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1.
J Autoimmun ; 145: 103206, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554656

RESUMO

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.


Assuntos
Doença de Crohn , Memória Imunológica , Células T de Memória , Células Th17 , Humanos , Doença de Crohn/imunologia , Doença de Crohn/genética , Doença de Crohn/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células T de Memória/imunologia , Células T de Memória/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Biomarcadores , Perfilação da Expressão Gênica , Adulto Jovem
2.
Clin Genitourin Cancer ; 22(2): 413-419, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38228412

RESUMO

INTRODUCTION: Metastatic disease affects approximately 15% to 17% of patients with pheochromocytomas and paragangliomas (PPGLs). Unfortunately, treatment options for metastatic PPGLs are limited and rely on small, nonrandomized clinical trials. The impact of germline mutation status on systemic treatment outcomes remains unclear. To address these gaps, we retrospectively evaluated treatment outcomes in patients with PPGL. PATIENTS AND METHODS: Between December 2004 and December 2021, 33 patients were diagnosed with metastatic PPGLs and received systemic treatment at the Department of Oncology, Asan Medical Center, Seoul, South Korea. RESULTS: The median age of the patients was 49. Germline mutations were revealed in nine patients (39.1%) out of 23 who underwent germline testing, with SDHB mutation being the most frequent in 5 patients. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapy was administered to 18 patients, with an objective response rate (ORR) of 22% and a disease control rate (DCR) of 67%. The median progression-free survival (PFS) was 7.9 and the median overall survival (OS) was 36.2 months. Sunitinib was given to 6 patients, which had an ORR of 33%, a DCR of 83%, and a median PFS of 14.6 months. Notably, patients with SDHB/SDHD mutation (4 patients and one patient, respectively) who received CVD treatment had a significantly better OS than those without (median OS 94.0 months vs. 13.7 months, P = .01). CONCLUSION: Our study reveals that CVD and sunitinib are effective treatments for metastatic PPGLs. The results are consistent with previous studies and patients with SDHB and SDHD mutations may benefit most from CVD treatment.


Assuntos
Neoplasias das Glândulas Suprarrenais , Doenças Cardiovasculares , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/tratamento farmacológico , Feocromocitoma/genética , Feocromocitoma/diagnóstico , Mutação em Linhagem Germinativa , Estudos Retrospectivos , Sunitinibe/uso terapêutico , Succinato Desidrogenase/genética , Paraganglioma/tratamento farmacológico , Paraganglioma/genética , Dacarbazina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Ciclofosfamida/uso terapêutico
3.
Ecotoxicol Environ Saf ; 272: 116014, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38295737

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are known to be representative carcinogenic environmental pollutants with high toxicity. However, information on the potential ecological and environmental risks of PAH contamination in soil remains scarce. Thus, this study was evaluated the potential ecological risks of PAHs in soils of five Korean areas (Gunsan (GS), Gwangju, Yeongnam, Busan, and Gangwon) using organic carbon (OC)-normalized analysis, mean effect range-median quotient (M-ERM-Q), toxic equivalent quantity (TEQ) analysis, and risk quotient (RQ) derived by the species sensitivity distribution model. In this study, atmospheric particulate matter has a significant effect on soil pollution in GS through the presence of hopanes and the similar pattern of PAHs in soil and atmospheric PAHs. From analysis of source identification, combustion sources in soils of GS were important PAH sources. For PAHs in soils of GS, the OC-normalized analysis, M-ERM-Q, and TEQ analysis have 26.78 × 105 ng/g-OC, 0.218, and 49.72, respectively. Therefore, the potential ecological risk assessment results showed that GS had moderate-high ecological risk and moderate-high carcinogenic risk, whereas the other regions had low ecological risk and low-moderate carcinogenic risk. The risk level (M-ERM-Q) of PAH contamination in GS was similar to that in Changchun and Xiangxi Bay in China. The Port Harcourt City in Nigeria for PAH has the highest risk (M-ERM-Q = 4.02 and TEQ = 7923). Especially, compared to China (RQPhe =0.025 and 0.05), and Nigeria (0.059), phenanthrene showed the highest ecological risk in Korea (0.001-0.18). Korea should focus on controlling the release of PAHs originating from the PM in GS.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo , Material Particulado/análise , Monitoramento Ambiental/métodos , Medição de Risco , Poluentes do Solo/análise , Nigéria , Carcinógenos/análise , China
5.
J Crohns Colitis ; 18(2): 223-232, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-37594364

