In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing ...evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.
Core–sheath fibers composed of a crystalline polymer poly(ethylene oxide) (PEO) in the core and amorphous polymers polystyrene (PS) and poly(methyl methacrylate) (PMMA) in the sheath were fabricated ...through coaxial electrospinning. Because the melting temperature of PEO is lower than the glass transition temperatures of PS and PMMA, PEO crystallization was hard-confined within the immobile sheath. In immiscible PEO/PS fibers and miscible PEO/PMMA fibers, hard confinement reduced the crystallizability of PEO; therefore, its crystallite size, degree of crystallinity, and crystallization kinetics decreased with decreases in the degree of confinement. Confinement hindered PEO crystallization to a greater extent when the core and sheath polymers were miscible than when they were not. The favorable interaction between PEO and PMMA facilitated their interdiffusion during electrospinning, which caused the increased confinement of PEO in the core. Furthermore, when the compatibility between the solvents used for coaxial electrospinning increased, they enhanced the interdiffusion of the core and sheath polymers, which hindered PEO crystallization. However, the compatibility between polymers influenced the crystallization behavior of PEO to a considerably greater extent than did the compatibility between solvents.
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•Hard confinement formed by the sheath hinders the PEO crystallization in the core.•Crystallization properties decrease when the degree of confinement increases.•The crystallizability of PEO is lower in miscible fibers than in immiscible fibers.•The solvents used for electrospinning affects the crystallization behavior of PEO.
Triple-negative breast cancer (TNBC) is characterized by the loss of expression of several biomarkers, which limits treatment strategies for the disease. In recent years, immunotherapy has shown ...promising results in the treatment of various tumors. Emerging evidence demonstrated that TNBC is an immune-activated cancer, suggesting that immunotherapy could be a feasible treatment option for TNBC. Cytokine-induced killer (CIK) cell therapy is considered as a potential treatment for cancer treatment. However, it is still not approved as a standard treatment in the clinical setting. Our previous study demonstrated that focal adhesion kinase (FAK) plays important role in regulating the sensitivity of TNBC cells to CIK cells. In this study, we further verify the role of FAK in regulating the immune response in vivo. Our in vitro study indicated that knockdown of FAK in TNBC cells or treat with the FAK inhibitor followed by co-culture with CIK cells induced more cell death than CIK cells treatment only. RNA-seq analysis indicated that suppression of FAK could affect several immune-related gene expressions in TNBC cells that affects the immune response in the tumor microenvironment of TNBC cells. The combination of FAK inhibitor and CIK cells significantly suppressed tumor growth than the treatment of FAK inhibitor or CIK cells alone in vivo. Our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment and indicate that the combination of CIK cell therapy with FAK inhibitors may be an alternative therapeutic strategy for patients with TNBC.
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This study focused on understanding the confined crystallization of poly(ethylene oxide) (PEO) in electrospun nanofibers. The effect of thermal treatment on PEO crystallization was also studied. An ...electrospinning process with a rotating drum collector enabled stretching and aligning of polymer chains, which resulted in the formation of a planar zigzag conformation. The confined environment in nanofibers facilitated an ordered crystal arrangement, resulting in an increase in the degree of crystallinity with a decrease in the fiber diameter. By contrast, large fibers extended solvent evaporation, which resulted in large crystallite sizes. The confined geometry and mechanical force provided by a rotating collector induced the preferred crystal orientation parallel to the fiber axis. Upon thermal annealing, the stretched PEO chains relaxed, resulting in a change from the metastable zigzag conformation to a stable helical conformation. Thermal treatment monotonically increased the melting temperature, degree of crystallinity, and crystallite size of PEO nanofibers regardless of the fiber diameter but did not influence the orientation of the organized crystals.The confinement effect on the chain conformation and crystallization behavior of poly(ethylene oxide) (PEO) in electrospun nanofibers was investigated. The PEO chains in electrospun nanofibers were tightly packed and exhibited a zigzag conformation. Increasing the fiber diameter reduced the packing of polymer chains, resulting in increases in the melting temperature and crystallite size. Thermal treatment relaxed the stretched chains, which induced a change from the metastable zigzag conformation to a stable helical conformation. Additionally, the melting temperature, degree of crystallinity, and crystallite size increased with increasing annealing temperature.
