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1.
J Anim Sci Biotechnol ; 15(1): 114, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118186

RESUMO

Obesity is a prevalent chronic disease that has significant negative impacts on humans and our companion animals, including dogs and cats. Obesity occurs with multiple comorbidities, such as diabetes, hypertension, heart disease and osteoarthritis in dogs and cats. A direct link between lipid metabolism dysregulation and obesity-associated diseases has been implicated. However, the understanding of such pathophysiology in companion animals is limited. This review aims to address the role of lipid metabolism in various metabolic disorders associated with obesity, emphasizing the involvement of the gut microbiota. Furthermore, we also discuss the management of obesity, including approaches like nutritional interventions, thus providing novel insights into obesity prevention and treatment for canines and felines.

2.
Zookeys ; 1208: 315-330, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39131664

RESUMO

Five new species of the Macrolycusligulatus species-group, M.expansus sp. nov., M.quartus sp. nov., M.costus sp. nov., M.opacipennis sp. nov. and M.curtus sp. nov., are reported from China and described with macrophotographs of the habitus of both sexes and aedeagi. Macrolycusguangxiensis Li, Bocak & Pang, 2015 is illustrated showing the female habitus and genitalia for the first time. In addition, a distribution map and a key to all species of the M.ligulatus species-group are provided.

3.
Cell Rep Med ; 5(8): 101688, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39168098

RESUMO

We evaluated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on prostate cancer by evidence triangulation. Using Mendelian randomization, we found that genetically proxied SGLT2 inhibition reduced the risk of overall (odds ratio = 0.56, 95% confidence interval [CI] = 0.38 to 0.82; 79,148 prostate cancer cases and 61,106 controls), advanced, and early-onset prostate cancer. Using electronic healthcare data (nSGLT2i = 24,155; nDPP4i = 24,155), we found that the use of SGLT2 inhibitors was associated with a 23% reduced risk of prostate cancer (hazard ratio = 0.77, 95% CI = 0.61 to 0.99) in men with diabetes. Using data from two prospective cohorts (n4C = 57,779; nUK_Biobank = 165,430), we found little evidence to support the association of HbA1c with prostate cancer, implying a non-glycemic effect of SGLT2 inhibition on prostate cancer. In summary, this study provides multiple layers of evidence to support the beneficial effect of SGLT2 inhibition on reducing prostate cancer risk. Future trials are warranted to investigate whether SGLT2 inhibitors can be recommended for prostate cancer prevention.


Assuntos
Análise da Randomização Mendeliana , Neoplasias da Próstata , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Estudos de Coortes , Idoso , Hemoglobinas Glicadas/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/genética , Registros Eletrônicos de Saúde
4.
Bioresour Technol ; 410: 131268, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142416

RESUMO

This study uncovered the response of novel micro-granule wastewater treatment technology to different powder carrier materials. Characteristics and distinctions among different systems were assessed based on process performance, sludge aggregation capacity, and microbial metabolism. Zeolite carrier system exhibited remarkable nitrogen removal efficiency of 89.6 ± 0.9 %, while diatomite carriers, in conjunction with intermittent aeration, enhanced simultaneous nitrification and denitrification from 2.6 % to 27.1 %. Iron-based carriers demonstrated efficient phosphorus removal (94.7 ± 1.2 %) through both chemical and microbial pathways. Specific surface area, pore structure and biocompatibility of powder carriers determined the formation and size of micro-granules. Tryptophan-like substances, C-(C/H), and Npr in extracellular polymeric substances strongly correlated with sludge hydrophobicity and granulation. Significant enrichment in norank_Comamonadaceae and Nitrosomonas in zeolite powder carrier system promoted partial nitrification and endogenous denitrification. Differences in metabolic pathways elucidated the up-regulation of amino acid synthesis, energy metabolism, and membrane transport as potential mechanisms driving micro-granule formation and efficient treatment performance.