RESUMO

BACKGROUND AND AIMS: Creeping fat [CF] is a poorly understood feature of Crohn's disease [CD], characterized by the wrapping of mesenteric adipose tissue [MAT] around the inflamed intestine. The aim of this study was to investigate the transcriptional profile and compositional features of CF. METHODS: We collected 59 MAT samples: 23 paired samples from patients with CD (CF [CD-CF] and MAT around the uninflamed intestine [CD-MAT]) and 13 MAT samples from non-CD patients [Con-MAT]. Differentially expressed gene [DEG], functional pathway, cell deconvolution, and gene co-expression network analyses were performed. RESULTS: By comparing three different MAT samples, we identified a total of 529 DEGs [|log2FoldChange| > 1.5; false discovery rate < 0.05]. Of these, 323 genes showed an incremental pattern from Con-MAT to CD-MAT, and to CD-CF, while 105 genes displayed a decremental pattern. Genes with an incremental pattern were related to immune cell responses, including B- and T-cell activation, while genes with a decremental pattern were involved in cell trafficking and migration. Cell deconvolution analysis revealed significant changes in cellular composition between the CD-CF and Con-MAT groups, with increased proportions of B-cells/plasma cells [p = 1.16 × 10-4], T-cells [p = 3.66 × 10-3], and mononuclear phagocytes [p = 3.53 × 10-2] in the CD-CF group. In contrast, only the B-cell/plasma cell component showed a significant increase [p = 1.62 × 10-2] in the CD-MAT group compared to Con-MAT. CONCLUSION: The distinct transcriptional profiles and altered cellular components of each MAT found in our study provide insight into the mechanisms behind CF and highlight its possible role in the pathogenesis of CD.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/patologia , Intestinos/patologia , Tecido Adiposo/metabolismo , Linfócitos T/metabolismo , Perfilação da Expressão Gênica
6.
J Orthop Surg Res ; 18(1): 976, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38115076

RESUMO

BACKGROUND: The rolling contact joint (RCJ) mechanism is a system of constraint that allows two circular bodies connected with flexible straps to roll relative to one another without slipping. This study aims to compare the biomechanical characteristics between the conventional proximal interphalangeal joint (PIPJ) flexible hinge (FH) implant and the novel PIPJ implant adopting a RCJ mechanism during PIPJ range of motion using finite element (FE) analysis. METHODS: The three-dimensional (3D) surface shape of a conventional PIPJ FH implant was obtained using a 3D laser surface scanning system. The configuration and parameters of the novel PIPJ implant were adapted from a previous study. The two implants were assumed to have the same material characteristics and each implant was composed of a hyperelastic material, silicone elastomers. The configuration data for both implants were imported to a computer-aided design program to generate 3D geometrical surface and hyperelastic models of both implants. The hyperelastic models of both implants were imported into a structural engineering software to produce the FE mesh and to perform FE analysis. The FE analysis modeled the changes of mechanics during flexion-extension motion between 0° and 90° of two PIPJ implants. The mean and maximum values of von-Mises stress and strain as well as the total moment reaction based on the range of motion of the PIPJs were calculated. The mean values within the PIPJ's functional range of motion of the mean and maxinum von-Mises stress and strain and the total moment reaction were also determined. RESULTS: The maximum values for the von-Mises stress, and strain, as well as the total moment reactions of the conventional PIPJ FH and novel PIPJ implants were all at 90° of PIPJ flexion. The maximum value of each biomechanical property for the novel PIPJ implant was considerably lower compared with that of the conventional PIPJ FH implant. The mean values within the PIPJ's functional range of motion of the maximum von-Mises stress and strain for the novel PIPJ implant was approximately 6.43- and 6.46-fold lower compared with that of the conventional PIPJ FH implant, respectively. The mean value within a PIPJ's functional range of motion of the total moment reaction of the novel PIPJ implant was approximately 49.6-fold lower compared with that of the conventional PIPJ FH implant. CONCLUSIONS: The novel PIPJ implant with an RCJ mechanism may offer improved biomechanical performance compared with conventional PIPJ FH implant.


