteristics in host-like metabolic and drug conditions. These fitness phenotypes were highly heritable, and we identified monogenic and phylogenetically linked variants associated with the fitness phenotypes. These data enabled us to define two genetic features that were associated with clinical outcomes. First, mutations in Rv1339, a phosphodiesterase, which were associated with slow growth in glycerol, were further associated with treatment failure (OR 5·34, 95% CI 1·21-23·58, p=0·027). Second, we identified a phenotypically distinct slow-growing subclade of lineage 1 strains (L1.1.1.1) that was associated with cavitary disease (OR 2·49, 1·11-5·59, p=0·027) and treatment failure (OR 4·76, 1·53-14·78, p=0·0069), and which had shorter terminal branch lengths on the phylogenetic tree, suggesting increased transmission. INTERPRETATION: Slow growth under various antibiotic and metabolic conditions served as in-vitro intermediate phenotypes underlying the association between M tuberculosis monogenic and phylogenetically linked mutations and outcomes such as cavitary disease, treatment failure, and transmission potential. These data suggest that M tuberculosis growth regulation is an adaptive advantage for bacterial success in human populations, at least in some circumstances. These data further suggest markers for the underlying bacterial processes that contribute to these clinical outcomes. FUNDING: National Health and Medical Research Council/A∗STAR, National Institutes of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the Wellcome Trust Fellowship in Public Health and Tropical Medicine.


Assuntos
Antituberculosos , Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Vietnã/epidemiologia , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia , Estudo de Associação Genômica Ampla , Resultado do Tratamento , Fenótipo , Filogenia , Mutação , Fenômica , Genótipo , Feminino , Adulto , Masculino
10.
Adv Mater ; : e2404357, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727713

RESUMO

Linear gold complexes of the "carbene-metal-amide" (CMA) type are prepared with a rigid benzoguanidine amide donor and various carbene ligands. These complexes emit in the deep-blue range at 424 and 466 nm with 100% quantum yields in all media. The deep-blue thermally activates delayed fluorescence originates from a charge transfer state with an excited state lifetime as low as 213 ns, resulting in fast radiative rates of 4.7 × 106 s-1. The high thermal and photo-stability of these carbene-metal-amide (CMA) materials enabled the authors to fabricate highly energy-efficient organic light-emitting diodes (OLED) in host-guest architectures. Deep-blue OLED devices with electroluminescence at 416 and 457 nm with practical external quantum efficiencies of up to 23% at 100 cd m-2 with excellent color coordinates CIE (x; y) = 0.16; 0.07 and 0.17; 0.18 are reported. The operating stability of these OLEDs is the longest reported to date (LT50 = 1 h) for deep-blue CMA emitters, indicating a high promise for further development of blue OLED devices. These findings inform the molecular design strategy and correlation between delayed luminescence with high radiative rates and CMA OLED device operating stability.

11.
Mol Clin Oncol ; 20(6): 44, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38799283

RESUMO

The increasing incidence of urothelial carcinoma, coupled with advancements in its therapeutic landscape, has resulted in improved survival rates for patients. This, in turn, has led to a growing population of patients requiring specialized oncological care, with Enfortumab vedotin (EV) emerging as a pivotal treatment for metastatic urothelial carcinoma. While EV is associated with hyperglycemia, ketoacidosis is exceedingly rare. To the best of our knowledge, the link between EV and hemophagocytic lymphohistiocytosis (HLH) has not yet been explored. A 56-year-old patient diagnosed with metastatic urothelial carcinoma underwent EV treatment as a third-line treatment after progression following treatment with cisplatin/gemcitabine and pembrolizumab. Notably, after receiving two doses of EV, the patient exhibited refractory insulin resistance, leading to ketoacidosis. Subsequently, HLH emerged, necessitating a treatment regimen involving dexamethasone and etoposide. Despite intensive efforts, the patient experienced septic shock, resulting in death. The present case report highlights refractory insulin resistance and ketoacidosis, followed by reactive HLH, in the context of EV therapy. The limited literature on these complications demonstrates the need for further research to improve the understanding of the underlying mechanisms. With growing evidence of the efficacy of EV and evolving survival rates in urothelial carcinoma, healthcare professionals must remain vigilant for potential adverse effects, ensuring early recognition and optimal patient care.

