Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.296
Filtrar
1.
Sci Rep ; 14(1): 10554, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719903

RESUMO

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 µmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.


Assuntos
Ferro , Sarcopenia , Transferrina , Humanos , Sarcopenia/sangue , Masculino , Feminino , Ferro/sangue , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Transferrina/metabolismo , Transferrina/análise , Índice de Massa Corporal , Força da Mão , Fatores de Risco , Músculo Esquelético/metabolismo , Modelos Logísticos , Idoso de 80 Anos ou mais
2.
PLoS One ; 19(5): e0296654, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728313

RESUMO

In the era of the rapid development of e-commerce, many retailers choose to launch promotional activities to become consumers' first choice for shopping. Since price discounts can greatly attract consumers, the e-commerce platforms have also begun to implement discount pricing. It is urgent for e-commerce platforms and retailers to formulate reasonable discount strategies to achieve sustainable business. In this paper, we construct a dynamic game model for implementing discount pricing on an e-commerce platform and two retailers, we study the market equilibrium between the two retailers and the e-commerce platform under various scenarios that considering consumers' strategic waiting behavior and competition between the two retailers, we further discuss the effectiveness of retailer discount pricing and the double discount pricing of the platform and retailers. We show that the optimal pricing decreases as the difference in product quality narrows under both pricing strategies. Low-quality retailers implementing a double discount pricing strategy are in relatively higher demand only when the difference in product quality is small. High-quality retailers implementing the retailer discount pricing strategy are in relatively higher demand only when the product quality difference is large. Double discount pricing is desirable for both e-commerce platforms and retailers and can be used to effectively achieve Pareto improvement in the market by increasing their expected profit. Our results emphasize the role of product quality and the value of the double discount pricing strategy. The double discount pricing strategy weakens the profit advantage that retailers and platforms gain from it as the rebate intensity and rebate redemption rates increase.


Assuntos
Comércio , Comportamento do Consumidor , Comércio/economia , Comportamento do Consumidor/economia , Humanos , Custos e Análise de Custo , Modelos Econômicos
3.
Front Immunol ; 15: 1383607, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715600

RESUMO

Background: The crucial role of inflammation in aortic aneurysm (AA) is gaining prominence, while there is still a lack of key cytokines or targets for effective clinical translation. Methods: Mendelian randomization (MR) analysis was performed to identify the causal relationship between 91 circulating inflammatory proteins and AA and between 731 immune traits and AA. Bulk RNA sequencing data was utilized to demonstrate the expression profile of the paired ligand-receptor. Gene enrichment analysis, Immune infiltration, and correlation analysis were employed to deduce the potential role of CX3CR1. We used single-cell RNA sequencing data to pinpoint the localization of CX3CL1 and CX3CR1, which was further validated by multiplex immunofluorescence staining. Cellchat analysis was utilized to infer the CX3C signaling pathway. Trajectory analysis and the Cytosig database were exploited to determine the downstream effect of CX3CL1-CX3CR1. Results: We identified 4 candidates (FGF5, CX3CL1, IL20RA, and SCF) in multiple two-sample MR analyses. Subsequent analysis of the expression profile of the paired receptor revealed the significant upregulation of CX3CR1 in AA and its positive correlation with pro-inflammatory macrophages. Two sample MR between immune cell traits and AA demonstrated the potential causality between intermediate monocytes and AA. We finally deciphered in single-cell sequencing data that CX3CL1 sent by endothelial cells (ECs) acted on CX3CR1 of intermediated monocytes, leading to its recruitment and pro-inflammatory responses. Conclusion: Our study presented a genetic insight into the pathogenetic role of CX3CL1-CX3CR1 in AA, and further deciphered the CX3C signaling pathway between ECs and intermediate monocytes.


