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1.
Int J Biol Macromol ; : 132229, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38734337

RESUMEN

In this study, the effect of hydrothermal treatment with different temperatures (120-180 °C) on the rheological properties of xanthan gum was evaluated. When the temperature of hydrothermal treatment was relatively low (120 °C), the rheological properties of the hydrothermally treated xanthan gum was similar to the untreated xanthan gum (pseudoplastic and solid-like/gel-like behavior). However, as the temperature of hydrothermal treatment was higher, the rheological properties of the hydrothermally treated xanthan gum changed greatly (e.g., a wider range of Newtonian plateaus in flow curves, existence of a critical frequency between the storage modulus (G') and the loss modulus (G") in the dynamic viscoelasticity measurement, variation of complex viscosity). Although the hydrothermal treatment showed little influence on the functional groups of xanthan gum, it altered the micromorphology of xanthan gum from uneven and rough lump-like to thinner and smoother flake-like. In addition, higher concentration (2 %) of hydrothermally treated xanthan gum made its viscosity close to that of the untreated xanthan gum (1 %). Besides, hydrothermal treatment also affected the effect of temperature and salt (CaCl2) adding on the rheological properties of xanthan gum. Overall, this study can provide some useful information on the rheological properties of xanthan gum after hydrothermal treatment.

2.
Mil Med Res ; 11(1): 22, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622688

RESUMEN

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.


Asunto(s)
Ferroptosis , Daño por Reperfusión , Animales , Ratones , Diclorodifenil Dicloroetileno , Hepatocitos , Interferón-alfa , ARN , ARN Mensajero
3.
Signal Transduct Target Ther ; 9(1): 91, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38627387

RESUMEN

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.


Asunto(s)
FN-kappa B , Enfermedad del Hígado Graso no Alcohólico , Animales , Humanos , Ratones , Regulación hacia Abajo/genética , Cirrosis Hepática/metabolismo , Macrófagos/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Receptores de Quimiocina , Proteína de Unión al Calcio S100A4
4.
Angew Chem Int Ed Engl ; : e202400494, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38598042

RESUMEN

The photoredox electron donor-acceptor (EDA) complex-mediated radical coupling reaction has gained prominence in the field of organic synthesis, finding widespread application in two-component coupling reactions. However, EDA complex-promoted multi-component reactions are not well developed with only a limited number of examples have been reported. Herein, we report a photoinduced and EDA complex-promoted highly chemoselective three-component radical arylalkylation of [1.1.1]propellane, which allows the direct functionalization of C(sp3)-H with bicyclo[1.1.1]pentanes (BCP)-aryl groups under mild conditions. A variety of unnatural α-amino acids, featuring structurally diversified 1,3-disubstituted BCP moieties, were synthesized in a single-step process. Notably, leveraging the high tension release of [1.1.1]propellane, the highly unstable transient aryl radical undergoes rapid conversion into a relatively stable tertiary alkyl transient radical, and consequently, the competing side-reaction of two-component coupling was entirely suppressed. The strategic use of this transient radical conversion approach would be useful for the design of diverse EDA complex-mediated multi-component reactions. It is noteworthy that the highly chemoselective late-stage incorporation of the 1,3-disubstituted BCP pharmacophores into peptides was achieved both in liquid-phase and solid-phase reactions. This advancement is anticipated to have significant application potential in the future development of peptide drugs.

5.
Res Sq ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38659762

RESUMEN

Epstein-Barr Virus (EBV) is associated with a range of B-cell malignancies, including Burkitt, Hodgkin, post-transplant, and AIDS-related lymphomas. Studies highlight EBV's transformative capability to induce oncometabolism in B-cells to support energy, biosynthetic precursors, and redox equivalents necessary for transition from quiescent to proliferation. Mitochondrial dysfunction presents an intrinsic barrier to EBV B-cell immortalization. Yet, how EBV maintains B-cell mitochondrial function and metabolic fluxes remains unclear. Here we show that EBV boosts cardiolipin(CL) biosynthesis, essential for mitochondrial cristae biogenesis, via EBNA2-induced CL enzyme transactivation. Pharmaceutical and CRISPR genetic analyses underscore the essentiality of CL biosynthesis in EBV-transformed B-cells. Metabolomic and isotopic tracing highlight CL's role in sustaining respiration, one-carbon metabolism, and aspartate synthesis, all vital for EBV-transformed B-cells. Targeting CL biosynthesis destabilizes mitochondrial one-carbon enzymes, causing synthetic lethality when coupled with a SHMT1/2 inhibitor. We demonstrate EBV-induced CL metabolism as a therapeutic target, offering new strategies against EBV-associated B-cell malignancies.

