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1.
Int J Biol Macromol ; 273(Pt 1): 132964, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852719

RESUMO

There is a growing interest in developing highly viscous lipid foods using plant protein and polysaccharide gum-based emulsion technology. However, gaps remain in understanding the rheological, microstructural, and digestive properties of plant proteins like soybean protein isolate (SPI) in combination with various gums. This study investigates how combining SPI and peach gum (PG) affects rheology and lipolysis of oil-in-water (O/W) emulsions containing 20 wt% soybean oil. Emulsions with varying SPI and PG compositions including SPI-PG single and SPI/PG mixed droplet systems were prepared. Heating induced alterations in viscosity (e.g., SPI-PG from 14.88 to 90.27 Pa·s and SPI/PG from 9.66 to 85.32 Pa·s) and microstructure revealing aggregate formation at oil-water interface. The viscosity decreased significantly from the oral to intestinal phase (SPI-PG: 28.10 to 0.19 Pa·s, SPI/PG: 21.27 to 0.10 Pa·s). These changes affected lipid digestion, notably in SPI-PG and SPI/PG emulsions where a compact interface hindered lipolysis during digestion. Interestingly, free fatty acid (FFA) release during small intestinal phase followed a different order: SPI (82.51 %) > SPI-PG (70.77 %) > SPI/PG (63.60 %) > PG (56.09 %). This study provides insights into creating highly viscous O/W spreads with improved rheology, stability, and delayed lipid digestion, offering potential benefits in food product formulation.

2.
Cells ; 13(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38891107

RESUMO

Over the past few decades, the worldwide incidence of cutaneous melanoma, a malignant neoplasm arising from melanocytes, has been increasing markedly, leading to the highest rate of skin cancer-related deaths. While localized tumors are easily removed by excision surgery, late-stage metastatic melanomas are refractory to treatment and exhibit a poor prognosis. Consequently, unraveling the molecular mechanisms underlying melanoma tumorigenesis and metastasis is crucial for developing novel targeted therapies. We found that the multiple endocrine neoplasia type 1 (MEN1) gene product Menin is required for the transforming growth factor beta (TGFß) signaling pathway to induce cell growth arrest and apoptosis in vitro and prevent tumorigenesis in vivo in preclinical xenograft models of melanoma. We further identified point mutations in two MEN1 family members affected by melanoma that led to proteasomal degradation of the MEN1 gene product and to a loss of TGFß signaling. Interestingly, blocking the proteasome degradation pathway using an FDA-approved drug and RNAi targeting could efficiently restore MEN1 expression and TGFß transcriptional responses. Together, these results provide new potential therapeutic strategies and patient stratification for the treatment of cutaneous melanoma.


Assuntos
Melanoma , Transdução de Sinais , Fator de Crescimento Transformador beta , Melanoma/genética , Melanoma/patologia , Melanoma/metabolismo , Humanos , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Metástase Neoplásica , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Apoptose/genética , Carcinogênese/genética , Carcinogênese/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
3.
Psychiatry Res ; 339: 116043, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38896930

RESUMO

3,4-methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, is one of the most widely used illicit substances worldwide. MDMA-assisted psychotherapy has become a novel treatment for posttraumatic stress disorder (PTSD), and many randomized controlled trials (RCTs) have been performed over the past decade. Therefore, this study aimed to systematically review and demonstrate the efficacy and safety of MDMA-assisted psychotherapy for the treatment of PTSD. We conducted a systematic search of PubMed, Embase, and Web of Science databases up to October 27, 2023, selected RCTs assessing the efficacy and safety of MDMA-assisted psychotherapy for the treatment of PTSD, and evaluated their quality using the Cochrane risk of bias tool. Seven RCTs were selected from the retrieved references. The results revealed that MDMA-assisted psychotherapy effectively reduced the change from baseline score in the Clinician-Administered PTSD Scale in patients with PTSD compared with either placebo or active controls. However, MDMA causes a series of adverse events, including muscle tightness, nausea, and decreased appetite. To a certain extent, MDMA-assisted psychotherapy may improve symptoms in patients with PTSD. However, side effects and abuse issues still seriously hinder clinical application of MDMA.

