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1.
Cell ; 184(3): 775-791.e14, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33503446

RESUMO

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.


Assuntos
COVID-19/metabolismo , Regulação da Expressão Gênica , Proteoma/biossíntese , Proteômica , SARS-CoV-2/metabolismo , Autopsia , COVID-19/patologia , COVID-19/terapia , Feminino , Humanos , Masculino , Especificidade de Órgãos
2.
BMC Cancer ; 24(1): 1150, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285347

RESUMO

PURPOSE: This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis. RESULTS: This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p < 0.0001], and fewer overall complications [OR 0.62; 95% CI 0.45 to 0.86; p = 0.004], but a higher recurrence rate [OR 7.83; 95% CI 4.32 to 14.19; p < 0.00001]. There were no significant differences between the two groups in terms of operative time, minor complications (Clavien-Dindo Grade 1-2), major complications (Clavien-Dindo Grade 3-5), changes in renal function at 12 months post-operation, RFS (Recurrence-Free Survival), and OS (Overall Survival). CONCLUSION: The evidence provided by this meta-analysis indicates that the therapeutic effects of Cryoablation (CA) are similar to those of Robot-Assisted Partial Nephrectomy (RAPN) in terms of perioperative outcomes and renal function. However, the recurrence rate of tumors treated with CA is significantly higher. SYSTEMATIC REVIEW REGISTRATION: The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023465846).


Assuntos
Criocirurgia , Neoplasias Renais , Nefrectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Criocirurgia/métodos , Criocirurgia/efeitos adversos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos , Nefrectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação/estatística & dados numéricos
3.
Inorg Chem ; 63(25): 11554-11565, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38815997

RESUMO

Efficient and multiple CO2 utilization into high-value-added chemicals holds significant importance in carbon neutrality and industry production. However, most catalysis systems generally exhibit only one type of CO2 transformation with the efficiency to be improved. The restricted abundance of active catalytic sites or an inefficient utilization rate of these sites results in the constraint. Consequently, we designed and constructed two metal hydrogen-bonded organic frameworks (M-HOFs) {[M3(L3-)2(H2O)10]·2H2O}n (M = Co (1), Ni (2); L = 1-(4-carboxyphenyl)-1H-pyrazole-3,5-dicarboxylic acid) in this research. 1 and 2 are well-characterized, and both show excellent stability. The networks connected by multiple hydrogen bonds enhance the structural flexibility and create accessible Lewis acidic sites, promoting interactions between the substrates and catalytic centers. This enhancement facilitates efficient catalysis for two types of CO2 transformations, encompassing both cycloaddition reactions with epoxides and aziridines to afford cyclic carbonates and oxazolidinones. The catalytic activities (TON/TOF) are superior compared with those of most other catalysts. These heterogeneous catalysts still exhibited high performance after being reused several times. Mechanistic studies indicated intense interactions between the metal sites and substrates, demonstrating the reason for efficient catalysis. This marks the first instance on M-HOFs efficiently catalyzing two types of CO2 conversions, finding important significance for catalyst design and CO2 utilization.

4.
Inorg Chem ; 63(36): 16878-16887, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39190825

RESUMO

Effective CO2 transformations hold essential significance for carbon neutrality and sustainable energy development. Carboxylative cyclization of propargylic amines with CO2 serves as an atom-economic reaction to afford oxazolidinones, showing broad applications in organic synthesis and pharmaceutical fields. However, most catalysts involved noble metals, exhibited low efficiency, or required large amounts of base. Hence, it is imperative to explore alternative noble-metal-free catalysts in order to achieve efficient conversion while minimizing the use of additives. Herein, a novel nanopore-based Cu(II)-organic framework (1) based on a new imidazole carboxylic ligand was successfully constructed and exhibited excellent stability. Catalytic investigations revealed that the combination of 1 with 1,4-diaza[2.2.2]bicyclooctane (DABCO) efficiently catalyzed the carboxylative cyclization of propargylic amines with CO2, achieving turnover numbers of 142 based on the catalyst and 7.1 based on DABCO. 1 as a heterogeneous catalyst maintained high catalytic performance even after being reused at least 5 cycles, with its structure remaining stable. The strong activation of Cu(II) cluster nodes of catalyst 1 toward -NH- groups within organic substrates, as demonstrated by mechanism experiments, along with excellent CO2 adsorption performance and the presence of regular 1D channels, synergistically facilitates the reaction rate. This research presents the first instance of a Cu(II)-organic framework achieving this cyclization reaction, offering wide prospects for novel catalyst design and CO2 utilization.

