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1.
Mol Cell ; 83(16): 3027-3040.e11, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37541260

RESUMO

The mechanistic target of rapamycin complex 1 (mTORC1) regulates metabolism and cell growth in response to nutrient levels. Dysregulation of mTORC1 results in a broad spectrum of diseases. Glucose is the primary energy supply of cells, and therefore, glucose levels must be accurately conveyed to mTORC1 through highly responsive signaling mechanisms to control mTORC1 activity. Here, we report that glucose-induced mTORC1 activation is regulated by O-GlcNAcylation of Raptor, a core component of mTORC1, in HEK293T cells. Mechanistically, O-GlcNAcylation of Raptor at threonine 700 facilitates the interactions between Raptor and Rag GTPases and promotes the translocation of mTOR to the lysosomal surface, consequently activating mTORC1. In addition, we show that AMPK-mediated phosphorylation of Raptor suppresses Raptor O-GlcNAcylation and inhibits Raptor-Rags interactions. Our findings reveal an exquisitely controlled mechanism, which suggests how glucose coordinately regulates cellular anabolism and catabolism.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Complexos Multiproteicos , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Células HEK293 , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Complexos Multiproteicos/metabolismo , Proteína Regulatória Associada a mTOR/genética , Proteína Regulatória Associada a mTOR/metabolismo , Fosforilação
2.
Mol Cell ; 82(4): 770-784.e9, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35114100

RESUMO

The mTOR complex 1 (mTORC1) is an essential metabolic hub that coordinates cellular metabolism with the availability of nutrients, including amino acids. Sestrin2 has been identified as a cytosolic leucine sensor that transmits leucine status signals to mTORC1. In this study, we identify an E3 ubiquitin ligase RING finger protein 167 (RNF167) and a deubiquitinase STAMBPL1 that function in concert to control the polyubiquitination level of Sestrin2 in response to leucine availability. Ubiquitination of Sestrin2 promotes its interaction with GATOR2 and inhibits mTORC1 signaling. Bioinformatic analysis reveals decreased RNF167 expression and increased STAMBPL1 expression in gastric and colorectal tumors. Knockout of STAMBPL1 or correction of the heterozygous STAMBPL1 mutation in a human colon cancer cell line suppresses xenograft tumor growth. Lastly, a cell-permeable peptide that blocks the STAMBPL1-Sestrin2 interaction inhibits mTORC1 and provides a potential option for cancer therapy.


Assuntos
Neoplasias Colorretais/enzimologia , Peptídeo Hidrolases/metabolismo , Neoplasias Gástricas/enzimologia , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Células CACO-2 , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HEK293 , Humanos , Leucina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação , Proteínas Nucleares/metabolismo , Peptídeo Hidrolases/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Carga Tumoral , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
3.
Plant J ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743909

RESUMO

Low temperature (LT) greatly restricts grain filling in maize (Zea mays L.), but the relevant molecular mechanisms are not fully understood. To better understand the effect of LT on grain development, 17 hybrids were subjected to LT stress in field trials over 3 years, and two hybrids of them with contrasting LT responses were exposed to 30/20°C and 20/10°C for 7 days during grain filling in a greenhouse. At LT, thousand-kernel weight declined, especially in LT-sensitive hybrid FM985, while grain-filling rate was on average about 48% higher in LT-tolerant hybrid DK159 than FM985. LT reduced starch synthesis in kernel mainly by suppression of transcript levels and enzyme activities for sucrose synthase and hexokinase. Brassinolide (BR) was abundant in DK159 kernel, and genes involved in BR and cytokinin signals were inducible by stress. LT downregulated the genes in light-harvesting complex and photosystem I/II subunits, accompanied by reduced photosynthetic rate and Fv/Fm in ear leaf. The LT-tolerant hybrid could maintain a high soluble sugar content and fast interconversion between sucrose and hexose in the stem internode and cob, improving assimilate allocation to kernel at LT stress and paving the way for simultaneous growth and LT stress responses.

