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1.
Cell ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38981481

RESUMO

All-RNA-mediated targeted gene integration methods, rendering reduced immunogenicity, effective deliverability with non-viral vehicles, and a low risk of random mutagenesis, are urgently needed for next-generation gene addition technologies. Naturally occurring R2 retrotransposons hold promise in this context due to their site-specific integration profile. Here, we systematically analyzed the biodiversity of R2 elements and screened several R2 orthologs capable of full-length gene insertion in mammalian cells. Robust R2 system gene integration efficiency was attained using combined donor RNA and protein engineering. Importantly, the all-RNA-delivered engineered R2 system showed effective integration activity, with efficiency over 60% in mouse embryos. Unbiased high-throughput sequencing demonstrated that the engineered R2 system exhibited high on-target integration specificity (99%). In conclusion, our study provides engineered R2 tools for applications based on hit-and-run targeted DNA integration and insights for further optimization of retrotransposon systems.

2.
J Am Chem Soc ; 146(6): 3675-3688, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305736

RESUMO

The extracellular matrix (ECM) in the tumor microenvironment (TME) and upregulated immune checkpoints (ICs) on antitumor immune cells impede the infiltration and killing effect of T cells, creating an immunosuppressive TME. Herein, a cholesterol oxidase (CHO) and lysyl oxidase inhibitor (LOX-IN-3) co-delivery copper-dibenzo-[g,p]chrysene-2,3,6,7,10,11,14,15-octaol single-site nanozyme (Cu-DBCO/CL) was developed. The conjugated organic ligand and well-distributed Cu-O4 sites endow Cu-DBCO with unique redox capabilities, enabling it to catalyze O2 and H2O2 to ·O2- and ·OH. This surge of reactive oxygen species (ROS) leads to impaired mitochondrial function and insufficient ATP supply, impacting the function of copper-transporting ATPase-1 and causing dihydrolipoamide S-acetyltransferase oligomerization-mediated cuproptosis. Moreover, multiple ROS storms and glutathione peroxidase 4 depletion also induce lipid peroxidation and trigger ferroptosis. Simultaneously, the ROS-triggered release of LOX-IN-3 reshapes the ECM by inhibiting lysyl oxidase activity and further enhances the infiltration of cytotoxic T lymphocytes (CD8+ T cells). CHO-triggered cholesterol depletion not only increases ·OH generation but also downregulates the expression of ICs such as PD-1 and TIM-3, restoring the antitumor activity of tumor-infiltrating CD8+ T cells. Therefore, Cu-DBCO/CL exhibits efficient properties in activating a potent antitumor immune response by cascade-enhanced CD8+ T cell viability. More importantly, ECM remodeling and cholesterol depletion could suppress the metastasis and proliferation of the tumor cells. In short, this immune nanoremodeler can greatly enhance the infiltration and antitumor activity of T cells by enhancing tumor immunogenicity, remodeling ECM, and downregulating ICs, thus achieving effective inhibition of tumor growth and metastasis.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Humanos , Proteína-Lisina 6-Oxidase , Cobre , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Colesterol , Linhagem Celular Tumoral , Imunoterapia , Microambiente Tumoral
3.
J Am Chem Soc ; 146(2): 1244-1249, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38180816

RESUMO

Superconductivity was discovered in (InSe2)xNbSe2. The materials are crystallized in a unique layered structure where bonded InSe2 layers are intercalated into the van der Waals gaps of 2H-phase NbSe2. The (InSe2)0.12NbSe2 superconductor exhibits a superconducting transition at 11.6 K and critical current density of 8.2 × 105 A/cm2. Both values are the highest among all transition metal dichalcogenide superconductors at ambient pressure. The present finding provides an ideal material platform for further investigation of superconducting-related phenomena in transition metal dichalcogenides.

