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1.
Nat Biomed Eng ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635419

RESUMO

The success of messenger RNA therapeutics largely depends on the availability of delivery systems that enable the safe, effective and stable translation of genetic material into functional proteins. Here we show that extracellular vesicles (EVs) produced via cellular nanoporation from human dermal fibroblasts, and encapsulating mRNA encoding for extracellular-matrix α1 type-I collagen (COL1A1) induced the formation of collagen-protein grafts and reduced wrinkle formation in the collagen-depleted dermal tissue of mice with photoaged skin. We also show that the intradermal delivery of the mRNA-loaded EVs via a microneedle array led to the prolonged and more uniform synthesis and replacement of collagen in the dermis of the animals. The intradermal delivery of EV-based COL1A1 mRNA may make for an effective protein-replacement therapy for the treatment of photoaged skin.

2.
J Infect Dis ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637115

RESUMO

Influenza imprinting reduces risks of influenza A virus clinical infection by 40-90% estimated from surveillance data in western countries. We analyzed surveillance data from 2010-2019 in Hong Kong. Based on the best model included HA group-level imprinting, we estimated that individuals imprinted to H1N1 or H2N2 had a 17% (95% CI: 3%, 28%) lower risk of H1N1 clinical infection, and individuals imprinted to H3N2 would have 12% (95% CI: -3%, 26%) lower risk of H3N2 clinical infection. These estimates were weaker than estimated in western countries. Identifying factors affecting imprinting protections is important for control policies and disease modeling.

3.
Phytomedicine ; 111: 154660, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36681051

RESUMO

BACKGROUND: Current therapeutics for ulcerative colitis (UC) have limitations. Classical Formula Gegen Qinlian decoction (GQD) is derived from Shang Han Lun and has a long history of treating gastrointestinal diseases such as diarrhea and UC. Nevertheless, the exact mechanism of it needs to be further clarified. PURPOSE: We aimed to investigate the treatment effects of modified GQD (MGQD) on dextran sodium sulfate (DSS)-induced chronic colitis in mice and conduct further exploration of its underlying mechanisms. METHODS: The protective effect of MGQD was estimated in a DSS-induced chronic colitis mouse model. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Alcian Blue/Phosphoric Acid Schiff (AB/PAS) staining, transmission electron microscopy (TEM), immunofluorescence and real time‒PCR (RT-PCR) were used to assess goblet cell function. ELISA, flow cytometry and immunofluorescence were applied to estimate the immunoinflammatory status. Western blot was performed to test the protein expression levels of relevant pathways and related receptors. All experiments were conducted in duplicate. RESULTS: MGQD alleviated DSS­induced chronic colitis symptoms in mice, protected goblet cell function and restored the intestinal mucus barrier. Furthermore, MGQD efficiently suppressed the abnormal immune inflammatory response and the activate of γδT17 cells and NLRP3 inflammasome. CONCLUSION: The mechanisms by which MGQD protects against DSS-induced chronic colitis may involve restoring goblet cell function, repairing the intestinal mucus barrier, and modulating the immune inflammatory response. More importantly, MGQD inhibited NLRP3 inflammasome-associated signaling pathway activation, which consequently reduced the activation of γδT17 cells.

4.
Org Lett ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662291

RESUMO

Reported here is a highly enantioselective homoenolate Michael addition/esterification sequence of cyclohexadienone-tethered enals via N-heterocyclic carbene (NHC) catalysis, affording the enantiopure cis-hydrobenzofurans, cis-hydroindoles, and cis-hydroindenes. The NHC catalyst bearing a nitro group greatly enhances the stereocontrol, and a bulky N-aryl substituent of the triazolium salt in the catalyst is helpful for inhibiting the further aldol condensation after homoenolate Michael addition. The utility of this protocol is highlighted by a gram-scale experiment and versatile downstream transformations.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36662514

