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BACKGROUND: As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC. PATIENTS AND METHODS: This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis. RESULTS: In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A, ATM, and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (Pâ =â .036 and Pâ =â .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HRâ =â 2.15, 95% CI: 1.04-4.41, Pâ =â .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis. CONCLUSION: Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.
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Neoplasias de la Mama , Receptor ErbB-2 , Reparación del ADN por Recombinación , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Estudios Retrospectivos , Pronóstico , Receptor ErbB-2/genética , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Adulto , AncianoRESUMEN
BACKGROUND: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. PATIENTS AND METHODS: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. RESULTS: F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). CONCLUSIONS: The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.
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Neoplasias de la Mama , Células Neoplásicas Circulantes , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Células Neoplásicas Circulantes/patología , Estudios Prospectivos , Terapia Neoadyuvante , Mastectomía Segmentaria , Ferritinas/uso terapéutico , Oxidorreductasas/uso terapéuticoRESUMEN
Powerful 1.2-µm laser operation was produced in Ho3+-doped single-cladding, in-house fabricated ZrF4-BaF2-YF3-AlF3 (ZBYA) glass fibers. The fibers were fabricated based on ZBYA glass with a composition of ZrF4-BaF2-YF3-AlF3. Pumped by an 1150-nm Raman fiber laser, the maximum combined laser output power emitted from both sides of a 0.5-mol% Ho3+-doped ZBYA fiber was 6.7 W, with a slope efficiency of 40.5%. We also observed lasing at 2.9â µm with an output power of 350â mW, which was ascribed to the transition of Ho3+:5I6 â 5I7. The effect of rare earth (RE) doping concentration and the length of the gain fiber were also investigated to determine their effect on laser performance at 1.2â µm and 2.9â µm.
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Terapia por Láser , VidrioRESUMEN
The pioneering work on the newly experimentally synthesized biphenylene network C has triggered a worldwide tide of research on its family material counterparts. In this study, a biphenylene network BN structure was theoretically characterized by density functional theory (DFT) calculations. Initially, the structure's mechanical and thermal stabilities were evaluated. There were no imaginary frequencies in the phonon dispersion curve, indicating that the structure was mechanically stable. Additionally, the energy barrier for forming a biphenylene network BN structure from perfect pristine 2D h-BN is substantially less than that for forming a biphenylene network C from a perfect graphene sheet, as can be explained from the greater structure distortion in the biphenylene network BN with lower bond stress which thus caused lower energy. The electronic band structure and detailed projected density of states analysis indicated that the biphenylene network BN is a semiconductor with the valence band maximum (VBM) and the conduction band minimum (CBM) states from the pz orbitals of N and B atoms with sp2 hybridization. Finally, a bilayer structure was also proposed. Our obtained results provide more insights into two-dimensional biphenylene network BN based structures and those family materials which could be widely used in relevant nanoelectronic devices.
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The expansion of power development industry is facing enormous pressure to reduce carbon emissions in the context of global decarbonization. Using solar energy instead of traditional fossil energy to adjust energy structure is one of the important means for reducing carbon emissions. Existing research focuses on the evaluation of the generation potential of centralized or distributed photovoltaic power plants, rather than the comprehensive evaluation of multi-type power plants. Based on multi-source remote sensing data for information extraction and suitability evaluation, this paper develops a method to comprehensively evaluate the construction potential of multi-type photovoltaic power stations and determine the potential of photovoltaic power generation and carbon emission reduction on the Qinghai-Tibet Plateau (QTP). The results showed that estimating the power generation potential of only single-type photovoltaic power stations cannot accurately reflect the photovoltaic power generation potential of QTP. It is also demonstrated that the emission reduction effect of the photovoltaic power generation in all prefecture-level cities of QTP can meet national emission reduction targets, showing high annual power generation potential, of which 86.59% is concentrated in Qinghai province's Guoluo, Yushu, and Haixi. An accurate estimation of the photovoltaic power generation potential in QTP can provide a useful theoretical basis for developing carbon-saving and emission reduction strategies for clean energy in China.