5.
Chirality ; 36(2): e23634, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38057950

RESUMO

To investigate the thermodynamic and molecular self-assembly mechanism of trans-1,2-cyclohexane dicarboxylic acid containing two carboxylic acid groups in the chiral resolution process, (S)-phenylethylamine was used as the chiral resolving agent. Two stoichiometric salts were formed when the raw materials were fed at different molar ratios: cyclohexane dicarboxylate monophenylethylamine salt and cyclohexane dicarboxylate diphenylethylamine salt. When the molar ratio of the (S)-phenylethylamine to trans-1,2-cyclohexane dicarboxylic acid was less than 3:1, trans-(1S,2S)-cyclohexane dicarboxylic acid was obtained with 97 e.e% purity. But when the molar ratio exceeded 3:1, the product was the racemic trans-(1,2)-cyclohexane dicarboxylic acid. In addition, single crystal structures of more soluble mono-salt, less soluble mono-salt, and less soluble di-salt were obtained. The weak intermolecular interactions and the way of the molecules packing in the crystals were analyzed. The hydrogen bond was stronger in the less soluble salt than that in the more soluble salt. And a "lock-and-key" structure in the hydrophobic layers makes it more tightly packed through the van der Waals interaction, which is responsible for the stability of less soluble salts.

6.
Chirality ; 36(4): e23662, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572642

RESUMO

In the present study, flat cellulose acetate ultrafiltration membranes were prepared first by nonsolvent induced phase separation method. Then chiral membranes for separating the enantiomers were prepared by grafting the ultrafiltration membranes using ethylenediamine-ß-cyclodextrin as the chiral selector and epichlorohydrin as the spacer arm. The pure water permeability of the ultrafiltration membrane was around 115 L·m-2·h-1·bar-1. The properties of the chiral membranes were characterized using infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The chiral membrane performance in enantiomer separation was evaluated with racemates, such as mandelic acid (MA), 2-chloromandelic acid (2-ClMA), 4-chloromandelic acid (4-ClMA), and methyl mandelate (MM). The influence of feed concentration on the separation efficiency was also investigated. The results indicated that the enantiomeric excess percentages (e.e%) of the racemic mixtures for these four chiral compounds were up to 31.8%, 25.4%, 17.8%, and 32.6%, respectively. The binding free energy of the chiral selector with the (S)-enantiomer calculated by molecular dynamics simulations was stronger than that with the (R)-enantiomer, which was consistent with the experimental results (higher concentration of (R)-enantiomer in the permeate). This supports the affinity absorption-separation mechanism.

7.
Molecules ; 29(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38611944

RESUMO

Two types of cellulose nanofibrils (CNFs) were isolated from cotton linter fibers and hardwood fibers through mechanical fibrillation methods. The dialdehyde cellulose nanofibrils (DACNFs) were prepared through the periodate oxidation method, and their morphological and structural properties were investigated. The characteristics of the DACNFs during the concentration process were also explored. The AFM analysis results showed that the mean diameters of wood fiber-based CNFs and cotton fiber-based CNFs were about 52.03 nm and 69.51 nm, respectively. However, the periodate oxidation treatment process obviously reduced the nanofibril size and destroyed the crystalline region of the nanofibrils. Due to the high crystallinity of cotton fibers, the cotton fiber-based DACNFs exhibited a lower aldehyde content and suspension stability compared to the wood fiber-based DACNFs. For the concentration process of the DACNF suspension, the bound water content of the concentrated cotton fiber-based DACNFs was lowered to 0.41 g/g, which indicated that the cotton fiber-based DACNFs could have good redispersibility. Both the wood fiber-based and cotton fiber-based DACNF films showed relatively good transmittance and mechanical strength. In addition, to the cotton fiber-based DACNF films had a very low swelling ratio, and the barrier water vapor and oxygen properties of the redispersed cotton fiber-based DACNF films decreased by very little. In sum, this study has demonstrated that cotton fibers could serve as an effective alternative to wood fibers for preparing CNFs, and that cotton fiber-based DACNFs have huge application prospects in the field of packaging film materials due to their stable properties during the concentration process.

