Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.935
Filtrar
1.
Ecotoxicol Environ Saf ; 280: 116524, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38838464

RESUMO

BACKGROUND: Organophosphate esters (OPEs) and Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with common exposure sources, leading to their widespread presence in human body. However, evidence on co-exposure to OPEs and PFAS and its impact on cardiovascular-kidney-liver-metabolic biomarkers remains limited. METHODS: In this cross-sectional study, 467 adults were enrolled from January to May 2022 during physical visits in Shijiazhuang, Hebei province. Eleven types of OPEs and twelves types of PFAS were detected, among which eight OPEs and six PFAS contaminants were detected in more than 60% of plasma samples. Seventeen biomarkers were assessed to comprehensively evaluate the cardiovascular-kidney-liver-metabolic function. Multiple linear regression, multipollutant models with sparse partial least squares, and Bayesian kernel machine regression (BKMR) models were applied to examine the associations of individual OPEs and PFAS and their mixtures with organ function and metabolism, respectively. RESULTS: Of the over 400 exposure-outcome associations tested when modelling, we observed robust results across three models that perfluorohexanoic acid (PFHxS) was significantly positively associated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and indirect bilirubin (IBIL). Perfluorononanoic acid was significantly associated with decreased AST/ALT and increased very-low-density lipoprotein cholesterol levels. Besides, perfluorodecanoic acid was correlated with increased high lipoprotein cholesterol and perfluoroundecanoic acid was consistently associated with lower glucose level. BKMR analysis showed that OPEs and PFAS mixtures were positively associated with IBIL and TBIL, among which PFHxS was the main toxic chemicals. CONCLUSIONS: Our findings suggest that exposure to OPEs and PFAS, especially PFHxS and PFNA, may disrupt organ function and metabolism in the general population, providing insight into the potential pathophysiological mechanisms of OPEs and PFAS co-exposure and chronic diseases.

2.
Microbiol Resour Announc ; : e0041124, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864618

RESUMO

We report the draft genome sequence of marine bacteria, Pseudomonas sp. XK-1. Strain XK-1 could facilitate Mn(II) oxidation with lignin as the sole carbon source. The genome length of XK-1 is 4,751,776 bp, with a G + C content of 62.61%. Genome analyses reveal the carbon and manganese cycling driven by bacteria.

3.
Onco Targets Ther ; 17: 423-438, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827823

RESUMO

Background: Nicotinamide (NAM+) regulates redox and metabolic activities in the mitochondria. The intention of the research was to identify key genes that relate to nicotinamide in hepatocellular carcinoma (HCC). Methods: Relevant clinical information were collected as well as RNA-seq data using the Cancer Genome Atlas (TCGA) database. Differential analysis was used to discover the genes that were differently expressed. On the key genes associated with NAM, functional enrichment analysis was carried out. Next, receiver operating characteristic (ROC) and prognosis Kaplan-Meier (K-M) curve analyses were used to evaluate the importance of important gene expression, respectively. The immune cell signatures were estimated using the CIBERSORT algorithm. Finally, the anticancer impact of NAM on HCC was experimentally confirmed, and important genes NADSYN1 and NT5C were validated at the protein level in clinical specimens. Results: Six prognostic key genes (NAXE, NADSYN1, NT5C, NT5C3A, PNP and NT5E) were identified. There is an association between the level of key gene expression and the clinical prognosis. Four key genes (NAXE, NADSYN1, NT5C and NT5C3A) have statistical significance of survival prognosis. Finally, the expression of NAM-related genes and the inhibitory effect of NAM on HCC were verified by experiments. Conclusion: The study first found some Nicotinamide metabolism-related differentially expressed genes (NMRDEGs) that are related to HCC can contribute to predicting survival and monitoring the treatment.

