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1.
Talanta ; 275: 126127, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38663073

RESUMO

Modified electrosynthetic sample introduction technique is a reliable means of solving the problem of high sensitivity analysis of trace arsenite. This article attempts to achieve selective electroreduction of AsIII through the construction of electrode surfaces with different structures and materials from the perspective of interface reactions. Among the four transition metal modifiers, the iron modified nickel foam electrode with nano-flower structure documented higher efficiency in inducing arsenic reduction and better species selectivity. Systematic electrochemical and spectroscopic tests suggest that strong adsorption effect between Fe and AsIII, appropriate hydrogen evolution potential, and catalytic activity jointly promote efficient electroreduction of AsIII. Optimization based on electrode materials and electrolysis conditions, with high sensitivity, wide linear range (0.1-50 µg L-1), and excellent species selectivity, this paper offers an efficient and economic sample introduction method for trace AsIII/V selective atomic spectroscopy direct determination.

2.
ACS Appl Mater Interfaces ; 16(15): 19283-19297, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38578950

RESUMO

Lead-free BiFeO3-BaTiO3 (BF-BT) piezoceramics have sparked considerable interest in recent years due to their high piezoelectric performance and high Curie temperature. In this paper, we show how the addition of highly aligned porosity (between 40 and 60 vol %) improves the piezoelectric performance, sensing, and energy harvesting figures of merit in freeze-cast 0.70BiFeO3-0.30BaTiO3 piezoceramics compared to conventionally processed, nominally dense samples of the same composition. The dense and porous BF-BT ceramics had similar longitudinal piezoelectric coefficients (d33) immediately after poling, yet the dense samples were observed to age faster than those of porous ceramics. After 24 h, for example, the porous samples had significantly higher d33 values ranging from 112 to 124 pC/N, compared to 85 pC/N for the dense samples. Porous samples exhibited 3 and 5 times higher longitudinal piezoelectric voltage coefficient g33 and energy harvesting figure of merit d33g33 than dense samples due to the unexpected increase in d33 and decrease in relative permittivity with porosity. Spontaneous polarization (Ps) and remnant polarization (Pr) decrease as the porosity content increased from 37 to 59 vol %, as expected due to the lower volume of active material; however, normalized polarization values with respect to porosity level showed a slight increase in the porous materials relative to the dense BF-BT. Furthermore, the porous ceramics showed improved temperature-dependent strain-field response compared to the dense. As a result, these porous materials show excellent potential for use in high temperature sensing and harvesting applications.

3.
Front Cell Infect Microbiol ; 14: 1327032, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596649

RESUMO

Aim: Mendelian randomization (MR) analysis has been used in the exploration of the role of gut microbiota (GM) in type 2 diabetes mellitus (T2DM); however, it was limited to the genus level. This study herein aims to investigate the relationship of GM, especially at the species level, with T2DM in order to provide some evidence for further exploration of more specific GM taxa and pathway abundance in T2DM. Methods: This two-sample MR study was based on the summary statistics of GM from the available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen consortium as well as the Dutch Microbiome Project (DMP), whereas the summary statistics of T2DM were obtained from the FinnGen consortium released data. Inverse variance weighted (IVW), MR-Egger, strength test (F), and weighted median methods were used to examine the causal association between GM and the onset of T2DM. Cochran's Q statistics was employed to quantify the heterogeneity of instrumental variables. Bonferroni's correction was conducted to correct the bias of multiple testing. We also performed reverse causality analysis. Results: The corrected IVW estimates suggested the increased relative abundance of family Oxalobacteraceae (OR = 1.0704) and genus Oxalobacter (OR = 1.0874), respectively, were associated with higher odds of T2DM, while that of species faecis (OR = 0.9460) had a negative relationship with T2DM. The relationships of class Betaproteobacteria, family Lactobacillaceae, species finegoldii, and species longum with T2DM were also significant according to the IVW results (all P < 0.05). Conclusions: GM had a potential causal association with T2DM, especially species faecis, finegoldii, and longum. Further studies are still needed to clarify certain results that are contradictory with previous findings.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Microbiota , Sulfaleno , Humanos , Diabetes Mellitus Tipo 2/genética , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Metanálise como Assunto
4.
Sci Rep ; 14(1): 9147, 2024 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644461

