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Our perception and decision-making are susceptible to prior context. Such sequential dependence has been extensively studied in the visual domain, but less is known about its impact on time perception. Moreover, there are ongoing debates about whether these sequential biases occur at the perceptual stage or during subsequent post-perceptual processing. Using functional magnetic resonance imaging, we investigated neural mechanisms underlying temporal sequential dependence and the role of action in time judgments across trials. Participants performed a timing task where they had to remember the duration of green coherent motion and were cued to either actively reproduce its duration or simply view it passively. We found that sequential biases in time perception were only evident when the preceding task involved active duration reproduction. Merely encoding a prior duration without reproduction failed to induce such biases. Neurally, we observed activation in networks associated with timing, such as striato-thalamo-cortical circuits, and performance monitoring networks, particularly when a "Response" trial was anticipated. Importantly, the hippocampus showed sensitivity to these sequential biases, and its activation negatively correlated with the individual's sequential bias following active reproduction trials. These findings highlight the significant role of memory networks in shaping time-related sequential biases at the post-perceptual stages.
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Percepción del Tiempo , Humanos , Percepción del Tiempo/fisiología , Memoria/fisiología , Señales (Psicología) , Imagen por Resonancia Magnética , Juicio , Percepción Visual/fisiologíaRESUMEN
BACKGROUND: Mitochondrial DNA copy number (mtDNA-CN) is associated with the severity and mortality in patients with stroke, but the associations in different stroke subtypes remain unexplored. METHODS: We conducted an observational prospective cohort analysis on patients with ischemic stroke or transient ischemic attack enrolled in the Third China National Stroke Registry. We applied logistic models to assess the association of mtDNA-CN with functional outcome (modified Rankin Scale score, 3-6 versus 0-2) and Cox proportional hazard models to assess the association with stroke recurrence (treating mortality as a competing risk) and mortality during a 12-month follow-up, adjusting for sex, age, physical activity, National Institutes of Health Stroke Scale at admission, history of stroke and peripheral artery disease, small artery occlusion, and interleukin-6. Subgroup analyses stratified by age and stroke subtypes were conducted. RESULTS: The Third China National Stroke Registry enrolled 15â 166 patients, of which 10â 241 with whole-genome sequencing data were retained (mean age, 62.2 [SD, 11.2] years; 68.8% men). The associations between mtDNA-CN and poststroke/transient ischemic attack outcomes were specific to patients aged ≤65 years, with lower mtDNA-CN significantly associated with stroke recurrence in 12 months (subdistribution hazard ratio, 1.15 per SD lower mtDNA-CN [95% CI, 1.04-1.27]; P=5.2×10-3) and higher all-cause mortality in 3 months (hazard ratio, 2.19 [95% CI, 1.41-3.39]; P=5.0×10-4). Across subtypes, the associations of mtDNA-CN with stroke recurrence were specific to stroke of undetermined cause (subdistribution hazard ratio, 1.28 [95% CI, 1.11-1.48]; P=6.6×10-4). In particular, lower mtDNA-CN was associated with poorer functional outcomes in stroke of undetermined cause patients diagnosed with embolic stroke of undetermined source (odds ratio, 1.53 [95% CI, 1.20-1.94]; P=5.4×10-4), which remained significant after excluding patients with recurrent stroke (odds ratio, 1.49 [95% CI, 1.14-1.94]; P=3.0×10-3). CONCLUSIONS: Lower mtDNA-CN is associated with higher stroke recurrence rate and all-cause mortality, as well as poorer functional outcome at follow-up, among stroke of undetermined cause, embolic stroke of undetermined source, and younger patients.
