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1.
Neural Regen Res ; 20(7): 1849-1863, 2025 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38934395

RESUMEN

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of mortality among infants aged less than 2 years. Biomarker research is currently receiving more attention, and new candidate biomarkers are constantly being discovered. This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons. We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy, which are classified as either specific or non-specific biomarkers. This review provides new insights into the pathogenesis of spinal muscular atrophy, the mechanism of biomarkers in response to drug-modified therapies, the selection of biomarker candidates, and would promote the development of future research. Furthermore, the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

2.
Biomaterials ; 312: 122707, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39121729

RESUMEN

Polypyrimidine tract-binding protein 1 (PTBP1) regulates numerous alternative splicing events during tumor progression and neurogenesis. Previously, PTBP1 downregulation was reported to convert astrocytes into functional neurons; however, how PTBP1 regulates astrocytic physiology remains unclear. In this study, we revealed that PTBP1 modulated glutamate uptake via ATP1a2, a member of Na+/K+-ATPases, and glutamate transporters in astrocytes. Ptbp1 knockdown altered mitochondrial function and energy metabolism, which involved PTBP1 regulating mitochondrial redox homeostasis via the succinate dehydrogenase (SDH)/Nrf2 pathway. The malfunction of glutamate transporters following Ptbp1 knockdown resulted in enhanced excitatory synaptic transmission in the cortex. Notably, we developed a biomimetic cationic triblock polypeptide system, i.e., polyethylene glycol44-polylysine30-polyleucine10 (PEG44-PLL30-PLLeu10) with astrocytic membrane coating to deliver Ptbp1 siRNA in vitro and in vivo, which approach allowed Ptbp1 siRNA to efficiently cross the blood-brain barrier and target astrocytes in the brain. Collectively, our findings suggest a framework whereby PTBP1 serves as a modulator in glutamate transport machinery, and indicate that biomimetic methodology is a promising route for in vivo siRNA delivery.


Asunto(s)
Astrocitos , Ácido Glutámico , Ribonucleoproteínas Nucleares Heterogéneas , Homeostasis , Factor 2 Relacionado con NF-E2 , Proteína de Unión al Tracto de Polipirimidina , ARN Interferente Pequeño , Animales , Astrocitos/metabolismo , Ácido Glutámico/metabolismo , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Proteína de Unión al Tracto de Polipirimidina/genética , Factor 2 Relacionado con NF-E2/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/genética , Ratones , Transducción de Señal , Membrana Celular/metabolismo , Ratones Endogámicos C57BL , Masculino , Humanos , Mitocondrias/metabolismo
3.
Neural Regen Res ; 20(2): 424-439, 2025 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38819046

RESUMEN

Alzheimer's disease is a debilitating, progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins, including amyloid plaques and intracellular tau tangles, primarily within the brain. Lysosomes, crucial intracellular organelles responsible for protein degradation, play a key role in maintaining cellular homeostasis. Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases, including Alzheimer's disease. Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer's disease. Currently, the efficacy of drugs in treating Alzheimer's disease is limited, with major challenges in drug delivery efficiency and targeting. Recently, nanomaterials have gained widespread use in Alzheimer's disease drug research owing to their favorable physical and chemical properties. This review aims to provide a comprehensive overview of recent advances in using nanomaterials (polymeric nanomaterials, nanoemulsions, and carbon-based nanomaterials) to enhance lysosomal function in treating Alzheimer's disease. This review also explores new concepts and potential therapeutic strategies for Alzheimer's disease through the integration of nanomaterials and modulation of lysosomal function. In conclusion, this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer's disease. The application of nanotechnology to the development of Alzheimer's disease drugs brings new ideas and approaches for future treatment of this disease.