4.
Cells Dev ; : 203932, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852677

RESUMO

Tooth morphogenesis is a critically ordered process manipulated by a range of signaling factors. Particularly, the involvement of fine-tuned signaling mediated by non-coding RNAs has been of longstanding interest. Here, we revealed a double-negative feedback loop acted by a long non-coding RNA (LOC102159588) and a microRNA (miR-133b) that modulated tooth morphogenesis of miniature swine. Mechanistically, miR-133b repressed the transcription of LOC102159588 through downstream target Sp1. Conversely, LOC102159588 not only inhibited the transport of pre-miR-133b from the nucleus to the cytoplasm by regulating exportin-5 but also served as a sponge in the cytoplasm, suppressing functional miR-133b. Together, the double-negative feedback loop maintained normal tooth morphogenesis by modulating endogenous apoptosis. Related disruptions would lead to an arrest of tooth development and may result in tooth malformations.

6.
Int Dent J ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38853053

RESUMO

OBJECTIVES: Studies have increasingly focussed on the relationship between periodontitis (PD) and preeclampsia (PE). However, conclusions have not been consistent, and it is unclear whether any causal relationship exists between them and whether causality is bidirectional. This study employed Mendelian randomisation (MR) analysis to investigate the potential bidirectional causal relationship between PD and PE. METHODS: Genetic variants strongly linked to PD (17,353 cases and 28,210 controls), chronic periodontitis (CP; 1817 cases and 2215 controls), aggressive periodontitis (AgP; 851 cases and 6580 controls), and PE (7212 cases and 194,266 controls) in the genome-wide association study (GWAS) of European ancestry were used as instrumental variables (IVs). Inverse variance weighting (IVW) served as the primary method for causal inference. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) was utilised to analyse horizontal pleiotropy. Cochrane Q tests and leave-one-out analyses were used to assess heterogeneity and stability amongst IVs. RESULTS: The MR analysis revealed no causal impacts of PD or its 2 subtypes-CP and AgP-on PE. Similarly, no significant causal effect of PE on PD was found in the reverse-MR analysis (IVW odds ratio, 0.97; 95% confidence interval, 0.91-1.05; P = .58). The findings from MR-Egger, weighted median, weighted mode, and the simple modelling approaches, as well as the pleiotropy and sensitivity analyses, aligned with those of the IVW method. CONCLUSIONS: The MR analysis suggests no bidirectional causal relationship between PD and PE; hence, PD and PE might not increase or prevent the risk of one other. CLINICAL RELEVANCE: Genetically, periodontitis or its subtypes chronic periodontitis and aggressive periodontitis may not require specific clinical attention to prevent the development of preeclampsia.

7.
Nano Lett ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848282

RESUMO

Gatemon qubits are the electrically tunable cousins of superconducting transmon qubits. In this work, we demonstrate the full coherent control of a gatemon qubit based on hole carriers in a Ge/Si core/shell nanowire, with the longest coherence times in group IV material gatemons to date. The key to these results is a high-quality Josephson junction obtained using a straightforward and reproducible annealing technique. We demonstrate that the transport through the narrow junction is dominated by only two quantum channels, with transparencies up to unity. This novel qubit platform holds great promise for quantum information applications, not only because it incorporates technologically relevant materials, but also because it provides new opportunities, like an ultrastrong spin-orbit coupling in the few-channel regime of Josephson junctions.

8.
Appl Opt ; 63(13): 3570-3575, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856542

RESUMO

Inspired by the demodulation algorithm of Fabry-Perot composite sensors in the field of fiber-optic sensing, this paper proposes a method based on a widely tunable modulated grating Y-branch (MG-Y) laser combined with the cross-correlation algorithm to achieve a highly precise measurement of the optical thickness of each layer of a multilayer optical sample. A sample consisting of a double glass stack was selected, and the interference spectrum of the stacked sample was acquired using a widely tunable MG-Y laser. A fast Fourier transform (FFT) algorithm combined with a finite impulse response (FIR) bandpass filter was utilized to separate the different frequency components of the multilayer optical sample. The normalized spectra of each layer were reconstructed using the Hilbert transform. Subsequently, a cross-correlation algorithm was employed to process the normalized spectrum and determine the optical thickness of each layer with high precision. The samples were measured at predetermined locations, with 150 consecutive measurements performed to assess the repetition of the thickness. The standard deviation of these measurements was found to be lower than 1.5 nm. The results show that the cross-correlation algorithm is advantageous in the optical thickness measurement of multilayer films.

