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1.
Natl Sci Rev ; 11(8): nwae194, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39007006

RESUMEN

Superconducting infinite-layer (IL) nickelates offer a new platform for investigating the long-standing problem of high-temperature superconductivity. Many models were proposed to understand the superconducting mechanism of nickelates based on the calculated electronic structure, and the multiple Fermi surfaces and multiple orbitals involved create complications and controversial conclusions. Over the past five years, the lack of direct measurements of the electronic structure has hindered the understanding of nickelate superconductors. Here we fill this gap by directly resolving the electronic structures of the parent compound LaNiO2 and superconducting La0.8Ca0.2NiO2 using angle-resolved photoemission spectroscopy. We find that their Fermi surfaces consist of a quasi-2D hole pocket and a 3D electron pocket at the Brillouin zone corner, whose volumes change upon Ca doping. The Fermi surface topology and band dispersion of the hole pocket closely resemble those observed in hole-doped cuprates. However, the cuprate-like band exhibits significantly higher hole doping in superconducting La0.8Ca0.2NiO2 compared to superconducting cuprates, highlighting the disparities in the electronic states of the superconducting phase. Our observations highlight the novel aspects of the IL nickelates, and pave the way toward the microscopic understanding of the IL nickelate family and its superconductivity.

2.
J Clin Transl Hepatol ; 12(7): 659-666, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-38993508

RESUMEN

The incidence of autoimmune liver diseases (ALDs) and research on their pathogenesis are increasing annually. However, except for autoimmune hepatitis, which responds well to immunosuppression, primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy. Besides the known effects of the environment, genetics, and immunity on ALDs, the heterogeneity of target cells provides new insights into their pathogenesis. This review started by exploring the heterogeneity in the development, structures, and functions of hepatocytes and epithelial cells of the small and large bile ducts. For example, cytokeratin (CK) 8 and CK18 are primarily expressed in hepatocytes, while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes. Additionally, emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs. This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.

3.
Aging Ment Health ; : 1-13, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38946249

RESUMEN

OBJECTIVES: To systematically evaluate the effects of telehealth interventions on the caregiver burden and mental health of caregivers for people with dementia (PWD). METHOD: Relevant randomized controlled trials (RCTs) of telehealth interventions on caregivers were extracted from nine electronic databases (PubMed, The Cochrane Library, Web of Science, Embase, CINAHL, SinoMed, CNKI, WanFang, and VIP). The retrieval time was from inception to 26 July 2023. RESULTS: Twenty-two articles with 2132 subjects were included in the final analysis. The meta-analysis demonstrated that telehealth interventions exerted a significant effect in reducing caregiver burden (SMD: -0.14, 95 % CI: -0.25, -0.02, p = 0.02), depression (SMD = -0.17; 95%CI: -0.27, -0.07, p < 0.001) and stress (SMD = -0.20, 95%CI: -0.37, -0.04, p = 0.01). However, no statistically significant effect was observed on anxiety (SMD = -0.12, 95%CI: -0.27, 0.03, p = 0.12). Moreover, subgroup analysis showed that tailored interventions were associated with more evident reductions in depression (SMD = -0.26; 95%CI: -0.40, -0.13, p < 0.001) than standardized interventions (SMD = -0.08; 95%CI: -0.22, 0.06, p = 0.25). In addition, telehealth was effective in relieving depression in Internet-based (SMD = -0.17, 95%CI: -0.30, -0.03, p = 0.01) and Telephone-based group (SMD = -0.18, 95%CI: -0.34, -0.02, p = 0.03), while there was no significant difference in the Internet and Telephone-based group (SMD = -0.18, 95%CI: -0.54, 0.18, p = 0.32). CONCLUSION: Telehealth could effectively reduce the burden and relieve the depression and stress of caregivers of PWD, while its effect on anxiety requires further research. Overall, telehealth has potential benefits in dementia care.