RESUMO

As a result of their radiation-free nature and deep-penetration ability, tumor theranostics mediated by ultrasound have become increasingly recognized as a modality with high potential for translation into clinical cancer treatment. The effective integration of ultrasound imaging and sonodynamic therapy (SDT) into one nanoplatform remains an enormous challenge yet to be fully resolved. Here, a novel theranostic system, consisting of rattle-type SiO2 (r-SiO2) loaded with Mn-doped In2S3/InOOH (SMISO), was designed and synthesized to enable an improved ultrasound imaging-guided therapy. With Mn-doped In2S3/InOOH (MISO) and a heterojunction structure, this novel sonosensitizer facilitates the generation of reactive oxygen species (ROS) for SDT. By coupling interfaces between the shell and core in rattle-type SiO2, multiple reflections/scattering are generated, while MISO has high acoustic impedance. By integrating r-SiO2 and MISO, the SMISO composite nanoparticles (NPs) increase the acoustic reflection and provide enhanced contrast for ultrasound imaging. Through the effective accumulation in tumors, which was monitored by B-mode ultrasound imaging in vivo, SMISO composite NPs effectively inhibited tumor growth without adverse side effects under ultrasound irradiation treatment. This work therefore provides a new approach to integrate a novel gas-free ultrasound contrast agent and a semiconductor sonosensitizer for cancer theranostics.

6.
J Biomater Appl ; : 8853282221150359, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607821

RESUMO

Polymethyl methacrylate (PMMA) bone cement is now widely used in percutaneous vertebro plasty (PVP) and percutaneous kyphoplasty (PKP). However, studies showed that the radiopacifiers (zirconia, barium sulfate, etc.) added to PMMA will have a negative impact on its use, e.g. barium sulfate will weaken the mechanical properties of bone cement and lead to bone absorption and aseptic loosening. Iodine is an element existing in the human body and has good imaging performance. Iodine contrast agent has been used in clinic for many years and has abundant clinical data. Therefore, using iodine instead of barium sulfate may be a promising choice. In this paper, the effect of different content of diatrizoate sodium (DTA, C11H8I3N2NaO4) on the properties of PMMA was studied and compared with the traditional PMMA bone cement containing 30 wt% barium sulfate. The mechanical properties, setting properties, radiopacity, and biocompatibility of bone cement were evaluated. The compressive strength of PMMA bone cement with 20 wt% DTA can reach 76.38 MPa. DTA released from bone cement up to 14 days accounted for only 2.3% of its dosage. The water contact angle was 62.3°. The contrast of bone cement on X-ray film was comparable to that of bone cement containing 30 wt% barium. The hemolysis rate was lower than 4%, and there was no obvious hemolysis. PMMA with 20 wt% DTA can maintain the relative growth rate of MC3T3-E1 and L929 cells above 80%. The results show that adding 20 wt% DTA into PMMA can obtain good radiopacity while maintaining its mechanical properties, setting properties, and biocompatibility. DTA can be used as a promising candidate material for PMMA bone cement radiopacifier.

7.
Nat Biotechnol ; 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593400

RESUMO

Mosaic variants (MVs) reflect mutagenic processes during embryonic development and environmental exposure, accumulate with aging and underlie diseases such as cancer and autism. The detection of noncancer MVs has been computationally challenging due to the sparse representation of nonclonally expanded MVs. Here we present DeepMosaic, combining an image-based visualization module for single nucleotide MVs and a convolutional neural network-based classification module for control-independent MV detection. DeepMosaic was trained on 180,000 simulated or experimentally assessed MVs, and was benchmarked on 619,740 simulated MVs and 530 independent biologically tested MVs from 16 genomes and 181 exomes. DeepMosaic achieved higher accuracy compared with existing methods on biological data, with a sensitivity of 0.78, specificity of 0.83 and positive predictive value of 0.96 on noncancer whole-genome sequencing data, as well as doubling the validation rate over previous best-practice methods on noncancer whole-exome sequencing data (0.43 versus 0.18). DeepMosaic represents an accurate MV classifier for noncancer samples that can be implemented as an alternative or complement to existing methods.

8.
Se Pu ; 41(1): 76-86, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36633079

RESUMO

With the increasing number of cosmetic products, their flavor and fragrance components are receiving greater and greater attention. Establishing an analytical method of determining these components in cosmetics is one of the most effective measures to eliminate consumers' concerns. In this study, a method for the simultaneous determination of 28 fragrance residues in cosmetics by gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed. The samples were extracted using methanol and those containing more oil and grease were purified using a neutral alumina solid-phase extraction column, whereas those with more complex compositions were purified by QuEChERS. The analytes in the samples were measured by GC-MS/MS, characterized using their retention times and characteristic ion pairs, and quantified with an external standard. The respective limits of detection (LODs, S/N=3) and quantification (LOQs, S/N>10) of the compounds were in the ranges 2-20 and 5-50 µg/kg. The linearities of the concentration curves of the 28 substances were good in the ranges 1-100, 2-200, 4-200, and 10-1000 µg/L, and the correlation coefficients of the quantitative ion pairs were >0.999. Twenty-eight fragrances were added to blank samples at spiked levels of 50-500 µg/kg, and the recoveries ranged from 71.3% to 120.4%, with RSDs of 1.5%-14.6%. The method could be applied in the determination of fragrances in cosmetics because it was simple, sensitive, and stable and could effectively exclude the interferences of complex matrices. The method was used to determine the fragrance components in 16 cosmetic products, and some fragrance components were detected in 12 samples. Increased attention should be paid to the safeties of fragrances and flavors used in cosmetics.


