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Introduction: We have recently demonstrated that Sox10 -expressing ( Sox10 + ) cells give rise to mainly type-III neuronal taste bud cells that are responsible for sour and salt taste. The two tissue compartments containing Sox10 + cells in the surrounding of taste buds include the connective tissue core of taste papillae and von Ebner's glands (vEGs) that are connected to the trench of circumvallate and foliate papillae., Methods: In this study, we performed single cell RNA-sequencing of the epithelium of Sox10-Cre/tdT mouse circumvallate/vEG complex and used inducible Cre mouse models to map the cell lineages of vEGs and/or connective tissue (including stromal and Schwann cells)., Results: Transcriptomic analysis indicated that Sox10 expression was enriched in the cell clusters of vEG ducts that contained abundant proliferating cells, while Sox10-Cre/tdT expression was enriched in type-III taste bud cells and vEG ductal cells. In vivo lineage mapping showed that the traced cells were distributed in circumvallate taste buds concurrently with those in the vEGs, but not in the connective tissue. Moreover, multiple genes encoding pathogen receptors were enriched in the vEG ducts hosting Sox10 + cells., Discussion: Our data supports that it is the vEGs, not connective tissue core, that serve as the niche of Sox10 + taste bud progenitors. If this is also true in humans, our data indicates that vEG duct is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Kastriti, Ishan, Choudhary, Rashid, Kramer, Do, Wang, Xu, Schwabe, Ye, Adameyko and Liu.)

Due to their high accuracy, excellent stability, minor size, and low cost, silicon piezoresistive pressure sensors are used to monitor downhole pressure under high-temperature, high-pressure conditions. However, due to silicon's temperature sensitivity, high and very varied downhole temperatures cause a significant bias in pressure measurement by the pressure sensor. The temperature coefficients differ from manufacturer to manufacturer and even vary from batch to batch within the same manufacturer. To ensure high accuracy and long-term stability for downhole pressure monitoring at high temperatures, this study proposes a temperature compensation method based on bilinear interpolation for piezoresistive pressure sensors under downhole high-temperature and high-pressure environments. A number of calibrations were performed with high-temperature co-calibration equipment to obtain the individual temperature characteristics of each sensor. Through the calibration, it was found that the output of the tested pressure measurement system is positively linear with pressure at the same temperatures and nearly negatively linear with temperature at the same pressures, which serves as the bias correction for the subsequent bilinear interpolation temperature compensation method. Based on this result, after least squares fitting and interpolating, a bilinear interpolation approach was introduced to compensate for temperature-induced pressure bias, which is easier to implement in a microcontroller (MCU). The test results show that the proposed method significantly improves the overall measurement accuracy of the tested sensor from 21.2% F.S. to 0.1% F.S. In addition, it reduces the MCU computational complexity of the compensation model, meeting the high accuracy demand for downhole pressure monitoring at high temperatures and pressures.

In this paper, a combination of theoretical modeling, finite element simulation, and experimental methods is employed to investigate the forming mechanism and evolutionary pattern of the stagnant region during mechanical scratching with a diamond wedge tool. The study is structured as follows: Firstly, a theoretical calculation model for the geometric parameters of the stagnant region on the formed groove surface is established based on the contact friction partition mechanism and slip-line field theory. The model indicates that the geometric parameters l B-sg , l V-sg , and ∆l sg of the stagnant region are determined by the length of the stagnant region l p-sg in the plastic flow plane and the transformation parameters. Secondly, the formation process of the stagnant region in mechanical scratching is investigated using an orthogonal cutting simulation model with a negative rake angle tool. The results reveal that the stagnant region is a plastic deformation region formed due to the geometrical characteristics of the negative front surface of the scratching tool and its excessive extrusion, which leads to the formation of adhesive friction within the material. Thirdly, the characteristics of the stagnant region are determined through scratching experiments. Compared to the material in the plastic flow region, the material within the stagnant region exhibits finer and denser microstructures, reduced surface hardening peaks and hardened layer depths, and significantly improved surface roughness. Finally, the evolutionary pattern of the stagnant region under the influence of scratching processing parameters is examined based on the theoretical calculation model of the geometric parameters and the scratching experiment. The findings indicate that as the wedge angle of the scratching tool decreases, the relief angle increases, the absolute value of the rotation angle around the Y-axis decreases, the scratching speed decreases, and the material's plastic adherence improves, the P I/k value decreases, the l p-sg value increases, and consequently, the geometric parameters l B-sg , l V-sg , and ∆l sg of the stagnant region on the formed groove surface also increase. The deviation analysis of the geometric parameters of the stagnant region reveals a consistent trend between the theoretical and experimental values of l V-sg and ∆l sg , with maximum deviations of 15 μm and 4.13%, respectively. This study provides theoretical and experimental evidence for the establishment of the theoretical model of the stagnant region in mechanical scratching, the analysis of its forming mechanism, and the control of the stagnant region geometric parameters on the formed groove surface., (© 2024. The Author(s).)

We present a PPh 3 /DDQ-mediated regiospecific selective N -functionalization of arylhydrazines with primary benzylic alcohols and aryl carboxylic acids for the synthesis of N 1 -benzyl arylhydrazines and N 2 -acyl arylhydrazines, respectively. This metal- and base-free approach features very short reaction times (about 10 min), broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, N 1 -benzlated products have also been successfully applied to the concise synthesis of N -substituted indoles and anticancer drug MDM2 inhibitor.

Background: The microneedle fractional radiofrequency system (MFRS) is able to rejuvenate facial appearance by heating and coagulating certain depth of skin tissue., Objective: To evaluate the safety and efficacy of a novel vacuum-assisted MFRS for facial contour tightening., Methods: This prospective, randomized, split-face study included 21 patients who underwent three treatments with a vacuum-assisted MFRS at 1-month intervals. Half of the face was treated with the MFRS; the other half was untreated (control). Facial volume changes and wrinkles were objectively measured using a three-dimensional imaging system and VISIA-CR., Results: Volume changes of the treated midface were -0.24 ± 0.75, -0.59 ± 0.92, and -0.55 ± 0.65 mL at 1, 3, 6 months follow-up; however, measurements of the control side were 0.08 ± 0.70, -0.08 ± 0.53, and - 0.10 ± 0.86 mL, indicating significant reductions (p < 0.05). The number of facial wrinkles on the treated side was significantly reduced to 12.44 ± 4.85 at 3 months and sustained at 6 months (11.11 ± 4.100) compared to the control side (14.89 ± 5.26 and 13.22 ± 4.44, respectively; p < 0.05). No long-term side effects occurred., Conclusion: The vacuum-assisted MFRS is safe and effective and is recommended for improving facial tightening and reducing wrinkles. This technology is sufficient to ensure the insertion depth, thus helping to improve the treatment accuracy and safety. The MFRS provides sustained effects for at least 6 months., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Increasing immunotherapy response rate and durability can lead to significant improvements in cancer care. To address this challenge, a novel multivalent immune checkpoint therapeutic platform is constructed through site-specific ligation of anti-PD-L1 nanobody (Nb) on ferritin (Ftn) nanocage. Nb-Ftn blocks PD-1/PD-L1 interaction and downregulates PD-L1 levels via endocytosis-induced degradation. In addition, the cage structure of Ftn allows encapsulation of indocyanine green (ICG), an FDA-approved dye. Photothermal treatment with Nb-Ftn@ICG induces immunogenic death of tumor cells, which improves systemic immune response via maturation of dendritic cells and enhanced infiltration of T cells. Moreover, Nb-Ftn encapsulation significantly enhances cellular uptake, tumor accumulation and retention of ICG. In vivo assays showed that this nanoplatform ablates the primary tumor, suppresses abscopal tumors and inhibits tumor metastasis, leading to a prolonged survival rate. This work presents a novel strategy for improving cancer immunotherapy using multivalent nanobody-ferritin conjugates as immunological targeting and enhancing carriers., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Protein phase separation plays a very important role in many biological processes and is closely related to the occurrence and development of some serious diseases. So far, the fluorescence imaging method and fluorescence correlation spectroscopy (FCS) have been frequently used to study the phase separation behavior of proteins. Due to the wide size distribution of protein condensates in phase separation from nano-scale to micro-scale in solution and living cells, it is difficult for the fluorescence imaging method and conventional FCS to fully reflect the real state of protein phase separation in the solution due to the low spatio-temporal resolution of the conventional fluorescence imaging method and the limited detection area of FCS. Here, we proposed a novel method for studying the protein phase separation process by objective scanning-based fluorescence cross-correlation spectroscopy (Scan-FCCS). In this study, CRDBP proteins were used as a model and respectively fused with fluorescent proteins (EGFP and mCherry). We first compared conventional FCS and Scan-FCS methods for characterizing the CRDBP protein phase separation behaviors and found that the reproducibility of Scan-FCS is significantly improved by the scanning mode. We studied the self-fusion process of mCherry-CRDBP and EGFP-CRDBP and observed that the phase change concentration of CRDBP was 25 nM and the fusion of mCherry-CRDBP and EGFP-CRDBP at 500 nM was completed within 70 min. We studied the effects of salt concentration and molecular crowding agents on the phase separation of CRDBP and found that salt can prevent the self-fusion of CRDBP and molecular crowding agents can improve the self-fusion of CRDBP. Furthermore, we found the recruitment behavior of CRDBP to β-catenin proteins and studied their recruitment dynamics. Compared to conventional FCS, Scan-FCCS can significantly improve the reproducibility of measurements due to the dramatic increase of detection zone, and more importantly, this method can provide information about self-fusion and recruitment dynamics in protein phase separation.