Assuntos
Aneurisma Aórtico , Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , Análise da Randomização Mendeliana , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Humanos , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Aneurisma Aórtico/genética , Aneurisma Aórtico/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Transdução de Sinais , Predisposição Genética para Doença
4.
Ann Bot ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38720433

RESUMO

BACKGROUND AND AIMS: There are intrinsic conflicts between signalling to mutualists and concealing (camouflaging) from antagonists. Like animals, plants also use camouflage as a defence against herbivores. However, this can potentially reduce their attractiveness to pollinators. METHODS: Using Fritillaria delavayi, an alpine camouflaged plant with inter-population floral colour divergence, we tested the influence of floral trait differences on reproduction. We conducted pollination experiments, measured floral morphological characteristics, estimated floral colours perceived by pollinators, analysed floral scent, and investigated the reproductive successes in five populations. KEY RESULTS: We found that the reproduction of F. delavayi depends on pollinators. Under natural conditions, a flower-camouflaged population had a 100% fruit set and similar seed set to three out of four yellow-flowered populations. Bumblebees are important pollinators in the visually conspicuous yellow-flowered populations, whereas flies are the only pollinator in the flower-camouflaged population, visiting flowers more frequently than bumblebees. The camouflaged flowers cannot be discriminated from the rock background as perceived by pollinators, but may be located by flies through olfactory cues. CONCLUSIONS: Collectively, our results demonstrate that the flower-camouflaged population has different reproductive traits from the visually conspicuous yellow-flowered ones. A pollinator shift from bumblebees to flies, combined with high visitation frequency, compensates the attractiveness disadvantage in camouflaged plants.

5.
Ecotoxicol Environ Saf ; 278: 116403, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38710145

RESUMO

RATIONALE: Diesel engine exhaust (DEE) is associated with the development and exacerbation of asthma. Studies have shown that DEE can aggravate allergen-induced eosinophilic inflammation in lung. However, it remains not clear that whether DEE alone could initiate non-allergic eosinophilic inflammation and airway hyperresponsiveness (AHR) through innate lymphoid cells (ILCs) pathway. OBJECTIVE: This study aims to investigate the airway inflammation and hyperresponsiveness and its relationship with ILC after DEE exposure. METHOD: Non-sensitized BALB/c mice were exposed in the chamber of diesel exhaust or filtered air for 2, 4, and 6 weeks (4 h/day, 6 days/week). Anti-CD4 mAb or anti-Thy1.2 mAb was administered by intraperitoneal injection to inhibit CD4+T or ILCs respectively. AHR、airway inflammation and ILCs were assessed. RESULT: DEE exposure induced significantly elevated level of neutrophils, eosinophils, collagen content at 4, 6 weeks. Importantly, the airway AHR was only significant in the 4weeks-DEE exposure group. No difference of the functional proportions of Th2 cells was found between exposure group and control group. The proportions of IL-5+ILC2, IL-17+ILC significantly increased in 2, 4weeks-DEE exposure group. After depletion of CD4+T cells, both the proportion of IL-5+ILC2 and IL-17A ILCs was higher in the 4weeks-DEE exposure group which induced AHR, neutrophilic and eosinophilic inflammation accompanied by the IL-5, IL-17A levels. CONCLUSION: Diesel engine exhaust alone can imitate asthmatic characteristics in mice model. Lung-resident ILCs are one of the major effectors cells responsible for a mixed Th2/Th17 response and AHR.

6.
Med Phys ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38721942

RESUMO

Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG-267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments.

7.
Nanomicro Lett ; 16(1): 188, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698113

RESUMO

As a new form of regulated cell death, ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells. The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells. Due to their high loading and structural tunability, nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting. This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis. Additionally, we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