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Social pain, a multifaceted emotional response triggered by interpersonal rejection or criticism, profoundly impacts mental well-being and social interactions. While prior research has implicated the right ventrolateral prefrontal cortex (rVLPFC) in mitigating social pain, the precise neural mechanisms and downstream effects on subsequent social attitudes remain elusive. This study employed transcranial magnetic stimulation (TMS) integrated with fMRI recordings during a social pain task to elucidate these aspects. Eighty participants underwent either active TMS targeting the rVLPFC (n = 41) or control stimulation at the vertex (n = 39). Our results revealed that TMS-induced rVLPFC facilitation significantly reduced self-reported social pain, confirming the causal role of the rVLPFC in social pain relief. Functional connectivity analyses demonstrated enhanced interactions between the rVLPFC and the dorsolateral prefrontal cortex, emphasizing the collaborative engagement of prefrontal regions in emotion regulation. Significantly, we observed that negative social feedback led to negative social attitudes, whereas rVLPFC activation countered this detrimental effect, showcasing the potential of the rVLPFC as a protective buffer against adverse social interactions. Moreover, our study uncovered the impact role of the hippocampus in subsequent social attitudes, a relationship particularly pronounced during excitatory TMS over the rVLPFC. These findings offer promising avenues for improving mental health within the intricate dynamics of social interactions. By advancing our comprehension of the neural mechanisms underlying social pain relief, this research introduces novel intervention strategies for individuals grappling with social distress. Empowering individuals to modulate rVLPFC activation may facilitate reshaping social attitudes and successful reintegration into communal life.
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Imagen por Resonancia Magnética , Corteza Prefrontal , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Masculino , Femenino , Adulto Joven , Corteza Prefrontal/fisiología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Adulto , Actitud , Interacción Social , Dolor/fisiopatología , Dolor/psicología , Mapeo Encefálico/métodos , Corteza Prefontal Dorsolateral/fisiología , Corteza Prefontal Dorsolateral/diagnóstico por imagenRESUMEN
BACKGROUND: Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. METHODS: Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. RESULTS: CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. CONCLUSIONS: Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.
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Depresión , Trastorno Depresivo Mayor , Animales , Ratones , Antidepresivos/farmacología , Autofagia , Citocinas/metabolismo , Depresión/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Hipocampo/metabolismo , Inflamasomas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The rapid advancement of triboelectric nanogenerators (TENGs) has introduced a transformative approach to energy harvesting and self-powered sensing in recent years. Nonetheless, the untapped potential of TENGs in practical scenarios necessitates multiple strategies like material selections and structure designs to enhance their output performance. Given the various superior properties, MXenes, a kind of novel 2D materials, have demonstrated great promise in enhancing TENG functionality. Here, this review comprehensively delineates the advantages of incorporating MXenes into TENGs, majoring in six pivotal aspects. First, an overview of TENGs is provided, stating their theoretical foundations, working modes, material considerations, and prevailing challenges. Additionally, the structural characteristics, fabrication methodologies, and family of MXenes, charting their developmental trajectory are highlighted. The selection of MXenes as various functional layers (negative and positive triboelectric layer, electrode layer) while designing TENGs is briefed. Furthermore, the distinctive advantages of MXene-based TENGs and their applications are emphasized. Last, the existing challenges are highlighted, and the future developing directions of MXene-based TENGs are forecasted.
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BACKGROUND: Previous research on ABO blood types and stroke has been controversial, predominantly suggesting heightened risk of stroke in non-O blood types. Nonetheless, investigations into the correlation and underlying mechanisms between ABO blood groups and stroke subtypes, especially within Chinese cohorts, remain limited. METHODS: The ABO blood types of 9,542 ischaemic stroke (IS) patients were inferred using two ABO gene loci (c.261G > del; c.802G > A). The healthy population was derived from the 1000 Genomes Project. Patients were classified by the causative classification system (CCS). Volcano plot and gene ontology (GO) analysis were employed to explore protein differential expression among blood types. Additionally, HT29 and SW480 cell lines with downregulated ABO expression were generated to evaluate its impact on cholesterol uptake and efflux. RESULTS: A greater proportion of stroke patients had non-O blood types (70.46%) than did healthy individuals (61.54%). Notable differences in blood type distributions were observed among stroke subtypes, with non-O blood type patients mainly classified as having large artery atherosclerosis (LAA). Clinical baseline characteristics, such as the low-density lipoprotein cholesterol level, activated partial thromboplastin time and thrombin time, varied significantly among blood types. A volcano plot revealed 17 upregulated and 42 downregulated proteins in the O blood type. GO term analysis indicated that downregulated proteins were primarily associated with lipid metabolism pathways. In vitro experiments revealed that reducing ABO gene expression decreased cholesterol uptake and increased cholesterol efflux. CONCLUSIONS: This study revealed that the non-O blood type increased the risk of LAA stroke through cholesterol metabolism.