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal-based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase-like activity of the non-metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential., (© 2024 Wiley‐VCH GmbH.)

We report herein the first examples of electrochemical radical retro-allylation of homoallylic alcohols via the cleavage of the C(sp 3 )-C(sp 3 ) bond. In this reaction, a variety of sulfonyl hydrazides were employed as the environmentally friendly radical sources via an electrochemical dehydrazination with the release of N 2 and H 2 as the byproducts, leading to sulfonyl allylic compounds in moderate to good yields. The reaction features metal- and base-free reaction conditions, broad functional group tolerance, and a broad substrate scope.

Liquid-liquid phase separation (LLPS) of fused in sarcoma (FUS) has emerged as a fundamental principle underpinning cellular function and malfunction. However, we know little about the FUS phase transition process from individual molecules to nanoscale condensates, which plays important roles in neurodegenerative diseases. Here, we propose the fluorescence correlation spectroscopy (FCS) method to quantitatively study the phase separation process of FUS protein with the fluorescent tag-enhanced green fluorescent protein (EGFP), from individual molecules to nanoscale condensates. The characteristic diffusion time (τ D ) of the protein condensates can be obtained from the FCS curve, which increases with the growth of the protein hydration radius. The bigger the τ D value of the protein condensates, the larger the condensates formed by the phase separation of FUS. By this method, we discovered that the critical concentration for FUS to phase separation was 20 nM. We then plotted FUS phase diagrams based on τ D under different concentrations of NaCl and found that both low-salt and high-salt concentrations tended to promote FUS-EGFP phase separation. Our results showed that ATP has a good inhibitory effect on FUS phase separation, and its inhibition constant IC 50 was 3.2 mM. Finally, we evaluated the inhibition efficiency of single-stranded DNA sequences (ssDNA) on FUS phase separation and demonstrated that ssDNA containing three copies of TCCCCGT had relatively strong inhibition efficiency. In summary, our work provides detailed insight into the FUS phase transition process from individual molecules to nanoscale condensates at nanomolar concentrations and can be exploited for drug screening of neurodegenerative diseases.

Background: The excellent efficacy is mitigated by the limited safety profile of microfocused ultrasound procedures., Objective: We sought to assess the safety and tightening efficacy of a novel microfocused ultrasound., Methods: The randomized middle and lower face and submental region of the participants were treated with the novel device using the following transducers: M4.5, D4.5, M3.0, and D3.0. Improvement in paired comparison of pretreatment and posttreatment photographs, three-dimensional (3D) volumetric assessments, skin thickness measured by B-ultrasonography, and skin photoaging parameters were evaluated. Adverse events and patient satisfaction were also recorded., Results: A total of 20 participants (20 female) were enrolled. Fourteen of 20 participants (70%) were judged to show clinically significant facial tightening during 3-month follow-up (P < 0.05). The mean volumetric change in the lower face, as quantitatively assessed after 3 months was -0.29 mL compared with +0.42 mL on the control side (P < 0.05). The VAS pain score was 3.00 ± 1.19 without any oral or intramuscular anesthesia., Conclusions: A small sample size, lack of clinical scales, and impersonalized treatment parameters. The novel microfocused ultrasound appears to be a safe and effective modality for lower-face tightening., Clinical Trial Registration Number: ChiCTR 2200064666., (© 2023. The Author(s).)

The Coding Region Determinant-Binding Protein (CRDBP) is a carcinoembryonic protein, and it is overexpressed in various cancer cells in the form of granules. We speculated the formation of CRDBP granules possibly through liquid-liquid phase separation (LLPS) processes due to the existence of intrinsically disordered regions (IDRs) in CRDBP. So far, we did not know whether or how phase separation processes of CRDBP occur in single living cells due to the lack of in vivo methods for studying intracellular protein phase separation. Therefore, to develop an in situ method for studying protein phase separation in living cells is a very urgent task. In this work, we proposed an efficient method for studying phase separation behavior of CRDBP in a single living cell by combining in situ fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) with a fluorescence protein fusion technique. We first predicted and confirmed that CRDBP has phase separation in solution by conventional fluorescence imaging and FCS methods. And then, we in situ studied the phase separation behaviors of CRDBP in living cells and observed three states of CRDBP phase separation such as monomer state, cluster state, and granule state. We studied the effects of CRDBP truncated forms and its inhibitor on the CRDBP phase separation. Furthermore, we discovered the recruitment of CRDBP to β-catenin protein in living cells and investigated the effects of CRDBP structures and inhibitor on CRDBP recruitment behavior. This finding may help us to further understand the mechanism of CRDBP protein for regulating Wnt signaling pathway. Additionally, our results documented that FCS/FCCS is an efficient and alternative method for studying protein phase separation in situ in living cells.

Background: Cutaneous erythema is one of the most common signs of arteriovenous malformations (AVMs) in the head and neck region, influencing aesthetic appearance. Surgical resection of AVMs may lead to cicatrization of the skin or aggravation of the lesion. Laser treatment, although effective in improving superficial vascular lesions, cannot prevent deep AVMs from further development., Objective: The authors propose an absolute ethanol embolization therapy that can effectively and safely eradicate the nidus with a favorable aesthetic outcome., Methods: The authors conducted a retrospective observational study of 14 AVM patients with distinct cutaneous erythema in the head and neck region undergoing embolotherapy in a single primary care center. Symptoms before and after treatment, complications, and degree of devascularization were recorded and assessed. Changes in cutaneous redness were evaluated using a previously reported quantitative measurement., Results: Complete symptomatic relief was observed in 5 patients, and major improvement was observed in 9 patients. The mean Δ a * value of the color change had a significant reduction of 6.50 ± 4.04, p < .001, indicating a remarkable remission of cutaneous erythema., Conclusion: Ethanol embolization is an effective and safe treatment for head and neck AVMs with excellent aesthetic outcomes and might become a potential treatment method for other superficial vascular anomalies., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The optimal timing of laser epilation with expanded forehead flaps in facial defect reconstruction remains undetermined. Objective: To compare the efficacy and safety of hair removal during or after flap expansion. Methods: This prospective exploratory study included 15 (11 women and 4 men, 16.47 ± 16.331 years of age) and 26 (19 women and 7 men, 10.69 ± 10.899 years of age) patients who underwent 755 nm long-pulsed alexandrite laser epilation during flap expansion and after surgery, respectively. Facial reconstruction was performed in these patients because of congenital melanin nevus, scar or port-wine stains. Evaluation included hair reduction rate, patient satisfaction, and adverse events. Results: The median number of laser sessions for hair removal during flap expansion was significantly lower than that after surgery (2.00 vs. 3.00, p  < 0.01), and the hair reduction rate was also significantly higher during flap expansion (79.5% ± 21.93% vs. 68.3% ± 17.44%, p  < 0.05). No severe adverse events were reported. Conclusion: Laser hair removal is safe and efficient when performed both during flap expansion period and after surgery, but its efficacy was significantly higher, and fewer sessions were required when performed during tissue expansion. Clinical trial registration information: ChiCTR1900026090.