4.
Plant J ; 114(2): 437-454, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36786687

RESUMO

Drought is a major abiotic stress reducing maize (Zea mays) yield worldwide especially before and during silking. The mechanism underlying drought tolerance in maize and the roles of different organs have not been elucidated. Hence, we conducted field trials under pre-silking drought conditions using two maize genotypes: FM985 (drought-tolerant) and ZD958 (drought-sensitive). The two genotypes did not differ in plant height, grain number, and yield under control conditions. However, the grain number per ear and the yield of FM985 were 38.1 and 35.1% higher and plants were 17.6% shorter than ZD958 under drought conditions. More 13 C photosynthates were transported to the ear in FM985 than in ZD958, which increased floret fertility and grain number. The number of differentially expressed genes was much higher in stem than in other organs. Stem-ear interactions are key determinants of drought tolerance, in which expression of genes related to abscisic acid, lignin, and flavonoid biosynthesis and carbon metabolism in the stem was induced by drought, which inhibited stem elongation and promoted assimilate allocation to the ear in FM985. In comparison with ZD958, the activities of trehalose 6-phosphate phosphatase and sucrose non-fermentation-associated kinase 1 were higher in the stem and lower in the kernel of FM985, which facilitated kernel formation. These results reveal that, beyond the ear response, stem elongation is involved in the whole process of drought tolerance before silking. Abscisic acid together with trehalose 6-phosphate, lignin, and flavonoid suppresses stem elongation and allocates assimilates into the ear, providing a novel and systematic regulatory pathway for drought tolerance in maize.


Assuntos
Ácido Abscísico , Resistência à Seca , Ácido Abscísico/metabolismo , Zea mays/metabolismo , Lignina/metabolismo , Flavonoides/metabolismo , Trealose/metabolismo , Grão Comestível , Secas , Fosfatos/metabolismo , Estresse Fisiológico
5.
J Autoimmun ; 142: 103148, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37967495

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints and produces pain, swelling, and stiffness. It has a lifetime prevalence of up to 1% worldwide. An extract of Tripterygium wilfordii Hook F (TwHF), a member of the Celastraceae herbal family widely available in south China, has been used for treatment of RA since 1960s. METHODS: The current consensus practice guidance (CPG) aims to offer guidance on the application of TwHF in the clinical management of active RA. The CPG followed World Health Organisation (WHO)'s recommended process, carried out three systematic reviews to synthesize data from 19 randomised controlled trials (RCT) involving 1795 participants. We utilized Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to evaluate certainty of evidence and derive recommendations. We rigorously followed The Appraisal of Guidelines for Research and Evaluation II (AGREE II) as conduct guides to minimise bias and promote transparency. RESULTS: There was no obvious difference between TwHF monotherapy and methotrexate (MTX) monotherapy on ACR20 (RCT = 2, N = 390, RR = 1.06, 95%CI 0.90-1.26, moderate certainty), ACR50 (RCT = 3, N = 419, RR = 1.03, 95%CI 0.80-1.34, moderate certainty), ACR70 (RCT = 2, N = 390, RR = 1.12, 95%CI 0.69-1.79, low certainty). TwHF monotherapy may be better than salicylazosulfapyridine monotherapy on ACR20 and the effect may be similar on ACR50 and ACR70. Seven RCTs compared MTX combined with TwHF versus MTX monotherapy, and the meta-analysis results favoured combination therapy group on ACR20 (RCT = 3, N = 470, RR = 1.44, 95%CI 1.28-1.62, moderate certainty), ACR50 (RCT = 4, N = 500, RR = 1.88, 95%CI 1.56-2.28, moderate certainty) and ACR70 (RCT = 2, N = 390, RR = 2.12, 95%CI 1.40-3.19, low certainty). We found no obvious difference between groups on critical safety outcomes, including infection (RCT = 3, N = 493, RR = 1.37, 95%CI 0.84-2.23), liver dysfunction (RCT = 5, N = 643, RR = 1.14, 95%CI 0.71-1.85), renal damage (RCT = 3, N = 450, RR = 2.20, 95%CI 0.50-9.72). CONCLUSION: Upon full review of the evidence, the guidance panel reached consensus on recommendations for the use of TwHF in people with active RA, either as monotherapy or as combination therapy with MTX.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Antirreumáticos/uso terapêutico , Tripterygium , Consenso , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Doença Crônica
6.
Pestic Biochem Physiol ; 200: 105830, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582593