4.
Phys Rev Lett ; 132(24): 243802, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38949371

RESUMEN

Orbital angular momentum (OAM) provides an additional degree of freedom for optical communication systems, and manipulating on-chip OAM is important in integrated photonics. However, there is no effective method to realize OAM topological charge conversion on chip. In this Letter, we propose a way to convert OAM by encircling two groups of exceptional points in different Riemann sheets. In our framework, any OAM conversion can be achieved on demand just by manipulating adiabatic and nonadiabatic evolution of modes in two on-chip waveguides. More importantly, the chiral OAM conversion is realized, which is of great significance since the path direction can determine the final topological charge order. Our Letter presents a special chiral behavior and provides a new method to manipulate OAM on the chip.

5.
Nat Commun ; 15(1): 5507, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951493

RESUMEN

Inverse vulcanization exploits S8 to synthesize polysulfides. However, evolution of products and its mechanism during inverse vulcanization remains elusive. Herein, inverse vulcanization curves are obtained to describe the inverse vulcanization process in terms of three stages: induction, curing and over-cure. The typical curves exhibit a moduli increment before declining or plateauing, reflecting the process of polysulfide network formation and loosing depending on monomers. For aromatic alkenes, in the over-cure, the crosslinked polysulfide evolves significantly into a sparse network with accelerated relaxation, due to the degradation of alkenyl moieties into thiocarbonyls. The inverse vulcanization product of olefins degrades slowly with fluctuated relaxation time and modulus because of the generation of thiophene moieties, while the inverse vulcanization curve of dicyclopentadiene has a plateau following curing stage. Confirmed by calculations, the mechanisms reveal the alkenyl groups react spontaneously into thiocarbonyls or thiophenes via similar sulfur-substituted alkenyl intermediates but with different energy barriers.

6.
J Neural Eng ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38986464

RESUMEN

Eye-tracking research has proven valuable in understanding numerous cognitive functions. Recently, Frey et al. provided an exciting deep learning method for learning eye movements from functional magnetic resonance imaging (fMRI) data. It employed the multi-step co-registration of fMRI into the group template to obtain eyeball signal, and thus required additional templates and was time consuming. To resolve this issue, in this paper, we propose a framework named MRGazer for predicting eye gaze points from fMRI in individual space. The MRGazer consists of an eyeball extraction module and a residual network-based eye gaze prediction module. Compared to the previous method, the proposed framework skips the fMRI co-registration step, simplifies the processing protocol, and achieves end-to-end eye gaze regression. The proposed method achieved superior performance in eye fixation regression (Euclidean error, EE=2.04°) than the co-registration-based method (EE=2.89°), and delivered objective results within a shorter time (~0.02 second/volume) than prior method (~0.3 second/volume). The code is available at https://github.com/ustc-bmec/MRGazer.

7.
Sci Adv ; 10(25): eadm7569, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38896615

RESUMEN

Realizing a multifunctional integrated photonic platform is one of the goals for future optical information processing, which usually requires large size to realize due to multiple integration challenges. Here, we realize a multifunctional integrated photonic platform with ultracompact footprint based on inverse design. The photonic platform is compact with 86 inverse designed-fixed couplers and 91 phase shifters. The footprint of each coupler is 4 µm by 2 µm, while the whole photonic platform is 3 mm by 0.2 mm-one order of magnitude smaller than previous designs. One-dimensional Floquet Su-Schrieffer-Heeger model and Aubry-André-Harper model are performed with measured fidelities of 97.90 (±0.52) % and 99.34 (±0.44) %, respectively. We also demonstrate a handwritten digits classification task with the test accuracy of 87% using on-chip training. Moreover, the scalability of this platform has been proved by demonstrating more complex computing tasks. This work provides an effective method to realize an ultrasmall integrated photonic platform.

