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1.
Environ Pollut ; 352: 124082, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38697246

RESUMO

Antimony (Sb) contamination in certain areas caused by activities such as antimony mining and smelting poses significant risks to human health and ecosystems. In this study, a stable composite material consisting of natural zeolite-supported nanoscale zero-valent iron (Z-ZVI) was successfully prepared. The immobilization effect of Z-ZVI on Sb in contaminated soil was investigated. Experimental results showed that Z-ZVI exhibited superior performance compared to pure nano zero-valent iron (nZVI) in terms of stability, with a lower zeta potential (-25.16 mV) at a pH of 7 and a higher specific surface area (54.54 m2/g). It can be easily applied and dispersed in contaminated soils. Additionally, Z-ZVI demonstrated a more abundant porous structure. After 60 days of treatment with 3% Z-ZVI, the leaching concentration of Sb in the contaminated soil decreased from 1.32 mg/L to 0.31 mg/L (a reduction of 76%), and the concentration of available Sb species decreased from 19.84 mg/kg to 0.71 mg/kg, achieving a fixation efficiency of up to 90%. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis confirmed the effective immobilization of Sb in the soil through reduction of antimonate to antimonite, precipitation, and adsorption processes facilitated by Z-ZVI. Moreover, the addition of Z-ZVI effectively reduced the bioavailability of Sb in the contaminated soil, thereby mitigating its toxicity to earthworms. In conclusion, Z-ZVI can be utilized as a promising material for the safe remediation and antimony and other heavy metal-contaminated soils.


Assuntos
Antimônio , Ferro , Poluentes do Solo , Solo , Zeolitas , Antimônio/química , Poluentes do Solo/química , Zeolitas/química , Ferro/química , Solo/química , Recuperação e Remediação Ambiental/métodos , Adsorção , Animais
2.
Biosens Bioelectron ; 255: 116255, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38565025

RESUMO

Single nucleotide polymorphisms (SNPs) are closely associated with many biological processes, including genetic disease, tumorigenesis, and drug metabolism. Accurate and efficient SNP determination has been proved pivotal in pharmacogenomics and diagnostics. Herein, a universal and high-fidelity genotyping platform is established based on the dual toeholds regulated Cas12a sensing methodology. Different from the conventional single stranded or double stranded activation mode, the dual toeholds regulated mode overcomes protospacer adjacent motif (PAM) limitation via cascade toehold mediated strand displacement reaction, which is highly universal and ultra-specific. To enhance the sensitivity for biological samples analysis, a modified isothermal recombinant polymerase amplification (RPA) strategy is developed via utilizing deoxythymidine substituted primer and uracil-DNA glycosylase (UDG) treatment, designated as RPA-UDG. The dsDNA products containing single stranded toehold domain generated in the RPA-UDG allow further incorporation with dual toeholds regulated Cas12a platform for high-fidelity human sample genotyping. We discriminate all the single-nucleotide polymorphisms of ApoE gene at rs429358 and rs7412 loci with human buccal swab samples with 100% accuracy. Furthermore, we engineer visual readout of genotyping results by exploiting commercial lateral flow strips, which opens new possibilities for field deployable implementation.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , Humanos , Sistemas CRISPR-Cas/genética , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Apolipoproteínas E , Uracila-DNA Glicosidase
3.
Phys Chem Chem Phys ; 26(5): 4716-4723, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38251958

