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Percolation theory has been widely used to study phase transitions in network systems. It has also successfully explained various macroscopic spreading phenomena across different fields. Yet, the theoretical frameworks have been focusing on direct interactions among nodes, while recent empirical observations have shown that indirect interactions are common in many network systems like social and ecological networks, among others. By investigating the detailed mechanism of both direct and indirect influence on scientific collaboration networks, here we show that indirect influence can play the dominant role in behavioral influence. To address the lack of theoretical understanding of such indirect influence on the macroscopic behavior of the system, we propose a percolation mechanism of indirect interactions called induced percolation. Surprisingly, our model exhibits a unique anisotropy property. Specifically, directed networks show first-order abrupt transitions as opposed to the second-order continuous transition in the same network structure but with undirected links. A mix of directed and undirected links leads to rich hybrid phase transitions. Furthermore, a unique feature of the nonmonotonic pattern is observed in network connectivities near the critical point. We also present an analytical framework to characterize the proposed induced percolation, paving the way to further understanding network dynamics with indirect interactions.
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Singlet oxygen (1O2) has a very short half-life of 10-5 s; however, it is a strong oxidant that causes growth arrest and necrotic lesions on plants. Its signaling pathway remains largely unknown. The Arabidopsis flu (fluorescent) mutant accumulates a high level of 1O2 and shows drastic changes in nuclear gene expression. Only two plastid proteins, EX1 (executer 1) and EX2 (executer 2), have been identified in the singlet oxygen signaling. Here, we found that the transcription factor abscisic acid insensitive 4 (ABI4) binds the promoters of genes responsive to 1O2-signals. Inactivation of the ABI4 protein in the flu/abi4 double mutant was sufficient to compromise the changes of almost all 1O2-responsive-genes and rescued the lethal phenotype of flu grown under light/dark cycles, similar to the flu/ex1/ex2 triple mutant. In addition to cell death, we reported for the first time that 1O2 also induces cell wall thickening and stomatal development defect. Contrastingly, no apparent growth arrest was observed for the flu mutant under normal light/dim light cycles, but the cell wall thickening (doubled) and stomatal density reduction (by two-thirds) still occurred. These results offer a new idea for breeding stress tolerant plants.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Luz , Oxigênio Singlete/metabolismo , Transcriptoma , Estômatos de Plantas/metabolismoRESUMO
Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.
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Depressão , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Infarto do Miocárdio , Animais , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/complicações , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Depressão/tratamento farmacológico , Masculino , Eixo Encéfalo-Intestino/efeitos dos fármacos , Eixo Encéfalo-Intestino/fisiologia , Glicosídeos/farmacologia , Transplante de Microbiota Fecal/métodos , Modelos Animais de DoençasRESUMO
Photon blockade (PB) is an important quantum phenomenon in cavity quantum electrodynamics (QED). Here, we investigate the PB effect in the simplest cavity QED systems (one cavity containing first a single atom and then two atoms), where only the atoms are weakly driven. Via the analytical calculation and numerical simulation, we show that the strong PB can be generated even with the weak-coupling regime at the total resonance. This blockade is ascribed to the two-photon absorption, which is fundamentally different from the conventional and unconventional blockade mechanisms. Therefore, our study provides an alternative approach to produce the PB in the atom-driven cavity QED system.
