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1.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 213-222, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38595236

RESUMO

OBJECTIVE: To evaluate the developmental toxicity of Cry1Ab protein by studying its effects on cell proliferation and differentiation ability using a developmental toxicity assessment model based on embryonic stem-cell. METHODS: Cry1Ab protein was tested in seven dose groups (31.25, 62.50, 125.00, 250.00, 320.00, 1 000.00, and 2 000.00 µg/L) on mouse embryonic stem cells D3 (ES-D3) and 3T3 mouse fibroblast cells, with 5-fluorouracil (5-FU) used as the positive control and phosphate buffer saline (PBS) as the solvent control. Cell viability was detected by CCK-8 assay to calculate the 50% inhibitory concentration (IC50) of the test substance for different cells. Additionally, Cry1Ab protein was tested in five dose groups (125.00, 250.00, 320.00, 1 000.00, and 2 000.00 µg/L) on ES-D3 cells, with PBS as the solvent control and 5-FU used for model validation. After cell treatment, cardiac differentiation was induced using the embryonic bodies (EBs) culture method. The growth of EBs was observed under a microscope, and their diameters on the third and fifth days were measured. The proportion of EBs differentiating into beating cardiomyocytes was recorded, and the 50% inhibition concentration of differentiation (ID50) was calculated. Based on a developmental toxicity discrimination function, the developmental toxicity of the test substances was classified. Furthermore, at the end of the culture period, mRNA expression levels of cardiac differentiation-related markers (Oct3/4, GATA-4, Nkx2.5, and ß-MHC) were quantitatively detected using real-time quantitative polymerase chain reaction (qPCR) in the collected EBs samples. RESULTS: The IC50 of 5-FU was determined as 46.37 µg/L in 3T3 cells and 32.67 µg/L in ES-D3 cells, while the ID50 in ES-D3 cells was 21.28 µg/L. According to the discrimination function results, 5-FU was classified as a strong embryotoxic substance. There were no statistically significant differences in cell viability between different concentrations of Cry1Ab protein treatment groups and the control group in both 3T3 cells and ES-D3 cells (P>0.05). Moreover, there were no statistically significant differences in the diameter of EBs on the third and fifth days, as well as their morphology, between the Cry1Ab protein treatment groups and the control group (P>0.05). The cardiac differentiation rate showed no statistically significant differences between different concentrations of Cry1Ab protein treatment groups and the control group (P>0.05). 5-FU significantly reduced the mRNA expression levels of ß-MHC, Nkx2.5, and GATA-4 (P < 0.05), showing a dose-dependent trend (P < 0.05), while the mRNA expression levels of the pluripotency-associated marker Oct3/4 exhibited an increasing trend (P < 0.05). However, there were no statistically significant differences in the mRNA expression levels of mature cardiac marker ß-MHC, early cardiac differentiation marker Nkx2.5 and GATA-4, and pluripotency-associated marker Oct3/4 between the Cry1Ab protein treatment groups and the control group (P>0.05). CONCLUSION: No developmental toxicity of Cry1Ab protein at concentrations ranging from 31.25 to 2 000.00 µg/L was observed in this experimental model.


Assuntos
Células-Tronco Embrionárias , Miócitos Cardíacos , Animais , Camundongos , Células-Tronco Embrionárias/metabolismo , Diferenciação Celular , Miócitos Cardíacos/metabolismo , Fluoruracila/toxicidade , RNA Mensageiro/metabolismo , Solventes/metabolismo , Solventes/farmacologia
2.
Pestic Biochem Physiol ; 199: 105797, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458690

