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1.
Chemistry ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33876453

RESUMO

Increasing the metal loading and downsizing the metal particle size are two effective ways to boost the electrochemical performance of catalysts. However, it is difficult to simultaneously increase the metal loading and reduce the particle size since isolated individual atoms are easy to aggregate into nanoparticles when increasing the metal loading. To tackle this contradiction, we report a bottom-up ligand-mediated strategy to facilely prepare ultrafine CoO x  nanoclusters anchored on a Co-N-containing carbon matrix (CoO x @Co-NC). The co-exist of N and O atoms prevent Co atoms agglomerating into large particles and allowing the formation of ultrafine dispersed Co species with large Co loading (up to 20 wt.%). Since the relationship between ultrasmall size and large metal loading is well balanced, the CoO x nanoclusters have no inhibitory effect, but facilitate the catalytic performance of Co-N 4 sites during OER process. Consequently, due to the synergistic effect of ultrafine CoO x nanoclusters and Co-N 4  macrocycles, the as-synthesized CoO x @Co-NC exhibit promising OER activity (η 10 =370 mV, Tafel plot=40 mV/dec), bettering than that of benchmark RuO 2  (η 10 =411 mV, Tafel plot=72 mV/dec). This ligand-mediated strategy to synthesize carbonaceous materials containing dual active centers with large metal loading is promising for developing active and stable catalysts for electrocatalytic applications.

2.
Transbound Emerg Dis ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33872465

RESUMO

Since 2014, highly pathogenic avian influenza H5N6 viruses have been responsible for outbreaks in poultry. In this study, four H5N6 virus strains were isolated from fecal samples of sick white ducks and dead chickens in Shandong in 2019. These H5N6 viruses were triple-reassortant viruses that have not been previously characterized. Their HA genes were derived from the H5 viruses and were closely related to the vaccine strain Re-11. Their NA genes all fell into the N6-like lineage and the internal gene were derived from H5N1 and H9N2 viruses. They all showed high pathogenicity in mice and caused lethal infection with high rates of transmission in chickens. Moreover, the SPF chickens inoculated with the current used H5 (Re-11 and Re-12 strains)/H7 (H7-Re-2 strain) trivalent inactivated vaccines in China were completely protected from these four H5N6 viruses. Our study indicated the necessity of continued surveillance for H5 Influenza A viruses and the importance of timely update of vaccine strains in poultry industry.

3.
Microb Pathog ; 156: 104915, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33930416

RESUMO

Staphylococcus aureus is one of the leading hospital-associated and community-associated pathogens, which has caused a global public health concern. The emergence of methicillin-resistant S. aureus (MRSA) along with the widespread use of different classes of antibiotics has become a significant therapeutic challenge. Antibiotic resistance is a disturbing problem that poses a threat to humans. Treatment options for S. aureus resistant to ß-lactam antibiotics include glycopeptide antibiotic, cyclic lipopeptide antibiotic, cephalosporins and oxazolidinone antibiotic. The most representative types of these antibiotics are vancomycin, daptomycin, ceftaroline and linezolid. The frequent use of the first-line drug vancomycin for MRSA treatment has increased the number of resistant strains, namely vancomycin intermediate resistant S. aureus (VISA) and vancomycin resistant S. aureus (VRSA). A systematic literature review of relevant published studies in PubMed before 2020 was conducted. In recent years, there have been some reports on the relevant resistant mechanisms of vancomycin, daptomycin, ceftaroline and linezolid. In this review, we have summarized the antibiotic molecular modes of action and different gene mutants at the whole-genome level, which will aid in further development on new drugs for effective MRSA treatment based on describing different resistance mechanisms of classic antibiotics.