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Sistema del Grupo Sanguíneo ABO , Aterosclerosis , Colesterol , Accidente Cerebrovascular , Humanos , Sistema del Grupo Sanguíneo ABO/genética , Masculino , Colesterol/sangre , Femenino , Persona de Mediana Edad , Aterosclerosis/sangre , Aterosclerosis/genética , Anciano , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/genética , Factores de Riesgo , LDL-Colesterol/sangre , Células HT29RESUMEN
BACKGROUND: Facial aging (FA) is a complex process influenced by both genetic and environmental factors. Gut microbiota (GM), gut microbiota metabolic pathways (GMMPs), and blood metabolites (BMs) have been implicated in the regulation of FA, but the causal and mediating effects of these factors remain unclear. METHODS: We used summary-level data from genome-wide association studies (GWAS) of 16S rRNA gene sequencing data for GM (n = 18 340), GWAS of GMMPs (n = 7738), BMs (n = 24 925), and GWAS of FA (n = 423 999). We applied Mendelian randomization (MR) methods to estimate the causal effects of GM, GMMPs, and BMs on FA. We performed mediation analysis to quantify the proportion of the effects mediated by blood metabolites. RESULTS: We identified nine genus, two phylum, two families of GM, nine GM metabolic pathways, and 73 BMs that showed potential causal effects on FA. After Bonferroni correction, three BMs remained causally associated with FA, including average number of methylene groups per double bond (ß, -0.023; 95% CI, -0.032â¼-0.014; p = 3.120×10-7) and average number of methylene groups in a fatty acid chain (ß, -0.031; 95% CI, -0.045â¼-0.016; p = 2.062×10-5), which had strong negative causal effects on FA, and ratio of bisallylic groups to total fatty acids (ß, 0.023; 95% CI, 0.017â¼-0.029; p = 8.441×10-15), which had a strong positive causal effect on FA. Mediation analysis revealed that histidine, average number of methylene groups in a fatty acid chain, and triglycerides in chylomicrons and largest VLDL particles mediated the effects of anaerofilum and/ or superpathway of Laspartate and Lasparagine biosynthesis on FA. CONCLUSION: Our study provides novel insights into the causal and mediating effects of GM, GMMPs, and BMs on FA. These findings may have implications for the development of new strategies for preventing or delaying FA.
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Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Redes y Vías Metabólicas , Humanos , Microbioma Gastrointestinal/fisiología , Envejecimiento de la Piel/fisiología , Análisis de Mediación , Cara , ARN Ribosómico 16S/genética , Envejecimiento/sangre , Envejecimiento/fisiologíaRESUMEN
Decisions about a current stimulus are influenced by previously encountered stimuli, leading to sequential bias. However, the specific processing levels at which serial dependence emerges remain unclear. Despite considerable evidence pointing to contributions from perceptual and post-perceptual processes, as well as response carryover effects impacting subsequent judgments, research into how different task measurements affect sequential dependencies is limited. To address this gap, the present study investigated the role of task type in shaping sequential effects in time perception, employing a random-dot kinematogram (RDK) in a post-cue paradigm. Participants had to remember both the duration and the direction of the RDK movement and perform the task based on a post-cue, which was equally likely to be direction or duration. To delineate the task type, we employed the temporal bisection task in Experiment 1 and the duration reproduction task in Experiment 2. Both experiments revealed a significant sequential bias: durations were perceived as longer following longer previous durations, and vice versa. Intriguingly, the sequential effect was enhanced in the reproduction task following the same reproduction task (Experiment 2), but did not show significant variation by the task type in the bisection task (Experiment 1). Moreover, comparable response carryover effects were observed across two experiments. We argue that the differential impacts of task types on sequential dependence lies in the involvement of memory reactivation process in the decision stage, while the post-decision response carryover effect may reflect the assimilation by subjective, rather than objective, durations, potentially linking to the sticky pacemaker rate and/or decisional inertia.