RESUMO

Antennae and legs (primarily the tarsal segments) of insects are the foremost sensory organs that contact a diverse range of toxic chemicals including insecticides. Binding proteins expressed in the two tissues are potential molecular candidates serving as the binding and sequestering of insecticides, like chemosensory proteins (CSPs). Insect CSPs endowed with multiple roles have been suggested to participate in insecticide resistance, focusing mainly on moths, aphids and mosquitos. Yet, the molecular underpinnings underlying the interactions of cerambycid CSPs and insecticides remain unexplored. Here, we present binding properties of three antenna- and tarsus-enriched RhorCSPs (RhorCSP1, CSP2 and CSP3) in Rhaphuma horsfieldi to eight insecticide classes totaling 15 chemicals. From the transcriptome of this beetle, totally 16 CSP-coding genes were found, with seven full-length sequences. In phylogeny, these RhorCSPs were distributed dispersedly in different clades. Expression profiles revealed the abundant expression of RhorCSP1, CSP2 and CSP3 in antennae and tarsi, thus as representatives for studying the protein-insecticide interactions. Binding assays showed that the three RhorCSPs were tuned differentially to insecticides but exhibited the highest affinities with hexaflumuron, chlorpyrifos and rotenone (dissociation constants <13 µM). In particular, RhorCSP3 could interact strongly with 10 of tested insecticides, of which four residues (Tyr25, Phe42, Val65 and Phe68) contributed significantly to the binding of six, four, three and four ligands, respectively. Of these, the binding of four mutated RhorCSP3s to a botanical insecticide rotenone was significantly weakened compared to the wildtype protein. Furthermore, we also evidenced that RhorCSP3 was a broadly-tuned carrier protein in response to a wide variety of plant odorants outside insecticides. Altogether, our findings shed light on different binding mechanisms and odorant-tuning profiles of three RhorCSPs in R. horsfieldi and identify key residues of the RhorCSP3-insecticide interactions.


Assuntos
Besouros , Inseticidas , Animais , Inseticidas/farmacologia , Inseticidas/metabolismo , Tornozelo , Rotenona , Besouros/genética , Besouros/metabolismo , Insetos/genética , Transcriptoma , Filogenia , Proteínas de Insetos/metabolismo , Antenas de Artrópodes/metabolismo , Perfilação da Expressão Gênica
3.
Drug Des Devel Ther ; 18: 443-452, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370564

RESUMO

Purpose: Dexmedetomidine (Dex) is a potent and highly selective α2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC). Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 µg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded. Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P>0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P<0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P<0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P<0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P<0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P<0.05 for all). Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 µg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.


Assuntos
Colecistectomia Laparoscópica , Dexmedetomidina , Humanos , Bradicardia/induzido quimicamente , Estudos Prospectivos , Anestesia Geral , Dor Pós-Operatória/tratamento farmacológico , Pré-Medicação/métodos , Método Duplo-Cego
4.
iScience ; 27(1): 108729, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38230259

RESUMO

CircRNAs are implicated in colorectal cancer (CRC) development and progression. Protein O-fucosyltransferase 1 (POFUT1) plays an oncogenic role via activating Notch1 signaling in CRC. However, the roles of circPOFUT1, which is originated from POFUT1, have not been investigated. Our study showed circPOFUT1 was highly expressed in CRC tissues and cells. CircPOFUT1 enhanced the proliferation, migration and invasion of CRC cells, and promoted tumor growth and liver metastasis in vivo. It also reinforced stemness and chemoresistance of CRC cells. Mechanistically, circPOFUT1 regulated the function of E2F7 via sponging miR-653-5p, thereby transcriptionally inducing WDR66 expression and further promoting metastasis in CRC. On the other hand, circPOFUT1 promoted stemness and chemoresistance of CRC cells via stabilizing BMI1 in an IGF2BP1-dependent manner. In conclusion, circPOFUT1 fosters CRC metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38061252

