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1.
J Environ Sci (China) ; 149: 394-405, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181652

RESUMO

Heterogeneous crystallization is a common occurrence during the formation of solid wastes. It leads to the encapsulation of valuable/hazardous metals within the primary phase, presenting significant challenges for waste treatment and metal recovery. Herein, we proposed a novel method involving the in-situ formation of a competitive substrate during the precipitation of jarosite waste, which is an essential process for removing iron in zinc hydrometallurgy. We observed that the in-situ-formed competitive substrate effectively inhibits the heterogeneous crystallization of jarosite on the surface of anglesite, a lead-rich phase present in the jarosite waste. As a result, the iron content on the anglesite surface decreases from 34.8% to 1.65%. The competitive substrate was identified as schwertmannite, characterized by its loose structure and large surface area. Furthermore, we have elucidated a novel mechanism underlying this inhibition of heterogeneous crystallization, which involves the local supersaturation of jarosite caused by the release of ferric and sulfate ions from the competitive substrate. The local supersaturation promotes the preferential heterogeneous crystallization of jarosite on the competitive substrate. Interestingly, during the formation of jarosite, the competitive substrate gradually vanished through a dissolution-recrystallization process following the Ostwald rule, where a metastable phase slowly transitions to a stable phase. This effectively precluded the introduction of impurities and reduced waste volume. The goal of this study is to provide fresh insights into the mechanism of heterogeneous crystallization control, and to offer practical crystallization strategies conducive to metal separation and recovery from solid waste in industries.


Assuntos
Cristalização , Compostos Férricos , Compostos Férricos/química , Sulfatos/química , Compostos de Ferro/química , Ferro/química , Eliminação de Resíduos/métodos
2.
Nat Plants ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300323

RESUMO

Chloroplasts regulate plant development and immunity. Here we report that potato chloroplast elongation factors StTuA and StTuB, targeted by Phytophthora infestans RXLR effector Pi22926, positively regulate immunity and growth. Plants expressing Pi22926, or silenced for TuA/B, show increased P. infestans susceptibility and decreased photosynthesis, plant growth and tuber yield. By contrast, StTuA/B overexpression reduces susceptibility, elevates chloroplast-derived reactive oxygen species production and increases photosynthesis and potato tuber yield by enhancing chloroplast protein translation. Another plant target of Pi22926, StMAP3Kß2, interacts with StTuB, phosphorylating it to promote its translocation into chloroplasts. However, Pi22926 attenuates StTuB association with StMAP3Kß2 and phosphorylation. This reduces StTuB translocation into chloroplasts, leading to its proteasome-mediated turnover in the cytoplasm. We uncover new mechanisms by which a pathogen effector inhibits immunity by disrupting key chloroplast functions. This work shows that StTuA/B break the growth-immunity trade-off, promoting both disease resistance and yield, revealing the enormous potential of chloroplast biology in crop breeding.

3.
Sci Rep ; 14(1): 21404, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271920

RESUMO

Accurately detecting voltage faults is essential for ensuring the safe and stable operation of energy storage power station systems. To swiftly identify operational faults in energy storage batteries, this study introduces a voltage anomaly prediction method based on a Bayesian optimized (BO)-Informer neural network. Firstly, the temporal characteristics and actual data collected by the battery management system (BMS) are considered to establish a long-term operational dataset for the energy storage station. The Pearson correlation coefficient (PCC) is used to quantify the correlations between these data. Secondly, an Informer neural network with BO hyperparameters is used to build the voltage prediction model. The performance of the proposed model is assessed by comparing it with several state-of-the-art models. With a 1 min sampling interval and one-step prediction, trained on 70% of the available data, the proposed model reduces the root mean square error (RMSE), mean square error (MSE), and mean absolute error (MAE) of the predictions to 9.18 mV, 0.0831 mV, and 6.708 mV, respectively. Furthermore, the influence of different sampling intervals and training set ratios on prediction results is analyzed using actual grid operation data, leading to a dataset that balances efficiency and accuracy. The proposed BO-based method achieves more precise voltage abnormity prediction than the existing methods.