4.
Mol Cancer ; 23(1): 118, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831405

RESUMO

Triple negative breast cancer (TNBC) remains exceptionally challenging to treat. While CDK4/6 inhibitors have revolutionized HR + breast cancer therapy, there is limited understanding of their efficacy in TNBC and meaningful predictors of response and resistance to these drugs remain scarce. We conducted an in vivo genome-wide CRISPR screen using palbociclib as a selection pressure in TNBC. Hits were prioritized using microarray data from a large panel of breast cancer cell lines to identify top palbociclib sensitizers. Our study defines TGFß3 as an actionable determinant of palbociclib sensitivity that potentiates its anti-tumor effects. Mechanistically, we show that chronic palbociclib exposure depletes p21 levels, contributing to acquired resistance, and that TGFß3 treatment can overcome this. This study defines TGFß3 as an actionable biomarker that can be used to improve patient stratification for palbociclib treatment and exploits the synergistic interaction between CDK4/6 and TGFß3 to propose a new combinatorial treatment for TNBC.


Assuntos
Biomarcadores Tumorais , Resistencia a Medicamentos Antineoplásicos , Piperazinas , Piridinas , Fator de Crescimento Transformador beta3 , Neoplasias de Mama Triplo Negativas , Humanos , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Piridinas/farmacologia , Piridinas/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Camundongos , Animais , Fator de Crescimento Transformador beta3/genética , Fator de Crescimento Transformador beta3/metabolismo , Sistemas CRISPR-Cas , Ensaios Antitumorais Modelo de Xenoenxerto , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
5.
Pest Manag Sci ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837578

RESUMO

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development. RESULTS: In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults. CONCLUSION: Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry.

6.
Angew Chem Int Ed Engl ; : e202408569, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837843

RESUMO

The integration of hostless battery-like metal anodes for hybrid supercapacitors is a realistic design method for energy storage devices with promising future applications. With significant Cr element deposits on Earth, exceptionally high theoretical capacity (1546 mAh g-1), and accessible redox potential (-0.74 V vs. reversible hydrogen electrode) of Cr metals, the design of Cr anodes has rightly come into our focus. This work presents a breakthrough design of a flexible Cr-ion hybrid supercapacitor (CHSC) based on a porous graphitized carbon fabric (PGCF) substrate prepared by K2FeO4 activation. In the CHSC device, PGCF acts as both a current collector and cathode material due to its high specific surface area and superior conductivity. The use of a highly concentrated LiCl-CrCl3 electrolyte with high Cr plating/stripping efficiency and excellent antifreeze properties enables the entire PGCF-based CHSC to achieve well-balanced performance in terms of energy density (up to 1.47 mWh cm-2), power characteristics (reaching 9.95 mW cm-2) and durability (95.4% capacity retention after 30,000 cycles), while realizing it to work well under harsh conditions of -40 °C. This work introduces a new concept for low-temperature energy storage technology and confirms the potential application of Cr anodes in hybrid supercapacitors.

7.
NPJ Precis Oncol ; 8(1): 128, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839871

RESUMO

Metastatic cancer remains incurable as patients eventually loose sensitivity to targeted therapies and chemotherapies, further leading to poor clinical outcome. Thus, there is a clear medical gap and urgent need to develop efficient and improved targeted therapies for cancer patients. In this study, we investigated the role of DYRK1A kinase in regulating cancer progression and evaluated the therapeutic potential of DYRK1A inhibition in invasive solid tumors, including colon and triple-negative breast cancers. We uncovered new roles played by the DYRK1A kinase. We found that blocking DYRK1A gene expression or pharmacological inhibition of its kinase activity via harmine efficiently blocked primary tumor formation and the metastatic tumor spread in preclinical models of breast and colon cancers. Further assessing the underlying molecular mechanisms, we found that DYRK1A inhibition resulted in increased expression of the G1/S cell cycle regulators while decreasing expression of the G2/M regulators. Combined, these effects release cancer cells from quiescence, leading to their accumulation in G1/S and further delaying/preventing their progression toward G2/M, ultimately leading to growth arrest and tumor growth inhibition. Furthermore, we show that accumulation of cancer cells in G1/S upon DYRK1A inhibition led to significant potentiation of G1/S targeting chemotherapy drug responses in vitro and in vivo. This study underscores the potential for developing novel DYRK1A-targeting therapies in colon and breast cancers and, at the same time, further defines DYRK1A pharmacological inhibition as a viable and powerful combinatorial treatment approach for improving G1/S targeting chemotherapy drugs treatments in solid tumors.