12.
Leukemia ; 38(6): 1236-1245, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643304

RESUMO

Targeting the metabolic dependencies of acute myeloid leukemia (AML) cells is a promising therapeutical strategy. In particular, the cysteine and methionine metabolism pathway (C/M) is significantly altered in AML cells compared to healthy blood cells. Moreover, methionine has been identified as one of the dominant amino acid dependencies of AML cells. Through RNA-seq, we found that the two nucleoside analogs 8-chloro-adenosine (8CA) and 8-amino-adenosine (8AA) significantly suppress the C/M pathway in AML cells, and methionine-adenosyltransferase-2A (MAT2A) is one of most significantly downregulated genes. Additionally, mass spectrometry analysis revealed that Venetoclax (VEN), a BCL-2 inhibitor recently approved by the FDA for AML treatment, significantly decreases the intracellular level of methionine in AML cells. Based on these findings, we hypothesized that combining 8CA or 8AA with VEN can efficiently target the Methionine-MAT2A-S-adenosyl-methionine (SAM) axis in AML. Our results demonstrate that VEN and 8CA/8AA synergistically decrease the SAM biosynthesis and effectively target AML cells both in vivo and in vitro. These findings suggest the promising potential of combining 8CA/8AA and VEN for AML treatment by inhibiting Methionine-MAT2A-SAM axis and provide a strong rationale for our recently activated clinical trial.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Sinergismo Farmacológico , Leucemia Mieloide Aguda , Metionina Adenosiltransferase , Metionina , S-Adenosilmetionina , Sulfonamidas , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Humanos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Sulfonamidas/farmacologia , Metionina/metabolismo , Metionina/análogos & derivados , Metionina Adenosiltransferase/metabolismo , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/genética , Animais , Camundongos , S-Adenosilmetionina/farmacologia , S-Adenosilmetionina/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral
13.
ACS Omega ; 9(12): 13680-13691, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38559940

RESUMO

Exploring structural biomimicry is a great opportunity to replicate hierarchical frameworks inspired by nature in advanced functional materials for boosting new applications. In this work, we present the biomimetic integration of polythiophene into chitosan nanofibrils in a twisted Bouligand structure to afford free-standing macroscopic composite membranes with electrochemical functionality. By considering the integrity of the Bouligand structure in crab shells, we can produce large, free-standing chitosan nanofibril membranes with iridescent colors and flexible toughness. These unique structured features lead the chitosan membranes to host functional additives to mimic hierarchically layered composites. We used the iridescent chitosan nanofibrils as a photonic platform to investigate the host-guest combination between thiophene and chitosan through oxidative polymerization to fabricate homogeneous polythiophene-wrapped chitosan composites. This biomimetic incorporation fully retains the twisted Bouligand organization of nanofibrils in the polymerized assemblies, thus giving rise to free-standing macroscopic electrochemical membranes. Our further experiments are the modification of the biomimetic polythiophene-wrapped chitosan composites on a glassy carbon electrode to design a three-electrode system for simultaneous electrochemical detection of uric acid, xanthine, hypoxanthine, and caffeine at trace concentrations.

14.
J Gerontol Soc Work ; : 1-17, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598561

RESUMO

The Senior Community Service Employment Program (SCSEP) is a U.S.-based job-training program that serves unemployed workers aged 55 and older with incomes at or below 125% of the federal poverty level. While federal funds are set aside to serve Asian workers in SCSEP, little is known about their characteristics and experiences. In response, this pilot study aimed to document the health, well-being, and experiences of older Asian SCSEP participants in Massachusetts through the completion of a survey. Respondents (N = 39) ranged in age from 58 to 73 and identified as either Chinese (72%) or Vietnamese (28%). All were immigrants, and almost all spoke a language other than English at home. Most reported "good" health as well as financial difficulties. They also stated that their supervisors in their placements were supportive. On average, respondents noted moderate interest in searching for a paid job after exiting SCSEP, although more reported interest in searching for a volunteer role. Key to the success of this study was a robust collaboration with a local human services organization with strong ties to the Chinese and Vietnamese communities. The findings highlight the importance of this growing group of older workers.