4.
Clin Chim Acta ; 564: 119940, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39178937

RESUMEN

BACKGROUND: Natriuretic peptide testing is guideline recommended as an aid to the diagnosis of heart failure (HF). We sought to evaluate the performance of the ADVIA Centaur (Siemens Healthcare Diagnostics, Tarrytown, NY) NT-proBNPII assay (PBNPII) in emergency department (ED) dyspneic patients. METHODS: Eligible patients presented to the ED with dyspnea, with their gold standard diagnosis determined by up to 3 cardiologists blinded to the PBNPII results. Patients were stratified into 3 groups based on PBNPII resultsa rule out group of NT-proBNP<300  pg/mL, an age-specific rule in group using cutoffs of 450, 900, and 1800 pg/mL, for <50, 50-75, and > 75 years respectively, and an intermediate cohort for results between the rule out and rule in groups. RESULTS: Of 3128 eligible patients, 1148 (36.7 %) were adjudicated as acute heart failure (AHF). The gold standard AHF diagnosis rate was 3.7, 24.3, and 67.2 % for patients with NTproBNPII in the negative, indeterminate, and positive groups, respectively. Overall likelihood ratios (LR) were 0.07 (95 % CI: 0.05,0.09), 0.55 (0.45,0.67), and 3.53 (3.26,3.83) for the same groups, respectively. Individual LR+for age dependent cutoffs were 5.01 (4.25,5.91), 3.71 (3.25,4.24), and 2.38 (2.10,2.69), respectively. NTproBNPII increased with increasing severity of HF when stratified by NYHA classification. CONCLUSIONS: The ADVIA Centaur PBNPII assay demonstrates acceptable clinical performance using the recommended single rule out and age dependent rule in cutoffs for an AHF diagnosis in dyspneic ED patients.


Asunto(s)
Servicio de Urgencia en Hospital , Insuficiencia Cardíaca , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Humanos , Péptido Natriurético Encefálico/sangre , Anciano , Femenino , Masculino , Persona de Mediana Edad , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/sangre , Fragmentos de Péptidos/sangre , Anciano de 80 o más Años
5.
J Environ Sci (China) ; 147: 259-267, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003045

RESUMEN

Arsenic (As) pollution in soils is a pervasive environmental issue. Biochar immobilization offers a promising solution for addressing soil As contamination. The efficiency of biochar in immobilizing As in soils primarily hinges on the characteristics of both the soil and the biochar. However, the influence of a specific property on As immobilization varies among different studies, and the development and application of arsenic passivation materials based on biochar often rely on empirical knowledge. To enhance immobilization efficiency and reduce labor and time costs, a machine learning (ML) model was employed to predict As immobilization efficiency before biochar application. In this study, we collected a dataset comprising 182 data points on As immobilization efficiency from 17 publications to construct three ML models. The results demonstrated that the random forest (RF) model outperformed gradient boost regression tree and support vector regression models in predictive performance. Relative importance analysis and partial dependence plots based on the RF model were conducted to identify the most crucial factors influencing As immobilization. These findings highlighted the significant roles of biochar application time and biochar pH in As immobilization efficiency in soils. Furthermore, the study revealed that Fe-modified biochar exhibited a substantial improvement in As immobilization. These insights can facilitate targeted biochar property design and optimization of biochar application conditions to enhance As immobilization efficiency.


Asunto(s)
Arsénico , Carbón Orgánico , Aprendizaje Automático , Contaminantes del Suelo , Suelo , Carbón Orgánico/química , Arsénico/química , Contaminantes del Suelo/química , Contaminantes del Suelo/análisis , Suelo/química , Modelos Químicos
6.
Gigascience ; 132024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-39283687

