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1.
Genome Res ; 31(12): 2340-2353, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34663689

RESUMO

Circular RNAs (circRNAs) are abundantly expressed in cancer. Their resistance to exonucleases enables them to have potentially stable interactions with different types of biomolecules. Alternative splicing can create different circRNA isoforms that have different sequences and unequal interaction potentials. The study of circRNA function thus requires knowledge of complete circRNA sequences. Here we describe psirc, a method that can identify full-length circRNA isoforms and quantify their expression levels from RNA sequencing data. We confirm the effectiveness and computational efficiency of psirc using both simulated and actual experimental data. Applying psirc on transcriptome profiles from nasopharyngeal carcinoma and normal nasopharynx samples, we discover and validate circRNA isoforms differentially expressed between the two groups. Compared with the assumed circular isoforms derived from linear transcript annotations, some of the alternatively spliced circular isoforms have 100 times higher expression and contain substantially fewer microRNA response elements, showing the importance of quantifying full-length circRNA isoforms.

2.
Small ; 20(28): e2310339, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38295011

RESUMO

The modulation of the coordination environment of single atom catalysts (SACs) plays a vital role in promoting CO2 reduction reaction (CO2RR). Herein, N or B doped Fe-embedded graphyne (Fe-GY), Fe-nXGYm (n = 1, 2, 3; X = N, B; m = 1, 2, 3), are employed as probes to reveal the effect of the coordination environment engineering on CO2RR performance via heteroatom doping in SACs. The results show that the doping position and number of N or B in Fe-GY significantly affects catalyst activity and CO2RR product selectivity. In comparison, Fe-1NGY exhibits high-performance CO2RR to CH4 with a low limiting potential of -0.17 V, and Fe-2NGY3 is demonstrated as an excellent CO2RR electrocatalyst for producing HCOOH with a low limiting potential of -0.16 V. With applied potential, Fe-GY, Fe-1NGY, and Fe-2NGY3 exhibit significant advantages in CO2RR to CH4 while hydrogen evolution reaction is inhibited. The intrinsic essence analysis illustrates that heteroatom doping modulates the electronic structure of active sites and regulates the adsorption strength of the intermediates, thereby rendering a favorable coordination environment for CO2RR. This work highlights Fe-nXGYm as outstanding SACs for CO2RR, and provides an in-depth insight into the intrinsic essence of the promotion effect from heteroatom doping.

3.
J Pathol ; 259(2): 163-179, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36420735

RESUMO

Invadopodia are actin-rich membrane protrusions that digest the matrix barrier during cancer metastasis. Since the discovery of invadopodia, they have been visualized as localized and dot-like structures in different types of cancer cells on top of a 2D matrix. In this investigation of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), a highly invasive cancer frequently accompanied by neck lymph node and distal organ metastases, we revealed a new form of invadopodium with mobilizing features. Integration of live-cell imaging and molecular assays revealed the interaction of macrophage-released TNFα and EBV-encoded latent membrane protein 1 (LMP1) in co-activating the EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for mobilizing the invadopodia with lateral movements. This phenomenon endows the invadopodia with massive degradative power, visualized as a shift of focal dot-like digestion patterns on a 2D gelatin to a dendrite-like digestion pattern. Notably, single stimulation of either LMP1 or TNFα could only enhance the number of ordinary dot-like invadopodia, suggesting that the EBV infection sensitizes the NPC cells to form mobilizing invadopodia when encountering a TNFα-rich tumor microenvironment. This study unveils the interplay of EBV and stromal components in driving the invasive potential of NPC via unleashing the propulsion of invadopodia in overcoming matrix hurdles. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Podossomos , Humanos , Carcinoma Nasofaríngeo/patologia , Podossomos/metabolismo , Podossomos/patologia , Herpesvirus Humano 4/metabolismo , Neoplasias Nasofaríngeas/patologia , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas de Membrana/metabolismo , Proteínas da Matriz Viral/metabolismo , Microambiente Tumoral
4.
Artigo em Inglês | MEDLINE | ID: mdl-38741468

