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1.
Nat Commun ; 15(1): 8205, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294150

RESUMEN

Holobionts are highly organized assemblages of eukaryotic hosts, cellular microbial symbionts, and viruses, whose interactions and evolution involve complex biological processes. It is largely unknown which specific determinants drive similarity or individuality in genetic diversity between holobionts. Here, we combine short- and long-read sequencing and DNA-proximity-linkage technologies to investigate intraspecific diversity of the microbiomes, including host-resolved viruses, in individuals of a model marine sponge. We find strong impacts of the sponge host and the cellular hosts of viruses on strain-level organization of the holobiont, whereas substantial overlap in nucleotide diversity between holobionts suggests frequent exchanges of microbial cells and viruses at intrastrain level in the local sponge population. Immune-evasive arms races likely restricted virus-host co-evolution at the intrastrain level, generated holobiont-specific genome variations, and linked virus-host genetics through recombination. Our work shows that a decoupling of strain- and intrastrain-level interactions is a key factor in the genetic diversification of holobionts.


Asunto(s)
Microbiota , Poríferos , Simbiosis , Animales , Microbiota/genética , Poríferos/microbiología , Poríferos/virología , Variación Genética , Virus/genética , Virus/clasificación , Filogenia
2.
J Clin Med ; 13(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39274552

RESUMEN

Background: Functional recovery following the surgical fixation of acetabular posterior wall fractures remains a challenge. This study compares outcomes of posterior wall fracture reconstruction using an anatomical posterior acetabular plate (APAP) versus conventional reconstruction plates. Methods: Forty patients with acetabular fractures involving the posterior wall or column underwent surgery, with 20 treated using APAPs (APAP group) and 20 with conventional pelvic reconstruction plates (control group). Baseline patient characteristics, intraoperative blood loss and time, reduction quality, postoperative function, and postoperative complications were compared using appropriate non-parametric statistical tests. A general linear model for repeated measures analysis of variance was employed to analyze trends in functional recovery. Results: No significant differences were observed in baseline characteristics. APAP significantly reduced surgical time by 40 min (186.5 ± 51.0 versus 225.0 ± 47.7, p =0.004) and blood loss (695 ± 393 versus 930 ± 609, p = 0.049) compared to conventional plates. At 3 and 6 months following surgery, the APAP group exhibited higher functional scores (modified Merle d'Aubigné scores 10 ± 1.8 versus 7.8 ± 1.4, p < 0.001; 13.4 ± 2.8 versus 10.1 ± 2.1, p = 0.001), converging with the control group by 12 months (modified Merle d'Aubigné scores 14.2 ± 2.6 versus 12.7 ± 2.6, p = 0.072; OHS 31.6 ± 12.3 versus 30.3 ± 10.1, p = 0.398). Radiologically, the APAP group demonstrated superior outcomes (p = 0.047). Complication and conversion rates to hip arthroplasty did not significantly differ between groups (10% versus 15%, p = 0.633). Conclusions: The use of an APAP in reconstructing the posterior acetabulum significantly reduces surgical time, decreases intraoperative blood loss, and leads to earlier functional recovery compared to conventional reconstruction plates. The APAP provides stable fixation of the posterior wall and ensures the durable maintenance of reduction, ultimately yielding favorable surgical outcomes.

3.
Laryngoscope ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263897

RESUMEN

Benign cutaneous apocrine sweat gland adenomas in the nose are rare. We present the novel case of a nasal ala cutaneous sweat gland lesion. A 43-year-old male presents with a one year history of a right nostril mass with intermittent clear discharge, triggered by periods of hot weather and increased humidity. Histopathological analysis post-excision revealed a solid-cystic lesion of bi-layered ducts, with snouts suggestive of apocrine secretions. Given the close relationship of tumour enlargement with heat and expression of clear liquid upon direct pressure, we postulate that the intermittent tumescence represents sweat production and accumulation within the lesion. Laryngoscope, 2024.