6.
Int J Cardiol ; 402: 131830, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38320669

RESUMEN

BACKGROUND: The existing ECG criteria for diagnosing left bundle branch block (LBBB) are insufficient to distinguish between true and false blocks accurately. METHODS: We hypothesized that the notch width of the QRS complex in the lateral leads (I, avL, V5, V6) on the LBBB-like ECG could further confirm the diagnosis of true complete left bundle branch block (t-LBBB). We conducted high-density, three-dimensional electroanatomical mapping in the cardiac chambers of 37 patients scheduled to undergo CRT. These patients' preoperative electrocardiograms met the ACC/AHA/HRS guidelines for the diagnosis of complete LBBB. If the left bundle branch potential could be mapped from the base of the heart to the apex on the left ventricular septum, it was defined as a false complete left bundle branch block (f-LBBB). Otherwise, it was categorized as a t-LBBB. We conducted a comparative analysis between the two groups, considering the clinical characteristics, real-time correspondence between the spread of ventricular electrical excitation and the QRS wave, QRS notch width of the lateral leads (I, avL, V5, V6), and the notch width/left ventricular end-diastolic diameter (Nw/LVd) ratio. We performed the ROC correlation analysis of Nw/LVd and t-LBBB to determine the sensitivity and specificity for diagnostic authenticity. RESULTS: Twenty-five patients were included in the t-LBBB group, while 12 patients were assigned to the f-LBBB group. Within the t-LBBB group, the first peak of the QRS notch correlated with the depolarization of the right ventricle and septum, the trough corresponded to the depolarization of the left ventricle across the left ventricle, and the second peak aligned with the depolarization of the left ventricular free wall. In contrast, within the f-LBBB group, the first peak coincided with the depolarization of the right ventricle and a majority of the left ventricle, the second peak occurred due to the depolarization of the latest, locally-activated myocardium in the left ventricle, and the trough was a result of delayed activation of the left ventricle that did not align with the usual peak timing. The QRS notch width (45.2 ± 12.3 ms vs. 52.5 ± 9.2 ms, P < 0.05) and the Nw/LVd ratio (0.65 ± 0.19 ms/mm vs. 0.81 ± 0.17 ms/mm, P < 0.05) were compared between the two groups. After conducting the ROC correlation analysis, a sensitivity of 56% and a specificity of 91.7% for diagnosing t-LBBB using Nw/LVd were obtained. CONCLUSION: By utilizing the current diagnostic criteria for LBBB, an increased Nw/LVd value can enhance the effectiveness of diagnosing LBBB.


Asunto(s)
Bloqueo de Rama , Terapia de Resincronización Cardíaca , Humanos , Terapia de Resincronización Cardíaca/métodos , Electrocardiografía , Sistema de Conducción Cardíaco , Ventrículos Cardíacos , Resultado del Tratamiento
7.
Nature ; 627(8004): 586-593, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38355797