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BACKGROUND: Dysfunction in the processes of autophagy and apoptosis within renal tubular epithelial cells (RTEc) contributes to renal ischemia-reperfusion injury (IRI). However, the factors influencing this dysfunction remain unclear. Leucine-rich alpha-2-glycoprotein 1 (Lrg1) plays a role in the progression of diabetic nephropathy and kidney fibrosis by modulating the activin receptor-like kinase 1 (ALK1)-Smad1/5/8 and TGF-ß1/Smad3 pathways, respectively. Therefore, we aimed to investigate whether Lrg1 is involved in the pathological mechanisms of renal IRI and whether its effects are related to the dysregulation of autophagy and apoptosis in RTEc. METHODS: We conducted in vitro and in vivo experiments using CoCl2-induced hypoxic human kidney-2 (HK-2) cells and mice with renal IRI, respectively. Lrg1 was silenced using siRNA and lentiviral vectors in HK-2 cells and mouse kidneys. Rapamycin (Rapa) and methyladenine were applied to regulate autophagy in renal IRI models. RESULTS: Increased Lrg1 expression was observed in hypoxic HK-2 cells and in the kidneys of mice with renal IRI. Silencing of Lrg1 through siRNA and lentiviral approaches restored autophagy and suppressed apoptosis in CoCl2-induced hypoxic HK-2 cells and renal IRI models. Additionally, reduced Lrg1 expression alleviated kidney damage caused by renal IRI. The downregulation of Lrg1 expression restrained the TGFß-Smad1/5 signaling pathway in hypoxic-induced HK-2 cells and renal IRI by reducing ALK1 expression. Lastly, the enhancement of autophagy, achieved through Rapa treatment, provided protection against renal IRI in mice. CONCLUSIONS: Our findings suggest that Lrg1 silencing can be applied as a potential therapeutic target to inhibit the TGFß1-Smad1/5 pathway, thereby enhancing autophagy and decreasing apoptosis in patients with acute kidney injury.
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Injúria Renal Aguda , Cobalto , Traumatismo por Reperfusão , Animais , Humanos , Camundongos , Injúria Renal Aguda/patologia , Apoptose/genética , Autofagia/fisiologia , Glicoproteínas/genética , Glicoproteínas/metabolismo , Isquemia/metabolismo , Isquemia/patologia , Rim/patologia , Reperfusão , Traumatismo por Reperfusão/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Proteína Smad1/metabolismoRESUMO
Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide-bond A oxidoreductase-like protein (DsbA-L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and its mechanisms of action in the context of GDM. The present study aims to investigate the underlying mechanism of cGAS-STING pathway and its regulatory relationship with chemerin in GDM. A total of 50 participants, including 25 cases of GDM patients and 25 pregnant women with normal glucose tolerance, were enrolled, and their placenta tissues at term labor were collected. Besides, an insulin resistance cell model was established on the human trophoblastic cell line to explore the molecular mechanism of chemerin on cGAS-STING pathway. Results showed that there were mitochondrial pathological changes in GDM placenta, accompanied by the decreased expression of DsbA-L, increased level of chemerin, and the activation of cGAS-STING pathway. In the insulin resistant cell model, overexpression of chemerin upregulated protein expression of DsbA-L, and recombinant chemerin presented time-dependent inhibition on the cGAS-STING pathway, but this effect was not dependent on DsbA-L. In conclusion, elevated chemerin is probably a protective mechanism, which may be a potential therapeutic strategy for GDM.
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Diabetes Gestacional , Feminino , Humanos , Gravidez , Adipocinas , Diabetes Gestacional/metabolismo , Nucleotidiltransferases/metabolismo , Placenta/metabolismo , Transdução de SinaisRESUMO
The emergence of photocatalysis has greatly advanced radical fluoroalkylation reactions. Central to this advancement is the introduction and refinement of radical reagents, which play a pivotal role in driving these reactions forward. Intriguingly, some of these reagents, previously not recognized for their radical properties, have emerged as key players in this area. In this Perspective, we provide an overview of four representative reagents pioneered by our laboratory, which have subsequently garnered extensive application in broader research contexts, including difluorocarbene precursors bromodifluoromethylphosphonium bromide, electrophilic sulfonylation reagent triflic anhydride, and nucleophilic trifluoromethylation reagent methyl fluorosulfonyldifluoroacetate (Chen's reagent). The integration of phosphonium reagents, triflic anhydride, and methyl fluorosulfonyldifluoroacetate into photocatalysis has enabled some unexpected reactivities and now notably expanded the capabilities in radical difluoromethylation, trifluoromethylation, and difluoroalkylation. Our discussion highlights how these atypical reagents have enriched the toolkit available for radical fluoroalkylations, offering insights that could inspire future research and application in this area.