8.
ACS Nano ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941536

RESUMEN

Noble metal nanocrystals face challenges in effectively catalyzing electrochemical ethanol oxidation reaction (EOR)-represented multistep, multielectron transfer processes due to the linear scaling relationship among binding energies of intermediates, impeding independent optimization of individual elemental steps. Herein, we develop noble metal nanocrystals with a range of local surface binding affinities in close proximity to overcome this challenge. Experimentally, this is demonstrated by applying tensile strain to a Pd surface and decorating it with discrete Au atoms, forming a diversity of binding sites with varying affinities in close proximity for guest molecules, as evidenced by CO probing and density functional theory calculations. Such a surface enables reaction intermediates to migrate between different binding sites as needed for each elemental step, thereby reducing the energy barrier for the overall EOR when compared to reactions at a single site. On these tailored surfaces, we attain specific and mass activities of 32.7 mA cm-2 and 47.8 A mgPd-1 in EOR, surpassing commercial Pd/C by 10.9 and 43.8 times, respectively, and outperforming state-of-the-art Pd-based catalysts. These results highlight the promise of this approach in improving a variety of multistep, multielectron transfer reactions, which are crucial for energy conversion applications.

9.
Macromol Rapid Commun ; : e2400339, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925556

RESUMEN

Chirality is ubiquitous in nature, and closely related to biological phenomena. Nature-originated nanomaterials such as cellulose nanocrystals (CNCs) are able to self-assemble into hierarchical chiral nematic CNC films and impart handedness to nano and micro scale. However, the effects of the chiral nematic surfaces on cell adhesion are still unknown. Herein, this work presents evidence that the left-handed self-assembled chiral nematic CNC films (L-CNC) significantly improve the adhesion of L929 fibroblasts compared to randomly arranged isotropic CNC films (I-CNC). The fluidic force microscopy-based single-cell force spectroscopy is introduced to assess the cell adhesion forces on the substrates of L-CNC and I-CNC, respectively. With this method, a maximum adhesion force of 133.2 nN is quantified for mature L929 fibroblasts after culturing for 24 h on L-CNC, whereas the L929 fibroblasts exert a maximum adhesion force of 78.4 nN on I-CNC under the same condition. Moreover, the instant SCFS reveals that the integrin pathways are involved in sensing the chirality of substrate surfaces. Overall, this work offers a starting point for the regulation of cell adhesion via the self-assembled nano and micro architecture of chiral nematic CNC films, with potential practical applications in tissue engineering and regenerative medicine.

10.
Sci Total Environ ; 940: 173584, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-38823692

RESUMEN

Pioneer plants are vital in stabilizing soil structure while restoring reservoir drawdown areas. However, uncertainties persist regarding the mechanism of pioneer plants to soil stability in these delicate ecosystems. This study aims to unravel the plant-soil feedback mechanisms from the roles of root traits and rhizosphere microorganisms. We conducted a mesocosm experiment focusing on four common pioneer plants from the drawdown area of Three Gorges Reservoir, China. Using the wet sieving methodology, trait-based approach and high-throughput sequencing technology, we explored soil aggregate stability parameters, plant root traits and rhizosphere microbial communities in experimental plant groups. The interacting effect of pioneer plant species richness, root traits, and rhizosphere microbial communities on soil aggregate stability was quantified by statistical and machine-learning models. Our results demonstrate that diverse pioneer plant communities significantly enhance soil aggregate stability. Notably, specific species, such as Cynodon dactylon (L.) Pers. and Xanthium strumarium L., exert a remarkably strong influence on soil stability due to their distinctive root traits. Root length density (RLD) and root specific surface area (RSA) were identified as crucial root traits mediating the impact of plant diversity on soil aggregate stability. Additionally, our study highlights the link between increased rhizosphere fungal richness, accompanied by plant species richness, and enhanced soil aggregate stability, likely attributable to elevated RLD and RSA. These insights deepen our understanding of the role of pioneer vegetation in soil structure and stability, providing valuable implications for ecological restoration and management practices in reservoir drawdown areas.