4.
BMC Cancer ; 24(1): 967, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39112947

RESUMEN

BACKGROUND: This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. CONCLUSIONS: Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Endostatinas , Neoplasias Pulmonares , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Endostatinas/administración & dosificación , Endostatinas/efectos adversos , Endostatinas/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
5.
Neural Netw ; 179: 106595, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39159535

RESUMEN

Graph neural networks (GNNs) leveraging metapaths have garnered extensive utilization. Nevertheless, the escalating parameters and data corpus within graph pre-training models incur mounting training costs. Consequently, GNN models encounter hurdles including diminished generalization capacity and compromised performance amidst small sample datasets. Drawing inspiration from the efficacy demonstrated by self-supervised learning methodologies in natural language processing, we embark on an exploration. We endeavor to imbue graph data with augmentable, learnable prompt vectors targeting node representation enhancement to foster superior adaptability to downstream tasks. This paper proposes a novel approach, the Metapath Integrated Graph Prompt Neural Network (MIGP), which leverages learnable prompt vectors to enhance node representations within a pretrained model framework. By leveraging learnable prompt vectors, MIGP aims to address the limitations posed by mall sample datasets and improve GNNs' model generalization. In the pretraining stage, we split symmetric metapaths in heterogeneous graphs into short metapaths and explicitly propagate information along the metapaths to update node representations. In the prompt-tuning stage, the parameters of the pretrained model are fixed, a set of independent basis vectors is introduced, and an attention mechanism is employed to generate task-specific learnable prompt vectors for each node. Another notable contribution of our work is the introduction of three patent datasets, which is a pioneering application in related fields. We will make these three patent datasets publicly available to facilitate further research on large-scale patent data analysis. Through comprehensive experiments conducted on three patent datasets and three other public datasets, i.e., ACM, IMDB, and DBLP, we demonstrate the superior performance of the MIGP model in enhancing model applicability and performance across a variety of downstream datasets. The source code and datasets are available in the website.1.


Asunto(s)
Redes Neurales de la Computación , Procesamiento de Lenguaje Natural , Algoritmos , Humanos
6.
Elife ; 122024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102287

RESUMEN

Bathymodioline mussels dominate deep-sea methane seep and hydrothermal vent habitats and obtain nutrients and energy primarily through chemosynthetic endosymbiotic bacteria in the bacteriocytes of their gill. However, the molecular mechanisms that orchestrate mussel host-symbiont interactions remain unclear. Here, we constructed a comprehensive cell atlas of the gill in the mussel Gigantidas platifrons from the South China Sea methane seeps (1100 m depth) using single-nucleus RNA-sequencing (snRNA-seq) and whole-mount in situ hybridisation. We identified 13 types of cells, including three previously unknown ones, and uncovered unknown tissue heterogeneity. Every cell type has a designated function in supporting the gill's structure and function, creating an optimal environment for chemosynthesis, and effectively acquiring nutrients from the endosymbiotic bacteria. Analysis of snRNA-seq of in situ transplanted mussels clearly showed the shifts in cell state in response to environmental oscillations. Our findings provide insight into the principles of host-symbiont interaction and the bivalves' environmental adaption mechanisms.


Asunto(s)
Simbiosis , Animales , Branquias/microbiología , Análisis de Secuencia de ARN/métodos , Bivalvos/microbiología , Bivalvos/genética , Mytilidae/genética , Mytilidae/microbiología , Bacterias/genética
7.
Heliyon ; 10(15): e33983, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170560

RESUMEN

This study analyzes the influences of evapotranspiration or substrate moisture variation on the indoor-temperature reduction of green roofs compared to the control group. A multiple linear regression (MLR) model for the operation stage based on observation and an integrated MLR model for the planning stage based on simulation are verified. The MLR model shows 0.64 °C of the Root Mean Square Error (RMSE) in predicting the hourly difference of temperature reduction based on the measured change in evapotranspiration and air temperature. The contributions of the hourly increment of air temperature (ΔTa) and increment of evapotranspiration (ΔET) are similar to the hourly increment of temperature reduction (ΔTdif). Then, the feasibility of the integrated MLR model is demonstrated based on the evapotranspiration and substrate moisture of a green roof simulated by a hydrological model as well as the indoor-temperature reduction simulated by a building energy model, which has fair performances in capturing the heat-transfer and water-balance physical process within a green roof. The integrated MLR model shows that evapotranspiration is relatively essential, followed by substrate moisture, air temperature, and vapor pressure. Despite the modeling bias, the integrated model quantitatively relates the influential factors to temperature reduction and predicts temperature reduction with an RMSE of 1.02 °C. The integrated model can quantify the influence of irrigation on temperature reduction under various climate conditions and green roof structures. This study demonstrates the procedure of establishing the integrated model. It shows the potential of the integrated model to provide decision support on irrigation for multi-purpose optimization of green roof performances.

