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1.
Chem Biol Interact ; 396: 111044, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38729284

RESUMO

Mastitis is an inflammatory disease of the mammary gland with a high incidence in lactating animals, significantly impacting their health and breastfeeding. Moreover, mastitis adversely affects milk quality and yield, resulting in substantial economic losses for the dairy farming industry. Forsythiaside A (FTA), a phenylethanol glycoside analog extracted from Forsythia, exhibits notable anti-inflammatory and antioxidant properties. However, its protective effects and specific mechanisms against mastitis remain unclear. In this study, a lipopolysaccharide (LPS)-induced mouse mastitis model was used to investigate the protective effect of FTA on LPS-induced mastitis and its potential mechanism using histological assays, Western blot, qRT-PCR, FITC-albumin permeability test, 16s rRNA gene sequencing analysis and non-targeted metabolomics assays to investigate the protective effect of FTA on LPS-induced mastitis model and its potential mechanism. The results demonstrated that FTA significantly mitigated LPS-induced mouse mastitis by reducing inflammation and apoptosis levels, modulating the PI3K/AKT/mTOR signaling pathways, inducing autophagy, and enhancing antioxidant capacity and the expression of tight junction proteins. Furthermore, FTA increased the abundance of beneficial microbiota while decreasing the levels of harmful microbiota in mice, thus counteracting the gut microbiota disruption induced by LPS stimulation. Intestinal metabolomics analysis revealed that FTA primarily regulated LPS-induced metabolite alterations through key metabolic pathways, such as tryptophan metabolism. This study confirms the anti-inflammatory and antioxidant effects of FTA on mouse mastitis, which are associated with key metabolic pathways, including the restoration of gut microbiota balance and the regulation of tryptophan metabolism. These findings provide a novel foundation for the treatment and prevention of mammalian mastitis using FTA.

2.
Acad Radiol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734578

RESUMO

RATIONALE AND OBJECTIVES: The conversion success rate (CSR) has crucial implication for clinical outcomes of initially unresectable colorectal liver metastases (CRLM) following conversion therapy. This study aimed to develop a simple predictive scoring model for identifying CSR according to baseline magnetic resonance imaging (MRI) features, and confirm its performance and prognostic significance in a validation cohort. METHODS: A total of 155 consecutive patients with initially unresectable CRLM were retrospectively reviewed in the study. A simple MRI-based predictive scoring model for identifying CSR was developed in the development cohort (n = 104) by using multivariable logistic regression analyzes. The diagnostic performance was evaluated for the predictive score. Thereafter, patients in the validation cohort (n = 51) were stratified into groups with predicted high CSR or low CSR according to the score. The progression-free survival (PFS) and overall survival (OS) were compared between two groups using the log-rank test. RESULTS: The predictive score of CSR, named mrNISE, incorporated the number of CRLM ≥ 10, the largest size ≥ 50 mm, poorly defined tumor-liver interface, and peritumoral enhancement. The AUC of the mrNISE score was 0.845 for the development cohort and 0.776 for the validation cohort. According to the score, patients with predicted high CSR had better PFS and OS than those with low CSR in both development and validation cohorts. CONCLUSION: The predictive score demonstrated great performance for identifying CSR of initially unresectable CRLM. Stratifying patients by the score, personalized treatment goals can be formulated before conversion therapy to improve clinical prognosis and reduce adverse events caused by ineffective treatment.

3.
Biochem Biophys Res Commun ; 716: 150020, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38692011

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality rates. It has been shown that pirfenidone (PFD) and nintedanib (Ofev) can slow down the decline in lung function of IPF patients, but their efficacy remains suboptimal. Some studies have suggested that the combination of PFD and Ofev may yield promising results. However, there is a lack of research on the combined application of these two medications in the treatment of IPF. A mouse model of bleomycin-induced (BLM) pulmonary fibrosis was established to investigate the impact of combination therapy on pulmonary fibrosis of mice. The findings demonstrated a significant reduction in lung tissue damage in mice treated with the combination therapy. Subsequent transcriptome analysis identified the differential gene secreted phosphoprotein 1 (SPP1), which was found to be associated with macrophages and fibroblasts based on multiple immunofluorescence staining results. Analysis of a phosphorylated protein microarray indicated that SPP1 plays a regulatory role in macrophages and fibroblasts via the AKT pathway. Consequently, the regulation of macrophages and fibroblasts in pulmonary fibrosis by the combination of PFD and Ofev is mediated by SPP1 through the AKT pathway, potentially offering a novel therapeutic option for IPF patients. Further investigation into the targeting of SPP1 for the treatment of pulmonary fibrosis is warranted.