8.
Br J Cancer ; 128(11): 2126-2139, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36977825

RESUMO

BACKGROUND: Enhancing the response rate of immunotherapy will aid in the success of cancer treatment. Here, we aimed to explore the combined effect of immunogenic radiotherapy with anti-PD-L1 treatment in immunotherapy-resistant HNSCC mouse models. METHODS: The SCC7 and 4MOSC2 cell lines were irradiated in vitro. SCC7-bearing mice were treated with hypofractionated or single-dose radiotherapy followed by anti-PD-L1 therapy. The myeloid-derived suppressive cells (MDSCs) were depleted using an anti-Gr-1 antibody. Human samples were collected to evaluate the immune cell populations and ICD markers. RESULTS: Irradiation increased the release of immunogenic cell death (ICD) markers (calreticulin, HMGB1 and ATP) in SCC7 and 4MOSC2 in a dose-dependent manner. The supernatant from irradiated cells upregulated the expression of PD-L1 in MDSCs. Mice treated with hypofractionated but not single-dose radiotherapy were resistant to tumour rechallenge by triggering ICD, when combined with anti-PD-L1 treatment. The therapeutic efficacy of combination treatment partially relies on MDSCs. The high expression of ICD markers was associated with activation of adaptive immune responses and a positive prognosis in HNSCC patients. CONCLUSION: These results present a translatable method to substantially improve the antitumor immune response by combining PD-L1 blockade with immunogenic hypofractionated radiotherapy in HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Inibidores de Checkpoint Imunológico , Células Supressoras Mieloides , Carcinoma de Células Escamosas de Cabeça e Pescoço , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Imunoterapia/métodos , Células Supressoras Mieloides/metabolismo , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico
9.
BMC Neurosci ; 24(1): 9, 2023 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709248

RESUMO

AIMS/INTRODUCTION: As a common complication in elderly patients after surgery/anesthesia, postoperative cognitive dysfunction (POCD) is mainly characterized by memory, attention, motor, and intellectual retardation. Neuroinflammation is one of the most uncontroversial views in POCD. The sevoflurane-induced neurotoxicity has attracted widespread attention in recent years. However, its mechanism has not been determined. This study aimed to observe the effects of sevoflurane on cognitive function and the changes in inflammatory indices and autophagy protein expression in the prefrontal cortex in aged rats. METHOD: Before the experiment, D-galactose was diluted with normal saline into a liquid with a concentration of 125 mg/kg and injected subcutaneously into the neck and back of rats for 42 days to establish the aging rat model. Morris water maze experiments were performed, including positioning navigation (5 days) and space exploration (1 day). The POCD model was established by 3.2% sevoflurane inhalation. The rats were treated with or without MCC950, a potent and selective nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inhibitor, followed by autophagy agonists and autophagy inhibitors. The expression levels of inflammasome-related protein NLRP3 and autophagy-related proteins LC3B and P62 were detected to test the behavior of rats with a water maze. RESULTS: We found that sevoflurane exposure affected learning and working memory ability in aged rats. We also observed microglia activation in the prefrontal cortex. NLRP3 protein expression was significantly upregulated after sevoflurane inhalation. NLRP3 inflammasome activation induced increased expression and mRNA expression of cleaved Caspase-1 and inflammatory cytokines IL-1ß and IL-18, and increased secretion of peripheral proinflammatory cytokines. The inhibitor MCC950 was used to improve cognitive ability and inflammation in rats and inhibit the secretion of cytokines. In addition, we demonstrated that significant inhibition of autophagy (decreased LC3-II/I and increased P62) was accompanied by increased activation of NLRP3 inflammasomes and more severe neural cell damage. However, autophagy inhibitor rapamycin administration to activate autophagy resulted in the inhibition of NLRP3 inflammasomes, ultimately attenuating neuronal injury. CONCLUSIONS: The activation of autophagy suppressed the formation of NLRP3 inflammasomes. It also alleviated cognitive impairment in aged rats.