Assuntos
Cosméticos , Perfumes , Espectrometria de Massas em Tandem , Odorantes/análise , Cromatografia Gasosa-Espectrometria de Massas , Cosméticos/análise , Perfumes/análise , Extração em Fase Sólida , Cromatografia Líquida de Alta Pressão
9.
Nat Genet ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635388

RESUMO

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.

10.
Int J Biol Macromol ; 231: 123203, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36623619

RESUMO

For food packaging, a novel composite film was prepared by solution casting method using hydroxyethyl cellulose (HEC), carboxymethyl chitosan (CMCS), and zinc oxide nanoparticles as raw materials. The composite film successfully compounded the nanoparticles, as deduced by spectroscopy, crystallography and morphology observation. The addition of CMCS and ZnO enhanced the solvent resistance (the water solubility of the composite film was reduced by 94.3 %) and UV shielding ability (the UV shielding capacity of the composite film was increased by 45.73 %) of the composite film, thus improving the application prospects of the composite film in water-rich foods. In addition, the synergistic effect of CMCS and ZnO helped the composite film to efficiently inhibit the pathogenic bacteria Listeria monocytogenes and Pseudomonas aeruginosa (rate of inhibition>99.99 %) in food. The addition of CMCS and ZnO also significantly improved the elasticity (improve 494.34 %) and maximum load capacity (improve 142.24 %) of the composite film.

11.
Metabolites ; 13(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36677032

RESUMO

Both genetic improvement and the application of N fertilizer increase the quality and yields of wheat. However, the molecular kinetics that underlies the differences between them are not well understood. In this study, we performed a non-targeted metabolomic analysis on wheat cultivars from different release years to comprehensively investigate the metabolic differences between cultivar and N treatments. The results revealed that the plant height and tiller number steadily decreased with increased ears numbers, whereas the grain number and weight increased with genetic improvement. Following the addition of N fertilizer, the panicle numbers and grain weights increased in an old cultivar, whereas the panicle number and grain number per panicle increased in a modern cultivar. For the 1950s to 2010s cultivar, the yield increases due to genetic improvements ranged from -1.9% to 96.7%, whereas that of N application ranged from 19.1% to 81.6%. Based on the untargeted metabolomics approach, the findings demonstrated that genetic improvements induced 1.4 to 7.4 times more metabolic alterations than N fertilizer supply. After the addition of N, 69.6%, 29.4%, and 33.3% of the differential metabolites were upregulated in the 1950s, 1980s, and 2010s cultivars, respectively. The results of metabolic pathway analysis of the identified differential metabolites via genetic improvement indicated enrichment in 1-2 KEGG pathways, whereas the application of N fertilizer enriched 2-4 pathways. Our results provide new insights into the molecular mechanisms of wheat quality and grain yield developments.

12.
Langenbecks Arch Surg ; 408(1): 51, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662263

RESUMO

BACKGROUND: Recently, indocyanine green (ICG) fluorescence imaging has been increasingly used in laparoscopic anatomic liver resection. The aim of this study was to investigate the efficacy of ICG-guided laparoscopic anatomic liver resection in hepatocellular carcinoma (HCC) compared with traditional laparoscopic anatomic liver resection. METHODS: A retrospective study was performed on patients with pathologically diagnosed HCC who successfully underwent laparoscopic anatomical liver resection from January 2019 to December 2021. The outcomes were compared between the two groups before and after the propensity score matching (PSM). RESULTS: A total of 110 patients were included in this study, including 50 patients in the ICG-guided group and 60 patients in the traditional group. Compared with the traditional group, the ICG-guided group had a shorter operative duration (P = 0.040), less intraoperative blood loss (P = 0.044), a lower incidence of postoperative complications (P = 0.023), and a shorter postoperative hospitalisation (P < 0.001). After PSM, significant differences remained between the two groups for the duration of postoperative hospitalisation (P = 0.018) and postoperative complications (P = 0.042). There was no significant difference in the recurrence rate between the two groups before and after PSM. CONCLUSION: Laparoscopic anatomic liver resection guided by ICG fluorescence imaging can reduce the duration of postoperative hospitalisation for patients and the incidence of postoperative complications. However, it has no impact on the long-term outcome of patients.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Verde de Indocianina , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Hepatectomia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Imagem Óptica/métodos
13.
Obesity (Silver Spring) ; 31(1): 123-138, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36504350

