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.
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.
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.
Although nude mice are an ideal photoaging research model, skin biopsies result in inflammation and are rarely performed at baseline. Meanwhile, studies on antiphotoaging antioxidants or rejuvenation ...techniques often neglect the spontaneous reversal capacity. Full-field optical coherence tomography (FFOCT) can acquire cellular details noninvasively. This study aimed to establish a photoaging and sequential function reversal nude mice model assisted by an in vivo cellular resolution FFOCT system. We investigated whether a picosecond alexandrite laser (PAL) with a diffractive lens array (DLA) accelerated the reversal. In the sequential noninvasive assessment using FFOCT, a spectrophotometer, and DermaLab Combo®, the photodamage percentage recovery plot demonstrated the spontaneous recovery capacity of the affected skin by UVB-induced transepidermal water loss and UVA-induced epidermis thickening. A PAL with DLA not only accelerated skin barrier regeneration with epidermal polarity, but also increased dermal neocollagenesis, whereas the nonlasered group still had >60% collagen intensity loss and 40% erythema from photodamage. Our study demonstrated that FFOCT images accurately resemble the living tissue. The photoaging and sequential function reversal model provides a reference to assess the spontaneous recovery capacity of nude mice from photodamage. This model can be utilized to evaluate the sequential noninvasive photodamage and reversal effects after other interventions.
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.
Background
Vascularized lymph node transfer (VLNT) is an emerging surgical treatment for lymphedema. However, literature‐comparing outcomes of upper limb lymphedema (ULL) and lower limb lymphedema ...(LLL) is limited. Hence, the aim of this study is to compare the long‐term clinical outcomes on ULL versus LLL in patients treated with VLNT.
Methods
A retrospective study retrieving data from patients with International Society of Lymphology (ISL) stages II–III who underwent different VLNTs from July 2010 to July 2016 in our institution was performed. Demographics preoperatively, and clinical data (limb circumference, infectious episodes, lymphoscintigraphic studies) preoperatively and postoperatively were recorded. Clinical outcomes by extremity were also analyzed.
Results
A total of 83 patients with lymphedema (ULL: n = 30, LLL: n = 53) were included. Mean follow‐up time was 32.8 months (range 24–49 months). Mean circumference reduction was higher in patients with ULL compared to with LLL (28.6 ± 8.6 vs. 22.3 ± 10.1, p < .001), and for patients with secondary lymphedema (24.8 ± 9.6, p < .001) than for patients with primary lymphedema (18.9 ± 14, p > .05). Infectious episodes per year preoperative and postoperative showed that LLL patients had higher reduction on infection rate compared with ULL patients (2.4 ± 1.1 vs. 1.9 ± 1.2, p < .001).
Conclusion
VLNT is a promising surgical treatment option for patients with lymphedema. This study suggests that VLNT may have a more beneficial outcome in patients with ULL and with secondary lymphedema.
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.
Background
Dynamic in vivo changes in melanin in melasma lesions after exposure to ultraviolet (UV) irradiation have not been described.
Objectives
To determine whether melasma lesions and nearby ...perilesions demonstrated different adaptive responses to UV irradiation and whether the tanning responses were different among different locations on face.
Methods
We collected sequential images from real‐time cellular resolution full‐field optical coherence tomography (CRFF‐OCT) at melasma lesions and perilesions among 20 Asian patients. Quantitative and layer distribution analyses for melanin were performed using a computer‐aided detection (CADe) system that utilizes spatial compounding‐based denoising convolutional neural networks.
Results
The detected melanin (D) is melanin with a diameter >0.5 µm, among which confetti melanin (C) has a diameter of >3.3 µm and corresponds to a melanosome‐rich package. The calculated C/D ratio is proportional to active melanin transportation. Before UV exposure, melasma lesions had more detected melanin (p = 0.0271), confetti melanin (p = 0.0163), and increased C/D ratio (p = 0.0152) in the basal layer compared to those of perilesions. After exposure to UV irradiation, perilesions have both increased confetti melanin (p = 0.0452) and the C/D ratio (p = 0.0369) in basal layer, and this effect was most prominent in right cheek (p = 0.030). There were however no significant differences in the detected, confetti, or granular melanin areas before and after exposure to UV irradiation in melasma lesions in all the skin layers.
Conclusions
Hyperactive melanocytes with a higher baseline C/D ratio were noted in the melasma lesions. They were “fixed” on the plateau and were not responsive to UV irradiation regardless of the location on face. Perilesions retained adaptability with a dynamic response to UV irradiation, in which more confetti melanin was shed, mainly in the basal layer. Therefore, aggravating effect of UV on melasma was mainly due to UV‐responsive perilesions rather than lesions.
Ovarian high‐grade serous carcinoma (HGSC) is the most lethal gynecological malignancy. Prevailing evidences suggest that drug resistance and recurrence of ovarian HGSC are caused by the presence of ...cancer stem cells. Therefore, targeting cancer stems is appealing, however, all attempts to date, have failed. To circumvent this limit, we analyzed differential transcriptomes at early differentiation of ovarian HGSC stem cells and identified the developmental transcription factor GATA3 as highly expressed in stem, compared to progenitor cells. GATA3 expression associates with poor prognosis of ovarian HGSC patients, and was found to recruit the histone H3, lysine 27 (H3K27) demethylase, UTX, activate stemness markers, and promote stem‐like phenotypes in ovarian HGSC cell lines. Targeting UTX by its inhibitor, GSKJ4, impeded GATA3‐driven stemness phenotypes, and enhanced apoptosis of GATA3‐expressing cancer cells. Combinations of gemcitabine or paclitaxel with GSKJ4, resulted in a synergistic cytotoxic effect. Our findings provide evidence for a new role for GATA3 in ovarian HGSC stemness, and demonstrate that GATA3 may serve as a biomarker for precision epigenetic therapy in the future.
What's new?
Cancer stem cells (CSCs) routinely evade conventional cancer therapies and fuel tumor regrowth. However, while CSC targeting is an appealing therapeutic strategy, studies are needed to better understand CSC differentiation. Here, in multipotent CSCs from ovarian high‐grade serous carcinomas (HGSCs), complexes consisting of the stemness regulator GATA3 and the histone demethylase UTX were found to maintain cancer stemness via epigenetic activation of c‐MYC, CD44, and NANOG. GATA3 was further identified as an independent risk factor in early‐stage ovarian HGSC. The results suggest that GATA3 is a prognostic marker in ovarian tumorigenesis and that targeting GATA3/UTX is a promising therapeutic approach.
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