Asunto(s)
Raíces de Plantas , Rizosfera , Microbiología del Suelo , Suelo , Raíces de Plantas/microbiología , China , Suelo/química , Microbiota , Plantas , Ecosistema
11.
J Neurol ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864881

RESUMEN

With the advancement of cancer treatment technologies, immunotherapy has begun to be widely utilized. Colon cancer is one of the most common types of cancer, with metastasis being a frequent occurrence in late-stage patients. Hence, immunotherapy, as an emerging and potentially effective treatment modality, merits exploration to enhance patient survival rates and clinical benefits. However, various immune-related adverse events cannot be entirely avoided. Myasthenia gravis induced by immunotherapy serves as a rare but potentially lethal adverse event, and it has been increasingly reported. Understanding the mechanisms of irAEs can aid in controlling the side effects induced by treatment. Here, we reported a case of myasthenia gravis occurring after anti-PD-1 therapy for late-stage colon cancer.

12.
Clin Med Insights Oncol ; 18: 11795549241254781, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855031

RESUMEN

Circular RNAs (circRNAs) are a type of non-coding RNA (ncRNA) that possesses a unique single-stranded circular structure. They are primarily formed through alternative splicing of pre-mRNA (messenger RNA). The primary biological function of circRNAs is to regulate gene expression at both the transcriptional and post-transcriptional levels. Recent studies have increasingly demonstrated a close association between the dysregulation of circRNAs and the progression of diverse cancers, where they can function as either tumor suppressors or oncogenes. circWHSC1 (circNSD2) is a circular ncRNA that originates from the first 2 exons of the Wolf-Hirschhorn syndrome candidate gene (WHSC1). As Chen 2019 discovery that circWHSC1 (circNSD2) functions as a sponge for miRNAs and promotes cancer, this circRNA has garnered significant interest among researchers. circWHSC1 (circNSD2) has been found to be up-regulated in various malignant tumors, including nasopharyngeal carcinoma, lung cancer, breast cancer, liver cancer, colorectal cancer, ovarian cancer, cervical cancer, and endometrial cancer. It exerts its effects on cancer by either inhibiting or promoting the expression of related genes through direct or indirect pathways, ultimately affecting cancer proliferation, invasion, and prognosis. This article provides a comprehensive review and discussion of the biological roles of circWHSC1 (circNSD2) and its target genes in various cancers, as well as the latest research progress on related molecular biological regulatory mechanisms. Furthermore, the potential significance of circWHSC1 (circNSD2) in future clinical applications and transformations is thoroughly analyzed and discussed.

13.
Nat Commun ; 15(1): 4755, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834568

RESUMEN

Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d18:1 [So(d18:1)] is selected from NASH patients. So(d18:1) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d18:1) promotes NASH and clarifies that So(d18:1) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Macrófagos , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico , Esfingosina , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/genética , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Masculino , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Humanos , Ratones , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Hígado/metabolismo , Hígado/patología , Hígado/efectos de los fármacos , Ratones Endogámicos C57BL , Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Translocador Nuclear del Receptor de Aril Hidrocarburo/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Cirrosis Hepática/genética , Modelos Animales de Enfermedad
14.
Nano Lett ; 24(27): 8303-8310, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38934420

RESUMEN

The discovery of interfacial superconductivity in monolayer FeSe/oxides has spurred intensive research interest. Here we not only extend the FeSe/FeOx superconducting interface to FeSe/NdFeO3 but also establish robust interface-enhanced superconductivity at a very low doping level. Specifically, well-annealed FeSe/NdFeO3 exhibits a low doping level of 0.038-0.046 e-/Fe with a larger superconducting pairing gap without a nematic gap, indicating an enhancement of the enhanced superconducting pairing strength and suppression of nematicity by the FeSe/FeOx interface compared with those of thick FeSe films. These results improve our understanding of the roles of the oxide interface in the low-electron-doped regime.

