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1.
Sensors (Basel) ; 24(8)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38676095

RESUMEN

Human factors are a primary cause of vehicle accidents. Driver monitoring systems, utilizing a range of sensors and techniques, offer an effective method to monitor and alert drivers to minimize driver error and reduce risky driving behaviors, thus helping to avoid Safety Critical Events (SCEs) and enhance overall driving safety. Artificial Intelligence (AI) tools, in particular, have been widely investigated to improve the efficiency and accuracy of driver monitoring or analysis of SCEs. To better understand the state-of-the-art practices and potential directions for AI tools in this domain, this work is an inaugural attempt to consolidate AI-related tools from academic and industry perspectives. We include an extensive review of AI models and sensors used in driver gaze analysis, driver state monitoring, and analyzing SCEs. Furthermore, researchers identified essential AI tools, both in academia and industry, utilized for camera-based driver monitoring and SCE analysis, in the market. Recommendations for future research directions are presented based on the identified tools and the discrepancies between academia and industry in previous studies. This effort provides a valuable resource for researchers and practitioners seeking a deeper understanding of leveraging AI tools to minimize driver errors, avoid SCEs, and increase driving safety.


Asunto(s)
Accidentes de Tránsito , Inteligencia Artificial , Conducción de Automóvil , Humanos , Accidentes de Tránsito/prevención & control , Seguridad
2.
Adv Ther ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656739

RESUMEN

INTRODUCTION: Laser and radiofrequency ablation are two thermal ablation methods currently widely used to treat lower limb venous insufficiency. However, very few studies have been conducted on the use of microwaves, a form of thermal ablation, for the treatment of small saphenous vein (SSV) insufficiency. This study aimed to examine the efficacy and safety of endovenous microwave ablation (EMA) for the treatment of SSV insufficiency. METHODS: The clinical data of 126 patients (126 lower limbs) with SSV insufficiency (SSV trunk reflux time ≥ 500 ms on lower limb color Doppler ultrasound) treated at the Surgery Department of The Sixth People's Hospital of Zhuji from January 2020 to June 2022 were analyzed retrospectively; 64 patients underwent EMA and 62 underwent endovenous laser ablation (EVLA). The perioperative marker data [duration of surgery, duration of hospitalization, length of thermal ablation, duration of thermal ablation, number of incisions, and numerical pain rating scale (NPRS)], complication data [skin ecchymosis, skin burns, surgical site infection, paresthesia, deep vein thrombosis (DVT), and heat-induced thrombosis (EHIT)], venous clinical severity score (VCSS), chronic venous disease quality of life questionnaire (CIVIQ-20) before and 1, 3, 12 months after surgery, and SSV trunk occlusion rate at 12 months after surgery were compared between the two groups. RESULTS: No significant differences in the surgery or hospitalization durations were observed between the two groups. There were no significant differences in the length of the SSV that required thermal ablation between the two groups; however, the thermal ablation time was shorter in the EMA group than that in the EVLA group (6.14 ± 1.47 min vs 7.05 ± 1.16 min, P < 0.001). There were no statistical differences in the number of incisions, volume of tumescent solution used, or quantity of sclerosing foam used. The NPRS scores of the EMA group at 24 h and 72 h after surgery were significantly greater than those of the EVLA group (4.03 ± 0.98 vs 3.52 ± 1.28, P = 0.013; 3.78 ± 1.06 vs 3.15 ± 1.03, P = 0.001). Moreover, the two groups showed no significant difference in the NPRS score at 1 month (1.14 ± 0.84 vs 1.07 ± 0.75, P = 0.623). The EMA and EVLA group patients experienced similar postoperative complications. The VCSS and CIVIQ-20 score significantly improved at 1, 3, and 12 months after surgery. The VCSS and CIVIQ-20 scores were compared between the two groups at 12 months after surgery, and there were no significant differences (1.44 ± 0.63 vs 1.56 ± 0.56, P = 0.261; 24.24 ± 4.96 vs 25.19 ± 5.36, P = 0.304). There was no significant difference in the incidence of SSV trunk occlusion at 12 months after surgery between the two groups (95.31% vs 96.77%, OR 1.475; 95% CI 0.238-9.146, P = 1.000). CONCLUSION: EMA and EVLA are equally effective treatment methods for SSV insufficiency. EMA is associated with higher NPRS scores in the early postoperative period.

