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1.
Ann Coloproctol ; 40(2): 89-113, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38712437

RESUMO

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

2.
BMC Musculoskelet Disord ; 25(1): 379, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745277

RESUMO

BACKGROUND: Biomarkers that predict the treatment response in patients with knee osteoarthritis are scarce. This study aimed to investigate the potential role of synovial fluid cell counts and their ratios as biomarkers of primary knee osteoarthritis. METHODS: This retrospective study investigated 96 consecutive knee osteoarthritis patients with knee effusion who underwent joint fluid aspiration analysis and received concomitant intra-articular corticosteroid injections and blood tests. The monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) were calculated. After 6 months of treatment, patients were divided into two groups: the responder group showing symptom resolution, defined by a visual analog scale (VAS) score of ≤ 3, without additional treatment, and the non-responder group showing residual symptoms, defined by a VAS score of > 3 and requiring further intervention, such as additional medication, repeated injections, or surgical treatment. Unpaired t-tests and univariate and multivariate logistic regression analyses were conducted between the two groups to predict treatment response after conservative treatment. The predictive value was calculated using the area under the receiver operating characteristic curve, and the optimal cutoff value was determined. RESULTS: Synovial fluid MLR was significantly higher in the non-responder group compared to the responder group (1.86 ± 1.64 vs. 1.11 ± 1.37, respectively; p = 0.02). After accounting for confounding variables, odds ratio of non-responder due to increased MLR were 1.63 (95% confidence interval: 1.11-2.39). The optimal MLR cutoff value for predicting patient response to conservative treatment was 0.941. CONCLUSIONS: MLR may be a potential biomarker for predicting the response to conservative treatment in patients with primary knee osteoarthritis.


Assuntos
Tratamento Conservador , Linfócitos , Monócitos , Osteoartrite do Joelho , Líquido Sinovial , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Líquido Sinovial/citologia , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Tratamento Conservador/métodos , Injeções Intra-Articulares , Biomarcadores/análise , Biomarcadores/sangue , Valor Preditivo dos Testes , Contagem de Leucócitos
3.
Small ; : e2401546, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38705853

RESUMO

The design of high-energy facets in electrocatalysts has attracted significant attention due to their potential to enhance electrocatalytic activity. In this review, the significance of high-energy facets in various electrochemical reactions are highlighted, including oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), nitrogen reduction reaction (NRR), and carbon dioxide reduction reaction (CRR). Their importance in various electrochemical reactions and present strategies for constructing high-energy facets are discussed, including alloying, heterostructure formation, selective etching, capping agents, and coupling with substrates. These strategies enable control over crystallographic orientation and surface morphology, fine-tuning electrocatalytic properties. This study also addresses future directions and challenges, emphasizing the need to better understand fundamental mechanisms. Overall, high-energy facets offer exciting opportunities for advancing electrocatalysis.

4.
Brain Tumor Res Treat ; 12(2): 148-151, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742265

RESUMO

Eosinophilic granuloma (EG), a subtype of Langerhans cell histiocytosis (LCH), the monostotic form, is a rare condition characterized by a solitary bone lesion. It is even more unusual for this condition to be accompanied by an epidural hematoma (EDH). This case is unique in that it is the first to involve delayed EDH following a seizure. We describe a remarkable example of EG accompanied by an EDH and consider the rarity of this comorbidity. A 32-month-old boy developed a rapidly growing skull mass following a minor head injury. During surgical preparation for a biopsy, the patient experienced a single convulsion. Imaging following the seizure revealed an EDH in the vicinity of the mass. The mass was excised and confirmed to be an EG, but with positive margins. The patient underwent chemotherapy after systemic skeletal evaluation, in accordance with the LCH III protocol established by the Histiocytosis Society. EG is a rare neoplasm that typically presents as a painless growth on the skull that gradually enlarges over time. The correlation between EG and EDH is exceedingly uncommon, with only a few documented cases. This case study underscores the significance of considering EG in the differential diagnosis of an expanding cranium mass, even when associated with EDH. Prompt diagnosis and treatment can prevent serious complications and improve patient outcomes.