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PURPOSE: This study aims to understand the molecular mechanisms underlying the aging process and identify potential interventions to mitigate age-related decline and diseases. METHODS: This study utilized the GSE168753 dataset to conduct comprehensive differential gene expression analysis and co-expression module analysis. Machine learning and Mendelian randomization analyses were employed to identify core aging-associated genes and potential drug targets. Molecular docking simulations and mediation analysis were also performed to explore potential compounds and mediators involved in the aging process. RESULTS: The analysis identified 4164 differentially expressed genes, with 1893 upregulated and 2271 downregulated genes. Co-expression analysis revealed 21 modules, including both positively and negatively correlated modules between older age and younger age groups. Further exploration identified 509 aging-related genes with distinct biological functions. Machine learning and Mendelian randomization analyses identified eight core genes associated with aging, including DPP9, GNAZ, and RELL2. Molecular docking simulations suggested resveratrol, folic acid, and ethinyl estradiol as potential compounds capable of attenuating aging through modulation of RELL2 expression. Mediation analysis indicated that eosinophil counts and neutrophil count might act as mediators in the causal relationship between genes and aging-related indicators. CONCLUSION: This comprehensive study provides valuable insights into the molecular mechanisms of aging and offers important implications for the development of anti-aging therapeutics. Key Messages What is already known on this topic - Prior research outlines aging's complexity, necessitating precise molecular targets for intervention. What this study adds - This study identifies novel aging-related genes, potential drug targets, and therapeutic compounds, advancing our understanding of aging mechanisms. How this study might affect research, practice, or policy - Findings may inform targeted therapies for age-related conditions, influencing future research and clinical practices.
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Acrylamide (AAM), a compound extensively utilized in various industrial applications, has been reported to induce toxic effects across multiple tissues in living organisms. Despite its widespread use, the impact of AAM on ovarian function and the mechanisms underlying these effects remain poorly understood. Here, we established an AAM-exposed mouse toxicological model using 21 days of intragastric AAM administration. AAM exposure decreased ovarian coefficient and impaired follicle development. Further investigations revealed AAM would trigger apoptosis and disturb tricarboxylic acid cycle in ovarian tissue, thus affecting mitochondrial electron transport function. Moreover, AAM exposure decreased oocyte and embryo development potential, mechanically associated with pericentrin and phosphorylated Aurora A cluster failure, leading to meiotic spindle assembly defects. Collectively, these results suggest that AAM exposure may lead to apoptosis, glucose metabolic disorders, and mitochondrial dysfunction in ovary tissue, ultimately compromising oocyte quality.
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Acrilamida , Ciclo del Ácido Cítrico , Oocitos , Ovario , Animales , Acrilamida/toxicidad , Oocitos/efectos de los fármacos , Femenino , Ciclo del Ácido Cítrico/efectos de los fármacos , Ratones , Ovario/efectos de los fármacos , Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacosRESUMEN
Identification of cancer metastatic sites is of importance for adjusting therapeutic interventions and treatment choice. However, identifying the location of metastatic lesions with easy accessibility and high safety is challenging. Here we demonstrate that cancer metastatic sites can be accurately detected by a triple targeting nanoprobe. Through coencapsulating molecular beacons probing a cancer biomarker (CXCR4 mRNA), a lung metastatic biomarker (CTSC mRNA), and a bone metastatic biomarker (JAG1 mRNA), the nanoprobe decorated by SYL3C conjugated hyaluronic acid and ICAM-1 specific aptamer conjugated hyaluronic acid can target diverse phenotyped circulating tumor cells (CTCs) during epithelial-mesenchymal and mesenchymal-epithelial transitions in whole blood for sensitive probing. The detection of CTCs from cancer patients shows that the nanoprobe can provide accurate information to distinguish different cancer metastasis statuses including nonmetastasis, lung metastasis, and bone metastasis. This study proposes an efficient screening tool for identifying the location of distant metastatic lesions via facile blood biopsy.