3.
J Nanobiotechnology ; 22(1): 52, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38321555

RESUMEN

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.


Asunto(s)
Dermis Acelular , Cistitis , Infecciones Urinarias , Porcinos , Animales , Levofloxacino , Hidrogeles
4.
Anal Chem ; 96(6): 2550-2558, 2024 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-38314707

RESUMEN

Cancer-related extracellular vesicles (EVs) are considered important biomarkers for cancer diagnosis because they can convey a large amount of information about tumor cells. In order to detect cancer-related EVs efficiently, an electrochemiluminescence (ECL) sensor for the specific identification and highly sensitive detection of EVs in the plasma of cancer patients was constructed based on dual recognitions by glycosyl-imprinted polymer (GIP) and aptamer. The characteristic glycosyl Neu5Ac-α-(2,6)-Gal-ß-(1-4)-GlcNAc trisaccharide on the surface of EVs was used as a template molecule and 3-aminophenylboronic acid as a functional monomer to form a glycosyl-imprinted polymer by electropolymerization. After glycosyl elution, the imprinted film specifically recognized and adsorbed the EVs in the sample, and then the CD63 aptamer-bipyridine ruthenium (Aptamer-Ru(bpy)) was added to combine with the CD63 glycoprotein on the extracellular vesicle's surface, thus providing secondary recognition of the EVs. Finally, the EVs were quantitatively detected according to the ECL signal produced by the labeled bipyridine ruthenium. When more EVs were captured by the imprinted film, more probes were obtained after incubation, and the ECL signal was stronger. Under the optimized conditions, the ECL signal showed a good linear relationship with the concentration of EVs in the range of 9.5 × 102 to 9.5 × 107 particles/mL, and the limit of detection was 641 particles/mL. The GIP sensor can discriminate between the EV contents of cancer patients and healthy controls with high accuracy. Because of its affordability, high sensitivity, and ease of use, it is anticipated to be employed for cancer early detection and diagnosis.


Asunto(s)
Técnicas Biosensibles , Vesículas Extracelulares , Neoplasias , Rutenio , Humanos , Mediciones Luminiscentes , Oligonucleótidos , Polímeros , Técnicas Electroquímicas , Neoplasias/diagnóstico
5.
J Diabetes ; 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38087869

RESUMEN

BACKGROUND: Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal-jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats. METHODS: High-fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro. RESULTS: DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system-related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system-related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors. CONCLUSIONS: DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway-and not solely by improving blood glucose-to improve oxidative stress in the heart of diabetic cardiomyopathy rats.

6.
BMC Surg ; 23(1): 235, 2023 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-37568176

RESUMEN

BACKGROUND: Preventive colostomy is required for colorectal surgery, and the incidence of complications associated with ileostomy and colostomy remains controversial. This study aimed to compare the incidence of postoperative complications between ileostomy and colostomy procedures. METHODS: Data analysis was conducted on 30 studies, and meta-analysis and trial sequential analysis (TSA) were performed on five studies. The basic indicators, such as stoma prolapse, leak, wound infection, ileus, and a series of other indicators, were compared. RESULTS: No statistically significant differences were observed with complications other than stoma prolapse. Meta-analysis and TSA showed that the incidence of ileostomy prolapse was lower than that of colostomy prolapse, and the difference was statistically significant. Apart from the four complications listed above, the general data analysis showed differences in incidence between the two groups. The incidence of skin irritation, parastomal hernia, dehydration, pneumonia, and urinary tract infections was higher with ileostomy than with colostomy. In contrast, the incidence of parastomal fistula, stenosis, hemorrhage, and enterocutaneous fistula was higher with colostomy than with ileostomy. CONCLUSIONS: There were differences in the incidence of ileostomy and colostomy complications in the selected studies, with a low incidence of ileostomy prolapse. PROSPERO REGISTRATION NUMBER: CRD42022303133.