4.
Cancers (Basel) ; 13(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805776

RESUMO

Because direct tumor biopsy is prohibited for retinoblastoma (RB), eye-specific molecular biomarkers are not used in clinical practice for RB. Recently, we demonstrated that the aqueous humor (AH) is a rich liquid biopsy source of cell-free tumor DNA. Herein, we detail clinically-relevant molecular biomarkers from the first year of prospective validation data. Seven eyes from 6 RB patients who had AH sampled at diagnosis and throughout therapy with ≥12 months of follow-up were included. Cell-free DNA (cfDNA) from each sample was isolated and sequenced to assess genome-wide somatic copy number alterations (SCNAs), followed by targeted resequencing for pathogenic variants using a RB1 and MYCN custom hybridization panel. Tumoral genomic information was detected in 100% of diagnostic AH samples. Of the seven diagnostic AH samples, 5/7 were positive for RB SCNAs. Mutational analysis identified RB1 variants in 5/7 AH samples, including the 2 samples in which no SCNAs were detected. Two eyes failed therapy and required enucleation; both had poor prognostic biomarkers (chromosome 6p gain or MYCN amplification) present in the AH at the time of diagnosis. In the context of previously established pre-analytical, analytical, and clinical validity, this provides evidence for larger, prospective studies to further establish the clinical utility of the AH liquid biopsy and its applications to precision oncology for RB.

5.
Exp Biol Med (Maywood) ; : 1535370221993424, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33641447

RESUMO

Abnormal lipid metabolism is regarded as a crucial cause of psoriasis. The specific mechanism of how phospholipase PLA2G4B mediates local immune dysfunction and skin lesions remains unclear. The aim of this study was to explore the mechanisms of anti-psoriasis and immune suppression effect by inhibiting PLA2G4B in psoriasis progression. We successfully transfected si-PLA2G4B in a murine keratinocyte cell-line PAM212 to verify the effect of progression by PLA2G4B. The Imiquimod psoriasis mouse model was then successfully constructed, followed by emulsion wrapped PLA2G4B-siRNA applied to the skin lesions. The phenotype, pathology, immunofluorescence staining of PLA2G4B, IL17, CD3, and CD1b, and bulk transcriptome analysis were performed to decipher the effect and mechanism of si-PLA2G4B. Interfering with PLA2G4B significantly inhibited the proliferation and migration of PAM212. The interference of PLA2G4B in vivo showed a therapeutic effect on psoriasis, comparable to that of betamethasone. The phenotype and pathology revealed reduced keratinocytes in the si-PLA2G4B group compared to the model mice. Immunofluorescence showed that CD1b, CD3+ T cells, and IL17 were suppressed in the skin lesions. RNA-seq and deconvolution revealed that immune cells such as myeloid dendritic cell and T cell CD8+ naive were inactivated. Th17 reduce the release of inflammatory factors such as IL17 and IL36. Pathway analysis revealed the potential therapeutic mechanism involved in the inhibition of sphingolipid or ceramide secretion. This study verified the anti-psoriatic effect of using si-PLA2G4B. The immune response was alleviated after administration. This phospholipase inhibition-based therapy sheds light on the pharmaceutical potential against psoriasis.

6.
Preprint | bioRxiv | ID: ppbiorxiv-434497

RESUMO

New SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS-CoV-2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N-E484K-N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

7.
Medicine (Baltimore) ; 100(11): e25150, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725999

RESUMO

BACKGROUND: The association between cytochrome P450 2C19 (CYP2C19) polymorphisms and neurological deterioration in stroke or transient ischemic attack (TIA) patients is not completely understood. Hence, we performed a systematic review and meta-analysis of prospective cohort studies to quantify this association. METHODS: PubMed, Cochrane Library, Excerpta Medica Database, China National Knowledge Infrastructure and WanFang databases were searched for studies published up to April 2019. Prospective cohort studies that reported an association between CYP2C19 polymorphisms and neurological deterioration in stroke/TIA patients were included. Data on risk ratio (RR) and 95% confidence intervals (CI) were extracted and pooled by the authors. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. RESULTS: Twelve eligible studies were included. Twelve studies reported CYP2C19∗2, ∗3 loss-of-function alleles and 5 studies reported CYP2C19∗17 gain-of-function allele. Compared to non-carriers, carriers of CYP2C19∗2, ∗3 loss-of-function alleles had a significantly higher risk of neurological deterioration (RR, 1.63; 95%CI, 1.32-2.02). Conversely, carriers of CYP2C19∗17 gain-of-function allele had a significantly lower risk of neurological deterioration (RR, 0.520; 95%CI, 0.393-0.689) compared to non-carriers. CONCLUSIONS: This meta-analysis demonstrated that the carriers of CYP2C19∗2, ∗3 loss-of-function alleles have an increased risk of neurological deterioration compared to non-carriers in stroke or TIA patients. Additionally, CYP2C19∗17 gain-of-function allele can reduce the risk of neurological deterioration.