9.
Adv Mater ; : e2405641, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877353

RESUMO

Osteoarthritis is a prevalent disease, characterized by subchondral fractures in its initial stages, which has no precise and specific treatment now. In this study, a novel multifunctional scaffold was synthesized by photopolymerizing glycidyl methacrylate-modified hyaluronic acid as the matrix in the presence of hollow porous magnetic microspheres based on hydroxyapatite. In vivo subchondral bone repairing results demonstrate that the scaffold's meticulous design has the most suitable properties for subchondral bone repair. The porous structure of inorganic particles within the scaffold facilitates efficient transport of loaded exogenous vascular endothelial growth factor. The Fe3O4 nanoparticles assembled in the microspheres could promote the osteogenic differentiation of bone marrow mesenchymal stem cells and accelerate the generation of new bone. These features enable the scaffold to exhibit favorable subchondral bone repair properties and attain high cartilage repair scores. The therapy results prove that the subchondral bone support considerably influences the upper cartilage repair process. Furthermore, magnetic resonance imaging monitoring demonstrates that Fe3O4 nanoparticles, which were gradually replaced by new bone during osteochondral defect repair, allow a noninvasive and radiation-free assessment to track the newborn bone during the osteoarthritis repair process. The composite hydrogel scaffold provides a versatile platform for biomedical applications in osteoarthritis treatment. This article is protected by copyright. All rights reserved.

10.
J Med Internet Res ; 26: e50149, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838328

RESUMO

BACKGROUND: This study aimed to investigate the relationships between adiposity and circadian rhythm and compare the measurement of circadian rhythm using both actigraphy and a smartphone app that tracks human-smartphone interactions. OBJECTIVE: We hypothesized that the app-based measurement may provide more comprehensive information, including light-sensitive melatonin secretion and social rhythm, and have stronger correlations with adiposity indicators. METHODS: We enrolled a total of 78 participants (mean age 41.5, SD 9.9 years; 46/78, 59% women) from both an obesity outpatient clinic and a workplace health promotion program. All participants (n=29 with obesity, n=16 overweight, and n=33 controls) were required to wear a wrist actigraphy device and install the Rhythm app for a minimum of 4 weeks, contributing to a total of 2182 person-days of data collection. The Rhythm app estimates sleep and circadian rhythm indicators by tracking human-smartphone interactions, which correspond to actigraphy. We examined the correlations between adiposity indices and sleep and circadian rhythm indicators, including sleep time, chronotype, and regularity of circadian rhythm, while controlling for physical activity level, age, and gender. RESULTS: Sleep onset and wake time measurements did not differ significantly between the app and actigraphy; however, wake after sleep onset was longer (13.5, SD 19.5 minutes) with the app, resulting in a longer actigraphy-measured total sleep time (TST) of 20.2 (SD 66.7) minutes. The obesity group had a significantly longer TST with both methods. App-measured circadian rhythm indicators were significantly lower than their actigraphy-measured counterparts. The obesity group had significantly lower interdaily stability (IS) than the control group with both methods. The multivariable-adjusted model revealed a negative correlation between BMI and app-measured IS (P=.007). Body fat percentage (BF%) and visceral adipose tissue area (VAT) showed significant correlations with both app-measured IS and actigraphy-measured IS. The app-measured midpoint of sleep showed a positive correlation with both BF% and VAT. Actigraphy-measured TST exhibited a positive correlation with BMI, VAT, and BF%, while no significant correlation was found between app-measured TST and either BMI, VAT, or BF%. CONCLUSIONS: Our findings suggest that IS is strongly correlated with various adiposity indicators. Further exploration of the role of circadian rhythm, particularly measured through human-smartphone interactions, in obesity prevention could be warranted.