RESUMO

To investigate the predictive value of baseline platelet count and its short-term dynamic changes in the prognosis of patients with acute heart failure (AHF) in the intensive care unit. Patients diagnosed with AHF in the medical information mart for intensive care III and their clinical data were retrospectively filtered. Patients were divided into survivor and non-survivor groups based on their prognosis during hospitalization, and differences in baseline data between groups were compared. Logistic regression models and restricted cubic spline (RCS) plots were performed to evaluate the relationship between baseline platelet counts and in-hospital mortality. Changes and trends in platelet counts were compared between the survivor and non-survivor groups after adjusting for confounders with the generalized additive mixing model (GAMM). A total of 2930 critical patients with acute heart failure were included, of which 2720 were survivors and 210 were non-survivors. Multiple logistic regression models revealed that baseline platelet count was an independent factor in hospital mortality (OR 0.997, 95% CI 0.994-0.999, P-value = 0.018). The RCS plot demonstrated a U-shaped dose-response relationship between baseline platelet count and in-hospital mortality. GAMM analysis suggested that the platelet counts decreased and then increased in the survivor group and gradually decreased in the non-survivor group, with a gradual increase of difference between two groups. After adjusting for confounders, the mean daily increase was -6.014 (95% CI -7.076-4.953, P-value < 0.001). Baseline platelet demonstrated a U-shaped dose-response relationship with adverse outcomes in critical patients with AHF. Early elevation of platelet was correlated with higher in-hospital mortality, indicating that tracking early changes in platelet might help determine the short-term prognosis of critical patients with AHF.


Assuntos
Insuficiência Cardíaca , Mortalidade Hospitalar , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Masculino , Feminino , Contagem de Plaquetas , Idoso , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Doença Aguda , Idoso de 80 Anos ou mais , Unidades de Terapia Intensiva
5.
Entropy (Basel) ; 26(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38667832

RESUMO

Accurate epidemic forecasting plays a vital role for governments to develop effective prevention measures for suppressing epidemics. Most of the present spatio-temporal models cannot provide a general framework for stable and accurate forecasting of epidemics with diverse evolutionary trends. Incorporating epidemiological domain knowledge ranging from single-patch to multi-patch into neural networks is expected to improve forecasting accuracy. However, relying solely on single-patch knowledge neglects inter-patch interactions, while constructing multi-patch knowledge is challenging without population mobility data. To address the aforementioned problems, we propose a novel hybrid model called metapopulation-based spatio-temporal attention network (MPSTAN). This model aims to improve the accuracy of epidemic forecasting by incorporating multi-patch epidemiological knowledge into a spatio-temporal model and adaptively defining inter-patch interactions. Moreover, we incorporate inter-patch epidemiological knowledge into both model construction and the loss function to help the model learn epidemic transmission dynamics. Extensive experiments conducted on two representative datasets with different epidemiological evolution trends demonstrate that our proposed model outperforms the baselines and provides more accurate and stable short- and long-term forecasting. We confirm the effectiveness of domain knowledge in the learning model and investigate the impact of different ways of integrating domain knowledge on forecasting. We observe that using domain knowledge in both model construction and the loss function leads to more efficient forecasting, and selecting appropriate domain knowledge can improve accuracy further.

6.
BMC Cancer ; 24(1): 411, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566028

RESUMO

BACKGROUND: Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group. METHODS: We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han. Incident cancer events were monitored in 1,005 participants from the healthy group, comprising 11 BRCA pathogenic/likely pathogenic (PLP) variant carriers and 994 PLP-free individuals, including 3 LGR carriers. RESULTS: Healthy Chinese Han individuals demonstrated a distinct BRCA mutational spectrum compared to cancer patients, with a 0.53% (1 in 189) prevalence of pathogenic/likely pathogenic (PLP) variant, alongside a 3 in 2,080 occurrence of LGR. BRCA1 c. 5470_5477del demonstrated high prevalence (0.44%) in the North Han Chinese and penetrance for breast cancer. None of the 3 LGR carriers developed cancer during the follow-up. We calculated a relative risk of 135.55 (95% CI 25.07 to 732.88) for the development of BRCA mutation-related cancers in the BRCA PLP variant carriers (mean age 42.91 years, median follow-up 10 months) compared to PLP-free individuals (mean age 48.47 years, median follow-up 16 months). CONCLUSION: The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.