Assuntos
Citocromo P-450 CYP2C19/genética , Ataque Isquêmico Transitório/patologia , Degeneração Neural/genética , Polimorfismo Genético/genética , Acidente Vascular Cerebral/patologia , Idoso , Feminino , Humanos , Ataque Isquêmico Transitório/genética , Mutação com Perda de Função/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/genética
8.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33688035

RESUMO

Modified vaccinia virus Ankara (MVA) is a replication-restricted smallpox vaccine, and numerous clinical studies of recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases, including COVID-19, are in progress. Here, we characterize rMVAs expressing the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Modifications of full-length S individually or in combination included two proline substitutions, mutations of the furin recognition site, and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) is flanked by the signal peptide and transmembrane domains of S was also constructed. Each modified S protein was displayed on the surface of rMVA-infected cells and was recognized by anti-RBD antibody and soluble hACE2 receptor. Intramuscular injection of mice with the rMVAs induced antibodies, which neutralized a pseudovirus in vitro and, upon passive transfer, protected hACE2 transgenic mice from lethal infection with SARS-CoV-2, as well as S-specific CD3+CD8+IFNγ+ T cells. Antibody boosting occurred following a second rMVA or adjuvanted purified RBD protein. Immunity conferred by a single vaccination of hACE2 mice prevented morbidity and weight loss upon intranasal infection with SARS-CoV-2 3 wk or 7 wk later. One or two rMVA vaccinations also prevented detection of infectious SARS-CoV-2 and subgenomic viral mRNAs in the lungs and greatly reduced induction of cytokine and chemokine mRNAs. A low amount of virus was found in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of low levels of subgenomic mRNAs in turbinates indicated that replication was aborted in immunized animals.


Assuntos
/imunologia , Vetores Genéticos/genética , Vacinas de DNA/imunologia , Vírus Vaccinia/genética , /genética , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , /genética , Modelos Animais de Doenças , Expressão Gênica , Humanos , Imunização , Imunização Passiva , Imunoglobulina G/imunologia , Camundongos , Camundongos Transgênicos , Glicoproteína da Espícula de Coronavírus/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética
9.
J Colloid Interface Sci ; 592: 116-126, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33647560

RESUMO

CuS materials exhibit excellent near infrared (NIR) photoabsorption and photothermal effect, but they are lack of magnetic resonance imaging (MRI) ability. Fe-based nanomaterials possess MRI capacity, but they usually exhibit poor NIR photoabsorption. In order to solve the above problems, we synthesize three kinds of CuxFeySz samples, including FeS2, CuFeS2 and Cu5FeS4 nanomaterials. With the Cu/Fe ratios increase from 0/1.0 to 1.0/1.0 and 5.0/1.0, the localized surface plasmon resonances (LSPRs) characteristic peaks shift to longer wavelength, and the photothermal transduction efficiencies go up from 24.4% to 36.6% and 45.9%. Thus, Cu5FeS4 is found to be the most excellent sample. Especially, Cu5FeS4 exhibits photothermal-enhanced Fenton effect, which can produce hydroxyl radical (·OH) under a wide pH range (e.g., pH = 5.4-7.4) to realize the chemodynamic effect. In addition, Cu5FeS4 can be employed as an efficient MRI contrast agent. When Cu5FeS4 dispersion is intravenously injected into the mouse, the tumor can be detected by MRI as well as thermal imaging, and eliminated through photothermal-enhanced chemodynamic effect. Therefore, Cu5FeS4 can be used as an efficient "one-for-all" type agent for MRI-guided photothermal-enhanced chemodynamic therapy of tumor.