RESUMO

Chlorantraniliprole (CAP) is a bis-amide pesticide used for pest control mainly in agricultural production activities and rice-fish co-culture systems. CAP residues cause liver damage in non-target organism freshwater fish. However, it is unclear whether CAP-exposure-induced liver injury in fish is associated with mitochondrial dysfunction-mediated mitophagy, ferroptosis, and cytokines. Therefore, we established grass carp hepatocyte models exposed to different concentrations of CAP (20, 40, and 80 µM) in vitro. MitoSOX probe, JC-1 staining, immunofluorescence double staining, Fe2+ staining, lipid peroxidation staining, qRT-PCR, and Western blot were used to verify the physiological regulatory mechanism of CAP induced liver injury. In the present study, the CAP-treated groups exhibited down-regulation of antioxidant-related enzyme activities and accumulation of peroxides. CAP treatment induced an increase in mitochondrial reactive oxygen species (mtROS) levels and altered expression of mitochondrial fission/fusion (Drp1, Fis1, Mfn1, Mfn2, and Opa1) genes in grass carp hepatocytes. In addition, mitophagy (Parkin, Pink1, p62, LC3II/I, and Beclin-1), ferroptosis (GPX4, COX2, ACSL4, FTH, and NCOA4), and cytokine (IFN-γ, IL-18, IL-17, IL-6, IL-10, IL-1ß, IL-2, and TNF-α)-related gene expression was significantly altered. Collectively, these findings suggest that CAP exposure drives mitophagy activation, ferroptosis occurrence, and cytokine homeostasis imbalance in grass carp hepatocytes by triggering mitochondrial dysfunction mediated by the mtROS-mitochondrial fission/fusion axis. This study partly explained the physiological regulation mechanism of grass carp hepatocyte injury induced by insecticide CAP from the physiological and biochemical point of view and provided a basis for evaluating the safety of CAP environmental residues to non-target organisms.


Assuntos
Carpas , Doença Hepática Crônica Induzida por Substâncias e Drogas , Ferroptose , Doenças Mitocondriais , ortoaminobenzoatos , Animais , Citocinas/genética , Transdução de Sinais , Dinâmica Mitocondrial , Mitofagia , Hepatócitos , Homeostase
7.
J Foot Ankle Surg ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866200

RESUMO

In order to evaluate the early radiographic characteristics of the lateral talocalcaneal (L-TC) angle in patients with idiopathic clubfoot (ICF) and to investigate its prognostic significance for relapse after initial treatment with the Ponseti method. We retrospectively included 151 patients (96 males and 55 females; 227 feet) with ICF treated at our Institution between January 2005 and December 2014. The age at initial treatment was less than 6 months, and radiographs were obtained within 3 months of the Achilles tenotomy (mean age: 2.3 months; range: 0.77-6.8). All patients were followed up for at least 7 years (range, 7-18). The participants' feet were classified into three groups: relapsed (Group A), not relapsed (Group B), and normal foot groups which consisted of healthy feet in patients with unilateral ICF (Group C). All angle measurements were expressed in degrees. Forty-seven ICF feet in 33 patients relapsed, while 180 feet in 118 patients did not, and the age at relapse was 5.92±1.91 years. Seventy-five normal feet were included in Group C. The average L-TC angle in Group A and B patients was 33.57°±12.05° and 39.37°±12.55°, respectively, while Group C was 49.61°±9.11°. A significant difference was found among the three groups of patients (F=31.48, P<0.001). The L-TC angle cut-off value below which a recurrence could be predicted was 36.1° (sensitivity, 74.47%). The L-TC angle of ICF patients treated using the Ponseti method were reduced compared to normal feet. An L-TC angle of <36.1° has relative value in predicting ICF relapse. LEVEL OF EVIDENCE: III.