4.
Breast Cancer Res ; 26(1): 27, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347651

RESUMO

BACKGROUND: A malignancy might be found at surgery in cases of atypical ductal hyperplasia (ADH) diagnosed via US-guided core needle biopsy (CNB). The objective of this study was to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in predicting ADH diagnosed by US-guided CNB that was upgraded to malignancy after surgery. METHODS: In this retrospective study, 110 CNB-diagnosed ADH lesions in 109 consecutive women who underwent US, CEUS, and surgery between June 2018 and June 2023 were included. CEUS was incorporated into US BI-RADS and yielded a CEUS-adjusted BI-RADS. The diagnostic performance of US BI-RADS and CEUS-adjusted BI-RADS for ADH were analyzed and compared. RESULTS: The mean age of the 109 women was 49.7 years ± 11.6 (SD). The upgrade rate of ADH at CNB was 48.2% (53 of 110). The sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for identification of malignant upgrading were 96.2%, 66.7%,72.9%, and 95.0%, respectively, based on BI-RADS category 4B threshold. The two false-negative cases were low-grade ductal carcinoma in situ. Compared with the US, CEUS-adjusted BI-RADS had better specificity for lesions smaller than 2 cm (76.7% vs. 96.7%, P = 0.031). After CEUS, 16 (10 malignant and 6 nonmalignant) of the 45 original US BI-RADS category 4A lesions were up-classified to BI-RADS 4B, and 3 (1 malignant and 2 nonmalignant) of the 41 original US BI-RADS category 4B lesions were down-classified to BI-RADS 4A. CONCLUSIONS: CEUS is helpful in predicting malignant upgrading of ADH, especially for lesions smaller than 2 cm and those classified as BI-RADS 4A and 4B on ultrasound.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Ultrassonografia Mamária , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Biópsia com Agulha de Grande Calibre
5.
Int J Obes (Lond) ; 48(6): 891-899, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38383717

RESUMO

OBJECTIVE: This study aims to estimate the prevalence of early-onset sarcopenia and sarcopenic obesity in the United States and its relative risk due to obstructive sleep apnea (OSA). METHODS: Data in this cross-sectional study were extracted from the National Health and Nutritional Examination Survey (NHANES) 2015-2018. Weighted multistage stratified probability sampling design was considered to estimate the prevalence of early-onset sarcopenia and sarcopenic obesity. Weighted multivariable logistic regression analyses and weighted multivariable mediation models were performed to evaluate the association between OSA and early-onset sarcopenia. RESULTS: The prevalence of early-onset sarcopenia and early-onset sarcopenic obesity was estimated to be 5.5% and 4.6%, respectively. A higher prevalence of sarcopenia (12% V.S. 5.5%, P < 0.01) and sarcopenic obesity (10.3% V.S. 4.0%, P < 0.01) was observed among participants with OSA than those without OSA. Multivariable logistic regression models suggested that participants with OSA had higher odds ratios of suffering from early-onset sarcopenia [Odds Ratio (OR): 1.5, 95% confidence interval (CI):1.1-2.7] and early-onset sarcopenic obesity [OR: 1.8, 95% CI: 1.1-3.1] after adjusting for potential confounding variables. Mediation analyses suggested serum chronic reaction protein (CRP) mediated 23.7% (P < 0.01) & 26.2% (P < 0.01), homeostasis model assessment insulin resistance index (HOMA-IR) mediated 24.8% (P < 0.01) & 20.7% (P < 0.05), body mass index (BMI) mediated 46.4% (P < 0.05) & 49.9% (P < 0.01), HEI-2015 mediated 23.3% (P < 0.01) & 25.6% (P < 0.01), and Vitamin D mediated 7.5% (P < 0.01) & 8.5% (P < 0.01) of the potential effects of OSA on early-onset sarcopenia and sarcopenic obesity, respectively. CONCLUSION: Early-onset sarcopenia and sarcopenic obesity were prevalent among young adults in the US. OSA is a significant independent risk factor and may induce muscle loss by unhealthy diet habits, higher BMI, chronic inflammation, insulin resistance, and Vitamin D. It was essential for clinicians to arrange appropriate screening and interventions for patients with OSA to prevent muscle loss as early as possible.


Assuntos
Inquéritos Nutricionais , Obesidade , Sarcopenia , Apneia Obstrutiva do Sono , Humanos , Sarcopenia/epidemiologia , Sarcopenia/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Masculino , Feminino , Obesidade/epidemiologia , Obesidade/complicações , Estudos Transversais , Estados Unidos/epidemiologia , Adulto , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
6.
Opt Lett ; 49(3): 570-573, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300061

RESUMO

Recently, there has been significant interest in the generation of coherent temporal solitons in optical microresonators. In this Letter, we present a demonstration of dissipative Kerr soliton generation in a microrod resonator using an auxiliary-laser-assisted thermal response control method. In addition, we are able to control the repetition rate of the soliton over a range of 200 kHz while maintaining the pump laser frequency, by applying external stress tuning. Through the precise control of the PZT voltage, we achieve a stability level of 3.9 × 10-10 for residual fluctuation of the repetition rate when averaged 1 s. Our platform offers precise tuning and locking capabilities for the repetition frequency of coherent mode-locked combs in microresonators. This advancement holds great potential for applications in spectroscopy and precision measurements.