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BACKGROUND: Early nutrition after acute ischemic stroke is crucial. We explored early enteral nutrition for stroke patients and evaluated changes in blood indicators as a predictor of stroke prognosis. METHODS: All hospitalized stroke patients receiving enteral nutrition were included in the study. We retrospectively collected the protein, energy, fat, and carbohydrate values for 7 days after admission. Serum albumin, total protein, and hemoglobin values were reviewed at admission and at one week. The main outcome indicators were the Modified Rankin Score, Barthel Index, and Quality of Life at 3 months. RESULTS: A total of 354 patients (mean age, 70.7 years; 59.0% male) were included. The change in serum albumin at day 7 relative to at admission was positively correlated with the Quality of Life score (p = 0.001), the Barthel Index (p = 0.004), and the modified Rankin Score (p = 0.029). The change in total protein at day 7 relative to at admission was positively correlated with the Quality of Life score (p = 0.002), the Barthel Index (p = 0.001), and the modified Rankin score (p = 0.011). The change in hemoglobin values at day 7 relative to at admission was positively correlated with the Barthel Index (p = 0.037 but not with the Quality of Life score (p = 0.237) or the modified Rankin score (p = 0.730). CONCLUSIONS: Improved nutrition-related blood indicators one week after admission were independently associated with good stroke outcomes. Nutritional support for acute ischemic stroke patients during the early hospitalization stage appears to be advisable. TRIAL REGISTRATION: This review was a retrospective cohort study. The study was retrospectively registered in the Chinese Clinical Trial Registry (No: ChiCTR2300077228). Registration date: 1/11/2023.
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Nutrição Enteral , AVC Isquêmico , Humanos , Masculino , Feminino , Nutrição Enteral/métodos , Estudos Retrospectivos , Idoso , AVC Isquêmico/sangue , AVC Isquêmico/terapia , Pessoa de Meia-Idade , Estado Nutricional/fisiologia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Qualidade de Vida , Estudos de Coortes , Hemoglobinas/análise , Hemoglobinas/metabolismo , Albumina Sérica/análise , Albumina Sérica/metabolismoRESUMO
An unusual pyridine-containing sesterterpenoid, leucosceptrodine (1), and five new nor-leucosceptrane sesterterpenoids, including bisnor- (C23, 2), tetranor- (C21, 3) and pentanor- (C20, 4-6) skeletons, were isolated from the leaves of Tibetan Leucosceptrum canum. Their structures including their absolute configurations were determined by extensive spectroscopic analyses and quantum chemical calculations. A single crystal of one epimer (5) was crystallized from a pair of inseparable epimers, and its structure including its absolute configuration was determined by X-ray crystallographic analysis. The immunosuppressive activities of compounds 1-4 with different potencies were evaluated by inhibiting the secretion of cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.
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Lamiaceae , Sesterterpenos , Sesterterpenos/química , Tibet , Lamiaceae/química , Cristalografia por Raios X , Piridinas/farmacologia , Estrutura MolecularRESUMO
Nocardia seriolae is the primary aetiological agent of nocardiosis in fish, which causes mass mortality in freshwater and marine fish. ß-ketoacyl-ACP synthase (KAS) is one of the essential enzymes in the synthesis of mycolic acids (MASs) in Mycobacterium spp. and has been chosen as the target for therapeutic intervention in mycobacterial diseases. In the present study, a kasB homologue gene (kasB) was identified in the genome of N. seriolae, and the gene-deficient mutant (ΔkasB) was generated based on a clinical isolate, XSYC-Ns. Compared to the wild-type (WT) strain, the ΔkasB showed a measurably growth defect in vitro but retained the acid-fastness in acid-fast staining. Observation of the cell ultrastructure showed some alterations in the cell wall of the ΔkasB strain. Compared to its original strain, the cell wall lipid layer seemed sparser, and a wider electron-transparent zone was observed in the cell wall of ΔkasB strain. Moreover, the ΔkasB strain showed impaired ability of cell invasion as well as intracellular survival in the cell line originating from the head-kidney of the large yellow croaker (LYC-hK), compared to its original strain. In addition, the deficiency of ΔkasB significantly attenuated the virulence of N. seriolae in largemouth bass. The present study suggested that the ΔkasB gene might be involved in the synthesis of extracellular cell-wall lipids in N. seriolae and play a crucial role in its pathogenicity.