5.
Nat Commun ; 15(1): 3182, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609352

RESUMO

Huntington's disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin's polyglutamine tract. Lowering mutant huntingtin has been proposed for treating HD, but genetic modifiers implicate somatic CAG repeat expansion as the driver of onset. We find that branaplam and risdiplam, small molecule splice modulators that lower huntingtin by promoting HTT pseudoexon inclusion, also decrease expansion of an unstable HTT exon 1 CAG repeat in an engineered cell model. Targeted CRISPR-Cas9 editing shows this effect is not due to huntingtin lowering, pointing instead to pseudoexon inclusion in PMS1. Homozygous but not heterozygous inactivation of PMS1 also reduces CAG repeat expansion, supporting PMS1 as a genetic modifier of HD and a potential target for therapeutic intervention. Although splice modulation provides one strategy, genome-wide transcriptomics also emphasize consideration of cell-type specific effects and polymorphic variation at both target and off-target sites.


Assuntos
Doença de Huntington , Humanos , Doença de Huntington/genética , Éxons/genética , Perfilação da Expressão Gênica , Heterozigoto , Homozigoto , Proteínas MutL , Proteínas de Neoplasias
6.
Proc Natl Acad Sci U S A ; 121(16): e2322924121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38607933

RESUMO

Many Mendelian disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, arise from expansions of CAG trinucleotide repeats. Despite the clear genetic causes, additional genetic factors may influence the rate of those monogenic disorders. Notably, genome-wide association studies discovered somewhat expected modifiers, particularly mismatch repair genes involved in the CAG repeat instability, impacting age at onset of HD. Strikingly, FAN1, previously unrelated to repeat instability, produced the strongest HD modification signals. Diverse FAN1 haplotypes independently modify HD, with rare genetic variants diminishing DNA binding or nuclease activity of the FAN1 protein, hastening HD onset. However, the mechanism behind the frequent and the most significant onset-delaying FAN1 haplotype lacking missense variations has remained elusive. Here, we illustrated that a microRNA acting on 3'-UTR (untranslated region) SNP rs3512, rather than transcriptional regulation, is responsible for the significant FAN1 expression quantitative trait loci signal and allelic imbalance in FAN1 messenger ribonucleic acid (mRNA), accounting for the most significant and frequent onset-delaying modifier haplotype in HD. Specifically, miR-124-3p selectively targets the reference allele at rs3512, diminishing the stability of FAN1 mRNA harboring that allele and consequently reducing its levels. Subsequent validation analyses, including the use of antagomir and 3'-UTR reporter vectors with swapped alleles, confirmed the specificity of miR-124-3p at rs3512. Together, these findings indicate that the alternative allele at rs3512 renders the FAN1 mRNA less susceptible to miR-124-3p-mediated posttranscriptional regulation, resulting in increased FAN1 levels and a subsequent delay in HD onset by mitigating CAG repeat instability.


Assuntos
Doença de Huntington , MicroRNAs , Humanos , Regiões 3' não Traduzidas/genética , Endodesoxirribonucleases , Exodesoxirribonucleases/genética , Estudo de Associação Genômica Ampla , Doença de Huntington/genética , MicroRNAs/genética , Enzimas Multifuncionais
7.
Nat Commun ; 15(1): 2814, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561403

RESUMO

The emergence of high-form-factor electronics has led to a demand for high-density integration of inorganic thin-film devices and circuits with full stretchability. However, the intrinsic stiffness and brittleness of inorganic materials have impeded their utilization in free-form electronics. Here, we demonstrate highly integrated strain-insensitive stretchable metal-oxide transistors and circuitry (442 transistors/cm2) via a photolithography-based bottom-up approach, where transistors with fluidic liquid metal interconnection are embedded in large-area molecular-tailored heterogeneous elastic substrates (5 × 5 cm2). Amorphous indium-gallium-zinc-oxide transistor arrays (7 × 7), various logic gates, and ring-oscillator circuits exhibited strain-resilient properties with performance variation less than 20% when stretched up to 50% and 30% strain (10,000 cycles) for unit transistor and circuits, respectively. The transistors operate with an average mobility of 12.7 ( ± 1.7) cm2 V-1s-1, on/off current ratio of > 107, and the inverter, NAND, NOR circuits operate quite logically. Moreover, a ring oscillator comprising 14 cross-wired transistors validated the cascading of the multiple stages and device uniformity, indicating an oscillation frequency of ~70 kHz.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38609169