8.
Nanotechnology ; 34(15)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36630705

RESUMO

The construction of an environmentally responsive drug-release system is of great significance for the treatment of special diseases. In particular, the construction of nanomaterials with pH- and thermal-responsiveness, which can effectively encapsulate drugs and control drug release, is becoming hot research. In this study, zwitterionic nanocapsules with stable core-shell structures were synthesized by inverse reversible addition-fragmentation transfer miniemulsion interfacial polymerization. To further study the structure and performance of the nanocapsules, the prepared nanocapsules were characterized by transmission electron microscopy, dynamic light dispersion, and zeta potential analysis. It was found that the nanocapsules had dual pH- and thermal- responsiveness, and the average particle size ranged from 178 to 142 nm when the temperature changed from 25 °C to 40 °C. In addition, bovine serum albumin (BSA) was encapsulated into nanocapsules, and sustained release experiments were conducted at 10 °C and 40 °C. The results showed that nanocapsules as carriers of BSA could achieve the purpose of sustained release of drugs, and showed different sustained release curves at different temperatures. Finally,in vitrocytotoxicity tests were performed to demonstrate the feasibility of their biomedical application. It is believed that the dual pH- and thermal- responsive nanocapsules are promising for drug-controlled release.


Assuntos
Nanocápsulas , Nanocápsulas/química , Liberação Controlada de Fármacos , Preparações de Ação Retardada , Microscopia Eletrônica de Transmissão , Soroalbumina Bovina , Concentração de Íons de Hidrogênio , Tamanho da Partícula
9.
Food Microbiol ; 111: 104207, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36681394

RESUMO

Nisin is a posttranslationally modified antimicrobial peptide that is widely used as a food preservative. It contains five cyclic thioethers of varying sizes. Nisin activity and stability are closely related to its primary and three dimensional structures. It has nine reported natural variants. Nisin A is the most studied nisin as it was the first one purified. Here, we review the sequence feature of nisin A and its natural variants, and their biosynthesis pathway, mode of action and application as a meat preservative. We systematically illustrate the functional domains of the main enzymes (NisB, NisC, and NisP) involved in nisin synthesis. NisB was shown to dehydrate its substrate NisA via a tRNA associated glutamylation mechanism. NisC catalysed the cyclization of the didehydro amino acids with the neighboring cysteine residues. After cyclization, the leader peptide is removed by the protease NisP. According to multiple sequence alignments, we detected five conserved sites Dha5, Pro9, Gly14, Leu16, and Lys22. These residues are probably the structural and functional important ones that can be modified to produce peptides versions with enhanced antimicrobial activity. Through comparing various application methods of nisin in different meats, the antimicrobial effects of nisin used individually or in combination with other natural substances were clarified.


Assuntos
Anti-Infecciosos , Conservação de Alimentos , Lactococcus lactis , Carne , Nisina , Anti-Infecciosos/metabolismo , Proteínas de Bactérias/metabolismo , Lactococcus lactis/metabolismo , Proteínas de Membrana , Nisina/farmacologia , Nisina/química , Carne/microbiologia
10.
Ecotoxicol Environ Saf ; 256: 114874, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37054469