RESUMEN

Over half of hepatocellular carcinoma (HCC) cases diagnosed worldwide are in China1-3. However, whole-genome analysis of hepatitis B virus (HBV)-associated HCC in Chinese individuals is limited4-8, with current analyses of HCC mainly from non-HBV-enriched populations9,10. Here we initiated the Chinese Liver Cancer Atlas (CLCA) project and performed deep whole-genome sequencing (average depth, 120×) of 494 HCC tumours. We identified 6 coding and 28 non-coding previously undescribed driver candidates. Five previously undescribed mutational signatures were found, including aristolochic-acid-associated indel and doublet base signatures, and a single-base-substitution signature that we termed SBS_H8. Pentanucleotide context analysis and experimental validation confirmed that SBS_H8 was distinct to the aristolochic-acid-associated SBS22. Notably, HBV integrations could take the form of extrachromosomal circular DNA, resulting in elevated copy numbers and gene expression. Our high-depth data also enabled us to characterize subclonal clustered alterations, including chromothripsis, chromoplexy and kataegis, suggesting that these catastrophic events could also occur in late stages of hepatocarcinogenesis. Pathway analysis of all classes of alterations further linked non-coding mutations to dysregulation of liver metabolism. Finally, we performed in vitro and in vivo assays to show that fibrinogen alpha chain (FGA), determined as both a candidate coding and non-coding driver, regulates HCC progression and metastasis. Our CLCA study depicts a detailed genomic landscape and evolutionary history of HCC in Chinese individuals, providing important clinical implications.


Asunto(s)
Carcinoma Hepatocelular , Genoma Humano , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Hepáticas , Mutación , Secuenciación Completa del Genoma , Humanos , Ácidos Aristolóquicos/metabolismo , Carcinogénesis , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , China , Cromotripsis , Progresión de la Enfermedad , ADN Circular/genética , Pueblos del Este de Asia/genética , Evolución Molecular , Genoma Humano/genética , Virus de la Hepatitis B/genética , Mutación INDEL/genética , Hígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Mutación/genética , Metástasis de la Neoplasia/genética , Sistemas de Lectura Abierta/genética , Reproducibilidad de los Resultados
8.
PLoS One ; 19(2): e0297096, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38306332

RESUMEN

BACKGROUND: Adults living alone represent a growing population group in China. Understanding the prevalence of body mass index (BMI) categories and their associations with demographic and lifestyle factors among this group is essential for informing targeted interventions and public health policies. METHODS: In this population-based cross-sectional study, we used individual-level data from the 2011-2021 China General Social Survey. Main outcomes were prevalence of BMI categories adjusted for gender and age, using logistic regression and model-predicted marginal prevalence to estimate BMI categories prevalence. RESULTS: We analyzed 9,077 single-living Chinese adult participants. The primary-adjusted prevalence of BMI categories varied across different genders and age groups. Underweight was more prevalent in females (12.73%; 95% CI: 12.31% - 13.14%) than in males (7.54%; 95% CI: 7.19% - 7.88%), while overweight and obesity were higher in males. Primary-adjusted underweight prevalence was highest among the 18-24 years age group (22.09%; 95% CI: 20.17% - 24.01%) and decreased with age. Primary-adjusted overweight prevalence increased with age, peaking in the 45-54 years age group (41.94%; 95% CI: 40.96% - 42.93%). Primary-adjusted obesity prevalence exhibited a fluctuating pattern across age groups, with the highest prevalence observed in the 45-54 years age group (9.81%; 95% CI: 9.19% - 10.44%). CONCLUSION: Our findings reveal significant associations between BMI categories and demographic and lifestyle factors among adults living alone in China. These results can inform targeted interventions and public health policies aimed at promoting healthy weight management and addressing the unique health challenges faced by single-living individuals in China.


Asunto(s)
Sobrepeso , Delgadez , Adulto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Sobrepeso/epidemiología , Índice de Masa Corporal , Delgadez/epidemiología , Prevalencia , Estudios Transversales , Ambiente en el Hogar , Obesidad/epidemiología , China/epidemiología , Factores de Riesgo
9.
Small ; : e2307610, 2024 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-38342695