15.
Neuroimage Clin ; 43: 103618, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38830274

RESUMEN

Extensive neuroimaging abnormalities in subcortical regions build the pathophysiological basis of Wilson's disease (WD). Yet, subcortical topographic organization fails to articulate, leaving a huge gap in understanding the neural mechanism of WD. Thus, how functional abnormalities of WD subcortical regions influence complex clinical symptoms and response to treatment remain unknown. Using resting-state functional MRI data from 232 participants (including 130 WD patients and 102 healthy controls), we applied a connectivity-based parcellation technique to develop a subcortical atlas for WD. The atlas was further used to investigate abnormalities in subcortical function (ASF) by exploring intrasubcortical functional connectivity (FC) and topographic organization of cortico-subcortical FC. We further used support vector machine (SVM) to integrate these functional abnormalities into the ASF score, which serves as a biomarker for characterizing individual subcortical dysfunction for WD. Finally, the baseline ASF score and one-year treatment data of the follow-up WD patients were used to assess treatment response. A group set of subcortical parcellations was evaluated, in which 26 bilateral regions well recapitulated the anatomical nuclei of the subcortical areas of WD. The results of cortico-subcortical FC and intrasubcortical FC reveal that dysfunction of the somatomotor networks-lenticular nucleus-thalamic pathways is involved in complex symptoms of WD. The ASF score was able to characterize disease progression and was significantly associated with treatment response of WD. Our findings provide a comprehensive elaboration of functional abnormalities of WD subcortical regions and reveal their association with clinical presentations, improving our understanding of the functional neural underpinnings in WD. Furthermore, abnormalities in subcortical function could serve as a potential biomarker for understanding the disease progression and evaluating treatment response of WD.

16.
RSC Adv ; 14(20): 14303-14310, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38690105

RESUMEN

The aim of this study was to evaluate the effect of five varieties on the quality of herbaceous peony tea by physicochemical analysis, sensory evaluation, antimicrobial capacity analysis and a combination of gas chromatography with quadruple time of flight mass spectrometry (GC-QTOF). Antibacterial and antioxidant analyses revealed that the ABTS free radical scavenging rate of HPT was high, ranging from 82.20% to 87.40% overall. 'Madame Claude Tain' had the strongest inhibitory ability against Staphylococcus aureus with an inhibitory effect of 12.65 mm. The sensory evaluation showed that 'Angel cheeks' had the highest overall sensory score. GC-QTOF combined with orthogonal projections to latent structures discriminant analysis showed that 22 volatile components were the key aroma components of herbaceous peony tea. Different varieties of herbaceous peony tea had a unique characteristic aroma. 'Angel cheeks' imparted lily-like and chestnut fragrances, which were attributed to linalool and 3,5-octadien-2-one. 'Sea Shell', 'Mother's Choice' and 'Angel Cheek' had a medicinal aroma, which may be due to the presence of o-cymene. Overall, 'Angel cheeks' was the most suitable for developing high-quality herbaceous peony tea in five varieties. This study provided a theoretical basis and technical guidance for the development of herbaceous peony.

17.
J Cancer ; 15(10): 2900-2912, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38706900

RESUMEN

Background: Gastric cancer (GC) is a common malignancy with early detection being crucial for survival. Liquid biopsy analysis using cell-free nucleic acid is a preferred method for detection. Hence, we conducted a systematic review to assess the diagnostic efficacy of cell-free nucleic acid markers for GC. Methods: We searched PubMed and ISI Web of Science databases for articles that conformed to our inclusion and exclusion criteria from 2012 to 2022. The following information was abstracted: first author, year of publication, country/region, age, male proportion, tumor stage for cases, specimen type, measurement method, targeted markers and diagnostic related indicators (including sensitivity, specificity, AUC, P-value). Results: Fifty-eight studies examined cell-free RNAs (cfRNAs) with a total of 62 individual circulating markers and 7 panels in serum or plasma, while 21 studies evaluated cell-free DNAs (cfDNAs) with 29 individual circulating markers and 7 panels. For individual cfRNAs, the median (range) sensitivity and specificity were 80% (21% - 98%) and 80% (54% - 99%), respectively. The median (range) sensitivity and specificity for cfRNA panels were 86% (83% - 90%) and 75% (60% - 98%), respectively. In comparison, the median (range) sensitivity and specificity reported for individual cfDNAs were 50% (18% - 96%) and 93% (57% - 100%), respectively, while cfDNA panels had a median (range) sensitivity and specificity of 85% (41% - 92%) and 73.5% (38% - 90%), respectively. The meta results indicate that cfRNA markers exhibit high sensitivity (80%) and low specificity (80%) for detecting GC, while cfDNA markers have lower sensitivity (59%) but higher specificity (92%). Conclusions: This review has demonstrated that cell-free nucleic acids have the potential to serve as useful diagnostic markers for GC. Given that both cfRNA and cfDNA markers have shown promising diagnostic performance for GC, the combination of the two may potentially enhance diagnostic efficiency.