RESUMO

Three tree-killing bark beetles belonging to the genus Tomicus, Tomicus yunnanensis, Tomicus brevipilosus and Tomicus minor (Coleoptera; Curculionidae, Scolytinae), are serious wood-borers with larvae feeding on the phloem tissues of Pinus yunnanensis. The three Tomicus beetles, in some cases, coexist in a same habitat, providing a best system for exploring the conservation and divergence of reproductive genes. Here, we applied comparative transcriptomics and molecular biology approaches to characterize reproductive-related genes in three sympatric Tomicus species. Illumina sequencing of female and male reproductive systems and residual bodies generated a large number of clean reads, representing 185,920,232 sequences in T. yunnanensis, 169,153,404 in T. brevipilosus and 178,493,176 in T. minor that were assembled into 32,802, 56,912 and 33,670 unigenes, respectively. The majority of the genes had detectable expression in reproductive tissues (FPKM >1), particularly those genes in T. brevipilosus accounting for 76.61 % of the total genes. From the transcriptomes, totally 838 genes encoding 463 detoxification enzymes, 339 chemosensory membrane proteins and 36 ionotropic glutamate receptors (iGluRs) were identified, including 622 reproductive tissue-expressed genes. Of these, members of carboxylesterases (COEs), ionotropic receptors (IRs), sensory neuron membrane proteins (SNMPs) and iGluRs were highly conserved in gene numbers and sequence identities across three Tomicus species. Further, expression profiling analyses revealed a number of genes expressed in reproductive tissues and the diverse expression characteristics in these beetles. The results provide evidence for the conservation and differences of reproductive genes among three sympatric closely related beetles, helping understand their different reproductive strategies and the maximization of the reproductive success.


Assuntos
Besouros , Gorgulhos , Animais , Gorgulhos/genética , Casca de Planta , Besouros/genética , Perfilação da Expressão Gênica , Transcriptoma , Proteínas de Membrana/genética
6.
Pestic Biochem Physiol ; 197: 105678, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38072535

RESUMO

The orientation of the oligophagous cone-feeding moth Dioryctria abietella (Lepidoptera: Pyralidae) to host plants primarily relies on olfactory-related proteins, particularly those candidates highly expressed in antennae. Here, through a combination of expression profile, ligand-binding assay, molecular docking and site-directed mutagenesis strategies, we characterized the chemosensory protein (CSP) gene family in D. abietella. Quantitative real-time PCR (qPCR) analyses revealed the detectable expression of all 22 DabiCSPs in the antennae, of which seven genes were significantly enriched in this tissue. In addition, the majority of the genes (19/22 relatives) had the expression in at least one reproductive tissue. In the interactions of four antenna-dominant DabiCSPs and different chemical classes, DabiCSP1 was broadly tuned to 27 plant-derived odors, three man-made insecticides and one herbicide with high affinities (Ki < 6.60 µM). By contrast, three other DabiCSPs (DabiCSP4, CSP6 and CSP17) exhibited a narrow odor binding spectrum, in response to six compounds for each protein. Our mutation analyses combined with molecular docking simulations and binding assays further identified four key residues (Tyr25, Thr26, Ile65 and Val69) in the interactions of DabiCSP1 and ligands, of which binding abilities of this protein to 12, 15, 16 and three compounds were significantly decreased compared to the wildtype protein, respectively. Our study reveals different odor binding spectra of four DabiCSPs enriched in antennae and identifies key residues responsible for the binding of DabiCSP1 and potentially active compounds for the control of this pest.


Assuntos
Mariposas , Humanos , Animais , Simulação de Acoplamento Molecular , Ligantes , Mariposas/metabolismo , Odorantes , Proteínas de Insetos/metabolismo , Antenas de Artrópodes/metabolismo
7.
ACS Macro Lett ; 12(11): 1423-1436, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37812608

