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1.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38493342

RESUMO

Dynamic compartmentalization of eukaryotic DNA into active and repressed states enables diverse transcriptional programs to arise from a single genetic blueprint, whereas its dysregulation can be strongly linked to a broad spectrum of diseases. While single-cell Hi-C experiments allow for chromosome conformation profiling across many cells, they are still expensive and not widely available for most labs. Here, we propose an alternate approach, scENCORE, to computationally reconstruct chromatin compartments from the more affordable and widely accessible single-cell epigenetic data. First, scENCORE constructs a long-range epigenetic correlation graph to mimic chromatin interaction frequencies, where nodes and edges represent genome bins and their correlations. Then, it learns the node embeddings to cluster genome regions into A/B compartments and aligns different graphs to quantify chromatin conformation changes across conditions. Benchmarking using cell-type-matched Hi-C experiments demonstrates that scENCORE can robustly reconstruct A/B compartments in a cell-type-specific manner. Furthermore, our chromatin confirmation switching studies highlight substantial compartment-switching events that may introduce substantial regulatory and transcriptional changes in psychiatric disease. In summary, scENCORE allows accurate and cost-effective A/B compartment reconstruction to delineate higher-order chromatin structure heterogeneity in complex tissues.


Assuntos
Cromatina , Cromossomos , Cromatina/genética , DNA , Conformação Molecular , Epigênese Genética
2.
BMC Neurosci ; 25(1): 24, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741048

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting 44 million people worldwide, leading to cognitive decline, memory loss, and significant impairment in daily functioning. The recent single-cell sequencing technology has revolutionized genetic and genomic resolution by enabling scientists to explore the diversity of gene expression patterns at the finest resolution. Most existing studies have solely focused on molecular perturbations within each cell, but cells live in microenvironments rather than in isolated entities. Here, we leveraged the large-scale and publicly available single-nucleus RNA sequencing in the human prefrontal cortex to investigate cell-to-cell communication in healthy brains and their perturbations in AD. We uniformly processed the snRNA-seq with strict QCs and labeled canonical cell types consistent with the definitions from the BRAIN Initiative Cell Census Network. From ligand and receptor gene expression, we built a high-confidence cell-to-cell communication network to investigate signaling differences between AD and healthy brains. RESULTS: Specifically, we first performed broad communication pattern analyses to highlight that biologically related cell types in normal brains rely on largely overlapping signaling networks and that the AD brain exhibits the irregular inter-mixing of cell types and signaling pathways. Secondly, we performed a more focused cell-type-centric analysis and found that excitatory neurons in AD have significantly increased their communications to inhibitory neurons, while inhibitory neurons and other non-neuronal cells globally decreased theirs to all cells. Then, we delved deeper with a signaling-centric view, showing that canonical signaling pathways CSF, TGFß, and CX3C are significantly dysregulated in their signaling to the cell type microglia/PVM and from endothelial to neuronal cells for the WNT pathway. Finally, after extracting 23 known AD risk genes, our intracellular communication analysis revealed a strong connection of extracellular ligand genes APP, APOE, and PSEN1 to intracellular AD risk genes TREM2, ABCA1, and APP in the communication from astrocytes and microglia to neurons. CONCLUSIONS: In summary, with the novel advances in single-cell sequencing technologies, we show that cellular signaling is regulated in a cell-type-specific manner and that improper regulation of extracellular signaling genes is linked to intracellular risk genes, giving the mechanistic intra- and inter-cellular picture of AD.


Assuntos
Doença de Alzheimer , Comunicação Celular , Análise de Célula Única , Transcriptoma , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Humanos , Comunicação Celular/fisiologia , Análise de Célula Única/métodos , Encéfalo/metabolismo , Encéfalo/patologia , Córtex Pré-Frontal/metabolismo , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Transdução de Sinais/genética
3.
J Formos Med Assoc ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521760

RESUMO

BACKGROUND: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. METHODS: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. RESULTS: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. CONCLUSION: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.

