PURPOSE:To assess the efficacy and safety of 'fractional' long-pulsed Nd:YAG (FLP-Nd:YAG) for the treatment of severe diffused glans penis venous malformations (GPVM). METHODS:Thirteen patients (Age 1.2-29 years) with diffused GPVM were enrolled in this study from August 2013 to January 2025. Twelve patients except one young male with erectile dysfunction underwent FLP-Nd:YAG laser treatment (there were intervals between circular spots). Outcome was graded using a five-point scale, and complications were documented after each session. RESULTS:Ten patients reached a 'nearly cured' status, and two patients achieved an 'excellent' outcome. The mean number of sessions was 3.2 (range 2 ∼ 5). Symptoms were significantly alleviated following treatment. The minor complications were blister formation or thin crusting (n = 4), temporary hyperpigmentation (n = 5), superficial scars (n = 2), and mild hypesthesia (n = 1). Major complications included localized tissue depression (n = 1) and long-term fibrous nodules (n = 1). All patients were followed up for 4 to 11 months. Mild recurrence was observed in three cases. CONCLUSION:FLP-Nd:YAG laser therapy achieved high lesion clearance rates with low incidence of major complications in severe diffused GPVMs. It offered rapid treatment with a noninvasive, bloodless procedure, making it especially suitable for pediatric patients.

BACKGROUND:Tattoo removal has advanced with the introduction of picosecond laser technology, offering theoretical advantages over traditional nanosecond approaches. However, high-level clinical evidence comparing these modalities utilizing 755-nm alexandrite lasers is lacking. METHODS:A prospective, randomized, split-tattoo trial was performed in 30 subjects with professional (53.3%), amateur (33.3%), or cosmetic (13.3%) black/blue tattoos. Each tattoo was divided, with one half treated using a 755-nm picosecond alexandrite laser (PSAL) and the other with a nanosecond alexandrite laser (NSAL). Treatments were performed at 3-month intervals for five sessions, with 6-month follow-up. The primary outcome was clearance score on a 10-point visual analogue scale (VAS). Secondary endpoints included proportion achieving satisfactory clearance (VAS ≥7), pain, and adverse events. RESULTS:PSAL achieved higher clearance scores versus NSAL (8, IQR: 6-9 vs. 5, IQR: 2.75-6.25; p < 0.0001) and greater rates of satisfactory clearance (73.3% vs. 23.3%; p = 0.0003). Complete clearance occurred in 10% of PSAL-treated sites versus none with NSAL. Pain scores were lower with PSAL (5, IQR: 3-6 vs. 5, IQR: 3-7, p = 0.023). Acute complication rates were reduced in PSAL versus NSAL: bleeding (2% vs. 8%, p = 0.031), blistering (7.33% vs. 15.33%, p = 0.044), and crusting (7.33% vs. 15.33%, p = 0.044), but hyperpigmentation occurred more frequently (21.33% vs. 12%; p = 0.043). CONCLUSIONS:The 755-nm PSAL significantly outperforms NSAL for tattoo removal. Optimization of pulse parameters may further improve outcomes and minimize pigmentary sequelae.Trial Registration: Chinese Clinical Trial Registry (https://www.chictr.org.cn/) identifier: ChiCTR2300069281.

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant multisystem disorder caused by NF1 gene variants. Although NF1 shows marked clinical and genetic heterogeneity, large Chinese cohorts integrating clinical features, NF1 variant spectrum, and external variant contextualization remain limited. We conducted a cross-sectional study of 847 clinically confirmed Chinese patients with NF1 to characterize demographic features, clinical manifestations, DNB-defined severity, and NF1 variant spectrum. Whole-exome sequencing was performed in 211 patients. Transcript-level variant distribution was assessed using a 500-bp sliding-window approach and further contextualized using ClinVar-derived NF1 variant data. Among 847 patients, the median age was 23 years, 27.5