15.
Noncoding RNA ; 10(2)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38668386

RESUMO

The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological questions are still not solved: (1) How many transcripts really exist in biological samples, such as liver samples and liver cell lines? (2) What are the expression patterns of different alternative HNF1A-AS1 transcripts at different conditions, including during cell growth and development, after exposure to xenobiotics (such as drugs), and in disease conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) cirrhosis, and obesity? (3) Does the siRNA used in previous studies knock down one or multiple transcripts? (4) Do different transcripts have the same or different functions for gene regulation? The presented data confirm the existence of several annotated HNF1A-AS1 transcripts in liver samples and cell lines, but also identify some new transcripts, which are not annotated in the Ensembl genome database. Expression patterns of the identified HNF1A-AS1 transcripts are highly correlated with the cell differentiation of matured hepatocyte-like cells from human embryonic stem cells (hESC), growth and differentiation of HepaRG cells, in response to rifampicin induction, and in various liver disease conditions. The expression levels of the HNF1A-AS1 transcripts are also highly correlated to the expression of cytochrome P450 enzymes, such as CYP3A4, during HepaRG growth, differentiation, and in response to rifampicin induction.

16.
J Clin Microbiol ; 62(4): e0128723, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38466092

RESUMO

Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB-a tNGS assay-to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected Mycobacterium tuberculosis complex DNA in 24/72 (33.3%) CSF samples and generated full DR reports for 22/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB/RIF Xpert. Alleles with <20% frequency were seen at canonical loci associated with first-line DR. Disregarding these low-frequency alleles, Deeplex had 100% concordance with the composite reference standard for all drugs except pyrazinamide and streptomycin. Three patients had positive CSF cultures after 30 days of treatment; reference tests and Deeplex identified isoniazid resistance in two, and Deeplex alone identified low-frequency rifampin resistance alleles in one. Five patients died, of whom one had pDST-identified pyrazinamide resistance. tNGS on CSF can rapidly and accurately detect drug-resistant TBM, but its application is limited to those with higher bacterial loads. In those with lower bacterial burdens, alternative approaches need to be developed for both diagnosis and resistance detection.


Assuntos
Mycobacterium tuberculosis , Tuberculose Meníngea , Tuberculose Resistente a Múltiplos Medicamentos , Adulto , Humanos , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Meníngea/líquido cefalorraquidiano , Mycobacterium tuberculosis/genética , Pirazinamida , Sensibilidade e Especificidade , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Líquido Cefalorraquidiano , Testes de Sensibilidade Microbiana
17.
PLoS One ; 19(3): e0300969, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38551952

RESUMO

This study employed novel extraction methods with natural deep eutectic solvents (NADES) to extract bioactive compounds and proteins from Bacopa monnieri leaves. The conditional influence of ultrasonic-assisted extraction (UAE), microwave-assisted extraction (MAE), and enzymatic-assisted extraction (EAE) on the recovery efficiency of phenolics, proteins, flavonoids, and terpenoids was evaluated. The conditions of UAE were 50 mL/g LSR, 600W of ultrasonic power, and 30% water content with 40°C for 1 min to obtain the highest bioactive compounds and protein contents. The conditions of MAE were 40 mL/g LSR, 400W of microwave power with 30% water content for 3 min to reach the highest contents of biological compounds. The conditions of EAE were 30 mL/g of LSR, 20 U/g of enzyme concentration with L-Gly-Na molar ratio at 2:4:1, and 40% water content for 60 min to acquire the highest bioactive compound contents. Scanning electron microscopy (SEM) is employed to analyze the surface of Bacopa monnieri leaves before and after extraction. Comparing seven extraction methods was conducted to find the most favorable ones. The result showed that the UMEAE method was the most effective way to exploit the compounds. The study suggested that UMEAE effectively extracts phenolics, flavonoids, terpenoids, and protein from DBMP.