Assuntos
Disfunção Cognitiva , Inflamassomos , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sevoflurano/farmacologia , Autofagia , Citocinas/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Proteínas de Transporte
10.
Hepatology ; 75(6): 1446-1460, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34662438

RESUMO

BACKGROUND AND AIMS: Ischemia-reperfusion (I/R) injury is an inevitable complication of liver transplantation (LT) and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain open for study in hepatic I/R (HIR) injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-acetylgalactosaminyltransferase-4 (GALNT4), in HIR injury. APPROACH AND RESULTS: By an RNA-sequencing data-based correlation analysis, we found a close correlation between GALNT4 expression and HIR-related molecular events in a murine model. mRNA and protein expression of GALNT4 were markedly up-regulated upon reperfusion surgery in both clinical samples from subjects who underwent LT and in a mouse model. We found that GALNT4 deficiency significantly exacerbated I/R-induced liver damage, inflammation, and cell death, whereas GALNT4 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration clarified that GALNT4 directly binds to apoptosis signal-regulating kinase 1 (ASK1) to inhibit its N-terminal dimerization and subsequent phosphorylation, leading to a robust inactivation of downstream c-Jun N-terminal kinase (JNK)/p38 and NF-κB signaling. Intriguingly, the inhibitory capacity of GALNT4 on ASK1 activation is independent of its glycosyltransferase activity. CONCLUSIONS: GALNT4 represents a promising therapeutic target for liver I/R injury and improves liver surgery prognosis by inactivating the ASK1-JNK/p38 signaling pathway.


Assuntos
Fígado , MAP Quinase Quinase Quinase 5 , N-Acetilgalactosaminiltransferases , Traumatismo por Reperfusão , Animais , Apoptose , Fígado/patologia , MAP Quinase Quinase Quinase 5/metabolismo , Camundongos , N-Acetilgalactosaminiltransferases/genética , Multimerização Proteica , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Polipeptídeo N-Acetilgalactosaminiltransferase
11.
Hepatology ; 75(2): 403-418, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34435375

RESUMO

BACKGROUND AND AIMS: Although the prevalence of NAFLD has risen dramatically to 25% of the adult population worldwide, there are as yet no approved pharmacological interventions for the disease because of uncertainty about the underlying molecular mechanisms. It is known that mitochondrial dysfunction is an important factor in the development of NAFLD. Mitochondrial antiviral signaling protein (MAVS) is a critical signaling adaptor for host defenses against viral infection. However, the role of MAVS in mitochondrial metabolism during NAFLD progression remains largely unknown. APPROACH AND RESULTS: Based on expression analysis, we identified a marked down-regulation of MAVS in hepatocytes during NAFLD progression. By using MAVS global knockout and hepatocyte-specific MAVS knockout mice, we found that MAVS is protective against diet-induced NAFLD. MAVS deficiency induces extensive mitochondrial dysfunction during NAFLD pathogenesis, which was confirmed as impaired mitochondrial respiratory capacity and membrane potential. Metabolomics data also showed the extensive metabolic disorders after MAVS deletion. Mechanistically, MAVS interacts with the N-terminal stretch of voltage-dependent anion channel 2 (VDAC2), which is required for the ability of MAVS to influence mitochondrial function and hepatic steatosis. CONCLUSIONS: In hepatocytes, MAVS plays an important role in protecting against NAFLD by helping to regulate healthy mitochondrial function. These findings provide insights regarding the metabolic importance of conventional immune regulators and support the possibility that targeting MAVS may represent an avenue for treating NAFLD.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Células Cultivadas , Progressão da Doença , Regulação para Baixo , Técnicas de Silenciamento de Genes , Células Estreladas do Fígado , Hepatócitos , Homeostase , Humanos , Lipogênese/genética , Masculino , Metabolômica , Camundongos , Camundongos Knockout , Mitocôndrias/fisiologia , Hepatopatia Gordurosa não Alcoólica/genética , Cultura Primária de Células , Canal de Ânion 2 Dependente de Voltagem/genética , Canal de Ânion 2 Dependente de Voltagem/metabolismo
12.
Appl Microbiol Biotechnol ; 107(5-6): 1697-1705, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36763116