8.
Angew Chem Int Ed Engl ; : e202414295, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39216012

RESUMEN

A concise synthetic strategy utilizing a Zr-catalyst for the construction of cyctetryptomycin A and B is herein reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers via a Zr-catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr-catalyzed radical coupling. The radical dimerization reaction mediated by the Zr-catalyst required dppe as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr-catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations.

9.
Bioengineering (Basel) ; 11(8)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39199728

RESUMEN

Medical datasets may be imbalanced and contain errors due to subjective test results and clinical variability. The poor quality of original data affects classification accuracy and reliability. Hence, detecting abnormal samples in the dataset can help clinicians make better decisions. In this study, we propose an unsupervised error detection method using patterns discovered by the Pattern Discovery and Disentanglement (PDD) model, developed in our earlier work. Applied to the large data, the eICU Collaborative Research Database for sepsis risk assessment, the proposed algorithm can effectively discover statistically significant association patterns, generate an interpretable knowledge base for interpretability, cluster samples in an unsupervised learning manner, and detect abnormal samples from the dataset. As shown in the experimental result, our method outperformed K-Means by 38% on the full dataset and 47% on the reduced dataset for unsupervised clustering. Multiple supervised classifiers improve accuracy by an average of 4% after removing abnormal samples by the proposed error detection approach. Therefore, the proposed algorithm provides a robust and practical solution for unsupervised clustering and error detection in healthcare data.

10.
Curr Med Sci ; 44(4): 771-788, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39096475

RESUMEN

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.


Asunto(s)
Metabolismo de los Hidratos de Carbono , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Humanos , Pronóstico , Metabolismo de los Hidratos de Carbono/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Perfilación de la Expresión Génica
12.
J Med Chem ; 67(15): 13197-13216, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39028938

RESUMEN

USP7 is an attractive therapeutic target for cancers, especially for acute lymphoblastic leukemia (ALL) with wild-type p53. Herein, we report the discovery of XM-U-14 as a highly potent, selective and efficacious USP7 proteolysis-targeting chimera degrader. XM-U-14 achieves DC50 values of 0.74 nM and Dmax of 93% in inducing USP7 degradation in RS4;11 cell lines, and also significantly inhibits ALL cell growth. XM-U-14 even at 5 mg/kg dosed daily effectively inhibits RS4;11 tumor growth with 64.7% tumor regressions and causes no signs of toxicity in mice. XM-U-14 is a promising USP7 degrader for further optimization for ALL treatment.


Asunto(s)
Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Peptidasa Específica de Ubiquitina 7 , Peptidasa Específica de Ubiquitina 7/metabolismo , Peptidasa Específica de Ubiquitina 7/antagonistas & inhibidores , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Animales , Ratones , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Descubrimiento de Drogas , Relación Estructura-Actividad , Proteolisis/efectos de los fármacos
13.
World J Clin Cases ; 12(18): 3636-3643, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38983391

