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Two-dimensional (2D) hybrid organic-inorganic metal halide perovskites offer enhanced stability for perovskite-based applications. Their crystal structure's soft and ionic nature gives rise to strong interaction between charge carriers and ionic rearrangements. Here, we investigate the interaction of photogenerated electrons and ionic polarizations in single-crystal 2D perovskite butylammonium lead iodide (BAPI), varying the inorganic lamellae thickness in the 2D single crystals. We determine the directionality of the transition dipole moments (TDMs) of the relevant phonon modes (in the 0.3-3 THz range) by the angle- and polarization-dependent THz transmission measurements. We find a clear anisotropy of the in-plane photoconductivity, with a â¼10% reduction along the axis parallel with the transition dipole moment of the most strongly coupled phonon. Detailed calculations, based on Feynman polaron theory, indicate that the anisotropy originates from directional electron-phonon interactions.
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BACKGROUND: Triple-negative breast cancers display heterogeneity in molecular drivers and immune traits. We previously classified triple-negative breast cancers into four subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). Here, we aimed to evaluate the efficacy and safety of subtyping-based therapy in the first-line treatment of triple-negative breast cancer. METHODS: FUTURE-SUPER is an ongoing, open-label, randomised, controlled phase 2 trial being conducted at Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Eligible participants were females aged 18-70 years, with an Eastern Cooperative Oncology Group performance status of 0-1, and histologically confirmed, untreated metastatic or recurrent triple-negative breast cancer. After categorising participants into five cohorts according to molecular subtype and genomic biomarkers, participants were randomly assigned (1:1) with a block size of 4, stratified by subtype, to receive, in 28-day cycles, nab-paclitaxel (100 mg/m2, intravenously on days 1, 8, and 15) alone (control group) or with a subtyping-based regimen (subtyping-based group): pyrotinib (400 mg orally daily) for the LAR-HER2mut subtype, everolimus (10 mg orally daily) for the LAR-PI3K/AKTmut and MES-PI3K/AKTmut subtypes, camrelizumab (200 mg intravenously on days 1 and 15) and famitinib (20 mg orally daily) for the immunomodulatory subtype, and bevacizumab (10 mg/kg intravenously on days 1 and 15) for the BLIS/MES-PI3K/AKTWT subtype. The primary endpoint was investigator-assessed progression-free survival for the pooled subtyping-based group versus the control group in the intention-to-treat population (all randomly assigned participants). Safety was analysed in all patients with safety records who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT04395989). FINDINGS: Between July 28, 2020, and Oct 16, 2022, 139 female participants were enrolled and randomly assigned to the subtyping-based group (n=69) or control group (n=70). At the data cutoff (May 31, 2023), the median follow-up was 22·5 months (IQR 15·2-29·0). Median progression-free survival was significantly longer in the pooled subtyping-based group (11·3 months [95% CI 8·6-15·2]) than in the control group (5·8 months [4·0-6·7]; hazard ratio 0·44 [95% CI 0·30-0·65]; p<0·0001). The most common grade 3-4 treatment-related adverse events were neutropenia (21 [30%] of 69 in the pooled subtyping-based group vs 16 [23%] of 70 in the control group), anaemia (five [7%] vs none), and increased alanine aminotransferase (four [6%] vs one [1%]). Treatment-related serious adverse events were reported for seven (10%) of 69 patients in the subtyping-based group and none in the control group. No treatment-related deaths were reported in either group. INTERPRETATION: These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway. FUNDING: National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Shanghai Hospital Development Center, and Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , China , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Although multiprotein membrane complexes play crucial roles in bacterial physiology and virulence, the mechanisms governing their quality control remain incompletely understood. In particular, it is not known how unincorporated, orphan components of protein complexes are recognised and eliminated from membranes. Rhomboids, the most widespread and largest superfamily of intramembrane proteases, are known to play key roles in eukaryotes. In contrast, the function of prokaryotic rhomboids has remained enigmatic. Here, we show that the Shigella sonnei rhomboid proteases GlpG and the newly identified Rhom7 are involved in membrane protein quality control by specifically targeting components of respiratory complexes, with the metastable transmembrane domains (TMDs) of rhomboid substrates protected when they are incorporated into a functional complex. Initial cleavage by GlpG or Rhom7 allows subsequent degradation of the orphan substrate. Given the occurrence of this strategy in an evolutionary ancient organism and the presence of rhomboids in all domains of life, it is likely that this form of quality control also mediates critical events in eukaryotes and protects cells from the damaging effects of orphan proteins.