RESUMO

Skyrmioniums, known for their unique transport and regulatory properties, are emerging as potential cornerstones for future data storage systems. However, the stability of skyrmionium movement faces considerable challenges due to the skyrmion Hall effect, which is induced by deformation. In response, our research introduces an innovative solution: we utilized micro-magnetic simulations to create a sandwiched trilayer nanowire structure augmented with a stray magnetic field. This combination effectively guides the skyrmionium within the ferromagnetic (FM) layer. Our empirical investigations reveal that the use of a stray magnetic field not only reduces the size of the skyrmionium but also amplifies its stability. This dual-effect proficiently mitigates the deformation of skyrmionium movement and boosts their thermal stability. We find these positive outcomes are most pronounced at a particular intensity of the stray magnetic field. Importantly, the required stray magnetic field can be generated using a heavy metal (HM1) layer of suitable thickness, rendering the practical application of this approach plausible in real-world experiments. Additionally, we analyze the functioning mechanism based on the Landau-Lifshitz-Gilbert (LLG) equation and energy variation. We also develop a deep spiking neural network (DSNN), which achieves a remarkable recognition accuracy of 97%. This achievement is realized through supervised learning via the spike timing dependent plasticity rule (STDP), considering the nanostructure as an artificial synapse device that corresponds to the electrical properties of the nanostructure. In conclusion, our study provides invaluable insights for the design of innovative information storage devices utilizing skyrmionium technology. By tackling the issues presented by the skyrmion Hall effect, we outline a feasible route for the practical application of this advanced technology. Our research, therefore, serves as a robust platform for continued investigations in this field.

4.
Analyst ; 149(3): 707-711, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38230655

RESUMO

A PfAgo-G4 sensing platform exploiting G4 as a signal reporter was proposed, validated, and optimized. By introducing two mismatches at the Link strand, a universal nucleotide design rule was established for accurate single nucleotide polymorphism discrimination with PfAgo-G4. The FUT2 gene was then successfully and accurately genotyped using human buccal swab samples.


Assuntos
Aptâmeros de Nucleotídeos , Quadruplex G , Humanos , Genótipo , Polimorfismo de Nucleotídeo Único , Aptâmeros de Nucleotídeos/genética
5.
Phytomedicine ; 123: 155249, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056144

RESUMO

BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood. PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota. MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays. RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice. CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.


Assuntos
Dor Crônica , Prostatite , Humanos , Masculino , Camundongos , Animais , Prostatite/tratamento farmacológico , RNA Ribossômico 16S , Inflamação/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Dor Pélvica/metabolismo , Intestinos , Akkermansia , Xantofilas
6.
J Alzheimers Dis ; 95(3): 869-885, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37661885

RESUMO

BACKGROUND: Blood-brain barrier (BBB) breakdown is a crucial aspect of Alzheimer's disease (AD) progression. Dysfunction in BBB is primarily caused by impaired tight junction and adherens junction proteins in brain microvascular endothelial cells (BMECs). The role of adherens junctions in AD-related BBB dysfunction remains unclear. Exosomes from senescent cells have unique characteristics and contribute to modulating the phenotype of recipient cells. However, it remains unknown if and how these exosomes cause BMEC dysfunction in AD. OBJECTIVE: This study aimed to investigate the impact of AD circulating exosomes on brain endothelial dysfunction. METHODS: Exosomes were isolated from sera of AD patients and age- and sex-matched cognitively normal controls using size-exclusion chromatography. The study measured the biomechanical nature of BMECs' endothelial barrier, the lateral binding forces between live BMECs. Paracellular expressions of the key adherens junction protein vascular endothelial (VE)-cadherin were visualized in BMEC cultures and a 3D BBB model using human BMECs and pericytes. VE-cadherin signals were also examined in brain tissues from AD patients and normal controls. RESULTS: Circulating exosomes from AD patients reduced VE-cadherin expression levels and impaired barrier function in recipient BMECs. Immunostaining analysis demonstrated that AD exosomes damaged VE-cadherin integrity in a 3D microvascular tubule formation model. The study found that AD exosomes weakened BBB integrity depending on their RNA content. Additionally, diminished microvascular VE-cadherin expression was observed in AD brains compared to controls. CONCLUSION: These findings highlight the significant role of circulating exosomes from AD patients in damaging adherens junctions of recipient BMECs, dependent on exosomal RNA.