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Células Neoplásicas Circulantes , Humanos , Ácido Hialurónico , Biomarcadores de Tumor/genética , Biopsia , ARN Mensajero/genética , Metástasis de la NeoplasiaRESUMEN
INTRODUCTION: To understand the incidence of postoperative constipation and the risk factors of constipation in patients with lumbar interbody fusion, we constructed and verified the constipation risk prediction model, so as to provide reference for the prevention and treatment of postoperative constipation. METHODS: The data of patients undergoing lumbar interbody fusion in our hospital were retrospectively analyzed from December 2021 to December 2022. According to postoperative constipation, the patients were divided into constipation group and non-constipation group. Univariate logistic regression analysis and multivariate logistic regression analysis were used to determine independent risk factors for postoperative constipation. Based on independent risk factors, a nomogram was developed to predict the risk of constipation after lumbar interbody fusion. The prediction performance was assessed using receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA). Finally, bootstrapping method for internal validation was further evaluated the nomogram. RESULTS: A total of 282 patients participated in the study. 176 patients (62.41%) after lumbar interbody occurred constipation, and 106 patients were asymptomatic. Multivariate regression analysis showed independent risk factors, including the use of calcium channel blockers, polypharmacy, postoperative bed time, and constipation history. Multivariate regression analysis was used to establish the model. The C-index of the nomogram was 0.827 (95% CI 0.779-0.875), and the C-index of interval bootstrapping validation was 0.813 (95% CI 0.765-0.861), and the area under the AUC was 0.800. The nomogram showed good discrimination ability. CONCLUSIONS: The use of calcium channel blockers, polypharmacy, postoperative bed time, and history of constipation are independent risk factors for postoperative constipation in patients undergoing lumbar interbody fusion. The constructed risk prediction model has good discriminative ability.
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Estreñimiento , Vértebras Lumbares , Nomogramas , Complicaciones Posoperatorias , Fusión Vertebral , Humanos , Fusión Vertebral/efectos adversos , Estreñimiento/etiología , Estreñimiento/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Vértebras Lumbares/cirugía , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Anciano , Medición de Riesgo/métodos , Adulto , Curva ROCRESUMEN
BACKGROUND: In large-scale high-throughput sequencing projects and biobank construction, sample tagging is essential to prevent sample mix-ups. Despite the availability of fingerprint panels for DNA data, little research has been conducted on sample tagging of whole genome bisulfite sequencing (WGBS) data. This study aims to construct a pipeline and identify applicable fingerprint panels to address this problem. RESULTS: Using autosome-wide A/T polymorphic single nucleotide variants (SNVs) obtained from whole genome sequencing (WGS) and WGBS of individuals from the Third China National Stroke Registry, we designed a fingerprint panel and constructed an optimized pipeline for tagging WGBS data. This pipeline used Bis-SNP to call genotypes from the WGBS data, and optimized genotype comparison by eliminating wildtype homozygous and missing genotypes, and retaining variants with identical genomic coordinates and reference/alternative alleles. WGS-based and WGBS-based genotypes called from identical or different samples were extensively compared using hap.py. In the first batch of 94 samples, the genotype consistency rates were between 71.01%-84.23% and 51.43%-60.50% for the matched and mismatched WGS and WGBS data using the autosome-wide A/T polymorphic SNV panel. This capability to tag WGBS data was validated among the second batch of 240 samples, with genotype consistency rates ranging from 70.61%-84.65% to 49.58%-61.42% for the matched and mismatched data, respectively. We also determined that the number of genetic variants required to correctly tag WGBS data was on the order of thousands through testing six fingerprint panels with different orders for the number of variants. Additionally, we affirmed this result with two self-designed panels of 1351 and 1278 SNVs, respectively. Furthermore, this study confirmed that using the number of genetic variants with identical coordinates and ref/alt alleles, or identical genotypes could not correctly tag WGBS data. CONCLUSION: This study proposed an optimized pipeline, applicable fingerprint panels, and a lower boundary for the number of fingerprint genetic variants needed for correct sample tagging of WGBS data, which are valuable for tagging WGBS data and integrating multi-omics data for biobanks.
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Genoma , Sulfitos , Humanos , Secuenciación Completa del Genoma , Genotipo , Metilación de ADN , ADN , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
RAD23 (RADIATION SENSITIVE23) proteins are a group of UBL-UBA (ubiquitin-like-ubiquitin-associated) proteins that shuttle ubiquitylated proteins to the 26S proteasome for breakdown. Drought stress is a major environmental constraint that limits plant growth and production, but whether RAD23 proteins are involved in this process is unclear. Here, we demonstrated that a shuttle protein, MdRAD23D1, mediated drought response in apple plants (Malus domestica). MdRAD23D1 levels increased under drought stress, and its suppression resulted in decreased stress tolerance in apple plants. Through in vitro and in vivo assays, we demonstrated that MdRAD23D1 interacted with a proline-rich protein MdPRP6, resulting in the degradation of MdPRP6 by the 26S proteasome. And MdRAD23D1 accelerated the degradation of MdPRP6 under drought stress. Suppression of MdPRP6 resulted in enhanced drought tolerance in apple plants, mainly because the free proline accumulation is changed. And the free proline is also involved in MdRAD23D1-mediated drought response. Taken together, these findings demonstrated that MdRAD23D1 and MdPRP6 oppositely regulated drought response. MdRAD23D1 levels increased under drought, accelerating the degradation of MdPRP6. MdPRP6 negatively regulated drought response, probably by regulating proline accumulation. Thus, "MdRAD23D1-MdPRP6" conferred drought stress tolerance in apple plants.