4.
Int J Biol Macromol ; 278(Pt 4): 134987, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39181359

RESUMO

Noisy tinnitus is a common auditory system disease characterized by persistent tinnitus symptoms. The TLR4/NF - κ B/NLRP3 signaling pathway plays an important role in neuroinflammatory response. Select 6 control and 6 noise exposed mice for transcriptome sequencing analysis in the hippocampus, conduct high-throughput data analysis, identify differentially expressed genes, and screen for pathways. Auditory brainstem response (ABR) detection was performed to understand the hearing changes, and the modeling effect was evaluated using the GPIAS% inhibition experiment of auditory startle reflex. Morphological observation of the basement membrane was performed to determine whether the inner hair cells were damaged. Immunohistochemistry and immunofluorescence were used to determine the activation of microglia in the hippocampus of noise induced tinnitus mice. Finally, qPCR and Western Blot were used to detect the expression of TLR4, NF kB, NLRP3, caspase-1, and IL-1 ß in the hippocampus of each group of mice. Through high-throughput data analysis, it was found that there was no significant difference in the auditory threshold of the three groups of mice; After 2 h of exposure to 100 dB SPL noise, the GPIAS% of mice decreased significantly compared to before exposure, and membrane construction was successful. After 7 days, the GPIAS% of the drug intervention group increased. After noise exposure, mice developed tinnitus, and hippocampus neuroinflammation. Roflupram can inhibit neuroinflammation and improve tinnitus through the TLR4/NF kB/NLRP3/caspase-1/IL-1 ß signaling pathway.


Assuntos
Caspase 1 , Interleucina-1beta , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ruído , Transdução de Sinais , Zumbido , Receptor 4 Toll-Like , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Caspase 1/metabolismo , NF-kappa B/metabolismo , Interleucina-1beta/metabolismo , Zumbido/tratamento farmacológico , Zumbido/metabolismo , Zumbido/patologia , Ruído/efeitos adversos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Masculino , Modelos Animais de Doenças , Sulfonamidas
5.
Artigo em Inglês | MEDLINE | ID: mdl-39154930

RESUMO

Insomnia is the second most prevalent psychiatric disorder worldwide, but the understanding of the pathophysiology of insomnia remains fragmented. In this study, we calculated the connectome gradient in 50 chronic insomnia disorder (CID) patients and 38 healthy controls (HC) to assess changes due to insomnia and utilized these gradients in a connectome-based predictive modeling (CPM) to predict clinical symptoms associated with insomnia. The results suggested that insomnia led to significant alterations in the functional gradients of some brain areas. Specifically, the gradient scores in the middle frontal gyrus, superior anterior cingulate gyrus, and right nucleus accumbens were significantly higher in the CID patients than in the HC group, whereas the scores in the middle occipital gyrus, right fusiform gyrus, and right postcentral gyrus were significantly lower than in the HC group. Further correlation analysis revealed that the right middle frontal gyrus is positively correlated with the self-rating anxiety scale (r=0.3702). Additionally, the prediction model built with functional gradients could well predict the sleep quality (r=0.5858), anxiety (r=0.6150), and depression (r=0.4022) levels of insomnia patients. This offers an objective depiction of the clinical diagnosis of insomnia, yielding a beneficial impact on the identification of effective biomarkers and the comprehension of insomnia.


Assuntos
Encéfalo , Conectoma , Imageamento por Ressonância Magnética , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Feminino , Adulto , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Ansiedade/fisiopatologia , Ansiedade/diagnóstico por imagem , Depressão/fisiopatologia , Depressão/diagnóstico por imagem
6.
Am Heart J ; 278: 33-40, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39182902

RESUMO

BACKGROUND: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. METHODS: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study. CONCLUSIONS: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT04347330).