Assuntos
Proteína BRCA1 , Neoplasias da Mama , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Proteína BRCA1/genética , Mutação em Linhagem Germinativa , Proteína BRCA2/genética , Predisposição Genética para Doença , Detecção Precoce de Câncer , China/epidemiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Mutação
7.
Phytomedicine ; 129: 155636, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38640860

RESUMO

BACKGROUD: Chronic fatigue syndrome (CFS) severely impact patients' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS. PURPOSE: To evaluate the efficacy and safety of SJZD for CFS. STUDY DESIGN: A multi-center, double-blinded, randomized controlled trial. METHODS: Participants with definite diagnoses of CFS and spleen deficiency syndrome were randomly assigned in 1:1 ratio to receive SJZD or placebo granules for 2 months. The primary outcome was the change of Chalder fatigue questionnaire (CFQ) scoring after treatment. Other outcomes included changes in short form-36 physical function (SF36-PF) score, spleen deficiency scale score, Euroqol Questionnaire-Visual Analogue Scale (ED-VAS) score, and clinical global impression (CGI) evaluating by corresponding questionnaires. Fecal metagenome sequencing was conducted to explore the potential mechanism of SJZD effect. RESULTS: From June 2020 to July 2021, 105 of 127 participants completed the study at four hospitals in China. After a 2-month treatment, intention-to-treat (ITT) analysis found participants who received SJZD had larger reduction than placebo control (mean change 6.65 [standard deviation (SD) 6.11] points vs. 5.31 [SD 5.19] points; difference 1.34, 95 % confidence interval [CI] -0.65 to 3.33). Per-protocol (PP) analysis reported confirmative results with a significant difference between SJZD and placebo groups (2.24, 95 % CI 0.10 to 4.39). SJZD also significantly improved overall health status compared with placebo in per-protocol population (p = 0.009). No significant difference was found between groups in changes of SF36-PF, spleen deficiency scale scoring, and CGI. Fecal metagenome sequencing and correlation analyses indicated that the beneficial effect of SJZD may be related to the abundance change of Pediococcus acidilactici. No serious adverse event or abnormal laboratory test was found during the whole study. CONCLUSION: Our results indicated that SJZD can improve fatigue symptom and overall health status in patients with CFS under good medication adherence. Potential therapeutic effects may be related to the regulation of gut microbiota. Large-scale trials with longer intervention period are encouraged to further support SJZD's application. CLINICAL TRIAL REGISTRATION: (ID, ISRCTN23930966, URL = https://www.isrctn.com/ISRCTN23930966).

9.
Environ Sci Technol ; 58(16): 6890-6899, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38606954

RESUMO

Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks.

10.
Neural Netw ; 175: 106315, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626618

RESUMO

Pre-trained Language Model (PLM) is nowadays the mainstay of Unsupervised Sentence Representation Learning (USRL). However, PLMs are sensitive to the frequency information of words from their pre-training corpora, resulting in anisotropic embedding space, where the embeddings of high-frequency words are clustered but those of low-frequency words disperse sparsely. This anisotropic phenomenon results in two problems of similarity bias and information bias, lowering the quality of sentence embeddings. To solve the problems, we fine-tune PLMs by leveraging the frequency information of words and propose a novel USRL framework, namely Sentence Representation Learning with Frequency-induced Adversarial tuning and Incomplete sentence filtering (Slt-fai). We calculate the word frequencies over the pre-training corpora of PLMs and assign words thresholding frequency labels. With them, (1) we incorporate a similarity discriminator used to distinguish the embeddings of high-frequency and low-frequency words, and adversarially tune the PLM with it, enabling to achieve uniformly frequency-invariant embedding space; and (2) we propose a novel incomplete sentence detection task, where we incorporate an information discriminator to distinguish the embeddings of original sentences and incomplete sentences by randomly masking several low-frequency words, enabling to emphasize the more informative low-frequency words. Our Slt-fai is a flexible and plug-and-play framework, and it can be integrated with existing USRL techniques. We evaluate Slt-fai with various backbones on benchmark datasets. Empirical results indicate that Slt-fai can be superior to the existing USRL baselines.