RESUMO

CONTEXT: Thyrotoxicosis requires accurate and expeditious differentiation between Graves' disease (GD) and thyroiditis to ensure effective treatment decisions. OBJECTIVE: This study aimed to develop a machine learning algorithm using ultrasonography and Doppler images to differentiate thyrotoxicosis subtypes, with a focus on GD. METHODS: This study included patients who initially presented with thyrotoxicosis and underwent thyroid ultrasonography at a single tertiary hospital. A total of 7,719 ultrasonography images from 351 patients with GD and 2,980 images from 136 patients with thyroiditis were used. Data augmentation techniques were applied to enhance the algorithm's performance. Two deep learning models, Xception and EfficientNetB0_2, were employed. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score were calculated for both models. Image pre-processing, neural network model generation, and neural network training results verification were performed using DEEP:PHI® platform. RESULTS: The Xception model achieved 84.94% accuracy, 89.26% sensitivity, 73.17% specificity, 90.06% PPV, 71.43% NPV, and an F1 score of 89.66 for the diagnosis of GD. The EfficientNetB0_2 model exhibited 85.31% accuracy, 90.28% sensitivity, 71.78% specificity, 89.71% PPV, 73.05% NPV, and an F1 score of 89.99. CONCLUSION: Machine learning models based on ultrasound and Doppler images showed promising results with high accuracy and sensitivity in differentiating GD from thyroiditis.

9.
Nano Lett ; 24(14): 4224-4232, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38557115

RESUMO

In this study, we identify the local structures of ex-solved nanoparticles using machine-learned potentials (MLPs). We develop a method for training machine-learned potentials by sampling local structures of heterointerface configurations as a training set with its efficacy tested on the Ni/MgO system, illustrating that the error in interface energy is only 0.004 eV/Å2. Using the developed scheme, we train an MLP for the Ni/La0.5Ca0.5TiO3 ex-solution system and identify the local structures for both exo- and endo-type particles. The established model aligns well with the experimental observations, accurately predicting a nucleation size of 0.45 nm. Lastly, the density functional theory calculations on the established atomistic model verify that the kinetic barrier for the dry reforming of methane are substantially reduced by 0.49 eV on the ex-solved catalysts compared to that on the impregnated catalysts. Our findings offer insights into the local structures, growth mechanisms, and underlying origin of the catalytic properties of ex-solved nanoparticles.

10.
Gynecol Oncol ; 183: 68-73, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38520881

RESUMO

OBJECTIVE: To investigate pathologic complete response (pCR) and recurrence outcomes using various progestin treatment strategies in patients with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN). METHODS: Medical records of patients diagnosed with AH/EIN and undergoing follow-up endometrial biopsy after progestin treatment between 2011 and 2020 were retrospectively reviewed. Clinical factors and treatment outcomes were analyzed according to initial progestin treatment (oral progestin [OP], levonorgestrel-releasing intrauterine device [LNG-IUD], and combination), OP dose, and maintenance treatment using Pearson's χ2, Fisher's exact test, and Kaplan-Meier analysis. RESULTS: Of 124 patients included, 74, 37, and 13 were in the OP, LNG-IUD, and combination groups, respectively. The pCR rate was 79.8% and recurrence rate was 21.2%. The pCR rates within 3 and 6 months were significantly higher in the OP group than in the LNG-IUD group, but were not significantly different within 12 and 24 months. Recurrence rate was significantly higher in the OP group than in the LNG-IUD group. The pCR rate and recurrence rate had no significant differences between the combination group and the other groups. Excluding the LNG-IUD group, 53 and 34 patients received low- and high-dose OP, respectively. The pCR and recurrence rates were comparable between the low- and high-dose OP groups. Maintenance therapy was significantly associated with lower recurrence rate. CONCLUSIONS: Although OP alone achieved more short-term pCR than the other groups, more recurrences occurred after pCR than LNG-IUD alone. High-dose OP as well as combination of OP and LNG-IUD did not increase pCR or reduce recurrence. Maintenance therapy may reduce the recurrence rate after pCR.