RESUMO

BACKGROUND: Provider payment reforms (PPRs) have demonstrated mixed results for improving health system efficiency. Since PPRs require health care organisations to interpret and implement policies, the organizational characteristics of hospitals may affect the effectiveness of PPRs. Hospitals with more autonomy have the flexibility to respond to PPRs more efficiently, but they may not if the autonomy previously facilitated behaviours that counter the PPR's objective. This study examines whether hospitals with higher autonomy responds to PPRs more effectively. METHODS: We used data from a matched-pair, cluster randomized controlled PPR intervention in a resource-limited Chinese province between 2014 and 2018. The intervention reformed the reimbursement method from the publicly administered New Cooperative Medical Scheme (NCMS) from fee-for-service to global budget. We interacted measures of hospital autonomy over surplus, hiring, and procurement (drugs, consumables, equipment, and overall index) with the difference-in-difference estimator to examine how autonomy moderated the intervention's effect. RESULTS: Autonomy over surplus (p < 0.01) and procurement of equipment (p < 0.01) were associated with relatively faster NCMS expenditure growth, demonstrating worse PPR response. They were also associated with higher expenditure shifting to out-of-pocket expenditures (p > 0.05). Post hoc analysis suggests that hospitals with surplus autonomy had higher OOP per admission (p < 0.01), suggesting profiteering tendencies. Other dimensions of autonomy demonstrated imprecise association. DISCUSSION: Hospitals with more autonomy may not necessarily respond more effectively to PPRs that incentivise efficiency when they had previously been encouraged to maximise profit. Policymakers should assess the extent of perverse incentives before granting autonomy and adjust the incentives accordingly.

5.
J Cell Sci ; 134(16)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34338780

RESUMO

One of the greatest unmet needs hindering the successful treatment of nasopharyngeal carcinomas (NPCs) is for representative physiological and cost-effective models. Although Epstein-Barr virus (EBV) infection is consistently present in NPCs, most studies have focused on EBV-negative NPCs. For the first time, we established and analyzed three-dimensional (3D) spheroid models of EBV-positive and EBV-negative NPC cells and compared these to classical two-dimensional (2D) cultures in various aspects of tumor phenotype and drug responses. Compared to 2D monolayers, the 3D spheroids showed significant increases in migration capacity, stemness characteristics, hypoxia and drug resistance. Co-culture with endothelial cells, which mimics essential interactions in the tumor microenvironment, effectively enhanced spheroid dissemination. Furthermore, RNA sequencing revealed significant changes at the transcriptional level in 3D spheroids compared to expression in 2D monolayers. In particular, we identified known (VEGF, AKT and mTOR) and novel (Wnt-ß-catenin and Eph-ephrin) cell signaling pathways that are activated in NPC spheroids. Targeting these pathways in 3D spheroids using FDA-approved drugs was effective in monoculture and co-culture. These findings provide the first demonstration of the establishment of EBV-positive and EBV-negative NPC 3D spheroids with features that resemble advanced and metastatic NPCs. Furthermore, we show that NPC spheroids have potential use in identifying new drug targets.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Efrinas , Herpesvirus Humano 4/metabolismo , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Transdução de Sinais , Microambiente Tumoral , beta Catenina/genética , beta Catenina/metabolismo
6.
Brief Bioinform ; 22(2): 1150-1160, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-32484220

RESUMO

The outbreak caused by the novel coronavirus SARS-CoV-2 has been declared a global health emergency. G-quadruplex structures in genomes have long been considered essential for regulating a number of biological processes in a plethora of organisms. We have analyzed and identified 25 four contiguous GG runs (G2NxG2NyG2NzG2) in the SARS-CoV-2 RNA genome, suggesting putative G-quadruplex-forming sequences (PQSs). Detailed analysis of SARS-CoV-2 PQSs revealed their locations in the open reading frames of ORF1 ab, spike (S), ORF3a, membrane (M) and nucleocapsid (N) genes. Identical PQSs were also found in the other members of the Coronaviridae family. The top-ranked PQSs at positions 13385 and 24268 were confirmed to form RNA G-quadruplex structures in vitro by multiple spectroscopic assays. Furthermore, their direct interactions with viral helicase (nsp13) were determined by microscale thermophoresis. Molecular docking model suggests that nsp13 distorts the G-quadruplex structure by allowing the guanine bases to be flipped away from the guanine quartet planes. Targeting viral helicase and G-quadruplex structure represents an attractive approach for potentially inhibiting the SARS-CoV-2 virus.