RESUMO

Lead (Pb), cadmium (Cd) and total mercury (THg) are toxic heavy metals (THMs) that are widely present in the environment and can cause substantial health problems. However, previous risk assessment studies have rarely focused on the elderly population and have usually targeted a single heavy metal, which might underestimate the long-term accumulative and synergistic effects of THMs in humans. Based on the food frequency questionnaire and inductively coupled plasma mass spectrometry, this study assessed external and internal exposures to Pb, Cd and THg in 1747 elderly people in Shanghai. Probabilistic risk assessment with the relative potential factor (RPF) model was used to assess the neurotoxicity and nephrotoxicity risks of combined THMs exposures. The mean external exposures of Pb, Cd and THg in Shanghai elderly were 46.8, 27.2 and 4.9 µg/day, respectively. Plant-based foods are the main source of Pb and THg exposure, while Cd is mainly from animal-based foods. The mean concentrations of Pb, Cd and THg were 23.3, 1.1 and 2.3 µg/L in the whole blood, and 6.2, 1.0 and 2.0 µg/L in the morning urine, respectively. Combined exposure to THMs leading to 10.0 % and 7.1 % of Shanghai elderly at risk of neurotoxicity and nephrotoxicity. The results of this study have important implications for understanding the profiles of Pb, Cd and THg exposure in the elderly living in Shanghai and provide data support for risk assessment and control of nephrotoxicity and neurotoxicity from combined THMs exposure in the elderly.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Mercúrio , Metais Pesados , Síndromes Neurotóxicas , Animais , Humanos , Idoso , Cádmio/toxicidade , Mercúrio/análise , Chumbo/análise , China , Metais Pesados/análise , Intoxicação por Metais Pesados , Medição de Risco
11.
Pestic Biochem Physiol ; 196: 105625, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37945258

RESUMO

Cypermethrin (CYP, IUPAC name: [cyano-(3-phenoxyphenyl)methyl] 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate) is a pyrethroid insecticide that poses a threat to the health of humans and aquatic animals due to its widespread use and environmental contamination. However, the mechanism of CYP on apoptosis, autophagy and inflammation in hepatocytes of carp (Cyprinus carpio) is unknown. We hypothesized that CYP caused damage to hepatocytes through the endoplasmic reticulum stress (ERS) pathway, CCK-8 was used to detect the toxic effects of different doses of CYP on hepatocytes, and finally low (L, 10 µM), medium (M, 40 µM), and high (H, 80 µM) doses of CYP was selected to construct the model. ROS staining, oxidative stress-related indices (MDA, CAT, T-AOC, SOD), AO/EB staining, MDC staining, and the expression levels of related genes were detected using qRT-PCR and western blot. Our results showed that CYP exposure resulted in an increase in ROS production, an increase in MDA content, and a decrease in the activity of CAT, SOD, and T-AOC in hepatocytes; the proportion of apoptotic, necrotic, and autophagic cells increased significantly in a dose-dependent manner. We also found that CYP exposure increased the expression levels of endoplasmic reticulum-related genes (GRP78, PERK, IRE-1, ATF-6 and CHOP), apoptosis (Bcl-2, Bax, Caspase-3, Caspase-9 and Cyt-c) and autophagy-related genes (LC3b, Beclin1 and P62) also showed dose-dependent changes, and the expression levels of inflammation-related genes (NF-κB, TNF-α, IL-1ß, IL-6) were also significantly elevated. Thus, we demonstrated that CYP exposure caused apoptosis, autophagy and inflammation in hepatocytes via ERS-ROS-NF-κB axis. This research contributes to our understanding of the molecular mechanisms underlying CYP-induced damage in hepatocytes of carp (Cyprinus carpio).