4.
Int J Mol Sci ; 25(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38542478

RESUMO

We reported that a 31-amino-acid Zfra protein (zinc finger-like protein that regulates apoptosis) blocks neurodegeneration and cancer growth. Zfra binds WW domain-containing oxidoreductase (WWOX) to both N- and C-termini, which leads to accelerated WWOX degradation. WWOX limits the progression of neurodegeneration such as Alzheimer's disease (AD) by binding tau and tau-hyperphosphorylating enzymes. Similarly, Zfra binds many protein targets and accelerates their degradation independently of ubiquitination. Furthermore, Zfra4-10 peptide strongly prevents the progression of AD-like symptoms in triple-transgenic (3xTg) mice during aging. Zfra4-10 peptide restores memory loss in 9-month-old 3xTg mice by blocking the aggregation of a protein cascade, including TPC6AΔ, TIAF1, and SH3GLB2, by causing aggregation of tau and amyloid ß. Zfra4-10 also suppresses inflammatory NF-κB activation. Zfra-activated Hyal-2+ CD3- CD19- Z cells in the spleen, via Hyal-2/WWOX/Smad4 signaling, are potent in cancer suppression. In this perspective review, we provide mechanistic insights regarding how Zfra overrides WWOX to induce cancer suppression and retard AD progression via Z cells.


Assuntos
Peptídeos beta-Amiloides , Neoplasias , Camundongos , Animais , Oxidorredutase com Domínios WW/genética , Oxidorredutase com Domínios WW/metabolismo , Apoptose , Transdução de Sinais/fisiologia , Neoplasias/metabolismo
5.
J Am Chem Soc ; 145(49): 27038-27044, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38040666

RESUMO

Donor-acceptor heterojunctions in organic photocatalysts can provide enhanced exciton dissociation and charge separation, thereby improving the photocatalytic activity. However, the wide choice of possible donors and acceptors poses a challenge for the rational design of organic heterojunction photocatalysts, particularly for large ternary phase spaces. We accelerated the exploration of ternary organic heterojunction photocatalysts (TOHP) by using a combination of machine learning and high-throughput experimental screening. This involved 736 experiments in all, out of possible 4320 ternary combinations. The top ten most active TOHPs discovered using this strategy showed outstanding sacrificial hydrogen production rates of more than 500 mmol g-1 h-1, with the most active ternary material reaching a rate of 749.8 mmol g-1 h-1 under 1 sun illumination. These rates of photocatalytic hydrogen generation are among the highest reported for organic photocatalysts in the literature.

6.
Biomacromolecules ; 24(8): 3858-3871, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37523499

RESUMO

The investigation of the effects of electrical and mechanical stimulations on chondrogenesis in tissue engineering scaffolds is essential for realizing successful cartilage repair and regeneration. The aim of articular cartilage tissue engineering is to enhance the function of damaged or diseased articular cartilage, which has limited regenerative capacity. Studies have shown that electrical stimulation (ES) promotes mesenchymal stem cell (MSC) chondrogenesis, while mechanical stimulation (MS) enhances the chondrogenic differentiation capacity of MSCs. Therefore, understanding the impact of these stimuli on chondrogenesis is crucial for researchers to develop more effective tissue engineering strategies for cartilage repair and regeneration. This study focuses on the preparation of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conductive polymer (CP) scaffolds using the freeze-drying method. The scaffolds were fabricated with varying concentrations (0, 1, 3, and 10 wt %) of (3-glycidyloxypropyl) trimethoxysilane (GOPS) as a crosslinker and an additive to tailor the scaffold properties. To gain a comprehensive understanding of the material characteristics and the phase aggregation phenomenon of PEDOT:PSS scaffolds, the researchers performed theoretical calculations of solubility parameters and surface energies of PSS, PSS-GOPS, and PEDOT polymers, as well as conducted material analyses. Additionally, the study investigated the potential of promoting chondrogenic differentiation of human adipose stem cells by applying external ES or MS on a PEDOT:PSS CP scaffold. Compared to the group without stimulation, the group that underwent stimulation exhibited significantly up-regulated expression levels of chondrogenic characteristic genes, such as SOX9 and COL2A1. Moreover, the immunofluorescence staining images exhibited a more vigorous fluorescence intensity of SOX9 and COL II proteins that was consistent with the trend of the gene expression results. In the MS experiment, the strain excitation exerted on the scaffold was simulated and transformed into stress. The simulated stress response showed that the peak gradually decreased with time and approached a constant value, with the negative value of stress representing the generation of tensile stress. This stress response quantification could aid researchers in determining specific MS conditions for various materials in tissue engineering, and the applied stress conditions could be further optimized. Overall, these findings are significant contributions to future research on cartilage repair and biophysical ES/MS in tissue engineering.