Assuntos
Doença de Alzheimer , Exossomos , Humanos , Células Endoteliais , Encéfalo/irrigação sanguínea , Barreira Hematoencefálica , Caderinas , RNA
8.
Food Sci Nutr ; 11(8): 4812-4828, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576054

RESUMO

Both edible fungal polysaccharides (Auricularia and Tremellan) and Crataegus flavonoids promote the balance of dyslipidemia, which have a positive biological regulating effect on intestinal flora. In this study, the extraction of water-soluble polysaccharides from Auricularia and Tremellan was investigated and optimized firstly. Polysaccharides and flavonoids were then combined to study the effects on the mediating role of abnormal blood lipid concentration and intestinal flora in vivo. The rats were divided into 10 groups, the NC (normal control), HM (model), PCI (Simvastatin control), PCII (Fenofibrate control), AAP (Auricularia auricular Polysaccharide), TFP (Tremella fuciformis Polysaccharide), HF (Crataegus Flavonoid), LDC (Low-dose combination), MDC (Medium dose combination), and HDC (High-dose combination), used to explore the impact of polysaccharides and flavonoids complex on state of blood lipid, liver, and intestinal flora of dyslipidemia rats. The results showed that the combination of polysaccharides and flavonoids could significantly decrease the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and increase the level of high-density lipoprotein cholesterol (HDL-C). It also significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and improved liver morphology. What is more, the HDC favorably alters the intestinal microflora balance, promotes intestinal integrity and mobility, and inhibits the growth of harmful bacteria such as Escherichia coli/Shigella and Clostridium compared with HM group. In brief, the combination of polysaccharides and flavonoids had a synergistic effect on the remission of dyslipidemia, and promoted health by improving lipid metabolism, protecting liver tissue, and regulating the intestinal flora in hyperlipidemia rats.

9.
Materials (Basel) ; 16(16)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37629798

RESUMO

Because of the significant difference between the thermal expansion coefficients of ceramic blank and glaze, the glaze typically undergoes more pronounced shrinkage than the blank during ceramic cooling, which results in high stress concentrations and cracking. In this study, the mechanical mechanism of glaze cracking is studied, based on the statistical strength theory, damage mechanics, and continuum mechanics. Furthermore, the influence of the glaze layer thickness, heat transfer coefficient, expansion coefficient, and temperature difference on the creation and propagation of inner microcracks is systematically investigated, and the final discrete fracture network of ceramics is discussed at the specific crack saturation state. The results show that (1) a higher heat transfer coefficient will lead to a more uniform distribution of the surface temperature and a faster cooling process of the ceramics, reducing the number of microcracks when the ambient temperature is reached; (2) the thinner glaze layer is less prone to cracking when its thickness is smaller than that of the blank. However, when the thickness of the glaze layer is similar to that of the blank, the increased thickness of the glaze layer will increase the number of cracks on its surface; and (3) when the expansion coefficient of the glaze layer is smaller than that of the blank, cracks will not occur inside the glaze layer. However, as the coefficient of the thermal expansion of the glaze layer continuously rises, the number of cracks on its surface will first increase and then decrease.

10.
J Endourol ; 37(9): 1028-1036, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37485569

RESUMO

Objective: To compare the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) vs laparoscopic partial nephrectomy (LPN) in the treatment of central renal angiomyolipomas (AMLs). Methods: We retrospectively analyzed the clinical data of 103 patients who were treated with either RAPN or LPN for central AMLs between January 2017 and June 2022. Propensity scores were matched according to sex, age, laterality, body mass index, symptoms, diameter of tumor, location of tumor distribution, R.E.N.A.L score, preoperative hemoglobin, preoperative serum creatinine, preoperative estimated glomerular filtration rate, chronic disease, previous abdominal surgery, preoperative selective arterial embolization, American Society of Anesthesiologists scale, and duration of follow-up, and after matching, perioperative and prognostic data of the two groups were compared. Results: A total of 57 patients underwent RAPN, and 46 patients underwent LPN. Before matching, there were more complex AMLs in the RAPN group, and R.E.N.A.L scores differed between the two groups (10 vs 9, p < 0.001). After matching, the median warm ischemic time in the RAPN group was significantly shorter than that in the LPN group (21.5 minutes vs 28 minutes, p = 0.034), as well as the median time of postoperative mobilization (1 day vs 2 days, p < 0.001). The other indicators were not significantly different between the groups. Conclusions: For central AMLs, both RAPN and LPN were safe and feasible surgical treatments, but RAPN might be associated with shorter warm ischemia time and earlier postoperative mobilization.


