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1.
Artículo en Inglés | MEDLINE | ID: mdl-38728621

RESUMEN

Two-dimensional (2D) transition metal carbides, known as MXenes, have captured much attention for their excellent electrical conductivity and electrochemical capability. However, the susceptibility of MXenes to oxidation, particularly Ti3C2Tx transforming into titanium dioxide upon exposure to ambient air, hinders their utilization for extended operational life cycles. This work introduces a simple and straightforward method for producing ultrathin MXene electrode films tailored for energy storage applications, employing centrifugal-gravity force. Our approach significantly suppresses the oxidation phenomenon that arises in MXene materials and also effectively prevents the recrystallization of potentially residual LiF during the film formation. Additionally, the utilization of this MXene electrode in an all-solid-state microsupercapacitor (MSC) with an interdigitated pattern demonstrates an exceptionally improved and stable electrochemical performance. This includes a high volumetric capacitance of approximately 467 F cm-3, an energy density of around 65 mWh cm-3, and impressive long-term cycle stability, retaining about 94% capacity after 10 000 cycles. Moreover, a downsized MSC device exhibits remarkable mechanical durability, retaining over 98% capacity even when folded and sustaining stability over extended periods. Therefore, we believe that this study provides valuable insights for advancing highly integrated energy storage devices, ensuring exceptional electrochemical efficiency and prolonged functionality in diverse environments, whether ambient or humid.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38718823

RESUMEN

Depth profiling is an essential method to investigate the physical and chemical properties of a solid electrolyte and electrolyte/electrode interface. In conventional depth profiling, various spectroscopic tools such as X-ray photoelectron spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS) are utilized to monitor the chemical states along with ion bombardment to etch a sample. Nevertheless, the ion bombardment during depth profiling results in an inevitable systematic error, i.e., the accumulation of mobile ions at the electrolyte/electrode interface, known as the ion pile-up phenomenon. Here, we propose a novel method using bias potential, the substrate-bias method, to prevent the ion pile-up phenomena during depth profiling of a solid electrolyte. When the positive bias potential is applied on the substrate (electrode), the number of accumulating ions at the electrolyte/electrode interface is significantly reduced. The in-depth XPS analysis with the biased electrode reveals not only the suppression of the ion pile-up phenomena but also the altered chemical states at the interfacial region between the electrolyte and electrode depending on the bias. The proposed substrate-bias method can be a good alternative scheme for an efficient yet precise depth profiling technique for a solid electrolyte.

3.
Cancer Discov ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563906

RESUMEN

IL-2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, while others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL-2 to CD8+ T cells, which are key anti-tumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, CD8 cis-targeted IL-2 that demonstrates over 500-fold preference for CD8+ T cells over NK and Treg cells, which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL-2's effects on CD8+ T cells in vitro and induced selective expansion of CD8+ T cells in primates. In mice, an AB248 surrogate demonstrated superior anti-tumor activity and enhanced tolerability as compared to an untargeted IL-2RBy agonist. Efficacy was associated with expansion and phenotypic enhancement of tumor-infiltrating CD8+ T cells, including the emergence of a "better effector" population. These data support the potential utility of AB248 in clinical settings.

4.
Nat Commun ; 15(1): 3368, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643233

RESUMEN

The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyze blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyze their B-cell receptor (BCR) repertoires at six time points in total. The concomitant reactivity to both ancestral and Omicron receptor-binding domain (RBD) is achieved by a limited number of BCR clonotypes depending on the accumulation of somatic hypermutation (SHM) after the third dose. Our findings suggest that SHM accumulation in the BCR space to broaden its specificity for unseen antigens is a counterprotective mechanism against virus variant immune escape.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacuna BNT162 , COVID-19/prevención & control , SARS-CoV-2/genética , Anticuerpos Neutralizantes , Anticuerpos Antivirales
5.
J Glob Infect Dis ; 16(1): 27-32, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38680753