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Endopeptidases/metabolismo , Proteínas de Membrana/metabolismo , Shigella sonnei/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Transporte de Elétrons , Endopeptidases/química , Domínios Proteicos , Proteólise , Shigella sonnei/metabolismo , Especificidade por SubstratoRESUMO
Autoimmune hepatitis (AIH) eventually progresses to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, causing irreversible damage to the liver. Concanavalin A-induced hepatitis in mice is a well-established model with pathophysiology similar to that of immune-mediated liver injury in human viral and autoimmune hepatitis, and it has been widely used to explore the pathogenesis and clinical treatment of human immune hepatitis. Artemisinin has been shown to exhibit anti-inflammatory effects through unclear mechanisms. In this study, we aimed to assess the effect of the artemisinin derivative TPN10466 on AIH. In vitro studies showed that TPN10466 dose dependently inhibited the percentage of IFN-γ-producing T cells. Further studies showed that TPN10466 attenuated the disease severity of AIH by downregulating the ability of lymphocytes to secrete IFN-γ and by reducing lymphocyte number in the liver. In addition, we found that TPN10466 treatment reduced T-cell responses by inhibiting JNK, ERK, and p38 pathways. In conclusion, our work suggests that TPN10466 provides protection against the autoimmune disease AIH by suppressing the inflammatory response of T cells, suggesting that TPN10466 may be a promising potential agent for the treatment of AIH.
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Artemisininas , Hepatite Autoimune , Animais , Humanos , Camundongos , Artemisininas/metabolismo , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Concanavalina A/metabolismo , Concanavalina A/farmacologia , Concanavalina A/uso terapêutico , Hepatite Autoimune/tratamento farmacológico , Fígado/patologia , Sistema de Sinalização das MAP QuinasesRESUMO
PURPOSE: To assess the diagnostic performance of breast MRI for BI-RADS 4A microcalcifications on mammography and propose a potential clinical pathway to avoid unnecessary biopsies. METHODS: Bibliometrics analysis of breast MRI and BI-RADS 4 was provided. A retrospective analysis was conducted on 139 women and 142 cases of BI-RADS 4A microcalcifications on mammography from Fudan University Shanghai Cancer Center. The mammographic BI-RADS level and the MRI reports were compared with the final pathological diagnosis. RESULTS: Much attention has been given to breast MRI and BI-RADS 4 in the literature. However, studies on BI-RADS 4A are limited. Pathological results showed 117 cases (82.4%) were benign lesions, malignant cases of 25 (17.6%) in our study. The positive predictive values (PPV), specificity, sensitivity and negative predictive values (NPV) of MRI were 44.2% (23/52), 75.2% (88/117), 92.0% (23/25), and 97.8% (88/90), respectively. Therefore, 75.2% (88/117) of biopsies for benign lesions could potentially be avoided. There were 2.2% (2/90) malignant lesions missed. Logistic regression indicated that patients who are postmenopausal (HR = 2.655, p = 0.012), have a history of breast cancer (family history) (HR = 2.833, p = 0.029), and exhibit clustered microcalcifications (HR = 2.179, p = 0.046) are more likely to have a higher MRI BI-RADS level. CONCLUSIONS: Breast MRI has the potential to improve the diagnosis of BI-RADS 4A microcalcifications on mammography. We propose a potential clinical pathway that patients with BI-RADS 4A on mammography who are premenopausal, have no personal history of breast cancer (family history) or have non-clustered distribution of calcifications can undergo MRI to avoid unnecessary biopsies.