7.
Arch Microbiol ; 206(8): 350, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995446

RESUMO

KKL-35 is a new oxadiazole compound with potent broad-spectrum antibacterial activity against a number of gram-positive and gram-negative bacteria. However, its influences on bacterial growth are unclear. This study is to investigate phenotypic changes of Staphylococcus aureus (SA) caused by KKL-35 and evaluate antibacterial activity of combinations of KKL-35 with 7 class of antibiotics available in medical facilities. KKL-35-treated SA showed significantly lower survival under stresses of NaCl and H2O2 than DMSO (21.03 ± 2.60% vs. 68.21 ± 5.31% for NaCl, 4.91 ± 3.14% vs. 74.78 ± 2.88% for H2O2). UV exposure significantly decreased survival of SA treated with KKL-35 than DMSO-treated ones (23.91 ± 0.71% vs. 55.45 ± 4.70% for 4.2 J/m2, 12.80 ± 1.03% vs. 31.99 ± 5.99% for 7.0 J/m2, 1.52 ± 0.63% vs. 6.49 ± 0.51% for 14.0 J/m2). KKL-35 significantly decreased biofilm formation (0.47 ± 0.12 vs. 1.45 ± 0.21) and bacterial survival in the serum resistance assay (42.27 ± 2.77% vs. 78.31 ± 5.64%) than DMSO. KKL-35 significantly decreased ethidium bromide uptake and efflux, as well as the cell membrane integrity. KKL-35 had low cytotoxicity and low propensity for resistance. KKL-35 inhibited SA growth in concentration-independent and time-dependent manners, and showed additivity when combined with the majority class of available antibiotics. Antibiotic combinations of KKL-35 with ciprofloxacin, rifampicin, or linezolid significantly decreased bacterial loads than the most active antibiotic in the corresponding combination. Thus, KKL-35 inhibits growth of SA by decreasing bacterial environmental adaptations, biofilm formation, membrane uptake and efflux, as well as increasing antibiotic sensitivity. Its potent antibacterial activity, low cytotoxicity, low propensity for resistance, and wide choices in antibiotic combinations make KKL-35 a promising leading compound to design new antibiotics in monotherapies and combination therapies to treat bacterial infections.


Assuntos
Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Oxidiazóis , Staphylococcus aureus , Humanos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Oxidiazóis/farmacologia , Fenótipo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
8.
Front Neurol ; 15: 1388544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974688

RESUMO

Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN). Methods: Four patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment. Results: Three of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient's score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment. Conclusion: Acupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.

9.
Front Nutr ; 11: 1403497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966420

RESUMO

Introduction: Resistant starch (RS) has garnered attention for its health benefits, including modulating the gut microbiota and promoting the production of short-chain fatty acids (SCFAs). Methods: This study investigates structural changes of type 3 resistant starch from Canna edulis (CE) during in vitro simulated digestion and explores its health-relevant properties using healthy individuals' fecal microbiota. Results: CE, prepared with a RS content of 59.38%, underwent a comprehensive analysis employing X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During simulated digestion, XRD analysis demonstrated a significant rise in CE's relative crystallinity from 38.92 to 49.34%. SEM illustrated the transition of CE from a smooth to a rough surface, a notable morphological shift. Post-digestion, CE was introduced into microbial fermentation. Notably, propionic acid and valeric acid levels significantly increased compared to the control group. Furthere more, beneficial Bifidobacterium proliferated while pathogenic Escherichia-Shigella was suppressed. When comparing CE to the well-known functional food fructo-oligosaccharide (FOS), CE showed a specific ability to support the growth of Bifidobacterium and stimulate the production of short-chain fatty acids (SCFAs) without causing lactic acid accumulation. Discussion: CE demonstrates potential as a functional health food, with implications for gut health enhancement and SCFAs production.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38970310

RESUMO

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has been reported to be helpful to identify high-risk individuals of developing prostate cancer. Our aim is to investigate the relationship between NAFLD and biochemical recurrence in metastatic prostate cancer patients. METHODS: We retrospectively investigated 602 patients with metastatic prostate cancer receiving the androgen deprivation therapy. Liver fat was estimated with liver-to-spleen ratio by computed tomography (CT) scans. The relationship between NAFLD and biochemical recurrence was investigated with Cox models. The model for biochemical recurrence was adjusted for multiple variables. RESULTS: NAFLD was significantly associated with biochemical recurrence in patients with Gleason score ≥4+3 when adjusting for each of body mass index (hazards ratio [HR] = 1.38; 95% confidence interval [CI] = 1.08-1.77; p = 0.01), visceral adipose tissue (HR = 1.36; 95% CI = 1.07-1.74; p = 0.01), hypertension (HR = 1.41; 95% CI = 1.10-1.80; p = 0.01), and diabetes mellitus (HR = 1.42; 95% CI = 1.11-1.82; p = 0.01), using age and prostate-specific antigen level as potential confounder. The 2-year biochemical recurrence rate in the Gleason score ≥4+3 patients with and without NAFLD was 84.0% (100/119) and 72.2% (130/180), respectively (p = 0.018). The median biochemical recurrence free survival of the Gleason score ≥4+3 patients with and without NAFLD were 17 and 21 months, respectively (p = 0.005). CONCLUSIONS: NAFLD is an independent risk factor for biochemical recurrence in patients with high-grade metastatic prostate cancer. If validated in prospective studies, future research should test whether treatment of NAFLD can lead to better prognosis.