RESUMEN

Introduction: The coronavirus disease 2019 (COVID-19) pandemic may have influenced the prevalence and seasonality of acute respiratory viral infections. The aim of the study was to investigate the prevalence of all viruses causing acute viral respiratory infections before and after social distancing measures were lifted. Methods: Cross-sectional study where outpatients and inpatients at Kyunghee University Hospital were examined. From January 2021 to December 2022, respiratory samples were analyzed using multiplex reverse transcriptase real-time polymerase chain reaction. Results: Of 3953 samples obtained, 412 (10.42%) were positive for acute respiratory viral infection, and 502 viruses were detected. The number of viral infections increased from 184 in 2021 to 318 in 2022. Human metapneumovirus was detected from August to November 2022. Human bocavirus (HBoV) was frequently detected from April to June 2021; however, in 2022, HBoV was frequently detected from July to October. Human parainfluenza virus 3 was rarely detected after its initial frequent detection from October to December 2021 but was continuously observed after frequent detection in September 2022. Co-infection occurred in 78 (18.9%) cases. The most common combination of simultaneous infections was human rhinovirus-HBoV (n = 30, 38.5%). Conclusions: During the COVID-19 pandemic, the incidence of acute respiratory viral infection decreased significantly but increased in 2022 when measures were lifted. The prevalence and seasonality of respiratory viral infections have changed since the pandemic. Our findings contribute to the prediction of an effective response to changes in the prevalence of respiratory viruses.

6.
Clin Exp Emerg Med ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38485262

RESUMEN

Airway management is a fundamental and intricate process that involves a sequence of integrated tasks. Situations requiring emergency airway management may occur in emergency department, intensive care units, and various other spaces. Emergency airway management can face a variety of challenges during preparation, intubation, and post-intubation, and may result in significant complications for the patients. Therefore, many countries are establishing step-by-step systemization and detailed guidelines, and updating the content based on the latest research. This clinical review introduces the current trends in emergency airway management, such as emergency airway management algorithms, comparison of video and direct laryngoscopy, rapid sequence intubation, pediatric airway management, pre-hospital airway management, surgical airway management, and airway management education.

7.
BMC Infect Dis ; 24(1): 259, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38402154

RESUMEN

BACKGROUND: While there is a high burden of methicillin-resistant Staphylococcus aureus (MRSA) infections among pediatric patients, studies on the molecular epidemiology of MRSA infections in Korean children since the 2010s are lacking. This study aimed to investigate the molecular genotypes and clinical characteristics of MRSA isolates from children with MRSA bacteremia at Asan Medical Center Children's Hospital from 2016 to 2021. METHODS: Clinical data were retrospectively reviewed, and the molecular types of MRSA were determined using multilocus sequence typing (MLST) and Staphylococcal cassette chromosome mec (SCCmec) typing. RESULTS: The overall methicillin resistance rate of S. aureus bacteremia was 44.8% (77/172); 49.5% in the period 2016-2018 (period 1) and 37.3% in the period 2019-2021 (period 2) (P = 0.116). Community-acquired infections accounted for only 3.9% of cases. The predominant ST group was ST72 group (67.6%), followed by ST5 group (18.9%) and ST1 group (5.4%). The proportion of ST5 was significantly lower in period 2 compared to period 1 (P = 0.02). Compared to the ST5 and ST1 groups, the ST72 group exhibited lower overall antibiotic resistance and multidrug-resistant (MDR) rates (12.0% [6/50] in ST72 group vs. 100.0% [14/14] in ST5 group vs. 50.0% [2/4] in ST1 group; P < 0.001). In the multivariate analysis, the ST1 group was an independent risk factor for 30-day all-cause mortality (aOR, 44.12; 95% CI, 3.46-562.19). CONCLUSION: The ST72-MRSA strain remained the most frequently isolated genotype in Korean children, while the ST1 group emerged as an independent risk factor for 30-day all-cause mortality in pediatric MRSA bacteremia. Ongoing efforts to uncover the evolving epidemiology of MRSA are essential for developing effective strategies for prevention and treatment.