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Carbono , Energía Solar , Tibet , Carbono/análisis , Monitoreo del Ambiente/métodos , ChinaRESUMEN
BACKGROUND: Approximate 25% HER2-positive (HER2+) breast cancer (BC) patients treated with trastuzumab recurred rapidly. However, the mechanisms underlying trastuzumab resistance remained largely unclear. METHODS: Trastuzumab-resistant associated circRNAs were identified by circRNAs high-throughput screen and qRT-PCR in HER2+ breast cancer tissues with different trastuzumab response. The biological roles of trastuzumab-resistant associated circRNAs were detected by cell vitality assay, colony formation assay, Edu assay, patient-derived xenograft (PDX) models and orthotopic animal models. For mechanisms research, the co-immunoprecipitation, Western blot, immunofluorescence, and pull down assays confirmed the relevant mechanisms of circRNA and binding proteins. RESULTS: We identified a circRNA circCDYL2, which was overexpressed in trastuzumab-resistant patients, which conferred trastuzumab resistance in breast cancer cells in vitro and in vivo. Mechanically, circCDYL2 stabilized GRB7 by preventing its ubiquitination degradation and enhanced its interaction with FAK, which thus sustained the activities of downstream AKT and ERK1/2. Trastuzumab-resistance of HER2+ BC cells with high circCDYL2 could be reversed by FAK or GRB7 inhibitor. Clinically, HER2+ BC patients with high levels of circCDYL2 developed rapid recurrence and had shorter disease-free survival (DFS) and overall survival (OS) following anti-HER2 therapy compared to those with low circCDYL2. CONCLUSIONS: circCDYL2-GRB7-FAK complex plays a critical role in maintaining HER2 signaling, which contributes to trastuzumab resistance and circCDYL2 is a potential biomarker for trastuzumab-resistance in HER2+ BC patients.
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Neoplasias de la Mama/genética , Proteínas Co-Represoras/genética , Resistencia a Antineoplásicos/genética , Hidroliasas/genética , ARN Circular , Receptor ErbB-2/metabolismo , Transducción de Señal , Animales , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Proteína Adaptadora GRB7/metabolismo , Humanos , Ratones , Unión Proteica , Proteolisis , Radioterapia , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/genética , UbiquitinaciónRESUMEN
To the best of our knowledge, we report here the first demonstration of 2.9 µm laser emission from in-house fabricated Ho3+/Pr3+ co-doped ZBYA glass fiber. The fiber was fabricated based on the ZBYA glass with compositions of ZrF4-BaF2-YF3-AlF3-PbF2-HoF3-PrF3. Under the pump of a 1150â nm Raman fiber laser, the maximum unsaturated output power of 2.16 W was obtained in a 15â cm long gain fiber with a slope efficiency of 24%. The influence of rare-earth doping concentration on laser performance was also investigated. The result indicates that ZBYA glass fibers have potential for using as a fluorozirconate glass gain fiber for mid-infrared fiber lasers.
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In this Letter, we report the fabrication of fiber Bragg gratings (FBGs) in home-made Ho3+/Pr3+ co-doped single-cladding fluoroaluminate (AlF3) glass fibers and its application in watt-level lasing at the mid-infrared (MIR) wavelength of 2.86 µm. The FBGs were inscribed using an 800 nm femtosecond (fs) laser direct-writing technique. The FBG properties were investigated for different pulse energies, inscription speeds, grating orders, and transversal lengths. A second-order FBG with a high reflectivity of 99% was obtained at one end of a 16.5-cm-long gain fiber. Under 1150 nm laser pumping, this fiber yielded a power exceeding 1 W at 2863.9 nm with an overall laser efficiency of 17.7%. The fiber laser showed a FWHM bandwidth of 0.46 nm and long-term spectral stability.
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Food safety, closely related to economic development of food industry and public health, has become a global concern and gained increasing attention worldwide. Effective detection technology is of great importance to guarantee food safety. Although several classical detection methods have been developed, they have some limitations in portability, selectivity, and sensitivity. The emerging CRISPR-Cas systems, uniquely integrating target recognition specificity, signal transduction, and efficient signal amplification abilities, possess superior specificity and sensitivity, showing huge potential to address aforementioned challenges and develop next-generation techniques for food safety detection. In this review, we focus on recent progress of CRISPR-Cas mediated biosensing and their applications in food safety monitoring. The properties and principles of commonly used CRISPR-Cas systems are highlighted. Notably, the frequently coupled nucleic acid amplification strategies to enhance their selectivity and sensitivity, especially isothermal amplification methods, as well as various signal output modes are also systematically summarized. Meanwhile, the application of CRISPR-Cas systems-based biosensors in food safety detection including foodborne virus, foodborne bacteria, food fraud, genetically modified organisms (GMOs), toxins, heavy metal ions, antibiotic residues, and pesticide residues is comprehensively described. Furthermore, the current challenges and future prospects in this field are tentatively discussed.