Assuntos
Angiomiolipoma , Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Angiomiolipoma/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Nefrectomia , Resultado do Tratamento
11.
Int Ophthalmol ; 43(11): 4079-4086, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37523104

RESUMO

PURPOSE: To investigate the clinical efficacy of conbercept 1 + pro re nata (PRN) (i.e., reinjection as needed after one injection) and 3 + PRN (reinjection as needed after 3 months of injection) regimens in choroidal neovascularization secondary to pathological myopia (PM-CNV). METHODS: From 06/2019 to 06/2020, 65 patients (65 eyes) confirmed with PM-CNV were included in this retrospective study. Intravitreal injection of 0.5 mg conbercept was conducted either with the 1 + PRN or 3 + PRN strategy. Patients were followed up for 12 months. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), CNV lesion leakage area, the number of injections, and postoperative adverse reactions were observed. RESULTS: The mean age of the patients was 42.10 ± 4.69 years, and the average diopter was - 11.26 ± 2.97D. The BCVA at month 3 in the 3 + PRN (n = 30) group was lower than in the 1 + PRN (n = 35) group (P < 0.001). The CRT at month 3 in the 3 + PRN group was lower than in the 1 + PRN group (P < 0.001). After 12 months, there were no differences in the BCVA and CRT between the two groups (P > 0.05). The number of injections was less in 1 + PRN than in 3 + PRN (2.14 ± 1.06 vs. 3.37 ± 0.76, P < 0.001) at 12 months. No serious treatment-related ocular complications or serious systemic adverse events were found. CONCLUSION: The 1 + PRN and 3 + PRN strategies of intravitreal injection of conbercept are effective in treating PM-CNV. The 1 + PRN regimen required fewer injections, and it might be more suitable for the treatment of PM-CNV.


Assuntos
Neovascularização de Coroide , Miopia Degenerativa , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Miopia Degenerativa/complicações , Miopia Degenerativa/tratamento farmacológico , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Resultado do Tratamento , Retina/patologia , Injeções Intravítreas , Inibidores da Angiogênese , Proteínas Recombinantes de Fusão/efeitos adversos , Tomografia de Coerência Óptica
12.
Cardiovasc Pathol ; 66: 107558, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37419163

RESUMO

The ongoing epidemic caused by the coronavirus SARS-CoV-2 is characterized by a variety of pathologic processes within the syndrome of COVID-19. Usually beginning as an upper respiratory infection with potential progression to a pneumonitis, many cases of COVID-19 that show minimal signs or symptoms initially may develop adverse systemic sequelae later, such as widespread thrombo-embolic phenomena, systemic inflammatory disorders (especially in children), or vasculitis. Here, we present a patient who suffered a sudden cardiac death following persistent SARS-CoV-2 viral positivity for four-and-one-half months after a mild clinical viral course. At routine autopsy, a remarkable plasma cell-rich necrotizing aortitis was uncovered. The aortic intima displayed diffuse, circumferential ongoing chronic intimal edema, inflammation, and neo-vascularization. The plasma cell-rich inflammatory process also involved the origin of the left main coronary artery (LM) causing a coronary arteritis accompanied by subacute, stenosing intimal vascular smooth muscle cell (VSMC) proliferation resulting in acute myocardial necrosis as a cause of death. A similar vasculitis and plaque were noted during the routine autopsy at the ostium of the celiac artery; vasculitis was not found systemically or in smaller caliber vessels. Through a variety of techniques including extensive histopathologic and immunohistochemical characterization, immunostaining localization of viral antigen, and transmission electron microscopy we present highly suggestive evidence that this unique necrotizing, plasma cell-rich aortitis is a rare sequela of COVID-19.