RESUMEN

BACKGROUND: The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, YFP) and the East Asian finless porpoise (Neophocaena asiaeorientalis sunameri, EFP) are 2 subspecies of the narrow-ridged finless porpoise that live in freshwater and saltwater, respectively. The main objective of this study was to provide contiguous chromosome-level genome assemblies for YFP and EFP. RESULTS: Here, we generated and upgraded the genomes of YFP and EFP at the telomere-to-telomere level through the integration of PacBio HiFi long reads, ultra-long ONT reads, and Hi-C sequencing data with a total size of 2.48 Gb and 2.50 Gb, respectively. The scaffold N50 of 2 genomes was 125.12 Mb (YFP) and 128 Mb (EFP) with 1 contig for 1 chromosome. The telomere repeat and centromere position were clearly identified in both YFP and EFP genomes. In total, 5,480 newfound genes were detected in the YFP genome, including 56 genes located in the newly identified centromere regions. Additionally, synteny blocks, structural similarities, phylogenetic relationships, gene family expansion, and inference of selection were studied in connection with the genomes of other related mammals. CONCLUSIONS: Our research findings provide evidence for the gradual adaptation of EFP in a marine environment and the potential sensitivity of YFP to genetic damage. Compared to the 34 cetacean genomes sourced from public databases, the 2 new assemblies demonstrate superior continuity with the longest contig N50 and scaffold N50 values, as well as the lowest number of contigs. The improvement of telomere-to-telomere gap-free reference genome resources supports conservation genetics and population management for finless porpoises.


Asunto(s)
Genoma , Marsopas , Telómero , Marsopas/genética , Telómero/genética , Animales , Especies en Peligro de Extinción , Filogenia , Genómica/métodos , Pueblos del Este de Asia
7.
Pharmacol Ther ; : 108721, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39284368

RESUMEN

Ischaemic stroke (IS) is the second leading cause of death and a major cause of disability worldwide. Currently, the clinical management of IS still depends on restoring blood flow via pharmacological thrombolysis or mechanical thrombectomy, with accompanying disadvantages of narrow therapeutic time window and risk of haemorrhagic transformation. Thus, novel pathophysiological mechanisms and targeted therapeutic candidates are urgently needed. The autophagy-lysosomal pathway (ALP), as a dynamic cellular lysosome-based degradative process, has been comprehensively studied in recent decades, including its upstream regulatory mechanisms and its role in mediating neuronal fate after IS. Importantly, increasing evidence has shown that IS can lead to lysosomal dysfunction, such as lysosomal membrane permeabilization, impaired lysosomal acidity, lysosomal storage disorder, and dysfunctional lysosomal ion homeostasis, which are involved in the IS-mediated defects in ALP function. There is tightly regulated crosstalk between transcription factor EB (TFEB), mammalian target of rapamycin (mTOR) and lysosomal function, but their relationship remains to be systematically summarized. Notably, a growing body of evidence emphasizes the benefits of naturally derived compounds in the treatment of IS via modulation of ALP function. However, little is known about the roles of natural compounds as modulators of lysosomes in the treatment of IS. Therefore, in this context, we provide an overview of the current understanding of the mechanisms underlying IS-mediated ALP dysfunction, from a lysosomal perspective. We also provide an update on the effect of natural compounds on IS, according to their chemical structural types, in different experimental stroke models, cerebral regions and cell types, with a primary focus on lysosomes and autophagy initiation. This review aims to highlight the therapeutic potential of natural compounds that target lysosomal and ALP function for IS treatment.

8.
Adv Healthc Mater ; : e2401532, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285808

RESUMEN

The rapid advancements in artificial intelligence, micro-nano manufacturing, and flexible electronics technology have unleashed unprecedented innovation and opportunities for applying flexible sensors in healthcare, wearable devices, and human-computer interaction. The human body's tactile perception involves physical parameters such as pressure, temperature, and humidity, all of which play an essential role in maintaining human health. Inspired by the sensory function of human skin, many bionic sensors have been developed to simulate human skin's perception to various stimuli and are widely applied in health monitoring. Given the urgent requirements for sensing performance and integration of flexible sensors in the field of wearable devices and health monitoring, here is a timely overview of recent advances in pressure, humidity, temperature, and multi-functional sensors for human health monitoring. It covers the fundamental components of flexible sensors and categorizes them based on different response mechanisms, including resistive, capacitive, voltage, and other types. Specifically, the application of these flexible tactile sensors in the area of human health monitoring is highlighted. Based on this, an extended overview of recent advances in dual/triple-mode flexible sensors integrating pressure, humidity, and temperature tactile sensing is presented. Finally, the challenges and opportunities of flexible sensors are discussed.

