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1.
Heliyon ; 10(12): e32833, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975231

RESUMO

Background: Bronchobiliary fistulas (BBFs), primarily stemming from choledocholithiasis, present considerable diagnostic and treatment challenges. Their prolonged nature can lead to life-threatening situations without timely management, often complicated by lung abscesses. Case presentation: A 64-year-old man, presenting with fever, chills, and a cough initially misdiagnosed as a common cold, developed severe respiratory distress and delirium upon admission. Urgent intensive care unit (ICU) admission was prompted by a computed tomography (CT) scan revealing a right lung abscess. Enhanced CT scans and elevated bilirubin levels confirmed the biliary origin of the BBFs. Comprehensive treatment included laparoscopic partial hepatectomy, choledochojejunostomy, stone extraction, choledochoscopy, T-tube drainage, and BBFs closure. The patient was discharged with a T-tube. Follow-up CT after two months showed no recurrence. Conclusions: Managing BBFs, especially with concurrent lung abscesses in choledocholithiasis patients, remains challenging but feasible. Early diagnosis and intervention are crucial to improving survival rates and quality of life, highlighting the need for vigilance. This case underscores the importance of early detection and comprehensive treatment for successful outcomes in such complex conditions.

2.
Bioorg Chem ; 150: 107584, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38964146

RESUMO

Developing multitargeted ligands as promising therapeutics for Alzheimer's disease (AD) has been considered important. Herein, a novel class of cinnamamide/ester-triazole hybrids with multifaceted effects on AD was developed based on the multitarget-directed ligands strategy. Thirty-seven cinnamamide/ester-triazole hybrids were synthesized, with most exhibiting significant inhibitory activity against Aß-induced toxicity at a single concentration in vitro. The most optimal hybrid compound 4j inhibited copper-induced Aß toxicity in AD cells. its action was superior to that of donepezil and memantine. It also moderately inhibited intracellular AChE activity and presented favorable bioavailability and blood-brain barrier penetration with low toxicity in vivo. Of note, it ameliorated cognitive impairment, neuronal degeneration, and Aß deposition in Aß1-42-injured mice. Mechanistically, the compound regulated APP processing by promoting the ADAM10-associated nonamyloidogenic signaling and inhibiting the BACE1-mediated amyloidogenic pathway. Moreover, it suppressed intracellular AChE activity and tau phosphorylation. Therefore, compound 4j may be a promising multitargeted active molecule against AD.

3.
Virol J ; 21(1): 116, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783310

RESUMO

OBJECTIVE: Cystic echinococcosis (CE) represents a profoundly perilous zoonotic disease. The advent of viral macrogenomics has facilitated the exploration of hitherto uncharted viral territories. In the scope of this investigation, our objective is to scrutinize disparities in the intestinal microbiotic ecosystems of canines dwelling in elevated terrains and those afflicted by Echinococcus infection, employing the tool of viral macrogenomics. METHODS: In this study, we collected a comprehensive total of 1,970 fecal samples from plateau dogs infected with Echinococcus, as well as healthy control plateau dogs from the Yushu and Guoluo regions in the highland terrain of China. These samples were subjected to viral macrogenomic analysis to investigate the viral community inhabiting the canine gastrointestinal tract. RESULTS: Our meticulous analysis led to the identification of 136 viral genomic sequences, encompassing eight distinct viral families. CONCLUSION: The outcomes of this study hold the potential to enhance our comprehension of the intricate interplay between hosts, parasites, and viral communities within the highland canine gut ecosystem. Through the examination of phage presence, it may aid in early detection or assessment of infection severity, providing valuable insights into Echinococcus infection and offering prospects for potential treatment strategies.


Assuntos
Doenças do Cão , Equinococose , Echinococcus , Fezes , Microbioma Gastrointestinal , Animais , Cães , Equinococose/veterinária , Doenças do Cão/parasitologia , Doenças do Cão/microbiologia , Doenças do Cão/virologia , China , Fezes/parasitologia , Fezes/microbiologia , Fezes/virologia , Echinococcus/genética , Echinococcus/isolamento & purificação , Genoma Viral , Vírus/classificação , Vírus/isolamento & purificação , Vírus/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-38655785