Background: As the body’s first line of defense against environmental stressors, the skin is highly susceptible to UVB-induced damage, which triggers inflammation and impairs barrier function. This study investigates the protective effects of safflower seed oil (SSO) and fermented Artemisia annua oil (FAAO) against UVB-induced skin injury. Methods: The protective effects of SSO and FAO against UVB irradiation was first tested in HaCaT keratinocyte. Subsequently, a UVB-irradiated SKH-1 mouse model was established to evaluate these two oils. RNA-seq analysis was employed to investigate the potential molecular mechanisms by which SSO and FAO repair the skin barrier. Results: In vitro experiments demonstrated that SSO (0.25%) and FAAO (0.1%) significantly enhanced HaCaT keratinocyte viability following UVB exposure while selectively modulating pro-inflammatory cytokine production. In a UVB-irradiated SKH-1 mouse model, standalone SSO or FAAO treatment partially ameliorated epidermal hyperplasia and restored UV-reduced collagen content, while the 1:1 SSO/FAAO combination exhibited superior efficacy in restoring skin architecture, reducing erythema and edema, and suppressing immune cell infiltration. Transcriptomic profiling revealed that the combined treatment promoted structural repair by attenuating inflammatory responses and preserving extracellular matrix homeostasis. Conclusions: Together, these findings underscore the potential of SSO/FAAO as a multifunctional botanical intervention for mitigating UVB-induced cutaneous damage.

This article reviews the evolving role of laser therapy in the management of vascular anomalies, emphasizing advances in selective photothermolysis, wavelength optimization, pulse modulation, and epidermal cooling that have improved treatment precision and safety. It outlines the principles of laser-tissue interaction and discusses how different laser systems, including pulsed dye laser, Nd:YAG, alexandrite laser, and IPL, are tailored to lesion depth and vascular characteristics. The article further examines lesion-specific management strategies for infantile hemangiomas and port-wine capillary malformations, highlighting indications, outcomes, limitations, and multimodal approaches. Emerging therapies such as photodynamic therapy are also discussed as promising options for resistant vascular lesions.

Background/Objectives: Androgenetic alopecia (AGA) is the most common hair loss disorder in dermatological practice. Its primary pathogenesis involves the conversion of testosterone to dihydrotestosterone (DHT) by type II 5α-reductase upon reaching dermal papilla cells (DPCs). DHT impairs DPCs’ activity and inhibits hair growth. Although the FDA-approved drugs finasteride and minoxidil show certain efficacy, they are also associated with severe side effects. This study aims to explore the effects of Terminalia chebula fruit extract (TCFE) on hair growth and its underlying molecular mechanisms. Methods: We investigated the therapeutic potential of TCFE in hair follicle regeneration, employing a multi-level experimental approach combining in vitro analyses of DPCs, in vivo animal models of AGA, and ex vivo cultures of human hair follicles and scalp tissue. Results: First, RNA-seq analysis and RT-PCR validation revealed that TCFE treatment activated the Wnt and TGF-β3 signaling pathways in DPCs, particularly upregulating the AKR1C gene family, which is involved in DHT metabolism. TCFE also potently inhibited type II 5α-reductase activity and mitigated DHT-induced damage to DPCs. In an AGA mouse model, TCFE reversed the AGA phenotype with efficacy comparable to finasteride. However, unlike finasteride, TCFE specifically enhanced the expression of AKR1C1 and AKR1C3, indicating a distinct mechanism. Finally, in ex vivo organ cultures, TCFE suppressed hair follicle cell apoptosis, promoted proliferation, and thereby stimulated hair growth. Conclusions: These findings suggest that TCFE is a promising natural treatment for AGA, likely acting through multiple mechanisms, including Wnt pathway activation, 5α-reductase inhibition, and enhanced DHT degradation.

Background Photodynamic therapy (PDT), an emerging treatment modality for port-wine stains (PWS) alongside pulsed dye laser (PDL) therapy, currently lacks clear guidelines regarding the optimal number of treatment sessions. In recent clinical practice, we found that for patients presented poor efficacy to initial PDT sessions, subsequent session exhibited significantly better efficacy than preceding ones. We termed this phenomenon "delayed cumulative response" (DCR). This study was to introduce and summarize the DCR for the first time, and to provide evidence for its existence, explore potential mechanisms. Methods We conducted a retrospective study based on clinical data analysis of 80 PWS patients, comparing the efficacies between the session that performed DCR and the session before DCR, identifying influencing factors, and analyzing related pathological results. Results All lesions were located on the head, face, and neck. Patients typically experience DCR at the 2.79th ± 0.74th PDT session. The clearance rate of DCR session markedly increased from 21.71% in the previous session to 59.43%, while the VAS score rose from 1.27 to 2.75. Patients with PWS lesions involving single site were more prone to experiencing DCR. Conclusion DCR phenomenon was observed in the PDT treatment of PWS. We defined DCR as a situation where the initial PDT sessions show limited efficacy (less than 25% improvement), followed by a subsequent session with significant efficacy (greater than 50% improvement). For patients with poor initial responses to PDT, we recommended scheduling at least 3 treatment sessions to achieve 60% clinical improvement.