Inorganic mineral particles play an important role in the formation of atmospheric aerosols in the Sichuan Basin. Atmospheric haze formation is accompanied by the phase transition of mineral particles under high humidity and stable climatic conditions. Backward trajectory analysis was used in this study to determine the migration trajectory of atmospheric mineral particles. Furthermore, Positive matrix factorization (PMF) was used to analyze the sources of atmospheric mineral particles. The phase transition mechanisms of atmospheric mineral particles were studied using ion chromatography, inductively coupled plasma emission spectrometry, total organic carbon analysis, X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy coupled with energy dispersive spectrometry, and grand canonical Monte Carlo methods. Three migration and phase transition paths were identified for the mineral particles. Sources of atmospheric mineral particles included combustion, vehicle emissions, industrial emissions, agricultural sources, and mineral dust. The main mineral phases in atmospheric particles, calcite and dolomite, were transformed into gypsum, and muscovite may be transformed into kaolinite. The phase transition of mineral particles seriously affects the formation of aerosols and worsens haze. Typically, along the Nanchong-Suining-Neijiang-Zigong-Yibin path, calcite is converted into gypsum under the influence of man-made inorganic pollution gases, which worsen the haze conditions and cause slight air pollution for 3-5 days. However, along the Guangyuan-Mianyang-Deyang-Chengdu-Meishan-Ya'an path, anthropogenic volatile organic compounds (VOCs) hindered gypsum formation from dolomite. Furthermore, dolomite and VOCs formed stable adsorption systems (system energies from -0.41 to -4.76 eV, long bonds from 0.20 to 0.24 nm). The adsorption system of dolomite and m/p-xylene, with low system energy (-1.46 eV/-1.33 eV) and significant correlation (r 2  = 0.991, p < 0.01), was the main cause of haze formation. Consequently, calcite gypsification and dolomite--VOC synergism exacerbated regional haze conditions. This study provides a theoretical reference for the mechanism of aerosol formation in basin climates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Image inpainting is an active area of research in image processing that focuses on reconstructing damaged or missing parts of an image. The advent of deep learning has greatly advanced the field of image restoration in recent years. While there are many existing methods that can produce high-quality restoration results, they often struggle when dealing with images that have large missing areas, resulting in blurry and artifact-filled outcomes. This is primarily because of the presence of invalid information in the inpainting region, which interferes with the inpainting process. To tackle this challenge, the paper proposes a novel approach called separable mask update convolution. This technique automatically learns and updates the mask, which represents the missing area, to better control the influence of invalid information within the mask area on the restoration results. Furthermore, this convolution method reduces the number of network parameters and the size of the model. The paper also introduces a regional normalization technique that collaborates with separable mask update convolution layers for improved feature extraction, thereby enhancing the quality of the restored image. Experimental results demonstrate that the proposed method performs well in restoring images with large missing areas and outperforms state-of-the-art image inpainting methods significantly in terms of image quality.

The metabolic reprogramming of tumors requires high levels of adenosine triphosphate (ATP) to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature helps in tumor ablation, it frequently leads to severe side effects. Therefore, improving the therapeutic response and promoting healing are critical considerations in the development of PTT. Here, we proposed a gas-mediated energy remodeling strategy to improve mild PTT efficacy while minimizing side effects. In the proof-of-concept study, a Food and Drug Administration (FDA)-approved drug-based hydrogen sulfide (H 2 S) donor was developed to provide a sustained supply of H 2 S to tumor sites, serving as an adjuvant to PTT. This approach proved to be highly effective in disrupting the mitochondrial respiratory chain, inhibiting ATP generation, and reducing the overexpression of heat shock protein 90 (HSP90), which ultimately amplified the therapeutic outcome. With the ability to reverse tumor thermotolerance, this strategy delivered a greatly potent antitumor response, achieving complete tumor ablation in a single treatment while minimizing harm to healthy tissues. Thus, it holds great promise to be a universal solution for overcoming the limitations of PTT and may serve as a valuable paradigm for the future clinical translation of photothermal nanoagents., (© 2023 Wiley-VCH GmbH.)

Introduction: Roxadustat treatment in PD patients is equivalent to ESAs in increasing hemoglobin (Hb). But blood pressure, cardiovascular parameters, cardio-cerebrovascular complications and prognosis in the two groups before and after treatment has not been sufficiently discussed., Methods: Sixty PD patients who were treated with roxadustat for renal anemia in our PD center recruited from June 2019 to April 2020 as roxadustat group. PD patients treated with rHuEPO were enrolled at a 1:1 ratio as rHuEPO group using the method of propensity score matching. Hb, blood pressure, cardiovascular parameters, cardio-cerebrovascular complications and prognosis were compared between the two group. All patients were followed up for at least 24 months., Results: There were no significant differences in baseline clinical data or laboratory values between roxadustat group and rHuEPO group. After 24 months of follow-up, there was no significant difference in Hb levels ( p > 0.05 ). There were no significant changes in blood pressure, or the incidence of nocturnal hypertension before and after treatment in roxadustat group ( p > 0.05 ), while blood pressure significantly increased in rHuEPO group after treatment ( p < 0.05 ). Compared with roxadustat group after follow-up, rHuEPO group had a higher incidence of hypertension, the levels of cardiovascular parameters were worse and cardio-cerebrovascular complications had a higher incidence ( p < 0.05 ). Cox regression analysis showed age, systolic blood pressure, fasting blood glucose, and rHuEPO use before baseline were risk factors for cardio-cerebrovascular complications in PD patients, while treatment with roxadustat was a protective factor for cardiovascular and cerebrovascular complications., Conclusion: Compared with rHuEPO, roxadustat had less influence on blood pressure or cardiovascular parameters, and it was associated with a lower risk of cardio-cerebrovascular complications in patients undergoing PD. Roxadustat has a cardio-cerebrovascular protective advantage in PD patients with renal anemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cheng, Zhou, Yu, Zhang, Chen, Zhang, Cui, Yu, Zhou and Yu.)