8.
Theory Biosci ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888845

RESUMO

Herbal medicines are frequently blended in the form of multi-drug combinations primarily based on the precept of medicinal compatibility, to achieve the purpose of treating diseases. However, due to the lack of appropriate techniques and the multi-component and multi-target nature of Chinese medicine compounding, it is tough to explain how the drugs interact with each other. As a rising discipline, cyber pharmacology has formed a new approach characterized by using holistic and systematic "network targets" via the cross-fertilization of computer technology, bioinformatics, and different multidisciplinary disciplines. It can broadly screen the active ingredients of traditional Chinese medicine, enhance the effective utilization of drugs, and elucidate the mechanism of drug action. We will overview the principles of Chinese medicine compounding and dispensing, the research methods of network pharmacology, and the software of network pharmacology in the lookup of compounded Chinese medicines, aiming to supply thoughts for the better application of network pharmacology in the research of Chinese medicines.

9.
J Ethnopharmacol ; 332: 118339, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38777083

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tao Hong Si Wu Decoction (THSWD), a traditional Chinese herbal medicine, is widely utilized in clinical settings, either alone or in combination with other medications, for the treatment of breast cancer. AIM OF THE STUDY: The specific targeting molecule(s) of THSWD and its associated molecular mechanisms remain unclear. This research aims to elucidate the underlying molecular mechanisms of THSWD in the treatment of breast cancer. MATERIALS AND METHODS: The pharmacological properties of THSWD were investigated in breast cancer cells and tumor tissues using a range of methods including Acridine Orange/Ethidium Bromide (AO/EB) staining, Transwell assay, flow cytometry, immunofluorescence assay, and breast cancer mice models. RESULTS: Our findings demonstrate that THSWD induces necrosis and/or apoptosis in breast cancer cells, while significantly inhibiting cell migration. Target proteins of THSWD in anticancer activity include EGFR, RAS, and others. THSWD treatment for breast cancer is associated with the EGFR/ERK1/2 signaling pathway. CONCLUSION: Our findings offer initial insights into the primary mechanism of action of THSWD in breast cancer treatment, indicating its potential as a complementary therapy deserving further investigation.


Assuntos
Apoptose , Neoplasias da Mama , Medicamentos de Ervas Chinesas , Receptores ErbB , Sistema de Sinalização das MAP Quinases , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Humanos , Receptores ErbB/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Movimento Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Células MCF-7
10.
J Pharm Biomed Anal ; 246: 116255, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38795427

RESUMO

Wilson disease (WD) is an inherited disorder characterized by abnormal copper metabolism with complex pathological features. Currently, this mechanism of copper overload-induced hepatic injury remains unclear. In this study, male toxic milk (TX) mice were selected as experimental subjects. Copper levels and biochemical indices were measured by atomic absorption spectroscopy (AAS) and kits. Liver tissue ultrastructure was observed by hematoxylin-eosin (H&E), sirius red staining and transmission electron microscopy. Plasma and liver metabolic profiles of TX mice were characterized by untargeted metabolomics. In addition, the expression of enzymes related to arachidonic acid metabolism in liver tissue was detected by Western blotting. The results showed the excessive copper content, concomitant oxidative stress, and hepatic tissue structural damage in TX mice. Seventy-eight metabolites were significantly different in WD, mainly involved in the metabolism of arachidonic acid, glycerophospholipids, sphingolipids, niacin and nicotinamide, and phenylalanine. Furthermore, the arachidonic acid metabolic pathway is an important pathway involved in WD metabolism. The level of arachidonic acid in the liver of TX mice was significantly lower (p < 0.01) compared to the control group. The expression of cytoplasmic phospholipase A2 (cPLA2) and arachidonic acid 12-lipoxygenase (ALOX12), related to the arachidonic acid metabolic pathway, was significantly different in the liver of TX mice (p < 0.01). Modulation of the arachidonic acid metabolic pathway could be a potential therapeutic strategy to alleviate WD symptoms.


