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1.
J Org Chem ; 89(11): 7812-7820, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38779840

RESUMO

In this paper, the regioselectivity of electrochemical Co(II)-catalyzed [2 + 2 + 2] cycloaddition of terminal alkynes was investigated using density functional theory. We explored in detail the energy profiles for both 1,2,4- and 1,3,5-regioselectivity pathways and revealed the origin of the regioselectivity. Two kinds of conformational isomers derived from the different coordination modes of alkynes with cobaltacyclopentadiene have been found, which were formed through electrochemically mediated redox processes. The regioselectivity of the reaction depends on the two coordination modes. When the Co(II) center attacks α-C of the third alkyne, while ß2-C in cyclopentadiene bonds to ß-C of the alkyne, the reaction favors the formation of 1,2,4-products. In contrast, when the Co(II) center connects to ß-C of the alkyne, it forms only the 1,3,5-products via [4 + 2] cycloaddition because of the steric repulsion between the bulky ligand on Co(II) and the phenyl group in the alkyne.

2.
Acta Pharmacol Sin ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982150

RESUMO

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

3.
Appl Microbiol Biotechnol ; 108(1): 32, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38175237

RESUMO

Black soldier fly larvae (BSFL) are considered a sustainable ingredient in livestock feed. However, addressing issues related to feed substrate and intestinal microbiota is essential to ensure optimal larval development. The aim of this study was to assess and elucidate the contribution of substrate nutrients and intestinal microbes to protein and fat synthesis in BSFL. The results showed that larvae that were fed high-quality feed (chicken feed) had high fat biomass, while larvae that were fed medium-quality feed (wheat bran) had high protein biomass. These results indicate that the original nutritional content of the feed cannot fully explain larval growth and nutrient utilization. However, the phenomenon could be explained by the functional metabolism of intestinal microbes. Chicken feed enhanced the fatty acid metabolism of middle intestine microorganisms in larvae within 0-7 days. This process facilitated larval fat synthesis. In contrast, wheat bran stimulated the amino acid metabolism in posterior intestine microorganisms in larvae within 4-7 days, leading to better protein synthesis. The findings of this study highlight the importance of the microbial functional potential in the intestine in regulating protein and lipid synthesis in BSFL, which is also influenced by the type of feed. In conclusion, our study suggests that both feed type and intestinal microbes play a crucial role in efficiently converting organic waste into high-quality insect protein and fat. Additionally, a mixed culture of chicken feed and wheat bran was found to be effective in promoting larval biomass while reducing feed costs. KEY POINTS: • Intestinal microbes explain BSFL growth better than feed substrates. • Chicken feed promotes fatty acid synthesis in the middle intestine • Wheat bran promotes amino acid synthesis in the posterior intestine.


Assuntos
Microbiota , Animais , Larva , Galinhas , Fibras na Dieta , Intestinos , Aminoácidos , Ácidos Graxos
4.
BMC Anesthesiol ; 24(1): 218, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956515

RESUMO

BACKGROUND: As a new type of intravenous anesthetic, ciprofol has the advantages of fast onset of action, fast recovery and high clearance rate. This study aimed to investigate the effectiveness and safety of ciprofol versus traditional propofol for anesthesia and sedation in and out of the operating room. METHODS: We searched the literature in PubMed, Web of Science, Cochrane Library, and Embase databases from January 2021 to December 2023. All clinical studies comparing the sedative effects of propofol and ciprofol, both inside and outside the operating room, were included in our trial. The main outcome measures were induction time and incidence of injection-site pain. Data are merged using risk ratio and standardized mean difference with 95% confidence interval. Subgroup analysis, meta-regression, sensitivity analysis, and publication bias were performed. The study protocol was prospectively registered with PROSPERO (CRD42023447747). RESULTS: A total of 15 randomized, controlled trials involving 2002 patients were included in this study. Compared with propofol, ciprofol has a longer induction time in the operating room but a shorter induction time in non-operating room settings. Ciprofol can effectively reduce the risk of injection-site pain and respiratory depression both inside and outside the operating room. In addition, the risk of drug-related hypotension induced with ciprofol in the operating room is lower, but the awakening time is also longer. Meta-regression analysis showed that neither age nor BMI were potential sources of heterogeneity. Funnel plot, egger and begg tests showed no significant publication bias. Sensitivity analyzes indicate that our results are robust and reliable. CONCLUSION: Ciprofol has absolute advantages in reducing the risk of injection-site pain and respiratory depression, both in and outside operating room. Intraoperative use of ciprofol reduces the risk of drug-related hypotension and may also reduce the risk of intraoperative physical movements. However, ciprofol may have longer induction and awakening time than propofol.