8.
Clin. transl. oncol. (Print) ; 26(4): 951-965, Abr. 2024. graf
Artigo em Inglês | IBECS | ID: ibc-VR-58

RESUMO

Background: Patients with pancreatic cancer have a dismal prognosis due to tumor cell infiltration and metastasis. Many reports have documented that EMT and PI3K–AKT–mTOR axis control pancreatic cancer cell infiltration and metastasis. Chloroxine is an artificially synthesized antibacterial compound that demonstrated anti-pancreatic cancer effects in our previous drug-screening trial. We have explored the impact of chloroxine on pancreatic cancer growth, infiltration, migration, and apoptosis. Methods: The proliferation of pancreatic cancer cell lines (PCCs) treated with chloroxine was assessed through real-time cell analysis (RTCA), colony formation assay, CCK-8 assay, as well as immunofluorescence. Chloroxine effects on the infiltrative and migratory capacities of PCCs were assessed via Transwell invasion and scratch experiments. To assess the contents of EMT- and apoptosis-associated proteins in tumor cells, we adopted Western immunoblotting as well as immunofluorescence assays, and flow cytometry to determine chloroxine effects on PCCs apoptosis. The in vivo chloroxine antineoplastic effects were explored in nude mice xenografts. Results: Chloroxine repressed pancreatic cancer cell growth, migration, and infiltration in vitro, as well as in vivo, and stimulated apoptosis of the PCCs. Chloroxine appeared to inhibit PCC growth by Ki67 downregulation; this targeted and inhibited aberrant stimulation of the PI3K–AKT–mTOR signaling cascade, triggered apoptosis in PCC via mitochondria-dependent apoptosis, and modulated the EMT to inhibit PCC infiltration and migration. Conclusions: Chloroxine targeted and inhibited the PI3K–AKT–mTOR cascade to repress PCCs growth, migration, as well as invasion, and triggered cellular apoptosis. Therefore, chloroxine may constitute a potential antineoplastic drug for the treatment of pancreatic cancer.(AU)


Assuntos
Humanos , Masculino , Feminino , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático , Antineoplásicos , Cloroquinolinóis/farmacocinética , Cloroquinolinóis/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo
9.
Infect Agent Cancer ; 19(1): 15, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654358

RESUMO

BACKGROUND: Epidemiological research and systematic meta-analyses indicate a higher risk of B-cell lymphomas in patients with chronic hepatitis C virus (HCV) compared to non-infected individuals. However, the genetic links between HCV and these lymphomas remain under-researched. METHODS: Mendelian randomization analysis was employed to explore the association between chronic hepatitis C (CHC) and B-cell lymphomas as well as chronic lymphocytic leukemia (CLL). Approximate Bayes Factor (ABF) localization analysis was conducted to find shared genetic variants that might connect CHC with B-cell lymphomas and chronic lymphocytic leukemia (CLL). Furthermore, The Variant Effect Predictor (VEP) was utilized to annotate the functional effects of the identified genetic variants. RESULTS: Mendelian randomization revealed a significant association between CHC and increased diffuse large B cell lymphoma (DLBCL) risk (OR: 1.34; 95% CI: 1.01-1.78; P = 0.0397). Subsequent colocalization analysis pinpointed two noteworthy variants, rs17208853 (chr6:32408583) and rs482759 (chr6:32227240) between these two traits. The annotation of these variants through the VEP revealed their respective associations with the butyrophilin-like protein 2 (BTNL2) and notch receptor 4 (NOTCH4) genes, along with the long non-coding RNA (lncRNA) TSBP1-AS1. CONCLUSION: This research provides a refined genetic understanding of the CHC-DLBCL connection, opening avenues for targeted therapeutic research and intervention.

10.
RSC Adv ; 14(18): 12624-12632, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38638821

RESUMO

A lot of solid waste coal gangue is produced every year in the process of coal mining and coal washing, which poses a great threat to human health. How to deal with coal gangue properly is still a serious problem. In this study the macro-micro composite porous mullite ceramic skeletons were successfully prepared using solid waste coal gangue and α-Al2O3 as main raw materials via twice pore-forming technology. The main phase composition of the porous ceramic skeletons was mullite tested by X-ray Diffractometer (XRD). The morphology and microstructure of the porous ceramic skeletons were analyzed by Scanning Electron Microscope (SEM). The results show that the microstructure of porous ceramic skeletons was mainly composed of mullite whiskers. With the increase of sintering temperature from 1200 °C to 1350 °C, the maximum length of mullite whiskers grew up from 2.68 µm to 8.10 µm and their average length grew up from 0.78 µm to 2.98 µm. The maximum compressive strength of the porous ceramic skeletons with 30 PPI and 45 PPI were 1.25 MPa and 1.54 MPa tested by Universal Testing Machine (UTM) at the sintering temperature of 1250 °C, respectively. The linear shrinkage, bulk density and pore stem density of the porous ceramic skeletons became larger with the rising of sintering temperatures from 1150 °C to 1350 °C. However, the corresponding performance values of 45 PPI porous ceramic skeletons were greater than that of 30 PPI at the same sintering temperature. The prepared porous ceramic skeletons will be used in ceramic-metal wear-resistant composites for the later research and the study provides a new idea for coal gangue on the comprehensive utilization with high added value and brings both good environmental and economic benefits.