7.
Phys Rev Lett ; 132(16): 163603, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38701459

RESUMO

Phonon-based frequency combs that can be generated in the optical and microwave frequency domains have attracted much attention due to the small repetition rates and the simple setup. Here, we experimentally demonstrate a new type of phonon-based frequency comb in a silicon optomechanical crystal cavity including both a breathing mechanical mode (∼GHz) and flexural mechanical modes (tens of MHz). We observe strong mode competition between two approximate flexural mechanical modes, i.e., 77.19 and 90.17 MHz, resulting in only one preponderant lasing, while maintaining the lasing of the breathing mechanical mode. These simultaneous observations of two-mode phonon lasing state and significant mode competition are counterintuitive. We have formulated comprehensive theories to elucidate this phenomenon in response to this intriguing outcome. In particular, the self-pulse induced by the free carrier dispersion and thermo-optic effects interacts with two approximate flexural mechanical modes, resulting in the repetition rate of the comb frequency-locked to exact fractions of one of the flexural mechanical modes and the mode hopping between them. This phonon-based frequency comb has at least 260 comblines and a repetition rate as low as a simple fraction of the flexural mechanical frequency. Our demonstration offers an alternative optomechanical frequency comb for sensing, timing, and metrology applications.

8.
Vet Res ; 55(1): 82, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937820

RESUMO

Respiratory diseases constitute a major health problem for ruminants, resulting in considerable economic losses throughout the world. Parainfluenza type 3 virus (PIV3) is one of the most important respiratory pathogens of ruminants. The pathogenicity and phylogenetic analyses of PIV3 virus have been reported in sheep and goats. However, there are no recent studies of the vaccination of sheep or goats against PIV3. Here, we developed a purified inactivated ovine parainfluenza virus type 3 (OPIV3) vaccine candidate. In addition, we immunized sheep with the inactivated OPIV3 vaccine and evaluated the immune response and pathological outcomes associated with OPIV3 TX01 infection. The vaccinated sheep demonstrated no obvious symptoms of respiratory tract infection, and there were no gross lesions or pathological changes in the lungs. The average body weight gain significantly differed between the vaccinated group and the control group (P < 0.01). The serum neutralization antibody levels rapidly increased in sheep post-vaccination and post-challenge with OPIV3. Furthermore, viral shedding in nasal swabs and viral loads in the lungs were reduced. The results of this study suggest that vaccination with this candidate vaccine induces the production of neutralizing antibodies and provides significant protection against OPIV3 infection. These results may be helpful for further studies on prevention and control strategies for OPIV3 infections.


Assuntos
Infecções por Respirovirus , Doenças dos Ovinos , Vacinas de Produtos Inativados , Vacinas Virais , Animais , Ovinos , Infecções por Respirovirus/veterinária , Infecções por Respirovirus/prevenção & controle , Infecções por Respirovirus/virologia , Infecções por Respirovirus/imunologia , Vacinas de Produtos Inativados/imunologia , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/virologia , Doenças dos Ovinos/imunologia , Vacinas Virais/imunologia , Respirovirus/imunologia , Imunogenicidade da Vacina , Vacinação/veterinária
9.
BMC Vet Res ; 20(1): 209, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38760785

RESUMO

BACKGROUND: Bovine coronavirus (BCoV) is implicated in severe diarrhea in calves and contributes to the bovine respiratory disease complex; it shares a close relationship with human coronavirus. Similar to other coronaviruses, remarkable variability was found in the genome and biology of the BCoV. In 2022, samples of feces were collected from a cattle farm. A virus was isolated from 7-day-old newborn calves. In this study, we present the genetic characteristics of a new BCoV isolate. The complete genomic, spike protein, and nucleocapsid protein gene sequences of the BCoV strain, along with those of other coronaviruses, were obtained from the GenBank database. Genetic analysis was conducted using MEGA7.0 and the Neighbor-Joining (NJ) method. The reference strains' related genes were retrieved from GenBank for comparison and analysis using DNAMAN. RESULTS: The phylogenetic tree and whole genome consistency analysis showed that it belonged to the GIIb subgroup, which is epidemic in Asia and America, and was quite similar to the Chinese strains in the same cluster. Significantly, the S gene was highly consistent with QH1 (MH810151.1) isolated from yak. This suggests that the strain may have originated from interspecies transmission involving mutations of wild strains. The N gene was conserved and showed high sequence identity with the epidemic strains in China and the USA. CONCLUSIONS: Genetic characterization suggests that the isolated strain could be a new mutant from a wild-type lineage, which is in the same cluster as most Chinese epidemic strains but on a new branch.