10.
Technol Cancer Res Treat ; 20: 1533033821997828, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33706618

RESUMO

PURPOSE: The goal of this study is to construct nomograms to effectively predict the distant metastatic sites and overall survival (OS) of soft tissue sarcoma (STS) patients. METHODS: STS case data between 2010 and 2015 for retrospective study were gathered from public databases. According to the chi-square and multivariate logistic regression analysis determined independent predictive factors of specific metastatic sites, the nomograms based on these factors were consturced. Subsequently, combined metastatic information a nomogram to predict 1-, 2-, and 3-year OS of STS patients was developed. The performance of models was validated by the area under the curve (AUC), calibration plots, and decision curve analyses (DCA). RESULTS: A total of 7001 STS patients were included in this retrospective study, including 4901 cases in the training group and the remaining 2,100 patients in the validation group. Three nomograms were established to predict lung, liver and bone metastasis, and satisfactory results have been obtained by internal and external validation. The AUCs for predicting lung, liver, and bone metastases in the training cohort were 0.796, 0.799, and 0.766, respectively, and in the validation cohort were 0.807, 0.787, and 0.775, respectively, which means that the nomograms have good discrimination. The calibration curves showed that the models have high precision, and the DCA manifested that the nomograms have great clinical application prospects. Through univariate and multivariate COX regression analyses, 8 independent prognosis factors of age, grade, histological type, tumor size, surgery, chemotherapy, radiatiotherapy and lung metastasis were determined. A nomogram was then constructed to predict the 1-, 2-, and 3-years OS, which has a good performance in both internal and external validations. CONCLUSION: The nomograms for predicting specific metastatic sites and OS have good discrimination, accuracy and clinical applicability. The models could accurately predict the metastatic risk and survival information, and help clinical decision-making.

11.
BMC Surg ; 21(1): 94, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33612095

RESUMO

BACKGROUND: During clinical practice we have noticed that some patients with hyperthyroidism have finer skin with less wrinkles, pores, and spots after thyroidectomy, and the improvement can be observed within a few weeks after the operation. However, there is no evidence or study in the literature to proof this finding. AIM AND OBJECTIVE: This study was designed to evaluate and quantify the skin characters of patients with hyperthyroidism before and after thyroidectomy. MATERIAL AND METHODS: This is a prospective study to include patients with hyperthyroidism who received total thyroidectomy between March 1st, 2018 and February 28th, 2019. The patients received blood test for T4 and TSH analysis and VISIA measurements for skin texture quantification, at the preoperative stage, three, and six months postoperatively. A total of 8 patients were included. Repeated measurement was used to determine the lab data and VISIA measurement changes before and after the operation. Mauchly's sphericity test was performed to determine whether the violation of sphericity occurs, and the Greenhouse-Geisser correction was used when the violation of sphericity occurs. RESULTS: All the patients were female and generally healthy without systemic medical disease except the hyperthyroidism. The T4 and TSH levels were not significantly different before and after the thyroidectomy. In terms of the skin character measurements, the wrinkles, texture, pores, UV spots, and brown spots were not improved after thyroidectomy. A trend of improvement in spots, red area, and porphyrin was noted, although not statistically significant. CONCLUSIONS: Surgical removal of the thyroid gland in patients with hyperthyroidism does not improve the skin quality and texture in examinations via the VISIA system.


Assuntos
Face , Hipertireoidismo , Pele , Tireoidectomia , Técnicas Cosméticas/instrumentação , Feminino , Humanos , Hipertireoidismo/cirurgia , Estudos Prospectivos
12.
PLoS Pathog ; 17(2): e1009303, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33529218

RESUMO

Metabolism is a crucial frontier of host-virus interaction as viruses rely on their host cells to provide nutrients and energy for propagation. Vaccinia virus (VACV) is the prototype poxvirus. It makes intensive demands for energy and macromolecules in order to build hundreds and thousands of viral particles in a single cell within hours of infection. Our comprehensive metabolic profiling reveals profound reprogramming of cellular metabolism by VACV infection, including increased levels of the intermediates of the tri-carboxylic acid (TCA) cycle independent of glutaminolysis. By investigating the level of citrate, the first metabolite of the TCA cycle, we demonstrate that the elevation of citrate depends on VACV-encoded viral growth factor (VGF), a viral homolog of cellular epidermal growth factor. Further, the upregulation of citrate is dependent on STAT3 signaling, which is activated non-canonically at the serine727 upon VACV infection. The STAT3 activation is dependent on VGF, and VGF-dependent EGFR and MAPK signaling. Together, our study reveals a novel mechanism by which VACV manipulates cellular metabolism through a specific viral factor and by selectively activating a series of cellular signaling pathways.

13.
Org Lett ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439028

RESUMO

Three emissive bridged-triphenylamine derivatives are designed and synthesized by incorporating carbon (DQAO), oxygen (OQAO), and sulfur (SQAO) atoms with two carbonyl groups. The fully bridged geometry and unique frontier molecular orbital distribution reveal its potential as narrowband thermally activated delayed fluorescence emitters. DQAO-, OQAO-, and SQAO-based organic light-emitting diodes exhibit the maximum external quantum efficiency (EQEmax) of 15.2%, 20.3%, and 17.8% for blue, green, and yellow, respectively.