Liupao tea as a type of dark tea can relieve irritable bowel syndrome by regulating gut microbiota, but the mechanism has not been fully explained. An ultra-high performance liquid chromatography along with quadrupole time of flight tandem mass spectrometry was used to analyze the phytochemicals in Liupao tea. Then, we explored the effects of Liupao tea against IBS. From the results of chemical analysis, we identified catechins, polyphenols, amino acids, caffeine, polysaccharides and other components in Liupao tea. The open-field test, gastrointestinal function-related indexes, histochemical assays, measurements of cytokine and aquaporin 3 (AQP3), and determination of serum metabolites were utilized to monitor the physiological consequences of Liupao tea administration in rats with irritable bowel syndrome. The results showed that Liupao tea had a significant protective effect on irritable bowel syndrome. Liupao tea increased locomotive velocity while reducing interleukin-6, interleukin-1β, and tumor necrosis factor-α levels, as well as gastrointestinal injury. Moreover, Liupao tea increased the AQP3 levels of renal tissues but reduced the AQP3 levels of gastrointestinal tissues. Liupao tea reduced the Firmicutes / Bacteroides ratio and significantly reconstructed the microbial pattern. Liupao tea relieved irritable bowel syndrome by repairing gastrointestinal dysfunction, regulating the secretion of pro-inflammatory cytokines, modulating water metabolism, and restoring microbial homeostasis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: We aimed to compare clinical and survival differences between B-cell (B-NHL) and NKT-cell non-Hodgkin lymphomas (NKT-NHL) located in the nasal cavity (NC), nasopharynx, and paranasal sinuses, which are always categorized as one sinonasal type., Study Design: Patients diagnosed with primary B-NHL and NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses from Surveillance, Epidemiology, and End Results (SEER) database were included (1975-2017)., Setting: Population-based cohort study., Methods: We conducted univariate and multivariate Cox regressions and Kaplan-Meier analysis to examine survival outcomes of B/NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses, respectively., Results: Overall, most B-NHL cases originated from the nasopharynx, while the majority of NKT-NHL cases occurred in the nasal cavity. Notably, the cancer-special survival (CSS) outcomes improved significantly in all sinonasal B-NHL cases over time, whereas no such improvement trend was observed in each sinonasal NKT-NHL type. Additionally, increasing age was linked with an elevated risk of death in B-NHL, particularly in the nasal cavity (Hazard ratio [HR]: 3.37), rather than in NKT-NHL. Compared with B-NHL, the adverse effect of a higher stage on CSS was more evident in NKT-NHL, particularly in its nasopharynx site (HR: 5.12). Furthermore, radiotherapy was beneficial for survival in patients with sinonasal B-NHL and NKT-NHL, except in the nasopharynx NKT-NHL. However, chemotherapy has only been beneficial for CSS in patients with paranasal sinuses B-NHL (HR: 0.42) since 2010, rather than in other types of B/NKT-NHL., Conclusion: Although B-NHL and NKT-NHL in the nasal cavity, nasopharynx and paranasal sinuses have similar anatomical locations, their clinicodemographics and prognoses are largely different and should be treated and studied as distinct diseases., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Nanocatalysts are promising tumor therapeutics due to their ability to induce reactive oxygen species in the tumor microenvironment. Although increasing metal loading can improve catalytic activity, the quandary of high metal content versus potential systemic biotoxicity remains challenging. Here, a fully exposed active site strategy by site-specific anchoring of single iridium (Ir) atoms on the outer surface of a nitrogen-doped carbon composite (Ir single-atom catalyst (SAC)) is reported to achieve remarkable catalytic performance at ultralow metal content (≈0.11%). The Ir SAC exhibits prominent dual enzymatic activities to mimic peroxidase and glutathione peroxidase, which catalyzes the conversion of endogenous H 2 O 2 into •OH in the acidic TME and depletes glutathione (GSH) simultaneously. With an advanced support of GSH-trapping platinum(IV) and encapsulation with a red-blood-cell membrane, this nanocatalytic agent (Pt@IrSAC/RBC) causes intense lipid peroxidation that boosts tumor cell ferroptosis. The Pt@IrSAC/RBC demonstrates superior therapeutic efficacy in a mouse triple-negative mammary carcinoma model, resulting in complete tumor ablation in a single treatment session with negligible side effects. These outcomes may provide valuable insights into the design of nanocatalysts with high performance and biosafety for biomedical applications., (© 2023 Wiley-VCH GmbH.)

Objective : A protein-based leaking-proof theranostic nanoplatform for dual-modality imaging-guided tumor photodynamic therapy (PDT) has been designed. Impact Statement : A site-specific conjugation of chlorin e6 (Ce6) to ferrimagnetic ferritin (MFtn-Ce6) has been constructed to address the challenge of unexpected leakage that often occurs during small-molecule drug delivery. Introduction : PDT is one of the most promising approaches for tumor treatment, while a delivery system is typically required for hydrophobic photosensitizers. However, the nonspecific distribution and leakage of photosensitizers could lead to insufficient drug accumulation in tumor sites. Methods : An engineered ferritin was generated for site-specific conjugation of Ce6 to obtain a leaking-proof delivery system, and a ferrimagnetic core was biomineralized in the cavity of ferritin, resulting in a fluorescent ferrimagnetic ferritin nanoplatform (MFtn-Ce6). The distribution and tumor targeting of MFtn-Ce6 can be detected by magnetic resonance imaging (MRI) and fluorescence imaging (FLI). Results : MFtn-Ce6 showed effective dual-modality MRI and FLI. A prolonged in vivo circulation and increased tumor accumulation and retention of photosensitizer was observed. The time-dependent distribution of MFtn-Ce6 can be precisely tracked in real time to find the optimal time window for PDT treatment. The colocalization of ferritin and the iron oxide core confirms the high stability of the nanoplatform in vivo. The results showed that mice treated with MFtn-Ce6 exhibited marked tumor-suppressive activity after laser irradiation. Conclusion : The ferritin-based leaking-proof nanoplatform can be used for the efficient delivery of the photosensitizer to achieve an enhanced therapeutic effect. This method established a general approach for the dual-modality imaging-guided tumor delivery of PDT agents., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2023 Duo Jin et al.)

Matrix metalloproteinase-9 (MMP-9) plays an important role in tumor progression. It is of great significance to establish a sensitive in situ assay strategy for MMP-9 activity in single living cells. Here a novel in situ single molecule spectroscopy method based on the fluorescence correlation spectroscopy (FCS) technique was proposed for measuring the MMP-9 activity at different locations within single living cells, using a fluorescent specific peptide and a reference dye as dual probes. The measurement principle is based on the decrease of the ratiometric translational diffusion time of dual probes in the detection volume due to the peptide cleavage caused by MMP-9. The peptide probe was designed to be composed of an MMP-9 cleavage and cell-penetrating peptide sequence that was labeled with a fluorophore and conjugated with a streptavidin (SAV) molecule. The ratiometric translational diffusion time was used as the measurement parameter to eliminate the effect of intracellular uncertain viscosity. The linear relationship between the ratiometric diffusion time and MMP-9 activity was established, and applied to the determination of enzymatic activity in cell lysates as well as the evaluation of the inhibitory effects of different inhibitors on MMP-9. More importantly, the method was successfully used to dynamically determine MMP-9 activity in single living cells or under the stimulation with phorbol 12-myristate 13-acetate (PMA) and inhibitors.