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Neoplasias da Mama , Calcinose , Imageamento por Ressonância Magnética , Mamografia , Humanos , Feminino , Imageamento por Ressonância Magnética/métodos , Calcinose/diagnóstico por imagem , Calcinose/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Mamografia/métodos , Adulto , Idoso , Estudos Retrospectivos , Sensibilidade e Especificidade , Mama/diagnóstico por imagem , Mama/patologia , BiópsiaRESUMO
BACKGROUND: Zinc oxide nanoparticle (ZnO NP) is one of the metal nanomaterials with extensive use in many fields such as feed additive and textile, which is an emerging threat to human health due to widely distributed in the environment. Thus, there is an urgent need to understand the toxic effects associated with ZnO NPs. Although previous studies have found accumulation of ZnO NPs in testis, the molecular mechanism of ZnO NPs dominated a decline in male fertility have not been elucidated. RESULTS: We reported that ZnO NPs exposure caused testicular dysfunction and identified spermatocytes as the primary damaged site induced by ZnO NPs. ZnO NPs led to the dysfunction of spermatocytes, including impaired cell proliferation and mitochondrial damage. In addition, we found that ZnO NPs induced ferroptosis of spermatocytes through the increase of intracellular chelatable iron content and lipid peroxidation level. Moreover, the transcriptome analysis of testis indicated that ZnO NPs weakened the expression of miR-342-5p, which can target Erc1 to block the NF-κB pathway. Eventually, ferroptosis of spermatocytes was ameliorated by suppressing the expression of Erc1. CONCLUSIONS: The present study reveals a novel mechanism in that miR-342-5p targeted Erc1 to activate NF-κB signaling pathway is required for ZnO NPs-induced ferroptosis, and provide potential targets for further research on the prevention and treatment of male reproductive disorders related to ZnO NPs.
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Ferroptose , MicroRNAs , NF-kappa B , Transdução de Sinais , Espermatócitos , Testículo , Óxido de Zinco , Animais , Masculino , Camundongos , Proliferação de Células/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Nanopartículas Metálicas/química , MicroRNAs/metabolismo , MicroRNAs/genética , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espermatócitos/metabolismo , Espermatócitos/efeitos dos fármacos , Testículo/metabolismo , Testículo/efeitos dos fármacos , Óxido de Zinco/farmacologia , Óxido de Zinco/químicaRESUMO
BACKGROUND: The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA). METHODS: We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2. RESULTS: Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively. DISCUSSION: By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Neoplasias da Mama/patologia , China , Análise Custo-Benefício , Mutação em Linhagem Germinativa , Neoplasias de Mama Triplo Negativas/patologia , Estados UnidosRESUMO
Harmful particles such as heavy metal particles in the human body can cause many problems such as kidney stones, gallstones, and cerebrovascular diseases. Therefore, it is critical to separate them from the blood and perform a systematic analysis as early as possible. Here, we apply eutectic gallium indium (EGaIn) microparticles as a model to study the separation of particles from blood, thanks to their properties of low toxicity, excellent degradability, and negligible vapor pressure. In particular, the dielectrophoresis (DEP) separation method is employed to separate EGaIn of different sizes and characteristics in blood. First, the screen-printing method is used to create EGaIn microparticles with diameters of 15, 23, 18, and 11 µm. According to the lifetime test, these microparticles can last more than 1 month, as evidenced by their surface oxidation characteristics. Moreover, a DEP platform with W-type electrodes is developed to sort EGaIn particles from whole human blood. The results show that a sorting efficiency of 95% can be attained, which is similar to the separation efficiency of 98% achieved by finite element analysis (FEA) using COMSOL software based on the orthogonal array experiment method. The proposed study successfully validates the use of the DEP method to separate particles from human blood, providing insights into heavy metal particle separating, drug screening, and cell sorting and potentially broadening the applications in environmental analysis, food engineering, and bioengineering.