Assuntos
Anestésicos Intravenosos , Salas Cirúrgicas , Propofol , Propofol/efeitos adversos , Propofol/administração & dosagem , Humanos , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
5.
BMC Anesthesiol ; 24(1): 243, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026147

RESUMO

OBJECTIVES: Currently, there remains debate regarding the optimal anesthesia approach for patients undergoing intra-arterial therapy for acute ischemic stroke. Therefore, we conducted a comparative analysis to assess the effects of general anesthesia versus non general anesthesia on patient outcomes. METHODS: The research methodology entailed comprehensive searches of prominent databases such as the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. Data synthesis employed techniques like risk ratio or standardized mean difference, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024523079). RESULTS: A total of 27 trials and 12,875 patients were included in this study. The findings indicated that opting for non-general anesthesia significantly decreased the risk of in-hospital mortality (RR, 1.98; 95% CI: 1.50 to 2.61; p<0.00001; I2 = 20%), as well as mortality within three months post-procedure (RR, 1.24; 95% CI: 1.15 to 1.34; p<0.00001; I2 = 26%), while also leading to a shorter hospitalization duration (SMD, 0.24; 95% CI: 0.15 to 0.33; p<0.00001; I2 = 44%). CONCLUSION: Ischemic stroke patients who undergo intra-arterial treatment without general anesthesia have a lower risk of postoperative adverse events and less short-term neurological damage. In routine and non-emergency situations, non-general anesthetic options may be more suitable for intra-arterial treatment, offering greater benefits to patients. In addition to this, the neuroprotective effects of anesthetic drugs should be considered more preoperatively and postoperatively.


Assuntos
AVC Isquêmico , Humanos , Anestesia Geral/métodos , Anestesia/métodos , Mortalidade Hospitalar
6.
BMC Surg ; 24(1): 182, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877438

RESUMO

PURPOSE: We describe a surgical technique for ACL reconstruction combined with anterolateral structure reinforcement and report early clinical follow-up results. METHODS: The semitendinosus and gracilis tendons are braided into 5 strands and the ACL femoral tunnel and tibial tunnel are created. The graft is passed through the tunnel with the use of a traction suture and the tibial end is fixed with absorbable interference screws at 30° of knee flexion. The ACL graft traction suture is used as an anterolateral reconstruction structure to pass through the proximal exit of the ACL femoral tunnel and then through the depth of the iliotibial bundle to the anterior to Gerdy's tubercle, a bony tunnel is created from the anterior to Gerdy's tubercle to the goose foot, and the traction suture is passed through this bony tunnel to form a Loop structure at 20° of knee flexion. Between March 2021 and May 2022 IKDC score, Lysholm score, and Tegner score were performed preoperatively and 6-12 months postoperatively in 24 consecutive patients who met the indications for this procedure and underwent surgery. The patient's maximum flexion angle, the circumference of the thigh, and the stress X-ray between the operated and healthy knee were measured. RESULTS: Patients showed significant improvement in IKDC score, Lysholm score and Tegner score at a mean follow-up of 7 months postoperatively compared to preoperatively. No significant increase in anterior tibial displacement was found between the patient's operated side and the healthy side. CONCLUSION: The Loop technique ACLR combined with ALSA can be used in patients with an ACL tear combined with a high degree of positive pivot shift. The patient's subjective perception was significantly improved from the preoperative period and knee stability was restored. LEVEL OF EVIDENCE: IV, therapeutic study.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Humanos , Reconstrução do Ligamento Cruzado Anterior/métodos , Adulto , Masculino , Feminino , Lesões do Ligamento Cruzado Anterior/cirurgia , Resultado do Tratamento , Adulto Jovem , Seguimentos , Técnicas de Sutura , Amplitude de Movimento Articular/fisiologia , Pessoa de Meia-Idade , Tendões/transplante , Tíbia/cirurgia , Adolescente
7.
Arch Pharm (Weinheim) ; : e2400137, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963324