11.
J Inflamm Res ; 17: 2245-2256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38623469

RESUMO

Background: Dorsal root ganglia (DRGs) contain sensory neurons that innervate intervertebral discs (IVDs) and may play a critical role in mediating low-back pain (LBP), but the potential pathophysiological mechanism needs to be clarified. Methods: A discogenic LBP model in rats was established by penetration of a lumbar IVD. The severity of LBP was evaluated through behavioral analysis, and the gene and protein expression levels of pro-algesic peptide substance P (SP) and calcitonin gene-related peptide (CGRP) in DRGs were quantified. The level of reactive oxygen species (ROS) in bilateral lumbar DRGs was also quantified using dihydroethidium staining. Subsequently, hydrogen peroxide solution or N-acetyl-L-cysteine was injected into DRGs to evaluate the change in LBP, and gene and protein expression levels of transient receptor potential vanilloid-1 (TRPV1) in DRGs were analyzed. Finally, an inhibitor or activator of TRPV1 was injected into DRGs to observe the change in LBP. Results: The rats had remarkable LBP after disc puncture, manifesting as mechanical and cold allodynia and increased expression of the pro-algesic peptides SP and CGRP in DRGs. Furthermore, there was significant overexpression of ROS in bilateral lumbar DRGs, while manipulation of the level of ROS in DRGs attenuated or aggravated LBP in rats. In addition, excessive ROS in DRGs stimulated upregulation of TRPV1 in DRGs. Finally, activation or inhibition of TRPV1 in DRGs resulted in a significant increase or decrease of discogenic LBP, respectively, suggesting that ROS-induced TRPV1 has a strong correlation with discogenic LBP. Conclusion: Increased ROS in DRGs play a primary pathological role in puncture-induced discogenic LBP, and excessive ROS-induced upregulation of TRPV1 in DRGs may be the underlying pathophysiological mechanism to cause nerve sensitization and discogenic LBP. Therapeutic targeting of ROS or TRPV1 in DRGs may provide a promising method for the treatment of discogenic LBP.

12.
Sci Rep ; 14(1): 8433, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600113

RESUMO

The objective of this research is to enhance the precision and efficiency of design concept assessments during the initial stages of new product creation. Design concept evaluation, which occurs at the end of the conceptual design phase, is a critical step in product development. The outcome of this evaluation significantly impacts the product's eventual success, as flawed design concepts are difficult to remedy in later stages. However, the evaluation of new product concepts is a procedure that encompasses elements of subjectivity and ambiguity. In order to deal with the problem, a novel decision-making method for choosing more logical new product concepts is introduced. Basically, the evaluation process is outlined in three main phases: the construction of evaluation index system for design concept alternatives, the calculation of weights for evaluation criteria and decision-makers, the selection of the best design concept alternatives. These stages are composed of a hybrid method based on kano model, multiplicative analytic hierarchy process (AHP) method, the entropy of IVPFS and improved grey relational projection (GRP) under interval-valued picture fuzzy set (IVPFS). The novel approach integrates the strength of interval-valued picture fuzzy number in handling vagueness, the advantage of multiplicative AHP and the merit of improved GRP method in modelling multi-criteria decision-making. In final, the effectiveness of the proposed model is validated through comparisons with other models. The potential applications of this study include but are not limited to product development, industrial design, and innovation management, providing decision-makers with a more accurate and comprehensive design concept evaluation tool.

13.
Lancet ; 403(10434): e21-e31, 2024 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582569

RESUMO

BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.