Assuntos
Aortite , COVID-19 , Criança , Humanos , Aortite/patologia , COVID-19/complicações , Plasmócitos/patologia , SARS-CoV-2 , Morte Súbita Cardíaca/etiologia , Progressão da Doença
13.
J Cell Physiol ; 238(8): 1937-1948, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37334929

RESUMO

We previously reported that microRNA (miR)23a and miR30b are selectively sorted into exosomes derived from rickettsia-infected endothelial cells (R-ECExos). Yet, the mechanism remains unknown. Cases of spotted fever rickettsioses have been increasing, and infections with these bacteria cause life-threatening diseases by targeting brain and lung tissues. Therefore, the goal of the present study is to further dissect the molecular mechanism underlying R-ECExos-induced barrier dysfunction of normal recipient microvascular endothelial cells (MECs), depending on their exosomal RNA cargos. Infected ticks transmit the rickettsiae to human hosts following a bite and injections of the bacteria into the skin. In the present study, we demonstrate that treatment with R-ECExos, which were derived from spotted fever group R parkeri infected human dermal MECs, induced disruptions of the paracellular adherens junctional protein VE-cadherin, and breached the paracellular barrier function in recipient pulmonary MECs (PMECs) in an exosomal RNA-dependent manner. We did not detect different levels of miRs in parent dermal MECs following rickettsial infections. However, we demonstrated that the microvasculopathy-relevant miR23a-27a-24 cluster and miR30b are selectively enriched in R-ECExos. Bioinformatic analysis revealed that common sequence motifs are shared exclusively among the exosomal, selectively-enriched miR23a cluster and miR30b at different levels. Taken together, these data warrant further functional identification and characterization of a monopartition, bipartition, or tripartition among ACA, UCA, and CAG motifs that guide recognition of microvasculopathy-relevant miR23a-27a-24 and miR30b, and subsequently results in their selective enrichments in R-ECExos.


Assuntos
MicroRNAs , Infecções por Rickettsia , Rickettsia , Rickettsiose do Grupo da Febre Maculosa , Humanos , Células Endoteliais , MicroRNAs/genética , Infecções por Rickettsia/genética , Infecções por Rickettsia/microbiologia , Rickettsia/genética
14.
Soft comput ; : 1-10, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37362289

RESUMO

The COVID-19 pandemic has had significant impacts on the health of individuals and communities around the world. While the immediate health impacts of the virus itself are well-known, there are also a number of post-pandemic health issues that have emerged as a result of the pandemic. The pandemic has caused increased levels of anxiety, depression, and other mental health issues among people of all ages. The isolation, uncertainty, and grief caused by the pandemic have taken a toll on people's mental well-being, and there is a growing concern that the long-term effects of the pandemic on mental health could be severe. Many people have delayed or avoided medical care during the pandemic, which could lead to long-term health problems. Additionally, people who have contracted COVID-19 may experience ongoing symptoms, such as fatigue, shortness of breath, and muscle weakness, which could impact their long-term health. Machine learning (ML) can be a powerful tool to analyze the health impact of the post-pandemic period. With the vast amounts of data available from electronic health records, public health databases, and other sources, this article is making use of ML methods which can help identify patterns and insights to conclude the study. The proposed ML models can analyze health data to identify trends and patterns that may indicate future health problems. By monitoring patterns in medical records and public health data, the proposed ML model can help public health officials detect and respond to outbreaks more quickly. The survey outcome reveals that the level of physical activities has been decreased by 22% during COVID-19-outbreak. The variance is shown at 49% during COVID-19 outbreak. The absence of physical activity (PA) and perceived stress (PS) are observed to be suggestively correlated with the QoL (quality of life) of adults. Deteriorated mental health also disrupts the normal lives and impacts the sleeping quality of people. The analysis of the data is performed using statistical analytical tools to depict the consequences of pandemic on the health of individuals aged between 50 to 80 years.

15.
Chem Commun (Camb) ; 59(49): 7615-7618, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37254851

RESUMO

A split G-quadruplex (G4)-programmed Cas12a platform was established, validated, and optimized. The split G4 motif was recruited as substrate for Cas12a, and the label-free sensing platform provided a concentration-dependent response towards the input target. Furthermore, exosomal surface proteins from cultured cancer cells and clinical samples were detected and profiled.