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Gálio , Índio , Humanos , Eletroforese/métodos , Eletrodos , Separação Celular/métodosRESUMO
An approach using pyrolysis with comprehensive two-dimensional gas chromatography with flame ionization detection is introduced for identifying common isolated plastic polymers. A quadrupole mass spectrometer is employed as a parallel detector to aid method development and improve polymer identification in complex matrices. Common plastic polymers including polyethylene, polypropylene, polystyrene, polyvinyl chloride, polyamide, poly(methyl methacrylate), styrene-butadiene rubber, and polyethylene terephthalate are accurately identified within a total analysis time of 45 min. A strategy to enhance compatibility of high-resolution capillary gas chromatography using a 150-µm internal diameter column technology and a larger internal volume microfurnace-based pyrolyzer is discussed. This strategy resulted in minimizing the band broadening effect caused by the pyrolyzer's internal volume and overcoming the slow pressure buildup when the sample is inserted into the furnace. Prolonged pressure buildup to reach a final pressure setting can cause a safety shutdown to the pneumatic control system. The developed approach is complementary to spectroscopic techniques by offering mass based, chemical composition analysis of plastics.
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BACKGROUND: Breast cancer has the highest incidence rate among malignant tumors in China, with a trend of affecting younger women. The treatment has short- and long-term adverse effects such as damage to the ovaries, which may result in infertility. Such consequences then increase patients' concerns over future reproduction. At present, nor do medical staffs continuously assess their overall well-being, or ensure that they have the knowledge necessary to manage their reproductive concerns. This qualitative study aimed to explore psychological and reproductive decision-making experiences of young women who had experienced childbirth after their diagnosis. METHODS: The phenomenological research, as a kind of qualitative study, was conducted on 12 young women who experienced childbirth after breast cancer diagnosis. Data collection was from September 2021 to January 2022 and content analysis method was used to analyze the data. RESULTS: Five main themes were identified: (1) desire for childbearing from individual, familial, and social aspects after the diagnosis of breast cancer; (2) emotional experiences through pregnancy till raising children; (3) support needs from professionals, family, and peer; (4) self and doctors' influencing factors on reproductive decision-making; and (5) satisfaction with the outcome of reproductive decision-making. CONCLUSIONS: The desire for childbearing of young women should be considered during the reproductive decision-making process. A multidisciplinary team is suggested to be set up to provide professional support. During the reproductive process, professional and peer support should be strengthened to improve decision-making abilities, alleviate negative emotional experience, and smoothen the process of reproductive experience for young patients.
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Neoplasias da Mama , Gravidez , Criança , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , Tomada de Decisões , Reprodução , China , Pesquisa QualitativaRESUMO
This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 µmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1ß(IL-1ß), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 µmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 µmol·L~(-1) BAI significantly increased the SOD activity and 5 µmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1ß, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.
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Microglia , NF-kappa B , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Superóxido Dismutase/metabolismoRESUMO
An analytical strategy to improve sample throughput with discrete frequency infrared image-based targeted analysis of microplastics using a laser direct infrared chemical imaging system was successfully developed and implemented. Leveraging a quantum cascade laser as a light source, the system could lock the frequency at predetermined wavelengths and use a discrete frequency infrared imaging technique to identify particles with absorption at desired wavelengths. In this way, targeted analysis can be achieved by selectively characterizing these particles. In the concept demonstration study, the targeted analysis was able to identify 87.7% of spiked polyethylene particles by scanning only 20% of the particles in the sample. The technique substantially improves sample throughput by at least a factor of 4 under conditions used. In the tests performed with real environmental samples, the targeted analysis workflow correctly identified eight types of common microplastics by only investigating around 60% of the particles and less than 30% of the sample area. Results obtained demonstrated that this scanning strategy is a game changer to enhance sample throughput in microplastic analysis. The technique has the potential of being applied to other infrared-based analytical platforms.