18.
Signal Transduct Target Ther ; 9(1): 121, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38755119

RESUMEN

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.


Asunto(s)
Aminopiridinas , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Inhibidores de Histona Desacetilasas , Linfoma Extranodal de Células NK-T , Humanos , Masculino , Femenino , Persona de Mediana Edad , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Benzamidas/efectos adversos , Anciano , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/patología , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Histona Desacetilasas/administración & dosificación , Inhibidores de Histona Desacetilasas/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Adulto , Aminopiridinas/administración & dosificación , Aminopiridinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología
19.
Vaccine ; 42(18): 3751-3755, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38714449

RESUMEN

To assess the levels of and neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its mutants in serum samples from patients with breakthrough infection. Sixty-four patients with breakthrough infections were recruited for this cross-sectional study. All samples were used to neutralizing antibodies (nAbs) against SARS-CoV-2 and its mutants using a focused reduction neutralization assay. A total of 512 serum samples were obtained from unvaccinated patients who received one dose of vaccine (n = 12), received two doses of vaccine (n = 15), and received three doses of vaccine (n = 37). The geometric mean titer (GMT) of neutralizing antibodies against the Omicron subvariant was significantly lower (GMT 66.8 and 56.1) compared to the original strain, regardless of whether two or three doses of vaccine were administered. This result highlights that sera from breakthrough infections induce broad neutralization, but Omicron XBB.1.16 exhibits high immune evasion potential.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Pruebas de Neutralización , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Estudios Transversales , Femenino , Masculino , Persona de Mediana Edad , Adulto , Inmunización Secundaria , Anciano , Evasión Inmune , Infección Irruptiva
20.
JCI Insight ; 9(13)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771644

RESUMEN

Hypotrichosis is a genetic disorder characterized by a diffuse and progressive loss of scalp and/or body hair. Nonetheless, the causative genes for several affected individuals remain elusive, and the underlying mechanisms have yet to be fully elucidated. Here, we discovered a dominant variant in a disintegrin and a metalloproteinase domain 17 (ADAM17) gene caused hypotrichosis with woolly hair. Adam17 (p.D647N) knockin mice mimicked the hair abnormality in patients. ADAM17 (p.D647N) mutation led to hair follicle stem cell (HFSC) exhaustion and caused abnormal hair follicles, ultimately resulting in alopecia. Mechanistic studies revealed that ADAM17 binds directly to E3 ubiquitin ligase tripartite motif-containing protein 47 (TRIM47). ADAM17 variant enhanced the association between ADAM17 and TRIM47, leading to an increase in ubiquitination and subsequent degradation of ADAM17 protein. Furthermore, reduced ADAM17 protein expression affected the Notch signaling pathway, impairing the activation, proliferation, and differentiation of HFSCs during hair follicle regeneration. Overexpression of Notch intracellular domain rescued the reduced proliferation ability caused by Adam17 variant in primary fibroblast cells.


Asunto(s)
Proteína ADAM17 , Alopecia , Folículo Piloso , Ubiquitina-Proteína Ligasas , Proteína ADAM17/metabolismo , Proteína ADAM17/genética , Animales , Alopecia/genética , Alopecia/metabolismo , Alopecia/patología , Ratones , Folículo Piloso/metabolismo , Folículo Piloso/patología , Humanos , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Masculino , Transducción de Señal/genética , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Femenino , Mutación , Técnicas de Sustitución del Gen , Proliferación Celular/genética , Diferenciación Celular/genética , Proteolisis , Modelos Animales de Enfermedad , Fibroblastos/metabolismo , Receptores Notch/metabolismo , Receptores Notch/genética
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