RESUMO

Dispersity (D) as a critical parameter indicates the level of uniformity of the polymer molar mass or chain length. In the past several decades, the development of explicit equations for calculating D experiences a continual revolution. This viewpoint tracks the historical evolution of the explicit equations from living to reversible-deactivation polymerization systems. Emphasis is laid on displaying the charm of explicit D equations in batch reversible-deactivation radical polymerization (RDRP), with highlights of the relevant elegant mathematical manipulations. Some representative emerging applications enabled by the existing explicit equations are shown, involving nitroxide-mediated polymerization (NMP), atom transfer radical polymerization (ATRP), and reversible addition-fragmentation chain transfer (RAFT) polymerization systems. Stemming from the several outlined challenges and outlooks, sustained concerns about the explicit D equations are still highly deserved. It is expected that these equations will continue to play an important role not only in traditional polymerization kinetic simulation and design of experiments but also in modern intelligent manufacturing of precision polymers and classroom education.

8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(5): 837-842, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37879911

RESUMO

There are some limitations in the localization of epileptogenic zone commonly used by human eyes to identify abnormal discharges of intracranial electroencephalography in epilepsy. However, at present, the accuracy of the localization of epileptogenic zone by extracting intracranial electroencephalography features needs to be further improved. As a new method using dynamic network model, neural fragility has potential application value in the localization of epileptogenic zone. In this paper, the neural fragility analysis method was used to analyze the stereoelectroencephalography signals of 35 seizures in 20 patients, and then the epileptogenic zone electrodes were classified using the random forest model, and the classification results were compared with the time-frequency characteristics of six different frequency bands extracted by short-time Fourier transform. The results showed that the area under curve (AUC) of epileptic focus electrodes based on time-frequency analysis was 0.870 (delta) to 0.956 (high gamma), and its classification accuracy increased with the increase of frequency band, while the AUC by using neural fragility could reach 0.957. After fusing the neural fragility and the time-frequency characteristics of the γ and high γ band, the AUC could be further increased to 0.969, which was improved on the original basis. This paper verifies the effectiveness of neural fragility in identifying epileptogenic zone, and provides a theoretical reference for its further clinical application.


Assuntos
Eletroencefalografia , Epilepsia , Humanos , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Convulsões , Técnicas Estereotáxicas
9.
Brain Res ; 1821: 148610, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37783260

RESUMO

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease in the elderly. Freezing of Gait (FOG) is one of the common motor symptoms of PD, but the potential mechanism remains unclear. This study aimed to investigate the changes of brain functional network topology in PD patients with FOG. METHODS: The resting electroencephalogram (EEG) were acquired from15 PD patients with FOG (PD-FOG), 13 PD patients without FOG (PD-nFOG), and 16 healthy control (HC). Cognitive and motor functions were assessed using subjective scales. The whole-brain functional networks were constructed based on transfer entropy. Transfer entropy was used to analyse the information flow and causality in the network and the network connectivity was analyzed by graph theory. The characteristics of PD-FOG and PD-nFOG were compared by receiver operator characteristic (ROC) curve analysis. RESULTS: The θ bands brain network of PD-FOG, PD-nFOG and HC group was significantly different (P < 0.05). The average characteristic path length of the θ bands brain network was positively correlated with FOG Questionnaire (FOGQ). PD-FOG and PD-nFOG get high classification accuracy according to this feature. The information inflow in the frontal and occipital lobes and information outflow in the temporal lobe of PD-FOG patients in the θ bands increased significantly. CONCLUSIONS: The whole-brain functional network characteristics of PD-FOG in the θ bands can serve as potential biomarkers for early diagnosis of PD-FOG. Abnormal information flow of the frontal, occipital, and temporal lobes in the θ bands may be an important factor leading to FOG.