Assuntos
Obesidade , Sobrepeso , Adulto , Humanos , Sobrepeso/tratamento farmacológico , Metanálise em Rede , Topiramato/uso terapêutico , Obesidade/tratamento farmacológico , Redução de Peso , Fentermina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Huan Jing Ke Xue ; 45(5): 2640-2650, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629528

RESUMO

DOM is the largest reservoir of organic carbon in the world, and it plays a crucial role in the biogeochemical cycles of natural water bodies. A river is a transition area connecting source water and receiving water that controls the DOM exchange between them. Therefore, in this study, ultraviolet visible spectroscopy (UV-vis) and three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC) were used to analyze the spectral characteristics and sources of dissolved organic matter in the Fuhe River, Xiaobai River, Baigouyin River, and Puhe River of Baiyangdian. The results showed that a245 and a355 in the Fuhe River and Xiaobai River were significantly higher than those in the Baigouyin River and Puhe River. E2/E3 showed that the DOM relative molecular mass of the inflow river water body was Puhe River > Baigouyin River > Fuhe River > Xiaobai River. Three components, tyrosine-like (C1), terrigenous humus (C2), and tryptophan-like (C3), were determined using three-dimensional fluorescence through PARAFAC. There was no difference among the fluorescence components (P>0.05), but there were differences among the C2 and C3 components (P<0.05). The proportion of easily degradable protein-like components (C1+C3) was higher than that of humus-like components (C2). The autogeny index BIX was greater than 1, and the humification index HIX was less than 4, indicating that the autogeny characteristics of the river bodies were obvious, and the humification degree was weak. The FI index was the highest (1.96±0.25), and the HIX index was the lowest (0.46±0.08), and the self-generated source characteristics gradually strengthened along the direction of the river entering the lake, indicating that the water body of the Fuhe River showed higher endogenous and autogenic characteristics. Based on the correlation analysis of fluorescence components and characteristic parameters of DOM, the correlations between the Fuhe River and Xiaobaihe River and between the Baigouyin River and Puhe River bodies were similar. The correlation between fluorescence components of DOM and water quality parameters of each lake was significantly different, and it was strongly correlated with nitrogen and phosphorus in water. According to multiple linear regression analysis, there was no significant difference among C1 components, but there was a significant difference between C2 and C3 components. In summary, the carbon cycle process of Baiyangdian Lake was further understood through the study on the DOM spectral characteristics and sources of the inflow river waters in the summer flood season.

15.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557887

RESUMO

Ensuring the safe operation of trains hinges on precise bearing condition monitoring, given the pivotal role bearings play in railway wagons. The status and maintenance of wagon bearings are of paramount concern, necessitating a shift from traditional maintenance approaches reliant on schedules and experience, which often lack real-time precision and efficiency. To address this challenge, our research focuses on enhancing the sparrow search algorithm by incorporating logistic chaos mapping and the levy flight strategy. This enhanced algorithm optimizes variational mode decomposition parameters, utilizing intrinsic mode components' average dispersion entropy as the fitness function. This optimization is integrated with a multi-level convolutional neural network for bearing fault diagnosis. Our findings demonstrate the improved algorithm's enhanced spatial search capabilities and reduced modal aliasing in the frequency components. Experimental validation on public datasets and the group's experimental platform for railway wagons shows that multi-level convolutional neural networks have higher diagnostic accuracy and faster convergence speeds than traditional models such as LeNet-5, AlexNet, and convolutional neural network. Our research introduces a highly accurate and widely applicable methodology for mechanical equipment fault diagnosis, aligning with the requirements of the "smart" era.

16.
bioRxiv ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38559023

RESUMO

During endosomal recycling, Sorting Nexin 17 (SNX17) facilitates the transport of numerous membrane cargo proteins by tethering them to the Retriever complex. Despite its importance, the mechanisms underlying this interaction have remained elusive. Here, we report the structure of the Retriever-SNX17 complex determined using cryogenic electron microscopy (cryo-EM). Our structure reveals that the C-terminal tail of SNX17 engages with a highly conserved interface between the VPS35L and VPS26C subunits of Retriever. Through comprehensive biochemical, cellular, and proteomic analyses, we demonstrate that disrupting this interface impairs the Retriever-SNX17 interaction, subsequently affecting the recycling of SNX17-dependent cargos and altering the composition of the plasma membrane proteome. Intriguingly, we find that the SNX17-binding pocket on Retriever can be utilized by other ligands that share a consensus acidic C-terminal tail motif. By showing how SNX17 is linked to Retriever, our findings uncover a fundamental mechanism underlying endosomal trafficking of critical cargo proteins and reveal a mechanism by which Retriever can engage with other regulatory factors.