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BACKGROUND: Although the prevalence of hepatitis B in Guangzhou, China, is high, the epidemiological trends are not well-documented. We aimed to analyse newly reported hepatitis B cases in Guangzhou between 2009 and 2020 to explore the epidemiological trends and provide insights for the development of control measures. METHODS: Information on the population and new cases of hepatitis B in Guangzhou between 2009 and 2020 was obtained from the China Information System for Disease Control and Prevention, which was used to calculate the annual notification rates of hepatitis B by sex, age group (0-9; 10-19; 20-29; 30-39; 40-49; 50-59; ≥ 60 years), and location (urban or rural). Joinpoint regression analysis was used to analyse the temporal trends and calculate the average annual percentage change (AAPC) and annual percentage change (APC) for each identified trend line segment. RESULTS: Between 2009 and 2020, 287,034 new cases of hepatitis B were cumulatively reported. The average annual notification rate was 181.13/100,000, and the notification rate showed a long-term downward trend during the period 2009-2020, with an annual decrease of 6.30% (APC - 6.30%; 95% CI - 7.56 to - 5.02%). Men had a significantly higher notification rate than women; however, the sex ratio decreased from a maximum of 2.34 in 2010 to a minimum of 1.54 in 2020. A downward trend in the notification rate was observed in urban areas and an upward trend was observed in rural areas, with an increase in the rural/urban ratio from 0.46 in 2012 to 1.57 in 2020. The notification rate for all age groups showed a decreasing trend from 2009, with the exception of the 50-59 years and ≥ 60 years groups, whose notification rates began to decrease from 2014 and 2015, respectively. CONCLUSIONS: Although the overall notification rate of hepatitis B in Guangzhou decreased annually, it remained high. Further, in rural areas, the notification rate has been increasing, and effective measures should be taken to control hepatitis B infection in Guangzhou.
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Hepatitis B , Razón de Masculinidad , Femenino , Humanos , Persona de Mediana Edad , China/epidemiología , Estudios Epidemiológicos , Hepatitis B/epidemiologíaRESUMEN
Broadband emission was obtained over 2.6 to 4.1 µm (Pr3+: 1G4â3F4, 3F3) in AlF3-based glass samples doped with different concentrations of praseodymium and 1 mol% ytterbium using a 976 nm laser pump. An efficient energy transfer process from Yb3+: 2F5/2 to Pr3+: 1G4 was analyzed through emission spectra and fluorescence lifetime values. The absorption and emission cross-sections were calculated by Füchtbauer-Ladenburg and McCumber theories and a positive gain can be obtained when P>0.3. To the best of the authors' knowledge, this work represents the first report of broadband mid-infrared emission of Pr3+ in an AlF3-based glass. The results show that praseodymium doped AlF3-based glass sensitized by ytterbium could be a promising candidate for fiber lasers operating in mid-infrared region.
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Whispering gallery mode (WGM) lasers at â¼2µm are demonstrated in PbO-PbF2-Bi2O3-Ga2O3 (PBG) heavy metal oxyfluoride glass microspheres. A 793 nm diode laser is used to pump the PBG microsphere and achieve single-mode and multimode WGM lasing. The fluorescence spectra of Tm3+-doped PBG glasses are measured under 793 nm diode laser pumping. The maximum absorption and emission cross sections of Tm3+:3F4â3H6 are calculated to be 8.23×10-21 and 4.42×10-20cm2, respectively. The experimental results indicate that these PBG glass microspheres could become an important photonic component for infrared laser applications.
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A room-temperature watt-level continuous-wave-output power mid-infrared fiber laser operating at $\lambda\sim 3\; \unicode{x00B5}{\rm m}$ is demonstrated using a ${{\rm Ho}^{3 +}}/{{\rm Pr}^{3 +}}$ co-doped ${{\rm AlF} _3}$ based glass fiber as a gain fiber. This fixed-wavelength laser had maximum output power of 1.13 W with a slope efficiency of 10.3% and a long-term operating stability of ${\gt}{40}\;{\min }$ without any additional packaging or active thermal management. A fiber laser with tunability from 2.842 to 2.938 µm showed a maximum output power of 110 mW.
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The use of Eu3+ codoping for enhancing the Ho3+:5I5â5I6 emission in fluoroindate glasses shows that Eu3+ could depopulate the lower laser state Ho3+:5I6 while having little effect on the upper state Ho3+:5I5, resulting in greater population inversion. The Ho3+/Eu3+ codoped glass has high spontaneous transition probability (6.31s-1) together with large emission cross section (7.68×10-21cm2). This study indicates that codoping of Ho3+ with Eu3+ is a feasible alternative to quench the lower energy level of the 3.9 µm emission and the Ho3+/Eu3+ codoped fluoroindate glass is a promising material for efficient 3.9 µm fiber lasers.