Assuntos
Transtornos Neurológicos da Marcha , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Idoso , Doença de Parkinson/complicações , Transtornos Neurológicos da Marcha/etiologia , Entropia , Encéfalo , Marcha
10.
Neuropsychologia ; 189: 108669, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37648106

RESUMO

To explore the relationship between pericardial meridian acupoints and brain, the electroencephalogram (EEG) signals were collected synchronously during transcutaneous electrical stimulation at PC3, PC5, PC7, and PC8 on the pericardial meridian in 21 healthy subjects. The cerebral cortex functional networks were constructed by standard low-resolution electromagnetic tomography (sLORETA), phase-locking value (PLV) and complex network methods. The prefrontal cortex (BA10), the orbitofrontal cortex (BA11), the middle temporal gyrus (BA21), the temporal gyrus (BA22), the temporal pole (BA38), the triangular part (BA44), the dorsolateral prefrontal cortex (BA46), and the inferior frontal cortex (BA47) were activated by electrical stimulation at PC3, PC5, PC7, and PC8 on the pericardium meridian. These activated brain regions are able to modulate both local and remote emotion and cognitive networks. Acupoint stimulation of pericardium meridian mainly activated the frontal and the temporal lobes. Compared with non-acupoint stimulation, the node degree in the frontal lobe of electrical stimulation at PC3 (p < 0.05), PC5 (p < 0.05), PC7 (p < 0.01), PC8 (p < 0.05) and the temporal lobe of PC3 (p < 0.05), PC5 (p < 0.05), PC7 (p < 0.05), PC8 (p < 0.01) were significantly increased. The clustering coefficient in the frontal lobe of the stimulation at PC3 (p < 0.05), PC5 (p < 0.05), PC7 (p < 0.01), PC8 (p < 0.05) and the temporal lobe of PC3 (p < 0.05), PC5 (p < 0.05), PC7 (p < 0.01), PC8 (p < 0.05) were significantly increased. The characteristic path length decreased and the global efficiency increased during acupoint stimulation. The changes of functional network of stimulated pericardium meridian through cerebral cortex may provide theoretical support for the specificity of meridian and acupoints.

11.
J Agric Food Chem ; 71(31): 11941-11956, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37526116

RESUMO

This study aimed to explore the enhancive effects of butterfly pea flower (BF) extracts on metabolic and immune homeostasis in a low-grade inflammation mouse model. The BF extract was found to contain mainly anthocyanins among other flavonoids. BF supplementation alleviated metabolic endotoxemia by lowering the plasma glucose, lipopolysaccharide (LPS), and tumor necrosis factor-α (TNF-α) levels and restored lipid metabolism and the balance between Treg and Th17 cells, thereby inhibiting the dysfunctional liver and abdominal white adipose tissues. BF extract increased the tight junction protein expression and reduced the expression of proinflammatory cytokines, therefore sustaining the colonic mucosa structure. Furthermore, BF extracts reshaped the gut microbiota structure characterized by significantly promoted SCFA-producing gut microbiota such as Akkermansia and Butyricicoccaceae. Additionally, BF extracts enhanced fecal primary bile acid (BA) levels and modulated bile acid signaling in the liver and ileum to facilitate BA synthesis for the restoration of lipid metabolism. In summary, anthocyanin-enriched BF extracts alleviated the profound negative dietary alterations and helped maintain the metabolic health by modulating the various aspects of the gut microenvironment and enhancing hepatic bile acid synthesis.


Assuntos
Antocianinas , Lipopolissacarídeos , Animais , Camundongos , Lipopolissacarídeos/efeitos adversos , Obesidade/metabolismo , Inflamação/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ácidos e Sais Biliares , Camundongos Endogâmicos C57BL
12.
Cell ; 186(16): 3414-3426.e16, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37541198

RESUMO

Lateral transduction (LT) is the process by which temperate phages mobilize large sections of bacterial genomes. Despite its importance, LT has only been observed during prophage induction. Here, we report that superantigen-carrying staphylococcal pathogenicity islands (SaPIs) employ a related but more versatile and complex mechanism of gene transfer to drive chromosomal hypermobility while self-transferring with additional virulence genes from the host. We found that after phage infection or prophage induction, activated SaPIs form concatamers in the bacterial chromosome by switching between parallel genomic tracks in replication bubbles. This dynamic life cycle enables SaPIbov1 to piggyback its LT of staphylococcal pathogenicity island vSaα, which encodes an array of genes involved in host-pathogen interactions, allowing both islands to be mobilized intact and transferred in a single infective particle. Our findings highlight previously unknown roles of pathogenicity islands in bacterial virulence and show that their evolutionary impact extends beyond the genes they carry.