RESUMO

Ca-substituted Ba1-xCaxMg2Al6Si9O30 ceramics were prepared to explore the relationships among their crystal structural parameters, phase compositions, dielectric properties, and coefficients of thermal expansion and applications in C-band antenna. The maximum solubility of Ba1-xCaxMg2Al6Si9O30 was located at x = 0.25, and Ba1-xCaxMg2Al6Si9O30 ceramics (0 ≤ x ≤ 0.25) crystallized in the space group P6/mcc. In Ba1-xCaxMg2Al6Si9O30 single-phase ceramics, εr was dominated by ionic polarizability and "rattling effects" of Ba2+ and Al(2)3+; Q × f was controlled by the roundness of [Si4Al2O18] inner rings and total lattice energy; and τf was affected by the bond valence of Si/Al(1)-O(1). Notably, the low average coefficients of thermal expansion (2.668 ppm/°C) at -150 °C ≤ T ≤ 850 °C and near-zero coefficients of thermal expansion (1.254 ppm/°C) at -150 °C ≤ T ≤ 260 °C were achieved for the Ba1-xCaxMg2Al6Si9O30 (x = 0.1) ceramic. Optimum microwave and terahertz dielectric properties were obtained for the Ba1-xCaxMg2Al6Si9O30 (x = 0.1) ceramic with εr = 5.80, Q × f = 31,174 at 13.99 GHz, τf = -7.10 ppm/°C, and εr = 5.71-5.85 at 0.2 THz ≤ f ≤ 1.0 THz. Also, the Ba1-xCaxMg2Al6Si9O30 (x = 0.1) ceramic substrate had been designed as a C-band patch antenna with a high simulated radiation efficiency (87.76%) and gain (6.30 dBi) at 7.70 GHz (|S11| = -38.41 dB).

5.
Polymers (Basel) ; 16(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38675058

RESUMO

Biodegradable polylactic acid (PLA) has been widely used in fused deposition modeling (FDM) 3D printing. In order to improve its comprehensive properties in 3D printing, in this study, 0-40% content of polybutylene adipate terephthalate(PBAT) was selected to be blended with PLA in a twin-screw extruder; the resulting pellets were drawn into a homogeneous filament; then, PBAT/PLA samples were prepared by FDM 3D printing, and the effects of the dosage of PBAT on the mechanical properties, thermal behavior, surface wettability and melt flowability of the samples were investigated. The results showed that all the samples could be printed smoothly, and the ductility was slightly improved by the increase in the PBAT dosage; the thermal stability of PLA was enhanced by blending with PBAT, and the crystallinity increased monotonically with the increase in PBAT. After blending with PBAT, the surfaces of the samples were more hydrophilic and flowable. The important conclusion achieved in this work was that the PBAT/PLA blends, especially those containing 30%PBAT, showed great potential to replace petroleum-based plastics and are suitable for use in FDM 3D printing technologies for different applications.

6.
Cell Mol Immunol ; 21(6): 575-588, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38632385

RESUMO

Neonates are susceptible to inflammatory disorders such as necrotizing enterocolitis (NEC) due to their immature immune system. The timely appearance of regulatory immune cells in early life contributes to the control of inflammation in neonates, yet the underlying mechanisms of which remain poorly understood. In this study, we identified a subset of neonatal monocytes characterized by high levels of neuropilin-1 (Nrp1), termed Nrp1high monocytes. Compared with their Nrp1low counterparts, Nrp1high monocytes displayed potent immunosuppressive activity. Nrp1 deficiency in myeloid cells aggravated the severity of NEC, whereas adoptive transfer of Nrp1high monocytes led to remission of NEC. Mechanistic studies showed that Nrp1, by binding to its ligand Sema4a, induced intracellular p38-MAPK/mTOR signaling and activated the transcription factor KLF4. KLF4 transactivated Nos2 and enhanced the production of nitric oxide (NO), a key mediator of immunosuppression in monocytes. These findings reveal an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for treating inflammatory disorders in neonates.


Assuntos
Animais Recém-Nascidos , Enterocolite Necrosante , Inflamação , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like , Monócitos , Neuropilina-1 , Monócitos/metabolismo , Monócitos/imunologia , Animais , Neuropilina-1/metabolismo , Neuropilina-1/genética , Inflamação/patologia , Inflamação/imunologia , Humanos , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Enterocolite Necrosante/imunologia , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/prevenção & controle , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Camundongos Endogâmicos C57BL , Recém-Nascido , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Camundongos Knockout
7.
Blood Adv ; 8(11): 2635-2645, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38564778