Assuntos
Articulações , Próteses e Implantes , Análise de Elementos Finitos , Estresse Mecânico , Software , Fenômenos Biomecânicos
7.
Rev Sci Instrum ; 94(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38015123

RESUMO

The dynamic diamond anvil cell (dDAC) technique has attracted great interest because it possibly provides a bridge between static and dynamic compression studies with fast, repeatable, and controllable compression rates. The dDAC can be a particularly useful tool to study the pathways and kinetics of phase transitions under dynamic pressurization if simultaneous measurements of physical quantities are possible as a function of time. We here report the development of a real-time event monitoring (RTEM) system with dDAC, which can simultaneously record the volume, pressure, optical image, and structure of materials during dynamic compression runs. In particular, the volume measurement using both Fabry-Pérot interferogram and optical images facilitates the construction of an equation of state (EoS) using the dDAC in a home-laboratory. We also developed an in-line ruby pressure measurement (IRPM) system to be deployed at a synchrotron x-ray facility. This system provides simultaneous measurements of pressure and x-ray diffraction in low and narrow pressure ranges. The EoSs of ice VI obtained from the RTEM and the x-ray diffraction data with the IRPM are consistent with each other. The complementarity of both RTEM and IRPM systems will provide a great opportunity to scrutinize the detailed kinetic pathways of phase transitions using dDAC.

8.
J Am Chem Soc ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37933129

RESUMO

Catalytic cross-couplings of tertiary alkyl electrophiles with carbon nucleophiles offer a powerful platform for constructing quaternary carbon centers, which are prevalent in bioactive molecules. However, these reactions remain underdeveloped primarily because of steric challenges that impede efficient bond formation. Herein, we describe the copper-catalyzed synthesis of such centers through the C(sp3)-C(sp2) bond-forming reaction between tertiary alkyl halides and arene rings of aniline derivatives, enabled by the strategic implementation of bidentate bis(cyclopropenimine) ligands. The copper catalyst bound by two imino-nitrogen atoms of these ligands, which have never been employed in metal catalysis previously, is highly effective in rapidly activating tertiary halides to generate alkyl radicals, allowing them to react with aryl nucleophiles under mild conditions with remarkably short reaction times (1-2 h). Various tertiary halides bearing carbonyl functional groups can be coupled with secondary or primary anilines, furnishing a range of quaternary carbon centers in good yields. Several mechanistic observations support the generation of copper(II) species and alkyl radicals which as a result elucidate the steps in the proposed catalytic cycle.

9.
Thromb Res ; 229: 219-224, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37562164

RESUMO

INTRODUCTION: The D-dimer to fibrinogen ratio (DFR) is a good indicator of clot-producing activity in thrombotic disease, but its clinical usefulness in stroke patients with nonvalvular atrial fibrillation (NVAF) has not been studied. We evaluated the association between the DFR and early neurological deterioration (END) in acute ischemic stroke (AIS) patients with NVAF. METHODS: We included consecutive AIS patients with NVAF between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. END was defined as an increase ≥2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. The DFR was calculated as follows: DFR = D-dimer (mg/L)/fibrinogen (mg/dL) x 100. RESULTS: A total of 1018 AIS patients with NVAF were evaluated. In multivariable logistic regression analysis, the highest DFR tertile was closely associated with END (adjusted odds ratio [aOR] = 2.14, 95 % confidence interval [CI]: 1.24-3.69). Hypertension (aOR = 1.71, 95 % CI: 1.09-2.70), initial NIHSS score (aOR = 1.05, 95 % CI: 1.02-1.07) and use of anticoagulants (aOR = 0.41, 95 % CI: 0.28-0.60) were also correlated with END. In addition to END, the DFR was correlated with discharge NIHSS and modified Rankin Scale (mRS) scores and the 3-month mRS score. CONCLUSIONS: High DFR values were associated with END in AIS patients with NVAF. As the DFR is an indicator directly related to the main pathological mechanism of NVAF patients (fibrinolysis and coagulation), it may be useful in predicting their prognosis.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Fibrinogênio , Isquemia Encefálica/complicações
10.
J Clin Neurol ; 19(5): 429-437, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37455504

RESUMO

BACKGROUND AND PURPOSE: The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs). METHODS: Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival. RESULTS: Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p=0.006), hypertension (HR 3.18, p=0.030), persistent AF type (HR 2.51, p=0.016), and initial hemoglobin level (HR 0.74, p=0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p=0.050). CONCLUSIONS: This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications.