Assuntos
Carpas , Piretrinas , Humanos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Carpas/metabolismo , Apoptose , Piretrinas/toxicidade , Hepatócitos , Inflamação/induzido quimicamente , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Autofagia , Estresse do Retículo Endoplasmático
12.
BMC Ophthalmol ; 22(1): 234, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606707

RESUMO

BACKGROUND: To compare the quantitative and qualitative optical outcomes of single-step transepithelial photorefractive keratectomy (TPRK) and off-flap epipolis-laser in situ keratomileusis (Epi-LASIK) in moderate to high myopia. METHODS: In this prospective self-control study, we included patients with moderate to high myopia who were randomized to undergo TPRK in one eye and Epi-LASIK in the other eye. Twelve-month follow-up results for visual acuity, refraction, ocular high-order aberrations, contrast sensitivity, postoperative pain, epithelial healing, and haze grade were assessed. RESULTS: A total of 64 eyes (32 patients) were enrolled in the study. More eyes completed re-epithelialization in the TPRK group than in the Off-flap Epi-LASIK group 3-4 days postoperatively, while all eyes completed re-epithelialization by 7 days. More eyes achieved a visual acuity (both UDVA and CDVA) of better than 20/20 in the TPRK group than in the Off-flap Epi-LASIK group. The ±0.50 D predictability for correction of the spherical equivalent (SE) was higher in the eyes of the TPRK group (91%) than in those of the off-flap Epi-LASIK group (80%) 12 months after surgery. No significant differences in ocular aberrations, including coma, spherical, and trefoil, were found between the two groups at 12 months. There were also no significant differences in visual acuity, contrast sensitivity, pain, and haze grading between the two groups. CONCLUSIONS: Both TPRK and off-flap Epi-LASIK are safe, effective, and predictable treatments for moderate to high myopia with comparable surgical outcomes. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrial.gov ( NCT05060094 , 17/09/2021).


Assuntos
Ceratomileuse Assistida por Excimer Laser In Situ , Miopia , Ceratectomia Fotorrefrativa , Seguimentos , Humanos , Hiperplasia , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Estudos Prospectivos , Refração Ocular , Resultado do Tratamento
13.
Mol Microbiol ; 114(3): 423-442, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32323346

RESUMO

Intracellular protein degradation is essential for the survival of all organisms, but its role in interspecies interaction is unknown. Here, we show that the ClpXP protease of Pseudomonas aeruginosa suppresses its antimicrobial activity against Staphylococcus aureus, a common pathogen co-isolated with P. aeruginosa from polymicrobial human infections. Using proteomic, biochemical, and molecular genetic approaches, we found that this effect is due to the inhibitory effects of ClpXP on the quorum sensing (QS) of P. aeruginosa, mainly by degrading proteins (e.g., PhnA, PhnB, PqsR, and RhlI) which are critical for the production of QS signal molecules PQS and C4-HSL. We provide evidence that co-culturing with S. aureus induces a decrease in the activity of ClpXP in P. aeruginosa, an effect which was also achieved by the treatment of P. aeruginosa with N-acetylglucosamine (GlcNAc), a widespread chemical present on the surface of diverse cell types from bacteria to humans. These findings extend the range of biological events governed by proteolytic machinery to microbial community structure, thus also suggesting that a chemical-induced alteration of protein homeostasis is a mechanism for interspecies interactions.


Assuntos
Acetilglucosamina/farmacologia , Endopeptidase Clp/metabolismo , Pseudomonas aeruginosa/fisiologia , Percepção de Quorum/genética , Staphylococcus aureus/fisiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Endopeptidase Clp/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Interações Microbianas , Mutação , Proteólise/efeitos dos fármacos , Proteômica , Proteostase , Infecções por Pseudomonas/microbiologia , Percepção de Quorum/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia
14.
J Environ Manage ; 298: 113474, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364244