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Malus , Ubiquitina , Ubiquitina/metabolismo , Proteínas Portadoras , Malus/genética , Proteínas de Plantas/genética , Sequías , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico , Plantas Modificadas Genéticamente/metabolismoRESUMEN
AIM: To examine the association between lipoprotein lipase (LPL) polymorphisms and susceptibility to diabetic kidney disease (DKD) and early renal function decline in Chinese patients with type 2 diabetes (T2D). METHODS: The association of eight LPL single nucleotide polymorphisms (SNPs) with DKD was analysed in 2793 patients with T2D from the third China National Stroke Registry. DKD was defined as either an urine albumin-to-creatinine ratio (UACR) of 30 mg/g or higher at baseline and 3 months, or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 at baseline and 3 months. Rapid decline in kidney function (RDKF) was defined as a reduction in the eGFR of 3 mL/min/1.73 m2 or greater per year. Logistic regression models were used to evaluate the association of LPL SNP and DKD with an additive model. RESULTS: The SNPs rs285 C>T (OR = 1.40, P = .0154), rs328 C>G (OR = 2.24, P = .0104) and rs3208305 A>T (OR = 1.85, P = .0015) were identified to be significantly associated with DKD defined by eGFR. Among 1241 participants with follow-up data, 441 (35.5%) showed RDKF over a mean follow-up period of 1 year, and the rs285 C allele was associated with higher odds of RDKF (OR = 1.31, 95% CI 1.04-1.66; P = .025) after adjustment for multiple variables. CONCLUSIONS: These results suggest that LPL-related SNPs are new candidate factors for conferring susceptibility to DKD and may promote rapid loss of renal function in Chinese patients with T2D.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/genética , Pueblos del Este de Asia , Tasa de Filtración Glomerular , Riñón , Pruebas de Función RenalRESUMEN
The rational design of photocatalysts with efficiency and stability is highly desirable but remains challenging. Here, we report a supramolecular self-assembly strategy to construct hollow phosphorus-doped g-C3N4 microboxes (PCNMs). Considering the effects of multiple parameters on the structure and activity of samples, the orthogonal design is innovatively introduced to optimize technology parameters for screening high-performance g-C3N4. Under visible light irradiation (λ ≥ 420 nm), rhodamine B (RhB, 4 mg L-1) is completely degraded in just 80 seconds in the presence of the optimal PCNM. The kinetic rate constant of RhB degradation with the PCNM is 3.4633 min-1, demonstrating unprecedented activity that is about 112 times higher than that of bulk g-C3N4 (0.0309 min-1) synthesized by direct polycondensation of melamine. Additionally, the optimal PCNM also shows enhanced degradation efficiency for tetracycline. The outstanding properties are primarily attributed to the hollow architecture, high specific surface area, and phosphorus doping. This work advances the design of photocatalysts correlating various factors, opening an avenue for optimizing photocatalytic synthesis and activity.
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Intestinal failure-associated liver disease (IFALD) is a common hepatobiliary complication resulting from long-term parenteral nutrition (PN) in patients with intestinal failure. The spectrum of IFALD ranges from cholestasis, steatosis, portal fibrosis, to cirrhosis. Development of IFALD is a multifactorial process, in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability, activation of hepatic immune responses, and administration of lipid emulsion. Gut microbiota manipulation including pre/probiotics, fecal microbiota transplantation, and antibiotics has been studied in IFALD with varying success. In this review, we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD. We also review the function of microbial metabolites and associated signalings in the context of IFALD. By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury, our review provides perspectives for future basic and translational investigations in the field.