RESUMO

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

8.
Int J Environ Health Res ; : 1-13, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041841

RESUMO

Evidence on the impacts of PM1, PM2.5, and PM10 on the hospital admissions, length of hospital stays (LOS), and hospital expenses among patients with cardiovascular disease (CVD) is still limited in China, especially in rural areas. This study was performed in eight counties of Fuyang from 1 January 2015 to 30 June 2017. We use a three-stage time-series analysis to explore the effects of short-term exposure to PM1, PM2.5, and PM10 on hospital admissions, LOS, and hospital expenses for CVDs. An increment of 10 ug/m3 in PM1, PM2.5, and PM10 corresponded to an increment of 1.82% (95% CI: 1.34, 2.30), 0.96% (95% CI: 0.44, 1.48), and 0.79% (95% CI: 0.63%, 0.95%) in CVD hospital admissions, respectively. We observed that daily concentrations of PMs were associated with an increase in hospital admissions, LOS, and expenses for CVDs. Sustained endeavors are required to reduce air pollution so as to attenuate disease burdens from CVDs.

9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 425-434, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38953267

RESUMO

Alzheimer's disease (AD) is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continuously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of ß-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-ß protein (Aß),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aß.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aß accumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treatment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.


Assuntos
Doença de Alzheimer , eIF-2 Quinase , Doença de Alzheimer/metabolismo , Humanos , eIF-2 Quinase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Fosforilação , Encéfalo/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo
10.
J Am Chem Soc ; 145(1): 359-376, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36538367

RESUMO

The intermediacy of alkoxy radicals in cerium-catalyzed C-H functionalization via H-atom abstraction has been unambiguously confirmed. Catalytically relevant Ce(IV)-alkoxide complexes have been synthesized and characterized by X-ray diffraction. Operando electron paramagnetic resonance and transient absorption spectroscopy experiments on isolated pentachloro Ce(IV) alkoxides identified alkoxy radicals as the sole heteroatom-centered radical species generated via ligand-to-metal charge transfer (LMCT) excitation. Alkoxy-radical-mediated hydrogen atom transfer (HAT) has been verified via kinetic analysis, density functional theory (DFT) calculations, and reactions under strictly chloride-free conditions. These experimental findings unambiguously establish the critical role of alkoxy radicals in Ce-LMCT catalysis and definitively preclude the involvement of chlorine radical. This study has also reinforced the necessity of a high relative ratio of alcohol vs Ce for the selective alkoxy-radical-mediated HAT, as seemingly trivial changes in the relative ratio of alcohol vs Ce can lead to drastically different mechanistic pathways. Importantly, the previously proposed chlorine radical-alcohol complex, postulated to explain alkoxy-radical-enabled selectivities in this system, has been examined under scrutiny and ruled out by regioselectivity studies, transient absorption experiments, and high-level calculations. Moreover, the peculiar selectivity of alkoxy radical generation in the LMCT homolysis of Ce(IV) heteroleptic complexes has been analyzed and back-electron transfer (BET) may have regulated the efficiency and selectivity for the formation of ligand-centered radicals.