Asunto(s)
Colostomía , Ileostomía , Humanos , Colostomía/efectos adversos , Colostomía/métodos , Ileostomía/efectos adversos , Ileostomía/métodos , Anastomosis Quirúrgica/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Prolapso
7.
Biomacromolecules ; 24(1): 400-412, 2023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36475673

RESUMEN

Multimodal collaborative therapy has been recognized as one of the more effective means to eliminate tumors in the current biomedicine research field as compared with monotherapy. Among them, by taking advantage of its high-precision and controllability, phototherapy has become a mainstay of treatment. However, physical encapsulation of free photosensitive units within nanocarriers was one of the main implementations, which might inevitably result in the photosensitizer leakage and side effect. For this purpose, a kind of multifunctional integrated polyprodrug amphiphiles, P(PFO-IG-CPT)-PEG, were prepared by reversible addition-fragmentation chain transfer polymerization from polymerizable pentadecafluorooctan monomers, indocyanine green monomers, reduction-responsive camptothecin monomers, and acid-responsive PEG based methacrylate monomers (GMA(-OH/-PEG)). The resultant copolymers could self-assemble into spherical nanoparticles in water, performing size-deformability in acidic conditions and subsequent disintegration in reduction environment as demonstrated by in vitro experiments. Furthermore, an enhanced CPT release ratio and rate from nanoparticles could be achieved by a NIR irradiation due to the hyperthermia induced by the covalently linked IG moieties. Not only that, because of the sufficient O2 content brought by PFO, the NIR light-triggered generation of 1O2 was also detected in cells. With the combination of CPT-guided chemotherapy as well as NIR light-guided photo-thermal and photodynamic therapies, fatal and irreversible damage to cancer cells was observed by cell experiments; the implanted tumor size in the mouse model was obviously shrunk upon receiving multimodal collaborative therapy. We speculate that such fabricated nanodiagnosis and treatment systems could meet the growing emergency for effective drug delivery, programmed and on-demand drug release, and multimodal integrated therapy.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Animales , Ratones , Fototerapia , Sistemas de Liberación de Medicamentos , Camptotecina/farmacología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Nanopartículas/uso terapéutico , Línea Celular Tumoral
8.
Sensors (Basel) ; 22(20)2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36298389

RESUMEN

Traditionally, pavement safety performance in terms of texture, friction, and hydroplaning speed are measured separately via different devices with various limitations. This study explores the feasibility of using a novel 0.1 mm 3D Safety Sensor for pavement safety evaluation in a non-contact and continuous manner with a single hardware sensor. The 0.1 mm 3D images were collected for pavement safety measurement from 12 asphalt concrete (AC) and Portland cement concrete (PCC) field sites with various texture characteristics. The results indicate that the Safety Sensor was able to measure pavement texture data as traditional devices do with better repeatability. Moreover, pavement friction numbers can be estimated using 0.1 mm 3D data via the proposed 3D texture parameters with good accuracy using an artificial neural network, especially for asphalt pavement. Lastly, a case study of pavement hydroplaning speed prediction was performed using the Safety Sensor. The results demonstrate the potential of using ultra high-resolution 3D imaging to measure pavement safety, including texture, friction, and hydroplaning, in a non-contact, continuous, and accurate manner.


Asunto(s)
Hidrocarburos , Imagenología Tridimensional , Rayos Láser , Tecnología
9.
Front Physiol ; 13: 826740, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370774

RESUMEN

Bile acid is a derivative of cholinergic acid (steroidal parent nucleus) that plays an important role in digestion, absorption, and metabolism. In recent years, bile acids have been identified as signaling molecules that regulate self-metabolism, lipid metabolism, energy balance, and glucose metabolism. The detection of fine changes in bile acids caused by metabolism, disease, or individual differences has become a research hotspot. At present, there are many related techniques, such as enzyme analysis, immunoassays, and chromatography, that are used for bile acid detection. These methods have been applied in clinical practice and laboratory research to varying degrees. However, mainstream detection technology is constantly updated and replaced with the passage of time, proffering new detection technologies. Previously, gas chromatography (GS) and gas chromatography-mass spectrometry (GC-MS) were the most commonly used for bile acid detection. In recent years, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has developed rapidly and has gradually become the mainstream bile acid sample separation and detection technology. In this review, the basic principles, development and progress of technology, applicability, advantages, and disadvantages of various detection techniques are discussed and the changes in bile acids caused by related diseases are summarized.

