Background The treatment of giant condyloma acuminatum in immunodeficient children remains change. In immunodeficient children, human papillomavirus infection may progress to extensive condyloma acuminatum (CA), where 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has shown favorable tissue-sparing properties. This case aims to highlight the safety and efficacy of ALA-PDT on giant condyloma acuminatum in an immunodeficient child induced by BCL11B mutation. Methods This report examines two affected siblings presenting with combined neurological and dermatological symptoms. Clinical assessments were conducted to evaluate intellectual development and skin manifestations. Genetic testing was performed to identify underlying mutations. The CA lesions were treated with the combined regimen of liquid nitrogen cryotherapy and ALA-PDT (90 mW/cm2, 20min). Results The CA lesions achieved nearly complete resolution with an absence of notable side effects by ALA-PDT with cryotherapy. In addition, both siblings exhibited pronounced intellectual developmental disorder alongside atopic dermatitis-like lesions. Genetic analysis revealed a previously unreported pathogenic mutation in the BCL11B gene (c.1585G>T[p.Glu529*]) in both patients. The recommended diagnosis was IDDSFTA with concomitant Hyper-IgE Syndrome (HIES). Notably, the dermatological manifestations showed improvement following treatment with Dupilumab. Conclusion This case provides novel evidence supporting the safety and potential advantages of ALA-PDT for CA in the immunodeficient pediatric settings. Meanwhile, these findings deepen the understanding of the clinical implications of the neurological gene BCL11B mutation (c.1585G>T[p.Glu529*]) in skin disorders.

Microtubule-associated protein 4 (MAP4) phosphorylates and translocates to the outer mitochondrial membrane, thus promoting keratinocyte migration under hypoxia; however, the underlying mechanism remains unclear. Given that a BCL2 homology 3-like (BH3-like) domain has been previously identified in MAP4, the mitochondrial outer membrane protein BCL2 is a potential molecule for elucidating the underlying pathway of MAP4 mitochondrial translocation. HaCaT keratinocytes were subjected to hypoxia and transfected with Ad-MAP4(Glu), Ad-MAP4(Ala), or si-SIRT5 to modulate MAP4 phosphorylation and SIRT5 expression, respectively, with or without the BCL2 inhibitor ABT-199. Keratinocyte migration, autophagy, and apoptosis were assessed using scratch wound healing assays, immunoblotting, transmission electron microscopy, and transferase dUTP nick end labeling staining. The BCL2–SIRT5 interaction was evaluated using molecular docking, yeast two-hybrid screening, and confocal immunofluorescence co-localization analysis. ABT-199, a BCL2-selective inhibitor, decreased the mitochondrial content of MAP4 under hypoxia, resulting in the inhibition of keratinocyte migration, autophagy, and apoptosis. These findings suggest that phosphorylated MAP4 translocates to the mitochondria mainly via BCL2. Sirtuin 5 (SIRT5), a mitochondrial matrix protein, is a potential effector molecule because of its importance in maintaining mitochondrial homeostasis and regulating autophagy and apoptosis. Unexpectedly, BCL2 was found to interact with SIRT5 and form a functional coupling complex on mitochondria. SIRT5 knockdown greatly influenced phosphorylated MAP4-induced keratinocyte autophagy, apoptosis, and migration. MAP4 triggers the formation of the BCL2/SIRT5 functional coupling complex after its mitochondrial translocation via BCL2, thereby inducing keratinocyte autophagy, apoptosis, and migration under hypoxia. The mechanistic pathways uncovered in this study provide strategic insights into wound treatment.

Diabetic wounds, a common complication of diabetes, can elicit intricate inflammatory responses and progressive tissue damage without proper treatment. Parthenolide (PTL), a natural compound isolated from the medicinal plant feverfew (Tanacetum balsamita), possesses antitumor, anti-inflammatory, and antioxidant properties. This study seeks to elucidate the molecular mechanisms by which PTL promotes diabetic wound healing. Using network pharmacology and molecular docking, we identified TNF-α and STAT3 as potential targets of PTL. In diabetic mouse models, PTL promoted wound healing with a distinct dose-dependent effect. Both 100 µM and 200 µM PTL significantly accelerated mouse wound repair, while 50 µM PTL failed to exert stable therapeutic effects, likely due to insufficient concentration. Histological and immunological staining assays confirmed that PTL promoted wound healing by enhancing keratinocyte proliferation, angiogenesis, and the conversion of macrophages to the M2 type. Furthermore, in vitro experiments were carried out by stimulating RAW264.7 macrophages with LPS. Through CCK-8 assays, immunofluorescence staining, and Western blotting, we further demonstrated that PTL might modulate the STAT3 and TNF-α/NF-κB signalling pathways, as well as regulate phenotypic switching of macrophages in the inflammatory microenvironment. Collectively, PTL promotes wound healing in diabetic conditions, a mechanism that may be mediated by the regulation of the STAT3 and TNF-α/NF-κB signalling pathways and the facilitation of macrophage phenotypic switching to the M2 phenotype to modulate wound-site inflammatory responses. Thus, PTL emerges as a potential therapeutic candidate for improving the healing of diabetic wounds.