Assuntos
Cobre , Modelos Animais de Doenças , Degeneração Hepatolenticular , Fígado , Metabolômica , Animais , Degeneração Hepatolenticular/metabolismo , Camundongos , Fígado/metabolismo , Masculino , Metabolômica/métodos , Cobre/metabolismo , Ácido Araquidônico/metabolismo , Estresse Oxidativo , Leite/metabolismo
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124496, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38796895

RESUMO

Rapidly and accurately grasp the change of soil organic carbon content in farmland, which is of great significance in guiding the timely and effective mastery of farmland soil fertility and improvement of soil physical properties. In this study, an ASD FieldSpec 4 spectrometer was used to collect spectral reflectance data on 128 agricultural soil samples taken from Jingbian County, Yulin City, Shaanxi Province, China. Firstly, descriptive statistics of the SOC in the study area were performed, and secondly, after 10 spectral transformations were performed, the correlation analysis and the Boruta algorithm were used to extract the characteristic wavebands of soil organic carbon, respectively, in order to reduce the redundancy of the data. Finally, by comparing the accuracies of different strategies, we constructed a spectral prediction model of soil organic carbon in farmland of the Northwest Agricultural and Animal Husbandry Intertwined Zone that integrates the optimal preprocessing, feature selection strategy and modelling method. The results indicate that: 1) The mean SOC content of the farmland in the study area was low and at the nutrient deficient level, with the standard errors and coefficients of variation for the modelling and validation sets were 1.596 g kg-1, 1.457 g kg-1, 54 % and 52 %, respectively; 2) The shape and trend of spectral special curves with different SOC contents show consistency, and the SOC content is negatively correlated with spectral reflectance; 3) CA selects more feature bands, but the feature bands are more homogeneous, while the Boruta algorithm can effectively remove irrelevant variables and improve the SOC feature selection effect; 4) The SOC prediction model based on Boruta-FD-RF can be better for soil organic carbon estimation, with R2 of 0.899 and 0.748 for the training set and validation set, respectively, RMSE of 1.432 g kg-1 and 1.967 g kg-1, and RPD of 2.557 and 1.647, respectively. The results show that the SOC model established by integrating optimal spectral pre-processing, feature selection strategy and chemometrics strategy has obvious improvement in prediction accuracy and stability, and this study provides an important reference for the fast and accurate estimation of SOC content in farmland of Agro-pastoral Transitional zone in northwest China.

12.
BMC Geriatr ; 24(1): 405, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714934

RESUMO

BACKGROUND: Cognitive dysfunction is one of the leading causes of disability and dependence in older adults and is a major economic burden on the public health system. The aim of this study was to investigate the risk factors for cognitive dysfunction and their predictive value in older adults in Northwest China. METHODS: A cross-sectional study was conducted using a multistage sampling method. The questionnaires were distributed through the Elderly Disability Monitoring Platform to older adults aged 60 years and above in Northwest China, who were divided into cognitive dysfunction and normal cognitive function groups. In addition to univariate analyses, logistic regression and decision tree modelling were used to construct a model to identify factors that can predict the occurrence of cognitive dysfunction in older adults. RESULTS: A total of 12,494 valid questionnaires were collected, including 2617 from participants in the cognitive dysfunction group and 9877 from participants in the normal cognitive function group. Univariate analysis revealed that ethnicity, BMI, age, educational attainment, marital status, type of residence, residency status, current work status, main economic source, type of chronic disease, long-term use of medication, alcohol consumption, participation in social activities, exercise status, social support, total scores on the Balanced Test Assessment, total scores on the Gait Speed Assessment total score, and activities of daily living (ADL) were significantly different between the two groups (all P < 0.05). According to logistic regression analyses, ethnicity, BMI, educational attainment, marital status, residency, main source of income, chronic diseases, annual medical examination, alcohol consumption, exercise status, total scores on the Balanced Test Assessment, and activities of daily living (ADLs) were found to influence cognitive dysfunction in older adults (all P < 0.05). In the decision tree model, the ability to perform activities of daily living was the root node, followed by total scores on the Balanced Test Assessment, marital status, educational attainment, age, annual medical examination, and ethnicity. CONCLUSIONS: Traditional risk factors (including BMI, literacy, and alcohol consumption) and potentially modifiable risk factors (including balance function, ability to care for oneself in daily life, and widowhood) have a significant impact on the increased risk of cognitive dysfunction in older adults in Northwest China. The use of decision tree models can help health care workers better assess cognitive function in older adults and develop personalized interventions. Further research could help to gain insight into the mechanisms of cognitive dysfunction and provide new avenues for prevention and intervention.