Assuntos
Doenças dos Bovinos , Infecções por Coronavirus , Coronavirus Bovino , Genoma Viral , Filogenia , Animais , Bovinos , Coronavirus Bovino/genética , Coronavirus Bovino/isolamento & purificação , China/epidemiologia , Doenças dos Bovinos/virologia , Doenças dos Bovinos/epidemiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Infecções por Coronavirus/epidemiologia , Fezes/virologia , Glicoproteína da Espícula de Coronavírus/genética , Animais Recém-Nascidos
10.
BMC Ophthalmol ; 24(1): 11, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182979

RESUMO

PURPOSE: The clinical aspects and prognosis of eyes with endogenous endophthalmitis were compared over the last ten years. The occurrence and progression of endophthalmitis are linked to the systemic immune inflammation index (SII) and clinical features. METHODS: The study comprised patients with endogenous endophthalmitis and 64 patients without endophthalmitis who were treated at Hebei Province Eye Hospital in the last ten years. According to the prognostic visual acuity, patients with endophthalmitis were split into two groups: Group A and Group B. Underlying disease (hypertension, diabetes, tuberculosis), infection risk (liver abscess, urinary tract infection, and recent abdominal surgery), signs and symptoms, and complete blood count were among the evaluation parameters (neutrophil count, lymphocyte count, monocyte count, platelet count, red blood cell distribution width). The NLR, PLR, MLR, and SII values were calculated. A nonparametric test was used to examine the clinical features and complete blood count results of patients in each group. To determine the parameters linked to endophthalmitis progression, researchers used principal component and ordinal logistic regression analyses. RESULTS: The study comprised a total of 25 eyes and 22 individuals with endogenous endophthalmitis. Infectious bacteria included Staphylococcus aureus, Micrococcus luteus, Staphylococcus hemolyticus, and so on. The visual acuity of the affected eye ranged from 2.7 (1.55, 2.7) LogMAR to 1.22 (0.6, 2.7) LogMAR during the 6-month to 8-year follow-up period. The neutrophil, monocyte, and PLT counts, NLR, PLR, and SII values and other markers were considerably higher in Groups A and B than in the control group. The likelihood model of the SII and sex, age, onset time, diabetes, hypertension, monocyte count, and red blood cell distribution was the best, and its increase was strongly connected with the occurrence and progression of endophthalmitis, according to ordinal regression analysis. CONCLUSION: Patients with endophthalmitis had significantly higher blood neutrophil, monocyte, and PLT counts and SII, NLR, PLR, and MLR values. The SII can be employed as a biomarker for predicting endophthalmitis severity and prognosis.


Assuntos
Diabetes Mellitus , Endoftalmite , Hipertensão , Humanos , Endoftalmite/diagnóstico , Inflamação , Olho
11.
J Cell Mol Med ; 27(14): 1975-1987, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37340587

RESUMO

The expression changes of baculovirus inhibitor of apoptosis repeat-containing protein5 in brain glioma after administration of Scutellarin was detected. To explore the effort of scutellarin on anti-glioma by downregulating BIRC5.The effect of scutellarin on tumour growth and animal survival was detected by administering scutellarin to nude mice subcutaneous tumour formation and SD rats in situ tumour formation models. A significantly different gene BIRC5 was found by using the combination of TCGA databases and network pharmacology. And then qPCR was performed to detect the expression of BIRC5 in glioma tissues, cells and normal brain tissues and glial cells. CCK-8 was used to detect the IC50 of scutellarin on glioma cells. The wound healing assay, flow cytometry and MTT test were used to detect the effect of scutellarin on the apoptosis and proliferation of glioma cells. The expression of BIRC5 in glioma tissues was significantly higher than that in normal brain tissues. Scutellarin can significantly reduce tumour growth and improve animal's survival. After scutellarin was administered, the expression of BIRC5 in U251 cells was significantly reduced. And after same time, apoptosis increased and cell proliferation was inhibited. This original research showed that scutellarin can promote the apoptosis of glioma cells and inhibit the proliferation by downregulating the expression of BIRC5.