Assuntos
Condrogênese , Alicerces Teciduais , Humanos , Condrogênese/fisiologia , Engenharia Tecidual/métodos , Polímeros/farmacologia , Células-Tronco , Diferenciação Celular
7.
PLoS Comput Biol ; 18(10): e1010636, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36301997

RESUMO

Early and accurate detection of viruses in clinical and environmental samples is essential for effective public healthcare, treatment, and therapeutics. While PCR detects potential pathogens with high sensitivity, it is difficult to scale and requires knowledge of the exact sequence of the pathogen. With the advent of next-gen single-cell sequencing, it is now possible to scrutinize viral transcriptomics at the finest possible resolution-cells. This newfound ability to investigate individual cells opens new avenues to understand viral pathophysiology with unprecedented resolution. To leverage this ability, we propose an efficient and accurate computational pipeline, named Venus, for virus detection and integration site discovery in both single-cell and bulk-tissue RNA-seq data. Specifically, Venus addresses two main questions: whether a tissue/cell type is infected by viruses or a virus of interest? And if infected, whether and where has the virus inserted itself into the human genome? Our analysis can be broken into two parts-validation and discovery. Firstly, for validation, we applied Venus on well-studied viral datasets, such as HBV- hepatocellular carcinoma and HIV-infection treated with antiretroviral therapy. Secondly, for discovery, we analyzed datasets such as HIV-infected neurological patients and deeply sequenced T-cells. We detected viral transcripts in the novel target of the brain and high-confidence integration sites in immune cells. In conclusion, here we describe Venus, a publicly available software which we believe will be a valuable virus investigation tool for the scientific community at large.


Assuntos
Infecções por HIV , Neoplasias Hepáticas , Vírus , Humanos , RNA-Seq , Análise de Sequência de RNA , Software
8.
Vet Res ; 54(1): 11, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36747286

RESUMO

Antimicrobial resistance (AMR) is a global health issue and surveillance of AMR can be useful for understanding AMR trends and planning intervention strategies. Salmonella, widely distributed in food-producing animals, has been considered the first priority for inclusion in the AMR surveillance program by the World Health Organization (WHO). Recent advances in rapid and affordable whole-genome sequencing (WGS) techniques lead to the emergence of WGS as a one-stop test to predict the antimicrobial susceptibility. Since the variation of sequencing and minimum inhibitory concentration (MIC) measurement methods could result in different results, this study aimed to develop WGS-based random forest models for predicting MIC values of 24 drugs using data generated from the same laboratories in Taiwan. The WGS data have been transformed as a feature vector of 10-mers for machine learning. Based on rigorous validation and independent tests, a good performance was obtained with an average mean absolute error (MAE) less than 1 for both validation and independent test. Feature selection was then applied to identify top-ranked 10-mers that can further improve the prediction performance. For surveillance purposes, the genome sequence-based machine learning methods could be utilized to monitor the difference between predicted and experimental MIC, where a large difference might be worthy of investigation on the emerging genomic determinants.