5.
Future Oncol ; : 1-10, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39155845

RESUMO

Background: In first/second generation EGFR-TKIs, strong PD-L1 expression contributes to primary resistance, significantly affecting patient prognosis. The relationship between PD-L1 expression levels and third-generation TKIs remains unclear.Methods: This study analyzed advanced NSCLC who received third-generation EGFR-TKIs as first-line systemic therapy from March 2019 to June 2022. The EGFR and PD-L1 status of the patients was also assessed.Results: Overall, 150 patients were included in this study. PD-L1 expression was negative (PD-L1 tumor proportion score <1%) in 89 cases, weak (1-49%) in 42 cases, and strong (≥50%) in 19 cases. mPFS for patients with negative, weak and strong PD-L1 expressions was 23.60, 26.12 and 16.60 months, respectively. The mPFS for strong PD-L1 expression was significantly shorter than that for with weak PD-L1 expression but was not associated with negativity. The same conclusions were shown in subgroup analyses of mutation types and TKI kinds. In addition, Relative to PD-L1-negative patients, resistance to TKIs may be associated with early progression for patients with strong PD-L1 expression.Conclusion: PD-L1 expression in tumor cells influenced the clinical outcomes of patients with advanced NSCLC treated with third-generation EGFR-TKIs. Stronger PD-L1 expression in TKIs-treated patients with advanced first-line EGFR-mutated NSCLC was associated with worse PFS.


[Box: see text].

6.
J Agric Food Chem ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39176472

RESUMO

ß-Myrcene is an important monoterpene compound widely used in the fragrance, agricultural, and food industries. The microbial production of ß-myrcene conforms to the trend of green biological manufacturing, which has great potential for development. The poor catalytic activity of ß-myrcene synthase (MS) and the insufficient supply of precursors are considered to be the bottlenecks of ß-myrcene production. Here, source screening, subcellular localization, enzyme fusion, and precursor-enhancing strategies were integrated for ß-myrcene biosynthesis with Saccharomyces cerevisiae. The ß-myrcene titer gradually increased by 218-fold (up to 63.59 mg/L) compared to that of the initial titer of the shake flask. Moreover, the titer reached 66.82 mg/L after the addition of antioxidants (1 mM glutathione, GSH, and 1% butylated hydroxytoluene, BHT). Ultimately, 142.64 mg/L ß-myrcene in S. cerevisiae was achieved in 5.0 L of fed-batch fermentation under a carbon restriction strategy, which was the highest reported titer in yeast thus far. This study not only established a platform for ß-myrcene production but also provided a reference for the efficient biosynthesis of other monoterpene compounds.

7.
Insects ; 15(7)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39057197

RESUMO

The firefly genus Oculogryphus Jeng, Engel & Yang, 2007 is a rare-species group endemic to Asia. Since its establishment, its position has been controversial but never rigorously tested. To address this perplexing issue, we are the first to present the complete mitochondrial sequence of Oculogryphus, using the material of O. chenghoiyanae Yiu & Jeng, 2018 determined through a comprehensive morphological identification. Our analyses demonstrate that its mitogenome exhibits similar characteristics to that of Stenocladius, including a rearranged gene order between trnC and trnW, and a long intergenic spacer (702 bp) between the two rearranged genes, within which six remnants (29 bp) of trnW were identified. Further, we incorporated this sequence into phylogenetic analyses of Lampyridae based on different molecular markers and datasets using ML and BI analyses. The results consistently place Oculogryphus within the same clade as Stenocladius in all topologies, and the gene rearrangement is a synapomorphy for this clade. It suggests that Oculogryphus should be classified together with Stenocladius in the subfamily Ototretinae at the moment. This study provides molecular evidence confirming the close relationship between Oculogryphus and Stenocladius and discovers a new phylogenetic marker helpful in clarifying the monophyly of Ototretinae, which also sheds a new light on firefly evolution.