11.
Int J Mol Sci ; 25(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39000025

RESUMO

3,4-disubstituted maleimides find wide applications in various pharmacologically active compounds. This study presents a highly effective approach for synthesizing derivatives of 3,4-disubstituted maleimides through the direct isomerization of α-succinimide-substituted allenoates, followed by a cascade γ'-addition and aryl imines using PR3 as a catalyst. The resulting series of 3,4-disubstituted maleimides exhibited excellent stereoselectivities, achieving yields of up to 86%. To our knowledge, the phosphine-mediated γ'-addition reaction of allenoates is seldom reported.


Assuntos
Iminas , Maleimidas , Fosfinas , Succinimidas , Maleimidas/química , Maleimidas/síntese química , Fosfinas/química , Catálise , Iminas/química , Succinimidas/química , Estereoisomerismo , Estrutura Molecular , Isomerismo
12.
J Ophthalmol ; 2024: 6685092, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39041005

RESUMO

This study aimed to evaluate the efficacy and safety of intravitreal dexamethasone implants in the treatment of ocular toxocariasis (OT). A retrospective analysis was performed on 6 cases in which laboratory tests diagnosed OT. All patients were administered with intravitreal dexamethasone implants with or without vitrectomy. The average follow-up time was 19.7 months. All operated eyes achieved anatomic success, and all patients' visual acuity was improved. Five of these six had a visual acuity of 20/100, and three had final acuity of 20/40 or even better. Intravitreal dexamethasone implants can be used to treat different types of OT, which not only effectively control inflammation and improve the patient's vision but also reduce the use of systemic glucocorticoids.

13.
Front Immunol ; 15: 1402074, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39044820

RESUMO

Background: Uveitis, characterized by inflammation of the iris, ciliary body, and choroid, presents a significant global clinical challenge, contributing substantially to visual impairment. Risk factors include autoimmune diseases and immune cell dysfunctions, yet many remain unidentified. Immune cells, notably T cells, B cells, and monocytes, play pivotal roles in uveitis pathogenesis. While biologic agents show promise, comprehensive studies on immune cell types in ocular diseases are lacking. Genome-wide association studies (GWAS) and Mendelian randomization (MR) present promising avenues to elucidate genetic susceptibilities and causal relationships between immune cell traits and uveitis risk. Methods: Two-sample MR analysis was used to evaluate the causal relationship between 731 immune cells and uveitis, and genome-wide significance analysis was performed for genetic variation in 731 immune cells traits (P < 5 × 10-8). Immune characteristics include median fluorescence intensity (MFI), relative cell counts (RC), absolute cell counts (AC), and morphological parameters (MP), which were determined by published GWAS, and public data from the IEU Open GWAS database. The main analysis method of MR is inverse variance weighting (IVW). Heterogeneity and horizontal pleiotropy were also assessed. Results: 5 immunophenotypes, including CD62L-DC %DC, IgD+ CD38dim %B cell, CD3 on CM CD4+T cell, CD3 on CD45RA-CD4 +T cell, and CD3 on CD39+ CD4+ Treg may increase the risk of uveitis. 5 immunophenotypes, including CD11b on CD33dim HLA DR-Myeloid cell, HLA DR on CD33dim HLA DR+ CD11b-myeloid cell, CD14-CD16 + %monocyte, HLA DR on CD14-CD16 + monocyte and PDL-1 on CD14-CD16 + monocyte was negatively associated with the risk of uveitis. Among them, HLA DR on CD14-CD16 + monocyte (OR=0.921, 95%CI =0.875-0.970, P=0.001) and HLA DR on CD33dim HLA DR+ CD11b- (OR=0.879, 95%CI = 0.833-0.927, P=0.00) were negatively associated with the risk of uveitis in bi-direction. Conclusion: These results indicate that 10 immune cells traits are significantly associated with the risk of developing uveitis and 2 of them were strongly associated with uveitis bi-directionally, after excluding the effects of confounding factors such as some immune diseases, which provided new ideas and therapeutic targets for the study of immune mechanism of uveitis.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Uveíte , Humanos , Uveíte/imunologia , Uveíte/genética , Polimorfismo de Nucleotídeo Único , Imunofenotipagem
14.
BMC Genomics ; 25(1): 673, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969975