BACKGROUND:Mycobacteroides abscessus is a common rapidly growing non-tuberculosis mycobacteria (NTM) that exhibits resistance to most antibiotics and is associated with low cure rates, highlighting an urgent need for new therapeutic strategies. Our previous clinical study has found that ALA-PDT may represent a novel and promising approach for treating M.abscessus infection, although its precise mechanism of action remains to be elucidated. METHODS:To investigate the mechanism by which ALA-PDT kills intracellular M. abscessus, we established an intracellular infection model using THP-1 to evaluate its bactericidal effect. Subsequently, RNA-sequencing analysis and targeted in vitro experiments were performed to explore the underlying mechanisms. RESULTS:ALA-PDT significantly reduced the intracellular survival of M. abscessus in THP-1. RNA-sequencing revealed that ALA-PDT modulates multiple cellular pathways, notably inducing the upregulation of autophagy-related genes. Consistently, ALA-PDT increased autophagosome formation and LC3 expression in both infected and uninfected macrophages. The bactericidal effect of ALA-PDT against intracellular M.abscessus was markedly attenuated by an autophagy inhibitor, confirming the functional role of autophagy. In addition, ALA-PDT promoted the generation of reactive oxygen species (ROS), while a ROS inhibitor suppressed the ALA-PDT induced increase in LC3 expression and the decrease in intracellular bacterial survival. Transcriptomic analysis suggested that EP300 may play a key regulatory role in this process. In vitro experiments confirmed that ALA-PDT downregulated EP300 expression, and an EP300 activator significantly reversed the ALA-PDT-mediated increase in LC3 expression and reduction in intracellular bacteria. Finally, it was found that ALA-PDT can alter the overall acetylation levels in macrophages, pointing to a potential epigenetic mechanism. CONCLUSIONS:These findings demonstrate that ALA-PDT activates antibacterial autophagy via the ROS-EP300 pathway to eliminate intracellular M. abscessus, uncovering a potential epigenetic immune mechanism. This work provides a theoretical foundation for the clinical application of ALA-PDT in treating M. abscessus infections.

Eccrine sweat glands (ESGs) are critical organs for human thermoregulation, yet their function progressively declines with aging. This study aims to investigate the underlying mechanisms responsible for the age-related impairment of ESG function. Through comparative analysis between skin tissues from young and aged mice/human, we observed structural loosening of aged ESG and a significant reduction in the expression of extracellular matrix (ECM) components—type I and type II collagen. Further investigation revealed a significant upregulation of the inflammatory cytokine interleukin (IL)-1β and matrix metalloproteinases and proteases (MMP)-1 in aged tissues, which can modulate the collagen degradation, suggesting that ECM degradation may be regulated by an inflammatory microenvironment. To validate this hypothesis, we established a model of chronic inflammation by intradermally injecting IL-1β into the footpads of mice. The results demonstrated suppressed ESG function, structural loosening of ESG tissues, and a marked reduction of type I and type II collagen surrounding the ESGs. In summary, this study reveals that type I and type II collagen are distributed around ESGs, providing structural and functional support. The activation of the IL-1β–MMP-1 inflammatory pathway in aging may contribute to ESG dysfunction and structural disruption by degrading the collagen around ESGs.