10.
Biomater Sci ; 10(5): 1373-1383, 2022 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-35133356

RESUMEN

Bacterial induced wound infection is very common in real life, but the abuse of antibiotics means that is poses a potential threat to human health. The development of non-antibiotic type antibacterial materials appears to be of importance. Herein, a microenvironment-responsive and biodegradable hydrogel complex, consisting of an acid-degradable antibacterial hydrogel and a hydrogen peroxide (H2O2)-responsive polymer/gold hybrid film with photothermal conversion ability was constructed based on polyethylenimine (PEI), polyethylene glycol (PEG), hexachlorocyclic triphosphonitrile (HCCP), and gold nanoparticles. The resultant hydrogel showed excellent adhesion to various surfaces, whether in air or underwater. However, a simple glycerine and water (v/v = 1/1) mixed solution could rapidly promote the detachment of the hydrogel from skin automatically, without any external force and no residue was left, exhibiting a manmade controllable flexible feature. Moreover, the in vitro antibacterial performance against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (S. aureus), as well as wound healing investigations conducted in living mice confirmed that these hydrogels possessed excellent antibacterial, antioxidative, and wound healing abilities. We believe this proof of concept could create a novel pathway for the design and construction of highly efficient hydrogel dressings using readily available polymeric materials and that the resulting dressing have potential for clinical applications.


Asunto(s)
Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antioxidantes/farmacología , Vendajes , Oro , Hidrogeles/química , Hidrogeles/farmacología , Peróxido de Hidrógeno , Ratones , Staphylococcus aureus , Cicatrización de Heridas
11.
Macromol Rapid Commun ; 43(14): e2100791, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34967061

RESUMEN

This Review focuses on the current research advances of the synthesis of various amphiphilic block copolymers (ABCs), such as conventional ABCs and newly presented polyprodrug amphiphiles, and the development of corresponding self-assemblies in selective solvents driven by the intermolecular interactions, like noncovalent hydrophobic interactions, π-π interactions, and hydrogen bonds, between ABCs or preformed small polymeric nanoparticles. The design of these assemblies is systematically introduced, and the diverse examples concerning the unique assembly structures along with the fast development of their exclusive properties and various applications in different fields are discussed. Possible perspectives on the existential challenges and glorious future are elucidated finally. It is hoped that this Review will provide a convenient way for readers to motivate more evolutional innovative concepts and methods to design next generation of novel polymeric nanoassemblies, and fill the gap between material design and practical applications.


Asunto(s)
Nanopartículas , Polímeros , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Polímeros/química
12.
Materials (Basel) ; 14(19)2021 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-34640166

RESUMEN

Pavement micro- and macro-texture have significant effects on roadway friction and driving safety. The influence of traffic polish on pavement texture has been investigated in many laboratory studies. This paper conducts field evaluation of pavement micro- and macro-texture under actual traffic polishing using three-dimensional (3D) areal parameters. A portable high-resolution 3D laser scanner measured pavement texture from a field site in 2018, 2019, and 2020. Then, the 3D texture data was decomposed to micro- and macro-texture using Fourier transform and Butterworth filter methods. Twenty 3D areal parameters from five categories, including height, spatial, hybrid, function, and feature parameters, were calculated to characterize pavement micro- and macro-texture. The results demonstrate that the 3D areal parameters provide an alternative to comprehensively characterize the evolution of pavement texture under traffic polish from different aspects.