RESUMEN

BACKGROUND: Human herpesvirus type 7 (HHV-7) is a less common herpes virus that usually causes mild, self-limiting illnesses. However, in recent years, there have been increasing reports of HHV-7 causing serious central nervous system infections, especially meningitis. The pathogenesis and clinical features of HHV-7 meningitis, particularly in adolescents with normal immune function, remain incompletely studied. Therefore, the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease. CASE SUMMARY: A 12-year-old female was admitted with fever, headache, and vomiting. 4 d before admission, the patient developed a fever without obvious induction, with a temperature up to 39.5 °C, no convulsions, accompanied by chills, headaches, fatigue, and no muscle aches. The patient was treated with fever reduction, which could be reduced to 38 °C; repeated high fever, accompanied by vomiting 7-8 times; and no abdominal pain or diarrhea. The patient was diagnosed with "acute suppurative tonsillitis" in a local hospital, and the blood routine was generally normal. The patient was given symptomatic support treatment such as "ceftriaxone sodium" and antiemetic rehydration for 2 d, and his condition did not improve. The patient's physical examination showed pharyngeal congestion, bilateral tonsil grade I hypertrophy, regression of purulent secretions, and cervical resistance. Ocular B-ultrasound: Opacity of the vitreous body and edema of the optic disc in both eyes. Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes, with edema of the optic disc. DNA virus monitoring results: HHV-7. We gave ganciclovir antiviral therapy, dexamethasone anti-inflammatory treatment, mannitol to reduce cranial pressure, omeprazole to protect gastrointestinal mucosa, and calcium and potassium supplementation. CONCLUSION: This study reports a case of HHV-7 meningitis in an adolescent with normal immune function. Through comprehensive analysis of the clinical manifestations, laboratory tests, and treatment methods of the patient, it is found that early identification and antiviral treatment are essential for the outcome of the disease. This case suggests that despite normal immune function, adolescents may still suffer from herpes virus type 7 meningitis, so clinicians should be vigilant and take effective treatment measures in time.

14.
Sci Rep ; 14(1): 16367, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014132

RESUMEN

As China strives to balance rapid urbanization with environmental conservation, increasing attention is being paid to the pursuit of green production efficiency (GPE) in the real estate industry. The undesirable super-SBM model was used to calculate the GPE of China's real estate industry from 2001 to 2020. Additionally, GPE spatial distribution characteristics in China's real estate industry were analyzed using the standard deviation ellipse (SDE), Moran's index, Theil index, random kernel density estimation (RKDA), and spatial Markov chain (SMC) methods. The GPE exhibited a U-shaped trend, with 2008 as the inflection point, first decreasing and then increasing. It reached a maximum value of 0.747 in 2020. The Theil index increased from 0.043 to 0.121 nationwide, indicating the overall characteristics of low-level slow growth, and imbalance. Discrepancies in input-output scales, the southward shift of economic centers, and population movements contribute significantly to the disparities between the east and west, north and south, and regions divided by the Hu Huanyong Line (Hu Line). The GPE exhibited club convergence characteristics; however, polarization phenomena exist in local areas. Spatial spillover effects were also observed in GPE. Finally, we provide recommendations for promoting green development in the real estate industry, including green building technology, fiscal subsidy investment, and population migration management.

15.
Sci Adv ; 10(30): eadn3053, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39047091

RESUMEN

Vestimentiferan tubeworms that thrive in deep-sea chemosynthetic ecosystems rely on a single species of sulfide-oxidizing gammaproteobacterial endosymbionts housed in a specialized symbiotic organ called trophosome as their primary carbon source. While this simple symbiosis is remarkably productive, the host-symbiont molecular interactions remain unelucidated. Here, we applied an approach for deep-sea in situ single-cell fixation in a cold-seep tubeworm, Paraescarpia echinospica. Single-cell RNA sequencing analysis and further molecular characterizations of both the trophosome and endosymbiont indicate that the tubeworm maintains two distinct metabolic "microniches" in the trophosome by controlling the availability of chemosynthetic gases and metabolites, resulting in oxygenated and hypoxic conditions. The endosymbionts in the oxygenated niche actively conduct autotrophic carbon fixation and are digested for nutrients, while those in the hypoxic niche conduct anaerobic denitrification, which helps the host remove ammonia waste. Our study provides insights into the molecular interactions between animals and their symbiotic microbes.


Asunto(s)
Poliquetos , RNA-Seq , Análisis de la Célula Individual , Simbiosis , Animales , Análisis de la Célula Individual/métodos , Poliquetos/metabolismo , Poliquetos/microbiología , Poliquetos/genética , RNA-Seq/métodos , Gammaproteobacteria/metabolismo , Gammaproteobacteria/genética , Análisis de Expresión Génica de una Sola Célula
16.
Brain Behav Immun ; 120: 413-429, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38925413

RESUMEN

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3-/- mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes.


