Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 369
Filtrar
1.
Blood Adv ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564778

RESUMO

Chimeric antigen receptor (CAR)-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 CAR-NK cells for safer and more effective off-the-shelf cellular therapy. In this study, CD70, a pan-target of lymphoma, specific fourth-generation CAR with 4-1BB co-stimulatory domain and IL-15 was constructed and transduced into cord blood-derived NK cells by Baboon envelope pseudotyped lenti-vector. CD70-CAR NK cells displayed superior cytotoxic activity in vitro and in vivo against CD19 negative B-cell lymphoma when compared to non-transduced NK cells and CD19-specific CAR-NK cells. Importantly, mice received two 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 to single dose of CAR-NK cells for the treatment of B-cell lymphoma.

2.
Cell Mol Immunol ; 2024 Apr 17.
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.

3.
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).

4.
J Genet Genomics ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657948

RESUMO

Environment 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 for 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.

5.
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
6.
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.

7.
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.

8.
Adv Mater ; : e2400904, 2024 Mar 22.
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.

9.
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
10.
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.

11.
Neuro Oncol ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38416702

RESUMO

BACKGROUND: Meningioma is the most common primary intracranial tumor with high frequency of postoperative recurrence, yet the biology of 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 animal model and cellular level. 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 I interferon pathway dependent on its secreted isoform, and the inhibition effect was enhanced by TNFα as TNFα also induced type I interferon pathway. The expression of CLU was upregulated by histone deacetylase inhibition. Meanwhile, both intra- and extra-cellular CLU overexpression enhanced macrophage polarization towards M1 phenotype and TNFα production, thus promoted tumor killing and phagocytosis. CONCLUSIONS: CLU might be a key brake of meningioma malignance by synchronous modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.

12.
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.

13.
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
14.
Adv Mater ; : e2312583, 2024 Feb 01.
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)3 O4 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.

15.
Cell Discov ; 10(1): 5, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38191529

RESUMO

Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 106-4.0 × 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL.

16.
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
17.
Nanotechnology ; 35(18)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38271731

RESUMO

Tunable phonon transport properties of two-dimensional materials are desirable for effective heat management in various application scenarios. Here, we demonstrate by first-principles calculations and Boltzmann transport theory that the lattice thermal conductivity of siligene could be efficiently engineered by forming various stacking configurations. Unlike few-layer graphene, the stacked siligenes are found to be covalently bonded along the out-of-plane direction, which leads to unique dependence of the thermal conductivity on both the stacking order and layer number. Due to the restricted flexural phonon scattering induced by the horizontal reflection symmetry, the AA stacking configuration of bilayer siligene exhibits obviously higher thermal conductivity compared with the AB stacking. In addition, we observe increasing thermal conductivity with the layer number, as evidenced by the reduced phonon scattering phase space and Grüneisen parameter. Interestingly, the Fuchs-Sondheimer model works well for the thickness-dependent thermal conductivity of stacked siligenes.

18.
Pediatr Surg Int ; 40(1): 38, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253735

RESUMO

PURPOSE: Hirschsprung's disease (HSCR) is the leading cause of neonatal functional intestinal obstruction, which has been identified in many familial cases. HSCR, a multifactorial disorder of enteric nervous system (ENS) development, is associated with at least 24 genes and seven chromosomal loci, with RET and EDNRB as its major genes. We present a genetic investigation of familial HSCR to clarify the genotype-phenotype relationship. METHODS: We performed whole exome sequencing (WES) on Illumina HiSeq X Ten platform to investigate genetic backgrounds of core family members, and identified the possibly harmful mutation genes. Mutation carriers and pedigree relatives were validated by Sanger sequencing for evaluating the gene penetrance. RESULTS: Four familial cases showed potential disease-relative variants in EDNRB and RET gene, accounting for all detection rate of 57.1%. Three familial cases exhibited strong pathogenic variants as frameshift or missense mutations in EDNRB gene. A novel c.367delinsTT mutation of EDNRB was identified in one family member. The other two EDNRB mutations, c.553G>A in family 2 and c.877delinsTT in family 5, have been reported in previous literatures. The penetrance of EDNRB variants was 33-50% according mutation carries. In family 6, the RET c.1858T>C (C620R) point mutation has previously been reported to cause HSCR, with 28.5% penetrance. CONCLUSION: We identified a novel EDNRB (deleted C and inserted TT) mutation in this study using WES. Heterozygote variations in EDNRB gene were significantly enriched in three families and RET mutations were identified in one family. EDNRB variants showed an overall higher incidence and penetrance than RET in southern Chinese families cases.


Assuntos
Doença de Hirschsprung , Obstrução Intestinal , Receptor de Endotelina B , Humanos , Recém-Nascido , China/epidemiologia , Doença de Hirschsprung/genética , Incidência , Mutação , Receptor de Endotelina B/genética
19.
Microbiol Spectr ; 12(1): e0261423, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38051057

RESUMO

IMPORTANCE: During the coronavirus disease 2019 epidemic, the Chinese government launched and used a series of nonpharmaceutical interventions (NPIs), including banning social gatherings, wearing face masks, home isolation, and maintaining hand hygiene, to control the disease spread. Whether and how NPIs influence other respiratory viruses in children remain unclear. In this article, we analyzed relative data and found that the number of samples and positive proportion of respiratory viruses decreased significantly compared with that before the epidemic. Clinicians and public health policymakers should pay attention to changes in the epidemic trends and types of respiratory viruses and maintain monitoring of respiratory-related viruses to avoid possible abnormal rebounds and epidemic outbreaks of these viruses.


Assuntos
COVID-19 , Epidemias , Criança , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Surtos de Doenças , Máscaras
20.
Molecules ; 28(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38138546

RESUMO

Biodegradable polymers have recently become attractive and have been increasingly used as matrix materials to replace fossil plastics due to concerns about the environmental issue. However, their application areas are limited due to their high costs and natural properties. In this study, we fabricated ecofriendly and economical polybutylene adipate terephthalate (PBAT) composites loaded with various concentrations of wood flour (WF) to investigate the effects on the PBAT and WF interfaces as well as the physical properties of the WF/PBAT biocomposites. Then, WF was acetylated with acetic anhydride, and the effect of WF acetylation on the mechanical and thermal properties of the biocomposites were investigated. The results showed that the tensile strength, tensile modulus, flexural strength and flexural modulus increased with WF loading in the composites, and acetylation could not only further increase these properties, but also increase the impact strength and elongation at break. The incorporation of WF would weaken the thermal stability of PBAT, but the thermal stability of the biocomposite could be improved after WF acetylation. The cold crystallization temperature and hydrophobicity of the WF/PBAT samples would be increased with the increasing load of the WF, while the melting enthalpy and the crystallinity of the samples reduced gradually. A morphological analysis of the modified composites revealed that the matrix exhibited greater interfacial interactions with the WF compared to the WF/PBAT. Considering the much lower cost of WF compared to PBAT, the improved properties of WF/PBAT biocomposites will make it economically competitive with other commercial polymers, and these biocomposites should have much wider application areas.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...