Assuntos
Sistemas CRISPR-Cas , Quadruplex G , Sistemas CRISPR-Cas/genética
16.
Acta Biochim Biophys Sin (Shanghai) ; 55(3): 343-355, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-37143326

RESUMO

Thermal stability is one of the most important properties of enzymes, which sustains life and determines the potential for the industrial application of biocatalysts. Although traditional methods such as directed evolution and classical rational design contribute greatly to this field, the enormous sequence space of proteins implies costly and arduous experiments. The development of enzyme engineering focuses on automated and efficient strategies because of the breakthrough of high-throughput DNA sequencing and machine learning models. In this review, we propose a data-driven architecture for enzyme thermostability engineering and summarize some widely adopted datasets, as well as machine learning-driven approaches for designing the thermal stability of enzymes. In addition, we present a series of existing challenges while applying machine learning in enzyme thermostability design, such as the data dilemma, model training, and use of the proposed models. Additionally, a few promising directions for enhancing the performance of the models are discussed. We anticipate that the efficient incorporation of machine learning can provide more insights and solutions for the design of enzyme thermostability in the coming years.


Assuntos
Engenharia de Proteínas , Estabilidade Enzimática
17.
bioRxiv ; 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37066187

RESUMO

Background: Blood-brain barrier (BBB) breakdown is a component of the progression and pathology of Alzheimer's disease (AD). BBB dysfunction is primarily caused by reduced or disorganized tight junction or adherens junction proteins of brain microvascular endothelial cell (BMEC). While there is growing evidence of tight junction disruption in BMECs in AD, the functional role of adherens junctions during BBB dysfunction in AD remains unknown. Exosomes secreted from senescent cells have unique characteristics and contribute to modulating the phenotype of recipient cells. However, it remains unknown if and how these exosomes cause BMEC dysfunction in AD. Objectives: This study aimed to investigate the potential roles of AD circulating exosomes and their RNA cargos in brain endothelial dysfunction in AD. Methods: We isolated exosomes from sera of five cases of AD compared with age- and sex-matched cognitively normal controls using size-exclusion chromatography technology. We validated the qualities and particle sizes of isolated exosomes with nanoparticle tracking analysis and atomic force microscopy. We measured the biomechanical natures of the endothelial barrier of BMECs, the lateral binding forces between live BMECs, using fluidic force miscopy. We visualized the paracellular expressions of the key adherens junction protein VE-cadherin in BMEC cultures and a 3D BBB model that employs primary human BMECs and pericytes with immunostaining and evaluated them using confocal microscopy. We also examined the VE-cadherin signal in brain tissues from five cases of AD and five age- and sex-matched cognitively normal controls. Results: We found that circulating exosomes from AD patients suppress the paracellular expression levels of VE-cadherin and impair the barrier function of recipient BMECs. Immunostaining analysis showed that AD circulating exosomes damage VE-cadherin integrity in a 3D model of microvascular tubule formation. We found that circulating exosomes in AD weaken the BBB depending on the RNA cargos. In parallel, we observed that microvascular VE-cadherin expression is diminished in AD brains compared to normal controls. Conclusion: Using in vitro and ex vivo models, our study illustrates that circulating exosomes from AD patients play a significant role in mediating the damage effect on adherens junction of recipient BMEC of the BBB in an exosomal RNA-dependent manner. This suggests a novel mechanism of peripheral senescent exosomes for AD risk.