RESUMO

ABSTRACT: Chimeric antigen receptor (CAR) natural killer (NK) cells can eliminate tumors not only through the ability of the CAR molecule to recognize antigen-expressed cancer cells but also through NK-cell receptors themselves. This overcomes some of the limitations of CAR T cells, paving the way for CAR NK cells for safer and more effective off-the-shelf cellular therapy. In this study, CD70-specific (a pan-target of lymphoma) fourth-generation CAR with 4-1BB costimulatory domain and interleukin-15 (IL-15) was constructed and transduced into cord blood-derived NK cells by Baboon envelope pseudotyped lentiviral vector. CD70-CAR NK cells displayed superior cytotoxic activity in vitro and in vivo against CD19-negative B-cell lymphoma when compared with nontransduced NK cells and CD19-specific CAR NK cells. Importantly, mice that received 2 doses of CD70-CAR NK cells showed effective eradication of tumors, accompanied by increased concentration of plasma IL-15 and enhanced CAR NK cell proliferation and persistence. Our study suggests that repetitive administration-based CAR NK-cell therapy has clinical advantage compared with a single dose of CAR NK cells for the treatment of B-cell lymphoma.


Assuntos
Antígenos CD19 , Ligante CD27 , Imunoterapia Adotiva , Interleucina-15 , Células Matadoras Naturais , Linfoma de Células B , Receptores de Antígenos Quiméricos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Animais , Humanos , Camundongos , Linfoma de Células B/terapia , Linfoma de Células B/imunologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva/métodos , Antígenos CD19/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Citotoxicidade Imunológica
8.
J Genet Genomics ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38657948

RESUMO

Environmental factors such as diet and lifestyle can influence the health of both mothers and offspring. However, its transgenerational transmission and underlying mechanisms remain largely unknown. Here, using a maternal lactation-period low-protein diet (LPD) mouse model, we show that maternal LPD during lactation causes decreased survival and stunted growth, significantly reduces ovulation and litter size, and alters the gut microbiome in the female LPD-F1 offspring. The transcriptome of LPD-F1 metaphase II (MII) oocytes shows that differentially expressed genes are enriched in female pregnancy and multiple metabolic processes. Moreover, maternal LPD causes early stunted growth and impairs metabolic health, which is transmitted over two generations. The methylome alteration of LPD-F1 oocytes can be partly transmitted to the F2 oocytes. Together, our results reveal that LPD during lactation transgenerationally affects offspring health, probably via oocyte epigenetic changes.

9.
Talanta ; 275: 126078, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38678921

RESUMO

A method for simultaneous determination of nitrogen content and 15N isotope abundance in plants was established by Elemental analysis-gas isotope ratio mass spectrometry. Taking poplar leaves and l-glutamic acid as standards, nitrogen content was determined using the standard curve established by weighted least squares regression between the mass of nitrogen element and the total peak height intensity at m/z 28 and 29. Then the 15N isotope abundance was calculated with the peak height intensity at m/z 28 and 29. Through the comparison of several sets of experiments, the impact of mass discrimination effect, tin capsule consumables, isotope memory effect, and the quality of nitrogen on the results were assessed. The results showed that with a weight of 1/x2, the standard curve has a coefficient of determination (R2) of 0.9996. Compared to the traditional Kjeldahl method, the measured nitrogen content deviated less than 0.2 %, and the standard deviation (SD) was less than 0.2 %. Compared to the sodium hypobromite method, the 15N isotopic abundances differed less than 0.2 atom%15N, and the SD was less than 0.2 atom% 15N. The established method offers the advantages of being fast, simple, accurate, and high throughput, providing a novel approach for the simultaneous determination of nitrogen content and 15N isotope abundance in plant samples.


Assuntos
Isótopos de Nitrogênio , Nitrogênio , Isótopos de Nitrogênio/análise , Nitrogênio/análise , Nitrogênio/química , Folhas de Planta/química , Espectrometria de Massas/métodos , Populus/química
10.
Small Methods ; : e2301675, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459803

RESUMO

Currently, it is widely reported that the photovoltaic effect in ferroelectric materials can be promoted by the application of a piezoelectric force, an external electric field, and intense light illumination. Here, a semiconducting ferroelectric composition is introduced, (1-x) Ba0.06 Bi0.47 Na0.47 TiO3 -xMgCoO3 (abbreviated as xMgCo, where x = 0.02-0.08), synthesized through Mg/Co ions codoping. This process effectively narrows the optical bandgaps to a spectrum of 1.38-3.06 eV. Notably, the system exhibits a substantial increase in short-circuit photocurrent density (Jsc ), by the synergy of the electric, light, and thermal fields. The Jsc can still be further enhanced by the extra introduction of a force field. Additionally, the Jsc also shows an obvious increase after the high field pre-poling. The generation of a considerable number of oxygen vacancies due to the Co2+ /Co3+ mixed valence state (in a 1:3 ratio) contributes to the reduced optimal bandgap. The integration of Mg2+ ion at the A-site restrains the loss and sustains robust ferroelectricity (Pr  = 24.1 µC cm-2 ), high polarizability under an electric field, and a significant piezoelectric coefficient (d33  = 102 pC N-1 ). This study provides a novel perspective on the physical phenomena arising from the synergy of multiple fields in ferroelectric photovoltaic materials.