11.
Clin Cardiol ; 47(4): e24264, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563389

RESUMO

BACKGROUND: Recently, patients with type 2 diabetes mellitus (T2DM) have experienced a higher incidence and severer degree of vascular calcification (VC), which leads to an increase in the incidence and mortality of vascular complications in patients with T2DM. HYPOTHESIS: To construct and validate prediction models for the risk of VC in patients with T2DM. METHODS: Twenty-three baseline demographic and clinical characteristics were extracted from the electronic medical record system. Ten clinical features were screened with least absolute shrinkage and selection operator method and were used to develop prediction models based on eight machine learning (ML) algorithms (k-nearest neighbor [k-NN], light gradient boosting machine, logistic regression [LR], multilayer perception [(MLP], Naive Bayes [NB], random forest [RF], support vector machine [SVM], XGBoost [XGB]). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, and precision. RESULTS: A total of 1407 and 352 patients were retrospectively collected in the training and test sets, respectively. Among the eight models, the AUC value in the NB model was higher than the other models (NB: 0.753, LGB: 0.719, LR: 0.749, MLP: 0.715, RF: 0.722, SVM: 0.689, XGB:0.707, p < .05 for all). The k-NN model achieved the highest sensitivity of 0.75 (95% confidence interval [CI]: 0.633-0.857), the MLP model achieved the highest accuracy of 0.81 (95% CI: 0.767-0.852) and specificity of 0.875 (95% CI: 0.836-0.912). CONCLUSIONS: This study developed a predictive model of VC based on ML and clinical features in type 2 diabetic patients. The NB model is a tool with potential to facilitate clinicians in identifying VC in high-risk patients.


Assuntos
Diabetes Mellitus Tipo 2 , Calcificação Vascular , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Teorema de Bayes , Calcificação Vascular/diagnóstico , Calcificação Vascular/epidemiologia , Calcificação Vascular/etiologia , Aprendizado de Máquina
12.
Appl Environ Microbiol ; : e0004624, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563787

RESUMO

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

13.
Sheng Li Xue Bao ; 76(2): 257-265, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38658375

RESUMO

The present study aims to observe the change in expression of heat shock protein 90 (HSP90) along with amyloid-ß (Aß) and phosphorylated Tau (p-Tau) protein levels in the hippocampus tissue of Alzheimer's disease (AD) transgenic animal model with age. APP/PS1 transgenic mice at age of 6-, 9- and 12-month and C57BL/6J mice of the same age were used. The cognitive abilities of these animals were evaluated using a Morris water maze. Western blot or immunohistochemistry was used to detect the expressions of HSP90 and Aß1-42, as well as the phosphorylation levels of Tau protein in the hippocampus. The hsp90 mRNA levels and the morphology and number of cells in the hippocampus were detected with real-time quantitative polymerase chain reaction (qRT-PCR) and Nissl staining, respectively. The results showed that compared with C57BL/6J mice of the same age, HSP90 and hsp90 mRNA expression were decreased (P < 0.05 or P < 0.01), while Aß1-42 and p-Tau protein levels were increased (P < 0.05 or P < 0.01) in the hippocampal tissue of APP/PS1 transgenic mice. Meanwhile, the decrease in HSP90 and hsp90 mRNA expression (P < 0.05 or P < 0.01), the increase in Aß1-42 and p-Tau levels (P < 0.01 or P < 0.05) in hippocampal tissue and the reduction in behavioral ability showed a progressive development with the advancing of age in the APP/PS1 transgenic mice. In conclusion, in the hippocampal tissue of APP/PS1 mice, the decrease in HSP90 expression and the increase in Aß1-42 and p-Tau levels together with the decline of their cognitive ability are age-dependent.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide , Proteínas de Choque Térmico HSP90 , Hipocampo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas tau , Animais , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Hipocampo/metabolismo , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Masculino , Modelos Animais de Doenças , Fosforilação , Fatores Etários , Envelhecimento/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/genética , Presenilina-1/genética , Presenilina-1/metabolismo
14.
J Sci Food Agric ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661233