Assuntos
Fibroblastos , Indóis , Macrófagos , Camundongos Endogâmicos C57BL , Osteopontina , Proteínas Proto-Oncogênicas c-akt , Piridonas , Animais , Piridonas/farmacologia , Piridonas/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Osteopontina/metabolismo , Osteopontina/genética , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Antifibróticos/farmacologia , Antifibróticos/uso terapêutico , Masculino , Quimioterapia Combinada , Bleomicina
4.
Sci Total Environ ; : 173156, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38763197

RESUMO

Understanding the disparities in carbon emission trend among cities is critical for achieving carbon peak goal. However, the status and trends of carbon peaking and reduction in various city types are still unclear. Therefore, this study classified 315 Chinese cities according to their economic and industrial structure by SOM-K-means, aiming to evaluate the trends and dynamic drivers of carbon peaking progress in different city types. The findings reveal a decline in carbon emissions in 110 cities (34.9 %) since 2020. Notably, all city types show potential for carbon reduction and achieving carbon peaking. Specifically, resource-based cities and high-end service cities have the most effect on reducing emissions, with 48.4 % and 42.1 % of the cities declining in carbon emissions. Energy-based and heavy industrial cities face heightened pressure to reduce carbon emissions. Additionally, in high-end service cities, energy efficiency and investment intensity contribute to emission reduction, while industrial structure adjustment decrease carbon emissions in resource-based cities. Furthermore, enhancing energy efficiency effects and R&D intensity are effective ways to significantly reduce carbon emissions in heavy industrial cities. We conclude that differentiating carbon reduction pathways for different cities should constitute be a breakthrough in achieving the goal of carbon peaking. These insights provide recommendations for cities that have yet to reach their carbon peak for both China and other developing countries.

5.
BMC Vet Res ; 20(1): 212, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764041

RESUMO

BACKGROUND: Acinetobacter lwoffii (A.lwoffii) is a serious zoonotic pathogen that has been identified as a cause of infections such as meningitis, bacteremia and pneumonia. In recent years, the infection rate and detection rate of A.lwoffii is increasing, especially in the breeding industry. Due to the presence of biofilms, it is difficult to eradicate and has become a potential super drug-resistant bacteria. Therefore, eradication of preformed biofilm is an alternative therapeutic action to control A.lwoffii infection. The present study aimed to clarify that baicalin could eradicate A.lwoffii biofilm in dairy cows, and to explore the mechanism of baicalin eradicating A.lwoffii. RESULTS: The results showed that compared to the control group, the 4 MIC of baicalin significantly eradicated the preformed biofilm, and the effect was stable at this concentration, the number of viable bacteria in the biofilm was decreased by 0.67 Log10CFU/mL. The total fluorescence intensity of biofilm bacteria decreased significantly, with a reduction rate of 67.0%. There were 833 differentially expressed genes (367 up-regulated and 466 down-regulated), whose functions mainly focused on oxidative phosphorylation, biofilm regulation system and trehalose synthesis. Molecular docking analysis predicted 11 groups of target proteins that were well combined with baicalin, and the content of trehalose decreased significantly after the biofilm of A.lwoffii was treated with baicalin. CONCLUSIONS: The present study evaluated the antibiofilm potential of baicalin against A.lwoffii. Baicalin revealed strong antibiofilm potential against A.lwoffii. Baicalin induced biofilm eradication may be related to oxidative phosphorylation and TCSs. Moreover, the decrease of trehalose content may be related to biofilm eradication.