11.
Nat Genet ; 55(5): 796-806, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37156999

RESUMO

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract with the following two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). To date, most IBD genetic associations were derived from individuals of European (EUR) ancestries. Here we report the largest IBD study of individuals of East Asian (EAS) ancestries, including 14,393 cases and 15,456 controls. We found 80 IBD loci in EAS alone and 320 when meta-analyzed with ~370,000 EUR individuals (~30,000 cases), among which 81 are new. EAS-enriched coding variants implicate many new IBD genes, including ADAP1 and GIT2. Although IBD genetic effects are generally consistent across ancestries, genetics underlying CD appears more ancestry dependent than UC, driven by allele frequency (NOD2) and effect (TNFSF15). We extended the IBD polygenic risk score (PRS) by incorporating both ancestries, greatly improving its accuracy and highlighting the importance of diversity for the equitable deployment of PRS.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/genética , Doença de Crohn/genética , População do Leste Asiático , População Europeia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Doenças Inflamatórias Intestinais/genética , Polimorfismo de Nucleotídeo Único/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
12.
Environ Sci Pollut Res Int ; 30(31): 77285-77298, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37256405

RESUMO

Bisphenol S (BPS), an organic compound and bisphenol analog, is commonly used as a substitute for bisphenol A. BPS is widely used in epoxy glues, can coatings, and thermal receipt papers; however, its risks have not been fully determined and the probability of its toxicity has been continuously suggested. In this study, we conducted BPS toxicity tests on aquatic plants (acute), cladocerans (acute and chronic), and fish (chronic) to determine its adverse effects, and calculated the toxicity values. Additionally, we conducted an ecological risk assessment of BPS in freshwater ecosystems with toxicity data from previous studies using the species sensitivity distribution method and BPS exposure data from 14 rivers in four countries in Asia (China, Japan, India, and South Korea). The chronic-based risk quotient (RQ) values of BPS in one river in China and two rivers in India were > 1, indicating a high ecological risk of BPS to aquatic organisms. The other four rivers in China showed medium ecological risk (0.1 < RQ < 1) and those in Japan and South Korea showed negligible chronic risk (RQ < 0.1) to aquatic organisms. We also suggest sensitive indicators in the model organism Danio rerio and highlighted the importance of the development of new method of ecological risk assessment. This study could provide new information that will assist in managing BPS and bisphenol analogs in freshwater ecosystems.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Ecossistema , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Organismos Aquáticos , Ásia , Medição de Risco , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/análise
13.
ACS Nano ; 17(11): 10898-10905, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37222273

RESUMO

Developing a methodology to enhance long-term stability is one of the most important issues in MXene research, since they are prone to oxidation in the ambient environment. Although various approaches have been suggested to improve the stability of MXene, they have suffered from complicated processes and limited applicability to various types of MXene nanostructures. Herein, we report a simple and versatile technique to enhance the environmental stability of MXenes. Ti3C2Tx MXene films were decorated with a highly hydrophobic polymer, 1H,1H,2H,2H-perfluorodecyl methacrylate (PFDMA), using initiated chemical vapor deposition (iCVD) where iCVD allows the facile postdeposition of polymer films of desired thickness on MXene films. The oxidation resistance was evaluated by fabricating MXene gas sensors and measuring the change in signal-to-noise ratio (SNR) of volatile organic compound (VOC) gases under harsh conditions (RH 100% at 50 °C) for several weeks where the performance in the absence and presence of PFDMA was compared. The results show that while the SNR of PFDMA-Ti3C2Tx sensors was retained, a dramatic increase of the noise level and a decrease in the SNR were observed in pristine Ti3C2Tx. We believe that this simple and nondestructive method will offer great potential to enhance the stability of a wide range of MXenes.