RESUMEN

Borophene, a 2D material exhibiting unique crystallographic phases like the anisotropic atomic lattices of ß12 and X3 phases, has attracted considerable attention due to its intriguing Dirac nature and metallic attributes. Despite surpassing graphene in electronic mobility, borophene's potential in energy storage and catalysis remains untapped due to its inherent electrochemical and catalytic limitations. Elemental doping emerges as a promising strategy to introduce charge carriers, enabling localized electrochemical and catalytic functionalities. However, effective doping of borophene has been a complex and underexplored challenge. Here, an innovative, one-pot microwave-assisted doping method, tailored for the ß12 phase of borophene is introduced. By subjecting dispersed ß12 borophene in dimethylformamide to controlled microwave exposure with sulfur powder and FeCl3 as doping precursors, S- and Fe doping in borophene can be controlled. Employing advanced techniques including high-resolution transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy, confirm successful sulfur and iron dopant incorporation onto ß12 borophene is confirmed, achieving doping levels of up to 11 % and 13 %, respectively. Remarkably, S- and Fe-doped borophene exhibit exceptional supercapacitive behavior, with specific capacitances of 202 and 120 F g-1 , respectively, at a moderate current density of 0.25 A g-1 .

10.
Food Chem ; 435: 137524, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37832336

RESUMEN

The aim of this study was to evaluate the effects of ultra-high pressure (UHP, 600 MPa/2 min), thermal pasteurization (TP, 95 °C/1 min) and ultra-high temperature (UHT, 115 °C/5 s) sterilization on the color, sensory evaluation, microorganisms, physicochemical characteristics and nutritional components of freshly-squeezed lettuce juice (FLJ). Results showed that three sterilization methods demonstrated desirable inactivation effects on total aerobic bacteria, yeast and mold, and there were no significant changes in the main nutritional components, including ash, protein, carbohydrate and total dietary fiber. However, UHT and TP significantly affected the color of FLJ from bright green to light brown and made chlorophyll, ß-carotene and vitamins (VE, VC, VK1, VB6, VB12, and folic acid) contents markedly decreased. By contrast, UHP maintained the original color, fresh-like sensory qualities, vitamins, and carotene of FLJ to the greatest extent. Our results provide a promising application of UHP in the large-scale processing of FLJ.


Asunto(s)
Lactuca , Pasteurización , Manipulación de Alimentos/métodos , Temperatura , Frutas/química , Calor , Esterilización , Vitaminas/análisis
11.
ACS Omega ; 8(45): 42379-42389, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38024722

RESUMEN

Water is ubiquitous in coal reservoirs, and its distribution can have a remarkable influence on the effective pore space of methane. This study conducted the combination experiments of moisture equilibrium and prefreezing nitrogen adsorption-desorption to explore the adsorption behavior of water in coal pores and thus to reveal the distribution characteristics of water in pores with different scales as well as the influence of water on pore structures. The results showed that the adsorption mechanism of water vapor undergoes a transition from monolayer to multilayer to condensation with the increase in relative humidity (RH). The occurrence characteristics of adsorbed water in coal pores are controlled by the RH and pore size. When the RH is increased from 0 to 98%, the nitrogen adsorption capacity, specific surface area, and effective pore volume of the samples were all decreased significantly due to the different adsorption modes of water, which is more significant in pores with d < 10 nm. Additionally, the relative pressure corresponding to the branching position of the nitrogen adsorption-desorption curve will be changed with the increase in moisture content. Based on this, it is calculated that the adsorbed water will change the smoothness of the pore wall and the complexity of the pore structure.

12.
AME Case Rep ; 7: 32, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37942039

RESUMEN

Background: Malignant mesothelioma (MM) is a rare cancer with poor prognosis. It is less common that two serosal cavities are involved when the patient seeks medical attention firstly. The current first-line chemotherapy for advanced MM is a combination with cisplatin and pemetrexed. However, nedaplatin, a second-generation platinum-based antitumor agent, has the similar therapeutic effects as cisplatin but lower toxicity and higher water solubility. To our knowledge, this is the first case of co-existing pericardial and pleural MM treated with nedaplatin and pemetrexed and responding well. Case Description: A 33-year-old woman, who had worked in a kiln for more than 10 years, suffered from dyspnea and chest tightness for 6 days. Chest computed tomography (CT) showed a massive pericardial effusion. She was diagnosed tuberculous pericarditis and received 6 months antituberculosis treatment (rifampicin, isoniazide, pyrazinamide, ethambutol). But it was ineffective and she was re hospitalized again due to massive pleural effusion and pericardial effusion. She was diagnosed with co-existing pericardial and pleural MM finally based on pleural biopsy and cytology of pericardial effusion. She was responding well excitedly to chemotherapy with nedaplatin and pemetrexed with high tolerance. Bone marrow toxicity or recurrent massive pericardial or pleural effusion were not observed during chemotherapy. However, she gave up chemotherapy and has survived for 22 months, from the onset symptoms. Conclusions: In terms of clinical tolerance and less adverse reactions, we suggest that chemotherapy of nedaplatin with pemetrexed may be a more appropriate treatment in advanced MM. Further clinical trials are warrant.