Wound infection remains a significant clinical challenge, exacerbated by the growing prevalence of bacterial resistance due to the overuse of conventional antibiotics. Photodynamic therapy (PDT) offers a promising approach for wound sterilization that circumvents the issue of antibiotic resistance. However, conventional photosensitizers are prone to inactivation and exhibit poor retention at the wound site, limiting their clinical efficacy. To overcome these limitations, we developed a biomimetic mineralization approach to encapsulate the small-molecule photosensitizer chlorin e6 (Ce6) within magnesium phosphate nanoparticles (CMP NPs), preserving its photodynamic activity. This mineralized CMP NPs were further integrated with gelatin and natural moisturizing factor to fabricate a composite hydrogel dressing (CMP/Gel) for infected wound healing. Gelatin functions as a structural matrix that prolongs the local retention of CMP NPs, while the natural moisturizing factor enhances the hydration capacity and mechanical integrity of the dressing. Notably, magnesium ions released during the degradation of CMP NPs contribute to accelerated wound healing through multiple therapeutic effects, including antioxidant, anti-inflammatory, and pro-angiogenic activities following PDT-mediated bacterial eradication. Both in vitro and in vivo experimental results demonstrate that CMP/Gel effectively promotes infected wound repair, highlighting its potential as a novel and multifunctional therapeutic strategy for infected wound management.

BACKGROUND AND OBJECTIVES:Viral warts are benign proliferative skin lesions caused by the human papillomavirus (HPV) and are contagious among humans. Currently, there are no effective treatments to address the high recurrence rate of viral warts, presenting challenges in achieving their complete eradication. The aim of this study was to evaluate the efficacy and safety of curettage combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of recalcitrant acral warts. METHODS:Our study was carried out between July 2023 to June 2025, and the clinical data of 50 patients diagnosed with acral warts were retrospectively collected. Patients were assigned to the curettage group (n = 24) or the combination group (n = 26) based on whether they received photodynamic therapy after curettage. The clinical response effects, recurrence rate and adverse reactions of the two groups were observed and compared. RESULTS:The cure rate in the combination group was 80.8% (21/26), which was significantly higher than 45.8% (11/24) in curettage group. The recurrence rate in the combination group was 19.2% (5/26), which was lower than 54.2% (13/24) in curettage group (P < 0.05). After three months of follow-up, moderate pain was the main adverse reaction in both groups, and no systemic adverse reactions were observed. CONCLUSION:Our results suggest that curettage combined with ALA-PDT is promising as a safe and effective therapy for patients with recalcitrant acral warts.

Background and ObjectiveAcne vulgaris is a prevalent dermatological condition with significant psychosocial impacts. While Photodynamic Therapy (PDT) has emerged as a promising non-invasive treatment, the global research landscape, particularly the shifts in immune mechanisms and clinical applications over the past two decades, lacks a comprehensive quantitative synthesis. This study aims to map the evolving intellectual structure and developmental trajectory of PDT for acne research from 2006 to 2026.MethodsA bibliometric analysis was conducted using data sourced exclusively from the PubMed database. The R package bibliometrix was employed to analyze annual output, geographic distribution, institutional collaboration, authorship networks, and keyword dynamics. To ensure data integrity amidst the "Time Lag" of database indexing, a "Lag Window" adjustment was applied, focusing on publications available online before April 1, 2026.ResultsThe analysis included 361 documents, revealing a 50-fold increase in publication volume, peaking in 2024. A distinct "dual-core" structure was identified: China dominates large-scale clinical validation and output, while the United States leads in fundamental photochemical innovation. Keyword burst analysis highlighted a paradigm shift from empirical methodology towards mechanism-driven research. Notably, "Animals" (2024–2026) and "Prospective Studies" (2023–2024) emerged as the strongest burst terms, indicating a surge in preclinical safety validation (often linked to nanotechnology) and rigorous clinical trial designs.ConclusionThe field of acne PDT is maturing from a clinical specialty into a mechanism-driven discipline. The integration of nanotechnology has transitioned from a distinct research hotspot into an "invisible" engineering infrastructure. Future advancements require bridging the gap between China's clinical scale and the US's fundamental innovation to optimize PDT as a precision, mechanism-based therapeutic strategy.

Tissue function and homeostasis are sustained through dynamic interactions between resident cells and their surrounding microenvironment. In the skin, these niche-specific signals coordinate epithelial metabolism and secretory activity. Although reduced sweating is a widely recognized phenomena of aging, the cellular and molecular mechanisms underlying eccrine sweat glands decline, particularly those involving age-associated niche remodeling, remain poorly understood. In this study, we combine multiomics profiling with functional assays to define an immune-epithelial circuit that governs sweat gland metabolism and is disrupted during aging. Spatial transcriptomics, single-cell RNA-sequencing, and immunostaining of aged murine paw and human palm skin reveal that structural shrinkage of eccrine sweat glands, elevated senescence-associated secretory phenotype factors, and dendritic cells (DCs) around sweat gland coils (SGCs) were significantly reduced. In youthful skin, DCs support sweat secretion by promoting oxidative phosphorylation SGCs through nicotinamide phosphoribosyltransferase-insulin receptor signaling. However, this signaling axis was perturbed with aging where SGCs secreted macrophage migration inhibitory factor, which signaled through major histocompatibility complex class II invariant chain (CD74) to impair the expression of lysosomal membrane protein and lysosomal protease in DCs through cytochrome b-245 beta chain, exacerbating DC dysfunction and reinforcing a deteriorating glandular niche. Our findings identify DCs as guardians of SGC metabolic homeostasis, revealing a reversible niche-dependent mechanism through DC-SGC crosstalk that drives age-related glandular decline.