IntroductionInfantile hemangioma (IH) is a common benign vascular tumor characterized by a proliferative phase followed by regression. N6-methyladenosine (m6A) methylation, a major RNA modification, plays a critical role in tumor development, though its function in IH remains unclear.MethodsThis study analyzed six IH samples (three from proliferative IH, three from involuting IH), using transcript-specific microarrays after m6A immunoprecipitation to explore dynamic methylation changes and their regulatory impact on gene expression.ResultsResults showed significantly lower m6A levels in involuting-phase hemangiomas. Differentially methylated genes (DMGs) were mainly involved in biological processes such as cell-cell junction and cell-matrix adhesion. KEGG pathway analysis revealed DMGs were enriched in MAPK, Calcium, and PI3K-Akt signaling pathways, suggesting that m6A modifications are closely linked to angiogenesis and tumor growth. MeRIP-qPCR showed that IGF1 and IGF2 exhibiting significant correlation in both m6A levels and expression. The overall downregulation of m6A modification for lncRNA and sncRNA suggested active demethylation processes may involve in involution of IH.DiscussionOverall, this study demonstrates that m6A methylation modulates key cellular pathways in IH progression and may serve as a promising target for future diagnostic and therapeutic strategies.

Reactive oxygen species (ROS) have double-edged effects on skin, serving as signaling molecules at low levels and inducing oxidative damage when overproduced. Synthetic antioxidants are extensively used but often induce skin irritation and provide temporary benefits. Microalgae and cyanobacteria synthesize a large variety of bioactive molecules with high antioxidant activities, such as carotenoids, polysaccharides, phycocyanin, polyphenols, mycosporine-like amino acids (MAAs), and scytonemin. These molecules exhibit multiple modes of actions: direct scavenging of ROS and metal ions, activation of endogenous antioxidant system, and modulation of expression of oxidative enzymes. Moreover, these antioxidants provide additional advantages in combating skin damages by alleviating inflammation, inhibiting matrix metalloproteinases (MMPs), suppressing tyrosinase to inhibit hyperpigmentation, and enhancing skin hydration and repair. These ingredients are commercially available in moisturizers, anti-aging cosmetics, sunscreens, and therapeutic formulations. However, challenges still exist in large-scale production, extraction methods, bioavailability, biosafety, and rigorous clinical validation. In conclusion, microalgae and cyanobacteria are a promising resource of multifunctional antioxidants that can meet the modern cosmetic needs as well as the “clean beauty” concept. Further studies should focus on technological inventions in processing and delivery systems, and large-scale clinical trials to fully harvest their potential in dermatology and cosmetics.

BACKGROUND:Despite ongoing advancements in medical aesthetics, there remains a lack of consensus regarding a standardized postoperative care protocol following laser treatment for skin pigmentation disorders. OBJECTIVES:To evaluate the influence of postoperative facial cleansing practices on the efficacy and safety of laser therapy among patients diagnosed with pigmentary skin diseases. METHODS:Thirty patients diagnosed with pigmented lesions (freckles and/or solar lentigines) were randomly allocated to two distinct groups. Following treatment with a 755-nm alexandrite laser, patients in one group were instructed to perform water cleansing, while the other followed a water-avoidance care protocol. Follow-up visits were conducted on days 1, 3, 7 and 14 after treatment and 3 months postoperatively. These visits included taking standardized photographs, performing VISIA imaging assessments, collecting patient satisfaction questionnaires and recording any potential adverse events. RESULTS:No serious complications were reported in either group. Most patients demonstrated improvement in their lesions to varying degrees with a single treatment session. No statistically significant differences were identified between the two groups in terms of postoperative visual analogue scale scores (P = 0.17). VISIA analysis revealed a significant decrease in brown spot count in both groups at the 3-month follow-up compared with baseline, with no significant differences between groups (P = 0.99). The average score of patients' satisfaction in the water-cleansing group was significantly higher than that in the water-avoidance group (P = 0.039). CONCLUSIONS:Our studies have demonstrated that laser treatment of epidermal hyperpigmentation disorders without strict water avoidance can have equally good results with no added adverse effects.