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Microbioma Gastrointestinal , Hipertensión Portal , Enfermedades Intestinales , Insuficiencia Intestinal , Hepatopatías , Fallo Hepático , Humanos , Hepatopatías/etiología , Enfermedades Intestinales/complicaciones , Fallo Hepático/complicaciones , Hipertensión Portal/complicacionesRESUMEN
PURPOSE: This study used a network meta-analysis to evaluate the efficacy and safety of different surgical approaches in patients with hemorrhoids. METHODS: PubMed, Embase, Web of science, and Cochrane Library were searched for randomized controlled trials on patients with hemorrhoids treated by different surgical procedures. The search was conducted until January 15, 2023. Two investigators independently screened the resulting literature, extracted information, evaluated the risk of bias of the included studies, and performed a network meta-analysis. RESULT: A total of 23 randomized controlled studies were included and involved 3573 patients and 10 interventions, namely L (Ligasure), M-M (Milligan-Morgan), F (Ferguson), H (Harmonic), OH (open Harmonic), CH (closed Harmonic), PPH (procedure for prolapse and hemorrhoids), TST (tissue selecting technique), T-S (TST STARE+; tissue selection therapy stapled transanal rectal resection plus), and STARR (stapled transanal rectal resection). Network meta-analysis results showed that L has the shortest mean operating time and STARR has the longest mean operating time, F and H have the longest length of hospitalization and T-S has the shortest length of hospitalization, PPH has the most intraoperative blood loss and L has the least intraoperative blood loss, TST has the shortest time to first defecation and M-M has the longest time to first defecation, STARR had the least recurrence and PPH had the most recurrence, PPH had the least anal stenosis and L had the most anal stenosis, and F had the least postoperative pain after 24 h and PPH had the most postoperative pain after 24 h. CONCLUSION: Current evidence suggests that L is best at reducing mean operative time and intraoperative bleeding, T-S is best at reducing mean length of stay, TST has the shortest time to first defecation, STARR is best at reducing recurrence rates, PPH is best at reducing postoperative anal stricture, and F is best at reducing postoperative pain after 24 h.
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Malformaciones Anorrectales , Hemorroides , Humanos , Hemorroides/cirugía , Pérdida de Sangre Quirúrgica/prevención & control , Constricción Patológica , Metaanálisis en Red , Dolor Postoperatorio/etiologíaRESUMEN
In recent decades, the rapid development of the global economy has led to a substantial increase in energy consumption, subsequently resulting in the emission of a significant quantity of toxic gases into the environment. So far, gas sensors based on polymer field-effect transistors (PFETs), a highly practical and cost-efficient strategy, have garnered considerable attention, primarily attributed to their inherent advantages of offering a plethora of material choices, robust flexibility, and cost-effectiveness. Notably, the development of functional organic semiconductors (OSCs), such as poly(3-hexylthiophene-2,5-diyl) (P3HT), has been the subject of extensive scholarly investigation in recent years due to its widespread availability and remarkable sensing characteristics. This paper provides an exhaustive overview encompassing the production, functionalization strategies, and practical applications of gas sensors incorporating P3HT as the OSC layer. The exceptional sensing attributes and wide-ranging utility of P3HT position it as a promising candidate for improving PFET-based gas sensors.
RESUMEN
The chemotherapeutic effectiveness of pancreatic ductal adenocarcinoma (PDAC) is severely hampered by insufficient intratumoral delivery of antitumor drugs. Here, we demonstrate that enhanced pancreatic cancer chemotherapy can be achieved by probiotic spore-based oral drug delivery system via gut-pancreas axis translocation. Clostridium butyricum spores resistant to harsh external stress are extracted as drug carriers, which are further covalently conjugated with gemcitabine-loaded mesoporous silicon nanoparticles (MGEM). The spore-based oral drug delivery system (SPORE-MGEM) migrates upstream into pancreatic tumors from the gut, which increases intratumoral drug accumulation by â¼3-fold compared with MGEM. In two orthotopic PDAC mice models, tumor growth is markedly suppressed by SPORE-MGEM without obvious side effects. Leveraging the biological contact of the gut-pancreas axis, this probiotic spore-based oral drug delivery system reveals a new avenue for enhancing PDAC chemotherapy.