Assuntos
Bacopa , Extratos Vegetais , Solventes Eutéticos Profundos , Solventes , Flavonoides , Água , Fenóis , Terpenos
18.
Nat Cancer ; 5(4): 601-624, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38413714

RESUMO

Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid leukemia (AML), eliminates disease via cancer-intrinsic mechanisms and cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation in AML cells decreased the arginine methylation of regulators of RNA translation and the DNA damage response, suppressing cell survival. Notably, PRMT9 inhibition promoted DNA damage and activated cyclic GMP-AMP synthase, which underlies the type I IFN response. Genetically activating cyclic GMP-AMP synthase in AML cells blocked leukemogenesis. We also report synergy of a PRMT9 inhibitor with anti-programmed cell death protein 1 in eradicating AML. Overall, we conclude that PRMT9 functions in survival and immune evasion of both LSCs and non-LSCs; targeting PRMT9 may represent a potential anticancer strategy.


Assuntos
Arginina , Leucemia Mieloide Aguda , Células-Tronco Neoplásicas , Nucleotidiltransferases , Proteína-Arginina N-Metiltransferases , Proteína-Arginina N-Metiltransferases/metabolismo , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Nucleotidiltransferases/metabolismo , Arginina/metabolismo , Metilação/efeitos dos fármacos , Animais , Camundongos , Interferon Tipo I/metabolismo , Dano ao DNA , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos
19.
PhytoKeys ; 238: 119-126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406663

RESUMO

Typhoniumobtusum is described as a new species endemic to Vietnam. It is unique in the genus in having an oblong-elliptic spathe limb with an obtuse apex and yellowish-greenish filiform staminodes with a down-curved acumen. The ecology, distribution and assessment of the conservation status of the new taxon, as well as a key to all known Typhonium species in Vietnam, are provided.

20.
Heliyon ; 10(4): e25245, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420455

RESUMO

Background: Houttuynia cordata Thunb. has long been widely used as a daily vegetable and traditional medicine. The flavonoid component of H. cordata has plenty of pharmacological effects, such as antibacterial, anti-inflammatory, and antioxidant. In this study, we applied the aqueous two-phase system (ATPS) combined with ultrasonic extraction for extracting H. cordata leaves. Methods: We optimized the extraction process to improve the extraction efficiency of the two flavonoids, hyperin and quercitrin, by Surface Method Response - Central Composite Design (RSM-CCD). Next, we investigated the antibacterial ability of H. cordata ATPS extract from optimal conditions against two bacterial strains, Cutibacterium acnes and Staphylococcus epidermidis. Results: The results showed that using 10% (NH4)2SO4 and 35% ethanol for ATPS extraction resulted in the highest hyperin and quercitrin contents. From the RSM-CCD results, the optimal extraction conditions were determined to be ultrasonic extraction at 50 °C for 30 min, giving results consistent with the predicted model and obtaining hyperin and quercitrin contents at 1.5681 ± 0.0114 and 4.6225 ± 0.0327 mg/g, respectively.Furthermore, ATPS extract has excellent antibacterial activity with a minimum inhibitory concentration (MIC) value of 250 µg/mL on both C. acnes and S. epidermidis. This MIC is significantly lower than the H. cordata ultrasound-assisted (UA) extract, with MICs of 1500.00 and 156.25 µg/mL on C. acnes and S. epidermidis, respectively. In addition, the results from the disk diffusion assay also showed that ATPS extraction has superior internal antibacterial activity with a zone of inhibition diameter at 250 µg/mL of 8.67 ± 1.15 and 5.00 ± 2.00 mm. Meanwhile, those of UA extract on C. acnes is 5.67 ± 1.53 mm (at 1500 µg/mL), and on S. epidermidis is 1.34 ± 0.58 mm (at 156.25 µg/mL). Conclusion: To sum up, our research highlights the potential of H. cordata ATPS extracts as the starting material for topical preparations for effectively treating acne.

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