8.
PLoS One ; 19(7): e0300213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954729

RESUMO

Rice wine, well known for its unique flavor, rich nutritional value, and health benefits, has potential for extensive market development. Rhizopus and Aspergillus are among several microorganisms used in rice wine brewing and are crucial for determining rice wine quality. The strains were isolated via Rose Bengal and starch as a combined separation medium, followed by oenological property and sensory evaluation screening. The strain exhibiting the best performance can be screened using the traditional rice wine Qu. The strains YM-8, YM-10, and YM-16, which exhibited strong saccharification and fermentation performance along with good flavor and taste, were obtained from traditional rice wine Qu. Based on ITS genetic sequence analysis, the YM-8, YM-10, and YM-16 strains were identified as Rhizopus microsporus, Rhizopus arrhizus, and Aspergillus oryzae. The optimum growth temperature of each of the three strains was 30°C, 32°C, and 30°C, and the optimum initial pH was 6.0, 6.5, and 6.5, respectively. The activities of α-amylase, glucoamylase, and protease of YM-16 were highest at 220.23±1.88, 1,269.04±30.32, and 175.16±1.81 U/g, respectively. The amino acid content of rice wine fermented in a 20-L bioreactor with the three mold strains was higher than that of the control group, except for arginine, which was significantly lower than that of the control group. The total amino acid content and the total content of each type of amino acid were ranked as YM-16 > YM-8 > YM-10 > control group, and the amino acid content varied greatly among the strains. The control group had a higher content, whereas YM-8 and YM-16 had lower contents of volatile aroma components than the control group and had the basic flavor substances needed for rice wine, which is conducive to the formation of rice wine aroma. This selected strain, YM-16, has strong saccharification and fermentation ability, is a rich enzyme system, and improves the flavor of rice wine, thereby demonstrating its suitability as a production strain for brewing.


Assuntos
Reatores Biológicos , Fermentação , Oryza , Vinho , Vinho/análise , Vinho/microbiologia , Oryza/microbiologia , Oryza/metabolismo , Reatores Biológicos/microbiologia , Rhizopus/metabolismo , Paladar , Aspergillus oryzae/metabolismo , Aspergillus oryzae/genética , Concentração de Íons de Hidrogênio
9.
Biodivers Data J ; 12: e129639, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39027381

RESUMO

Background: Dolichosoma Stephens, 1830 is small genus belonging to the tribe Dasytini of the family Dasytidae (Coleoptera, Cleroidea), with two subgenera and five species hitherto known. It is widespread in the Palearctic Region of Eurasia, but has never been reported from China until now. New information: The genus Dolichosoma Stephens, 1830 is reported from China for the first time, with discoveries of two newly-recorded species, including D. (Dolichomorphus) femorale Morawitz, 1861 and D. (Dolichosoma) lineare (Rossi, 1794) from Xinjiang Autonomous Region. They are re-described in detail and illustrated with habitus, ultimate abdominal tergites and sternites and genitalia of both sexes, as well as tarsal claws of male. In addition, a macrohabitat photograph and a distribution map of the two species occurring in China are provided.

10.
Front Pharmacol ; 15: 1419844, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978980

RESUMO

Introduction: The gastrointestinal tract is integral to defending against external contaminants, featuring a complex array of immunological, physical, chemical, and microbial barriers. Mycotoxins, which are toxic metabolites from fungi, are pervasive in both animal feed and human food, presenting substantial health risks. Methods: This review examines the pharmacological, toxicological, and microbiological impacts of natural products on mycotoxicosis, with a particular focus on the gut-x axis. The analysis synthesizes current understanding and explores the role of natural products rich in polysaccharides, polyphenols, flavonoids, and saponins. Results: The review highlights that mycotoxins can disrupt intestinal integrity, alter inflammatory responses, damage the mucus layer, and disturb the bacterial balance. The toxins' effects are extensive, potentially harming the immune system, liver, kidneys, and skin, and are associated with serious conditions such as cancer, hormonal changes, genetic mutations, bleeding, birth defects, and neurological issues. Natural products have shown potential anticancer, anti-tumor, antioxidant, immunomodulatory, and antitoxic properties. Discussion: The review underscores the emerging therapeutic strategy of targeting gut microbial modulation. It identifies knowledge gaps and suggests future research directions to deepen our understanding of natural products' role in gut-x axis health and to mitigate the global health impact of mycotoxin-induced diseases.