Assuntos
Cloro , Hidrogênio , Hidrogênio/química , Cinética , Ligantes , Metais , Etanol , Catálise
11.
Small ; 19(50): e2304233, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37616506

RESUMO

Monolayer tungsten disulfide (ML WS2 ) is believed as an ideal photosensitive material due to its small direct bandgap, large exciton/trion binding energy, high carrier mobility, and considerable quantum conversion efficiency. Compared with other photosensitive devices, planar field emission (FE)-type photodetectors with a full-plane structure should simultaneously have rapider switching speed and lower power consumption. In this work, ML WS2 microtips are fabricated by electron beam lithography (EBL) way and used to construct a planar FE-type photodetector. By optimization design, ML WS2 with three microtips can exhibit the maximum current density as high as  52 A cm-2 (@300 V µm-1 ), and the largest photoresponsivity is up to 6.8 × 105 A W-1 under green light irradiation, superior to that of many other ML transition metal dichalcogenide (TMDC) detectors. More interestingly, ML WS2 devices with microtips can effectively solve the contradictory problem between large photoresponsivity and rapid switching speed. The excellent photoresponse performances of ML WS2 with microtips should be attributed to their high carrier mobility, sharp emission edge, ultrahigh quantum yield, and unique planar FE device structure. Our research may shed new light on exploring the fabrication technology and photosensitive mechanism of two dimensional (2D) material-based planar FE photodetectors.

12.
Acta Pharmacol Sin ; 44(11): 2151-2168, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37420104

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 µM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aß generation by inhibiting the ß-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aß plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aß generation in early AD, which is a potential therapeutic intervention for early AD treatment.


Assuntos
Doença de Alzheimer , Neuroblastoma , Doenças Neurodegenerativas , Camundongos , Humanos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Camundongos Transgênicos , Retina/metabolismo , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo
13.
Lipids Health Dis ; 22(1): 214, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049817

RESUMO

BACKGROUND: Steatosis and inflammation are the hallmarks of nonalcoholic steatohepatitis (NASH). Rotundic acid (RA) is among the key triterpenes of Ilicis Rotundae Cortex and has exhibited multipronged effects in terms of lowering the lipid content and alleviating inflammation. The study objective is to systematically evaluate the potential mechanisms through which RA affects the development and progression of NASH. METHODS: Transcriptomic and proteomic analyses of primary hepatocytes isolated from the control, high-fat diet-induced NASH, and RA treatment groups were performed through Gene Ontology analysis and pathway enrichment. Hub genes were identified through network analysis. Integrative analysis revealed key RA-regulated pathways, which were verified by gene and protein expression studies and cell assays. RESULTS: Hub genes were identified and enriched in the Toll-like receptor 4 (TLR4)/activator protein-1 (AP1) signaling pathway and glycolysis pathway. RA reversed glycolysis and attenuated the TLR4/AP1 pathway, thereby reducing lipid accumulation and inflammation. Additionally, lactate release in L-02 cells increased with NaAsO2-treated and significantly decreased with RA treatment, thus revealing that RA had a major impact on glycolysis. CONCLUSIONS: RA is effective in lowering the lipid content and reducing inflammation in mice with NASH by ameliorating glycolysis and TLR4/AP1 pathways, which contributes to the existing knowledge and potentially sheds light on the development of therapeutic interventions for patients with NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Triterpenos , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Fígado/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteômica , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Transdução de Sinais/genética , Inflamação/metabolismo , Lipídeos , Camundongos Endogâmicos C57BL
14.
Sensors (Basel) ; 24(1)2023 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-38202955

RESUMO

This work aims at providing a solution to data scarcity by allowing end users to generate new images while carefully controlling building shapes and environments. While Generative Adversarial Networks (GANs) are the most common network type for image generation tasks, recent studies have only focused on RGB-to-RGB domain transfer tasks. This study utilises a state-of-the-art GAN network for domain transfer that effectively transforms a multi-channel image from a 3D scene into a photorealistic image. It relies on a custom dataset that pairs 360° images from a simulated domain with corresponding 360° street views. The simulated domain includes depth, segmentation map, and surface normal (stored in seven-channel images), while the target domain is composed of photos from Paris. Samples come in pairs thanks to careful virtual camera positioning. To enhance the simulated images into photorealistic views, the generator is designed to preserve semantic information throughout the layers. The study concludes with photorealistic-generated samples from the city of Paris, along with strategies to further refine model performance. The output samples are realistic enough to be used to train and improve future AI models.