9.
Int J Colorectal Dis ; 39(1): 142, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289219

RESUMEN

OBJECTIVE: The aim of this study is to evaluate the significance of combined detection of Septin9 and syndecan-2 (SDC2) methylation markers and serum tumor markers for the early diagnosis of colorectal cancer. METHODS: A total of 116 patients diagnosed with colorectal cancer between December 2022 and February 2024 were designated as the colorectal cancer group. Additionally, 31 patients with colorectal adenoma were assigned to the adenoma group, while 44 individuals undergoing routine physical examinations were included in the control group. Concentrations of Septin9, SDC2, fecal occult blood (FOB), and four tumor markers-carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 724 (CA724)-were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves for Septin9, SDC2, the four tumor markers, FOB, the combination of Septin9 and SDC2, and the combined use of all seven indicators (CEA, CA19-9, CA125, CA72-4, FOB, Septin9, and SDC2). RESULTS: The colorectal cancer group exhibited the highest positive rates for Septin9, SDC2, the four tumor markers, the combined detection of Septin9 and SDC2, and the combined detection of all seven indicators, compared to both the adenoma and control groups (P < 0.05). The adenoma group also showed higher positive rates than the control group (P < 0.05). For patients with stage I-III colorectal cancer, the positive rates for the combined detection of Septin9 and SDC2 were 81.3%, 78.9%, and 90.2%, respectively, surpassing those for the combined detection of the four tumor markers (43.8%, 55.3%, and 61.0%). Additionally, the positive rates for the two-gene combination in stage III colorectal cancer were higher than those for FOB (P < 0.05). The sensitivity and area under the curve (AUC) for SDC2 were 73.3% and 0.855, respectively, exceeding the sensitivity and AUC for the combined four tumor markers, which were 60.3% and 0.734 (P < 0.05). The combined detection of the two methylated genes demonstrated a sensitivity of 86.2% and an AUC of 0.908, outperforming both FOB and the combined detection of the four tumor markers (P < 0.05). CONCLUSION: The detection of SDC2 exhibits high sensitivity for colorectal cancer, and when combined with Septin9, it significantly enhances the diagnostic accuracy for early-stage colorectal cancer, offering substantial clinical value.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales , Detección Precoz del Cáncer , Septinas , Sindecano-2 , Humanos , Septinas/sangre , Septinas/genética , Sindecano-2/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/diagnóstico , Biomarcadores de Tumor/sangre , Femenino , Masculino , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Anciano , Curva ROC , Adulto , Sangre Oculta
10.
Hum Genomics ; 18(1): 104, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39289776

RESUMEN

BACKGROUND: High-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent. OBJECTIVES: This study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin. RESULTS: Population genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f3/f4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture. CONCLUSIONS: The study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape.


Asunto(s)
Alelos , Genética de Población , Selección Genética , Humanos , Adaptación Biológica/genética , China , Pueblos del Este de Asia/genética , Etnicidad/genética , Variación Genética , Haplotipos , Polimorfismo de Nucleótido Simple
11.
Sci Data ; 11(1): 1012, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294137

RESUMEN

Coptis teeta Wall. (Ranunculaceae), an endangered plant species of significant medicinal value, predominantly undergoes clonal propagation, potentially compromising the species' evolutionary potential and ultimately increase its risk of extinction. In this study, we successfully assembled two sets of haploid genomes (Hap1 and Hap2) for C. teeta, comprising nine homologous chromosome pairs, by employing Illumina and PacBio sequencing technologies. The genome annotation identified a total of 43,979 and 46,311 protein-coding genes in Hap1 and in Hap2, and most of them were functionally annotated. The high-quality reference genome will serve as an indispensable genomic resource for conservation and comprehensive exploitation of this endangered species. Between the two haploid genomes, numerous structural alterations were detected within the nine homologous chromosome pairs, potentially resulting in aberrant synapsis and irregular chromosomal segregation and thus contributing to the sustained preservation of clonal propagation in C. teeta. The findings offer new perspective for elucidating the genetic mechanism underlying the compromised sexual reproductive capacity of C. teeta, thereby facilitating its enhancement though molecular breeding and genetic improvement.