RESUMO

BACKGROUND: Wheat distillers' grains (WDG) and seaweeds are recommended as alternative protein sources and enteric methane mitigators in dairy cow diets, respectively, but little is known about their impact on milk quality and safety. In the present study, 16 cows in four 4 × 4 latin squares were fed iso-nitrogenous diets (50:50 forage: concentrate ratio), with rapeseed meal (RSM)-based or WDG-based concentrate (230 and 205 g kg-1 DM) and supplemented with or without Saccharina latissima. RESULTS: Replacement of RSM with WDG enhanced milk nutritional profile by decreasing milk atherogenicity (P = 0.002) and thrombogenicity (P = 0.019) indices and the concentrations of the nutritionally undesirable saturated fatty acids, specifically lauric (P = 0.045), myristic (P = 0.022) and palmitic (P = 0.007) acids. It also increased milk concentrations of the nutritionally beneficial vaccenic (P < 0.001), oleic (P = 0.030), linoleic (P < 0.001), rumenic (P < 0.001), α-linolenic (P = 0.012) acids and total monounsaturated (P = 0.044), polyunsaturated (P < 0.001), and n-6 (P < 0.001) fatty acids. Feeding Saccharina latissima at 35.7 g/cow/d did not affect the nutritionally relevant milk fatty acids or pose any risk on milk safety, as bromoform concentrations in milk were negligible and unaffected by the dietary treatments. It however slightly reduced milk concentrations of pantothenate. CONCLUSION: Feeding WDG to dairy cows improved the milk FA profiles, by increasing the concentrations of the nutritionally beneficial fatty acids and reducing the concentration of the nutritionally undesirable saturated fatty acids; while feeding seaweed slightly reduced pantothenate concentrations. However, when considering the current average milk intakes in the population, the milk compositional differences between treatments in this study appear relatively small to affect human health. This article is protected by copyright. All rights reserved.

15.
EMBO Rep ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594391

RESUMO

Cancer patients undergoing treatment with antineoplastic drugs often experience chemotherapy-induced neuropathic pain (CINP), and the therapeutic options for managing CINP are limited. Here, we show that systemic paclitaxel administration upregulates the expression of neurotrophin-3 (Nt3) mRNA and NT3 protein in the neurons of dorsal root ganglia (DRG), but not in the spinal cord. Blocking NT3 upregulation attenuates paclitaxel-induced mechanical, heat, and cold nociceptive hypersensitivities and spontaneous pain without altering acute pain and locomotor activity in male and female mice. Conversely, mimicking this increase produces enhanced responses to mechanical, heat, and cold stimuli and spontaneous pain in naive male and female mice. Mechanistically, NT3 triggers tropomyosin receptor kinase C (TrkC) activation and participates in the paclitaxel-induced increases of C-C chemokine ligand 2 (Ccl2) mRNA and CCL2 protein in the DRG. Given that CCL2 is an endogenous initiator of CINP and that Nt3 mRNA co-expresses with TrkC and Ccl2 mRNAs in DRG neurons, NT3 likely contributes to CINP through TrkC-mediated activation of the Ccl2 gene in DRG neurons. NT3 may be thus a potential target for CINP treatment.

16.
Int Immunopharmacol ; 132: 112024, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608475

RESUMO

Ulcerative colitis (UC) is a recurrent intestinal disease with an increasing incidence worldwide that seriously affects the life of patients. Turtle peptide (TP) is a bioactive peptide extracted from turtles that has anti-inflammatory, antioxidant and anti-aging properties. However, studies investigating the effect of TP on the progression of UC are lacking. The aim of this study was to investigate effects and underlying mechanisms of TP and its derivative peptide GPAGPIGPV (GP-9) in alleviating UC in mice. The results showed that 500 mg/kg TP treatment significantly ameliorated colitis symptoms and oxidative stress in UC mice. TP alleviated intestinal barrier damage in UC mice by promoting mucosal repair and increasing the expression of tight junction proteins (ZO1, occludin and claudin-1). TP also modulated the composition of the gut microbiota by increasing the abundance of the beneficial bacteria Anaerotignum, Prevotellaceae_UCG-001, Alistipes, and Lachno-spiraceae_NK4A136_group and decreasing the abundance of the harmful bacteria Prevotella_9 and Parasutterella. Furthermore, we characterized the peptide composition of TP and found that GP-9 ameliorated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by inhibiting the TLR4/NF-κB signaling pathway. In conclusion, TP and its derivative peptides ameliorated DSS-induced ulcerative colitis by inhibiting the expression of inflammatory factors and modulating the composition of the intestinal microbiota; this study provides a theoretical basis for the application of TP and its derivative peptides for their anti-inflammatory activity.