Assuntos
Acinetobacter , Antibacterianos , Biofilmes , Flavonoides , Leite , Biofilmes/efeitos dos fármacos , Animais , Flavonoides/farmacologia , Acinetobacter/efeitos dos fármacos , Bovinos , Leite/microbiologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Feminino , Infecções por Acinetobacter/veterinária , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia
6.
Sensors (Basel) ; 24(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38732850

RESUMO

Standard beams are mainly used for the calibration of strain sensors using their load reconstruction models. However, as an ill-posed inverse problem, the solution to these models often fails to converge, especially when dealing with dynamic loads of different frequencies. To overcome this problem, a piecewise Tikhonov regularization method (PTR) is proposed to reconstruct dynamic loads. The transfer function matrix is built both using the denoised excitations and the corresponding responses. After singular value decomposition (SVD), the singular values are divided into submatrices of different sizes by utilizing a piecewise function. The regularization parameters are solved by optimizing the piecewise submatrices. The experimental result shows that the MREs of the PTR method are 6.20% at 70 Hz and 5.86% at 80 Hz. The traditional Tikhonov regularization method based on GCV exhibits MREs of 28.44% and 29.61% at frequencies of 70 Hz and 80 Hz, respectively, whereas the L-curve-based approach demonstrates MREs of 29.98% and 18.42% at the same frequencies. Furthermore, the PREs of the PTR method are 3.54% at 70 Hz and 3.73% at 80 Hz. The traditional Tikhonov regularization method based on GCV exhibits PREs of 27.01% and 26.88% at frequencies of 70 Hz and 80 Hz, respectively, whereas the L-curve-based approach demonstrates PREs of 29.50% and 15.56% at the same frequencies. All in all, the method proposed in this paper can be extensively applied to load reconstruction across different frequencies.

7.
Biomed Pharmacother ; 175: 116716, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38735084

RESUMO

Biofilms often engender persistent infections, heightened antibiotic resistance, and the recurrence of infections. Therefor, infections related to bacterial biofilms are often chronic and pose challenges in terms of treatment. The main transcription regulatory factor, CsgD, activates csgABC-encoded curli to participate in the composition of extracellular matrix, which is an important skeleton for biofilm development in enterobacteriaceae. In our previous study, a wide range of natural bioactive compounds that exhibit strong affinity to CsgD were screened and identified via molecular docking. Tannic acid (TA) was subsequently chosen, based on its potent biofilm inhibition effect as observed in crystal violet staining. Therefore, the aim of this study was to investigate the specific effects of TA on the biofilm formation of clinically isolated Escherichia coli (E. coli). Results demonstrated a significant inhibition of E. coli Ec032 biofilm formation by TA, while not substantially affecting the biofilm of the ΔcsgD strain. Moreover, deletion of the csgD gene led to a reduction in Ec032 biofilm formation, alongside diminished bacterial motility and curli synthesis inhibition. Transcriptomic analysis and RT-qPCR revealed that TA repressed genes associated with the csg operon and other biofilm-related genes. In conclusion, our results suggest that CsgD is one of the key targets for TA to inhibit E. coli biofilm formation. This work preliminarily elucidates the molecular mechanisms of TA inhibiting E. coli biofilm formation, which could provide a lead structure for the development of future antibiofilm drugs.

8.
Nanomicro Lett ; 16(1): 189, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698120

RESUMO

Monolithic textured perovskite/silicon tandem solar cells (TSCs) are expected to achieve maximum light capture at the lowest cost, potentially exhibiting the best power conversion efficiency. However, it is challenging to fabricate high-quality perovskite films and preferred crystal orientation on commercially textured silicon substrates with micrometer-size pyramids. Here, we introduced a bulky organic molecule (4-fluorobenzylamine hydroiodide (F-PMAI)) as a perovskite additive. It is found that F-PMAI can retard the crystallization process of perovskite film through hydrogen bond interaction between F- and FA+ and reduce (111) facet surface energy due to enhanced adsorption energy of F-PMAI on the (111) facet. Besides, the bulky molecular is extruded to the bottom and top of perovskite film after crystal growth, which can passivate interface defects through strong interaction between F-PMA+ and undercoordinated Pb2+/I-. As a result, the additive facilitates the formation of large perovskite grains and (111) preferred orientation with a reduced trap-state density, thereby promoting charge carrier transportation, and enhancing device performance and stability. The perovskite/silicon TSCs achieved a champion efficiency of 30.05% based on a silicon thin film tunneling junction. In addition, the devices exhibit excellent long-term thermal and light stability without encapsulation. This work provides an effective strategy for achieving efficient and stable TSCs.