Background: Obesity is a state of accumulating excessive body fat, charactering by a high blood lipid and associating with various metabolic diseases. As a kind of dark tea, many studies revealed that long-term drinking Liupao tea (LT) can reduce weight (Liu et al., 2014). However, the anti-obesity mechanism and active ingredients of LT are not known., Methods: Liquid chromatography-mass spectrometry (LC-MS) combined with network pharmacology was used to screen the active components and related targets of Liupao tea water extract (LTWE). The key anti-obesity targets and pathways of LTWE were predicted by protein-protein interaction (PPI) networks, and enrichment analyses using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. Then, the active components selected by high-performance liquid chromatography (HPLC) fingerprinting were used together with LTWE in an adipogenic model and insulin resistance (IR) model in vitro., Results: Most of the compounds identified from LTWE were flavonofids, esters, and amides. Key targets such as RAC-alpha serine/threonine-protein kinase, insulin, and tumor necrosis factor (TNF) were involved in the phosphatidylinositol-3-kinase-protein kinase B (PI3K-AKT) signaling pathway, pathways in cancer, and other pathways. Four active components were screened by network pharmacology combined with HPLC fingerprinting. The in vitro experiment of LTWE and its four active components showed that in insulin-resistant 3T3-L1 cells, LTWE, (-)-epigallocatechin gallate (EGCG) and gallic acid (GA) inhibited adipocyte differentiation. Three factors could inhibit the differentiation of 3T3-L1 cells by decreasing gene expression of peroxisome proliferators-activated receptor γ (PPARγ), fatty acid synthase (FAS), CCAAT/enhancer binding proteins-α (C/EBPα) and interleukin-6 (IL-6). Caffeine and ellagic acid (EA) showed opposite results, but their effects on promoting adipose differentiation diminished with increasing concentrations of drug. In dexamethasone-induced insulin-resistant 3T3-L1 cells, the fluorescence intensity of 2-Deoxy-2-[(7-nitro-2,1,3-Benzoxadiazol-4-yl)amino]-d-glucose revealed that LTWE, GA, EGCG, caffeine, and EA significantly promoted glucose consumption. LTWE, GA, and EA improved insulin resistance in adipocytes by upregulating gene expression of insulin receptor substrate-1 (IRS-1), PI3K, AKT, and glucose transporter 4 (GLUT4)., Conclusion: LC-MS combined with network pharmacology preliminarianized that LTWE acts mainly on the PI3K-AKT signaling pathway. Cell experiments revealed that the anti-obesity effect of LTWE is the result of multi-component action, which inhibits the proliferation and differentiation of preadipocytes by regulating gene expression of adipogenic transcription factors and proinflammatory factors, and improves IR by activating the IRS-1/PI3K/AKT/GLUT4 pathway., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: The surgical management of macrocheilia secondary to port-wine stains is complicated., Objective: This study aimed to propose an innovative method for treating macrocheilia on the lower lip., Methods: Patients who underwent the reconstruction of macrocheilia on the lower lip through the innovative approach were examined. Their preoperative and postoperative standard photographs were taken to evaluate the changes in lip length and thickness. The scores on Vancouver scar scale (VSS) and visual analog scale (VAS) were evaluated., Results: Thirty-two patients who underwent the reconstruction of macrocheilia were examined. A follow-up of 12.2 months (6-36 months) was conducted. The lower lip contour and the mentolabial groove were reconstructed to normal appearance. The lip length was shortened from 5.38 ± 0.49 cm pretreatment to 4.59 ± 0.30 cm posttreatment (p = .016). The exposed vermilion was shortened from 2.05 ± 0.48 cm to 1.26 ± 0.12 cm posttreatment (p < .01). The mean VSS and VAS scores were 2.2 ± 1.5 and 8.4 ± 1.3, respectively., Conclusion: The bilateral limited excision and stepwise single-stage approach were safe and effective for reconstructing prominent macrocheilia on the lower lip. The technique was also easy to command for the beginners., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Enzyme-mimicking nanocatalysts, also termed nanozymes, have attracted much attention in recent years. They are considered potential alternatives to natural enzymes due to their multiple catalytic activities and high stability. However, concerns regarding the colloidal stability, catalytic specificity, efficiency and biosafety of nanomaterials in biomedical applications still need to be addressed. Proteins are biodegradable macromolecules that exhibit superior biocompatibility and inherent bioactivities; hence, the protein modification of nanocatalysts is expected to improve their bioavailability to match clinical needs. The diversity of amino acid residues in proteins provides abundant functional groups for the conjugation or encapsulation of nanocatalysts. Moreover, protein encapsulation can not only improve the overall performance of nanocatalysts in biological systems, but also bestow materials with new features, such as targeting and retention in pathological sites. This review aims to report the recent developments and perspectives of protein-encapsulated catalysts in their functional improvements, modification methods and applications in biomedicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Glioma is the most common primary malignancy of the central nervous system (CNS), and 50% of patients present with glioblastoma (GBM), which is the most aggressive type. Currently, the most popular therapies are progressive chemotherapy and treatment with temozolomide (TMZ), but the median survival of glioma patients is still low as a result of the emergence of drug resistance, so we urgently need to find new therapies. A growing number of studies have shown that the diversity, bioactivity, and manipulability of microorganisms make microbial therapy a promising approach for cancer treatment. However, the many studies on the research progress of microorganisms and their derivatives in the development and treatment of glioma are scattered, and nobody has yet provided a comprehensive summary of them. Therefore, in this paper, we review the research progress of microorganisms and their derivatives in the development and treatment of glioma and conclude that it is possible to treat glioma by exogenous microbial therapies and targeting the gut-brain axis. In this article, we discuss the prospects and pressing issues relating to these therapies with the aim of providing new ideas for the treatment of glioma.

Familial dysautonomia (FD), a rare neurodevelopmental and neurodegenerative disorder affects the sympathetic and sensory nervous system. Although almost all patients harbor a mutation in ELP1, it remains unresolved exactly how function of sympathetic neurons (symNs) is affected; knowledge critical for understanding debilitating disease hallmarks, including cardiovascular instability or dysautonomic crises, that result from dysregulated sympathetic activity. Here, we employ the human pluripotent stem cell (hPSC) system to understand symN disease mechanisms and test candidate drugs. FD symNs are intrinsically hyperactive in vitro, in cardiomyocyte co-cultures, and in animal models. We report reduced norepinephrine transporter expression, decreased intracellular norepinephrine (NE), decreased NE re-uptake, and excessive extracellular NE in FD symNs. SymN hyperactivity is not a direct ELP1 mutation result, but may connect to NET via RAB proteins. We found that candidate drugs lowered hyperactivity independent of ELP1 modulation. Our findings may have implications for other symN disorders and may allow future drug testing and discovery., (© 2022. The Author(s).)

Background: Conventional high fluence Q-switched (HFQS) Alexandrite 755-nm are widely used in clinical café-au-lait macules (CALMs) treatment. There have been recent concerns regarding the efficacy and safety of low fluence Q-switched (LFQS) Nd: YAG 1064-nm lasers., Objective: To evaluate the efficacy and safety of the conventional HFQS and LFQS laser in the treatment of CALMs., Methods: Within 3 months, 20 patients underwent prospective self-controlled split-lesion treatments with HFQS once or twice depending on the recovery rate, and with LFQS six times biweekly. Then the more effective laser was selected for continued treatments. Efficacy outcomes were evaluated by a visual analog scale (VAS) biweekly during the comparative trail. Recovery process, side effects and recurrence were recorded during the trial and follow-up visit. Patient and physician preferences for laser selection were also recorded., Results: The average VAS scores of areas treated with HFQS and LFQS were 2.92 ± 0.86 and 2.93 ± 1.13, respectively (p > 0.05). The most significant efficacy change of LFQS was after the fourth laser treatment (VAS score: 1.82-2.37, p < 0.001). 11 lesions treated with LFQS and 7 with HFQS achieved an optimal treatment response (3.67 ≤ VAS ≤ 4). Three patients relapsed on one side (one on LFQS, two on HFQS) and five on both sides. Adverse effects included temporary hypopigmentation, hyperpigmentation, uneven pigmentation, and mottled hypopigmentation. Doctors thought 80% of patients were suitable for LFQS. 70% of patients preferred LFQS posttreatment., Conclusions: The efficacy difference between the LFQS 1064-nm laser and HFQS 755-nm laser in treating CALMs in a 3-month comparative trial was statistically insignificant. LFQS is preferred by doctors and patients and is likely to help more patients achieve treatment efficacy than the HFQS within a short time, with fewer temporary adverse reactions, and a more even pigmentation. But it can cause mottled hypopigmentation. The LFQS had obvious lesion clearance after the fourth treatment., (© 2022 Wiley Periodicals LLC.)