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Microplásticos , Poluentes Químicos da Água , Monitoramento Ambiental , Plásticos/análise , Polietileno , Poluentes Químicos da Água/análiseRESUMO
PURPOSE: Salvage mastectomy is traditionally recommended for patients who developed ipsilateral breast tumor recurrence (IBTR) in light of previous breast irradiation. However, it remains controversial whether surgical axillary staging (SAS) is necessary for IBTR patients with negative nodes. This study aimed to evaluate the oncologic safety of omitting SAS for IBTR. METHODS: We retrospectively identified patients who developed invasive IBTR with negative nodes after undergoing breast-conserving surgery (BCS) from 2010 to 2018. Patterns of care in nodal staging were analyzed based on prior axillary staging status. Clinicopathologic characteristics and adjuvant treatment of the initial tumor, as well as the IBTR, were compared between the SAS and no SAS groups. Kaplan-Meier method and Cox regression model were utilized to compare the locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates after IBTR removal between the two groups. RESULTS: A total of 154 IBTR patients were eligible for final analysis. Compared to the no SAS group, SAS group was less likely to undergo ALND (15.1 vs 73.3%, p < 0.001) at initial BCS, had a longer recurrence interval (2.8 vs 2.1 years, p = 0.03), and were more likely to have discordant molecular subtype (35.8 vs 12.9%, p = 0.001) and different quadrant location (37.7 vs 19.8%, p = 0.02) with primary tumor. However, the extent of axillary staging did not affect systemic or radiation recommendations. In the subgroup of patients without previous ALND, the clinicopathologic characteristics were roughly comparable. No significant differences were observed in LRRFS, DMFS or OS between the two groups. CONCLUSION: For node-negative IBTR patients, we observed selection bias on the basis of prior ALND, shorter recurrence interval, and concordant molecular subtype favoring no SAS but comparable LRRFS, DMFS, and OS. These results support a wider consideration of sparing SAS in the management of IBTR, especially in patients without previous ALND.
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Neoplasias da Mama , Mastectomia Segmentar , Neoplasias da Mama/patologia , Feminino , Humanos , Mastectomia , Mastectomia Segmentar/efeitos adversos , Recidiva Local de Neoplasia/patologia , Estudos RetrospectivosRESUMO
It is increasingly being recognised that the interplay between commensal and pathogenic bacteria can dictate the outcome of infection. Consequently, there is a need to understand how commensals interact with their human host and influence pathogen behaviour at epithelial surfaces. Neisseria meningitidis, a leading cause of sepsis and meningitis, exclusively colonises the human nasopharynx and shares this niche with several other Neisseria species, including the commensal Neisseria cinerea. Here, we demonstrate that during adhesion to human epithelial cells N. cinerea co-localises with molecules that are also recruited by the meningococcus, and show that, similar to N. meningitidis, N. cinerea forms dynamic microcolonies on the cell surface in a Type four pilus (Tfp) dependent manner. Finally, we demonstrate that N. cinerea colocalises with N. meningitidis on the epithelial cell surface, limits the size and motility of meningococcal microcolonies, and impairs the effective colonisation of epithelial cells by the pathogen. Our data establish that commensal Neisseria can mimic and affect the behaviour of a pathogen on epithelial cell surfaces.