11.
J Leukoc Biol ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38447557

RESUMO

Immune functional decline and remodeling accompany aging and frailty. It is still largely unknown how changes in the immune cellular composition differentiate healthy individuals from those become frail at a relatively early age. Our aim in this exploratory study was to investigate immunological changes from newborn to frailty, and the association between health statute and various immune cell subtypes. The participants analyzed in this study covered human cord blood cells and peripheral blood cells collected from young adults, healthy and frail old individuals. A total of 30 immune cell subsets was performed by flow cytometry based on the surface markers of immune cells. Furthermore, frailty was investigated for its relations with various leukocyte subpopulations. Frail individuals exhibited a higher CD4/CD8 ratio, a higher proportion of CD4+ central memory T (TCM) cells, CD8+ effector memory T cells, CD27- switched memory B (CD27-BSM) cells, CD27+ switched memory B cells, age-associated B cells (ABCs) and CD38-CD24- B cells, and a lower proportion of naïve CD8 + T cells and progenitor B cells. The Frailty index score was found to be associated with naïve T cells, CD4/CD8 ratio, ABCs, CD27-BSM cells, and CD4+ TCM cells. Our findings conducted a relatively comprehensive and extensive atlas of age- and frailty-related changes in peripheral leukocyte subpopulations from newborn to frailty. The immune phenotypes identified in this study can contribute to a deeper understanding of immunosenescence in frailty and may provide a rationale for future interventions and diagnosis.

12.
Eur Arch Otorhinolaryngol ; 281(6): 3157-3166, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503971

RESUMO

PURPOSE: The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). METHODS: A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05-1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13-2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23-1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11-2.12; P = 0.009). CONCLUSION: Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings.


Assuntos
Neoplasias Orofaríngeas , Programa de SEER , Humanos , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Medição de Risco , Infecções por Papillomavirus/radioterapia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Pontuação de Propensão , Estudos Retrospectivos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia
13.
Adv Mater ; 36(25): e2400904, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38516720

RESUMO

The application of hardware-based neural networks can be enhanced by integrating sensory neurons and synapses that enable direct input from external stimuli. This work reports direct optical control of an oscillatory neuron based on volatile threshold switching in V3O5. The devices exhibit electroforming-free operation with switching parameters that can be tuned by optical illumination. Using temperature-dependent electrical measurements, conductive atomic force microscopy (C-AFM), in situ thermal imaging, and lumped element modelling, it is shown that the changes in switching parameters, including threshold and hold voltages, arise from overall conductivity increase of the oxide film due to the contribution of both photoconductive and bolometric characteristics of V3O5, which eventually affects the oscillation dynamics. Furthermore, V3O5 is identified as a new bolometric material with a temperature coefficient of resistance (TCR) as high as -4.6% K-1 at 423 K. The utility of these devices is illustrated by demonstrating in-sensor reservoir computing with reduced computational effort and an optical encoding layer for spiking neural network (SNN), respectively, using a simulated array of devices.

14.
Commun Biol ; 7(1): 301, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461223

RESUMO

Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal membrane rupture at parturition remains unknown. Here, we reveal that versican (VCAN) is the major hyalectan in the amnion, where its cleavage increases at parturition with spontaneous rupture of membrane. We further reveal that ADAMTS4 is a crucial proteolytic enzyme for VCAN cleavage in the amnion. Inflammatory factors may enhance VCAN cleavage by inducing ADAMTS4 expression and inhibiting ADAMTS4 endocytosis in amnion fibroblasts. In turn, versikine, the VCAN cleavage product, induces inflammatory factors in amnion fibroblasts, thereby forming a feedforward loop between inflammation and VCAN degradation. Mouse studies show that intra-amniotic injection of ADAMTS4 induces preterm birth along with increased VCAN degradation and proinflammatory factors abundance in the fetal membranes. Conclusively, there is enhanced VCAN cleavage by ADAMTS4 in the amnion at parturition, which can be reenforced by inflammation.