Assuntos
Árvores de Decisões , Humanos , Masculino , Feminino , China/epidemiologia , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Modelos Logísticos , Fatores de Risco , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Transtornos Cognitivos/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Inquéritos e Questionários , Atividades Cotidianas
13.
ACS Catal ; 14(9): 6749-6798, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38721380

RESUMO

Thermal approaches have played a dominant role in driving chemical reactions within the chemicals and fuels industries, benefiting from ongoing enhancements in efficiency via heat integration, catalyst development, and process intensification. Nevertheless, these traditional thermal approaches remain heavily reliant on fossil fuels, and there exists an urgent demand for the implementation of renewable energy technologies to synthesize fuels, commodity chemicals, and specialty chemicals. Nonthermal plasmas have gained considerable attention in recent years as a promising solution, and the prospects of combining plasmas with suitable catalysts have become even more appealing. Moreover, the evolution of nonthermal plasma catalysis approaches for the generation of clean hydrogen could be transformative in reducing greenhouse gas emissions. This comprehensive review highlights the influential contributions in plasma catalysis for hydrogen production, discusses recent advancements, and provides future prospects for researchers aiming to advance the production of clean hydrogen.

14.
Nat Commun ; 15(1): 3773, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710738

RESUMO

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive chorioretinal degenerative disease without approved therapeutic drugs. It is caused by mutations in CYP4V2 gene, and about 80% of BCD patients carry mutations in exon 7 to 11. Here, we apply CRISPR/Cas9 mediated homology-independent targeted integration (HITI)-based gene editing therapy in HEK293T cells, BCD patient derived iPSCs, and humanized Cyp4v3 mouse model (h-Cyp4v3mut/mut) using two rAAV2/8 vectors via sub-retinal administration. We find that sgRNA-guided Cas9 generates double-strand cleavage on intron 6 of the CYP4V2 gene, and the HITI donor inserts the carried sequence, part of intron 6, exon 7-11, and a stop codon into the DNA break, achieving precise integration, effective transcription and translation both in vitro and in vivo. HITI-based editing restores the viability of iPSC-RPE cells from BCD patient, improves the morphology, number and metabolism of RPE and photoreceptors in h-Cyp4v3mut/mut mice. These results suggest that HITI-based editing could be a promising therapeutic strategy for those BCD patients carrying mutations in exon 7 to 11, and one injection will achieve lifelong effectiveness.


Assuntos
Sistemas CRISPR-Cas , Distrofias Hereditárias da Córnea , Família 4 do Citocromo P450 , Edição de Genes , Terapia Genética , Células-Tronco Pluripotentes Induzidas , Doenças Retinianas , Humanos , Edição de Genes/métodos , Animais , Células HEK293 , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/terapia , Distrofias Hereditárias da Córnea/patologia , Distrofias Hereditárias da Córnea/metabolismo , Camundongos , Células-Tronco Pluripotentes Induzidas/metabolismo , Terapia Genética/métodos , Família 4 do Citocromo P450/genética , Família 4 do Citocromo P450/metabolismo , Modelos Animais de Doenças , Mutação , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Vetores Genéticos/genética , Íntrons/genética , Éxons/genética
16.
Ann Clin Microbiol Antimicrob ; 23(1): 40, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702782

RESUMO

BACKGROUND: Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. METHODS: To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. RESULTS: We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2-4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. CONCLUSIONS: Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.


Assuntos
Antituberculosos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , China/epidemiologia , Humanos , Antituberculosos/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Prevalência , Nitroimidazóis/farmacologia , Genótipo , Mutação , Sequenciamento Completo do Genoma
17.
Pestic Biochem Physiol ; 201: 105902, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685224

RESUMO

CRF-like diuretic hormone receptor (CRF/DHR), also known as DH44R in insects, are G-protein coupled receptors (GPCRs) that play a role in regulating osmotic balance in various insect species. These receptors have the potential to be targeted for the development of insecticides. However, our understanding of the role of DHR genes in aphids, including Rhopalosiphum padi, a major wheat pest, is currently limited. In this study, we isolated and characterized two R. padi DHRs (RpDHR1 and RpDHR2). The expression levels of RpDHR1 increased after starvation and were restored after re-feeding. The expression levels of RpDHR1 gene decreased significantly 24 h after injection of dsRNA targeting the gene. Knockdown of RpDHR1 increased aphid mortality under starvation conditions (24, 36, 48 and 60 h). Under starvation and desiccation condition, the aphid mortality decreased after knockdown of RpDHR1. This is the first study to report the role of DHR genes in the starvation and desiccation response of aphids. The results suggest that RpDHR1 is involved in the resistance of R. padi to starvation and dehydration, making it a potential target for insecticide development. Novel insecticides could be created by utilizing DHR agonists to disrupt the physiological processes of insect pests.