11.
J Neurosurg Spine ; : 1-7, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552235

RESUMO

OBJECTIVE: Conus medullaris arteriovenous malformation (AVM) is rare and challenging to treat. To better define the presentation, prognosis, and optimal treatment of these lesions, the authors present their treatment experiences for conus medullaris AVM. METHODS: Eleven patients with AVM of the conus medullaris were identified between March 2013 and December 2021. Among these patients, 7 who underwent microsurgical treatment were included. Patient data, including age, sex, symptoms at presentation, neurological status, radiological findings, nidus depth (mainly pial lesion vs intramedullary lesion), type of treatment, and recurrence at follow-up, were collected. Postoperative angiography was performed in all patients. Spinal cord function was evaluated using the Frankel grade at the time of admission and 1 year after surgery. RESULTS: All 7 patients presenting with myeloradiculopathy were treated surgically. Four patients (57.1%) underwent endovascular embolization, followed by resection. The other 3 patients underwent microsurgery only. Complete occlusion was confirmed with postoperative angiography in all patients. Of the 3 patients who were nonambulatory before surgery (Frankel grade C), 2 were able to walk after surgery (Frankel grade D) and 1 remained nonambulatory (Frankel grade C) at 1-year follow-up. CONCLUSIONS: Based on the authors' clinical experiences, the results of multimodal treatment for conus medullaris AVM are good, with microsurgical treatment playing an important role. The microsurgical strategy can differ depending on the location of the nidus, and when possible, good results can be expected through microsurgical resection.

12.
J Am Chem Soc ; 146(11): 7752-7762, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38447176

RESUMO

Electrochemical nitrogen reduction reaction (eNRR) offers a sustainable route for ammonia synthesis; however, current electrocatalysts are limited in achieving optimal performance within narrow potential windows. Herein, inspired by the heliotropism of sunflowers, we present a biomimetic design of Ru-VOH electrocatalyst, featuring a dynamic Ru-O-V pyramid electron bridge for eNRR within a wide potential range. In situ spectroscopy and theoretical investigations unravel the fact that the electrons are donated from Ru to V at lower overpotentials and retrieved at higher overpotentials, maintaining a delicate balance between N2 activation and proton hydrogenation. Moreover, N2 adsorption and activation were found to be enhanced by the Ru-O-V moiety. The catalyst showcases an outstanding Faradaic efficiency of 51.48% at -0.2 V (vs RHE) with an NH3 yield rate exceeding 115 µg h-1 mg-1 across the range of -0.2 to -0.4 V (vs RHE), along with impressive durability of over 100 cycles. This dynamic M-O-V pyramid electron bridge is also applicable to other metals (M = Pt, Rh, and Pd).

13.
Brain Commun ; 6(2): fcae016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449714

RESUMO

Expansions of glutamine-coding CAG trinucleotide repeats cause a number of neurodegenerative diseases, including Huntington's disease and several of spinocerebellar ataxias. In general, age-at-onset of the polyglutamine diseases is inversely correlated with the size of the respective inherited expanded CAG repeat. Expanded CAG repeats are also somatically unstable in certain tissues, and age-at-onset of Huntington's disease corrected for individual HTT CAG repeat length (i.e. residual age-at-onset), is modified by repeat instability-related DNA maintenance/repair genes as demonstrated by recent genome-wide association studies. Modification of one polyglutamine disease (e.g. Huntington's disease) by the repeat length of another (e.g. ATXN3, CAG expansions in which cause spinocerebellar ataxia 3) has also been hypothesized. Consequently, we determined whether age-at-onset in Huntington's disease is modified by the CAG repeats of other polyglutamine disease genes. We found that the CAG measured repeat sizes of other polyglutamine disease genes that were polymorphic in Huntington's disease participants but did not influence Huntington's disease age-at-onset. Additional analysis focusing specifically on ATXN3 in a larger sample set (n = 1388) confirmed the lack of association between Huntington's disease residual age-at-onset and ATXN3 CAG repeat length. Additionally, neither our Huntington's disease onset modifier genome-wide association studies single nucleotide polymorphism data nor imputed short tandem repeat data supported the involvement of other polyglutamine disease genes in modifying Huntington's disease. By contrast, our genome-wide association studies based on imputed short tandem repeats revealed significant modification signals for other genomic regions. Together, our short tandem repeat genome-wide association studies show that modification of Huntington's disease is associated with short tandem repeats that do not involve other polyglutamine disease-causing genes, refining the landscape of Huntington's disease modification and highlighting the importance of rigorous data analysis, especially in genetic studies testing candidate modifiers.