13.
Pharmaceuticals (Basel) ; 16(10)2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37895951

RESUMEN

Recently, a G-protein coupled receptor 44 (GPR44) was discovered to play a significant role in the process of inflammation-related diseases, including cancer and diabetes. However, the precise role of GPR44 has yet to be fully elucidated. Currently, there is a strong and urgent need for the development of GPR44 radiotracers as a non-invasive methodology to explore the exact mechanism of GPR44 on inflammation-related diseases and monitor the progress of therapy. TM-30089 is a potent GPR44 antagonist that exhibits a high specificity and selectivity for GPR44. Its structure contains a fluorine nuclide, which could potentially be replaced with 18F. In the present study, we successfully took a highly effective synthesis strategy that pretreated the unprotected carboxylic acid group of the precursor and developed a feasible one-step automatic radiosynthesis strategy for [18F]TM-30089 with a high radiochemical purity and a good radiochemical yield. We further evaluated this radiotracer using mice models implanted with 1.1 B4 cell lines (GPR44-enriched cell lines) and human islets (high GPR44 expression), respectively. The results revealed the persistent and specific uptake of [18F]TM-30089 in GPR44 region, indicating that [18F]TM-30089 is a promising candidate for targeting GPR44. Further evaluation is ongoing.

14.
Molecules ; 28(18)2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37764389

RESUMEN

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1ß and IL-8 and increase the expression of anti-inflammatory cytokine IL-10.


Asunto(s)
Gentiana , Neumonía , Humanos , Terpenos/farmacología , Factor de Necrosis Tumoral alfa , Glucósidos/farmacología , Células A549 , Citocinas , Extractos Vegetales/farmacología
15.
Pharmaceuticals (Basel) ; 16(9)2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37765011

RESUMEN

Recently, growing evidence of the relationship between G-protein coupled receptor 44 (GPR44) and the inflammation-cancer system has garnered tremendous interest, while the exact role of GPR44 has not been fully elucidated. Currently, there is a strong and urgent need for the development of non-invasive in vivo GPR44 positron emission tomography (PET) radiotracers that can be used to aid the exploration of the relationship between inflammation and tumor biologic behavior. Accordingly, the choosing and radiolabeling of existing GPR44 antagonists containing a fluorine group could serve as a viable method to accelerate PET tracers development for in vivo imaging to this purpose. The present study aims to evaluate published (2000-present) indole-based and cyclopentenyl-indole-based analogues of the GPR44 antagonist to guide the development of fluorine-18 labeled PET tracers that can accurately detect inflammatory processes. The selected analogues contained a crucial fluorine nuclide and were characterized for various properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile. Overall, 26 compounds with favorable to strong binding properties were identified. This review highlights the potential of GPR44 analogues for the development of PET tracers to study inflammation and cancer development and ultimately guide the development of targeted clinical therapies.

16.
Adv Mater ; : e2305828, 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37677048

RESUMEN

At the intersection of synthetic biology and materials science, engineered living materials (ELMs) exhibit unprecedented potential. Possessing unique "living" attributes, ELMs represent a significant paradigm shift in material design, showcasing self-organization, self-repair, adaptability, and evolvability, surpassing conventional synthetic materials. This review focuses on reviewing the applications of ELMs derived from bacteria, fungi, and plants in environmental remediation, eco-friendly architecture, and sustainable energy. The review provides a comprehensive overview of the latest research progress and emerging design strategies for ELMs in various application fields from the perspectives of synthetic biology and materials science. In addition, the review provides valuable references for the design of novel ELMs, extending the potential applications of future ELMs. The investigation into the synergistic application possibilities amongst different species of ELMs offers beneficial reference information for researchers and practitioners in this field. Finally, future trends and development challenges of synthetic biology for ELMs in the coming years are discussed in detail.