14.
PLoS Pathog ; 17(1): e1009183, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33444388

RESUMO

The antiviral protein kinase R (PKR) is an important host restriction factor, which poxviruses must overcome to productively infect host cells. To inhibit PKR, many poxviruses encode a pseudosubstrate mimic of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2), designated K3 in vaccinia virus. Although the interaction between PKR and eIF2α is highly conserved, some K3 orthologs from host-restricted poxviruses were previously shown to inhibit PKR in a species-specific manner. To better define this host range function, we compared the sensitivity of PKR from 17 mammals to inhibition by K3 orthologs from closely related orthopoxviruses, a genus with a generally broader host range. The K3 orthologs showed species-specific inhibition of PKR and exhibited three distinct inhibition profiles. In some cases, PKR from closely related species showed dramatic differences in their sensitivity to K3 orthologs. Vaccinia virus expressing the camelpox virus K3 ortholog replicated more than three orders of magnitude better in human and sheep cells than a virus expressing vaccinia virus K3, but both viruses replicated comparably well in cow cells. Strikingly, in site-directed mutagenesis experiments between the variola virus and camelpox virus K3 orthologs, we found that different amino acid combinations were necessary to mediate improved or diminished inhibition of PKR derived from different host species. Because there is likely a limited number of possible variations in PKR that affect K3-interactions but still maintain PKR/eIF2α interactions, it is possible that by chance PKR from some potential new hosts may be susceptible to K3-mediated inhibition from a virus it has never previously encountered. We conclude that neither the sensitivity of host proteins to virus inhibition nor the effectiveness of viral immune antagonists can be inferred from their phylogenetic relatedness but must be experimentally determined.


Assuntos
Antivirais/antagonistas & inibidores , Especificidade de Hospedeiro , Orthopoxvirus/classificação , Orthopoxvirus/fisiologia , Infecções por Poxviridae/virologia , Replicação Viral , eIF-2 Quinase/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Antivirais/metabolismo , Células HeLa , Humanos , Fosforilação , Filogenia , Infecções por Poxviridae/genética , Infecções por Poxviridae/metabolismo , Homologia de Sequência , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
15.
Sci Rep ; 11(1): 2350, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504947

RESUMO

This study was designed to compare the outcome and analyze the operation-related risk factors in free flap reconstruction for patients with primary and recurrent head and neck cancers. A 1:1 propensity score-matched analysis of the microsurgery registry database of the hospital. The primary outcome of the free flap reconstruction had a higher failure rate in the recurrent group than the primary group (5.1% vs. 3.1%, p = 0.037). Among the 345 pairs in the matched study population, there were no significant differences between the primary and recurrent groups regarding the rate of total flap loss (3.5% vs. 5.5%, p = 0.27) and secondary outcomes. This study revealed that free flap reconstruction had a higher failure rate in the recurrent group than the primary group, but such a difference may be attributed by the different patient characteristics.

16.
Sci Total Environ ; 751: 141816, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32861186

RESUMO

Human coronaviruses are RNA viruses that are sensitive to ultraviolet (UV) radiation. Sunlight contains UVA (320-400 nm), UVB (260-320 nm) and UVC (200-260 nm) action spectra. UVC can inactivate coronaviruses, including severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The incidence and mortality of coronavirus disease 2019 (COVID-19) are considered to be correlated with vitamin D levels. Vitamin D synthesis in human skin is closely related to exposure to UVB radiation. Therefore, the incidence and mortality of COVID-19 are also considered to be correlated with Vitamin D levels. In this study, Spearman and Kendall rank correlation analysis tests were used to analyze the correlation between the average percent positive of five human coronaviruses (SARS-CoV-2, CoVHKU1, CoVNL63, CoVOC43, and CoV229E) in the U.S. and the corresponding sunlight UV radiation dose The results indicated that the monthly average percent positive of four common coronaviruses was significantly negatively correlated with the sunlight UV radiation dose. The weekly percent positive of SARS-CoV-2 during April 17, 2020 to July 10, 2020 showed a significant negative correlation with the sunlight UV radiation dose in census regions 1 and 2 of the U.S. while no statistical significance in the other regions. Additionally, sunlight UV radiation also showed some negative effects with respect to the early SARS-CoV-2 transmission.