Assuntos
COVID-19/virologia , Quadruplex G , SARS-CoV-2/química , Humanos , Simulação de Acoplamento Molecular , Fases de Leitura Aberta
7.
J Med Virol ; 95(7): e28895, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37403902

RESUMO

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.


Assuntos
COVID-19 , Convulsões Febris , Masculino , Feminino , Humanos , Criança , COVID-19/complicações , SARS-CoV-2 , Convulsões Febris/etiologia , Interleucina-6 , Interleucina-8 , RNA Viral , Convulsões/etiologia
8.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674885

RESUMO

Our previous study reported that mesenchymal stem cells (MSCs) accelerated the wound healing process through anti-inflammatory, anti-apoptotic, and pro-angiogenetic effects in a rodent skin excision model. NF3 is a twin-herb formula, which presents similar effects in promoting wound healing. Research focusing on the interaction of MSCs and Chinese medicine is limited. In this study, we applied MSCs and the twin-herb formula to the wound healing model and investigated their interactions. Wound healing was improved in all treatment groups (MSCs only, NF3 only, and MSCs + NF3). The combined therapy further enhanced the effect: more GFP-labelled ADMSCs, collagen I and collagen III expression, Sox9 positive cells, and CD31 positive cells, along with less ED-1 positive cells, were detected; the expressions of proinflammatory cytokine IL-6 and TNF-α were downregulated; and the expression of anti-inflammatory cytokine IL-10 was upregulated. In vitro, NF3 promoted the cell viability and proliferation ability of MSCs, and a higher concentration of protein was detected in the NF3-treated supernatant. A proteomic analysis showed there were 15 and 22 proteins in the supernatants of normal ADMSCs and NF3-treated ADMSCs, respectively. After PCR validation, the expressions of 11 related genes were upregulated. The results of a western blot suggested that the TGFß/Smad and Wnt pathways were related to the therapeutic effects of the combined treatment. Our study suggests for the first time that NF3 enhanced the therapeutic effect of MSCs in the wound healing model and the TGFß/Smad and Wnt pathways were related to the procedure.


Assuntos
Medicamentos de Ervas Chinesas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Medicamentos de Ervas Chinesas/farmacologia , Roedores , Proteômica , Cicatrização , Colágeno/farmacologia , Citocinas/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Anti-Inflamatórios/farmacologia
9.
Clin Infect Dis ; 75(4): 673-681, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34849657

RESUMO

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Miocardite , Pericardite , Adolescente , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Criança , Estudos de Coortes , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Miocardite/complicações , Miocardite/etiologia , Pericardite/epidemiologia , Pericardite/etiologia , Vacinação/efeitos adversos
10.
Proc Biol Sci ; 289(1977): 20220504, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35765840

RESUMO

The assumption that differences in species' traits reflect their different niches has long influenced how ecologists infer processes from assemblage patterns. For instance, many assess the importance of environmental filtering versus classical limiting-similarity competition in driving biological invasions by examining whether invaders' traits are similar or dissimilar to those of residents, respectively. However, mounting evidence suggests that hierarchical differences between species' trait values can distinguish their competitive abilities (e.g. for the same resource) instead of their niches. Whether such trait-mediated hierarchical competition explains invasions and structures assemblages is less explored. We integrate morphological, dietary, physiological and behavioural trait analyses to test whether environmental filtering, limiting-similarity competition or hierarchical competition explain invasions by fire ants on ant assemblages. We detect both competition mechanisms; invasion success is not only explained by limiting similarity in body size and thermal tolerance (presumably allowing the invader to exploit different niches from residents), but also by the invader's superior position in trait hierarchies reflecting competition for common trophic resources. We find that the two mechanisms generate complex assemblage-level functional diversity patterns-overdispersion in some traits, clustering in others-suggesting their effects are likely missed by analyses restricted to a few traits and composite trait diversity measures.