Assuntos
Afídeos , Proteínas de Insetos , Animais , Afídeos/genética , Afídeos/fisiologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Inanição/genética , Dessecação , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Filogenia
18.
J Colloid Interface Sci ; 667: 157-165, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38636217

RESUMO

The practical application of zinc ion batteries (ZIBs) can be facilitated by designing cathode materials with unique structures that can overcome the critical problems of slow reaction kinetics and large volume expansion associated with the intercalation reaction of divalent zinc ions. In this study, a novel urchin-like (NH4)2V10O25·8H2O assembled from nanorods was synthesized by a simple hydrothermal method, noted as U-NVO. The interlayer organic pillar of cetyltrimethylammonium cation (CTAB) has been intercalated between layers to regulate the interlayer microstructure and expand the interlayer spacing to 1.32 nm, which effectively increased the contact between the electrode and electrolyte interface and shortened the diffusion path of electrolyte ions. The interlayer pillars of structural H2O and NH4+ provide a flexible framework structure and enhance the cohesion of the layered structure, which helps to maintain structural stability during the charging and discharging process, resulting in long-term durability. These unique properties result in the U-NVO cathodes demonstrating high specific capacity (401.7 mA h g-1 at 0.1 A g-1), excellent rate capability (99.6 % retention from 0.1 to 5 A g-1 and back to 0.1 A g-1), and long-term cycling performance (∼87.5 % capacity retention after 2600 cycles). These results offer valuable insights into the design of high-performance vanadium oxide cathode materials.

19.
Adv Sci (Weinh) ; : e2402196, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650164

RESUMO

Fiber-based artificial muscles are promising for smart textiles capable of sensing, interacting, and adapting to environmental stimuli. However, the application of current artificial muscle-based textiles in wearable and engineering fields has largely remained a constraint due to the limited deformation, restrictive stimulation, and uncomfortable. Here, dual-responsive yarn muscles with high contractile actuation force are fabricated by incorporating a very small fraction (<1 wt.%) of Ti3C2Tx MXene/cellulose nanofibers (CNF) composites into self-plied and twisted wool yarns. They can lift and lower a load exceeding 3400 times their own weight when stimulated by moisture and photothermal. Furthermore, the yarn muscles are coiled homochirally or heterochirally to produce spring-like muscles, which generated over 550% elongation or 83% contraction under the photothermal stimulation. The actuation mechanism, involving photothermal/moisture-mechanical energy conversion, is clarified by a combination of experiments and finite element simulations. Specifically, MXene/CNF composites serve as both photothermal and hygroscopic agents to accelerate water evaporation under near-infrared (NIR) light and moisture absorption from ambient air. Due to their low-cost facile fabrication, large scalable dimensions, and robust strength coupled with dual responsiveness, these soft actuators are attractive for intelligent textiles and devices such as self-adaptive textiles, soft robotics, and wearable information encryption.

20.
Sci Adv ; 10(14): eadk3674, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38569027

RESUMO

The immune system substantially influences age-related cognitive decline and Alzheimer's disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 (N = 298), we measured 365 CSF inflammatory molecules, finding age, sex, and diabetes status predominantly influencing their levels. We observed age-related correlations with AD biomarkers such as total tau, phosphorylated tau-181, neurofilament light chain (NfL), and YKL40. APOE4 was associated with lower Aß42 and higher SNAP25 in CSF. We explored baseline variables predicting cognitive decline risk, finding age, CSF Aß42, NfL, and REG4 to be independently correlated. Subjects with older age, lower Aß42, higher NfL, and higher REG4 at baseline had increased cognitive impairment risk during follow-up. This suggests that assessing CSF inflammatory molecules and AD biomarkers could predict cognitive impairment risk in the elderly.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/etiologia , Doença de Alzheimer/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Proteínas tau , Biomarcadores , Peptídeos beta-Amiloides , Fragmentos de Peptídeos
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