PHACE syndrome is a neurocutaneous syndrome characterized by large facial segmental hemangiomas as the most typical manifestation. Its prevalence in East Asian is not well studied. The retrospective study included 98 infants with facial segmental hemangiomas who underwent brain MRI/MRA, cardiac ultrasound, and ophthalmology examinations. The prevalence along with documentation of its clinical characteristics of PHACE syndrome was analyzed. Among 98 patients, 5 (5.1%) were diagnosed with “definite” PHACE, while none (0.0%) exhibited “possible” PHACE. Most patients with PHACE syndrome had 2 or more segments, of which the frontotemporal segment was most frequently involved. Structural brain anomalies were identified in two patients, four exhibited cerebrovascular anomalies, four displayed cardiovascular anomalies, and two presented ocular anomalies. Following standardized oral propranolol therapy, all patients showed significant regression. One patient received laser treatment for a residual hemangioma. The prevalence of PHACE syndrome in facial segmental hemangiomas was 5.1%, predominantly characterized by anomalies in the cerebrovascular and cardiovascular systems. Collaborative multidisciplinary diagnosis and treatment are critical for PHACE patients.

Abstract Background Adaptive metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis in hypoxia plays a protective role in cardiomyocyte survival by reducing reactive oxygen species (ROS) and increasing ATP. Cytoplasmic polyadenylation element binding protein 3 (CPEB3) influences protein translation by modulating 3' untranslated region (3'UTR) lengths through alternative polyadenylation (APA). However, the role of CPEB3 in cardiomyocyte after myocardial infarction (MI) remains unknown. Purpose This study aims to explore the function of CPEB3 in cardiomyocyte after MI. Methods Three GEO databases of mice MI (GSE110209, GSE114695 and GSE236374) were analyzed to identify CPEB3 dysregulation. Cardiomyocyte-specific CPEB3 knockout mice and CPEB3-knockdown neonatal mouse cardiomyocytes (NMCMs), RNA sequencing, flow cytometry, TUNEL staining, Seahorse, ROS and ATP measurements were used to investigate the impact of CPEB3. APA events analysis, RIP sequencing, CUT-TAG, 3’RACE, polysome profiling and dual luciferase report were performed to elucidate the mechanisms of CPEB3. Recombinant adeno-associated virus carrying cardiac troponin T promoter was used to evaluate the therapeutic efficacy of CPEB3 in mice with MI. Results CPEB3 expression was markedly reduced in the heart tissue after MI and in NMCMs after hypoxia. Cardiomyocyte-specific CPEB3 deletion aggravated cardiomyocyte apoptosis, enlarged infarct size, and exacerbated cardiac injury after MI. RNA sequencing revealed that CPEB3 deficiency predominantly inhibited glycolysis-related pathway, with a notable decrease in pyruvate dehydrogenase kinase 1 (PDK1) expression. In CPEB3-knockdown NMCMs, adaptive metabolic reprogramming from OXPHOS to glycolysis and ATP level were decreased in hypoxia, whereas ROS production was significantly enhanced, all of which resulted in apoptosis and were regulated by PDK1. Besides, PDK1 overexpression counteracted the effects of CPEB3 knockdown on metabolic pattern, ROS, ATP and apoptosis. Mechanistically, CPEB3 deficiency led to a shortened 3’UTR of the transcription factor forkhead box O3 (FOXO3), and a decline of FOXO3 protein level. CPEB3 protein was confirmed to directly bind to FOXO3 mRNA, and the translation efficiency of FOXO3 was decreased with CPEB3 knockdown. Furthermore, FOXO3 was found to activate the transcription of PDK1, and FOXO3 overexpression alleviated the decline of PDK1 and attenuated CPEB3 knockdown-induced apoptosis in hypoxia. Finally, cardiomyocyte-specific CPEB3 overexpression reduced cardiomyocyte apoptosis, suppressed myocardial fibrosis, and improved cardiac function by upregulating FOXO3 and PDK1 levels after MI. Conclusion CPEB3 could promote FOXO3 protein expression via APA of FOXO3 3’UTR, activate transcription of PDK1 and ultimately protect cardiomyocyte from apoptosis by restoring metabolic balance in hypoxia. CPEB3 may serve as a promising therapeutic target for cardiomyocyte apoptosis after MI.Schematic diagram