18.
Microorganisms ; 11(4)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37110425

RESUMO

Chlorella vulgaris is one of the most commonly used microalgae in aquaculture feeds. It contains high concentrations of various kinds of nutritional elements that are involved in the physiological regulation of aquaculture animals. However, few studies have been conducted to illustrate their influence on the gut microbiota in fish. In this work, the gut microbiota of Nile tilapia (Oreochromis niloticus) (average weight is 6.64 g) was analyzed by high-throughput sequencing of the 16S rRNA gene after feeding with 0.5% and 2% C. vulgaris additives in diets for 15 and 30 days (average water temperature was 26 °C). We found that the impact of C. vulgaris on the gut microbiota of Nile tilapia was feeding-time dependent. Only by feeding for 30 days (not 15 days) did the addition of 2% C. vulgaris to diets significantly elevate the alpha diversity (Chao1, Faith pd, Shannon, Simpson, and the number of observed species) of the gut microbiota. Similarly, C. vulgaris exerted a significant effect on the beta diversity (Bray-Curtis similarity) of the gut microbiota after feeding for 30 days (not 15 days). During the 15-day feeding trial, LEfSe analysis showed that Paracoccus, Thiobacillus, Dechloromonas, and Desulfococcus were enriched under 2% C. vulgaris treatment. During the 30-day feeding trial, Afipia, Ochrobactrum, Polymorphum, Albidovulum, Pseudacidovorax, and Thiolamprovum were more abundant in 2% C. vulgaris-treated fish. C. vulgaris promoted the interaction of gut microbiota in juvenile Nile tilapia by increasing the abundance of Reyranella. Moreover, during the feeding time of 15 days, the gut microbes interacted more closely than those during the feeding time of 30 days. This work will be valuable for understanding how C. vulgaris in diets impacts the gut microbiota in fish.

19.
Artigo em Inglês | MEDLINE | ID: mdl-37018294

RESUMO

Tinnitus is an auditory phantom percept that affects the perception of sound in the patient's ears, and the incidence of prolonged tinnitus is as high as ten to fifteen percent. Acupuncture is a unique treatment method in Chinese medicine, and it has great advantages in the treatment of tinnitus. However, tinnitus is a subjective symptom of patients, and there is currently no objective detection method to reflect the improvement effect of acupuncture on tinnitus. We used functional near-infrared spectroscopy (fNIRS) to explore the effect of acupuncture on the cerebral cortex of tinnitus patients. We collected the scores of the tinnitus disorder inventory (THI), tinnitus evaluation questionnaire (TEQ), hamilton anxiety scale (HAMA), and hamilton depression scale (HAMD) of eighteen subjects before and after acupuncture treatment, and the fNIRS signals of these subjects in sound-evoked activity before and after acupuncture treatment. According to the fNIRS detection results of tinnitus patients, acupuncture increased the concentration of oxygenated hemoglobin in the temporal lobe of tinnitus patients, and affected the activation of the auditory cortex. The study may reflect the neural mechanisms of acupuncture treatment for tinnitus and ultimately help to provide an objective evaluation method for the therapeutic effect of acupuncture treatment for tinnitus.

20.
Rev Sci Instrum ; 94(2): 025105, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859031

RESUMO

Clarifying the creep behaviors of hydrate-bearing sediment (HBS) under long-term loading is crucial for evaluating reservoir stability during hydrate exploitation. Figuring out a way of characterizing deformation behaviors and their geophysical responses to HBS is the basis for modeling creep behaviors. In this study, we propose a novel device to test time-dependent deformation and the ultrasonic response of HBS under high-pressure and low-temperature. The experimental device consists of a high-pressure chamber, an axial-load control system, a confining pressure system, a pore pressure system, a back-pressure system, and a data collection system. This testing assembly allows temperature regulation and independent control of four pressures, e.g., confining pressure, pore pressure, back pressure, and axial loading. Columned artificial HBS samples, with a diameter of 39 mm and a height of 120 mm, can be synthesized in this device. Afterward, in situ creep experiments can be achieved by applying stable confining pressure and axial load, together with geophysical signals acquisition. During loading, the stress-strain relationships and ultrasonic data can be obtained simultaneously. Through analyzing the stress-strain relationship and ultrasonic data, the macroscopical failure and microcosmical creep deformation law of the samples can be figured out. Preliminary experiments verified the applicability of the device. The method provides some significance for field observation of reservoir failure via geophysical techniques during hydrate exploitation.

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