Assuntos
Neoplasias Encefálicas , Glioma , Camundongos , Ratos , Animais , Camundongos Nus , Ratos Sprague-Dawley , Apoptose , Proliferação de Células , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Linhagem Celular Tumoral , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica
12.
J Am Chem Soc ; 145(16): 8965-8978, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37058189

RESUMO

Immunotherapy is currently the most promising treatment strategy for long-term tumor regression. However, current cancer immunotherapy shows low response rates due to insufficient immunogenicity of tumor cells. Herein, we report a strategy to keep tumor cells highly immunogenic by triggering cascade immunogenic tumor ferroptosis. We developed a six-enzyme co-expressed nanoplatform: lipoxygenase (LOX) and phospholipase A2 (PLA2)-co-loaded FeCo/Fe-Co dual-metal atom nanozyme (FeCo/Fe-Co DAzyme/PL), which can not only induce initial immunogenic tumor ferroptosis through its own multi-enzyme mimetic activities but also up-regulate arachidonic acid (AA) expression to synergize with CD8+ T cell-derived IFN-γ to induce ACSL4-mediated immunogenic tumor ferroptosis. During this process, FeCo/Fe-Co DAzyme/PL can induce lipid peroxidation (LPO) by efficiently generating reactive oxygen species (ROS) and depleting GSH and GPX4 at tumor sites. Additionally, free AA released from PLA2 catalysis is converted into arachidonyl-CoA under the activation of ACSL4 stimulated by IFN-γ, which is further incorporated into phospholipids on membranes and peroxidized with the participation of LOX. Consequently, FeCo/Fe-Co DAzyme/PL can promote irreversible cascade immunogenic ferroptosis through multiple ROS storms, GSH/GPX4 depletion, LOX catalysis, and IFN-γ-mediated ACSL4 activation, constructing an effective pathway to overcome the drawbacks of current immunotherapy.


Assuntos
Ferroptose , Neoplasias , Humanos , Interferon gama , Ácido Araquidônico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fosfolipases A2 , Neoplasias/metabolismo , Linhagem Celular Tumoral
13.
Opt Express ; 31(10): 16781-16794, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37157750

RESUMO

Whispering gallery mode (WGM) resonators provide an important platform for fine measurement thanks to their small size, high sensitivity, and fast response time. Nevertheless, traditional methods focus on tracking single-mode changes for measurement, and a great deal of information from other resonances is ignored and wasted. Here, we demonstrate that the proposed multimode sensing contains more Fisher information than single mode tracking and has great potential to achieve better performance. Based on a microbubble resonator, a temperature detection system has been built to systematically investigate the proposed multimode sensing method. After the multimode spectral signals are collected by the automated experimental setup, a machine learning algorithm is used to predict the unknown temperature by taking full advantage of multiple resonances. The results show the average error of 3.8 × 10-3°C within the range from 25.00°C to 40.00°C by employing a generalized regression neural network (GRNN). In addition, we have also discussed the influence of the consumed data resource on its predicted performance, such as the amount of training data and the case of different temperate ranges between the training and test data. With high accuracy and large dynamic range, this work paves the way for WGM resonator-based intelligent optical sensing.

14.
Microb Pathog ; 181: 106155, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37301331

RESUMO

Type I interferon has great broad-spectrum antiviral ability and immunomodulatory function, and its receptors are expressed in almost all types of cells. Bovine viral diarrhea virus (BVDV) is an important pathogen causing significant economic losses in cattle. In this study, a recombinant expression plasmid carrying bovine interferon-α(BoIFN-α)gene was constructed and transformed into E. coli BL21 (DE3) competent cells. SDS-PAGE and Westernblotting analysis showed that the recombinant BoIFN-α protein (rBoIFN-α) was successfully expressed. It is about 36KD and exists in the form of inclusion body. When denatured, purified and renatured rBoIFN-α protein stimulated MDBK cells, the expression of interferon stimulating genes (ISGs) such as ISG15, OAS1, IFIT1, Mx1 and IFITM1 were significantly up-regulated, and reached the peak at 12 h (P< 0.001). MDBK cells were infected with BVDV with moi of 0.1 and 1.0, respectively. The virus proliferation was observed after pretreatment with rBoIFN-α protein and post-infection treatment. The results showed that the denatured, purified and renatured BoIFN-α protein had good biological activity and could inhibit the replication of BVDV in MDBK cells in vitro, which provided a basis for BoIFN-α as an antiviral drug, immune enhancer and clinical application of BVDV.