13.
BMJ Open ; 11(10): e045530, 2021 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-34697109

RESUMEN

INTRODUCTION: Inferior vena cava (IVC) filters are commonly used in patients with venous thromboembolism to prevent fatal pulmonary embolism, but the thrombosis risk increases after filter placement. Warfarin is a widely anticoagulant, but long-term monitoring and dose adjustments are required. Anticoagulation with rivaroxaban is more straightforward as it dose not require laboratory monitoring. This study compares the efficacy and safety of rivaroxaban and warfarin as an in anticoagulation therapy for patients with IVC filter placement. METHODS AND ANALYSIS: This is a multicentre, randomised controlled trial. In total, 200 patients with deep vein thrombosis (DVT) with IVC filter implantation from 10 hospitals will be recruited. The patients will be randomised to the experimental group (rivaroxaban) or the control group (nadroparin overlapped with warfarin). The primary outcomes include death of any cause, pulmonary embolism (PE)-related death, bleeding and recurrent PE/DVT. The secondary outcomes include the percentage of other vascular events, IVC filter retrieval failure and net clinical benefits. This study aims to provide reliable, verification for the efficacy and safety of rivaroxaban antithrombotic therapy after IVC filter placement. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (approval number: (2019) 295). The results will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals TRIAL REGISTRATION NUMBER: NCT04066764.


Asunto(s)
Embolia Pulmonar , Filtros de Vena Cava , Anticoagulantes/efectos adversos , Contraindicaciones , Humanos , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Embolia Pulmonar/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán/efectos adversos , Resultado del Tratamiento
14.
Front Cardiovasc Med ; 8: 659769, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34589524

RESUMEN

The long non-coding RNA regulator of reprogramming (lncRNA ROR) is involved in atherosclerosis (AS), but the specific mechanism remains unclear. The expressions of lncRNA ROR, let-7b-5p, Homeobox A1 (HOXA1), and apoptosis-associated proteins in the serum of AS patients and human umbilical vein endothelial cells (HUVECs) were determined by quantitative real-time PCR (qRT-PCR) and Western blot. The relationships of lncRNA ROR, let-7b-5p, and HOXA1 were analyzed by Pearson's correlation test. The viability and the migration of HUVECs were measured by Cell Counting Kit-8, wound healing, and Transwell assays. The predicted target gene and the potential binding sites were confirmed by dual-luciferase reporter assay. lncRNA ROR was highly expressed in AS, which promoted the cell viability and migration of HUVECs, while lncRNA ROR silencing produced the opposite results. The expression of let-7b-5p, which bound to lncRNA ROR, was downregulated in AS, indicating that the two genes were negatively correlated. Besides this, let-7b-5p reversed the effects of upregulated lncRNA ROR expression on let-7b-5p expression, cell viability, and migration as well as the expressions of apoptosis-related proteins of ox-LDL-treated HUVECs. HOXA1 was targeted by let-7b-5p and upregulated in AS, with its expression being negatively correlated with let-7b-5p but positively correlated with lncRNA ROR. In ox-LDL-treated HUVECs, overexpressed HOXA1 reversed the effects of let-7b-5p, and HOXA1 silencing reversed the effects of lncRNA ROR. In AS, lncRNA ROR promoted the biological characteristics of oxidation of low-density lipoprotein-induced HUVECs via the let-7b-5p/HOXA1 axis.

15.
Viruses ; 13(8)2021 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-34452363

RESUMEN

Despite the recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of the SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2, retains full activity against the variant of concern (VOC) B.1.1.7 and still neutralizes the VOC B.1.351, although with reduced potency. Importantly, not only systemic but also intranasal application of DZIF-10c abolished the presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology when administered prophylactically. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Antivirales/administración & dosificación , COVID-19/prevención & control , SARS-CoV-2/inmunología , Administración Intranasal , Animales , COVID-19/virología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/inmunología
16.
Front Pharmacol ; 12: 638209, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34054520