11.
Water Res ; 262: 122102, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39018580

RESUMO

Anaerobic digestion (AD) is a promising technology to realize the conversion from organic matters to methane, which is highly mediated by syntrophic microbial community via mutualistic interactions. However, small energy available in methanogenic conversion usually limits the metabolic activity. To adapt such energy-limited environment, efficient energy conservation is critical to support active physiological functions of anaerobic consortia for methanogenic metabolism. In this study, the contribution of extracellular proton transfer (EPT) enhancement to achieving energy-conserving methanogenesis in AD was explored. Proton-conductive medium (PCM) was applied to construct efficient proton transport pathway, and a large number of protons from extracellular water were found available to upregulate methanogenesis in AD, as indicated by the increase in the content of 2H (D) in methane molecules (over 40.7%), among which CO2-reduction-to-CH4 was effectively enhanced. The increases of adenosine triphosphate (ATP) concentration (+54.1%) and gene expression activities related to ATPase (+100.0%) and proton pump (+580.1%) revealed that enhanced EPT by PCM promoted transmembrane proton motive force generation to facilitate ATP synthesis. Based on genome-centric metatranscriptomic analyses, MAG14, MAG63 and MAG61 with high energy conservation activity displayed most pronounced positive response to the EPT enhancement. In these core MAGs, the metabolic pathway reconstruction and the key genes activity identification further proved that EPT enhancement-driven efficient ATP synthesis stimulated the cross-feeding of carbon and proton/electron to facilitate microbial mutualism, thereby resulting in the high energy-conserving methanogenesis. Overall, our work provides new insights into how EPT enhancement drives high energy-conserving methanogenesis, expanding our understanding of the ecological role of EPT in AD.


Assuntos
Metano , Prótons , Metano/metabolismo , Anaerobiose , Reatores Biológicos , Trifosfato de Adenosina/metabolismo
12.
Zookeys ; 1205: 101-113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947166

RESUMO

The clonal raider ant, Ooceraeabiroi, is a queenless species that reproduces asexually, and these traits make it an attractive model system for laboratory research. However, it is unclear where on the ant phylogeny these traits evolved, partly because few closely related species have been described and studied. Here, we describe a new raider ant species, Ooceraeahainingensis sp. nov., from Zhejiang, China. This species is closely related to O.biroi but can be distinguished by the following features: 1) workers of O.hainingensis sp. nov. have an obvious promesonotal suture and a metanotal groove, whereas these characters are ambiguous in O.biroi; and 2) the subpetiolar process of O.hainingensis is prominent and anteroventrally directed like a thumb with sublinear posteroventral margin, while in O.biroi, it is anteroventrally directed but slightly backward-bent. Molecular phylogenetic analyses confirm that O.hainingensis is genetically distinct from O.biroi. Importantly, unlike O.biroi, O.hainingensis has a queen caste with wings and well-developed eyes. This suggests that the loss of the queen caste and transition to asexual reproduction by workers is specific to O.biroi and occurred after that species diverged from closely related congeneric species.

13.
Zookeys ; 1203: 325-354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855787

RESUMO

The lycid genus Ponyalis Fairmaire, 1899 is reviewed. Six new species are described from China, including P.longicornis sp. nov., P.truncata sp. nov., P.dabieshanensis sp. nov., P.hainanensis sp. nov., P.quadricollimima sp. nov., and P.zhejiangensis sp. nov. Nine previously known species, including P.alternata (Pic, 1927), P.fukiensis (Bocak, 1999), P.gracilis (Bocak, 1999), P.himalejica (Bourgeois, 1885), P.klapperichi (Bocak, 1999), P.laticornis Fairmaire, 1899, P.nigrohumeralis (Pic, 1939), P.quadricollis (Kiesenwetter, 1874), and P.variabilis Li, Bocak & Pang, 2015 are illustrated with images of the habitus and aedeagi to make the comparisons with the new species. In addition, a distribution map and an identification key to all 24 species of Ponyalis are provided.

14.
Anim Microbiome ; 6(1): 34, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907293

RESUMO

BACKGROUND: Dietary fiber (DF) consumption was reported to improve insulin sensitivity, change the tryptophan metabolism, and alter the gut microbiota. Herein, this study aimed to investigate the effects of DF consumption on insulin sensitivity, tryptophan metabolism, and gut microbiota composition in sows during late pregnancy, and explore the relationship between tryptophan metabolites and insulin sensitivity regulated by DF supplementation. RESULTS: Twelve sows were randomly assigned to two dietary treatment groups (six/group): the low-fiber (LF) group, which was fed a basal diet, and the high-fiber (HF) group, which was fed the basal diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulose. During late pregnancy, meal test, glucose tolerance test, and insulin challenge test were used to investigate the insulin sensitivity of sows, using the percutaneous brachiocephalic vein catheterization technique. High DF consumption resulted in improved insulin sensitivity, especially during the second and third trimesters, and promoted serotonin production from tryptophan. Additionally, plasma serotonin concentration was positively correlated with the insulin sensitivity index during late pregnancy. Moreover, DF consumption elevated fecal short-chain fatty acid (SCFA) concentrations, altered fecal microbial diversity, and increased the abundances of Rikenellaceae_RC9_gut_group, Alloprevotella, Parabacteroides, Roseburia, and Sphaerochaeta, which were positively correlated to plasma serotonin concentration. CONCLUSIONS: DF consumption improved insulin sensitivity during late pregnancy in sows, which improved microbial diversity in fecal samples and increased fecal SCFA concentrations, resulting in a positive correlation with plasma serotonin level.