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Bass , Doenças dos Peixes , Nocardiose , Nocardia , Animais , Virulência/genética , Doenças dos Peixes/microbiologia , Nocardia/genética , Nocardiose/veterinária , Nocardiose/microbiologiaRESUMO
In biological neural networks, it has been well recognized that a healthy brain exhibits 1/f noise patterns. However, in artificial neural networks that are increasingly matching or even out-performing human cognition, this phenomenon has yet to be established. In this work, we found that similar to that of their biological counterparts, 1/f noise exists in artificial neural networks when trained on time series classification tasks. Additionally, we found that the activations of the neurons are the closest to 1/f noise when the neurons are highly utilized. Conversely, if the network is too large and many neurons are underutilized, the neuron activations deviate from 1/f noise patterns toward that of white noise.
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Redes Neurais de Computação , Neurônios , Humanos , Neurônios/fisiologia , Modelos NeurológicosRESUMO
OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive disorder mainly affecting the neuromuscular system, which seriously threatens the life and health of patients. But few studies have reported the acceptance rate of SMA gene screening and SMA carrier rate in China. The present study aimed to clarify the two issues in China through a retrospective analysis of 18,818 reproductive age women in Wuhan area of China. METHODS: The copy number (CN) of exons 7 and 8 in survival motor neuron 1 (SMN1) gene was detected by real-time quantitative PCR, and the results were verified by multiplex ligation-dependent probe amplification. RESULTS: Carrier screening was offered to 44,953 women of childbearing age in our medical center from March, 2018, to February, 2022, of whom 18,818 were enrolled in the program. A total of 336 women were identified as carriers (1.73%; 326/18,808; without fertility history of the children with SMA). Among 18,818 reproductive age women, 286 spouses (85.12%; 286/336) were successfully recalled for screening. The results showed 17 couples at high risk of having children with SMA, of whom prenatal diagnosis was implemented in 11, and 6 fetuses were identified with SMA. All the 5 pregnant women bearing the 6 SMA fetuses chose to terminate the pregnancy by artificial abortion. CONCLUSION: Reproductive age women and their spouses in Wuhan area showed a positive attitude toward general screening for SMA carriers. Given the high early mortality of children with SMA, screening for SMA carriers in women of reproductive age is necessary and feasible.
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Atrofia Muscular Espinal , Criança , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Triagem de Portadores Genéticos/métodos , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/epidemiologia , Atrofia Muscular Espinal/genética , China/epidemiologia , Neurônios Motores , Proteína 1 de Sobrevivência do Neurônio Motor/genéticaRESUMO
PURPOSE: This study aimed to investigate the correlation between chromosomal abnormalities in spontaneous abortion with clinical features and seek copy number variations (CNVs) and genes that might be connected to spontaneous abortion. METHODS: Over 7 years, we used CNV-seq and STR analysis to study POCs, comparing chromosomal abnormalities with clinical features and identifying critical CNVs and genes associated with spontaneous abortion. RESULTS: Total chromosomal variants in the POCs were identified in 66.8% (2169/3247) of all cases, which included 45.2% (1467/3247) numerical abnormalities and 21.6% (702/3247) copy number variants (CNVs). Chromosome number abnormalities, especially aneuploidy abnormalities, were more pronounced in the group of mothers aged ≥ 35 years, the early miscarriage group, and the chorionic villi group. We further analyzed 212 pathogenic and likely pathogenic CNVs in 146 POCs as well as identified 8 statistically significant SORs through comparison with both a healthy population and a group of non-spontaneously aborted fetuses. Our analysis suggests that these CNVs may play a crucial role in spontaneous abortion. Furthermore, by utilizing the RVIS score and MGI database, we identified 86 genes associated with spontaneous abortion, with particular emphasis on PARP6, ISLR, ULK3, FGFRL1, TBC1D14, SCRIB, and PLEC. CONCLUSION: We found variability in chromosomal abnormalities across clinical features, identifying eight crucial copy number variations (CNVs) and multiple key genes that may be linked to spontaneous abortion. This research enhances the comprehension of genetic factors contributing to spontaneous abortion.