Assuntos
Ilhas Genômicas , Fagos de Staphylococcus , Staphylococcus , Genoma Bacteriano , Staphylococcus/genética , Staphylococcus/patogenicidade , Virulência , Transdução Genética
13.
BMC Geriatr ; 23(1): 484, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563583

RESUMO

BACKGROUND AND AIM: DRP1 and OPA1 play important roles in mitochondrial fusion and fission. However, the role of DRP1 and OPA1 amplification in mitochondrial cognitive impairment has not been reported. This study aimed to investigate the relationship between DRP1 and OPA1 and the risk of cognitive impairment. METHODS: In this study, 45 elderly patients with diabetes admitted to the Lianyungang Second People's Hospital from September 2020 to January 2021 were included. The patients were divided into normal group, mild cognitive impairment group and dementia group by using MMSE score, and the clinical characteristics of the three groups were compared. The amplification multiples of the two genes' DNA were calculated by ΔΔCT and defined as 2- K. Spearman rank correlation was used to analyze the correlation between the DNA amplification multiples of patients' DRP1 and OPA1 and AD8 and MoCA scores. The sensitivity and specificity of DNA amplification multiples of DRP1 and OPA1 to predict clinical outcomes of diabetic cognitive impairment were evaluated using Receiver operator characteristic (ROC) curves. Multiple logistic regression was used to evaluate the relationship between DNA amplification factor of DRP1 and OPA1 and cognitive function. RESULTS: DRP1(2- K) and OPA1(2- K) significantly increased and decreased in dementia and MCI groups compared with the normal group (P ≤ 0.001). The DNA amplification factor of DRP1 was positively correlated with AD8 score and negatively correlated with MoCA score (P < 0.001). The DNA amplification factor of OPA1 was positively correlated with the MoCA score (P = 0.0002). Analysis of ROCs showed that the DNA amplification factor of OPA1 had a higher predictive value for dementia (P < 0.0001), and that it had a higher predictive value when used in combination with DRP1. Multiple logistic regression results showed that increased DNA amplification in DRP1 was associated with increased risk of dementia (OR 1.149;95%CI,1.035-1.275), and increased DNA amplification in OPA1 was associated with decreased risk of MCI (OR 0.004;95%CI,0.000-0.251) and dementia (OR 0.000;95%CI,0.000-0.134). CONCLUSION: DNA amplification multiples of DRP1 and OPA1 are associated with the risk of dementia in elderly patients and may serve as potential biomarkers.


Assuntos
Disfunção Cognitiva , Demência , Diabetes Mellitus , GTP Fosfo-Hidrolases , Utrofina , Idoso , Humanos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Demência/psicologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , DNA , Diagnóstico Precoce , GTP Fosfo-Hidrolases/genética , Dinâmica Mitocondrial/genética , Utrofina/genética
14.
Br J Anaesth ; 131(2): 253-265, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37474241

RESUMO

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).


Assuntos
Anestésicos Inalatórios , Delírio do Despertar , Neoplasias , Propofol , Humanos , Feminino , Idoso , Masculino , Propofol/efeitos adversos , Sevoflurano/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Seguimentos , Anestesia Geral/efeitos adversos , Delírio do Despertar/induzido quimicamente , Neoplasias/cirurgia
15.
Br J Anaesth ; 131(2): 266-275, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37474242

RESUMO

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.