17.
Biomolecules ; 14(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38672526

RESUMO

The Biomolecules Editorial Office retracts the article, "Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function" [...].

18.
World Neurosurg ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679379

RESUMO

OBJECTIVE: Biportal endoscopic spinal surgery (BESS) technique is a novel, useful and minimally invasive therapeutic strategy for lumbar degenerative diseases, which has advantages over other surgical techniques. However, the degree of technical difficulty in learning BESS is controversial and not well established. This study aims to determine the learning curve of BESS technique through cumulative sum (CUSUM) analysis. METHODS: A total of 144 consecutive patients who underwent BESS with lumbar decompressive discectomy between 2017 and 2023 were included. A retrospective bi-center study was performed. RESULTS: Three doctors with endoscopy experience employed the BESS technique for 51, 42 and 46 procedures, respectively. The CUSUM test of the three doctors showed adequate technical ability at the 45th, 41st and 44th operations respectively. Two doctors without endoscopy experience gave up further use of BESS technique due to technical difficulties after initial attempt. The overall complication rates of the three surgeons using the BESS technique were 3.92% (n = 2), 6.82% (n = 3), and 2.17% (n = 1), respectively. CONCLUSIONS: Our study demonstrated that BESS is an effective treatment, and the learning curves of BESS for lumbar discectomy using CUSUM analysis were 41 ∼ 45 cases in trainees with endoscopic experience. Endoscopic experience contributes to the learning curve of the BESS technique.

19.
Heliyon ; 10(7): e28952, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596098

RESUMO

Amino acid variants in protein may result in deleterious effects on enzymatic activity. In this study we investigate the DNA variants on activity of CYP2B6 gene in a Chinese Han population for potential use in precision medicine. All exons in CYP2B6 gene from 1483 Chinese Han adults (Zhejiang province) were sequenced using Sanger sequencing. The effects of nonsynonymous variants on recombinant protein catalytic activity were investigated in vitro with Sf12 system. The haplotype of novel nonsynonymous variants with other single nucleotide variants in the same allele was determined using Nanopore sequencing. Of 38 alleles listed on the Pharmacogene Variation Consortium, we detected 7 previously reported alleles and 18 novel variants, of which 11 nonsynonymous variants showed lower catalytic activity (0.00-0.60) on bupropion compared to CYP2B6*1. Further, these 11 novel star-alleles (CYP2B6*39-49) were assigned by the Pharmacogene Variation Consortium, which may be valuable for pharmacogenetic research and personalized medicine.

20.
Cancer Discov ; : OF1-OF24, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593348

RESUMO

RAS-driven cancers comprise up to 30% of human cancers. RMC-6236 is a RAS(ON) multi-selective noncovalent inhibitor of the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms with broad therapeutic potential for the aforementioned unmet medical need. RMC-6236 exhibited potent anticancer activity across RAS-addicted cell lines, particularly those harboring mutations at codon 12 of KRAS. Notably, oral administration of RMC-6236 was tolerated in vivo and drove profound tumor regressions across multiple tumor types in a mouse clinical trial with KRASG12X xenograft models. Translational PK/efficacy and PK/PD modeling predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses, respectively, in patients with RAS-driven tumors. Consistent with this, we describe here objective responses in two patients (at 300 mg daily) with advanced KRASG12X lung and pancreatic adenocarcinoma, respectively, demonstrating the initial activity of RMC-6236 in an ongoing phase I/Ib clinical trial (NCT05379985). SIGNIFICANCE: The discovery of RMC-6236 enables the first-ever therapeutic evaluation of targeted and concurrent inhibition of canonical mutant and wild-type RAS-GTP in RAS-driven cancers. We demonstrate that broad-spectrum RAS-GTP inhibition is tolerable at exposures that induce profound tumor regressions in preclinical models of, and in patients with, such tumors.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...