RESUMO

Fusion expression is widely employed to enhance the solubility of recombinant proteins. However, removal of the fusion tag is often required due to its potential impact on the structure and activity of passenger proteins. Tobacco etch virus (TEV) protease is widely used for this purpose due to its stringent sequence recognition. In the present work, fusion to the acyl carrier protein from E. coli fatty acid synthase (ACP) significantly increased the yield of recombinant soluble TEV, and the ACP tag also greatly improved TEV stability. The cleavage activity of TEV was not affected by the ACP fusion tag, and ACP-TEV retained high activity, even at unfavourable pH values. Moreover, ACP-TEV could be efficiently modified by co-expressed E. coli holo-ACP synthase (AcpS), leading to covalent attachment of 4'-phosphopantetheine (4'-PP) group to ACP. The sulfhydryl group of the long, flexible 4'-PP chain displayed high specific reactivity with iodoacetyl groups on the solid support. Thus, TEV could be immobilised effectively and conveniently via the active holo-ACP, and immobilised TEV retained high cleavage activity after a long storage period and several cycles of reuse. As a low-cost and recyclable biocatalyst, TEV immobilised by this method holds promise for biotechnological research and development. KEY POINTS: • The ACP tag greatly increased the soluble expression and stability of TEV protease. • The ACP tag did not affect the cleavage activity of TEV. • The holo-ACP Tag effectively mediated the covalent immobilisation of TEV.


Assuntos
Proteína de Transporte de Acila , Escherichia coli , Escherichia coli/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/metabolismo , Endopeptidases/metabolismo
13.
BMC Urol ; 23(1): 177, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37915019

RESUMO

BACKGROUND: Telomerase reverse transcriptase (TERT) mutation represents the most prevalent genetic mutation found in urothelial carcinoma (UC) and holds potential as a prognostic indicator for tumor outcomes. However, the association between TERT mutation and prognosis in UC patients remains poorly elucidated due to conflicting findings in existing literature. Therefore, this study aimed to investigate the effect of the TERT mutation on the survival of UC patients. METHODS: We systematically searched the PubMed, Embase, and Cochrane Library databases for studies that investigated the relationship between the TERT mutation and the prognosis of UC patients. Endpoints included the 2-year and 5-year recurrence-free survival (RFS) and overall survival (OS). The Newcastle-Ottawa Scale (NOS) tool was used to assess the risk of bias in the included studies. Review Manager 5.3 was used for the meta-analysis. RESULTS: Nine studies with a total of 1,552 patients were included in the analysis. Two studies were prospective, and seven were retrospective. The TERT promoter mutation was associated with a lower 2-year OS (relative risk [RR] = 0.92, 95% confidence interval [CI] 0.86-0.98; P = 0.007) and a lower 5-year OS (RR = 0.80, 95% CI 0.68-0.94; P = 0.008) compared with the TERT wild type. However, no significantly differences were found between two groups in terms of HR for OS (hazard ratio [HR] = 1.29, 95% CI 0.80-2.08; P = 0.29). Furthermore, we investigated the differences in RFS and disease-specific survival (DSS) between the two groups. CONCLUSION: The TERT mutation increases the risk of death and decreases the survival time of UC patients. TERT may be a valuable marker with individual prognostic value.