RESUMO

BACKGROUND: Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. RESULTS: In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P < 0.05), indicating many low-frequency mutations in the populations and that the populations might be in the process of expansion. Moreover, Wolbachia infection was detected only in SDJN (Jining) (2.24%), and all Wolbachia genotypes belonged to supergroup B. To understand the influence of environmental factors on mosquito-borne viruses, we examined the prevalence of Culex tritaeniorhynchus infection in three ecological environments in Shandong Province. We discovered that the incidence of JEV infection was notably greater in Culex tritaeniorhynchus from lotus ponds compared to those from irrigation canal regions. In this study, the overall JEV infection rate was 15.27 per 1000, suggesting the current risk of Japanese encephalitis outbreaks in Shandong Province. CONCLUSIONS: Tropical and subtropical populations of Culex tritaeniorhynchus showed higher genetic diversity and those climatic conditions provide great advantages for the establishment and expansion of Culex tritaeniorhynchus. There are differences in JEV infection rates in wild populations of Culex tritaeniorhynchus under different ecological conditions. Our results suggest a complex interplay of genetic differentiation, population structure, and environmental factors in shaping the dynamics of Culex tritaeniorhynchus. The low prevalence of Wolbachia in wild populations may reflect the recent presence of Wolbachia invasion in Culex tritaeniorhynchus.


Assuntos
Culex , Haplótipos , Filogenia , Culex/genética , Culex/virologia , Culex/microbiologia , Animais , China , Clima , Variação Genética , Genética Populacional , Wolbachia/genética , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , Mosquitos Vetores/microbiologia , Complexo IV da Cadeia de Transporte de Elétrons/genética
15.
Molecules ; 29(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38893468

RESUMO

In this paper, an interesting γ'-carbon 1,6-conjugate addition for phosphine-catalyzed α-succinimide substituted allenoates has been disclosed. A wide array of substrates was found to participate in the reaction, resulting in the production of diverse 4-diarylmethylated 3,4-disubstituted maleimides with satisfactory to outstanding yields. Furthermore, a plausible mechanism for the reaction was proposed by the investigators.

16.
Sci Transl Med ; 16(750): eadi4125, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838135

RESUMO

Chronic inflammation is a constitutive component of many age-related diseases, including age-related macular degeneration (AMD). Here, we identified interleukin-1 receptor-associated kinase M (IRAK-M) as a key immunoregulator in retinal pigment epithelium (RPE) that declines during the aging process. Rare genetic variants of IRAK3, which encodes IRAK-M, were associated with an increased likelihood of developing AMD. In human samples and mouse models, IRAK-M abundance in the RPE declined with advancing age or exposure to oxidative stress and was further reduced in AMD. Irak3-knockout mice exhibited an increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M led to a disruption in RPE cell homeostasis, characterized by compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of adeno-associated virus (AAV)-expressing human IRAK3 rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in Irak3-knockout mice. Our data show that replenishment of IRAK-M in the RPE may redress dysregulated pro-inflammatory processes in AMD, suggesting a potential treatment for retinal degeneration.


Assuntos
Quinases Associadas a Receptores de Interleucina-1 , Camundongos Knockout , Estresse Oxidativo , Degeneração Retiniana , Epitélio Pigmentado da Retina , Animais , Humanos , Masculino , Camundongos , Senescência Celular , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Quinases Associadas a Receptores de Interleucina-1/genética , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Degeneração Macular/genética , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/genética , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia
17.
Pharmacol Res ; 205: 107232, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38825157

RESUMO

Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20 g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16 S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16 S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871).


Assuntos
Microbioma Gastrointestinal , Hiperlipidemias , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Método Duplo-Cego , Masculino , Pessoa de Meia-Idade , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/sangue , Hiperlipidemias/microbiologia , Feminino , Adulto , Lipídeos/sangue , Amido Resistente , Amido , Hipolipemiantes/uso terapêutico , Hipolipemiantes/farmacologia , Idoso
18.
Materials (Basel) ; 17(10)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38793518