14.
BMC Cancer ; 24(1): 397, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553680

RESUMO

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Estudos Multicêntricos como Assunto , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Fluoruracila/uso terapêutico
15.
Obstet Gynecol Sci ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38484700

RESUMO

Objective: We aimed to predict the risk posed by postoperative adjuvant therapy using preoperative variables in young patients with early stage cervical cancer. The predicted risk can guide whether ovarian transposition should be performed during surgery. Methods: This multicenter retrospective study was conducted using data from the Korean Gynecologic Oncology Group (KGOG) 1028 study. In total, 886 patients with stage IB1-IIA cervical cancer aged 20-45 years who underwent modified radical or radical hysterectomy between January 2000 and December 2008 were included. Preoperative variables, preoperative laboratory findings, International Federation of Gynaecology and Obstetrics stage, tumor size, and pathological variables were collected. Patients with high risk factors or those who met the Sedlis criteria were considered adjuvant therapy risk (+); others were considered adjuvant therapy risk (-). A decision-tree model using preoperative variables was constructed to predict the risk of adjuvant therapy. Results: Of 886 patients, 362 were adjuvant therapy risk (+) (40.9%). The decision-tree model with four distinct adjuvant therapy risks using tumor size and age were generated. Specifically, patients with tumor size ≤2.45 cm had low risk (49/367; 13.4%), those with tumor size ≤3.85 cm and >2.45 cm had moderate risk (136/314; 43.3%), those with tumor size >3.85 cm and age ≤39.5 years had high risk (92/109; 84.4%), and those with tumor size >3.85 cm and age >39.5 years had the highest risk (85/96; 88.5%). Conclusion: The risk of postoperative adjuvant therapy in young patients with early stage cervical cancer can be predicted using preoperative variables. We can decide whether ovarian transposition should be performed using the predicted risk.

16.
ACS Nano ; 18(14): 9942-9957, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38552006

RESUMO

Highly efficient, cost-effective, and durable electrocatalysts, capable of accelerating sluggish reaction kinetics and attaining high performance, are essential for developing sustainable energy technologies but remain a great challenge. Here, we leverage a facile heterostructure design strategy to construct atomically thin Os@Pd metallenes, with atomic-scale Os nanoclusters of varying geometries confined on the surface layer of the Pd lattice, which exhibit excellent bifunctional properties for catalyzing both hydrogen evolution (HER) and oxygen reduction reactions (ORR). Importantly, Os5%@Pd metallenes manifest a low η10 overpotential of only 11 mV in 1.0 M KOH electrolyte (HER) as well as a highly positive E1/2 potential of 0.92 V in 0.1 M KOH (ORR), along with superior mass activities and electrochemical durability. Theoretical investigations reveal that the strong electron redistribution between Os and Pd elements renders a precise fine-tuning of respective d-band centers, thereby guiding adsorption of hydrogen and oxygen intermediates with an appropriate binding energy for the optimal HER and ORR.

17.
Chem Soc Rev ; 53(5): 2693-2737, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38318782

RESUMO

In recent decades, significant progress has been achieved in rational developments of electrocatalysts through constructing novel atomistic structures and modulating catalytic surface topography, realizing substantial enhancement in electrocatalytic activities. Numerous advanced catalysts were developed for electrochemical energy conversion, exhibiting low overpotential, high intrinsic activity, and selectivity. Yet, maintaining the high catalytic performance under working conditions with high polarization and vigorous microkinetics that induce intensive degradation of surface nanostructures presents a significant challenge for commercial applications. Recently, advanced operando and computational techniques have provided comprehensive mechanistic insights into the degradation of surficial functional structures. Additionally, various innovative strategies have been devised and proven effective in sustaining electrocatalytic activity under harsh operating conditions. This review aims to discuss the most recent understanding of the degradation microkinetics of catalysts across an entire range of anodic to cathodic polarizations, encompassing processes such as oxygen evolution and reduction, hydrogen reduction, and carbon dioxide reduction. Subsequently, innovative strategies adopted to stabilize the materials' structure and activity are highlighted with an in-depth discussion of the underlying rationale. Finally, we present conclusions and perspectives regarding future research and development. By identifying the research gaps, this review aims to inspire further exploration of surface degradation mechanisms and rational design of durable electrocatalysts, ultimately contributing to the large-scale utilization of electroconversion technologies.