9.
Talanta ; 275: 126180, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38703480

RESUMO

Organic Electrochemical Transistors (OECTs) are integral in detecting human bioelectric signals, attributing their significance to distinct electrochemical properties, the utilization of soft materials, compact dimensions, and pronounced biocompatibility. This review traverses the technological evolution of OECT, highlighting its profound impact on non-invasive detection methodologies within the biomedicalfield. Four sensor types rooted in OECT technology were introduced: Electrocardiogram (ECG), Electroencephalogram (EEG), Electromyography (EMG), and Electrooculography (EOG), which hold promise for integration into wearable detection systems. The fundamental detection principles, material compositions, and functional attributes of these sensors are examined. Additionally, the performance metrics and delineates viable optimization strategies for assorted physiological electrical detection sensors are discussed. The overarching goal of this review is to foster deeper insights into the generation, propagation, and modulation of electrophysiological signals, thereby advancing the application and development of OECT in medical sciences.

10.
J Microbiol Biotechnol ; 34(6): 1-9, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38693049

RESUMO

Filamentous fungi are important cell factories for the production of high-value enzymes and chemicals for the food, chemical, and pharmaceutical industries. Under submerged fermentation, filamentous fungi exhibit diverse fungal morphologies that are influenced by environmental factors, which in turn affect the rheological properties and mass transfer of the fermentation system, and ultimately the synthesis of products. In this review, we first summarize the mechanisms of mycelial morphogenesis and then provide an overview of current developments in methods and strategies for morphological regulation, including physicochemical and metabolic engineering approaches. We also anticipate that rapid developments in synthetic biology and genetic manipulation tools will accelerate morphological engineering in the future.

11.
Biomed Pharmacother ; 175: 116698, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38713946

RESUMO

Neurotoxicity can cause a range of symptoms and disorders in humans, including neurodegenerative diseases, neurodevelopmental disorders, nerve conduction abnormalities, neuroinflammation, autoimmune disorders, and cognitive deficits. The cyclic guanosine-adenosine synthase (cGAS)-stimulator of interferon genes (STING) pathway and NF-κB pathway are two important signaling pathways involved in the innate immune response. The cGAS-STING pathway is activated by the recognition of intracellular DNA, which triggers the production of type I interferons and pro-inflammatory cytokines, such as tumor necrosis factor, IL-1ß, and IL-6. These cytokines play a role in oxidative stress and mitochondrial dysfunction in neurons. The NF-κB pathway is activated by various stimuli, such as bacterial lipopolysaccharide, viral particle components, and neurotoxins. NF-κB activation may lead to the production of pro-inflammatory cytokines, which promote neuroinflammation and cause neuronal damage. A potential interaction exists between the cGAS-STING and NF-κB pathways, and NF-κB activation blocks STING degradation by inhibiting microtubule-mediated STING transport. This review examines the progress of research on the roles of these pathways in neurotoxicity and their interrelationships. Understanding the mechanisms of these pathways will provide valuable therapeutic insights for preventing and controlling neurotoxicity.