RESUMEN

Objective: The present study explored whether levetiracetam (LEV) could protect against experimental brain ischemia and enhance angiogenesis in rats, and investigated the potential mechanisms in vivo and in vitro. Methods: The middle cerebral artery was occluded for 60 min to induce middle cerebral artery occlusion (MCAO). The Morris water maze was used to measure cognitive ability. The rotation test was used to assess locomotor function. T2-weighted MRI was used to assess infarct volume. The neuronal cells in the cortex area were stained with cresyl purple. The anti-inflammatory effects of LEV on microglia were observed by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISA) were used to measure the production of pro-inflammatory cytokines. Western blotting was used to detect the levels of heat shock protein 70 (HSP70), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in extracts from the ischemic cortex. Flow cytometry was used to observe the effect of LEV on neuronal cell apoptosis. Results: LEV treatment significantly increased the density of the surviving neurons in the cerebral cortex and reduced the infarct size (17.8 ± 3.3% vs. 12.9 ± 1.4%, p < 0.01) after MCAO. Concurrently, the time required to reach the platform for LEV-treated rats was shorter than that in the saline group on day 11 after MCAO (p < 0.01). LEV treatment prolonged the rotarod retention time on day 14 after MCAO (84.5 ± 6.7 s vs. 59.1 ± 6.2 s on day 14 compared with the saline-treated groups, p < 0.01). It also suppressed the activation of microglia and inhibited TNF-α and Il-1ß in the ischemic brain (135.6 ± 5.2 pg/ml vs. 255.3 ± 12.5 pg/ml, 18.5 ± 1.3 pg/ml vs. 38.9 ± 2.3 pg/ml on day 14 compared with the saline-treated groups, p < 0.01). LEV treatment resulted in a significant increase in HIF-1α, VEGF, and HSP70 levels in extracts from the ischemic cerebral cortex. At the same time, LEV reduced neuronal cell cytotoxicity and apoptosis induced by an ischemic stroke (p < 0.01). Conclusion: LEV treatment promoted angiogenesis and functional recovery after cerebral ischemia in rats. These effects seem to be mediated through anti-inflammatory and antiapoptotic activities, as well as inducing the expression of HSP70, VEGF, and HIF-1α.

17.
Anim Biosci ; 34(11): 1739-1748, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33152223

RESUMEN

OBJECTIVE: In recent years, long noncoding RNAs (lncRNAs) have been identified in many species, and some of them have been shown to play important roles in muscle development and myogenesis. However, the differences in lncRNAs between Kazakh cattle and Xinjiang brown cattle remain undefined; therefore, we aimed to confirm whether lncRNAs are differentially expressed in the longissimus dorsi between these two types of cattle and whether differentially expressed lncRNAs regulate muscle differentiation. METHODS: We used RNA-seq technology to identify lncRNAs in longissimus muscles from these cattle. The expression of lncRNAs were analyzed using StringTie (1.3.1) in terms of the fragments per kilobase of transcript per million mapped reads values of the encoding genes. The differential expression of the transcripts in the two samples were analyzed using the DESeq R software package. The resulting false discovery rate was controlled by the Benjamini and Hochberg's approach. KOBAS software was utilized to measure the expression of different genes in Kyoto encyclopedia of genes and genomes pathways. We randomly selected eight lncRNA genes and validated them by quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: We found that 182 lncRNA transcripts, including 102 upregulated and 80 downregulated transcripts, were differentially expressed between Kazakh cattle and Xinjiang brown cattle. The results of RT-qPCR were consistent with the sequencing results. Enrichment analysis and functional annotation of the target genes revealed that the differentially expressed lncRNAs were associated with the mitogen-activated protein kinase, Ras, and phosphatidylinositol 3-kinase (PI3k)/Akt signaling pathways. We also constructed a lncRNA/mRNA coexpression network for the PI3k/Akt signaling pathway. CONCLUSION: Our study provides insights into cattle muscle-associated lncRNAs and will contribute to a more thorough understanding of the molecular mechanism underlying muscle growth and development in cattle.