18.
medRxiv ; 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38352343

RESUMO

Myofibrillar myopathy 6 (MFM6) is a rare childhood-onset myopathy characterized by myofibrillar disintegration, muscle weakness, and cardiomyopathy. The genetic cause of MFM6 is p.Pro209Leu mutation (rs121918312-T) in the BAG3 gene, which generates the disease outcomes in a dominant fashion. Since the consequences of the BAG3 mutation are strong and rapidly progressing, most MFM6 patients are due to de novo mutation. There are no effective treatments for MFM6 despite its well-known genetic cause. Given p.Pro209Leu mutation is dominant, regenerative medicine approaches employing orthologous stem cells in which mutant BAG3 is inactivated offer a promising avenue. Here, we developed personalized allele-specific CRISPR-Cas9 strategies capitalizing on PAM-altering SNP and PAM-proximal SNP. In order to identify the disease chromosome carrying the de novo mutation in our two affected individuals, haplotype phasing through cloning-sequencing was performed. Based on the sequence differences between mutant and normal BAG3, we developed personalized allele-specific CRISPR-Cas9 strategies to selectively inactivate the mutant allele 1) by preventing the transcription of the mutant BAG3 and 2) by inducing nonsense-mediated decay (NMD) of mutant BAG3 mRNA. Subsequent experimental validation in patient-derived induced pluripotent stem cell (iPSC) lines showed complete allele specificities of our CRISPR-Cas9 strategies and molecular consequences attributable to inactivated mutant BAG3. In addition, mutant allele-specific CRISPR-Cas9 targeting did not alter the characteristics of iPSC or the capacity to differentiate into cardiomyocytes. Together, our data demonstrate the feasibility and potential of personalized allele-specific CRISPR-Cas9 approaches to selectively inactivate the mutant BAG3 to generate cell resources for regenerative medicine approaches for MFM6.

19.
Chemosphere ; 352: 141511, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38401862

RESUMO

The surface hydrophilicity of a photocatalyst is an important factor that directly influences its interactions with organic pollutants and significantly impacts its degradation. In this study, we investigated the impact of increased hydrophilicity of g-C3N4 (CN) by alkaline solvothermal treatment on the degradations of three antibiotics (oxytetracycline (OTC), oxolinic acid (OA), and sulfamethoxazole (SMX)) with different log Kow values. Scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), and Fourier-transform infrared (FT-IR) spectroscopy showed no significant differences in the morphology, crystalline structure, and surface functional groups of CN after alkaline solvothermal treatment (Nv-HPCN). However, contact angle analysis revealed that Nv-HPCN (31.8°) was more hydrophilic than CN (61.1°). To assess the hydrophilicity of the antibiotics, the log Kow values of SMX (0.77), OA (0.43), and OTC (-0.34) were measured. Nv-HPCN showed faster OTC degradation than CN, whereas the opposite pattern was observed for the degradation of OA. Scavenger tests showed that O2•- and h+ mainly contributed to the degradation of these antibiotics. Furthermore, the influences of NOM and coexisting anions on antibiotic degradation were investigated. This study thus offers perspectives on the impact of surface hydrophilicity of photocatalysts on the degradation of antibiotics.


Assuntos
Grafite , Compostos de Nitrogênio , Oxitetraciclina , Antibacterianos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Oxitetraciclina/química , Grafite/química , Catálise
20.
J Chem Theory Comput ; 20(5): 2284-2296, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38358319

RESUMO

Numerous systematic methods have been developed to search for the global minimum of the potential energy surface, which corresponds to the optimal atomic structure. However, the majority of them still demand a substantial computing load due to the relaxation process that is embedded as an inner step inside the algorithm. Here, we propose a hybrid approach that combines Bayesian optimization (BO) and a local search that circumvents the relaxation step and efficiently finds the optimum structure, particularly in supported metal systems. The hybridization strategy combining the capabilities of BO's effective exploration and the local search's fast convergence expedites structural search. In addition, the formulation of physical constraints regarding the materials system and the feature of screening structure similarity enhance the computational efficiency of the proposed method. The proposed algorithm is demonstrated in two supported metal systems, showing the potential of the proposed method in the field of structural optimization.

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