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Aderência Bacteriana , Células Epiteliais/microbiologia , Fímbrias Bacterianas/metabolismo , Neisseria cinerea/crescimento & desenvolvimento , Neisseria meningitidis/crescimento & desenvolvimento , Células A549 , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Neisseria cinerea/patogenicidade , Neisseria meningitidis/patogenicidadeRESUMO
Multiple sclerosis (MS) was one of the major conditions causing neurological dysfunction and was an incurable progressive central nervous system disease. Experimental autoimmune encephalomyelitis (EAE) was the most commonly used experimental model of MS. Artemisinin have been shown to exhibit anti-inflammatory effects through unclear mechanisms. In this study, we aimed to evaluate the effect of administration of the artemisinin derivative TPN10466 in EAE. TPN10466 alleviated the severity of disease in EAE. Further studies showed that TPN10466 inhibited lymphocyte migration by downregulating chemokine expression and adhesion molecules. In addition, studies showed that TPN10466 directly inhibited Th1 and Th17 differentiation and reduced Th1 and Th17 infiltration into the central nervous system. In conclusion, our work demonstrated that TPN10466 provided protection against the autoimmune disease EAE by inhibiting the migration of immune cells and suppressing Th1/Th17 differentiation, suggesting that TPN10466 could be a potential for promising potential agent for the treatment of MS/EAE.
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Artemisininas , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Artemisininas/metabolismo , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Diferenciação Celular , Movimento Celular , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Índice de Gravidade de Doença , Células Th1 , Células Th17RESUMO
The aim of our study was to determine whether silencing or overexpression of estrogen receptor ß (ERß) regulates cell proliferation, steroidogenesis, autophagy and signalling pathways in bovine ovarian granulosa cells in vitro. In this study, bovine ovarian granulosa cells (BGCs) were cultured and transfected with ERß siRNA (si-ERß) or a plasmid overexpressing ERß (oe-ERß), and CCK-8 kit was used to assess cell proliferation. Real-time PCR was used to measure gene transcription. Western blotting was used to measure protein expression, and a specific kit was used to measure the production of steroid hormones. The results showed the expression level of ERß affects BGC proliferation according to the gene transcription levels of FSHR, CYP19A1, HSD3ß1 and STAR and the production of E2 and P4. ERß was identified as an important nuclear receptor that induced BGC autophagy based on the mRNA and protein expression of autophagy-related genes. Furthermore, the role of ERß in BGC autophagy was confirmed through treatment with rapamycin (RAPA) or 3-methyladenine (3-MA) in BGCs by cotransfection with si-ERß or oe-ERß in BGCs. The results related to AKT/mTOR signalling and phosphorylation suggested that ERß induces BGC autophagy through attenuating AKT/mTOR signalling. In summary, this study demonstrates that silencing or overexpression of ERß regulates BGC proliferation and function and induces BGC autophagy by targeting AKT/mTOR signalling. These data reveal a novel regulatory mechanism of autophagy via ERß and provide insights into the role of autophagy in BGCs.
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Receptor beta de Estrogênio , Proteínas Proto-Oncogênicas c-akt , Animais , Autofagia/fisiologia , Bovinos , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Células da Granulosa/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: To better understand the difference between traditional breast-conserving surgery (BCS) and oncoplastic surgery (OPS), we conducted a retrospective cohort study involving breast cancer patients who received neoadjuvant chemotherapy (NAC) and then underwent breast conservation at the Fudan University Shanghai Cancer Center. METHODS: A retrospective chart review was conducted. All breast cancer patients who received NAC and then underwent traditional BCS or OPS at the Fudan University Shanghai Cancer Center from January 1, 2008, to December 31, 2019, were included. RESULTS: Three hundred ninety-nine breast cancer patients received NAC and underwent traditional BCS, and 99 patients underwent OPS. The average age of the patients in the OPS group was younger than that in the BCS group (43 vs 48 years, P = 0.017). The size of the tumor assessed by ultrasonography at baseline in the OPS group was larger than that in the BCS group (31.3 vs 28.1 mm, P = 0.013). The same trend was observed in the clinical T stage and overall staging assessments before the administration of NAC in these 2 groups. Oncoplastic techniques were more frequently applied when tumors were located in areas with relatively few glands, such as the upper inner quadrant. There were no significant differences in the margins and distributions of pathological types and molecular subtypes between these 2 groups. The rates of pathological complete response were similar in the traditional BCS and OPS groups. CONCLUSIONS: Unlike traditional BCS, in breast cancer patients after NAC, the adoption of oncoplastic techniques makes breast conservation feasible, even in patients with large tumors, late stages, and unfavorable tumor locations.