Background: Infraorbital dark circles (IDC) are commonly consulted in aesthetic practice. There is not yet a multifactorial approach to facilitating their treatment., Objective: To investigate the safety and efficacy of the microneedle fractional radiofrequency (MRF) system for the treatment of IDC., Methods: A prospective, split-face, evaluator-blind clinical trial was conducted to study the change in the overall appearance, color, and wrinkles in 21 female patients with mixed type IDC before and after MFR treatment., Results: Both patients and independent evaluators found significant improvement on the global aesthetic scales after the MFR treatment, especially on periorbital wrinkles (p=0.031). Trends in decreased melanin density in the IDC area were found, but no statistical differences were established. No side effects were observed., Conclusion: MFR is a safe and effective modality for improving mixed type IDC by correcting the structural factors., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Wu et al.)

Aim: This study aimed to evaluate the safety and efficacy of a novel therapeutic strategy, a microneedle fractional radiofrequency system, for hand rejuvenation., Material and Method: Sixteen subjects were enrolled in a self-controlled evaluator-blind prospective trial. All subjects received three microneedle fractional radiofrequency treatments at 4 weeks intervals. Hand volume was evaluated through subjective (Hand Volume Rating Scale) and quantitative measurements. Patients were also assessed on the Global Aesthetic Improvement Scale using digital photographs. Patients were followed up at 1, 3, and 6 months after the last radiofrequency treatment., Results: Statistically significant improvements on the Global Aesthetic Improvement Scale and Hand Rating Volume Scale were noted (p < 0.05). Compared with the control side, the treated hand showed a 44% improvement in dorsal skin surface roughness (p < 0.05). Quantitative measurements of hand volume showed a trend toward increased volume for the treated hand, but the difference was not statistically significant., Conclusion: We conclude that microneedle fractional radiofrequency is a safe therapeutic option for hand rejuvenation., (© 2022 Wiley Periodicals LLC.)

Background: Studies have demonstrated that glycerol can act as an optical clearing agent (OCA) to increase the light penetration through the skin and laser deposition to the target chromophore, thus potentially increasing the efficacy of laser treatment., Objective: To evaluate whether a pulsed dye laser (PDL) in combination with an OCA can increase the efficacy in treating port-wine stains (PWSs)., Methods: Thirteen patients with untreated PWSs underwent 3 treatment sessions at 6-week intervals. Each PWS was divided into OCA + PDL sites (PDL treatment after topical use of 0.5 mL hydrous glycerol for 5 minutes), PDL sites, and untreated sites. The chromametric evaluation and visual evaluation (VAS) of the efficacy and the assessment of side effects were conducted 3 months after the final treatment., Results: Visual evaluation was 2.69 versus 2.07 (p = .025) and 3.38 versus 3.07 (p = .04) for OCA + PDL and PDL-only sites after the first and second sessions. After the third session, the chromameter and VAS indicated no significant difference between the 2 sites. Permanent side effects were not observed., Conclusion: Greater efficacy was observed after the first 2 treatments on the OCA + PDL sites. Although after multiple sessions, the OCA + PDL treatment did not improve efficacy over just PDL alone., (Copyright © 2022 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The identification of molecular targets for achieving beneficial effects from small-molecule drugs is a crucial and currently unsolved challenge, which leads to high costs and long development cycles. Therefore, it is urgent to develop methods for easily and quickly acquiring information about protein-drug interaction at a molecular level. In this study, we propose a novel method for the study of protein-drug interaction by fluorescence correlation spectroscopy (FCS) based on organic solvent-induced protein aggregation. We used β-secretase (BACE-1) and dihydrofolate reductase (DHFR) as model proteins. Fluorescence-labelled proteins aggregated in aqueous solutions containing organic solvents. In the presence of drugs, the aggregation of proteins was inhibited greatly, and FCS was used to characterize protein aggregates. The decrease in the characteristic diffusion time ( τ D ) of protein aggregates demonstrated a strong interaction between proteins and drug molecules. We presented a new parameter IC 50 to assess the inhibitory effects of drugs on the basis of the changes in the τ D of fluorescence-labelled proteins under different concentrations of the drugs in the presence of organic solvents. We acquired a remarkable difference in the IC 50 values for different drugs and in terms of the trend, our results were consistent with those reported by other methods. Compared with current methods, our approach is simple, low-cost, and time-saving, and has the potential to become a promising and universal tool for drug screening at the molecular level.

Background: Vascular-targeted photodynamic therapy (PDT) is an effective alternative treatment choice for port-wine stains (PWSs). The histological characteristics of PWSs after PDT treatment have not yet been reported. Objective: To investigate the morphological features of PWSs treated by PDT and define the histopathological characteristics of PWS that achieve clinical cure. Methods: Thirteen patients with facial PWSs, who presented with complete regressive PWS lesions after a mean of 4.38 (standard deviation = 4.907) sessions of PDT. Post-treatment biopsy samples were obtained from each patient. The number of blood vessels, vascular diameter, and depth were measured and compared in all samples of PDT-regressive sites, PDT-resistant sites, and normal skin. Results: Within the 7-year follow-up after PDT, there was no recurrence in the regression area of PDT. In the PDT-regressive sites, within 800 μm of the dermal-epidermal junction, the dilated vessels were occluded and remained fissure-like after PDT. Conclusions: When the vascular lesions within 800 μm of the dermal-epidermal junction were closed after PDT, a stable clinical cure (no recurrence) was achieved.

As an important basis for lesion determination and diagnosis, medical image segmentation has become one of the most important and hot research fields in the biomedical field, among which medical image segmentation algorithms based on full convolutional neural network and U-Net neural network have attracted more and more attention by researchers. At present, there are few reports on the application of medical image segmentation algorithms in the diagnosis of rectal cancer, and the accuracy of the segmentation results of rectal cancer is not high. In this paper, a convolutional network model of encoding and decoding combined with image clipping and pre-processing is proposed. On the basis of U-Net, this model replaced the traditional convolution block with the residual block, which effectively avoided the problem of gradient disappearance. In addition, the image enlargement method is also used to improve the generalization ability of the model. The test results on the data set provided by the "Teddy Cup" Data Mining Challenge showed that the residual block-based improved U-Net model proposed in this paper, combined with image clipping and preprocessing, could greatly improve the segmentation accuracy of rectal cancer, and the Dice coefficient obtained reached 0.97 on the verification set.

Objectives: The mammalian tongue develops from the branchial arches (1-4) and comprises highly organized tissues compartmentalized by mesenchyme/connective tissue that is largely derived from neural crest (NC). This study aimed to understand the roles of tumour suppressor Neurofibromin 2 (Nf2) in NC-derived tongue mesenchyme in regulating Hippo signalling and cell proliferation for the proper development of tongue shape and size., Materials and Methods: Conditional knockout (cKO) of Nf2 in NC cell lineage was generated using Wnt1-Cre (Wnt1-Cre/Nf2 cKO ). Nf2 expression, Hippo signalling activities, cell proliferation and tongue shape and size were thoroughly analysed in different tongue regions and tissue types of Wnt1-Cre/Nf2 cKO and Cre - /Nf2 fx/fx littermates at various stages (E10.5-E18.5)., Results: In contrast to many other organs in which the Nf2/Hippo pathway activity restrains growth and cell proliferation and as a result, loss of Nf2 decreases Hippo pathway activity and promotes an enlarged organ development, here we report our observations of distinct, tongue region- and stage-specific alterations of Hippo signalling activity and cell proliferation in Nf2 cKO in NC-derived tongue mesenchyme. Compared to Cre - /Nf2 fx / fx littermates, Wnt1-Cre/Nf2 cKO depicted a non-proportionally enlarged tongue (macroglossia) at E12.5-E13.5 and microglossia at later stages (E15.5-E18.5). Specifically, at E12.5 Nf2 cKO mutants had a decreased level of Hippo signalling transcription factor Yes-associated protein (Yap), Yap target genes and cell proliferation anteriorly, while having an increased Yap, Yap target genes and cell proliferation posteriorly, which lead to a tip-pointed and posteriorly widened tongue. At E15.5, loss of Nf2 in the NC lineage resulted in distinct changes in cell proliferation in different regions, that is, high in epithelium and mesenchyme subjacent to the epithelium, and lower in deeper layers of the mesenchyme. At E18.5, cell proliferation was reduced throughout the Nf2 cKO tongue., (© 2021 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.)