Assuntos
Neoplasias , Propofol , Sevoflurano , Propofol/efeitos adversos , Sevoflurano/efeitos adversos , Neoplasias/cirurgia , Humanos , Masculino , Feminino , Idoso , Seguimentos , Anestésicos Intravenosos , Anestesia por Inalação , Sobreviventes de Câncer
16.
Physiol Mol Biol Plants ; 29(6): 783-790, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37520815

RESUMO

Root systems anchor plants to the substrate in addition to transporting water and nutrients, playing a fundamental role in plant survival. The LAZY1 gene mediates gravity signal transduction and participates in root and shoot development and auxin flow in many plants. In this study, a regulator, LsLAZY1, was identified from Leymus secalinus based on previous transcriptome data. The conserved domain and evolutionary relationship were further analyzed comprehensively. The role of LsLAZY1 in root development was investigated by genetic transformation and associated gravity response and phototropism assay. Subcellular localization showed that LsLAZY1 was localized in the nucleus. LsLAZY1 overexpression in Arabidopsis thaliana (Col-0) increased the length of the primary roots (PRs) and the number of lateral roots (LRs) compared to Col-0. Furthermore, 35S:LsLAZY1 transgenic seedlings affected auxin transport and showed a stronger gravitational and phototropic responses. It also promoted auxin accumulation at the root tips. These results indicated that LsLAZY1 affects root development and auxin transport. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01326-4.

17.
Skin Res Technol ; 29(7): e13402, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37522495

RESUMO

BACKGROUND: Age prediction powered by artificial intelligence (AI) can be used as an objective technique to assess the cosmetic effect of rejuvenation surgery. Existing age-estimation models are trained on public datasets with the Caucasian race as the main reference, thus they are impractical for clinical application in Chinese patients. METHODS: To develop and select an age-estimation model appropriate for Chinese patients receiving rejuvenation treatment, we obtained a face database of 10 529 images from 1821 patients from the author's hospital and selected two representative age-estimation algorithms for the model training. The prediction accuracies and the interpretability of calculation logic of these two facial age predictors were compared and analyzed. RESULTS: The mean absolute error (MAE) of a traditional support vector machine-learning model was 10.185 years; the proportion of absolute error ≤6 years was 35.90% and 68.50% ≤12 years. The MAE of a deep-learning model based on the VGG-16 framework was 3.011 years; the proportion of absolute error ≤6 years was 90.20% and 100% ≤12 years. Compared with deep learning, traditional machine-learning models have clearer computational logic, which allows them to give clinicians more specific treatment recommendations. CONCLUSION: Experimental results show that deep-learning exceeds traditional machine learning in the prediction of Chinese cosmetic patients' age. Although traditional machine learning model has better interpretability than deep-learning model, deep-learning is more accurate for clinical quantitative evaluation. Knowing the decision-making logic behind the accurate prediction of deep-learning is crucial for deeper clinical application, and requires further exploration.


Assuntos
Inteligência Artificial , População do Leste Asiático , Humanos , Algoritmos , Bases de Dados Factuais , Aprendizado de Máquina , Face , Reconhecimento Facial Automatizado , Envelhecimento
18.
J Craniofac Surg ; 34(5): 1550-1555, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37410575

RESUMO

Upper eyelid aging with lateral hooding is common among Asian women older than 40 years. Since Asians tend to develop more visible scars than White people, we used an extended upper blepharoplasty technique to correct lateral hooding and conceal the scar, combined with the removal of the thick subbrow skin for women over 60 years of age, to achieve a stable, improved outcome. An extended cutaneous scalpel-shaped excision was designed and hid the extended part of the excision in the patient's upward crow's feet to address the redundant skin of lateral hooding. For patients older than 60 years, we used a crescent-shaped excision and simultaneously removed the thick skin under the eyebrow to reduce the likelihood of long-term postoperative pseudoexcess. A retrospective study was conducted on 40 Asian women who underwent upper eyelid rejuvenation surgery with the above methods from July 2020 to March 2021 (follow-up, 12-15 mo). Extended blepharoplasty notably corrected the lateral hooding and achieved a natural double eyelid. The postoperative scar was inconspicuous. For patients older than 60 years, the long-term rejuvenation outcome was stable when associated with subbrow skin removal. However, two patients older than 60 years in whom the subbrow skin was not removed developed pseudoexcess of the upper eyelid 1 year postoperatively. Extended blepharoplasty is a simple and effective technique for improving periorbital aging in Asian women, and the postoperative scarring was inconspicuous. For patients older than 60 years, we recommend removal of the thick subbrow skin to avoid long-term postoperative pseudoexcess.