Assuntos
Antibacterianos , Anti-Infecciosos , Animais , Antibacterianos/farmacologia , Taiwan , Algoritmo Florestas Aleatórias , Salmonella/genética , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana/veterinária , Farmacorresistência Bacteriana
9.
Org Biomol Chem ; 21(19): 4022-4027, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37128802

RESUMO

Amino acids play an important role in the formation of proteins, enzymes, hormones and peptides in animals. Moreover, aspartic acid and glutamic acid have a critical impact on the central nervous system as excitatory neurotransmitters. Here, we report the highly selective detection of L-glutamic acid (L-Glu) and L-aspartic acid (L-Asp) using fluorescent microparticles constructed by the combination of aggregation-induced emission and self-assembly-induced Förster resonance energy transfer.


Assuntos
Ácido Aspártico , Ácido Glutâmico , Animais , Ácido Aspártico/química , Transferência Ressonante de Energia de Fluorescência , Aminoácidos , Peptídeos , Corantes
10.
Int J Med Sci ; 20(1): 87-101, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36619227

RESUMO

The complexity of lung adenocarcinoma (LUAD) including many interacting biological processes makes it difficult to find therapeutic biomarkers for treatment. Previous studies demonstrated that PSMG (proteasome assembly chaperone) family members regulate the degradation of abnormal proteins. However, transcript expressions of this gene family in LUAD still need to be more fully investigated. Therefore, we used a holistic bioinformatics approach to explore PSMG genes involved in LUAD patients by integrating several high-throughput databases and tools including The Cancer Genome Atlas (TCGA), and Kaplan-Meier plotter database. These data demonstrated that PSMG3 and PSMG4 were expressed at significantly higher levels in neoplastic cells than in normal lung tissues. Notably, increased expressions of these proteins were correlated with poor prognoses of lung cancer patients, which probably confirmed their fundamental roles in the staging of LUAD tumors. Meanwhile, it was also indicated that there were positive correlations between PSMG family genes and the immune response, metabolism of ubiquinone, cell cycle regulatory pathways, and heat shock protein 90 (HSP90)/phosphatidylinositol 3-kinase (PI3K)/Wnt signaling. Experimental data also confirmed that the knockdown of PSMG4 in LUAD cell lines decreased cell proliferation and influenced expressions of downstream molecules. Collectively, this study revealed that PSMG family members are novel prognostic biomarkers for LUAD progression, which also provide new therapeutic targets of LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Complexo de Endopeptidases do Proteassoma/genética , Fosfatidilinositol 3-Quinases , Adenocarcinoma de Pulmão/genética , Chaperonas Moleculares , Neoplasias Pulmonares/genética , Regulação Neoplásica da Expressão Gênica
11.
Arch Phys Med Rehabil ; 104(2): 260-269, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36055380

RESUMO

OBJECTIVES: To explore the subacromial motion metrics in patients with and without subacromial impingement syndrome (SIS) and to investigate whether the abnormality was associated with rotator cuff pathologies. DESIGN: This cross-sectional observational study used dynamic quantitative ultrasonography imaging for shoulder joint assessment. SETTING: Outpatient rehabilitation clinic. PARTICIPANTS: Individuals with SIS on at least 1 shoulder (n=32) and asymptomatic controls (n=32) (N=64). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Frame-by-frame, the humeral greater tuberosity against the lateral edge of the acromion was traced to obtain the minimal vertical acromiohumeral distance (AHD). The rotation angle and radius of the humerus were computed using the least-squares curve fitting method. RESULTS: Approximately two-thirds of the shoulders with SIS did not have any sonographically identifiable rotator cuff pathologies. There was a consistent trend of nonsignificantly increased humeral rotation angles in painful shoulders. The generalized estimating equation demonstrated that the decreased minimal vertical AHD was associated with painful subacromial impingement (ß coefficient: -0.123cm, 95% confidence interval [CI], -0.199 to -0.047). The area under the curve for the minimal vertical AHD to discriminate painful or impinged shoulders ranged from 0.624-0.676. The increased rotation angle (ß coefficient: 10.516°; 95% CI, 3.103-17.929) and decreased rotation radius (ß coefficient: -2.903cm; 95% CI, -5.693 to -0.111) were shown to be significantly related to the presence of supraspinatus tendinopathy. CONCLUSIONS: Shoulders with SIS were characterized by a decreased minimal vertical AHD during dynamic examination. Abnormal subacromial metrics can develop in patients with mild (or no) rotator cuff pathologies. More prospective cohort studies are warranted to investigate the changes in subacromial motion metrics in populations at risk for painful or impinged shoulders.