Assuntos
Proteína ADAMTS4 , Âmnio , Versicanas , Feminino , Humanos , Recém-Nascido , Gravidez , Proteína ADAMTS4/metabolismo , Âmnio/metabolismo , Inflamação/metabolismo , Parto/metabolismo , Peptídeo Hidrolases/metabolismo , Nascimento Prematuro/metabolismo , Versicanas/metabolismo , Animais , Camundongos
15.
Nat Commun ; 15(1): 2339, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490987

RESUMO

Taxol is a widely-applied anticancer drug that inhibits microtubule dynamics in actively replicating cells. Although a minimum 19-step biosynthetic pathway has been proposed and 16 enzymes likely involved have been characterized, stepwise biosynthetic reactions from the well-characterized di-oxygenated taxoids to Taxol tetracyclic core skeleton are yet to be elucidated. Here, we uncover the biosynthetic pathways for a few tri-oxygenated taxoids via confirming the critical reaction order of the second and third hydroxylation steps, unearth a taxoid 9α-hydroxylase catalyzing the fourth hydroxylation, and identify CYP725A55 catalyzing the oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. After identifying a acetyltransferase catalyzing the formation of C7-OAc, the pathway producing the highly-oxygenated 1ß-dehydroxybaccatin VI with the Taxol tetracyclic core skeleton is elucidated and its complete biosynthesis from taxa-4(20),11(12)-diene-5α-ol is achieved in an engineered yeast. These systematic studies lay the foundation for the complete elucidation of the biosynthetic pathway of Taxol.


Assuntos
Paclitaxel , Taxoides , Taxoides/metabolismo , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Hidroxilação , Oxirredução
16.
Neuro Oncol ; 26(7): 1262-1279, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38416702

RESUMO

BACKGROUND: Meningioma is the most common primary intracranial tumor with a high frequency of postoperative recurrence, yet the biology of the meningioma malignancy process is still obscure. METHODS: To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high-grade in situ tumors, and lung metastases, for extensive transcriptome characterization. Tumor suppressor candidate gene and molecular mechanism were functionally validated at the animal model and cellular levels. RESULTS: Comprehensive analysis and validation in mice and clinical cohorts indicated clusterin (CLU) had suppressive function for meningioma tumorigenesis and malignancy by inducing mitochondria damage and triggering type 1 interferon pathway dependent on its secreted isoform, and the inhibition effect was enhanced by TNFα as TNFα also induced type 1 interferon pathway. Meanwhile, both intra- and extracellular CLU overexpression enhanced macrophage polarization towards M1 phenotype and TNFα production, thus promoting tumor killing and phagocytosis. CONCLUSIONS: CLU might be a key brake of meningioma malignance by synchronously modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.


Assuntos
Clusterina , Macrófagos , Neoplasias Meníngeas , Meningioma , Clusterina/metabolismo , Clusterina/genética , Meningioma/patologia , Meningioma/metabolismo , Animais , Humanos , Camundongos , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Carcinogênese/metabolismo , Microambiente Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Células Tumorais Cultivadas , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética
17.
Front Mol Neurosci ; 17: 1342371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410694

RESUMO

Purpose: The TRAK1 gene is mapped to chromosome 3p22.1 and encodes trafficking protein kinesin binding 1. The aim of this study was to investigate the genotype-phenotype of TRAK1-associated epilepsy. Methods: Trio-based whole-exome sequencing was performed on a cohort of 98 patients with epilepsy of unknown etiologies. Protein modeling and the VarCards database were used to predict the damaging effects of the variants. Detailed neurological phenotypes of all patients with epilepsy having TRAK1 variants were analyzed to assess the genotype-phenotype correlations. Results: A novel TRAK1 compound heterozygous variant comprising variant c.835C > T, p.Arg279Cys and variant c.2560A > C, p.Lys854Gln was identified in one pediatric patient. Protein modeling and VarCards database analyses revealed that the variants were damaging. The patient received a diagnosis of early infantile epileptic spasms with a developmental disorder; he became seizure-free through valproate and adrenocorticotropic hormone treatment. Further results for six variants in 12 patients with epilepsy indicated that biallelic TRAK1 variants (including homozygous or compound heterozygous variants) were associated with epilepsy with developmental disorders. Among these patients, eight (67%) had epileptic spasms and seven (58%) were intractable to anti-seizure medicines. Moreover, eight patients experienced refractory status epilepticus, of which seven (88%) died in early life. To our knowledge, this is the first reported case of epilepsy caused by TRAK1 compound heterozygous variants. Conclusion: Biallelic TRAK1 variants can cause epilepsy and developmental disorders. In these patients, seizures progress to status epilepticus, suggesting a high risk for poor outcomes and the requirement of early treatment.