Assuntos
Actigrafia , Adiposidade , Algoritmos , Ritmo Circadiano , Smartphone , Humanos , Feminino , Actigrafia/instrumentação , Actigrafia/métodos , Masculino , Adulto , Ritmo Circadiano/fisiologia , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Aplicativos Móveis , Sono/fisiologia
11.
J Clin Pathol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862215

RESUMO

AIMS: This meta-analysis assessed the relative diagnostic accuracy of optical coherence tomography (OCT) versus frozen section (FS) in evaluating surgical margins during breast-conserving procedures. METHODS: PubMed and Embase were searched for relevant studies published up to October 2023. The inclusion criteria encompassed studies evaluating the diagnostic accuracy of OCT or FS in patients undergoing breast-conserving surgery. Sensitivity and specificity were analysed using the DerSimonian and Laird method and subsequently transformed through the Freeman-Tukey double inverse sine method. RESULTS: The meta-analysis encompassed 36 articles, comprising 16 studies on OCT and 20 on FS, involving 10 289 specimens from 8058 patients. The overall sensitivity of OCT was 0.93 (95% CI: 0.90 to 0.96), surpassing that of FS, which was 0.82 (95% CI: 0.71 to 0.92), indicating a significantly higher sensitivity for OCT (p=0.04). Conversely, the overall specificity of OCT was 0.89 (95% CI: 0.83 to 0.94), while FS exhibited a higher specificity at 0.97 (95% CI: 0.95 to 0.99), suggesting a superior specificity for FS (p<0.01). CONCLUSIONS: Our meta-analysis reveals that OCT offers superior sensitivity but inferior specificity compared with FS in assessing surgical margins in breast-conserving surgery patients. Further larger well-designed prospective studies are needed, especially those employing a head-to-head comparison design. PROSPERO REGISTRATION NUMBER: CRD42023483751.

12.
Adv Sci (Weinh) ; : e2305593, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873820

RESUMO

Centromere protein A (CENP-A), a histone H3 variant specific to centromeres, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure-activity relationship (SAR) study of the cell-cycle-arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis reveals that both molecules bind to the colchicine-binding site of ß-tubulin. Treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, results in CENP-A accumulation by destabilizing Cdh1, a co-activator of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.

13.
Front Immunol ; 15: 1339680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881906

RESUMO

Background: SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear. Methods: We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes. Results: Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response. Conclusion: Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.


Assuntos
Proliferação de Células , Ácido Fólico , Lúpus Eritematoso Sistêmico , Monócitos , Receptor 4 Toll-Like , Transcobalaminas , Humanos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Monócitos/metabolismo , Monócitos/imunologia , Transcobalaminas/metabolismo , Transcobalaminas/genética , Feminino , Ácido Fólico/metabolismo , Masculino , Adulto , Inflamação/metabolismo , Inflamação/imunologia , Pessoa de Meia-Idade , Células THP-1 , Carbono/metabolismo , Vitamina B 12/metabolismo , Estudos de Casos e Controles
14.
Pharmacotherapy ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884415

RESUMO

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

15.
Adv Mater ; : e2404900, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857942

RESUMO

Single atom catalyst (SAC) is one of the most efficient and versatile catalysts with well-defined active sites. However, its facile and large-scale preparation, the prerequisite of industrial applications, has been very challenging. This dilemma originates from the Gibbs-Thomson effect, which renders it rather difficult to achieve high single atom loading (< 3 mol%). Further, most synthesizing procedures are quite complex, resulting in significant mass loss and thus low yields. Herein, a novel metal coordination route is developed to address these issues simultaneously, which is realized owing to the rapid complexation between ligands (e.g., biuret) and metal ions in aqueous solutions and subsequent in situ polymerization of the formed complexes to yield SACs. The whole preparation process involves only one heating step operated in air without any special protecting atmospheres, showing general applicability for diverse transition metals. Take Cu SAC for an example, a record yield of up to 3.565 kg in one pot and an ultrahigh metal loading 16.03 mol% on carbon nitride (Cu/CN) are approached. The as-prepared SACs are demonstrated to possess high activity, outstanding selectivity, and robust cyclicity for CO2 photoreduction to HCOOH. This research explores a robust route toward cost-effective, massive production of SACs for potential industrial applications.