This paper estimates the yields of DNA double-strand breaks (DSBs) induced by ultrasoft X-rays and uses the DSB yields and the repair outcomes to evaluate the relative biological effectiveness (
) of ...ultrasoft X-rays. We simulated the yields of DSB induction and predicted them in the presence and absence of oxygen, using a Monte Carlo damage simulation (MCDS) software, to calculate the
. Monte Carlo excision repair (MCER) simulations were also performed to calculate the repair outcomes (correct repairs, mutations, and DSB conversions). Compared to
Co γ-rays, the
values for ultrasoft X-rays (titanium K-shell, aluminum K-shell, copper L-shell, and carbon K-shell) for DSB induction were respectively 1.3, 1.9, 2.3, and 2.6 under aerobic conditions and 1.3, 2.1, 2.5, and 2.9 under a hypoxic condition (2% O
). The
values for enzymatic DSBs were 1.6, 2.1, 2.3, and 2.4, respectively, indicating that the enzymatic DSB yields are comparable to the yields of DSB induction. The synergistic effects of DSB induction and enzymatic DSB formation further facilitate cell killing and the advantage in cancer treatment.
Radiation therapy (RT) recruits myeloid cells, leading to an immunosuppressive microenvironment that impedes its efficacy against tumors. Combination of immunotherapy with RT is a potential approach ...to reversing the immunosuppressive condition and enhancing tumor control after RT. This study aimed to assess the effects of local interleukin-12 (IL-12) therapy on improving the efficacy of RT in a murine prostate cancer model. Combined treatment effectively shrunk the radioresistant tumors by inducing a T helper-1 immune response and influx of CD8+ T cells. It also delayed the radiation-induced vascular damage accompanied by increased α-smooth muscle actin-positive pericyte coverage and blood perfusion. Moreover, RT significantly reduced the IL-12-induced levels of alanine aminotransferase in blood. However, it did not further improve the IL-12-induced anti-tumor effect on distant tumors. Upregulated expression of T-cell exhaustion-associated genes was found in tumors treated with IL-12 only and combined treatment, suggesting that T-cell exhaustion is potentially correlated with tumor relapse in combined treatment. In conclusion, this study illustrated that combination of radiation and local IL-12 therapy enhanced the host immune response and promoted vascular maturation and function. Furthermore, combination treatment was associated with less systemic toxicity than IL-12 alone, providing a potential option for tumor therapy in clinical settings.
Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction-L5-is the ...only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD.
In 30 asymptomatic individuals with metabolic syndrome (MetS) and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score.
L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01). The Jonckheere trend test revealed that the percent L5 of total LDL (L5%) and L5 concentration increased with the number of MetS criteria (P<0.001). L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference.
Our findings show that LDL electronegativity was associated with multiple CVD risk factors and CVD risk, suggesting that the LDL electronegativity index may have the potential to be a novel index for predicting CVD. Large-scale clinical trials are warranted to test the reliability of this hypothesis and the clinical importance of the LDL electronegativity index.
The significance of shortwave infrared (SWIR) photodetectors spans across various applications. Nevertheless, the limited spectral response of silicon‐based photodetectors and the high cost ...associated with materials like germanium (Ge) have impeded the widespread adoption of SWIR sensors, particularly in the realm of consumer electronics. This study explores the transformative impact of incorporating a cross‐linkable naphthalenediimide (c‐NDI) as both an electron transporting layer and a hole blocking layer in organic photodetectors (OPDs). The introduction of c‐NDI as an interlayer leads to substantial enhancements in SWIR OPD performance, particularly in terms of reducing dark current and augmenting external quantum efficiency. These improvements are most notable in ultra‐narrow bandgap SWIR systems, where c‐NDI demonstrates superior hole‐blocking capabilities. Besides, OPDs with c‐NDI interlayers also exhibit exceptional stability over time when compared to OPDs based on zinc oxide interlayer, underscoring c‐NDI‘s versatility as an interlayer. Most importantly, when compared to a commercially available Ge photodetector, c‐NDI‐based OPD demonstrates competitive detectivity, achieving 2.67 × 1011 Jones at a wavelength of 1300 nm. This performance even surpasses that of the Ge photodetector, highlighting the substantial potential of OPDs for SWIR imaging applications.
Integrating the naphthalenediimide molecule into the organic photodetector as a hole‐blocking layer can simultaneously reduce dark current and enhance quantum efficiency, resulting in outstanding detectivity of 2.67 × 1011 Jones at 1300 nm, which stands as one of the best values reported to date, and surpasses that of the germanium photodetector.
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