Assuntos
Vírus da Diarreia Viral Bovina , Interferon Tipo I , Animais , Bovinos , Escherichia coli , Interferon-alfa/genética , Interferon-alfa/farmacologia , Interferon-alfa/metabolismo , Antivirais/uso terapêutico , Interferon Tipo I/metabolismo , Vírus da Diarreia Viral Bovina/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/metabolismo
15.
Eur Radiol ; 33(9): 6482-6491, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37074423

RESUMO

OBJECTIVES: To develop a predictive model using conventional ultrasound combined with CEUS to identify thoracic wall recurrence after mastectomy. METHODS: A total of 162 women with pathologically confirmed thoracic wall lesions (benign 79, malignant 83; median size 1.9 cm, ranging 0.3-8.0 cm) underwent a mastectomy and were checked by both conventional ultrasound and CEUS and were retrospectively included. Logistic regression models of B-mode ultrasound (US) and color Doppler flow imaging (CDFI) with or without CEUS were established to assess the thoracic wall recurrence after mastectomy. The established models were validated by bootstrap resampling. The models were evaluated using calibration curve. The clinical benefit of models were assessed using decision curve analysis. RESULTS: The area under the receiver characteristic was 0.823 (95% CI: 0.76, 0.88) for model using US alone, 0.898 (95% CI: 0.84, 0.94) for model using US combined with CDFI, and 0.959 (95% CI: 0.92, 0.98) for model using US combined with both CDFI and CEUS. The diagnostic performance of the US combined with CDFI was significantly higher than that of the US alone (0.823 vs 0.898, p = 0.002) but significantly lower than that of the US combined with both CDFI and CEUS (0.959 vs 0.898, p < 0.001). Moreover, the unnecessary biopsy rate of the US combined with both CDFI and CEUS was significantly lower than that of the US combined with CDFI (p = 0.037). CONCLUSIONS: Compared to B-mode ultrasound and CDFI, CEUS improves the diagnostic performance to evaluate thoracic wall recurrence after mastectomy. KEY POINTS: • CUES is an effective supplementary method for US in the diagnosis of thoracic wall recurrence after mastectomy. • CEUS combined with both US and CDFI can significantly improve the accuracy of diagnosis of thoracic wall recurrence after mastectomy. • CEUS combined with both US and CDFI can reduce the rate of unnecessary biopsy of thoracic wall lesions after mastectomy.


Assuntos
Neoplasias da Mama , Meios de Contraste , Recidiva Local de Neoplasia , Parede Torácica , Ultrassonografia , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Diagnóstico Diferencial , Mastectomia , Estudos Retrospectivos , Sensibilidade e Especificidade , Parede Torácica/diagnóstico por imagem , Ultrassonografia/métodos , Ultrassonografia/normas , Recidiva Local de Neoplasia/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Idoso , Modelos Logísticos
16.
Org Biomol Chem ; 21(41): 8263-8266, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37807637

RESUMO

A DABCO-catalyzed allylic alkylation of tertiary propargylic alcohol-derived MBH carbonates with nitromethane was developed. A series of substituted 1,4-enynes with an all-carbon quaternary stereocenter were efficiently obtained in moderate to high yields. The synthetic utility of the product was demonstrated by facile synthesis of 1,4-enyne-embedded 2-pyrrolidinones.

17.
Breast J ; 2023: 1682084, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37771427

RESUMO

Purpose: To evaluate the prognosis of patients with benign phyllodes tumors (PTs) treated by different surgical methods and to explore the influencing factors of local recurrence. Methods: We retrospectively analyzed 215 benign PTs from 193 patients who underwent surgery at Chinese PLA General Hospital between October 2008 and December 2020. We stratified our analysis according to surgical factors and explored the clinicopathological factors to influence local recurrence. Results: Among 193 patients, a total of 17 (8.8%, 17/193) recurred during follow-up. There were 89 patients in the US-VAE group, of whom 6 (6.7%) recurred; 8 of 57 patients (14%) in the local lumpectomy group recurred, while 3 of 47 patients (6.4%) in the extended lumpectomy group recurred (P=0.252). Multivariate logistic regression analysis showed that tumor diameter, mitosis, and history of breast myoma were independent risk factors for tumor recurrence (P=0.005, P=0.006, and P=0.004, respectively). The intraoperative blood loss, operation time, and scar length of the US-VAE group were shorter than those of the other two groups (P < 0.05). Conclusion: Negative surgical margins of benign PTs can obtain similar prognosis as negative surgical margins >10 mm. Therefore, we recommend that a follow-up observation policy be adopted for patients with unexpected benign PTs, rather than unnecessary open surgical resection. Patients' maximum tumor diameter, mitosis, and fibroadenoma history were independent predictors for recurrence of benign PTs.