16.
Front Bioeng Biotechnol ; 12: 1356158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707505

RESUMO

Introduction: Silicon is a major trace element in humans and a prospective supporting biomaterial to bone regeneration. Submicron silicon pillars, as a representative surface topography of silicon-based biomaterials, can regulate macrophage and osteoblastic cell responses. However, the design of submicron silicon pillars for promoting bone regeneration still needs to be optimized. In this study, we proposed a submicron forest-like (Fore) silicon surface (Fore) based on photoetching. The smooth (Smo) silicon surface and photoetched regular (Regu) silicon pillar surface were used for comparison in the bone regeneration evaluation. Methods: Surface parameters were investigated using a field emission scanning electron microscope, atomic force microscope, and contact angle instrument. The regulatory effect of macrophage polarization and succedent osteogenesis was studied using Raw264.7, MC3T3-E1, and rBMSCs. Finally, a mouse calvarial defect model was used for evaluating the promoting effect of bone regeneration on the three surfaces. Results: The results showed that the Fore surface can increase the expression of M2-polarized markers (CD163 and CD206) and decrease the expression of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Fore surface can promote the osteogenesis in MC3T3-E1 cells and osteoblastic differentiation of rBMSCs. Furthermore, the volume fraction of new bone and the thickness of trabeculae on the Fore surface were significantly increased, and the expression of RANKL was downregulated. In summary, the upregulation of macrophage M2 polarization on the Fore surface contributed to enhanced osteogenesis in vitro and accelerated bone regeneration in vivo. Discussion: This study strengthens our understanding of the topographic design for developing future silicon-based biomaterials.

17.
Plant Physiol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38696768

RESUMO

Nondestructive plant phenotyping forms a key technique for unraveling molecular processes underlying plant development and response to the environment. While the emergence of high-throughput phenotyping facilities can further our understanding of plant development and stress responses, their high costs greatly hinder scientific progress. To democratize high-throughput plant phenotyping, we developed sets of low-cost image- and weight-based devices to monitor plant shoot growth and evapotranspiration. We paired these devices to a suite of computational pipelines for integrated and straightforward data analysis. The developed tools were validated for their suitability for large genetic screens by evaluating a cowpea (Vigna unguiculata) diversity panel for responses to drought stress. The observed natural variation was used as an input for a genome-wide association study, from which we identified nine genetic loci that might contribute to cowpea drought resilience during early vegetative development. The homologs of the candidate genes were identified in Arabidopsis (Arabidopsis thaliana) and subsequently evaluated for their involvement in drought stress by using available T-DNA insertion mutant lines. These results demonstrate the varied applicability of this low-cost phenotyping system. In the future, we foresee these setups facilitating the identification of genetic components of growth, plant architecture, and stress tolerance across a wide variety of plant species.

18.
Nat Commun ; 15(1): 3702, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697969

RESUMO

Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.


Assuntos
Região CA1 Hipocampal , Animais , Feminino , Região CA1 Hipocampal/fisiologia , Região CA1 Hipocampal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Células de Lugar/fisiologia , Recompensa , Comportamento Animal/fisiologia
19.
Aging Dis ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38739934

RESUMO

Amyotrophic lateral sclerosis (ALS) stands as a rare, yet severely debilitating disorder marked by the deterioration of motor neurons (MNs) within the brain and spinal cord, which is accompanied by degenerated corticobulbar/corticospinal tracts and denervation in skeletal muscles. Despite ongoing research efforts, ALS remains incurable, attributed to its intricate pathogenic mechanisms. A notable feature in the pathology of ALS is the prevalence of TAR DNA-binding protein 43 (TDP-43) proteinopathy, detected in approximately 97% of ALS cases, underscoring its significance in the disease's progression. As a result, strategies targeting the aberrant TDP-43 protein have garnered attention as a potential avenue for ALS therapy. This review delves into the existing drug screening systems aimed at TDP-43 proteinopathy and the models employed for drug efficacy validation. It also explores the hurdles encountered in the quest to develop potent medications against TDP-43 proteinopathy, offering insights into the intricacies of drug discovery and development for ALS. Through this comprehensive analysis, the review sheds light on the critical aspects of identifying and advancing therapeutic solutions for ALS.

20.
Cancer Med ; 13(10): e7127, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38770540

RESUMO

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.


Assuntos
Neoplasias Bucais , Humanos , Masculino , Feminino , Neoplasias Bucais/radioterapia , Neoplasias Bucais/cirurgia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Pessoa de Meia-Idade , Idoso , Taiwan/epidemiologia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Resultado do Tratamento , Pontuação de Propensão , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Adulto , Estudos Retrospectivos , Taxa de Sobrevida , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...