12.
Pediatr Res ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710942

RESUMO

BACKGROUND: This study aims to investigate the role of endoplasmic reticulum stress (ER stress) in human dermal lymphatic endothelial cells (HDLECs) and lymphatic malformations (LMs) and its relationship with aerobic glycolysis and inflammation. METHODS: The proliferation and apoptosis of HDLECs were examined with lipopolysaccharide (LPS) treatment. ER stress-associated proteins and glycolysis-related markers were detected by western blot. Glycolysis indexes were detected by seahorse analysis and lactic acid production assay kits. Immunohistochemistry was used to reveal the ER stress state of lymphatic endothelial cells (LECs) in LMs. RESULTS: LPS induced ER stress in HDLECs but did not trigger detectable apoptosis. Intriguingly, LPS-treated HDLECs also showed increased glycolysis flux. Knockdown of Hexokinase 2, a key enzyme for aerobic glycolysis, significantly inhibited the ability of HDLECs to resist ER stress-induced apoptosis. Moreover, compared to normal skin, glucose-regulated protein 78 (GRP78/BIP), and phosphorylation protein kinase R-like kinase (p-PERK), two key ER stress-associated markers, were upregulated in LECs of LMs, which was correlated with the inflected state. In addition, excessively activated ER stress inhibited the progression of LMs in rat models. CONCLUSIONS: These data indicate that glycolysis could rescue activated ER stress in HDLECs, which is required for the accelerated development of LMs. IMPACT: Inflammation enhances both ER stress and glycolysis in LECs while glycolysis is required to attenuate the pro-apoptotic effect of ER stress. Endoplasmic reticulum (ER) stress is activated in lymphatic endothelial cells (LECs) of LMs, especially in inflammatory condition. The expression of ER stress-related proteins is increased in LMs and correlated with Hexokinase 2 expression. Pharmacological activation of ER stress suppresses the formation of LM lesions in the rat model. ER stress may be a promising and effective therapeutic target for the treatment of LMs.

13.
Heliyon ; 10(9): e30120, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707277

RESUMO

Capital needs transportation channels. Following successful communication and cooperation with Central Asian and European states, the China railway express (CRE) has been built by central and western cities. This new international freight service will greatly enhance the transport conditions in the central and western cities. Therefore, it is necessary to conduct an in-depth analysis of the impact of CRE operations on foreign direct investment (FDI) flows in the central and western regions. For analyses, a panel data of 152 Chinese cities from 2008 to 2020 is used and staggered difference in differences (DID) model is applied as a quasi-natural experiment. The results demonstrated that the operation of the CRE had a positive and significant impact on FDI inflows in the central and western cities, particularly in western cities, large cities, and non-resource based cities in China. Mechanism analysis shows that CRE operations can enhance the ability to attract foreign investment in the central and western regions through the promotion of industrial agglomeration and the expansion of market size. Therefore, the government should actively optimize the layout of CRE transportation routes and establish an inter-regional coordinating mechanism for freight sources, thus allowing the radiating effect of CRE central cities to reach out to peripheral cities.

14.
J Psychiatr Res ; 175: 316-322, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38759497

RESUMO

Anxiety disorders (AD) usually onset in childhood or adolescence and are related to brain development and early experiences during this period. As the hub of the fear circuit, the amygdala plays a crucial role in the development of emotional processing, and abnormalities in its structure and function are associated with anxiety disorders. We aim to uncover the amygdala volume's moderation between parenting and anxiety severity in children and adolescents with AD. 129 children and adolescents with anxiety and 135 age- and sex-matched Health controls (HC) using the publicly available Healthy Brain Network (HBN) dataset were included. Anxiety severity was measured using the Screen for Child Anxiety Related Disorders Self-report (SCARED-SR) and parenting was measured using the Alabama Parenting Questionnaire Self-Report (APQ-SR). We investigated age-related differences in amygdala volume in children and adolescents with anxiety disorders. Further, we examined the role of amygdala volume in moderating the association between parental involvement, particularly the maternal involvement, and anxiety symptoms in this population. We found larger bilateral amygdala in the AD group compared with the HC among the age range of 7-12. And increases in amygdala volume tended to negatively moderate the linear relationships between maternal involvement and anxiety symptoms in the AD group. These findings provide new evidence of abnormal brain alteration in children and adolescents with anxiety and may reflect proactive adaptations of adolescent brain development.

15.
Sci Rep ; 14(1): 11240, 2024 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755191

RESUMO

Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen-glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.


Assuntos
AVC Isquêmico , Fator 2 Relacionado a NF-E2 , Óxido Nítrico Sintase Tipo III , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , AVC Isquêmico/prevenção & controle , Ratos , Fosfatidilinositol 3-Quinases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Apoptose/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular
16.
Food Chem ; 453: 139625, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38754349