This study presents a robust setup for absolute light yield measurement across a wide dynamic range using GAGG Scintillators, which are known for their tunable light output and decay times through formula adjustments. Our system combines PMTs with reflectors and SiPINs to achieve high repeatability and stability in measuring light yields of large-range output crystals. The PMT, paired with a reflector, facilitates the relative measurements, while the SiPIN provides calibration for absolute measurements, ensuring precision across a broad spectrum of light yields. To address the impact of crystal size relative to the PMT and reflector dimensions, we conducted extensive Geant4 simulations which helped define the optimal crystal sizes for our measurement setup, offering guidelines for selecting crystal dimensions that maximize light collection efficiency. This setup aims to offer a practical reference for designing similar systems, potentially assisting in adapting this approach to various scintillation crystals.

Abstract Background Cardiac fibroblasts (CFs) play a crucial role in tissue repair and remodeling following myocardial infarction (MI). Furthermore, CFs possess the ability to sense signals of myocardial injury and secrete cytokines, thereby eliciting a pro-inflammatory response during the early post-MI phase. Our previous studies have demonstrated that CFs located in the infarcted region release small extracellular vesicles (sEVs) abundant in damaged mitochondria, termed "mt-sEVs". These mt-sEVs are internalized by macrophages, prompting the secretion of IL-6 and IL-1β via NLRP3/Caspase-1 pathway. Nonetheless, the precise mechanisms underlying the promotion of mt-sEVs release remain elusive. Objective This study aimed to investigate the pivotal genes involved in mediating the release of CFs-derived mt-sEVs, with potential implications for post-MI therapeutic strategies. Methods Primary CFs were cultured for 24 hours in sugar-free medium with 1% oxygen (OGD) in vitro. Conditioned medium was subjected to ultracentrifugation to isolate sEVs. The presence of damaged mitochondrial components within the sEVs was confirmed using Mito-tracker and nanoflowmetry. Subcellular structures were visualized via transmission electron microscopy (TEM). Protein interactions were validated through co-immunoprecipitation (co-IP) assays. CF-specific gene knockout mice were generated and subjected to MI surgery. The proportion of F4/80+/CD86+ cells was quantified using flow cytometry. Cardiac function was evaluated using echocardiography, and the extent of cardiac fibrosis was assessed via Masson staining. Results Re-analysis of single-cell RNA sequencing data (GSE153480) unveiled a significant upregulation of the mitophagy receptor Bnip3 in CF sub-populations following MI, and the up-regulated trend was also observed in OGD-CFs. Deletion of Bnip3 hindered the expression of LC3 and its co-localization with mitochondria. TEM observed extensive fusion of mitophagosomes with multivesicular bodies in OGD-CFs. Fluorescence signal detected by nano flowmetry significantly decreased in Bnip3 knockdown sEVs incubated with Mito-tracker. Bnip3 deletion in CFs resulted in a significant downregulation of the sEVs release key factor Rab27a, concomitant with a striking increase in Rab27a ubiquitination. Predicted binding sites of both Bnip3 and Rab27a with the deubiquitinase Usp7 were validated through co-IP assays. Immunofluorescence staining demonstrated the co-localization of Usp7 with Bnip3 in OGD-CFs. CF-specific deletion of Bnip3 reduced the proportion of M1 macrophages, reversed left ventricular dysfunction, and mitigated myocardial fibrosis in post-MI hearts. Conclusion Collectively, our study reveals that Bnip3-mediated mitochondrial secretory autophagy in CFs was significantly activated to drive the release of mt-sEVs. Additionally, Bnip3 interacts with Usp7 to deubiquitinate Rab27a, promoting the release of mt-sEVs in CFs, exacerbating the inflammatory response after MI.Graphical abstract