Hyperpigmentation is a common complaint and distressing problem in dermatology, and tranexamic acid (TA) is an effective treatment agent but limited by the delivery to melanocytes in the epidermis. Herein, a novel TA naogels (named HA/TA-LP), combining the advantages of liposomes and hyaluronic acid (HA), are prepared and assessed for topical hyperpigmentation treatment with targeting delivery and minimizing epidermal diffusion. Morphological characteristics indicate numerous TA-loaded liposomes packed in HA gels. In vitr o cell studies using human A375 melanoma cells show that HA/TA-LP can promote the uptake of TA by targeting delivery with resulting inhibition of tyrosinase activity and melanin production. Guinea pigs are used to construct hyperpigmentation models and investigate the topical delivery and treatment efficacy of HA/TA-LP. In vivo topical delivery studies indicate HA/TA-LP realize the effective delivery into melanocytes with an ideal balance of effective permeability and minimizing epidermal diffusion. Subsequently, hyperpigmentation treatment assessments reveal that HA/TA-LP inhibit tyrosinase activity and melanin production under the radiation of UVB. Our study identifies favorable properties of HA/TA-LP for treating hyperpigmentation, and provides an experimental basis for further clinical application.

Objective: Recurrence or redarkening of port-wine stain (PWS) after laser treatment occurs frequently. Background: Vascular-targeted photodynamic therapy (PDT) is an alternative adjuvant treatment for PWS. Methods: We report the first case of PWS recurrence after PDT with a 22-year follow-up. Results: Histological analysis was performed to indicate the possible mechanisms of PWS recurrence. Conclusions: This case demonstrates the possibility of PWS recurrence and suggests that patients be notified of this possibility before treatment.

Background: Broadband light (BBL) is one of the intense pulsed light. BBL treatment for nonablative, noninvasive skin tightening and rejuvenation reportedly elicits satisfactory clinical outcomes. Up until now, self-controlled case series with objective evaluation of efficacy of facial pores in response to BBL treatment have not been reported. We aimed to assess its safety and efficacy on enlarged facial pores by objective measuring technique., Objective: To evaluate the efficacy and safety of BBL on the appearance of facial pores., Methods: 25 patients received five treatments with BBL at 2-week intervals. One split-face was treated by BBL, another split-face was untreated as a control. Objective measurements of the quantitative number of pores were calculated with a VISIA-CR imaging system. Skin elasticity, transepidermal water loss, skin sebum excretion, and skin surface hydration values were also evaluated by using an Elastimeter, Vapometer, Sebumscale, and Moisturemeter., Results: Pretreatment, the total average number of facial pores was 835.88 and 835.68 for BBL-treated facial sides and untreated facial sides, respectively ( p  = .993). These values were 801.44 and 811.8, respectively, 2 months after the final treatment ( p  = .606). There were no long-term side effects., Conclusion: BBL seems to be a safe and mildly effective approach to reduce detectable pores.

Background and Objective: The long-term efficacy of a picosecond alexandrite laser (PSAL) with a diffractive lens array (DLA) for the treatment of photoaging is absent. To observe the long-term efficacy of PSAL for the treatment of photoaging., Study Design/materials and Methods: Each patient (n = 10) received 10 treatments at 2-week intervals. One side of the face was randomly selected for treatment. At 1, 3, 6, and 36 months after the final treatment, two blinded physicians evaluated photographs with four clinical indicators of photoaging (dyschromia, skin texture, skin laxity, and rhytids). A quartile scale was used., Results: At baseline, there were no significant differences in dyschromia, skin texture, facial laxity, or rhytids between the treated and control sides (P > 0.05). Picosecond laser-treated side showed 0.85 and 1.05 (both P < 0.05) better for dyschromia at 3- and 6-month follow-up, and 0.6 (P < 0.05) better for skin texture at 6-month follow-up. At 36-month follow-up, the degree of photoaging is intensified on the control side while the rejuvenation efficacy maintained on the treated side, with 1.4, 0.75, and 0.8 (all P < 0.05) better for dyschromia, skin texture, and rhytids relative to the control side measures., Conclusion: Our results demonstrate the long-term efficacy and safety of PSAL with DLA for the treatment of facial photoaging., Limitation: Small sample size and the lack of objective evaluation. Lasers Surg. Med. © 2021 Wiley Periodicals LLC., (© 2021 Wiley Periodicals LLC.)

Background: Port-wine stain (PWS) patients may simultaneously have accompanied soft tissue hypertrophy. The outcome of laser therapy can be poor. Objective: To study the imaging and histopathological characteristics of PWS patients with facial overgrowth. Materials and methods: We retrospectively assessed the effect of therapy on a subset of PWS patients with facial overgrowth. The degree of hypertrophy and the density of enhanced signals on T1-weighted magnetic resonance imaging (MRI) were independently graded by two radiologists using a quartile scale. Biopsies/resection of tissue deep to the facial muscle was reviewed and compared with flat PWS. Results: Thirty-two PWS patients with facial hypertrophy and 15 patients with flat PWS were included. MRI revealed a statistically significant correlation between the degree of hypertrophy and the density of enhanced signals (3.02 ± 0.92 vs. 2.47 ± 0.69; p  < 0.01). Histological features of a subset of patients showed that vascular malformations existed in the dermis and also in the subcutaneous fat and muscle with much larger vessel diameters (fat, 0.048 vs. 0.020; muscle, 0.035 vs. 0.017) and thicker vessel walls (fat, 0.014 vs. 0.006; muscle, 0.010 vs. 0.006) (both p  < 0.05). Conclusions: The imaging and pathological findings indicate that capillary malformation in subcutaneous tissue might be a major cause of poor therapeutic effect of laser therapy for PWS. Clinical trial registration no.: ChiCTR1800014278.

Background: Pulsed dye laser (PDL) treatment currently represents the mainstream choice for port-wine stain (PWS) treatment in accordance with selective photothermolysis. However, most PWS lesions cannot be removed despite several treatments. Intense pulsed light (IPL) is reportedly an effective alternative to PDL for PWS treatment. No studies have thus far been reported on the combination therapy of PDL with IPL in PWS treatment., Objective: This study evaluated the efficacy and safety of PDL with IPL for PWS treatment., Methods: A total of 33 PWS lesions underwent 3 treatment sessions. Each PWS was divided into IPL + PDL, PDL, and untreated sites. Therapeutic outcomes were evaluated by visual assessment and chromametric assessment 3 months after the final treatment., Results: The overall average blanching rates were 36.2% and 32.6% at the sites treated with IPL + PDL and PDL, respectively (p > .05). No permanent side effects were reported., Conclusion: In this laser setting, although IPL + PDL is a safe and effective PWS treatment, no significant improvement in the efficacy was observed using IPL + PDL in contrast to PDL alone., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Port-wine stains (PWS) on proximal limbs respond better to pulsed dye laser (PDL) than PWS on distal limbs. Objective: To investigate whether the superiority of PDL efficacy on the proximal limbs is related to variations in blood perfusion. Methods: Patients with untreated PWS on the extremities underwent three sessions of PDL. Blood perfusion of the selected sites on both the proximal and distal limbs, as well as control sites, was detected by laser speckle imaging before treatment. After treatment was completed, the therapeutic effect was evaluated both objectively and subjectively. Results: A total of 19 patients were included. Seventeen of them presented with PWS on the upper extremities and 2 patients on the lower extremities. The mean speckle flow imaging value of the PWS on the upper arms and thighs was significantly lower [80.51 ± 16.96 perfusion unit (PU), control: 66.36 ± 13.18 PU] than that on the hands and feet (155.68 ± 71.86 PU, control: 72.82 ± 18.97 PU). Meanwhile, the average blanching rate on the proximal and distal limbs was 48.33% and 22.12%, respectively. Significant correlations were identified between blood perfusion and PDL efficacy ( r  = -0.351, p  = 0.031). Conclusions: PWS in the proximal limbs responded better to PDL than PWS on distal limbs. This variation in efficacy may be attributed to differences in blood perfusion. Clinical trial registration no. ChiCTR-OCB-15007326.