RESUMO

OBJECTIVE: Genetic variants in ninjurin-2 (NINJ2; nerve injury-induced protein 2) confer risk of ischemic strokes and coronary artery disease as well as endothelial activation and inflammation. However, little is known about NINJ2's in vivo functions and underlying mechanisms. METHODS: The phenotypes of NINJ2 knockout mice were analyzed, and mechanisms of NINJ2 that regulate body weight, insulin resistance, and glucose homeostasis and lipogenesis were investigated in vivo and in vitro. RESULTS: This study found that mice lacking NINJ2 showed impaired adipogenesis, increased insulin resistance, and abnormal glucose homeostasis, all of which are risk factors for strokes and coronary artery disease. Mechanistically, NINJ2 directly interacts with insulin receptor/insulin-like growth factor 1 receptor (INSR/IGF1R), and NINJ2 knockdown can block insulin-induced mitotic clonal expansion during preadipocyte differentiation by inhibiting protein kinase B/extracellular signal-regulated kinase (AKT/ERK) signaling and by decreasing the expression of key adipocyte transcriptional regulators CCAAT/enhancer-binding protein ß (C/EBP-ß), C/EBP-α, and peroxisome proliferator-activated receptor γ (PPAR-γ). Furthermore, the interaction between NINJ2 and INSR/IGF1R is needed for maintaining insulin sensitivity in adipocytes and muscle via AKT and glucose transporter type 4. Notably, adenovirus-mediated NINJ2 overexpression can ameliorate diet-induced insulin resistance in mice. CONCLUSIONS: In conclusion, these findings reveal NINJ2 as an important new facilitator of insulin receptors, and the authors propose a unique regulatory mechanism between insulin signaling, adipogenesis, and insulin resistance.


Assuntos
Moléculas de Adesão Celular Neuronais , Resistência à Insulina , Animais , Camundongos , Células 3T3-L1 , Adipogenia/genética , Diferenciação Celular/genética , Doença da Artéria Coronariana , Glucose/metabolismo , Insulina , Resistência à Insulina/genética , PPAR gama/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Moléculas de Adesão Celular Neuronais/genética
14.
Neural Netw ; 158: 359-368, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36516542

RESUMO

Unsupervised graph-level representation learning has recently shown great potential in a variety of domains, ranging from bioinformatics to social networks. Plenty of graph contrastive learning methods have been proposed to generate discriminative graph-level representations recently. They typically design multiple types of graph augmentations and enforce a graph to have consistent representations under different views. However, these techniques mostly neglect the intrinsic hierarchical structure of the graph, resulting in a limited exploration of semantic information for graph representation. Moreover, they often rely on a large number of negative samples to prevent collapsing into trivial solutions, while a great need for negative samples may lead to memory issues during optimization in graph domains. To address the two issues, this paper develops an unsupervised graph-level representation learning framework named Hierarchical Graph Contrastive Learning (HGCL), which investigates the hierarchical structural semantics of a graph at both node and graph levels. Specifically, our HGCL consists of three parts, i.e., node-level contrastive learning, graph-level contrastive learning, and mutual contrastive learning to capture graph semantics hierarchically. Furthermore, the Siamese network and momentum update are further involved to release the demand for excessive negative samples. Finally, the experimental results on both benchmark datasets for graph classification and large-scale OGB datasets for transfer learning demonstrate that our proposed HGCL significantly outperforms a broad range of state-of-the-art baselines.