Assuntos
Formigas , Animais , Formigas/fisiologia , Tamanho Corporal , Ecossistema , Fenótipo
12.
Opt Express ; 30(18): 32565-32576, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36242314

RESUMO

Focusing light into an arbitrary pattern through complex media is desired in energy delivery-related scenarios and has been demonstrated feasible with the assistance of wavefront shaping. However, it still encounters challenges in terms of pattern fidelity and focusing contrast, especially in a noisy and perturbed environment. In this work, we show that the strategy relying on natural gradient ascent-based parameter optimization can help to resist noise and disturbance, enabling rapid wavefront optimization towards high-quality pattern projection through complex media. It is revealed that faster convergence and better robustness can be achieved compared with existing phase control algorithms. Meanwhile, a new fitness function based on cosine similarity is adopted for the algorithm, leading to higher focusing contrast without sacrificing similarity to the target pattern. As a result, long-distance projection of an arbitrary pattern can be accomplished with considerably enhanced performance through a 15-meter multimode fiber that is not fixed and susceptible to perturbation. With further engineering, the approach may find special interests for many biomedical applications, such as deep-tissue photon therapy and optogenetics, where free-space localized optical delivery encounters challenges.


Assuntos
Algoritmos , Fótons
13.
Eur J Nucl Med Mol Imaging ; 49(5): 1497-1507, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862520

RESUMO

PURPOSE: We longitudinally evaluated the tumour growth and metabolic activity of three nasopharyngeal carcinoma (NPC) cell line models (C666-1, C17 and NPC43) and two xenograft models (Xeno76 and Xeno23) using a micropositron emission tomography and magnetic resonance (microPET/MR). With a better understanding of the interplay between tumour growth and metabolic characteristics of these NPC models, we aim to provide insights for the selection of appropriate NPC cell line/xenograft models to assist novel drug discovery and evaluation. METHODS: Mice were imaged by 18F-deoxyglucose ([18F]FDG) microPET/MR twice a week for consecutive 3-7 weeks. [18F]FDG uptake was quantified by standardized uptake value (SUV) and presented as SUVmean tumour-to-liver ratio (SUVRmean). Longitudinal tumour growth patterns and metabolic patterns were recorded. SUVRmean and histological characteristics were compared across the five NPC models. Cisplatin was administrated to one selected optimal tumour model, C17, to evaluate our imaging platform. RESULTS: We found variable tumour growth and metabolic patterns across different NPC tumour types. C17 has an optimal growth rate and higher tumour metabolic activity compared with C666-1. C666-1 has a fast growth rate but is low in SUVRmean at endpoint due to necrosis as confirmed by H&E. NPC43 and Xeno76 have relatively slow growth rates and are low in SUVRmean, due to severe necrosis. Xeno23 has the slowest growth rate, and a relative high SUVRmean. Cisplatin showed the expected therapeutic effect in the C17 model in marked reduction of tumour size and metabolism. CONCLUSION: Our study establishes an imaging platform that characterizes the growth and metabolic patterns of different NPC models, and the platform is well able to demonstrate drug treatment outcome supporting its use in novel drug discovery and evaluation for NPC.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Animais , Cisplatino , Fluordesoxiglucose F18 , Humanos , Camundongos , Modelos Animais , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Necrose , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X
14.
Inorg Chem ; 61(10): 4428-4441, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35234043

RESUMO

The syntheses of valence tautomeric compounds with multistep transitions using new redox-active ligands are the long-term goal of the field of bistable materials. The redox-active tetraoxolene ligand, 2,7-di-tert-butylpyrene-4,5,9,10-tetraone (pyreneQ-Q), is now developed to synthesize a pair of dinuclear compounds {[CoL2]2(pyreneSq-Sq)}[Co(CO)4]2·xCH2Cl2·2C6H5CH3 (1, x = 2, L = 1,10-phenanthroline, phen; 2, x = 1.5, L = 2,2'-bipyridine, bpy). Variable-temperature magnetic susceptibilities and single-crystal X-ray diffraction measurements indicate a partial one-step valence tautomeric transition for 1 and a rare two-step valence tautomeric transition for 2, respectively. DFT calculation results are consistent with the experimental data, revealing the correlation between thermodynamic parameters and the one-step/two-step valence tautomeric behaviors.