Background and Objectives: Many types of lasers have been used to treat café-au-lait macules (CALMs) since the introduction of the selective photothermolysis theory. However, the efficacy and safety of picosecond lasers, compared with those of nanosecond lasers, have not been researched. To compare the efficacy and safety of 755 nm picosecond laser (PS-755 nm), Q-switched (QS) Alexandrite 755 nm nanosecond laser (QS-755 nm), and QS Nd:YAG 532 nm nanosecond laser (QS-532 nm) for treating CALMs., Study Design/materials and Methods: Forty-one patients received several treatments at 3-month intervals. Lesions were divided into two or three approximately equal parts, which were randomly treated with PS-755 nm, QS-755 nm, and QS-532 nm. The safety and efficacy of three lasers were determined based on blinded visual assessments and self-reports of patients three months after the comparative trial., Results: Visual assessment 3 months after the comparative trial revealed that there was no statistically significant difference among the sites treated by QS-755 nm (2.84 ± 1.11), QS-532 nm (2.63 ± 1.06), and PS-755 nm (2.74 ± 1.05) lasers. Five (26.32%) of 19 patients showed lesion recurrence. Adverse effects included acneiform miliaris, hypopigmentation, and hyperpigmentation, which were resolved within 12 months. Five (26.32%) of 19 patients who showed lesion recurrence 1-5 months after laser treatment had lightened or cleared at least 50% of the lesion. 46.67% of patients were satisfied or very satisfied with the outcome of the overall treatment., Conclusions: PS-755 nm, QS-755 nm, and QS-532 nm laser treatments were equally effective in treating and improving CALMs. PS-755 nm caused fewer adverse effects. Individuals can react differently to different types of lasers. Patch tests should be conducted before the treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC., (© 2020 Wiley Periodicals LLC.)

Our lineage tracing studies using multiple Cre mouse lines showed a concurrent labeling of abundant taste bud cells and the underlying connective tissue with a neural crest (NC) origin, warranting a further examination on the issue of whether there is an NC derivation of taste bud cells. In this study, we mapped NC cell lineages in three different models, Sox10-iCreER T2 /tdT mouse, GFP + neural fold transplantation to GFP - chickens, and Sox10-Cre/GFP-RFP zebrafish model. We found that in mice, Sox10-iCreER T2 specifically labels NC cell lineages with a single dose of tamoxifen at E7.5 and that the labeled cells were widely distributed in the connective tissue of the tongue. No labeled cells were found in taste buds or the surrounding epithelium in the postnatal mice. In the GFP + /GFP - chicken chimera model, GFP + cells migrated extensively to the cranial region of chicken embryos ipsilateral to the surgery side but were absent in taste buds in the base of oral cavity and palate. In zebrafish, Sox10-Cre/GFP-RFP faithfully labeled known NC-derived tissues but did not label taste buds in lower jaw or the barbel. Our data, together with previous findings in axolotl, indicate that taste buds are not derived from NC cells in rodents, birds, amphibians or teleost fish., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Multiple lasers have been used for the treatment of café au lait macules (CALMs) with various results. Objective tools to predict therapeutic efficacy of CALMs treatment is lacking., Objective: To determine whether reflectance confocal microscopy (RCM) characteristics correlate with CALMs response to laser treatment., Materials and Methods: All CAMLs underwent RCM examination of length and density of dermal papillae followed by 3 sessions of Q-switched alexandrite laser (QSAL). A visual analog scale was used to assess clinical treatment efficacy., Results: Forty-three patients were included, 22 had CALMs with irregular borders and 21 with smooth borders. Café au lait macules with irregular border had shorter rete pegs and less papillae (p < .05) on RCM compared with smooth border CAMLs and responded better to QSAL treatment (2.32 vs 1.10)., Conclusion: Reflectance confocal microscopy measurement of length and density of papillae were inversely correlated with treatment response. Reflectance confocal microscopy may be a useful tool to predict CALMs response to laser treatment., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Cell dissociation has been an essential procedure for studies at the individual-cell level and/or at a cell-population level (e.g., single cell RNA sequencing and primary cell culture). Yielding viable, healthy cells in large quantities is critical, and the optimal conditions to do so are tissue dependent. Cell populations in the tongue epithelium and underlying mesenchyme/connective tissue are heterogeneous and tissue structures vary in different regions and at different developmental stages. We have tested protocols for isolating cells from the mouse tongue epithelium and mesenchyme/connective tissue in the early developmental [embryonic day 12.5 (E12.5)] and young adult (8-week) stages. A clean separation between the epithelium and underlying mesenchyme/connective tissue was easy to accomplish. However, to further process and isolate cells, yielding viable healthy cells in large quantities, and careful selection of enzymatic digestion buffer, incubation time, and centrifugation speed and time are critical. Incubation of separated epithelium or underlying mesenchyme/connective tissue in 0.25% Trypsin-EDTA for 30 min at 37 °C, followed by centrifugation at 200 x g for 8 min resulted in a high yield of cells at a high viability rate (>90%) regardless of the mouse stages and tongue regions. Moreover, we found that both dissociated epithelial and mesenchymal/connective tissue cells from embryonic and adult tongues could survive in the cell culture-based medium for at least 3 h without a significant decrease of cell viability. The protocols will be useful for studies that require the preparation of isolated cells from mouse tongues at early developmental (E12.5) and young adult (8-week) stages requiring cell dissociation from different tissue compartments.

Objective: The objective of this study was to retrospectively review the clinical and radiographic outcomes of patients with venous malformations (VMs) treated with bleomycin-polidocanol foam (BPF) sclerotherapy., Methods: The Institutional Review Board waived ethical approval for this retrospective review in which 55 patients (31 female and 24 male patients; mean age, 18.8 years; range, 2-60 years) were treated with BPF sclerotherapy. The stability (half-life) of BPF compared with polidocanol foam was studied. Standard sclerotherapy techniques were used. A total of 111 sclerotherapy sessions were performed, with a mean of 2.0 treatments per patient (range, 1-6). An average of 10 mL of BPF was used per procedure, with the total amount ranging from 2.5 to 30 mL. Symptoms before and after treatment, follow-up time, complications, and volume reduction on magnetic resonance imaging were recorded., Results: The median half-lives of the BPF and polidocanol foam were 238.25 ± 3.86 seconds and 194.33 ± 3.5 seconds, respectively. A t-test indicated significant differences between the groups (P < .01). The mean follow-up was 14 months (range, 6-24 months). All 55 patients (100%) reported improvement in symptoms. The total excellent and good response rate was 94.6%. An excellent response was achieved in 32 cases (58.2% [32/55]), a good response in 20 cases (36.4% [20/55]), and a poor response in 3 cases (5.4% [3/55]). Postprocedural magnetic resonance imaging demonstrated volume reduction of treated lesions in 54 of 55 patients (98%), with a mean lesion volume reduction of 84.6%. Postprocedure complications were minor in 13 of 111 procedures (12%) that were performed on 10 of 55 patients (18.2%), and no major complications occurred., Conclusions: BPF sclerotherapy of VMs is safe and effective. BPF sclerotherapy can be a promising first-line treatment of VMs., (Copyright © 2020. Published by Elsevier Inc.)