18.
mSystems ; 5(6)2020 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-33144310

RESUMEN

ABSRTACTKlebsiella pneumoniae is a common cause of human-pneumonia-derived sepsis with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis. The mechanisms by which the gut microbiota affects the host defenses in the respiratory system systematically, however, remain poorly understood. Here, we show that gut microbiota depletion increases susceptibility to extracellular K. pneumoniae infections in terms of increased bacterial burdens in lung and decreased survival rates. Oral supplementation with gut microbiota-derived short-chain fatty acids (SCFAs), subsequently activating G protein-coupled receptor 43 (GPCR43), enhances a macrophage's capacity to phagocytose invading K. pneumoniae Furthermore, SCFAs and GPR43 increase macrophage bacterial clearance by upregulating LAMTOR2, which is further identified as an antibacterial effector and elucidated to facilitate phagosome-lysosome fusion and extracellular signal-regulated kinase (ERK) phosphorylation. Lastly, conditional ablation of Lamtor2 in macrophages decreases their antimicrobial activity, even though mice were pretreated with exogenous SCFA supplementation.IMPORTANCE These observations highlight that SCFAs promote macrophage elimination of K. pneumoniae via a LAMTOR2-dependent signal pathway and suggest that it is possible to intervene in K. pneumoniae pneumonia by targeting the gut microbiota.

19.
Front Hum Neurosci ; 14: 300, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32922272

RESUMEN

Objective: We aimed to evaluate the activity of the human glymphatic system in type 2 diabetes mellitus (T2DM) using diffusion tensor image analysis along with the perivascular space (DTI-ALPS). Methods: Diffusion tensor images were acquired to calculate the diffusivities in the direction of the x-axis (right-to-left; Dx), y-axis (anterior-to-posterior; Dy), and z-axis (inferior-to-superior; Dz) of the plane of the lateral ventricle body in 20 patients with type 2 diabetes and 10 people in a control group. We evaluated the diffusivity along with the perivascular spaces, as well as the projection fibers and association fibers, separately. The analysis along the perivascular space (ALPS-index) was defined as the mean (Dxpro, Dypro)/mean (Dypro, Dzasc), where the Dxpro and Dxasc were the Dx values in the projection and association fiber areas, respectively. Results: There were significant differences in diffusivity along the projection fibers and the association fibers among the groups. The significant differences among the groups along the perivascular spaces, shown as the ALPS-index and medical history of T2DM, indicating lower water diffusivity along the perivascular space concerning type 2 diabetes severity, was also observed. Conclusion: Lower diffusivity along the perivascular space on DTI-APLS can reflect impairment of the glymphatic system in T2DM. This study showed that the activity of the glymphatic system could be evaluated by diffusion tensor image analysis.

20.
Aging (Albany NY) ; 12(2): 1171-1185, 2020 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-31977318

RESUMEN

Hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis. It is of great importance to identify biomarkers for the prediction of patients' survival.The mRNA expression level of deoxyribonuclease 1 like 3 (DNASE1L3) and its correlation with survival were accessed in 424 samples from The Cancer Genome Atlas database. Its expression level was confirmed by real-time quantitative polymerase chain reaction and western blotting in 20 pairs of postsurgical specimens. In addition, immunohistochemistry staining of DNASE1L3 was also performed in 113 postoperative samples, using a histochemistry score system. The relationship between patients' survival and DNASE1L3 expression level was evaluated by the Kaplan-Meier method.DNASE1L3 is downregulated in both mRNA and protein levels in HCC tissues, compared with adjacent normal tissues. 52 of 113 HCC specimens showed positive DNASE1L3 protein expression. Patients with positive DNASE1L3 expression had significantly longer overall survival, compared with patients with negative expression (p = 0.023). However, the DNASE1L3 fails to discriminate progression-free survival (p = 0.134). Multivariate COX analysis revealed that positive DNASE1L3 expression and higher differentiation were significantly associated with better overall survival.This study demonstrated that positive DNASE1L3 expression is an independent prognostic factor for better survival in HCC patients following radical resection.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , Endodesoxirribonucleasas/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Biología Computacional/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Hepatectomía , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Reproducibilidad de los Resultados , Análisis de Supervivencia , Transcriptoma , Carga Tumoral
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