Asunto(s)
Coptis , Especies en Peligro de Extinción , Genoma de Planta , Haplotipos , Plantas Medicinales , Plantas Medicinales/genética , Coptis/genética , Haploidia
12.
Sci Data ; 11(1): 1011, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294147

RESUMEN

The upas tree (Antiaris toxicaria Lesch.) is a medically important plant that contains various specialized metabolites with significant bioactivity. The lack of a reference genome hinders the in-depth study as well as rational exploitation and conservation of this plant. Here, we present the first holotype-resolved chromosome-scale genome of the upas tree. The assembled genome consisted of 26 chromosomes that contain 1.34 Gb of sequencing data with a contig N50 length of 60 Mb. Genome annotation identified 43,500 protein-coding genes in the upas tree genome, of which 98.75% were functionally annotated. This high-quality reference genome will lay the foundation for further studies on the evolution and functional genomics of the upas tree.


Asunto(s)
Genoma de Planta , Haplotipos , Anotación de Secuencia Molecular , Cromosomas de las Plantas/genética
13.
Heliyon ; 10(17): e36911, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296053

RESUMEN

Background: Recent studies have shown that the serum glucose-potassium ratio (GPR) upon admission is correlated with the prognosis of cerebrovascular disorders. Herein, we investigated the relationship between GPR and 90-day functional outcomes in patients with acute ischaemic stroke (AIS). Methods: Clinical data were collected from patients with AIS registered at the Stroke Center of Jiangsu Provincial Hospital of Chinese Medicine. The relationship between the GPR and 90-day outcomes was analysed using univariate and multivariate logistic regression analyses, linear regression analyses, and subgroup analyses. Results: A total of 1826 patients met the enrolment requirements. The number of patients with a glucose-to-potassium ratio greater than the median value increased proportionally with increases in the NIHSS at admission and the 90-day modified Rankin scale (mRS). Univariate logistic regression analysis revealed a significant relationship between GPR and 90-day negative prognosis (OR 1.34 [95%Cl, 1.17-1.54], P < 0.001). After adjusting for all confounding variables, the relationship between GPR and 90-day adverse prognosis was shown to be nonlinearly U-shaped, with an inflection point of the curve for GPR of 1.347. Two linear regression analyses were performed on the basis of the inflection points of the curves. The results of this analysis revealed a negative correlation between GPR and 90-day adverse outcomes at GPR<1.347 (OR 0.86 [95%CI,0.09-7.86], P = 0.897), as well as a positive correlation between GPR and 90-day adverse outcomes at GPR≥1.347 (OR1.52 [95%CI, 1.19-1.93], P = 0.001). Subgroup analyses verified that the association between GPR and 90-day poor prognosis still existed, regardless of whether the patient had a history of diabetes mellitus (DM). (with DM: OR 1.39 [ 95%Cl, 1.05-1.83], P = 0.001); without DM: OR 0.93 [ 95%Cl,0.56-1.55], P = 0.016). Conclusions: GPR significantly correlated with poor prognosis at 90-days in patients with AIS. Early intervention and control of GPR are expected to enhance functional outcomes in patients with AIS.

14.
Heliyon ; 10(17): e37110, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296110

RESUMEN

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by multi-organ involvement and the presence of autoantibodies, pathogenic factors that can serve as diagnostic biomarkers. The current research has been focusing on exploring specific autoantigens with clinical relevance for SLE subtypes. In line with this objective, this study investigated potential antigenic targets associated with specific phenotypes in SLE by leveraging an omics-based approach combined with immunoassay techniques. Methods: A transcriptomic analysis was conducted in a cohort of 70 SLE patients to identify genes significantly correlated to the relevant phenotype. Epitope mapping and sequence analysis techniques were used to predict autoantigens, and the corresponding antibodies were subsequently quantified by enzyme-linked immunosorbent assay (ELISA) and validated by Western blot. Results: Transcriptomic data analysis revealed a group of hub genes exhibiting a significant correlation with the neuropsychiatric phenotype and a positive relationship with platelets. Subsequent epitope prediction for the corresponding proteins highlighted vasodilator-stimulated phosphoprotein (VASP) as a potential autoantigen. Moreover, ELISA and immunoblotting confirmed that the anti-VASP antibody present in the serum was significantly elevated in SLE patients with neuropsychiatric involvement and positively associated with demyelination. Conclusion: VASP harbors autoantigenic epitopes associated with neuropsychiatric phenotype, especially the demyelination symptom in SLE, and its antibodies may serve as promising biomarkers in this disease.