RESUMO

In recent years, asphalt pavement has been subjected to varied environmental conditions during its service life, conditions that predispose it to deformation and cracking. To enhance the performance of asphalt pavement, rock asphalt has been selected as a modifier due to its good compatibility with virgin asphalt binder and its ability to improve the fatigue cracking resistance of asphalt mixtures. Although scholars have conducted some studies on rock asphalt mixtures, research on the fatigue and self-healing performance of these mixtures under conditions such as ultraviolet (UV) aging and freeze-thaw remains limited. This paper presents findings from a study that employs a combined fatigue-healing test to assess the impact of such complex environmental factors on the fatigue and self-healing properties of fine aggregate matrix (FAM) mixtures containing three types of rock asphalts, i.e., Buton, Qingchuan (QC), and Uintaite Modifier (UM). The analysis of fatigue-healing test results, grounded in viscoelastic continuum damage (VECD) theory, indicates that rock asphalt can extend the fatigue life of FAM mixtures, albeit with a concomitant decrease in their self-healing capabilities. The study further reveals that UV aging, freeze-thaw, and UV aging-freeze-thaw conditions all led to a diminution in the fatigue and self-healing properties of FAM mixtures. However, FAM mixtures containing rock asphalt demonstrated greater resilience against these reductions. Atomic force microscope (AFM) results indicate that UV aging reduced the number of bee-structures and enlarged their area, whereas the incorporation of rock asphalt enhanced the uniformity of these structures' distribution, thereby improving the fatigue cracking resistance of FAM mixtures. Fourier transform infrared spectroscopy (FTIR) analysis reveals that while UV aging increased the carbonyl and sulfoxide indices within the asphalt binder, rock asphalt is effective in mitigating this effect to a certain degree, thereby enhancing the aging resistance of FAM mixtures.

19.
Int J Biol Macromol ; 271(Pt 1): 132340, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38816293

RESUMO

In this study, the high amylose corn starch and Canna edulis native starch were compounded with lauric acid and fermented by human fecal inoculation in vitro. Changes in beneficial metabolite profile and microbiota composition were evaluated. The structural properties showed that both NS-12C and HAMS-12C formed V-shaped crystals under the same preparation method, but NS-12C had a higher composite index and resistance content than HAMS-12C. At the end of fermentation, the starch-lauric acid complexes prepared from the two types of starch significantly promoted the formation of short-chain fatty acids and the contents of acetic acid, butyric acid and valeric acid produced by NS-12C were higher than those of HAMS-12C(p>0.05). HAMS-12C and NS-12C both increased the relative abundance of Blautia. Notably, NS-12C also increased the relative abundance of beneficial bacteria Bifidobacterium and Meganomas, while HAMS-12C did not. These results suggested that this effect may be related to starch type and provide a basis for designing and producing functional foods to improve intestinal health in Canna edulis native starch.


Assuntos
Amilose , Fermentação , Amido , Amilose/química , Amido/química , Humanos , Fezes/microbiologia , Fezes/química , Microbioma Gastrointestinal , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/química , Ácidos Láuricos/química , Zea mays/química
20.
J Pharm Biomed Anal ; 245: 116194, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38704878

RESUMO

A miniature mass spectrometer (mMS) based point-of-care testing (POCT) method was evaluated for on-site detecting the hypertension drugs, amlodipine and benazepril. The instrument parameters, including voltage, ISO1, ISO2, and CID, were optimized, under which the target compounds could be well detected in MS2. When these two drugs were injected simultaneously, the mutual ionization inhibition and mutual reduction between amlodipine and benazepril were evaluated. This phenomenon was severe on the precursor ions but had a small impact on the product ions, thus making this POCT method suitable for analysis using product ions. Finally, the method was validated and applied. The blood samples from patients were tested one hour after oral administration of the drugs (20 mg), and the benazepril was quantitatively analyzed using a standard curve, with detected concentrations ranging from 190.6 to 210 µg L-1 and a relative standard deviation (RSD) of 8.6 %. In summary, amlodipine has low sensitivity and can only be detected at higher concentrations, while benazepril has high sensitivity, good linearity, and even meets semi-quantitative requirements. The research results of this study are of great clinical significance for monitoring blood drug concentrations during hypertension medication, predicting drug efficacy, and customizing individualized medication plans.


Assuntos
Anlodipino , Anti-Hipertensivos , Benzazepinas , Anlodipino/sangue , Humanos , Benzazepinas/sangue , Anti-Hipertensivos/sangue , Anti-Hipertensivos/administração & dosagem , Espectrometria de Massas/métodos , Testes Imediatos , Reprodutibilidade dos Testes , Limite de Detecção , Sistemas Automatizados de Assistência Junto ao Leito
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