Taxol serves as an efficient natural anticancer agent with extensive applications in the treatment of diverse malignancies. Although advances in synthetic biology have enabled the de novo synthesis of taxol precursors in various microbial chassis, the total biosynthesis of taxol remains challengable owing to the restricted oxidation efficiency in heterotrophic microbes. Here, we engineered Synechocystis sp. PCC 6803 with modular metabolic pathways consisting of the methylerythritol phosphate pathway enzymes and taxol biosynthetic enzymes for production of taxadiene-5α-ol (T5α-ol), the key oxygenated intermediate of taxol. The best strain DIGT-P560 produced up to 17.43 mg/L of oxygenated taxanes and 4.32 mg/L of T5α-ol. Moreover, transcriptomic analysis of DIGT-P560 revealed that establishing a oxygenated taxane flux may enhance photosynthetic electron transfer efficiency and central metabolism in the engineered strain to ameliorate the metabolic disturbances triggered by the incorporation of exogenous genes. This is the first demonstration of photosynthetic production of taxadiene-5α-ol from CO2 in cyanobacteria, highlighting the broad prospects of engineered cyanobacteria as bio-solar cell factories for valuable terpenoids production and expanding the ideas for further rational engineering and optimization.

Abstract Purpose The adult mammalian heart has limited regenerative capacity after injury, mostly attributable to postnatal cardiomyocyte (CM) cell cycle arrest. The key to unlocking the regenerative potential of the adult hearts may lie within the developmental transitions occurring during neonatal life. Gas6, a secretory protein, stimulates the proliferation of various type cells through binding to TAM receptor family, such as endothelial progenitor cells, tumor cells, and hair follicle stem-cell. However, no study to date has studied the role of Gas6 during the proliferation of CMs. Herein, our study uncovers that Gas6 is transiently expressed during early postnatal heart and regenerative heart, and functions through intracellular pathway by regulating Yap activity to promote CM proliferation. Methods CM isolation was conducted to assess the change of Gas6 expression in both postnatal development and regenerated stages using the CM-specific Tdtomato mice. Cardiac deletion of Gas6 gene mice was used to evaluate the impaired heart regeneration. CM-specific Gas6 overexpression mice were generated using adeno-associated virus system to evaluate Gas6 pro-proliferate and protect effect after ischemic injury. Secreted signal peptide truncation (ΔSP-Gas6) and predicted functional region truncation (ΔCC-Gas6) were generated to identify the intracellular mechanism of Gas6 via Sav1/p-mst1/p-lats1/ p-yap axis. Results We found that Gas6 expression is enriched in CM4 and the expression profile correlates with the expression of the CM4 marker Acta2, as well as cell-cycle genes Mki67 and Aurora B, in individual CM. Gas6 was highly expressed in the neonatal heart and continued to increase during the neonatal heart regenerative process, but was nearly absent in the adult heart under physiological and ischemia conditions. CM-specific Gas6 deletion resulted in significantly reduced CM proliferation rate and increased CM size in P0 hearts, and congestive heart failure in P28 hearts. Conversely, sustained CM-specific overexpression of Gas6 in postnatal hearts increased CM division, elevated CM numbers, and reduced CM size; and reduced infarct scar area and enhanced cardiac function after ischemia injury. Pre-overexpression of Gas6 in adult CMs protected adult cardiac function against ischemia injury, indicated by the activation of mitosis, angiogenesis and reduced oxidative phosphorylation. In primary neonatal CMs, both Gas6 and ΔSP-Gas6promoted CM proliferation with sarcomere disassembly. Mechanistically, Gas6 interacted with Sav1to inhibit Mst1recruitment and Mst1/Lats1/Yap phosphorylation cascade, therefore, promoted Yap translocation into nucleus. Conclusions We demonstrate that Gas6 is an important intrinsic regulator of neonatal heart regeneration, which acts as a promoter of Yap transcriptional activity to enhance CM proliferation. Supplementing Gas6 in the adult heart represents a potential therapeutic approach for cardiac repair.