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Aborto Espontâneo , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Humanos , Feminino , Aborto Espontâneo/genética , Aborto Espontâneo/patologia , Variações do Número de Cópias de DNA/genética , Gravidez , Adulto , AneuploidiaRESUMO
OBJECTIVE: To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency. METHODS: Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities. RESULTS: There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5-3.4 mm, 38.64% in the NT group of 3.5-4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05). CONCLUSION: The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5-3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.
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Variações do Número de Cópias de DNA , Medição da Translucência Nucal , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Medição da Translucência Nucal/métodos , Aberrações Cromossômicas , Feto , Ultrassonografia Pré-NatalRESUMO
Trypsin is one of the most diverse and widely studied protease hydrolases. However, the diversity and characteristics of the Trypsin superfamily of genes have not been well understood, and their role in insecticide resistance is yet to be investigated. In this study, a total of 342 Trypsin genes were identified and classified into seven families based on homology, characteristic domains and phylogenetics in Anopheles sinensis, and the LY-Domain and CLECT-Domain families are specific to the species. Four Trypsin genes, (Astry2b, Astry43a, Astry90, Astry113c) were identified to be associated with pyrethroid resistance based on transcriptome analyses of three field resistant populations and qRT-PCR validation, and the knock-down of these genes significantly decrease the pyrethroid resistance of Anopheles sinensis based on RNAi. The activity of Astry43a can be reduced by five selected insecticides (indoxacarb, DDT, temephos, imidacloprid and deltamethrin); and however, the Astry43a could not directly metabolize these five insecticides, like the trypsin NYD-Tr did in earlier reports. This study provides the overall information frame of Trypsin genes, and proposes the role of Trypsin genes to insecticide resistance. Further researches are necessary to investigate the metabolism function of these trypsins to insecticides.
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Anopheles , Resistência a Inseticidas , Inseticidas , Piretrinas , Tripsina , Animais , Anopheles/genética , Anopheles/efeitos dos fármacos , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Tripsina/genética , Tripsina/metabolismo , Piretrinas/farmacologia , Filogenia , Mosquitos Vetores/genética , Mosquitos Vetores/efeitos dos fármacos , Malária/transmissão , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismoRESUMO
AIM: This study explored the impact of different care modes on the outcome of hospitalized patients with acute ischaemic stroke (AIS) during hospitalization and 3 months after discharge. METHODS: This was a prospective cohort study comparing the outcomes at hospitalization, at discharge, and at 3 months post discharge among AIS patients with different caregiving arrangements from 9, December 2022 to 20, August 2023. The general information questionnaire, Modified Barthel Index, Shortened General Comfort Questionnaire, Perceived Social Support scale, Herth Hope Index, modified Rankin scale and EQ-5D-5L were utilized for the investigation. RESULTS: The psychological evaluation scores during hospitalization, including comfort, perceived social support, and hope, did not significantly differ between the two groups of AIS patients (p > .05). Moreover, there were no significant impacts observed in terms of length of stay (LOS) at the hospital or hospitalization expense (p > .05). The proportion of patients with intact functionality was greater in the family caregiver group 3 months after discharge (16.5%). However, when stratified based on prognosis, the difference in outcomes between the two groups of patients did not reach statistical significance (p > .05). The analysis of ADL, quality of life and stroke recurrence in 276 surviving ischaemic stroke patients 3 months post discharge indicated no differences between the two groups across all three aspects (p > .05). CONCLUSION: Older and divorced or widowed AIS patients tend to prefer professional caregivers. The psychological state during hospitalization, length of hospital stay and hospitalization expenses are not influenced by the caregiving model. Three months post discharge, a greater proportion of patients in the family caregiving group had intact mRS functionality, but this choice did not impact patient prognosis, stroke recurrence, quality of life or independence in ADL.