14.
J Radiol Prot ; 43(2)2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-36996806

RESUMO

The objective of this study is to update the national and regional indoor radon concentrations in South Korea and assess indoor radon exposure. Based on the previously published survey results and the collected measurement data of surveys conducted since 2011, a total of 9271 indoor radon measurement data covering 17 administrative divisions are finally used for analysis. The annual effective dose from the indoor radon exposure is calculated using dose coefficients recommended by the International Commission on Radiological Protection. The population-weighted average indoor radon concentration was estimated to be a geometric mean of 46 Bq m-3(GSD = 1.2) with 3.9% of all samples showing values exceeding 300 Bq m-3. The regional average indoor radon concentration ranged from 34 to 73 Bq m-3. The radon concentrations in detached houses were relatively higher than those in public buildings and multi-family houses. The annual effective doses to the Korean population due to indoor radon exposure were estimated to be 2.18 mSv. The updated values in this study might better represent the national indoor radon exposure level in South Korea because they contain more samples and cover a wider range of geographical areas than previous studies.


Assuntos
Poluentes Radioativos do Ar , Poluição do Ar em Ambientes Fechados , Monitoramento de Radiação , Radônio , Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Radônio/análise , República da Coreia , Habitação
15.
BMB Rep ; 56(2): 145-152, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36724905

RESUMO

Mechanosensitive ion channels sense mechanical stimuli applied directly to the cellular membranes or indirectly through their tethered components, provoking cellular mechanoresponses. Among others, Piezo1 mechanosensitive ion channel is a relatively novel Ca2+-permeable channel that is primarily present in non-sensory tissues. Recent studies have demonstrated that Piezo1 plays an important role in Ca2+-dependent cell death, including apoptosis and ferroptosis, in the presence of mechanical stimuli. It has also been proven that cancer cells are sensitive to mechanical stresses due to higher expression levels of Piezo1 compared to normal cells. In this review, we discuss Piezo1-mediated cell death mechanisms and therapeutic strategies to inhibit or induce cell death by modulating the activity of Piezo1 with pharmacological drugs or mechanical perturbations induced by stretch and ultrasound. [BMB Reports 2023; 56(3): 145-152].


Assuntos
Ferroptose , Canais Iônicos/metabolismo , Apoptose , Membrana Celular/metabolismo , Mecanotransdução Celular/fisiologia
16.
ACS Sens ; 8(3): 1151-1160, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36799655

RESUMO

The design of new nanomaterials for rapid and reversible detection of molecules in existence is critical for real-world sensing applications. Current nanomaterial libraries such as carbon nanotubes, graphene, MoS2, and MXene are fundamentally limited by their slow detection speed and small signals; thus, the atomic-level material design of molecular transport pathways and active binding sites must be accompanied. Herein, we fully explore the chemical and physical properties of a hydrogen-substituted graphdiyne (HsGDY) for its molecular sensing properties. This new carbon framework comprises reactive sp carbons in acetylenic linkages throughout the 16.3 Å nanopores and allows for detecting target molecules (e.g., H2) with an exceptionally high sensitivity (ΔR/Rb = 542%) and fast response/recovery time (τ90 = 8 s and τ10 = 38 s) even without any postmodification process. It possesses 2 orders of magnitude higher sensing ability than that of existing nanomaterial libraries. We demonstrate that rapid and reversible molecular binding is attributed to the cooperative interaction with adjacent double sp carbon in the layered nanoporous structure of HsGDY. This new class of carbon framework provides fundamental solutions for nanomaterials in reliable sensor applications that accelerate real-world interfacing.