Asunto(s)
Bacteriemia , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Niño , Staphylococcus aureus , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Estudios Retrospectivos , Infecciones Estafilocócicas/epidemiología , Pruebas de Sensibilidad Microbiana , Bacteriemia/epidemiología , Genotipo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
8.
Heliyon ; 10(4): e26663, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38420468

RESUMEN

Myasthenia Gravis (MG) patients with anti-acetylcholine receptor (AChR) antibodies frequently show hyperplastic thymi with ectopic germinal centers, where autoreactive B cells proliferate with the aid of T cells. In this study, thymus and peripheral blood (PB) samples were collected from ten AChR antibody-positive MG patients. T cell receptor (TCR) repertoires were analyzed using next-generation sequencing (NGS), and compared with that of an age and sex matched control group generated from a public database. Certain V genes and VJ gene recombination pairs were significantly upregulated in the TCR chains of αß-T cells in the PB of MG patients compared to the control group. Furthermore, the TCR chains found in the thymi of MG patients had a weighted distribution to longer CDR3 lengths when compared to the PB of MG patients, and the TCR beta chains (TRB) in the MG group's PB showed increased clonality encoded by one upregulated V gene. When TRB sequences were sub-divided into groups based on their CDR3 lengths, certain groups showed decreased clonality in the MG group's PB compared to the control group's PB. Finally, we demonstrated that stereotypic MG patient-specific TCR clonotypes co-exist in both the PB and thymi at a much higher frequency than that of the clonotypes confined to the PB. These results strongly suggest the existence of a biased T cell-mediated immune response in MG patients, as observed in other autoimmune diseases.

9.
Small ; : e2307542, 2023 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-38044288

RESUMEN

With the rapid development of human-friendly wearable devices, energy storage components are required to have skin-like stretchability or free-form to fit closer and more comfortably to the human body. This study introduces a hierarchically interpenetrated reentrant microcellular structure combined with 2D cellular graphene/MXene/carbon nanotubes (CNTs) and 3D cellular melamine foam. This composite structure works as a stretchable framework of lithium metal composite electrodes to provide stretchability for lithium metal electrodes, which are promising as next-generation energy storage systems. The interpenetrated but independent cellular structures successfully obtain stable structural deformability from the nonconductive and deformable melamine foam, while at the same time, high electrical conductivity, lithiophilicity, and mechanical stability of the graphene/CNT/MXene network serve as a lithium deposition support during the electrodeposition of lithium. The reentrant structure is fabricated by radial compressing the hierarchical cellular structures to take advantage of the structural stretchability of the accordion-like reentrant frameworks. The lithium-deposited composite electrodes exhibit much lower overpotential during Li stripping and plating than lithium metal foil anodes and show stable electrochemical performances under 30% of mechanical strain. The reentrant microcellular electrodes offer great potential for advanced designs of lithium metal electrodes for stretchable batteries with high energy density.

10.
Opt Express ; 31(22): 35624-35631, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-38017729

RESUMEN

We demonstrate the quantitative pressure measurement of gas molecules in the mid-infrared using chip-based supercontinuum and cepstrum analysis without additional measurements for baseline normalization. A supercontinuum generated in an on-chip waveguide made of chalcogenide glass having high nonlinearity passes through CO gas and provides a transmission spectrum. The gas absorption information is deconvoluted from the original supercontinuum spectral information containing temporal fluctuation by cepstrum analysis and extracted simply by applying a bandpass filter in the temporal domain. The gas pressure estimated from the extracted absorption information is consistent with the value measured by a pressure gauge within a difference of 1.25%, despite spectral fluctuations in the supercontinuum baseline comparable to the spectral depth of the gas absorption lines.

11.
J Neuroinflammation ; 20(1): 225, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37794409

RESUMEN

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing. METHODS: From a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups. RESULTS: Blood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups. CONCLUSIONS: NMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual's lifetime.