Assuntos
Neoplasias da Mama , Tumor Filoide , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Tumor Filoide/cirurgia , Tumor Filoide/patologia , Margens de Excisão , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Prognóstico
18.
Biochem Biophys Res Commun ; 612: 188-195, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35567901

RESUMO

Glioblastoma (GBM) stem cells (GSCs) are responsible for GBM initiation, progression, infiltration, standard therapy resistance, and recurrence. However, the mechanisms underlying GSC invasion remain incompletely understood. Using public single-cell RNA-Seq data, we identified MAP3K1 as a master regulator of infiltrative GSCs through c-JUN signaling regulation. MAP3K1 knockdown significantly decreased GSC invasion capacity, proliferation, and stemness in vitro. Moreover, in an orthotopic xenograft model, knockdown of MAP3K1 prominently suppressed GSC infiltration along the corpus callosum and tumor progression and prolonged mouse survival. Mechanistically, MAP3K1 regulates GSC invasion through phosphorylation of downstream c-JUN at serine 63 and 73, as confirmed using the CPTAC phosphoproteome dataset. Furthermore, the c-JUN inhibitor JNK-IN-8 significantly decreased GSC invasion, proliferation, and stemness. Taken together, our study demonstrates that MAP3K1 regulates GSC invasion and tumor progression via activation of c-JUN signaling and indicates that the MAP3K1/c-JUN signaling axis is a therapeutic target for infiltrative GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , MAP Quinase Quinase Quinase 1 , Animais , Benzamidas , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Glioblastoma/patologia , Humanos , Camundongos , Células-Tronco Neoplásicas/patologia , Piridinas , Pirimidinas
19.
Opt Express ; 30(15): 26251-26265, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236820

RESUMO

Optical performance evaluation is a critical process in the production of collimating lenses. However, the current visual inspection of lens light-spot images is inefficient and prone to fatigue. Intelligent detection based on machine vision and deep learning can improve evaluation efficiency and accuracy. In this study, a dual-branch structure light-spot evaluation model based on deep learning is proposed for collimating lens optical performance evaluation, and a lens light-spot image dataset is built, containing 9000 images with corresponding labels. Experimental results show that the proposed model achieves accurate classification of lens optical performance evaluation. Combined with the proposed weighted multi-model voting strategy, the performance of the model is further improved, and the classification accuracy successfully reaches 98.89%. Through the developed application software, the proposed model can be well applied to the quality inspection in collimating lens production.

20.
Opt Express ; 30(20): 36155-36166, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36258551

RESUMO

We propose two polarization interference filters (PIF1 and PIF2) used in the backlight unit of a liquid crystal display (LCD) to achieve a wide color gamut. Both PIF1 and PIF2 consist of two polarizers and two 720° super twisted nematic liquid crystal polymer (LCP) layers, where two polarizers are crossed in PIF1, and two polarizers are parallel in PIF2. The PIFs can eliminate unwanted cyan and yellow parts in the output spectrum, which can improve the color gamut of LCD. In our calculation, when the PIF1 is employed in the LCD with normal color filter and QD-LED backlight, the color gamut increases from 107.3% NTSC to 124.6% NTSC, which is 13.7% NTSC larger than that of the LCD with high-performance color filter. When the PIF2 is employed in the LCD with normal color filter and QD-LED backlight, the color gamut of LCD with a normal color filter is improved by 6.8% NTSC larger than that of LCD with high-performance color film, and the transfer efficiency is close to that of the LCD with high-performance color film. We define the color gamut enhancement ratio (CGER) to compare the influence of PIFs and the high-performance color filter on the color gamut enhancement performance of LCD. Compared with the high-performance color filter, the two kinds of PIFs have a higher CGER. The PIFs have a great potential for achieving a wide color gamut.

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