Assuntos
Aprendizado Profundo , Aprendizagem , Benchmarking , Biologia Computacional , Movimento (Física)
15.
Environ Pollut ; 317: 120845, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36496063

RESUMO

Efficient degradation of residual antibiotics in livestock and poultry feces by black soldier flies (BSFs) has been widely reported. Nevertheless, the effects of widely detected microplastics in feces on the dynamic reduction of antibiotics and the transfer of gut bacterial resistome remain unclear. In this study, red fluorescence-labeled microplastics are observed to be abundantly distributed in BSFs gut, which caused epithelial cell damage along with gut peristalsis and friction, thereby releasing reactive oxygen species and activating the antioxidant enzyme system. In addition, they result in not only in inflammatory cytokine release to induce gut inflammation, but fecal hardening because of mucus released from the BSFs, thereby hindering organic mineralization and antibiotic degradation. Besides, the gut pathogenic bacteria easily obtain growth energy and crowded out ecological niches by reducing nitrate produced by inflammatory host cells to nitrite with nitrate reductase. Consequently, linear discriminant analysis effect size and detrended correspondence analysis found that microplastic intake significantly reshape the microbial community structure and cause the significant reduction of several important organic-decomposing bacteria and probiotics (e.g., Pseudomonadales, Coriobacteriales, Lachnospirales, and Ruminococcaceae). In addition, a large number of pathogenic bacteria (e.g., Enterococcaceae, Hungateiclostridiaceae, and Clostridia) are enriched in feces and BSFs gut. Weighted correlation network analysis and bubble diagram analysis indicate that microplastic intake intensified gut colonization of pathogenic bacteria carrying antibiotic-resistant genes/mobile genetic elements, driving the bloom of antibiotic resistance in transformed fecal piles. Therefore, microplastics in feces should be isolated as much as possible before insect transformation.


Assuntos
Dípteros , Microplásticos , Animais , Plásticos/farmacologia , Gado , Resistência Microbiana a Medicamentos/genética , Bactérias , Antibacterianos/toxicidade , Fezes/microbiologia , Genes Bacterianos
16.
Proc Natl Acad Sci U S A ; 120(1): e2211282119, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574646

RESUMO

Growing evidence suggests that fine particulate matter (PM2.5) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO3-), sulfate (SO42-), ammonium (NH4+), and soil dust (DUST). To investigate the impact of long-term exposure to PM2.5 constituents on incident all-cause dementia and Alzheimer's disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration-response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM2.5 and its major constituents. An interquartile range increase in PM2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM2.5 constituents, associations remained significant for BC, OM, SO42-, and NH4+ for both end points (even after adjustments of other constituents), among which BC and SO42- showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM2.5 is significantly associated with higher rates of incident dementia and AD and that SO42-, BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Demência , Humanos , Idoso , Estados Unidos/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Estudos de Coortes , Medicare , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Poeira , Demência/induzido quimicamente , Demência/epidemiologia , Exposição Ambiental/efeitos adversos , China
17.
ACS Appl Mater Interfaces ; 15(1): 416-431, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36562739

RESUMO

Oral wounds under diabetic conditions display a significant delay during the healing process, mainly due to oxidative stress-induced inflammatory status and abnormal immune responses. Besides, the wet and complicated dynamic environment of the oral cavity impedes stable treatment of oral wounds. To overcome these, a biomimetic hydrogel adhesive was innovatively developed based on a mussel-inspired multifunctional structure. The adhesive displays efficient adhesion and mechanical harmony on the oral mucosa through enhanced bonding in an acidic proinflammatory environment. The bioadhesive hydrogel exhibits excellent antioxidative properties by mimicking antioxidative enzymatic activities to reverse reactive oxygen species (ROS)-mediated immune disorders. Experiments on oral wounds of diabetic rats showed that this hydrogel adhesive could effectively protect against mucosal wounds and obviously shorten the inflammatory phase, thus promoting the wound-healing process. Therefore, this study offers a promising therapeutic choice with the potential to advance the clinical treatment of diabetic oral wounds.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus , Animais , Ratos , Hidrogéis/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Aceleração , Antioxidantes , Cicatrização
18.
Med Biol Eng Comput ; 61(2): 511-523, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36534372