17.
Pediatr Dermatol ; 40(5): 841-850, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37529963

RESUMEN

BACKGROUND: Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children and adolescents. Previous systematic reviews explored the effectiveness and safety of dupilumab in adults with AD. However, the underlying mechanisms of AD can vary among different age groups, emphasizing the need for separate investigation into the use of dupilumab in children and adolescents with AD. OBJECTIVE: To evaluate the efficacy and safety of dupilumab in children and adolescents with AD based on evidence from clinical trials and observational studies. METHODS: The process of meta-analysis was conducted according to preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: Seven clinical trials and 11 observational studies involving 1275 children and adolescents with AD were eligible for quantitative analysis. Overall, the pooled percentages of eczema area and severity index (EASI) 50, EASI 75, EASI 90, EASI 100, and investigator's global assessment (IGA) 0/1 were 72.9% (95% CI: 61.6%-81.9%), 57.4% (48.1%-66.2%), 31.3% (24.0%-39.7%), 29.7% (23.3%-37.0%), and 35.2% (29.3%-41.5%). With prolonged treatment time, an increase was seen in the pooled rate of EASI response, indicating that dupilumab may provide sustained benefits for children and adolescents over the long term. The reported adverse events were primarily mild and manageable, with an overall incidence rate of 7.2% across clinical trials and 7.6% across observational studies. CONCLUSION: Dupilumab was an effective and safe treatment option for children and adolescents with AD, with positive results observed from long-term use and an acceptable safety profile. More long-term, high-quality, controlled studies in different regions are needed for further verification.


Asunto(s)
Dermatitis Atópica , Adulto , Humanos , Adolescente , Niño , Dermatitis Atópica/tratamiento farmacológico , Inyecciones Subcutáneas , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Método Doble Ciego
18.
Plant Physiol Biochem ; 202: 107962, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37625252

RESUMEN

Potato greening under light causes post-harvest loss and compromises progress being made in the potato industry. In this study, we investigated the inhibiting effects of ethanol fumigation treatment on potato greening and water loss under light. This paper also examined the different treatments on the relationship between starch granule size and potato greening. Our results suggested that ethanol fumigation combined with modified atmosphere packaging have an effective in improving the overall visual quality and maintained a higher a* value and lower chlorophyll concentration. Ethanol fumigation combined with modified atmosphere packaging treatment deterred greening and water loss compared to the alone treatment. This was due to the larger starch granule size and fewer grana lamellae around the amyloplasts. Our results provide an effectively strategy that treating potatoes with 600 µL L-1 ethanol combined with modified atmosphere packaging to delay potato greening and explain the underlying mechanism of ethanol inhibition of potato greening.


Asunto(s)
Solanum tuberosum , Fumigación , Atmósfera , Etanol/farmacología , Agua , Almidón
20.
Nat Commun ; 14(1): 3295, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37280209

RESUMEN

Alkylnitriles play important roles in many fields because of their unique electronic properties and structural characteristics. Incorporating cyanoalkyl with characteristic spectroscopy and reactivity properties into amino acids and peptides is of special interest for potential imaging and therapeutic purposes. Here, we report a copper-catalyzed asymmetric cyanoalkylation of C(sp3)-H. In the reactions, glycine derivatives can effectively couple with various cycloalkanone oxime esters with high enantioselectivities, and the reaction can be applied to the late-stage modification of peptides with good yields and excellent stereoselectivities, which is useful for modern peptide synthesis and drug discovery. The mechanistic studies show that the in situ formed copper complex by the coordination of glycine derivatives and chiral phosphine Cu catalyst can not only mediate the single electronic reduction of cycloalkanone oxime ester but also control the stereoselectivity of the cyanoalkylation reaction.


Asunto(s)
Cobre , Glicina , Glicina/química , Cobre/química , Estructura Molecular , Péptidos , Ésteres , Catálisis
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