Asunto(s)
Neuromielitis Óptica , Humanos , Acuaporina 4 , Estudios Prospectivos , Glicoproteína Mielina-Oligodendrócito , Autoanticuerpos , Receptores de Antígenos de Linfocitos B
12.
J Ginseng Res ; 47(4): 593-603, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37397419

RESUMEN

Background: Korean Red Ginseng is a major source of bioactive substances such as ginsenosides. Efficacy of red ginseng extract (RGE), which contains not only saponins but also various non-saponins, has long been studied. In the water-soluble component-rich fraction of RGE (WS), a byproduct generated in the process of extracting saponins from the RGE, we identified previously unidentified molecules and confirmed their efficacy. Methods: The RGE was prepared and used to produce WS, whose components were isolated sequentially according to their water affinity. The new compounds from WS were fractionized and structurally analyzed using nuclear magnetic resonance spectroscopy. Physiological applicability was evaluated by verifying the antioxidant and anti-inflammatory efficacies of these compounds in vitro. Results: High-performance liquid chromatography confirmed that the obtained WS comprised 11 phenolic acid and flavonoid substances. Among four major compounds from fractions 1-4 (F1-4) of WS, two compounds from F3 and F4 were newly identified in red ginseng. The analysis results show that these compound molecules are member of the maltol-structure-based glucopyranose series, and F1 and F4 are particularly effective for decreasing oxidative stress levels and inhibiting nitric oxide secretion, interleukin (IL)-1ß and IL-6, and tumor necrosis factor-α. Conclusion: Our findings suggest that a few newly identified maltol derivatives, such as red ginseng-derived non-saponin in the WS, exhibit antioxidant and anti-inflammatory effects, making them viable candidates for application to pharmaceutical, cosmetic, and functional food materials.

13.
Nanomaterials (Basel) ; 13(13)2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37446462

RESUMEN

Surface undulation was formed while growing InGaN/GaN multi-quantum wells on a semi-polar m-plane (1-100) sapphire substrate. Two distinct facets, parallel to 112¯2 and 011¯1, were formed in the embedded multi-quantum wells (MQWs). The structural and luminescence characteristics of the two facets were investigated using transmission electron microscopy equipped with cathodoluminescence. Those well-defined quantum wells, parallel and slanted to the growth plane, showed distinct differences in indium incorporation from both the X-ray yield and the contrast difference in annular darkfield images. Quantitative measurements of concentration in 011¯1 MQWs show an approximately 4 at% higher indium incorporation compared to the corresponding 112¯2 when the MQWs were formed under the same growth condition.

14.
Clin Cancer Res ; 29(16): 3004-3016, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37249619

RESUMEN

PURPOSE: Resistance to third-generation EGFR inhibitors including osimertinib arises in part from the C797S mutation in EGFR. Currently, no targeted treatment option is available for these patients. We have developed a new EGFR tyrosine kinase inhibitor (TKI), BBT-176, targeting the C797S mutation. PATIENTS AND METHODS: Recombinant EGFR proteins and Ba/F3 cell lines, patient-derived cells, and patient-derived xenografts expressing mutant EGFRs were used to test the inhibitory potency and the anticancer efficacy of BBT-176 both in vitro and in vivo. Patient case data are also available from an ongoing phase I clinical trial (NCT04820023). RESULTS: The half maximal inhibitory concentration (IC50) of BBT-176 against EGFR 19Del/C797S, EGFR 19Del/T790M/C797S, and EGFR L858R/C797S proteins were measured at 4.36, 1.79, and 5.35 nmol/L, respectively (vs. 304.39, 124.82, and 573.72 nmol/L, for osimertinib). IC50 values of BBT-176 against Ba/F3 cells expressing EGFR 19Del/C797S, EGFR 19Del/T790M/C797S, EGFR L858R/C797S, and EGFR L858R/T790M/C797S were 42, 49, 183, and 202 nmol/L, respectively (vs. 869, 1,134, 2,799, and 2,685 nmol/L for osimertinib). N-ethyl-N-nitrosourea mutagenesis suggested that BBT-176 treatment does not introduce any secondary mutations in the EGFR gene but increases EGFR expression levels. Combined with the EGFR antibody cetuximab, BBT-176 effectively suppressed the growth of BBT-176-resistant clones. BBT-176 strongly inhibited the tumor growth, and in some conditions induced tumor regression in mouse models. In the clinical trial, two patients harboring EGFR 19Del/T790M/C797S in blood showed tumor shrinkage and radiologic improvements. CONCLUSIONS: BBT-176 is a fourth-generation EGFR inhibitor showing promising preclinical activity against NSCLC resistant to current EGFR TKI, with early clinical efficacy and safety.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Resistencia a Antineoplásicos/genética
15.
ACS Nano ; 17(11): 10353-10364, 2023 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-37017522

RESUMEN

Flexible see-through displays are considered to be the next generation smart display, providing improved information flow, safety, situational awareness, and overall user experience in smart windows, automotive displays, glass-form biomedical displays, and augmented reality systems. 2D titanium carbides (MXenes) are promising material as electrodes of the transparent and flexible displays due to their high transparency, metallic conductivity, and flexibility. However, current MXene-based devices have insufficient air stability and lack engineering schemes to develop matrix-addressable display forms with sufficient pixels to display information. Here, we develop an ultraflexible and environmentally stable MXene-based organic light-emitting diode (OLED) display by combining high performance MXene electrodes, flexible OLEDs, and ultrathin and functional encapsulation systems. The MXene material was synthesized and used to fabricate a highly reliable MXene-based OLED that can stably operate in air condition for over 2000 h, endure repetitive bending deformation of 1.5 mm radius, and maintain environmental stability for 6 h when exposed to wet surroundings. The RGB MXene-based OLEDs were fabricated, (1691 cd m-2 at 40.4 mA cm-2 for red, 1377 cd m-2 at 4.26 mA cm-2 for green, and 1475 cd m-2 at 18.6 mA cm-2 for blue) and a matrix-addressable transparent OLED display was demonstrated that could display letters and shapes.

16.
Int J STEM Educ ; 10(1): 19, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36915857

RESUMEN

Background: Much of researchers' efforts to foster wider implementation of educational innovations in STEM has focused on understanding and facilitating the implementation efforts of faculty. However, student engagement in blended learning and other innovations relies heavily on students' self-directed learning behaviors, implying that students are likely key actors in the implementation process. This paper explores the ways in which engineering students at multiple institutions experience the self-directed selection and implementation of blended learning resources in the context of their own studies. To accomplish this, it adopts a research perspective informed by Actor-Network Theory, allowing students themselves to be perceived as individual actors and implementors rather than a population that is implemented upon. Results: A thematic analysis was conducted in two parts. First, analysis identified sets of themes unique to the student experience at four participant institutions. Then, a second round of analysis identified and explored a subset of key actors represented in students' reported experiences across all institutions. The findings show clear similarities and differences in students' experiences of blended learning across the four institutions, with many themes echoing or building upon the results of prior research. Distinct institutional traits, the actions of the instructors, the components of the blended learning environment, and the unique needs and preferences of the students themselves all helped to shape students' self-directed learning experiences. Students' engagement decisions and subsequent implementations of blended learning resulted in personally appropriate, perhaps even idiosyncratic, forms of engagement with their innovative learning opportunities. Conclusion: The institutional implementation of blended learning, and perhaps other educational innovations, relies in part on the self-directed decision-making of individual students. This suggests that instructors too hold an additional responsibility: to act as facilitators of their students' implementation processes and as catalysts for growth and change in students' learning behaviors. Developing a greater understanding of students' implementation behaviors could inform the future implementation efforts of faculty and better empower students to succeed in the innovative classroom.

17.
Sensors (Basel) ; 23(3)2023 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-36772463

RESUMEN

In a connected car, the vehicle's internal network is connected to the outside through communication technology. However, this can cause new security vulnerabilities. In particular, V2X communication, to provide the safety of connected cars, can directly threaten the lives of passengers if a security attack occurs. For V2X communication security, standards such as IEEE 1609.2 define the technical functions that digital signature and encryption to provide security of V2X messages. However, it is difficult to verify the security technology by applying it to the environment with real roads because it can be made up of other safety accidents. In addition, vehicle simulation R&D is steadily being carried out, but there is no simulation that evaluates security for the V2X application level. Therefore, in this paper, a virtual machine was used to implement a V2X communication simulation environment that satisfies the requirements for the security evaluation of connected cars. Then, we proposed scenarios for cybersecurity testing and evaluation, implemented and verified through CANoe Option.Car2X. Through this, it is possible to perform sufficient preliminary verification to minimize the variables before verifying security technology in a real road environment.