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Background and Objectives: The escalating prevalence of gestational diabetes mellitus (GDM) and the limitations associated with utilizing body mass index (BMI) as a predictive measure underscore the imperative need for identifying an optimal early pregnancy predictor. Such a predictor not only mitigates the risk of GDM but also allows for timely implementation of interventions. Materials and Methods: This meta-analysis aimed to explore the association between visceral adipose tissue (VAT) depth and the risk of GDM. A thorough search of PubMed, Embase, and Web of Science databases was conducted up to 30 September 2023. The analysis employed a random-effects model to assess the relationship between VAT depth and the likelihood of GDM. Results: The inclusion criteria encompassed seven studies involving 1315 women, including 225 diagnosed with GDM. Significantly lower VAT depth was observed in the non-GDM group in comparison to the GDM group (Standardized Mean Difference [SMD]: 0.84; 95% Confidence Interval [CI]: 0.52-1.15; p < 0.001). Substantial statistical heterogeneity was noted among studies (I2 = 72.88%, p = 0.001). Through meticulous sensitivity and subgroup analyses, the source of heterogeneity was identified and thoroughly discussed. Subgroup analyses suggest that different GDM diagnostic criteria and VAT definitions all indicate higher VAT depth in GDM patients during early pregnancy. Conclusions: Our findings propose that, during the first trimester, GDM patients exhibit higher VAT depth compared to non-GDM women, highlighting VAT depth as a potential predictive factor for GDM in early pregnancy. This study contributes valuable evidence to the growing body of knowledge surrounding novel predictors for GDM, emphasizing the importance of early intervention strategies.
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Diabetes Gestacional , Gordura Intra-Abdominal , Humanos , Diabetes Gestacional/diagnóstico , Gravidez , Gordura Intra-Abdominal/diagnóstico por imagem , Feminino , Índice de Massa Corporal , Fatores de RiscoRESUMO
To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.
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Apoptose , Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Naftoquinonas , Transdução de Sinais , Proteína Supressora de Tumor p53 , Humanos , Naftoquinonas/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismoRESUMO
The reaction regioselectivity of gem-difluoroalkenes is dependent on the intrinsic polarity. Thus, the reversal of the regioselectivity of the addition reaction of gem-difluoroalkenes remains a formidable challenge. Herein, we described an unprecedented reversal of regioselectivity of hydrogen atom transfer (HAT) to gem-difluoroalkenes triggered by Fe-H species for the formation of difluoroalkyl radicals. Hydrogenation of the in situ generated radicals gave difluoromethylated products. Mechanism experiments and theoretical studies revealed that the kinetic effect of the irreversible HAT process resulted in the reversal of the regioselectivity of this scenario, leading to the formation of a less stable α-difluoroalkyl radical regioisomer. On basis of this new reaction of gem-difluoroalkene, the iron-promoted hydrohalogenation of gem-difluoroalkenes for the efficient synthesis of aliphatic chlorodifluoromethyl-, bromodifluoromethyl- and iododifluoromethyl-containing compounds was developed. Particularly, this novel hydrohalogenation of gem-difluoroalkenes provided an effect and large-scale access to various iododifluoromethylated compounds of high value for synthetic application.
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We report the discovery and biosynthesis of new piperazine alkaloids-arizonamides, and their derived compounds-arizolidines, featuring heterobicyclic and spirocyclic isoquinolone skeletons, respectively. Their biosynthetic pathway involves two crucial non-heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3-alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG.