Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we investigated the anti-oxidation ...and anti-inflammation effects of
extract (CAE) and its regulation of the skin barrier and immune functions in AD. In vitro experiments revealed that CAE decreased the reactive oxygen species levels and inhibited the translocation of nuclear factor-κB (NF-κB), further reducing the secretion of interleukin (IL)-1β and IL-6 induced by interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α). Moreover, CAE decreased IFN-γ/TNF-α-induced NLR family pyrin domain-containing 3 (NLRP3), caspase-1, high-mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) expression levels. It also restored the protein levels of skin barrier function-related markers including filaggrin and claudin-1. In vivo experiments revealed that CAE not only reduced the redness of the backs of mice caused by 2,4-dinitrochlorobenzene (DNCB) but also reduced the levels of pro-inflammatory factors in their skin. CAE also reduced transepidermal water loss (TEWL) and immune cell infiltration in DNCB-treated mice. Overall, CAE exerted anti-oxidation and anti-inflammation effects and ameliorated skin barrier dysfunction, suggesting its potential as an active ingredient for AD treatment.
Inspired by natural photosynthesis, constructing inorganic/organic heterojunctions is regarded as an effective strategy to design high‐efficiency photocatalysts. Herein, a step (S)‐scheme ...heterojunction photocatalyst is prepared by in situ growth of an inorganic semiconductor firmly on an organic semiconductor. A new pyrene‐based conjugated polymer, pyrene‐alt‐triphenylamine (PT), is synthesized via the typical Suzuki–Miyaura reactions, and then employed as a substrate to anchor CdS nanocrystals. The optimized CdS/PT composite, coupling 2 wt% PT with CdS, exhibits a robust H2 evolution rate of 9.28 mmol h−1 g−1 with continuous release of H2 bubbles, as well as a high apparent quantum efficiency of 24.3%, which is ≈8 times that of pure CdS. The S‐scheme charge transfer mechanism between PT and CdS, is systematically demonstrated by photoirradiated Kelvin probe measurement and in situ irradiated X‐ray photoelectron spectroscopy analyses. This work provides a protocol for preparing specific S‐scheme heterojunction photocatalysts on the basis of inorganic/organic coupling.
The construction of a CdS/PT inorganic/organic S‐scheme heterojunction not only leads to efficient charge separation and transfer, but also increased redox ability and enhanced stability for photocatalytic hydrogen evolution.
The primary cause of death from breast cancer is the progressive growth of tumors and resistance to conventional therapies. It is currently believed that recurrent cancer is repopulated according to ...a recently proposed cancer stem cell hypothesis. New therapeutic strategies that specifically target cancer stem-like cells may represent a new avenue of cancer therapy. We aimed to discover novel compounds that target breast cancer stem-like cells. We used a dye-exclusion method to isolate side population (SP) cancer cells and, subsequently, subjected these SP cells to a sphere formation assay to generate SP spheres (SPS) from breast cancer cell lines. Surface markers, stemness genes, and tumorigenicity were used to test stem properties. We performed a high-throughput drug screening using these SPS. The effects of candidate compounds were assessed in vitro and in vivo. We successfully generated breast cancer SPS with stem-like properties. These SPS were enriched for CD44(high) (2.8-fold) and CD24(low) (4-fold) cells. OCT4 and ABCG2 were overexpressed in SPS. Moreover, SPS grew tumors at a density of 10(3), whereas an equivalent number of parental cells did not initiate tumor formation. A clinically approved drug, niclosamide, was identified from the LOPAC chemical library of 1,258 compounds. Niclosamide downregulated stem pathways, inhibited the formation of spheroids, and induced apoptosis in breast cancer SPS. Animal studies also confirmed this therapeutic effect. The results of this proof-of-principle study may facilitate the development of new breast cancer therapies in the near future. The extension of niclosamide clinical trials is warranted.
Abstract Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic ...malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
With advances in technology, wireless and sensor technologies represent a method for continuously recording people's biomedical signals, which may enhance the diagnosis and treatment of users' ...everyday health conditions. These technologies mostly target older adults. In this study, we examine a smart clothing system targeting clinically high-risk patients, including older adults with cardiovascular disease (31 outpatients) and older adults in general (81 participants), to obtain an understanding of the patients' perception of using wearable healthcare technologies. Given that technology anxiety has been shown to affect users' resistance to using new technology and that perceived ubiquity is considered a characteristic of wearable devices and other mobile wireless technologies, we included three external variables: i.e., technology anxiety, perceived ubiquity, and resistance to change, in addition to the traditional components of the technology acceptance model (TAM). The results of the hypothesized model showed that among older adults in general, technology anxiety had a negative effect on the perceived ease of use and perceived ubiquity. The perceived ubiquity construct affects both user groups' perceived ease of use and perceived usefulness of wearing smart clothes. Most relationships among the original constructs of the TAM were validated in older adults in general. Interestingly, we found that perceived usefulness had an indirect effect on behavioral intention through attitude. These results further confirm the validity of the extended TAM in determining older users' technology acceptance behavior.
The present study aimed to examine the effectiveness of the flipped classroom learning environment on learner's learning achievement and motivation, as well as to investigate the effects of flipped ...classrooms on learners with different achievement levels in learning mathematics concepts. The learning achievement and motivation were measured by the Mathematics Achievement Test (MAT) and Course Interest Survey (CIS), respectively. A pretest posttest quasi-experimental design was employed for this study. A total of 82 high-school students participated in this study, divided into experimental and control groups. The experimental group (41) was taught trigonometry using the flipped classroom method, while the control group (41) was taught by traditional teaching methods. The researchers employed independent sample t-test, analysis of covariance (ANCOVA), and multivariate analysis of variance (MANOVA) to analyze the data obtained. Findings indicated a significant difference in the learning achievement and motivation between the two groups, with students using the flipped classroom performing better. Further analysis showed a significant difference in the performance of low achievers in the experimental and control groups.
Every year cervical cancer affects more than 300,000 people, and on average one woman is diagnosed with cervical cancer every minute. Early diagnosis and classification of cervical lesions greatly ...boosts up the chance of successful treatments of patients, and automated diagnosis and classification of cervical lesions from Papanicolaou (Pap) smear images have become highly demanded. To the authors' best knowledge, this is the first study of fully automated cervical lesions analysis on whole slide images (WSIs) of conventional Pap smear samples. The presented deep learning-based cervical lesions diagnosis system is demonstrated to be able to detect high grade squamous intraepithelial lesions (HSILs) or higher (squamous cell carcinoma; SQCC), which usually immediately indicate patients must be referred to colposcopy, but also to rapidly process WSIs in seconds for practical clinical usage. We evaluate this framework at scale on a dataset of 143 whole slide images, and the proposed method achieves a high precision 0.93, recall 0.90, F-measure 0.88, and Jaccard index 0.84, showing that the proposed system is capable of segmenting HSILs or higher (SQCC) with high precision and reaches sensitivity comparable to the referenced standard produced by pathologists. Based on Fisher's Least Significant Difference (LSD) test (P < 0.0001), the proposed method performs significantly better than the two state-of-the-art benchmark methods (U-Net and SegNet) in precision, F-Measure, Jaccard index. For the run time analysis, the proposed method takes only 210 seconds to process a WSI and is 20 times faster than U-Net and 19 times faster than SegNet, respectively. In summary, the proposed method is demonstrated to be able to both detect HSILs or higher (SQCC), which indicate patients for further treatments, including colposcopy and surgery to remove the lesion, and rapidly processing WSIs in seconds for practical clinical usages.
Cancer stem cell survival is the leading factor for tumor recurrence after tumor-suppressive treatments. Therefore, specific and efficient inhibitors of cancer stemness must be discovered for ...reducing tumor recurrence. YM155 has been indicated to significantly reduce stemness-derived tumorsphere formation. However, the pharmaceutical mechanism of YM155 against cancer stemness is unclear. This study investigated the potential mechanism of YM155 against cancer stemness in lung cancer. Tumorspheres derived from epidermal growth factor receptor (EGFR)-mutant HCC827 and EGFR wild-type A549 cells expressing higher cancer stemness markers (CD133, Oct4, and Nanog) were used as cancer stemness models. We observed that EGFR autophosphorylation (Y1068) was higher in HCC827- and A549-derived tumorspheres than in parental cells; this autophosphorylation induced tumorsphere formation by activating G9a-mediated stemness. Notably, YM155 inhibited tumorsphere formation by blocking the autophosphorylation of EGFR and the EGFR-G9a-mediated stemness pathway. The chemical and genetic inhibition of EGFR and G9a revealed the significant role of the EGFR-G9a pathway in maintaining the cancer stemness property. In conclusion, this study not only revealed that EGFR could trigger tumorsphere formation by elevating G9a-mediated stemness but also demonstrated that YM155 could inhibit this formation by simultaneously blocking EGFR autophosphorylation and G9a activity, thus acting as a potent agent against lung cancer stemness.
An innovative wireless device for bioimpedance analysis was developed for post-dual-site free vascularized lymph node transfer (VLNT) evaluation. Seven patients received dual-site free VLNT for ...unilateral upper or lower limb lymphedema. A total of 10 healthy college students were enrolled in the healthy control group. The device was applied to the affected and unaffected limbs to assess segmental alterations in bioimpedance. The affected proximal limb showed a significant increase in bioimpedance at postoperative sixth month (3.3 2.8, 3.6,
= 0.001) with 10 kHz currents for better penetration, although the difference was not significant (3.3 3.3, 3.8) at 1 kHz. The bioimpedance of the affected distal limb significantly increased after dual-site free VLNT surgery, whether passing with the 1 kHz (1.6 0.7, 3.4,
= 0.030, postoperative first month; 2.8 1.0, 4.2,
= 0.027, postoperative third month; and 1.3 1.3, 3.4,
= 0.009, postoperative sixth month) or 10 kHz current ((1.4 0.5, 2.7,
= 0.049, postoperative first month; 3.2 0.9, 6.3,
= 0.003, postoperative third month; and 3.6 2.5, 4.1,
< 0.001, postoperative sixth month). Bioimpedance alterations on the affected distal limb were significantly correlated with follow-up time (
= 0.456,
= 0.029 detected at 10 kHz). This bioimpedance wireless device could quantitatively monitor the interstitial fluid alterations, which is suitable for postoperative real-time surveillance.
The S‐scheme heterojunction is flourishing in photocatalysis because it concurrently realizes separated charge carriers and sufficient redox ability. Steady‐state charge transfer has been confirmed ...by other methods. However, an essential part, the transfer dynamics in S‐scheme heterojunctions, is still missing. To compensate, a series of cadmium sulfide/pyrene‐alt‐difluorinated benzothiadiazole heterojunctions were constructed and the photophysical processes were investigated with femtosecond transient absorption spectroscopy. Encouragingly, an interfacial charge‐transfer signal was detected in the spectra of the heterojunction, which provides solid evidence for S‐scheme charge transfer to complement the results from well‐established methods. Furthermore, the lifetime for interfacial charge transfer was calculated to be ca. 78.6 ps. Moreover, the S‐scheme heterojunction photocatalysts exhibit higher photocatalytic conversion of 1,2‐diols and H2 production rates than bare cadmium sulfide.
The construction of CdS/pyrene‐alt‐difluorinated benzothiadiazole (PDB) inorganic/organic S‐scheme heterojunction leads to efficient photocatalytic H2 production coupled with selective 1,2‐diols oxidation. The interfacial S‐scheme charge‐transfer process was explored with transient absorption spectroscopy.
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