15.
Angew Chem Int Ed Engl ; 63(35): e202408574, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-38859545

RESUMO

All-solid-state potassium batteries emerge as promising alternatives to lithium batteries, leveraging their high natural abundance and cost-effectiveness. Developing potassium solid electrolytes (SEs) with high room-temperature ionic conductivity is critical for realizing efficient potassium batteries. In this study, we present the synthesis of K2.98Sb0.91S3.53Cl0.47, showcasing a room-temperature ionic conductivity of 0.32 mS/cm and a low activation energy of 0.26 eV. This represents an increase of over two orders of magnitude compared to the parent compound K3SbS4, marking the highest reported ionic conductivity for non-oxide potassium SEs. Solid-state 39K magic-angle-spinning nuclear magnetic resonance on K2.98Sb0.91S3.53Cl0.47 reveals an increased population of mobile K+ ions with fast dynamics. Ab initio molecular dynamics (AIMD) simulations further confirm a delocalized K+ density and significantly enhanced K+ diffusion. This work demonstrates diversification of the anion sublattice as an effective approach to enhance ion transport and highlights K2.98Sb0.91S3.53Cl0.47 as a promising SE for all-solid-state potassium batteries.

16.
Anal Chem ; 96(21): 8791-8799, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38742926

RESUMO

MicroRNAs (miRNAs) are novel tumor biomarkers owing to their important physiological functions in cell communication and the progression of multiple diseases. Due to the small molecular weight, short sequence length, and low concentration levels of miRNA, miRNA detection presents substantial challenges, requiring the advancement of more refined and sensitive techniques. There is an urgent demand for the development of a rapid, user-friendly, and sensitive miRNA analysis method. Here, we developed an enhanced biotin-streptavidin dual-mode phase imaging surface plasmon resonance (PI-SPR) aptasensor for sensitive and rapid detection of miRNA. Initially, we evaluated the linear sensing range for miRNA detection across two distinct sensing modalities and investigated the physical factors that influence the sensing signal in the aptamer-miRNA interaction within the PI-SPR aptasensor. Then, an enhanced biotin-streptavidin amplification strategy was introduced in the PI-SPR aptasensor, which effectively reduced the nonspecific adsorption by 20% and improved the limit of detection by 548 times. Furthermore, we have produced three types of tumor marker chips, which utilize the rapid sensing mode (less than 2 min) of PI-SPR aptasensor to achieve simultaneous detection of multiple miRNA markers in the serum from clinical cancer patients. This work not only developed a new approach to detect miRNA in different application scenarios but also provided a new reference for the application of the biotin-streptavidin amplification system in the detection of other small biomolecules.


Assuntos
Aptâmeros de Nucleotídeos , Biotina , MicroRNAs , Estreptavidina , Ressonância de Plasmônio de Superfície , MicroRNAs/análise , MicroRNAs/sangue , Biotina/química , Ressonância de Plasmônio de Superfície/métodos , Estreptavidina/química , Humanos , Aptâmeros de Nucleotídeos/química , Limite de Detecção , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Técnicas Biossensoriais/métodos
17.
Bioresour Technol ; 403: 130856, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763204

RESUMO

The inductive effect of conductive materials (CMs) on enhancing methanogenesis metabolism has been overlooked. Herein, we highlight role of CMs in inducing the spatial optimisation of methanogenic consortia by altering the Lewis acid-base (AB) interactions within microbial aggregates. In the presence of CMs and after their removal, the methane production and methane proportion in biogas significantly increase, with no significant difference between the two situations. Analyses of interactions between CMs and extracellular polymer substances (EPSs) with and without D2O reveal that CMs promote release and transfer potential of electron in EPSs, which induce and enhance the role of water molecules being primarily as proton acceptors in the hydrogen bonding between EPSs and water, thereby changing the electron-donor- and electron-acceptor-based AB interactions. Investigations of succession dynamics of microbial communities, co-occurrence networks, and metagenomics further indicate that electron transfer drives the microbial spatial optimisation for efficient methanogenesis through intensive interspecies interactions.