15.
Infect Drug Resist ; 17: 3989-4000, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296777

RESUMEN

Objective: We retrospectively review consecutive patients with nontuberculous mycobacterium (NTM) pulmonary disease reported from a designated hospital for infectious diseases in the Fuyang district of China to determine the clinical characteristics of these patients. Methods: This research enrolled 234 patients with NTM pulmonary disease between January 2018 and May 2023 in the Fuyang district of China. Data were collected from the electronic medical records. The NTM strain composition and clinical characteristics of NTM pulmonary disease were retrospectively analyzed. Results: 73 (31.20%) patients had previous tuberculosis (TB) or TB exposure history and bronchiectasis. Mixed NTM infection accounted for 12.39%. Mycobacterium intracellulare strain was detected in 132 patients (49.62%). Women were found to be more affected by Mycobacterium avium infection, and men by Mycobacterium abscessus infection. Mycobacterium avium (34.21%) and Mycobacterium abscessus (33.33%) strains were most common in people with previous TB or TB exposure history. Among respiratory tract-related diseases, patients with bronchiectasis had the highest isolation rate of Mycobacterium avium (55.36%). Women were susceptible to bronchiectasis (P <0.01). The median of mononuclear-to-lymphocyte ratio (MLR) was higher in men than in women (P < 0.01). The serum albumin (ALB) level was lower in patients with TB or TB exposure history than in those without TB history (P = 0.034). The prognostic nutritional index (PNI) was lower in patients with TB or TB exposure history than in those without tuberculosis history (P = 0.021). Patients with NTM lung disease were poorly treated. Conclusion: Clinical symptoms of the disease were not species-specific. Mycobacterium intracellulare and Mycobacterium avium strains were predominant in the Fuyang district of China. Previous TB or TB exposure history immensely enhanced the risk of NTM disease.

16.
Chem Commun (Camb) ; 60(76): 10512-10515, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39225283

RESUMEN

A novel selenium dioxide promoted selenylation/cyclization of leucosceptrane sesterterpenoids was reported. Two types of leucosceptrane derivatives with different valence states of selenium atoms (Se2+ and Se4+) were obtained. The mechanisms of these two processes were proposed, and the selenium-containing derivates may serve as intermediates of Riley oxidation that could be trapped with appropriate substrates. Immunosuppressive activity screening revealed that 10 and 11 had obvious inhibitory effects on IFN-γ production, with IC50 values of 5.29 and 17.60 µM, respectively, which were more active than their precursor leucosceptroid A.


Asunto(s)
Óxidos de Selenio , Sesterterpenos , Ciclización , Óxidos de Selenio/química , Sesterterpenos/química , Sesterterpenos/farmacología , Interferón gamma/metabolismo , Inmunosupresores/química , Inmunosupresores/farmacología , Estructura Molecular , Animales , Ratones , Selenio/química , Selenio/farmacología
17.
J Affect Disord ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293598