17.
Nanomaterials (Basel) ; 14(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38607121

RESUMO

The magnetization mechanism of Co-doped BaTiO3 ultrathin films is a subject of debate, which results in difficulties with the design of new multiferroics based on BaTiO3 matrixes. With the aid of a first-principles approach, it was observed that when the interstitial site and Ti vacancy were filled with Co, the configuration behaved in a nonmagnetic manner, indicating the significance of the Co content. Moreover, in the case of Co substituting two neighboring Ti atoms, when a direct current field was applied in the [100] direction, the magnetic domains excluding those in the [100], [010], and [001] directions were directed away. Further, the magnetoelectric constant was evaluated at ~449.3 mV/cmOe, showing strong magnetoelectric coupling at room temperature. Clearly, our study indicates that strict control of Ba, Ti, O, and Co stoichiometry can induce an electric and magnetic field conversion in two-dimensional BaTiO3 and may provide a new candidate for single-phase multiferroics for application in next-generation multifunctional devices.

18.
Int J Biol Macromol ; : 131620, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631578

RESUMO

Transparent wood (TW) has attracted much attention in the field of energy saving building structural materials because of its high light transmittance, good thermal insulation performance and good toughness. However, the polymeric resins used in the present study to impregnate lignin-based wood templates are usually derived from petroleum-based chemical resources, which pose a fatal threat to human beings both in terms of consuming large amounts of resources and causing environmental pollution problems. It is therefore important to develop alternatives to petroleum-derived chemicals in renewable natural resources. Here, we report a green and sustainable TW production process based on the bio-recycling concept. Lignin-based sustainable resin (LSR) was prepared from waste lignin produced during delignification by polymerization of guaiacol. At the same time, according to FT-IR and NMR data analysis combined with previous studies, the synthesis mechanism of LSR was proposed, and this result provided a reference for bio-based resins made from biomass materials. The prepared lignin-based sustainable transparent wood (LSTW) has good light transmittance and good dimensional stability. In addition, the LSTW also shows good thermal insulation and indoor temperature regulation capabilities compared with the common glass.

20.
Nat Commun ; 15(1): 3186, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622114

RESUMO

Transcription termination factor ρ is a hexameric, RNA-dependent NTPase that can adopt active closed-ring and inactive open-ring conformations. The Sm-like protein Rof, a homolog of the RNA chaperone Hfq, inhibits ρ-dependent termination in vivo but recapitulation of this activity in vitro has proven difficult and the precise mode of Rof action is presently unknown. Here, our cryo-EM structures of ρ-Rof and ρ-RNA complexes show that Rof undergoes pronounced conformational changes to bind ρ at the protomer interfaces, undercutting ρ conformational dynamics associated with ring closure and occluding extended primary RNA-binding sites that are also part of interfaces between ρ and RNA polymerase. Consistently, Rof impedes ρ ring closure, ρ-RNA interactions and ρ association with transcription elongation complexes. Structure-guided mutagenesis coupled with functional assays confirms that the observed ρ-Rof interface is required for Rof-mediated inhibition of cell growth and ρ-termination in vitro. Bioinformatic analyses reveal that Rof is restricted to Pseudomonadota and that the ρ-Rof interface is conserved. Genomic contexts of rof differ between Enterobacteriaceae and Vibrionaceae, suggesting distinct modes of Rof regulation. We hypothesize that Rof and other cellular anti-terminators silence ρ under diverse, but yet to be identified, stress conditions when unrestrained transcription termination by ρ may be detrimental.


Assuntos
Fator Rho , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator Rho/química , Transcrição Gênica , RNA/genética , Sítios de Ligação , Regulação Bacteriana da Expressão Gênica , RNA Bacteriano/genética
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