18.
Cell Rep ; 40(12): 111391, 2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-36130492

RESUMEN

Alzheimer's disease (AD) is the most prevalent type of dementia. Reports have revealed that the peripheral immune system is linked to neuropathology; however, little is known about the contribution of B lymphocytes in AD. For this longitudinal study, 133 participants are included at baseline and second-year follow-up. Also, we analyze B cell receptor (BCR) repertoire data generated from a public dataset of three normal and 10 AD samples and perform BCR repertoire profiling and pairwise sharing analysis. As a result, longitudinal increase in B lymphocytes is associated with increased cerebral amyloid deposition and hyperactivates induced pluripotent stem cell-derived microglia with loss-of-function for beta-amyloid clearance. Patients with AD share similar class-switched BCR sequences with identical isotypes, despite the high somatic hypermutation rate. Thus, BCR repertoire profiling can lead to the development of individualized immune-based therapeutics and treatment. We provide evidence of both quantitative and qualitative changes in B lymphocytes during AD pathogenesis.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Linfocitos B/metabolismo , Humanos , Estudios Longitudinales , Receptores de Antígenos de Linfocitos B
19.
FEBS Open Bio ; 12(9): 1634-1643, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35866358

RESUMEN

B cells recognize antigens via membrane-expressed B-cell receptors (BCR) and antibodies. Similar human BCR sequences are frequently found at a significantly higher frequency than that theoretically calculated. Patients infected with SARS-CoV2 and HIV or with autoimmune diseases share very similar BCRs. Therefore, in silico reconstitution of BCR repertoires and identification of stereotypical BCR sequences related to human pathology have diagnostic potential. Furthermore, monitoring changes of clinically significant BCR sequences and isotype conversion has prognostic potential. For BCR repertoire analysis, peripheral blood (PB) is the most convenient source. However, the optimal human PB volume for in silico reconstitution of the BCR repertoire has not been studied in detail. Here, we sampled 5, 10, and 20 mL PB from the left arm and 40 mL PB from the right arm of two volunteers, reconstituted in silico PB BCR repertoires, and compared their composition. In both volunteers, PB sampling over 20 mL resulted in slight increases in functional unique sequences (FUSs) or almost no increase in repertoire diversity. All FUSs with a frequency above 0.08% or 0.03% in the 40 mL PB BCR repertoire were detected even in the 5 mL PB BCR repertoire from each volunteer. FUSs with a higher frequency were more likely to be found in BCR repertoires from reduced PB volume, and those coexisting in two repertoires showed a statistically significant correlation in frequency irrespective of sampled anatomical site. The correlation was more significant in higher-frequency FUSs. These observations support the potential of BCR repertoire analysis for diagnosis.


Asunto(s)
COVID-19 , ARN Viral , Volumen Sanguíneo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Receptores de Antígenos de Linfocitos B/genética , SARS-CoV-2
20.
Nat Commun ; 13(1): 3467, 2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35725850

RESUMEN

The need for miniaturized and high-performance devices has attracted enormous attention to the development of quantum silicon nanowires. However, the preparation of abundant quantities of silicon nanowires with the effective quantum-confined dimension remains challenging. Here, we prepare highly dense and vertically aligned sub-5 nm silicon nanowires with length/diameter aspect ratios greater than 10,000 by developing a catalyst-free chemical vapor etching process. We observe an unusual lattice reduction of up to 20% within ultra-narrow silicon nanowires and good oxidation stability in air compared to conventional silicon. Moreover, the material exhibits a direct optical bandgap of 4.16 eV and quasi-particle bandgap of 4.75 eV with the large exciton binding energy of 0.59 eV, indicating the significant phonon and electronic confinement. The results may provide an opportunity to investigate the chemistry and physics of highly confined silicon quantum nanostructures and may explore their potential uses in nanoelectronics, optoelectronics, and energy systems.

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