15.
Int J Mol Sci ; 25(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38203500

RESUMO

Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Hormônios Peptídicos , Animais , Camundongos , Angiotensina II , Enzima de Conversão de Angiotensina 2/genética , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antivirais , Quimases/genética , Nefropatias Diabéticas/genética , Dieta Hiperlipídica , Modelos Animais de Doenças , Camundongos Knockout , Sistema Renina-Angiotensina , Serina Proteases
16.
Eur J Neurosci ; 56(12): 6215-6226, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36266211

RESUMO

Motion opponency, first observed within the primate middle temporal cortex (MT), refers to the suppressing effect of opposite motion directions on neuronal activity. Namely, when opposing motion directional signals stimulate an MT neuron's receptive field, this neuron's response is comparable with that induced by flicker noise. Under such suppression, it is unknown whether any directional information is still represented at MT. In this study, we applied support vector machine (SVM) learning to human functional magnetic resonance imaging data to investigate if any motion defined orientation information was still available from suppressed MT. We found that, at least at the level of ±45° discrimination, such orientation information was still available. Interestingly, after behavioural perceptual learning that improved human discrimination of fine orientation discrimination (e.g. 42° vs. 48°) using the MT-suppressive motion stimuli, the SVM discrimination of ±45° worsened when functional magnetic resonance imaging (fMRI) signals at post-learning MT were used. This result is consistent with findings in Thompson et al. (2013) that, post-perceptual learning, MT suppression was not released, suggesting that motion opponency was perhaps functionally too important for perceptual learning to overcome.


Assuntos
Percepção de Movimento , Animais , Humanos , Percepção de Movimento/fisiologia , Lobo Temporal/fisiologia , Movimento (Física) , Aprendizagem , Imageamento por Ressonância Magnética/métodos , Estimulação Luminosa/métodos
17.
Arch Virol ; 167(2): 493-499, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34997320

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in the global swine industry. A rapid and sensitive on-site detection method for PRRS virus (PRRSV) is critically important for diagnosing PRRS. In this study, we established a method that combines reverse transcription recombinase polymerase amplification (RT-RPA) with a lateral flow dipstick (LFD) for detecting North American PRRSV (PRRSV-2). The primers and probe were designed based on the conserved region of all complete PRRSV-2 genomic sequences available in China (n = 512) from 1996 to 2020. The detection limit of the assay was 5.6 × 10-1 median tissue culture infection dose (TCID50) per reaction within 30 min at 42 °C, which was more sensitive than that of reverse transcription polymerase chain reaction (RT-PCR) (5.6 TCID50 per reaction). The assay was highly specific for the epidemic lineages of PRRSV-2 in China and did not cross-react with pseudorabies virus, porcine circovirus 2, classical swine fever virus, or porcine epidemic diarrhea virus. The assay performance was evaluated by testing 179 samples and comparing the results with those of quantitative RT-PCR (RT-qPCR). The results showed that the detection coincidence rate of RT-RPA and RT-qPCR was 100% when the cycle threshold values of RT-qPCR were < 32. The assay provides a new alternative for simple and reliable detection of PRRSV-2 and has great potential for application in the field.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Síndrome Respiratória e Reprodutiva Suína/diagnóstico , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Recombinases , Transcrição Reversa , Sensibilidade e Especificidade , Suínos
18.
BMC Cardiovasc Disord ; 22(1): 326, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35869446