18.
J Cell Sci ; 137(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38345101

RESUMO

Understanding how biophysical and biochemical microenvironmental cues together influence the regenerative activities of muscle stem cells and their progeny is crucial in strategizing remedies for pathological dysregulation of these cues in aging and disease. In this study, we investigated the cell-level influences of extracellular matrix (ECM) ligands and culture substrate stiffness on primary human myoblast contractility and proliferation within 16 h of plating and found that tethered fibronectin led to stronger stiffness-dependent responses compared to laminin and collagen. A proteome-wide analysis further uncovered cell metabolism, cytoskeletal and nuclear component regulation distinctions between cells cultured on soft and stiff substrates. Interestingly, we found that softer substrates increased the incidence of myoblasts with a wrinkled nucleus, and that the extent of wrinkling could predict Ki67 (also known as MKI67) expression. Nuclear wrinkling and Ki67 expression could be controlled by pharmacological manipulation of cellular contractility, offering a potential cellular mechanism. These results provide new insights into the regulation of human myoblast stiffness-dependent contractility response by ECM ligands and highlight a link between myoblast contractility and proliferation.


Assuntos
Matriz Extracelular , Membrana Nuclear , Humanos , Antígeno Ki-67/metabolismo , Matriz Extracelular/metabolismo , Mioblastos/metabolismo , Proliferação de Células
19.
Adv Mater ; 36(19): e2312583, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38302690

RESUMO

Hollow multishelled structures (HoMSs) are attracting great interest in lithium-ion batteries as the conversion anodes, owing to their superior buffering effect and mechanical stability. Given the synthetic challenges, especially elemental diffusion barrier in the multimetal combinations, this complex structure design has been realized in low- and medium-entropy compounds so far. It means that poor reaction reversibility and low intrinsic conductivity remain largely unresolved. Here, a hollow multishelled (LiFeZnNiCoMn)3O4 high entropy oxide (HEO) is developed through integrating molecule and microstructure engineering. As expected, the HoMS design exhibits significant targeting functionality, yielding satisfactory structure and cycling stability. Meanwhile, the abundant oxygen defects and optimized electronic structure of HEO accelerate the lithiation kinetics, while the retention of the parent lattice matrix enables reversible lithium storage, which is validated by rigorous in situ tests and theoretical simulations. Benefiting from these combined properties, such hollow multishelled HEO anode can deliver a specific capacity of 967 mAh g-1 (89% capacity retention) after 500 cycles at 0.5 A g-1. The synergistic lattice and volume stability showcased in this work holds great promise in guiding the material innovations for the next-generation energy storage devices.

20.
J Int Med Res ; 52(1): 3000605231220827, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38180895

RESUMO

OBJECTIVE: We aimed to explore the prognostic value of Septin9 DNA methylation in breast cancer. METHODS: Breast cancer patients with and without recurrence or metastasis and matched non-breast cancer patients were screened retrospectively from 2014 to 2016. Bisulfite conversion and fluorescence quantitative methylation-specific polymerase chain reaction were used to detect the Septin9 methylation status and distribution levels in patient breast tissues. RESULTS: Septin9 DNA methylation was more frequent in breast cancer tissues than in non-breast cancer tissues, but was not significantly correlated with any relevant breast cancer patient clinicopathological characteristic. Septin9 methylation rates were higher in patients with recurrence or metastasis. Septin9 methylation, tumor size, lymph node status, and progesterone receptor (PR) expression could influence prognosis. Septin9 methylation was significantly associated with worse disease-free survival in breast cancer patients, with receiver operating characteristic curve analysis indicating that it had good prognostic ability, with an area under the curve (AUC) value of 0.719. The AUC values increased when Septin9 methylation was combined with tumor size, lymph node status, and PR to predict prognosis. CONCLUSIONS: Septin9 DNA methylation was an independent predictors of breast cancer prognostic risk. This could possibly help improve comprehensive prognosis prediction methods when combined with other risk factors.


Assuntos
Neoplasias da Mama , Metilação de DNA , Septinas , Feminino , Humanos , Mama , Neoplasias da Mama/genética , Proteínas do Citoesqueleto , Metilação de DNA/genética , Recidiva Local de Neoplasia/genética , Estudos Retrospectivos , Septinas/genética
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