Assuntos
Metano , Consórcios Microbianos , Metano/metabolismo , Transporte de Elétrons , Anaerobiose , Consórcios Microbianos/fisiologia , Elétrons , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Biocombustíveis , Condutividade Elétrica , Ácidos de Lewis
18.
Front Endocrinol (Lausanne) ; 15: 1365321, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779454

RESUMO

Background: Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies. Objective: We aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC. Methods: In vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing. Results: PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed CTNNB1 somatic alterations were only found in responders (3/5) while ZNRF3 alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst CYP27A1 and ABCA1 expression were positively correlated to in vitro mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs. Conclusion: ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. CYP27A1 and ABCA1 expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Antineoplásicos Hormonais , Mitotano , Testes Farmacogenômicos , Humanos , Mitotano/uso terapêutico , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/metabolismo , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/metabolismo , Feminino , Masculino , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Pessoa de Meia-Idade , Adulto , Idoso , Farmacogenética
19.
Pharmaceutics ; 16(5)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794336

RESUMO

The escalating demand for enhanced therapeutic efficacy and reduced adverse effects in the pharmaceutical domain has catalyzed a new frontier of innovation and research in the field of pharmacy: novel drug delivery systems. These systems are designed to address the limitations of conventional drug administration, such as abbreviated half-life, inadequate targeting, low solubility, and bioavailability. As the disciplines of pharmacy, materials science, and biomedicine continue to advance and converge, the development of efficient and safe drug delivery systems, including biopharmaceutical formulations, has garnered significant attention both domestically and internationally. This article presents an overview of the latest advancements in drug delivery systems, categorized into four primary areas: carrier-based and coupling-based targeted drug delivery systems, intelligent drug delivery systems, and drug delivery devices, based on their main objectives and methodologies. Additionally, it critically analyzes the technological bottlenecks, current research challenges, and future trends in the application of novel drug delivery systems.

20.
Water Res ; 257: 121746, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38733966

RESUMO

Sewage sludge is promising for the recovery and utilisation of nutrient components, but its complex nature hinders the release of these components. The combination of pH and thermal modifications shows promise for the release of nutrient components from sludge. However, comprehensive studies on the full spectrum of pH levels and corresponding mechanisms of pH-varying thermal modification are lacking. In this study, the main nutrient components, physicochemical properties, molecular structure, and noncovalent interactions of sludge were comprehensively investigated through pH-varying thermal modification (within a pH range of 2.0 to 12.0 under the same thermal condition). The experimental results showed that the release of main organics, particularly nitrogen (N)-containing organics, was well-fitted, with a tick-like function (R2: 0.74-0.96). The thermal protons exhibited a notable accumulative mutagenic effect on the N-containing organics release, while the thermal hydroxyl ions had a more direct effect, as revealed by the changes in multivalent metals and molecular structures with the protonation-deprotonation of carboxyl groups. The driving force for the release of N-containing organics was identified as the fluctuation of electrostatic interactions at the solid-liquid interface of the sludge. However, the release of phosphorus (P)-containing substances exhibited a contrasting response to that of N-containing substances with varying pH, likely because the reaction sites of thermal protons and thermal hydroxyl ions for P-containing substances were different. Moreover, high concentrations of thermal protons and hydroxyl ions collapsed the Lifshitz-van der Waals interactions of sludge, resulting in a decrease in viscoelasticity and binding strength. These propositions were further confirmed through statistical analyses of the main indicators of the main nutrient components, physicochemical properties, and noncovalent interactions of sludge. These findings can provide a basis for optimising characteristic-specific methods to recovery nutrient components (N/P) from sludge.


Assuntos
Nitrogênio , Fósforo , Esgotos , Esgotos/química , Fósforo/química , Nitrogênio/química , Concentração de Íons de Hidrogênio , Eliminação de Resíduos Líquidos/métodos
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