Asunto(s)
Modelos Animales de Enfermedad , Progresión de la Enfermedad , Enfermedad de Huntington , Microglía , Proteínas de Transporte de Nucleósidos , Animales , Humanos , Masculino , Ratones , Encéfalo/metabolismo , Proteína Huntingtina/metabolismo , Proteína Huntingtina/genética , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , Proteínas de Transporte de Nucleósidos/metabolismo , Proteínas de Transporte de Nucleósidos/genética
17.
Sci Rep ; 14(1): 14642, 2024 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918442

RESUMEN

People procrastinate, but why? One long-standing hypothesis is that temporal discounting drives procrastination: in a task with a distant future reward, the discounted future reward fails to provide sufficient motivation to initiate work early. However, empirical evidence for this hypothesis has been lacking. Here, we used a long-term real-world task and a novel measure of procrastination to examine the association between temporal discounting and real-world procrastination. To measure procrastination, we critically measured the entire time course of the work progress instead of a single endpoint, such as task completion day. This approach allowed us to compute a fine-grained metric of procrastination. We found a positive correlation between individuals' degree of future reward discounting and their level of procrastination, suggesting that temporal discounting is a cognitive mechanism underlying procrastination. We found no evidence of a correlation when we, instead, measured procrastination by task completion day or by survey. This association between temporal discounting and procrastination offers empirical support for targeted interventions that could mitigate procrastination, such as modifying incentive systems to reduce the delay to a reward and lowering discount rates.


Asunto(s)
Descuento por Demora , Motivación , Procrastinación , Recompensa , Humanos , Masculino , Femenino , Adulto , Adulto Joven
18.
Sci Rep ; 14(1): 14091, 2024 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890510

RESUMEN

Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn's disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D levels and those with vitamin D deficiency after multivariate adjustment, female sex and early age at diagnosis were identified as statistically significant risk factors. We found a prevalence of 42.5% of vitamin D deficiency in the Taiwanese IBD population. Understanding this issue is essential for teaching patients and doctors about vitamin D deficiency screening and improving patient outcomes.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Deficiencia de Vitamina D , Humanos , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/sangre , Femenino , Masculino , Taiwán/epidemiología , Adulto , Prevalencia , Persona de Mediana Edad , Factores de Riesgo , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/complicaciones , Vitamina D/sangre , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/sangre , Enfermedad de Crohn/complicaciones , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/complicaciones , Adulto Joven , Anciano
19.
J Endod ; 50(8): 1082-1090, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38782183

RESUMEN

INTRODUCTION: The aim of this prospective study was to investigate the 1-year pulp survival of cracked teeth with reversible pulpitis managed with initial stabilization using orthodontic bands, followed by coronal coverage restorations. METHODS: One-hundred-and-twenty-five patients with a cracked tooth with reversible pulpitis each were recruited. Preoperative patient and tooth data were collected. After definitive pulp diagnoses were determined following an interim period of orthodontic banding, coronal coverage restorations were placed. Cox and logistic regression analyses were used to assess possible prognostic factors and to correlate initial time to pulp stabilization while in orthodontic bands with eventual outcome. Pulp survival was determined using both clinical and radiographic findings. RESULTS: One-hundred-and-six cracked teeth were followed up at 1 year. Pulp survival based on clinical and radiographic findings was found in 81 teeth (76.4%). Out of 25 failures, 11 (44%) required root canal treatment (RCT) in the orthodontic band stage and 10 (40%) required RCT during the process of or after coronal coverage restorations. Four teeth (16%) had incidental findings of periapical radiolucencies at the 1-year review without clinical symptoms. Teeth requiring RCT were found to have required longer periods in orthodontic bands prior to a definitive pulp diagnosis (P < .05). CONCLUSION: A step-by-step approach by using orthodontic banding to monitor pulp status may reduce the incidence of RCT required through definitive coronal coverage restorations for cracked teeth with reversible pulpitis.


Asunto(s)
Pulpitis , Humanos , Estudios Prospectivos , Femenino , Masculino , Estudios de Seguimiento , Pulpitis/etiología , Pulpitis/terapia , Adolescente , Síndrome de Diente Fisurado/etiología , Adulto Joven , Adulto , Pulpa Dental/lesiones , Pulpa Dental/diagnóstico por imagen , Restauración Dental Permanente/métodos , Tratamiento del Conducto Radicular
20.
World J Pediatr ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713366

RESUMEN

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

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