15.
Proc Natl Acad Sci U S A ; 116(28): 14144-14153, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31235597

RESUMO

Epstein-Barr virus (EBV) induces histone modifications to regulate signaling pathways involved in EBV-driven tumorigenesis. To date, the regulatory mechanisms involved are poorly understood. In this study, we show that EBV infection of epithelial cells is associated with aberrant histone modification; specifically, aberrant histone bivalent switches by reducing the transcriptional activation histone mark (H3K4me3) and enhancing the suppressive mark (H3K27me3) at the promoter regions of a panel of DNA damage repair members in immortalized nasopharyngeal epithelial (NPE) cells. Sixteen DNA damage repair family members in base excision repair (BER), homologous recombination, nonhomologous end-joining, and mismatch repair (MMR) pathways showed aberrant histone bivalent switches. Among this panel of DNA repair members, MLH1, involved in MMR, was significantly down-regulated in EBV-infected NPE cells through aberrant histone bivalent switches in a promoter hypermethylation-independent manner. Functionally, expression of MLH1 correlated closely with cisplatin sensitivity both in vitro and in vivo. Moreover, seven BER members with aberrant histone bivalent switches in the EBV-positive NPE cell lines were significantly enriched in pathway analysis in a promoter hypermethylation-independent manner. This observation is further validated by their down-regulation in EBV-infected NPE cells. The in vitro comet and apurinic/apyrimidinic site assays further confirmed that EBV-infected NPE cells showed reduced DNA damage repair responsiveness. These findings suggest the importance of EBV-associated aberrant histone bivalent switch in host cells in subsequent suppression of DNA damage repair genes in a methylation-independent manner.


Assuntos
Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Código das Histonas/genética , Histonas/genética , Ilhas de CpG/genética , Dano ao DNA/genética , Metilação de DNA/genética , Reparo de Erro de Pareamento de DNA/genética , Reparo do DNA/genética , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Regulação da Expressão Gênica/genética , Herpesvirus Humano 4/patogenicidade , Recombinação Homóloga/genética , Humanos , Proteína 1 Homóloga a MutL/genética , Nasofaringe/crescimento & desenvolvimento , Nasofaringe/patologia , Nasofaringe/virologia , Regiões Promotoras Genéticas
16.
Molecules ; 27(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36431781

RESUMO

Herein, we report synthetic strategies for the development of a bifunctional Janus T4 tetrapod (Janus ring), in which the orthogonal silsesquioxane and organic faces are independently functionalized. An all-cis T4 tetrasilanolate was functionalized to introduce thiol moieties on the silsesquioxane face and naphthyl groups on the organic face to introduce luminescent and self-organization properties. The stepwise synthesis conditions required to prepare such perfectly defined oligomers via a suite of well-defined intermediates and to avoid polymerization or reactions over all eight positions of the tetrapod are explored via 29Si, 13C and 1H NMR, FTIR and TOF-ESI mass spectroscopy. To the best of our knowledge, this is one of the few reports of Janus T4 tetrapods, with different functional groups located on both faces of the molecule, thus expanding the potential range of applications for these versatile precursors.


Assuntos
Compostos de Sulfidrila , Polimerização , Espectroscopia de Ressonância Magnética
17.
Semin Cancer Biol ; 61: 84-100, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31521748

RESUMO

Nasopharyngeal carcinoma (NPC), also named the Cantonese cancer, is a unique cancer with strong etiological association with infection of the Epstein-Barr virus (EBV). With particularly high prevalence in Southeast Asia, the involvement of EBV and genetic aberrations contributive to NPC tumorigenesis have remained unclear for decades. Recently, genomic analysis of NPC has defined it as a genetically homogeneous cancer, driven largely by NF-κB signaling caused by either somatic aberrations of NF-κB negative regulators or by overexpression of the latent membrane protein 1 (LMP1), an EBV viral oncoprotein. This represents a landmark finding of the NPC genome. Exome and RNA sequencing data from new EBV-positive NPC models also highlight the importance of PI3K pathway aberrations in NPC. We also realize for the first time that NPC mutational burden, mutational signatures, MAPK/PI3K aberrations, and MHC Class I gene aberrations, are prognostic for patient outcome. Together, these multiple genomic discoveries begin to shape the focus of NPC therapy development. Given the challenge of NF-κB targeting in human cancers, more innovative drug discovery approaches should be explored to target the unique atypical NF-κB activation feature of NPC. Our next decade of NPC research should focus on further identification of the -omic landscapes of recurrent and metastatic NPC, development of gene-based precision medicines, as well as large-scale drug screening with the newly developed and well-characterized EBV-positive NPC models. Focused preclinical and clinical investigations on these major directions may identify new and effective targeting strategies to further improve survival of NPC patients.