Assuntos
Síndrome de Colisão do Ombro , Articulação do Ombro , Humanos , Síndrome de Colisão do Ombro/diagnóstico por imagem , Estudos Transversais , Estudos Prospectivos , Ombro , Dor , Ultrassonografia , Amplitude de Movimento Articular
12.
Biochem Eng J ; 1992023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37692450

RESUMO

Viruses and virus-like particles are powerful templates for materials synthesis because of their capacity for precise protein engineering and diverse surface functionalization. We recently developed a recombinant bacterial expression system for the production of barley stripe mosaic virus-like particles (BSMV VLPs). However, the applicability of this biotemplate was limited by low stability in alkaline conditions and a lack of chemical handles for ligand attachment. Here, we identify and validate novel residues in the BSMV Caspar carboxylate clusters that mediate virion disassembly through repulsive interactions at high pH. Point mutations of these residues to create attractive interactions that increase rod length ~2 fold, with an average rod length of 91 nm under alkaline conditions. To enable diverse chemical surface functionalization, we also introduce reactive lysine residues at the C-terminus of BSMV coat protein, which is presented on the VLP surface. Chemical conjugation reactions with this lysine proceed more quickly under alkaline conditions. Thus, our alkaline-stable VLP mutants are more suitable for rapid surface functionalization of long nanorods. This work validates novel residues involved in BSMV VLP assembly and demonstrates the feasibility of chemical functionalization of BSMV VLPs for the first time, enabling novel biomedical and chemical applications.

13.
Molecules ; 28(9)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37175152

RESUMO

Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.


Assuntos
Sulfatos de Condroitina , Versicanas , Ratos , Animais , Versicanas/genética , Sulfatos de Condroitina/farmacologia , Ratos Wistar , Axônios/metabolismo , Regeneração Nervosa , RNA Interferente Pequeno/farmacologia
14.
Zhonghua Nan Ke Xue ; 29(1): 71-75, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-37846836

RESUMO

OBJECTIVE: To explore the effect of comprehensive nursing intervention in advanced PCa patients receiving chemoradiotherapy. METHODS: This study included 70 patients with advanced PCa undergoing chemoradiotherapy in our department from January 2020 to April 2022, who were randomly divided into a control (n = 35) and an intervention group (n = 35), the former receiving routine nursing care while the latter comprehensive nursing intervention, including such measures as health education, psychological care, radiotherapy care, chemotherapy care, and complication care. After intervention, comparisons were made between the two groups of patients in the Expanded Prostate Cancer Index Composite (EPIC) scores and incidence of adverse reactions to chemoradiotherapy. RESULTS: The scores on all the dimensions of EPIC were significantly higher in the intervention than in the control group (P < 0.05) and the incidence rate of radiation-induced proctitis and cystitis remarkably lower in the former than in the latter (36.11% vs 71.43%, P < 0.05). CONCLUSION: Comprehensive nursing intervention can improve the quality of life of the PCa patients undergoing chemoradiotherapy, increase their compliance with treatment and reduce their adverse reactions, and therefore deserves clinical promotion.