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Neoplasias da Mama , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , China , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The development of the smartphone and computer vision technique provides customers with a convenient approach to identify tea species, as well as qualities. However, the prediction model may not behave robustly due to changes in illumination conditions. Fluorescence imaging can induce the fluorescence signal from typical components, and thus may improve the prediction accuracy. In this paper, a tea classification method based on fluorescence imaging and convolutional neural networks (CNN) is proposed. Ultra-violet (UV) LEDs with a central wavelength of 370 nm were utilized to induce the fluorescence of tea samples so that the fluorescence images could be captured. Five kinds of tea were included and pre-processed. Two CNN-based classification models, e.g., the VGG16 and ResNet-34, were utilized for model training. Images captured under the conventional fluorescent lamp were also tested for comparison. The results show that the accuracy of the classification model based on fluorescence images is better than those based on the white-light illumination images, and the performance of the VGG16 model is better than the ResNet-34 model in our case. The classification accuracy of fluorescence images reached 97.5%, which proves that the LED-induced fluorescence imaging technique is promising to use in our daily life.
Assuntos
Redes Neurais de Computação , Imagem Óptica , CháRESUMO
As it is high in value, extra virgin olive oil (EVOO) is frequently blended with inferior vegetable oils. This study presents an optical method for determining the adulteration level of EVOO with soybean oil as well as peanut oil using LED-induced fluorescence spectroscopy. Eight LEDs with central wavelengths from ultra-violet (UV) to blue are tested to induce the fluorescence spectra of EVOO, peanut oil, and soybean oil, and the UV LED of 372 nm is selected for further detection. Samples are prepared by mixing olive oil with different volume fractions of peanut or soybean oil, and their fluorescence spectra are collected. Different pre-processing and regression methods are utilized to build the prediction model, and good linearity is obtained between the predicted and actual adulteration concentration. This result, accompanied by the non-destruction and no pre-treatment characteristics, proves that it is feasible to use LED-induced fluorescence spectroscopy as a way to investigate the EVOO adulteration level, and paves the way for building a hand-hold device that can be applied to real market conditions in the future.
Assuntos
Arachis , Óleo de Soja , Contaminação de Alimentos/análise , Azeite de Oliva/análise , Óleos de Plantas/análise , Espectrometria de FluorescênciaRESUMO
Imidazole and tetrazole derivatives are widely used as clinical drugs since they possess a variety of pharmaceutical function. Zinc and iron are essential trace elements of the human body, with less toxicity and good biocompatibility. In this paper, two new essential metal mononuclear complexes [M(H2tmidc)2(H2O)2]·2H2O (M = Zn (1), Fe (2)) were synthesized through the reaction of 2-((1H-tetrazol-1-yl)methylene)-1H-imidazole-4,5-dicarboxylic acid (H3tmidc) and ZnSO4·7H2O or FeSO4·7H2O. The crystal structures were determined by means of the X-ray single crystal diffraction technique. Results from fluorescence investigations show that both complexes could interact with BSA as well as HSA through the static quenching mechanism. van der Waals forces and hydrogen bonds play important roles in the interaction of complexes and BSA/HSA since both ΔH and ΔS values are negative. The results of molecular docking are consistent with those in experimental studies. Furthermore, the anticancer activity of H3tmidc and both complexes against Eca-109 were preliminarily evaluated and the results show that both complexes have better anticancer activity than the corresponding ligand H3tmidc.