RESUMO

During flexible gastroscopy, physicians have extreme difficulties to self-localize. Camera tracking method such as simultaneous localization and mapping (SLAM) has become a research hotspot in recent years, allowing tracking of the endoscope. However, most of the existing solutions have focused on tasks in which sufficient texture information is available, such as laparoscope tracking, and cannot be applied to gastroscope tracking since gastroscopic images have fewer textures than laparoscopic images. This paper proposes a new monocular SLAM framework based on scale-invariant feature transform (SIFT) and narrow-band imaging (NBI), which extracts SIFT features instead of oriented features from accelerated segment test (FAST) and rotated binary robust independent elementary features (BRIEF) features from gastroscopic NBI images, and performs feature retention based on the response sorting strategy for achieving more matches. Experimental results show that the root mean squared error of the proposed algorithm can reach a minimum of 2.074 mm, and the pose accuracy can be improved by up to 25.73% compared with oriented FAST and rotated BRIEF (ORB)-SLAM. SIFT features and response sorting strategy can achieve more accurate matching in gastroscopic NBI images than other features and homogenization strategy, and the proposed algorithm can also run successfully on real clinical gastroscopic data. The proposed algorithm has the potential clinical value to assist physicians in locating the gastroscope during gastroscopy.


Assuntos
Algoritmos , Gastroscópios
19.
Clin Neurophysiol ; 146: 89-96, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36563555

RESUMO

OBJECTIVE: We aimed to investigate the transcranial direct current stimulation (tDCS)-induced facilitation of early consolidation over a period of extended training sessions and explored the effect of tDCS on visual perceptual learning (VPL) improvement during online learning and offline consolidation. METHODS: In the current double-blind sham-controlled study, twenty-four healthy participants were trained on coherent motion direction identification for 5 consecutive sessions. Performance was assessed at the pre- and posttests. Anodal or sham tDCS of the left human middle temporal region (hMT+) was applied immediately after the completion of daily training (termed early consolidation). RESULTS: The magnitude of improvement between anodal and sham tDCS was marginally significant, supporting the beneficial effect of anodal tDCS on VPL by stimulating early consolidation. Additionally, anodal tDCS induced a larger improvement between the first two training sessions than sham tDCS. No effect of anodal tDCS was found on the within-session improvement. CONCLUSIONS: The above results indicated that anodal tDCS facilitates offline consolidation during the early period of the whole training series, not online learning. The possible neural mechanisms and limitations (sample size and persistent effects) were discussed. SIGNIFICANCE: Our findings support the use of the combination of tDCS and behavioral training in facilitating visual rehabilitation and contribute to a deeper understanding of learning processes by neuromodulation procedures.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Aprendizagem/fisiologia , Voluntários Saudáveis , Método Duplo-Cego
20.
Clin Transl Med ; 13(1): e1149, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36578176

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) play a crucial role in tumour initiation and progression. However, little is known about their contributions to p53-related bladder cancer (BC) inhibition. METHODS: By using high-throughput sequencing, we screened the expression profiles of lncRNAs in BC and adjacent non-tumour tissues. The roles of a novel lncRNA, named LNPPS [a lncRNA for programmed cell death 5 (PDCD5) and p53 stability], were determined by gain- and loss-of-function assays. RNA pull-down followed by mass spectrometry analysis, RNA immunoprecipitation assays and other immunoprecipitation assays were performed to reveal the interactions among LNPPS, PDCD5 and p53, and the regulatory effect of LNPPS on the complex ubiquitination network comprising PDCD5, p53 and mouse double minute 2 homologue (MDM2). RESULTS: LNPPS was downregulated in BC and markedly inhibited the viability of BC cells by inducing PDCD5/p53-related apoptosis in vivo and in vitro. Mechanistically, LNPPS, serving as a scaffold, connected PDCD5 and p53 with nucleotides (nt) located at 121-251 nt and 251-306 nt of LNPPS, respectively. This process allowed LNPPS to protect PDCD5 from proteasomal degradation by blocking its K20 site ubiquitination. On the other hand, the increased interaction between PDCD5 and p53 displaced p53 from the MDM2-p53 ubiquitination complex, resulting in an increase in p53 expression and related apoptosis levels. Moreover, LNPPS could induce the accumulation of PDCD5 and p53 in the nucleus and exert a synergistic effect on the prevention of protein degradation. In addition, we confirmed that the downregulation of LNPPS in BC was mediated by the decreased N6-methyladenosine (m6 A) modification. CONCLUSION: Our findings highlight a novel cross-talk between LNPPS and the PDCD5/p53/MDM2 ubiquitination axis in BC development, indicating its potential as a therapeutic target for BC patients.


Assuntos
RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Animais , Camundongos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Dano ao DNA , Proteínas de Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/genética , Humanos
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