Assuntos
Neoplasias da Próstata , Qualidade de Vida , Masculino , Humanos , Quimiorradioterapia , Neoplasias da Próstata/terapia
15.
BMC Bioinformatics ; 22(Suppl 10): 629, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138350

RESUMO

BACKGROUND: The placental barrier protects the fetus from exposure to some toxicants and is vital for drug development and risk assessment of environmental chemicals. However, in vivo experiments for assessing the placental barrier permeability of chemicals is not ethically acceptable. Although ex vivo placental perfusion methods provide good alternatives for the assessment of placental barrier permeability, the application to a large number of test chemicals could be time- and resource-consuming. Computational prediction models for ex vivo placental barrier permeability are therefore desirable. METHODS: A total of 87 chemicals and corresponding 1444 physicochemical properties were divided into training and test datasets. Three types of algorithms including linear regression, random forest, and ensemble models were applied to develop prediction models for ex vivo placental barrier permeability. RESULTS: Among the tested models, the ensemble model integrating the previous two methods performed best for predicting ex vivo human placental barrier permeability with correlation coefficients of 0.887 and 0.825 when considering the applicability domain. An additional test on seven newly curated chemicals from the literature showed a good correlation coefficient of 0.879 which was further improved to 0.921 by considering the variation of experiments. CONCLUSION: In this study, the first valid predicting model for ex vivo human placental barrier permeability was developed following the OECD guideline. The model is expected to be useful for assessing the human placental barrier permeability and can be integrated with developmental toxicity prediction models for investigating the toxic effects of chemicals on the fetus.


Assuntos
Algoritmos , Placenta , Feminino , Humanos , Aprendizado de Máquina , Permeabilidade , Gravidez
16.
Small ; 18(10): e2105306, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34994521

RESUMO

Polymeric semiconductors are crucial candidates for the construction of next-generation flexible and printable electronic devices. By virtue of the successful preparation of monodispersed colloidal solution in orthogonal solvent, poly(3-hexylthiophene) (P3HT) nanofibers are developed into versatile building blocks for nanoelectronics and their compatibilities are verified with photolithographic lift-off technology. Then, the joint efforts from both the bottom-up hierarchical self-assembly and top-down self-alignment technology have led to the realization of lateral asymmetric heterojunctions with resolution better than 1 µm. As a result, planar photovoltaic devices incorporating N,N'-dioctyl-3,4,9,10-perylenedicarboximide and P3HT supramolecular nanowires as active components are constructed with the cathode-to-anode distance being tuned from ≈0.1 to 1-2 µm. Based on such a novel device configuration, an interesting phenomenon of channel-length-dependent photovoltaic efficiency is observed for the first time, strongly suggesting the impact of near-field light intensity on the performance of nanophotonic devices.

17.
Pharmacol Res ; 186: 106532, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36334876

RESUMO

The stress of the abnormal stromal matrix of solid tumors is a major limiting factor that prevents drug penetration. Controlled, accurate, and efficient delivery of theranostic agents into tumor cells is crucial. Combining ultrasound with nanocarrierbased drug delivery systems have become a promising approach for targeted drug delivery in preclinical cancer therapy. In this study, to ensure effective tumor barrier penetration, access to the tumor microenvironment, and local drug release, we designed targeted nanoparticle (NP)-conjugated microbubbles (MBs); ultrasound could then help deliver acoustic energy to release the NPs from the MBs. The ultrasound-targeted MB destruction (UTMD) system of negatively charged NPs was conjugated with positively charged MBs using an ionic gelation method. We demonstrated the transfer of targeted NPs and their entry into gastric cancer cells through ligand-specific recognition, followed by enhanced cell growth inhibition owing to drug delivery-induced apoptosis. Moreover, the UTMD system combining therapeutic and ultrasound image properties can effectively target gastric cancer, thus significantly enhancing antitumor activity, as evident by tumor localization in an orthotopic mouse model of gastric cancer. The combination of ultrasound and NP-based drug delivery systems has become a promising approach for targeted drug delivery in preclinical cancer therapy.