RESUMO

BACKGROUND: Percutaneous left atrial appendage (LAA) occlusion is effective for stroke prevention in patients with atrial fibrillation. LAA can have a complex anatomy, such as multiple lobes or a large orifice, which may render it unsuitable for occlusion using regular devices. We aimed to investigate the feasibility, safety, and short-term efficacy of the small-umbrella LAmbre device for morphologically complicated LAA. METHODS: We retrospectively enrolled 129 consecutive patients who underwent LAA occlusion using the LAmbre device; the small-umbrella LAmbre device was used in 30 of these patients. We analyzed patients' characteristics, procedural details, and outcomes. RESULTS: Twenty-two patients (73.3%) had multilobed (≥ 2) LAA. The umbrella of the occluder was anchored in the branch in 9 patients and in the common trunks of branches in 13 patients. The landing zone and orifice diameters were 19.0 ± 4.39 mm and 27.4 ± 3.95 mm, respectively. The sizes of the umbrella and occluder cover were 22.0 ± 3.42 mm and 34.3 ± 2.75 mm, respectively. At 3-month follow-up transesophageal echocardiography in 24 patients, no peri-device residual flow was reported. Device thrombosis was detected in one patient at 3 months and disappeared after 3 months of anticoagulation. Ischemic stroke occurred in one patient; no other adverse events were reported. CONCLUSIONS: Occlusion of morphologically complicated LAA using the small-umbrella LAmbre device was feasible, safe, and effective in patients with atrial fibrillation in this study. This occluder provides an alternative for patients who cannot be treated with regular-sized LAA occlusion devices.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Dispositivo para Oclusão Septal , Acidente Vascular Cerebral , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Cateterismo Cardíaco/efeitos adversos , Ecocardiografia Transesofagiana/efeitos adversos , Humanos , Estudos Retrospectivos , Dispositivo para Oclusão Septal/efeitos adversos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
19.
BMC Surg ; 22(1): 298, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915446

RESUMO

BACKGROUND: Stapled haemorrhoidopexy (SH) has resulted in a unique collection of procedural complications with postoperative mucocele a particularly rare example. This study is designed to comprehensively describe the characteristics of rectal mucocele and discuss its pathogenesis following SH surgery. METHODS: A database of patients presenting with a rectal mucocele following an SH procedure was established and studied retrospectively. RESULTS: Seven patients (5 males; median age 32 years, range 20-75 years) were identified. All patients complained of variable anal discomfort with 5/7 presenting with inconstant anal pain, 2 with de novo evacuatory difficulty. These cases appeared at a median time of 6 months (range 2-84 months) after SH surgery. CONCLUSION: Rectal Mucocele develops when mucosal fragments become embedded and isolated under the mucosa. It is a preventable complication of SH surgery by ensuring correct purse string placement prior to stapled haemorrhoid excision.


Assuntos
Hemorroidas , Mucocele , Adulto , Idoso , Hemorroidas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mucocele/etiologia , Mucocele/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reto/cirurgia , Estudos Retrospectivos , Grampeamento Cirúrgico/efeitos adversos , Grampeamento Cirúrgico/métodos , Resultado do Tratamento , Adulto Jovem
20.
Sensors (Basel) ; 22(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36560049

RESUMO

Path planning plays an important role in navigation and motion planning for robotics and automated driving applications. Most existing methods use iterative frameworks to calculate and plan the optimal path from the starting point to the endpoint. Iterative planning algorithms can be slow on large maps or long paths. This work introduces an end-to-end path-planning algorithm based on a fully convolutional neural network (FCNN) for grid maps with the concept of the traversability cost, and this trains a general path-planning model for 10 × 10 to 80 × 80 square and rectangular maps. The algorithm outputs the lowest-cost path while considering the cost and the shortest path without considering the cost. The FCNN model analyzes the grid map information and outputs two probability maps, which show the probability of each point in the lowest-cost path and the shortest path. Based on the probability maps, the actual optimal path is reconstructed by using the highest probability method. The proposed method has superior speed advantages over traditional algorithms. On test maps of different sizes and shapes, for the lowest-cost path and the shortest path, the average optimal rates were 72.7% and 78.2%, the average success rates were 95.1% and 92.5%, and the average length rates were 1.04 and 1.03, respectively.


Assuntos
Veículos Autônomos , Robótica , Algoritmos , Redes Neurais de Computação , Robótica/métodos , Movimento (Física)
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