Nail lichen planus is a chronic inflammatory condition that may be isolated to the nail, resulting in longitudinal nail ridging, trachyonychia, and splinter hemorrhages, and may be highly refractory to conventional treatment. The management of nail lichen planus remains challenging because of the lack of standardized treatment guidelines, and the efficacy of existing therapies, both topical and systemic, is often inconsistent or unsatisfactory. Emerging reports have suggested that abrocitinib, a selective Janus kinase 1 inhibitor, may be safe and effective in treating severe nail lichen planus. This report describes the case of a woman in her late 40s with refractory nail lichen planus who was successfully treated with abrocitinib.

Significance The need for innovative, antibiotic-independent antibacterial strategies is urgent. Our study offers a comprehensive approach to infected wound management. Approach We synthesized ICG@Fe-Qu via a one-step process and characterized them. Subsequent assessments focused on the photodynamic and photothermal properties of nanoparticles, which are pivotal for their therapeutic potential. The in vitro antibacterial efficacy of ICG@Fe-Qu was rigorously tested against common bacterial pathogens, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Furthermore, the in vivo antibacterial effectiveness of the nanoparticles was evaluated using a mouse model featuring wounds. Results ICG@Fe-Qu+NIR demonstrated a 90% inhibition rate against S. aureus and E. coli, with significant wound area reduction and accelerated healing in vitro and in vivo. Conclusions ICG@Fe-Qu presents proven efficacy in vitro and in vivo, as a leading candidate for clinical translation in wound care.

Protein S-palmitoylation is a pivotal yet poorly integrated research field in dermatology. This reversible post-translational lipid modification primarily occurs on cysteine residues and is principally catalyzed by zinc finger and Asp-His-His-Cys DHHC-domain containing proteins (zDHHCs). The S-palmitoylation/depalmitoylation cycle directly affects protein localization, trafficking, stability, and protein–protein interaction, thereby regulating a variety of signaling pathways, including those mediating inflammation and immune reaction. Accumulating evidence has indicated that S-palmitoylation regulates various skin biological functions, including skin inflammation, skin barrier function, hair growth, and melanin synthesis, and is ultimately implicated in the initiation and development of massive dermatoses, such as alopecia and psoriasis. The recent development of new research tools, coupled with S-palmitoylation’s therapeutic potential, makes the timely synthesis of its role in skin pathophysiology both critical and opportune. Here, we summarize recent advances in understanding the mechanistic roles of S-palmitoylation in dermatological conditions and evaluate its potential as a therapeutic target for innovative treatment strategies.

Mycobacteroides abscessus poses a considerable and growing threat to public health due to its resistance against most antibiotics and low cure rate. For a comprehensive understanding of the genomic characteristics and drug resistance mechanisms of M. abscessus, clinical isolates from diverse sources were collected and analyzed. The clinical M. abscessus complex analyzed herein primarily comprised two subspecies: Mycobacteroides abscessus subsp. abscessus and Mycobacteroides abscessus subsp. massiliense. Furthermore, comparative genomic and single nucleotide polymorphism analyses revealed distinct metabolic activities among subspecies. Subsequent examination of core hub gene mutations confirmed the presence of distinct metabolic and biosynthetic pathways between M. abscessus subspecies, which may have contributed to their differential drug resistance and may aid in providing targeted interventions. Understanding this subtle genomic variation is crucial for improving treatment strategies and patient outcomes. Additional analyses identified potential novel amikacin and moxifloxacin resistance genes, offering a promising avenue for investigating M. abscessus drug resistance. Through comparative genomic analysis, we revealed the unique metabolic activities of M. abscessus subsp. abscessus and M. abscessus subsp. massiliense, providing a scientific basis for future diagnostic and personalized management strategies. Identifying possible novel amikacin and moxifloxacin resistance genes within these subspecies offers insights for future drug development efforts and enhances our understanding of the mechanisms underlying M. abscessus drug resistance.