Assuntos
Infecções por Coronavirus , Coronavirus , Pandemias , Pneumonia Viral , Raios Ultravioleta , Betacoronavirus , Humanos , Luz Solar
17.
Artigo em Inglês | MEDLINE | ID: mdl-33274470

RESUMO

BACKGROUND AND AIM: Approximately 42%-95% of working channels have been reported to show the presence of residual fluid despite endoscope reprocessing. The aim of this study was to design two novel protocol for cleaning residual simethicone and demonstrate its efficiency by evaluating the residual fluid and cleanliness in the working channels of patient-ready duodenoscopes. METHODS: The designed protocol for cleaning residual simethicone was implemented in manual cleaning and/or high-level disinfection (HLD). The residual fluid inside the working channels was estimated by visual inspection. Adenosine triphosphate (ATP) values were evaluated to determine cleanliness after manual cleaning. RESULTS: Manual cleaning with novel simethicone cleaning protocol demonstrated a significant decrease in fluid droplets (14.6 ± 29.9 vs 0 ± 0, P < 0.001) and ATP values (157 ± 196 RLUs vs 52 ± 41 RLUs, P = 0.031). HLD with simethicone cleaning protocol, using either enzymatic detergent with effective for cleaning simethicone or cleaning time set in the automatic endoscope reprocessor (AER) program 8 minutes, demonstrated significant decrease in the number of fluid droplets. Follow-up after the implementation of the simethicone cleaning protocol showed a significant decrease in fluid droplets (37.4 ± 41.0 vs 2.1 ± 5.5, P = 0.003) and ATP values (271 ± 268 RLUs vs 82 ± 136 RLUs, P = 0.021). CONCLUSIONS: Simethicone cleaning protocol is advantageous for significantly decrease fluid droplets and ATP values within endoscope working channels. After manual cleaning with the simethicone cleaning protocol, in particular, no retained fluid droplet was observed in patient-ready duodenoscopes.

18.
Adv Healthc Mater ; : e2001463, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33274856

RESUMO

Ultrasound-driven sonodynamic therapy (SDT) catches numerous attentions for destroying deep-seated tumors, but its applications suffer from unsatisfactory therapeutic effects and metabolism. Furthermore, SDT is usually weakened by the complex tumor microenvironment, such as the overexpression of glutathione (GSH). To address these issues, Mn(III)-hemoporfin frameworks (Mn(III)-HFs) are reported as nanosonosensitizers by using biocompatible hematoporphyrin monomethyl-ether (HMME) to coordinate with Mn(III) ions. Mn(III)-HFs/PEG can react with GSH to produce Mn(II) ions and oxidized glutathione (GSSG), resulting in three fascinating features: 1) the redox reaction facilitates the decomposition of Mn(III)-HFs/PEG and then collapse of nanostructures, improving the biodegradability; 2) Mn(II) ions with five unpaired 3d-electrons exhibit better magnetic resonance imaging (MRI) ability compared to Mn(III) ions with four electrons; 3) both the depletion of endogenous GSH and the dissociated HMME boost 1 O2 generation ability under US irradiation. As a result, when Mn(III)-HFs/PEG dispersion is intravenously administered into mice, it exhibits high-contrast T1 /T2 dual-modal MRI and significant suppression for the growth rate of the deep-seated tumor. Furthermore, Mn(III)-HFs/PEG can be efficiently metabolized from the mice. Therefore, Mn(III)-HFs/PEG exhibit GSH-enhanced degradation, MRI, and SDT effects, which provide some insights on the developments of other responsive nanosonosensitizers.

19.
Nat Commun ; 11(1): 5679, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173047

RESUMO

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama , Terapia de Alvo Molecular , Mutação , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , China , Gerenciamento de Dados , Feminino , Marcadores Genéticos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neurofibromina 2/genética , Oncogenes , Medicina de Precisão , Estudos Prospectivos , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/genética
20.
Neurol Ther ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33140286

RESUMO

INTRODUCTION: The globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients. METHODS: The literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping. RESULTS: There are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD. CONCLUSION: GPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages.

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