RESUMO

China is the second largest irrigated country in the world. Increasing irrigation intensity costs more water and energy, and produces more greenhouse gas (GHG). In the present study, the responses of maize economic and environmental benefits to different irrigation managements were analyzed in a 2-year field study. A purposely designed tube-study was conducted to explore mechanism underlying effects of irrigation managements in detail. Three treatments, rainfed (RF), flood irrigation (FI), and drip irrigation (DI) were included in the field. Five treatments, no irrigation, flood irrigation, irrigation in 0-30, 30-60, and 0-90 cm depth were conducted in the tube study. Compared to RF, grain yields of FI and DI significantly increased by 22.1 % and 35.7 %, respectively, the net ecosystem economic budget significantly increased by 34.2 % and 35.6 %, and carbon footprint decreased by 7.0 % and 12.7 % in the field study. The irrigation treatments in the tube study increased the global warming potential by 12.0-32.8 % and grain yield by 44.5-203.9 %, and reduced GHG intensity by 24.3-57.4 %, compared with no irrigation treatment. Water content at the top soil layer had the greatest impact on GHG emissions. In conclusion, the differences in grain yield and GHG emissions among irrigation managements are mainly due to the soil water content in space and time. Drip irrigation decreases GHG intensity by producing more grain yield due to the optimized soil water distribution in the root zone. Irrigation management with appropriate amount and frequency can increase economic benefit and reduce environmental cost in maize production.


Assuntos
Aquecimento Global , Zea mays , Irrigação Agrícola , Agricultura , China , Ecossistema , Óxido Nitroso/análise , Solo
15.
Angew Chem Int Ed Engl ; 60(1): 24-40, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592283

RESUMO

ß-Lactam antibiotics are generally perceived as one of the greatest inventions of the 20th century, and these small molecular compounds have saved millions of lives. However, upon clinical application of antibiotics, the ß-lactamase secreted by pathogenic bacteria can lead to the gradual development of drug resistance. ß-Lactamase is a hydrolase that can efficiently hydrolyze and destroy ß-lactam antibiotics. It develops and spreads rapidly in pathogens, and the drug-resistant bacteria pose a severe threat to human health and development. As a result, detecting and inhibiting the activities of ß-lactamase are of great value for the rational use of antibiotics and the treatment of infectious diseases. At present, many specific detection methods and inhibitors of ß-lactamase have been developed and applied in clinical practice. In this Minireview, we describe the resistance mechanism of bacteria producing ß-lactamase and further summarize the fluorogenic probes, inhibitors of ß-lactamase, and their applications in the treatment of infectious diseases. It may be valuable to design fluorogenic probes with improved selectivity, sensitivity, and effectiveness to further identify the inhibitors for ß-lactamases and eventually overcome bacterial resistance.


Assuntos
Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Corantes Fluorescentes/uso terapêutico , Resistência beta-Lactâmica/efeitos dos fármacos , Inibidores de beta-Lactamases/uso terapêutico , Humanos , Inibidores de beta-Lactamases/farmacologia
16.
Liver Int ; 40(12): 2982-2997, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32652799

RESUMO

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low- (LP) or high-protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved. METHODS: 19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500-1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery. RESULTS: IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA-seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of ß-oxidation genes did not increase in the HP group. CONCLUSIONS: HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.


Assuntos
Dieta Rica em Proteínas , Dieta com Restrição de Proteínas , Autofagia , Dieta , Dieta Hiperlipídica , Proteínas Alimentares , Fatores de Crescimento de Fibroblastos , Humanos , Fígado
17.
J Sci Food Agric ; 100(14): 5102-5110, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29691867

RESUMO

Over the last 27 years (1990-2017), based on the revolutionary progresses of basic nutrition research, novel methods and techniques have been developed which bring a profound technological revolution to pig production from free-range system to intensive farming all over the world. Basic theoretical innovations and feed production studies have provided vital advancements in pig nutrition by developing formula feed, utilizing balanced diets, determining feed energy value, dividing pig physiological stages, enhancing gut health, and improving feed processing technique. Formula feed is the primary contributor of the rise of the mechanized farming industry, and meets comprehensive nutritional needs of the pig. The focuses of the development of a balanced diet by optimizing nutrient levels are the amino acids balance, the balance between amino acids and energy, the balance between calcium and phosphorus. Multiple-site-production and targeted feeding program have been applied extensively. Early weaning of piglets improves production efficiency, but piglets that have not yet fully developed their intestine are prone to diarrhea. Therefore, intestinal health has received special attention in recent years. Feed processing technologies, such as granulation, puffing, fermentation and enzymatic hydrolysis, can improve the utilization of feed nutrients and reduce production cost. However, increasing a sow's potential for production, seeking alternatives to antibiotics, reducing drug treatment in piglets, developing functional additives and improving meat quality remain future challenges. Herein, we outline the important progresses of pig nutrition in the past 27 years, which will shed light on the basic nutrition rules of pig production, and help to push forward its future development. © 2018 Society of Chemical Industry.