The differentiation of skin dermal fibroblast into myofibroblast is a critical process in tissue repair and granulation tissue formation, directly affecting the progression of wound healing. While autophagy has been implicated in regulating dermal fibroblast differentiation during wound repair, the underlying molecular mechanisms remain incompletely defined. In the current study, Transforming Growth Factor-Beta 1 (TGFβ1) was applied to induce the differentiation of skin dermal fibroblast into myofibroblast. We demonstrated that the activation of autophagy by TGFβ1 stimulation and p38 Mitogen-Activated Protein Kinase (p38/MAPK) coincided with an increase in stathmin expression. Moreover, the inhibition of p38/MAPK, transfection of small interfering RNA of stathmin or beclin1 significantly suppressed autophagy and differentiation of skin dermal fibroblast into myofibroblast. In contrast, p38/MAPK activation or stathmin overexpression, led to autophagy induction and fibroblast differentiation under TGFβ1 stimulation. Our findings elucidate a novel role of stathmin in regulating differentiation of skin dermal fibroblast into myofibroblast, and suggest its potential as a therapeutic target for clinical wound healing interventions.

BACKGROUND:Wound healing is a complex process, and numerous factors affect the healing of skin ulcers. OBJECTIVES:In order to identify the factors associated with wound healing, it is necessary to establish a visualized predictive model for evaluating the risk factors of patients with skin ulcers and to validate its effectiveness. METHODS:A retrospective observational study was conducted on 453 patients with skin ulcers admitted to the Dermatology ward of the Army Medical Center (Daping Hospital) in Chongqing, China, from January 2011 to July 2022. The nomogram was formulated according to a multivariate logistic regression analysis identifying seven potential predictors of prognosis, including age, area, pre-admission course, etiology, diabetes, medical treatment, and self-medication. This nomogram model was validated by bootstrap internal validation (1000 replicated samplings). RESULTS:Logistic regression analysis showed that age, skin ulcer area, pre-admission course, etiology, comorbidity of diabetes, medical treatment, and self-medication were independently related to skin ulcer prognosis. These indicators were utilized to develop nomogram models. The predictive ability for skin ulcer prognosis was 0.814 based on the area under the curve values. The calibration curve showed a close match between the actual and predicted probabilities. Decision-making analysis demonstrated the clinical application value of this nomogram. CONCLUSION:The prediction nomogram developed in this study exhibits good accuracy in predicting the risk factors of skin ulcers and provides an objective tool for clinical staff to assess and target the risk factors concerning the prognosis of skin ulcers.

Sweat glands (SGs) play pivotal roles in systemic and skin homeostasis. However, due to the extremely limited regenerative capacity of SGs, burns and traumas often result in irreversible SGs loss. Recent advancements in three-dimensional (3D) cell culture technology and stem cell research have highlighted the potential of organoid technology in regenerative medicine. This review summarizes the molecular regulatory mechanisms underlying SG development and focuses on the latest progress in sweat gland organoid (SGO) construction. By examining various cell sources, including SG stem cells, mesenchymal stem cells (MSCs), and reprogrammed cells, as well as the influence of 3D culture microenvironments on SGO assembly, we highlighted the promising applications of SGOs in post-burn SG regeneration. Despite challenges in cell induction efficiency and functional reconstruction, SGO technology offers a novel therapeutic strategy for restoring SG function in burn patients.

Significance Bacterial wound infections are a global health crisis, worsened by antibiotic resistance. PS-loaded hydrogels offer a promising alternative, using PS to combat infections without antibiotics, aligning with global health goals to curb resistance. Approach This review systematically assesses the role of PS-loaded hydrogels in bacterial wound treatment, synthesizing literature from multiple databases. It details PS design, hydrogel formulation, and integration techniques, focusing on their synergistic potential in PDT. Results PS-loaded hydrogels show robust antibacterial activity and overcome PS limitations, with hydrogels enhancing PDT efficacy, offering targeted treatment and real-time imaging. Conclusions PS-loaded hydrogel dressings are a strategic approach to bacterial infections, particularly in wounds. They reduce PS dosage, lower resistance risks, and mitigate phototoxicity. A decade of development positions them as a mature alternative in bacterial treatment, with promising clinical prospects.

The sequences of the shRNA and siRNA oligonucleotides are listed.