Assuntos
Carcinoma de Células de Transição , Telomerase , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Estudos Prospectivos , Estudos Retrospectivos , Prognóstico , Mutação , Telomerase/genética
14.
Mar Drugs ; 22(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38248646

RESUMO

Crocin is one of the most valuable components of the Chinese medicinal plant Crocus sativus and is widely used in the food, cosmetics, and pharmaceutical industries. Traditional planting of C. sativus is unable to fulfill the increasing demand for crocin in the global market, however, such that researchers have turned their attention to the heterologous production of crocin in a variety of hosts. At present, there are reports of successful heterologous production of crocin in Escherichia coli, Saccharomyces cerevisiae, microalgae, and plants that do not naturally produce crocin. Of these, the microalga Dunaliella salina, which produces high levels of ß-carotene, the substrate for crocin biosynthesis, is worthy of attention. This article describes the biosynthesis of crocin, compares the features of each heterologous host, and clarifies the requirements for efficient production of crocin in microalgae.


Assuntos
Clorofíceas , Microalgas , Carotenoides , beta Caroteno , Indústria Farmacêutica , Escherichia coli , Saccharomyces cerevisiae
15.
Molecules ; 28(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38138631

RESUMO

Water electrolysis is currently a major technique to produce clean hydrogen, which is regarded as a promising and sustainable energy carrier. The efficiency of water electrolysis is highly dependent on the oxygen evolution reaction (OER) on the anode. The evaluation of an OER electrocatalyst is frequently carried out on a three-electrode system in a container of electrolyte. Herein, we found that the electrode positions in the electrolyte container could significantly affect the data acquisition of OER performance. After a detailed investigation, we reveal that the difference of the OER activity of an electrocatalyst at a different position is originated from their different iRu drop and the gas diffusion resistance. For the first time, this work evokes concerns on the accurate evaluation of electrocatalysts regarding the electrode position. For fair comparisons and reliable results, it is strongly suggested to keep the electrode position unchanged in the electrochemical measurements. In addition, the establishment of a standard electrolyzer setup for electrocatalysis evaluation in the electrochemical community is also called for.

16.
Angew Chem Int Ed Engl ; 62(15): e202300314, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36788422

RESUMO

Hole transport materials (HTMs) with high hole mobility, good band alignment and ease of fabrication are highly desirable for perovskite solar cells (PSCs). Here, we designed and synthesized novel organic HTMs, named T3, which can be synthesized in high yields with commercially available materials, featuring a substituted pyrrole core and triphenylamine peripheral arms. The capability of functionalization in the final synthetic step provides an efficient way to obtain a variety of T3-based HTMs with tunable energy levels and other properties. Among them, fluorine-substituted T3 (T3-F) exhibits the best band alignment and hole extraction properties, leading to PSCs with outstanding PCEs of 24.85 % and 24.03 % (certified 23.46 %) for aperture areas of 0.1 and 1 cm2 , respectively. The simple structure and tunable performance of T3 can inspire further optimization for efficient PSCs.

17.
Hepatology ; 74(4): 2133-2153, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34133792

RESUMO

BACKGROUND AND AIMS: Hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, causes a large proportion of early graft failure and organ rejection cases. The identification of key regulators of hepatic I/R injury may provide potential strategies to clinically improve the prognosis of liver surgery. Here, we aimed to identify the role of tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in hepatic I/R injury and further reveal its immanent mechanisms. APPROACH AND RESULTS: In the present study, we found that hepatocyte TNIP3 was markedly up-regulated in livers of both persons and mice subjected to I/R surgery. Hepatocyte-specific Tnip3 overexpression effectively attenuated I/R-induced liver necrosis and inflammation, but improved cell proliferation in mice, whereas TNIP3 ablation largely aggravated liver injury. This inhibitory effect of TNIP3 on hepatic I/R injury was found to be dependent on significant activation of the Hippo-YAP signaling pathway. Mechanistically, TNIP3 was found to directly interact with large tumor suppressor 2 (LATS2) and promote neuronal precursor cell-expressed developmentally down-regulated 4-mediated LATS2 ubiquitination, leading to decreased Yes-associated protein (YAP) phosphorylation at serine 112 and the activated transcription of factors downstream of YAP. Notably, adeno-associated virus delivered TNIP3 expression in the liver substantially blocked I/R injury in mice. CONCLUSIONS: TNIP3 is a regulator of hepatic I/R injury that alleviates cell death and inflammation by assisting ubiquitination and degradation of LATS2 and the resultant YAP activation.TNIP3 represents a promising therapeutic target for hepatic I/R injury to improve the prognosis of liver surgery.