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Ho3+/Pr3+ co-doped AlF3-based glass fibers were fabricated by using a rod-in-tube method based on the matrix glass composition of AlF3-BaF2-CaF2-YF3-SrF2-MgF2-LiF-ZrF4-PbF2. Under the pump of a 1150 mW Raman fiber laser, a 2.9 µm laser was observed in a 19 cm long Ho3+/Pr3+ co-doped AlF3-based glass fiber with an output power of 173 mW and a slope efficiency of 10.4%. Ho3+/Pr3+ co-doped AlF3-based glasses were fabricated to investigate the deactivation effects of Pr3+ ions on the Ho3+:5I7 level. Our results showed that the Ho3+/Pr3+ co-doped AlF3-based glass fibers are potential gain media for â¼2.9µm lasers.
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This publisher's note contains corrections to Opt. Lett. 45, 1216 (2020).
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Broadband emission at 2.7 µm is observed in an Er3+-doped PbO-PbF2-Bi2O3-Ga2O3 glass. The measured emission band full-width-at-half-maximum (FWHM) is â¼184.4nm, approximately 36 nm wider than that of fluoride glasses. The 2.7 µm emission intensity is almost twice as strong as that of fluoride glasses. The peak values of emission and absorption cross-sections are calculated to be 1.54×10-20cm2 and 1.19×10-20cm2, respectively. This oxyfluoride heavy metal glass shows potential as broadband mid-infrared emission gain material.
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In this Letter, we report lasing at 2.3 µm in Tm3+-single-doped and Tm3+/Ho3+-codoped fluorotellurite glass microsphere resonators. By employing a 793 nm diode laser as a pump and exploiting whispering gallery mode microresonators (WGMRs), dual-wavelength lasing at 1.9 and 2.3 µm and triple-wavelength lasing at 1.9, 2.07, and 2.3 µm are achieved in Tm3+-doped and Tm3+/Ho3+-codoped microspheres, respectively. The introduction of Ho3+ ions significantly reduces the lasing threshold of Tm3+ at 2.3 µm because of energy transfer.
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Intense mid-infrared emission at 3.9 µm in Ho3+-doped ZBYA glasses with direct upper laser level (Ho3+:5I5) pumping at a wavelength of 888 nm is reported for the first time, to the best of our knowledge. Spectroscopic parameters were determined using the Judd-Ofelt theory and the measured absorption spectrum. The maximum emission cross section of the Ho3+-doped ZBYA glass is estimated to be 2.7×10-21cm2 at 3906 nm. Additionally, fluorescence spectra and lifetimes of ZBYA glasses with different Ho3+ ion doping concentrations were measured. The results provide theoretical and experimental basis for better selection of rare-earth-doped matrix glasses to achieve a fluorescence output centered on a wavelength of 3.9 µm.
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Chronic hepatitis B virus (HBV) infection (CHB) in children remains a public health challenge despite significant success in programme is established to prevent mother-to-child transmission. In particular, CHB in Chinese children are mostly acquired through vertical transmission, which differs from the common infection route reported in other countries and regions. This situation has resulted in a high endemic prevalence of CHB in Chinese adults. Thus, successful treatment of children with CHB will prevent the development of advanced liver diseases in late adulthood. However, there is still no consensus on the clinical guideline to treat paediatric CHB. In this study, we evaluated the potential of interferon alpha (IFNa) treatment for Chinese children with CHB. A total of 41 patients with CHB aged 3-17 years were enrolled in this retrospective study: 21 patients were treated with pegylated (PEG)-IFNa and 20 patients without treatment served as the control group. The rates of HBV DNA suppression, hepatitis B e antigen (HBeAg) clearance and hepatitis B surface antigen (HBsAg) clearance were significantly higher in the PEG-IFNa treatment group than in the control group (P < 0.05 at 48 weeks). Unexpectedly, PEG-IFNa treatment achieved a high rate of HBsAb production, far exceeding the clinical outcome in documented PEG-IFNa-treated CHB adults. Further analysis revealed that younger children (3-6 years old) were more responsive to PEG-IFNa treatment with respect to achieving a protective level of HBsAb in a short treatment cycle than adolescents (10-17 years old). Overall, these results indicate that the immune system of children might have a preserved PEG-IFNa-mediated mechanism to completely control HBV, which can help to design new strategies to treat CHB patients.