RESUMO

Simultaneous inoculation of non-Saccharomyces cerevisiae during the alcoholic fermentation process has been found to be an effective strategy for enhancing wine flavor. This study aimed to investigate the effect of Torulaspora delbrueckii NCUF305.2 on the flavor of navel orange original brandy (NOOB) using E-nose combined with HS-SPME-GC-MS. The results showed a significant increase (p < 0.05) in the sensitivity of NOOB to W5C, W3C, W1S, and W3S sensors by mixed fermentation (MF). Esters in NOOB increased by 4.13%, while higher alcohols increased by 21.93% (p < 0.001), terpenes and others increased by 52.07% and 40.99% (p < 0.01), respectively. Notably, several important volatile compounds with relative odor activity values above 10 showed an increase. Sensory analysis revealed that a more pronounced citrus-like flavor and higher overall appearance scores were found in MF than in pure fermentation (PF). These findings offer valuable theoretical guidance for enhancing the quality of fruit brandies.

17.
Angew Chem Int Ed Engl ; : e202407025, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742866

RESUMO

The adsorbate-mediated strong metal-support interaction (A-SMSI) offers a reversible means of altering the selectivity of supported metal catalysts, thereby providing a powerful tool for facile modulation of catalytic performance. However, the fundamental understanding of A-SMSI remains inadequate and methods for tuning A-SMSI are still in their nascent stages, impeding its stabilization under reaction conditions. Here, we report that the initial concentration of oxygen vacancy in oxide supports plays a key role in tuning the A-SMSI between Ru nanoparticles and defected titania (TiO2-x). Based on this new understanding, we demonstrate the in-situ formation of A-SMSI under reaction conditions, obviating the typically required CO2-rich pretreatment. The as-formed A-SMSI layer exhibits remarkable stability at various temperatures, enabling excellent activity, selectivity and long-term stability in catalyzing the reverse water gas-shift reaction. This study deepens the understanding of the A-SMSI and the ability to stabilize A-SMSI under reaction conditions represents a key step for practical catalytic applications.

18.
Front Immunol ; 15: 1374486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745651

RESUMO

A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2) -binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Vetores Genéticos , SARS-CoV-2 , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Camundongos , Humanos , Feminino , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Adenoviridae/genética , Adenoviridae/imunologia , Camundongos Endogâmicos BALB C , Administração Intranasal , Injeções Intramusculares , Imunidade Humoral , Citocinas/metabolismo , Imunidade Celular
19.
Interdiscip Sci ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581626

RESUMO

Exploration of the intricate connections between long noncoding RNA (lncRNA) and diseases, referred to as lncRNA-disease associations (LDAs), plays a pivotal and indispensable role in unraveling the underlying molecular mechanisms of diseases and devising practical treatment approaches. It is imperative to employ computational methods for predicting lncRNA-disease associations to circumvent the need for superfluous experimental endeavors. Graph-based learning models have gained substantial popularity in predicting these associations, primarily because of their capacity to leverage node attributes and relationships within the network. Nevertheless, there remains much room for enhancing the performance of these techniques by incorporating and harmonizing the node attributes more effectively. In this context, we introduce a novel model, i.e., Adaptive Message Passing and Feature Fusion (AMPFLDAP), for forecasting lncRNA-disease associations within a heterogeneous network. Firstly, we constructed a heterogeneous network involving lncRNA, microRNA (miRNA), and diseases based on established associations and employing Gaussian interaction profile kernel similarity as a measure. Then, an adaptive topological message passing mechanism is suggested to address the information aggregation for heterogeneous networks. The topological features of nodes in the heterogeneous network were extracted based on the adaptive topological message passing mechanism. Moreover, an attention mechanism is applied to integrate both topological and semantic information to achieve the multimodal features of biomolecules, which are further used to predict potential LDAs. The experimental results demonstrated that the performance of the proposed AMPFLDAP is superior to seven state-of-the-art methods. Furthermore, to validate its efficacy in practical scenarios, we conducted detailed case studies involving three distinct diseases, which conclusively demonstrated AMPFLDAP's effectiveness in the prediction of LDAs.

20.
Dev Cell ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38574731

RESUMO

Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, GSK3ß inhibition countered the actions of Wnt antagonists on intestinal stem cells, resulting in impaired adenoma formation of telomere dysfunctional Apc-mutant cells. Thus, telomere dysfunction contributes to cancer initiation through altered stem cell dynamics, identifying an interception strategy for human APC-mutant cancers with shortened telomeres.

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