Assuntos
Via de Sinalização Hippo/fisiologia , Hepatopatias , Proteínas Serina-Treonina Quinases/metabolismo , Traumatismo por Reperfusão , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas de Sinalização YAP/metabolismo , Animais , Proliferação de Células , Descoberta de Drogas , Hepatócitos/fisiologia , Humanos , Inflamação/metabolismo , Hepatopatias/metabolismo , Hepatopatias/prevenção & controle , Camundongos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Regulação para Cima
18.
Opt Express ; 30(10): 16847-16855, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36221519

RESUMO

We propose a lithography-free wide-angle polarization-insensitive ultra-broadband absorber by using three pairs of tungsten (W) and calcium fluoride (CaF2) films. The simulation results show that the absorptivity is larger than 0.9 with normal incidence in the wavelength range from 400 nm to 1529 nm. By adding a pair of CaF2-W films, we can get a broader absorption bandwidth with absorptivity larger than 0.9 over the wavelength of 400-1639 nm. In addition, the absorption performance is insensitive to the polarization and angle of incidence. The electric field distributions at the absorption peaks show that the absorption is originated from the destructive interference between the reflection waves from the top and bottom interfaces of the multilayer CaF2-W films. Furthermore, the ultra-broad bandwidth is attributed to the anti-reflection effect from the increased effective refractive index from top to down of the proposed absorber. Such physical mechanism of broadening bandwidth based on anti-reflection effect provides a new idea for the design of broadband absorber. Meanwhile, this broadband absorber is a good candidate for potential applications such as detection and energy harvesting.

19.
Int J Mol Sci ; 23(6)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35328636

RESUMO

Serotonin (5-hydroxytryptamine) plays an important role in many developmental processes and biotic/abiotic stress responses in plants. Although serotonin biosynthetic pathways in plants have been uncovered, knowledge of the mechanisms of serotonin accumulation is still limited, and no regulators have been identified to date. Here, we identified the basic leucine zipper transcription factor OsbZIP18 as a positive regulator of serotonin biosynthesis in rice. Overexpression of OsbZIP18 strongly induced the levels of serotonin and its early precursors (tryptophan and tryptamine), resulting in stunted growth and dark-brown phenotypes. A function analysis showed that OsbZIP18 activated serotonin biosynthesis genes (including tryptophan decarboxylase 1 (OsTDC1), tryptophan decarboxylase 3 (OsTDC3), and tryptamine 5-hydroxylase (OsT5H)) by directly binding to the ACE-containing or G-box cis-elements in their promoters. Furthermore, we demonstrated that OsbZIP18 is induced by UV-B stress, and experiments using UV-B radiation showed that transgenic plants overexpressing OsbZIP18 exhibited UV-B stress-sensitive phenotypes. Besides, exogenous serotonin significantly exacerbates UV-B stress of OsbZIP18_OE plants, suggesting that the excessive accumulation of serotonin may be responsible for the sensitivity of OsbZIP18_OE plants to UV-B stress. Overall, we identified a positive regulator of serotonin biosynthesis and demonstrated that UV-B-stress induced serotonin accumulation, partly in an OsbZIP18-dependent manner.


Assuntos
Oryza , Descarboxilases de Aminoácido-L-Aromático/genética , Descarboxilases de Aminoácido-L-Aromático/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Serotonina/metabolismo
20.
Clin Immunol ; 222: 108600, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33197619

RESUMO

OBJECTIVES: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multinucleated giant cell (MGC) in esophageal cancer. MATERIALS AND METHODS: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers. RESULTS: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063). CONCLUSIONS: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker.


Assuntos
Neoplasias Esofágicas/patologia , Esôfago/citologia , Células Gigantes/imunologia , Macrófagos/imunologia , Fagocitose/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , China , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/imunologia , Esôfago/imunologia , Esôfago/patologia , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de IgG/imunologia
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