Assuntos
Nanopartículas , Neoplasias Gástricas , Camundongos , Animais , Microbolhas , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular Tumoral , Ultrassonografia , Sistemas de Liberação de Medicamentos/métodos , Microambiente Tumoral
18.
Am J Emerg Med ; 51: 427.e3-427.e4, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34274191

RESUMO

Vaccine-associated cerebral venous thrombosis has become an issue following the extensive vaccination program of the Coronavirus Disease of 2019 (COVID-19) Vaccine AstraZeneca (ChAdOx1 vaccine). The importance of early diagnosis should be emphasized due to the high mortality rate without appropriate treatment. Young female populations in western countries have been reported to be at a greater risk of this vaccine related thrombotic event, but cases in East Asia are lacking. Herein, we present the first case of cerebral venous sinus thrombosis 10 days after ChAdOx1 vaccination in a middle-age Asian male in Taiwan.


Assuntos
COVID-19/prevenção & controle , ChAdOx1 nCoV-19/efeitos adversos , Trombose Intracraniana/induzido quimicamente , Vacinação/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade
19.
Int J Mol Sci ; 23(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36232679

RESUMO

In ideal circumstances, a fractured bone can heal properly by itself or with the aid of clinical interventions. However, around 5% to 10% of bone fractures fail to heal properly within the expected time even with the aid of clinical interventions, resulting in nonunions. Platelet gel is a blood-derived biomaterial used in regenerative medicine aiming to promote wound healing and regeneration of damaged tissues. The purpose of this paper is to review relevant articles in an attempt to explore the current consensus on the treatment effect of platelet gel on reconstructing bone defects and nonunions, hoping to provide a valuable reference for clinicians to make treatment decisions in clinical practice. Based on the present review, most of the studies applied the combination of platelet gel and bone graft to reconstruct bone defects and nonunions, and most of the results were positive, suggesting that this treatment strategy could promote successful reconstruction of bone defects and nonunions. Only two studies tried to apply platelet gel alone to reconstruct bone defects and nonunions, therefore a convincing conclusion could not be made yet regarding the treatment effect of platelet gel alone on reconstructing bone defects and nonunions. Only one study applied platelet gel combined with extracorporeal shock wave therapy to reconstruct nonunions, and the results were positive; the hypothetical mechanism of this treatment strategy is reasonable and sound, and more future clinical studies are encouraged to further justify the effectiveness of this promising treatment strategy. In conclusion, the application of platelet gel could be a promising and useful treatment method for reconstructing bone defects and nonunions, and more future clinical studies are encouraged to further investigate the effectiveness of this promising treatment method.


Assuntos
Fraturas Ósseas , Fraturas não Consolidadas , Materiais Biocompatíveis , Transplante Ósseo/métodos , Consolidação da Fratura , Fraturas Ósseas/terapia , Fraturas não Consolidadas/cirurgia , Humanos
20.
Angew Chem Int Ed Engl ; 61(31): e202203837, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35522947

RESUMO

Dual-ion batteries that use anions and cations as charge carriers represent a promising energy-storage technology. However, an uncharted area is to explore transition metals as electrodes to host carbonate in conversion reactions. Here we report the reversible conversion reaction from copper to Cu2 CO3 (OH)2 , where the copper electrode comprising K2 CO3 and KOH solid is self-sufficient with anion-charge carriers. This electrode dissociates and associates K+ ions during battery charge and discharge. The copper active mass and the anion-bearing cathode exhibit a reversible capacity of 664 mAh g-1 and 299 mAh g-1 , respectively, and relatively stable cycling in a saturated mixture electrolyte of K2 CO3 and KOH. The results open an avenue to use carbonate as a charge carrier for batteries to serve for the consumption and storage of CO2 .

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