RESUMEN

BACKGROUND: The rapid increase in the number of patients with chronic diseases and depression, as well as the rapid spread of their effects, have led to these two health problems gradually developing into major public health issues in China and around the world. Currently, many individuals with chronic diseases are experiencing depressive symptoms one after another. Therefore, it is imperative to conduct research on how to prevent depression in this growing population of individuals with chronic diseases in a timely manner. METHODS: Based on the data of the 2015 and 2018 national follow-up surveys of the China Health and Elderly Care Longitudinal Survey, a total of 7641 patients with short-term increase in the number of chronic diseases were selected as the study objects, and a binary logistic regression model was constructed according to the five dimensions of the health ecology model. The neural network model was used to explore the main (first two) factors affecting the increase in the number of chronic diseases in China in the short term, and the random forest and extreme value gradient lifting algorithm were used to verify them, and effective suggestions were put forward. RESULTS: The detection rate of depression in the population with increasing number of chronic diseases from 2015 to 2018 was 42.13 %. The model was established based on five dimensions of the health ecology model: Model 1 (Personal trait layer), Model 2 (Personal trait layer plus Behavioral feature layer), Model 3 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer), Model 4 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer plus Networking layer) and Model 5 (Personal trait layer plus Behavioral feature layer plus Living and working conditions layer plus Networking layer plus Policy environment layer).The prediction accuracy of the five models was 66.4 %, 68.3 %, 70.7 %, 71.6 % and 71.6 %, respectively, and Model 5 showed that the P values of gender, self-rated health, night's sleep time (h), disability, life satisfaction, child satisfaction, place of residence and highest level of education were all <0.05, life satisfaction and self-rated health importance were 0.249 (100 %) and 0.226 (90.8 %). CONCLUSION: Gender, self-rated health, night sleep duration, disability, satisfaction with life, satisfaction with children, place of residence and highest level of education were the main influencing factors for the increase of depressive symptoms in the population with chronic diseases in the short term, among which life satisfaction and self-rated health have the greatest impact on depressive symptoms, and there is an interaction between the two.

18.
Neuroscience ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293730

RESUMEN

Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In the current study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissues and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and evaluated its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and microglial repopulation was primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Moreover, expression of complement-related genes, such as C4b and Cd47, were substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis, and provides new insight into its potential role in SAE.

19.
Lab Chip ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39289895

RESUMEN

We propose an innovative design for interdigital transducers (IDTs), enabling phase modulation of surface acoustic waves (SAWs) with a dislocated electrode structure. By designing the size and arrangement of these dislocated IDTs, a novel type of Airy SAWs can be generated, exhibiting self-accelerating, self-bending, and self-healing characteristics. The acceleration of the generated Airy SAW is 0.081 cm-1. Furthermore, particles and bubbles can be precisely manipulated using the generated Airy SAW. The proposed dislocated IDTs could be used for generation of many other types of SAWs, hence holding great promise for applications including SAW shaping, particle manipulation/sorting, and acoustic sensing/detection.

20.
Behav Brain Res ; 476: 115247, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39277141

RESUMEN

Glutamatergic alteration is one of the potential mechanisms of depression. However, there is no consensus on whether glutamate metabolism changes affect the myelin structure of depression in mouse models. Glutamate chemical exchange saturation transfer (GluCEST) is a novel and powerful molecular imaging technique that can visualize glutamate distribution. In this study, we used the GluCEST imaging technique to look at glutamate levels in mice under chronic unpredictable mild stress (CUMS) and how they relate to demyelination. The CUMS mice were exposed to different stress factors for 6 weeks. Evaluated of depression in CUMS mice by behavioral tests. MRI scans were then performed, including T2-mapping, GluCEST, and diffusion tensor imaging (DTI) sequences. Brain tissues were collected for Luxol Fast Blue staining and immunofluorescence staining to analyze the changes in the myelin sheath. Artificially sketched regions of interest (ROI) (corpus callosum, hippocampus, and thalamus) were used to calculate the GluCEST value, fractional anisotropy (FA), and T2 value. Compared with the control group, the GluCEST value in the ROIs of CUMS mice significantly decreased. Similarly, the FA value in ROIs was lower in the CUMS group than in the CTRL group, but the T2 value did not differ significantly between the two groups. The histological results showed that ROIs in the CUMS group had demyelination compared with the CTRL group, indicating that DTI was more sensitive than T2 mapping in detecting myelin abnormalities. Furthermore, the GluCEST value in the ROIs correlates positively with the FA value. These findings suggest that altered glutamate metabolism may be one of the important factors leading to demyelination in depression, and GluCEST is expected to serve as an imaging biological marker for the diagnosis of demyelination in depression.

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