Assuntos
Grafite , Nanoporos , Nanotubos de Carbono , Hidrogênio
17.
Hum Mol Genet ; 32(4): 677-684, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36164742

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of these two diseases, we performed a genome-wide association study (GWAS) between CD (n = 2359) and UC (n = 2175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergent effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2. In addition, the seven established susceptibility loci [major histocompatibility complex (MHC), TNFSF15, OTUD3, USP12, IL23R, FCHSD2 and RIPK2] reached genome-wide significance. Of the nine loci, six (MHC, TNFSF15, OTUD3, USP12, IL23R and CD200) were replicated in the case-case GWAS of European populations. The proportion of variance explained in CD-UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver-operating characteristic curve value was 0.74, suggesting acceptable discrimination between CD and UC. This CD-UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.


Assuntos
Colite Ulcerativa , Doença de Crohn , Humanos , Colite Ulcerativa/genética , Doença de Crohn/genética , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Loci Gênicos , Polimorfismo de Nucleotídeo Único/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Proteínas de Transporte/genética , Proteínas de Membrana/genética , Proteases Específicas de Ubiquitina/genética
18.
Int J Mol Sci ; 25(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38203383

RESUMO

The fruit flesh of watermelons differs depending on the distinct carotenoid composition. Orange-colored flesh relates to the accumulation of ß-carotene, which is beneficial to human health. Canary-yellow-fleshed OTO-DAH and orange-ß-fleshed (orange-fleshed with high ß-carotene) NB-DAH near-isogenic lines (NILs) were used to determine the genetic mechanism attributed to orange watermelon flesh. For genetic mapping, an F2 population was developed by crossing the two NILs. The segregation ratio of flesh color in the F2 population indicated that the orange-ß flesh of the NB-DAH NIL was controlled by a single incompletely dominant gene. Through a comparative analysis of the whole-genome sequences of the parent lines and NILs, a major introgression region unique to the NB-DAH NIL was detected on Chr. 1; this was considered a candidate region for harboring genes that distinguish orange from canary-yellow and red flesh. Among the 13 genes involved in the carotenoid metabolic pathway in watermelons, only ClPSY1 (ClCG01G008470), which encodes phytoene synthase 1, was located within the introgression region. The genotyping of F2 plants using a cleaved amplified polymorphic sequence marker developed from a non-synonymous SNP in ClPSY1 revealed its relationship with orange-ß flesh. The insights gained in this study can be applied to marker-assisted breeding for this desirable trait.


Assuntos
Melhoramento Vegetal , beta Caroteno , Humanos , Carotenoides , Marcadores Genéticos , Mapeamento Cromossômico
19.
Phys Rev E ; 106(4-1): 044212, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36397529

RESUMO

Mechanical computing has seen resurgent interest recently owing to the potential to embed sensing and computation into new classes of programmable metamaterials. To realize this, however, one must push signals from one part of a device to another and do so in a way that can be reset robustly. We investigate the propagation of signals in a bistable mechanical cascade uphill in energy. By identifying a penetration length for perturbations, we show that signals can propagate uphill for finite distances and map out parameters for this to occur. Experiments on soft elastomers corroborate our results.

20.
ACS Nano ; 16(10): 17210-17219, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36223595

RESUMO

Metal oxide semiconductors (MOS) have proven to be most powerful sensing materials to detect hydrogen sulfide (H2S), achieving part per billion (ppb) level sensitivity and selectivity. However, there has not been a way of extending this approach to the top-down H2S sensor fabrication process, completely limiting their commercial-level productions. In this study, we developed a top-down lithographic process of a 10 nm-scale SnO2 nanochannel for H2S sensor production. Due to high-resolution (15 nm thickness) and high aspect ratio (>20) structures, the nanochannel exhibited highly sensitive H2S detection performances (Ra/Rg = 116.62, τres = 31 s at 0.5 ppm) with selectivity (RH2S/Racetone = 23 against 5 ppm acetone). In addition, we demonstrated that the nanochannel could be efficiently sensitized with the p-n heterojunction without any postmodification or an additional process during one-step lithography. As an example, we demonstrated that the H2S sensor performance can be drastically enhanced with the NiO nanoheterojunction (Ra/Rg = 166.2, τres = 21 s at 0.5 ppm), showing the highest range of sensitivity demonstrated to date for state-of-the-art H2S sensors. These results in total constitute a high-throughput fabrication platform to commercialize the H2S sensor that can accelerate the development time and interface in real-life situations.

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