Assuntos
Blefaroplastia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Blefaroplastia/métodos , Cicatriz/cirurgia , Pálpebras/cirurgia , Estudos Retrospectivos , Povo Asiático
19.
Angew Chem Int Ed Engl ; 62(32): e202307490, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37318956

RESUMO

Photocatalytic hydrogen (H2 ) production is significant to overcome challenges like fossil fuel depletion and carbon dioxide emission, but its efficiency is still far below that which is needed for commercialization. Herein, we achieve long-term stable H2 bubbling production from water (H2 O) and lactic acid via visible-light-driven photocatalysis in a porous microreactor (PP12); the catalytic system benefits from photocatalyst dispersion, charge separation, mass transfer, and dissociation of O-H bonds associated with H2 O. With the widely used platinum/cadmium-sulfide (Pt/CdS) photocatalyst, PP12 leads to a H2 bubbling production rate of 602.5 mmol h-1 m-2 , which is 1000 times higher than that in a traditional reactor. Even when amplifying PP12 into a flat-plate reactor with an area as large as 1 m2 and extending the reaction time to 100 h, the H2 bubbling production rate still remains at around 600.0 mmol h-1 m-2 , offering great potential for commercialization.

20.
Cell Signal ; 109: 110781, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37354963

RESUMO

Extraordinary excitability (hyperexcitability) is closely related to retinal ganglion cell (RGC) injury in glaucoma. Dopamine (DA) and its receptors are involved in modulating RGC excitability. We investigated how DA system affects RGC injury in chronic ocular hypertension (COH) experimental glaucoma model. Western blotting and immunohistochemistry results revealed that expression of DA D2-like receptor (D2R) in RGCs was increased in COH retinas. Patch-clamp recordings showed that outward K+ currents were downregulated, while Na+ currents and NaV1.6 expression were upregulated in RGCs of COH retinas, which could be reversed by intravitreal pre-injection of the D2R antagonist sulpiride, but not by the D1-like receptor (D1R) antagonist SCH23390. However, pre-injection of the D1R agonist SKF81297 could partially reverse the increased expression of NaV1.6 proteins. Consistently, the numbers of evoked action potentials induced by current injections were increased in RGCs of COH retinas, indicating that RGCs may be in a condition of hyperexcitability. The increased frequency of evoked action potentials could be partially block by pre-injection of sulpiride, SKF81297 or DA, respectively. Furthermore, the increased number of TUNEL-positive RGCs in COH retinas could be partially reduced by intravitreal pre-injection of sulpiride, but not by pre-injection of SCH23390. Moreover, pre-injection of SKF81297 or DA could reduce the number of TUNEL-positive RGCs in COH retinas. All these results indicate that in COH retina, activation of D2R enhances RGC hyperexcitability and injury, while activation of D1R results in the opposite effects. Selective inhibition of D2R or activation of D1R may be an effective strategy for treatment of glaucoma.


Assuntos
Glaucoma , Hipertensão Ocular , Ratos , Animais , Células Ganglionares da Retina/metabolismo , Sulpirida/metabolismo , Sulpirida/farmacologia , Ratos Sprague-Dawley , Glaucoma/metabolismo , Hipertensão Ocular/metabolismo , Receptores de Dopamina D1/metabolismo , Modelos Animais de Doenças
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