Assuntos
Transformação Celular Neoplásica/genética , Genômica , Neoplasias Nasofaríngeas/etiologia , Pesquisa Translacional Biomédica , Apoptose/genética , Sobrevivência Celular/genética , Transformação Celular Neoplásica/metabolismo , Epigênese Genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Genômica/métodos , Saúde Global , Herpesvirus Humano 4/fisiologia , Humanos , Vigilância Imunológica , Incidência , Terapia de Alvo Molecular , NF-kappa B/metabolismo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais
18.
J Clin Microbiol ; 59(4)2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33436456

RESUMO

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A (flu A), influenza B (flu B), and respiratory syncytial virus (RSV) have overlapping clinical presentations, but the approaches to treatment and management of infections caused by these viruses are different. Therefore, rapid diagnosis in conjunction with infection prevention measures is important to prevent transmission of the diseases. Recently, a new Xpert Xpress SARS-CoV-2/Flu/RSV (Xpert 4-in-1) assay enables the detection and differentiation of SARS-CoV-2, flu A, flu B, and RSV in upper respiratory tract specimens. In this study, we evaluated the performance of the Xpert 4-in-1 assay by comparing it with that of the Xpert Xpress SARS-CoV-2 and Xpert Xpress Flu/RSV assays for the detection of the four viruses in nasopharyngeal (NP) specimens. A total of 279 NP specimens, including 66, 56, 64, and 53 specimens positive for SARS-CoV-2, flu A, flu B, and RSV, respectively, were included. The Xpert 4-in-1 assay demonstrated high concordance with the comparator assays, with overall agreement for SARS-CoV-2, flu A, flu B, and RSV at 99.64%, 100%, 99.64%, and 100%, respectively, and a high Cohen's kappa (κ) value ranging from 0.99 to 1.00, indicating an almost perfect correlation between assays. The cycle threshold value association between positive samples also showed a good correlation between assays. In conclusion, the overall performance of the Xpert 4-in-1 assay was highly comparable to that of the Xpert SARS-CoV-2 and Xpert Flu/RSV assays for the detection and differentiation of SARS CoV-2, flu A, flu B, and RSV in NP specimens.


Assuntos
COVID-19 , Herpesvirus Cercopitecino 1 , Vírus da Influenza A , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Humanos , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Técnicas de Diagnóstico Molecular , Nasofaringe , SARS-CoV-2 , Sensibilidade e Especificidade
19.
J Med Virol ; 93(1): 533-536, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32621616

RESUMO

Nasopharyngeal swabs (NPS) are widely accepted as specimens for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the current pandemic of coronavirus disease 2019. However, the collection procedures for NPS specimens causes sneezing and coughing in most patients, which generate droplets or aerosol particles that are hazardous to the healthcare workers collecting these specimens. In this study, 95 patient-matched paired deep throat saliva (DTS) and NPS specimens from 62 patients were analyzed. Samples were tested for SARS-CoV-2 by reverse-transcription polymerase chain reaction (RT-PCR). The rates of detection for DTS (53.7%) and NPS (47.4%) samples were comparable (P = .13). It is important to note that the patients should be clearly instructed or supervised during DTS collection. In conclusion, SARS-CoV-2 detection by RT-PCR was equivalent in DTS and NPS specimens.


Assuntos
COVID-19/diagnóstico , Faringe/virologia , SARS-CoV-2/isolamento & purificação , Saliva/virologia , Humanos , Nasofaringe/virologia , Manejo de Espécimes
20.
Opt Express ; 29(12): 18420-18426, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34154097

RESUMO

Particle swarm optimization (PSO) is a well-known iterative algorithm commonly adopted in wavefront shaping for focusing light through or inside scattering media. The performance is, however, limited by premature convergence in an unstable environment. Therefore, we aim to solve this problem and enhance the focusing performance by adding a dynamic mutation operation into the plain PSO. With dynamic mutation, the "particles," or the optimized masks, are mutated with quantifiable discrepancy between the current and theoretical optimal solution, i.e., the "error rate." Gauged by that, the diversity of the "particles" is effectively expanded, and the adaptability of the algorithm to noise and instability is significantly promoted, yielding optimization approaching the theoretical optimum. The simulation and experimental results show that PSO with dynamic mutation demonstrates considerably better performance than PSO without mutation or with a constant mutation, especially under a noisy environment.

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