Assuntos
Ração Animal/análise , Ciências da Nutrição Animal/história , Suínos/metabolismo , Aminoácidos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , História do Século XX , História do Século XXI , Carne/análise , Minerais/metabolismo , Suínos/crescimento & desenvolvimento
18.
Chembiochem ; 20(6): 831-837, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30485616

RESUMO

A fast-response fluorogenic probe-compound D1-for monitoring hypochlorite (ClO- ), based on specific ClO- cleavage of a C=N bond and producing results observable to the naked eye, has been developed. The response of the probe to ClO- increases linearly, and the fluorescence intensity was heightened by a factor of about 25. D1 responses to ClO- , with high selectivity and sensitivity, were observable by naked eye within 10 s. D1 can not only detect levels of hypochlorite in vitro, such as in urine, but is also capable of monitoring hypochlorite content under extremely cold conditions, as low as -78 °C. Meanwhile, its good biocompatibility permitted the use of D1 to detect intracellular ClO- by confocal microscopy. Moreover, D1 was successfully applied to monitor exogenous and endogenous ClO- in zebrafish through fluorescence imaging.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/urina , Naftóis/química , Oximas/química , Animais , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Naftóis/toxicidade , Oximas/toxicidade , Temperatura , Peixe-Zebra
19.
J Nutr ; 149(6): 989-995, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31070764

RESUMO

BACKGROUND: Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown. OBJECTIVES: This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil-supplemented diet. METHODS: Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil-supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05). RESULTS: SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05). CONCLUSIONS: TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease.


Assuntos
Suplementos Nutricionais/efeitos adversos , Tamanho da Ninhada de Vivíparos/fisiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Óleo de Soja/administração & dosagem , Óleo de Soja/efeitos adversos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Modelos Animais de Doenças , Feminino , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Masculino , Troca Materno-Fetal/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Carneiro Doméstico
20.
Phys Chem Chem Phys ; 21(5): 2453-2462, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30652710

RESUMO

Soft thermal interface materials (TIMs) composed of thermally conductive fillers and polymer matrixes have been widely employed for thermal management in electronic and energy devices. However, the thermal conductivity (κ) of TIMs is significantly smaller than the intrinsic κ of fillers due to the large interfacial thermal contact resistance between fillers. Here we achieve a very efficient thermal percolation network of flower-shaped silver nanoparticles (silver nanoflowers, Ag NFs) in soft polyurethane (PU) matrix TIMs. A record high κ (42.4 W m-1 K-1) is achieved compared with soft isotropic TIMs in the literature. Ag nanoflake-PU and Ag nanosphere-PU TIMs provide significantly smaller κ (7.9 and 15.0 W m-1 K-1) at an identical filler concentration (38 vol%). Surprisingly, the phonon transport of the Ag NF-PU TIM dramatically increases (κlat = 22.2 W m-1 K-1) compared with Ag nanoflake-PU and Ag nanosphere-PU (κlat = 0.2 and 1.2 W m-1 K-1) TIMs. Kinetic theory reveals that the phonon mean free path (39.6 nm) is significantly increased for the Ag NF-PU TIM by the active coalescence of metallic Ag NFs. The hierarchically structured Ag NFs construct an excellent thermal percolation network in soft isotropic TIMs.

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