Hair follicle (HF) stem cells are multipotent adult stem cells that play a key role in the hair follicle cycle. However, it remains poorly understood how the outer root sheath (ORS)-specifically, the stem cells in the bulge region of the hair follicle-promotes skin repair. This study aims to investigate the role of bulge stem cells in tissue growth and repair and to determine whether the ORS of transplanted hair follicles can facilitate skin repair. We further seek to elucidate the mechanisms by which bulge stem cells contribute to hair follicle development, regeneration, and skin wound healing. In this study, hair follicle samples were obtained from neonatal mice using microdissection. Hair follicle morphology was assessed by Sirius red staining, H&E staining, and transmission electron microscopy. Immunofluorescence staining was used to detect changes in CD34 and SOX9 protein expression. Additionally, microdissection-based hair follicle transplantation and Western blotting were employed to investigate protein activation and inhibition in the Wnt/β-catenin signaling pathway. The results show that the hair follicle bulge, inner root sheath, and dermal papilla all increase in size as hair follicles grow, with each structure growing relatively rapidly on day 7. Treatment with Teplinovivint effectively inhibits the expression of Wnt/β-catenin signaling pathway-related proteins and hair follicle stem cell markers. Damaged hair follicle tissues cultured in vitro are capable of self-repair. At the transplantation site, the skin gradually closes as the outer root sheath wound heals. In contrast, the central region of the outer root sheath becomes progressively filled with numerous dividing cells and extracellular matrix. The inner portion of the outer root sheath is densely populated with cells, and the markers CD34 and SOX9 are also widely distributed. This indicates that activation of the Wnt/β-catenin signaling pathway enhances the proliferation and differentiation of hair follicle stem cells, thereby promoting hair follicle growth, repair of damaged follicles, and healing of skin wounds. Furthermore, this study demonstrates the feasibility of using transplanted outer root sheath (ORS) to repair skin wounds-specifically, the potential to achieve large-scale hair regeneration from a limited number of hair follicle stem cells-providing a new approach for the clinical treatment of skin injury disorders. Nevertheless, achieving long-term, stable, and scalable clinical translation of ORS stem cells for hair follicle regeneration remains a major challenge.
Stem cells and their paracrine factors hold promise for alopecia treatment, yet research on human skin-derived precursors (hSKPs), which are closely related to hair follicles in biological positioning and function, remains limited. We demonstrated that extracellular vesicles of human transformed skin-derived precursors (htSKP-EVs), harvested utilizing our directed induction, culture transition and gradient ultracentrifugation technology, exhibited superior efficiency and quality determined by transmission electron microscopy, nanoparticle tracking analysis, and detection of specific markers. Using CCK8, scratch assay, immunofluorescence, H&E staining, immunohistochemistry staining, dermoscope, qRT-PCR and Western blotting, it was found that htSKP-EVs significantly promoted the proliferation of hair follicle stem cells (hHFSCs) by effectively modulating the Wnt signaling pathway, thereby enhancing overall hair follicle growth. Notably, miR-221-3p, highly expressed in htSKP-EVs, suppressed DKK2 expression, activated the Wnt pathway in human dermal papilla cells (hDPCs), and induced hair follicles to enter and sustain the anagen phase, based on the aforementioned similar in vivo and in vitro experiments. These findings, validated in hHFSCs, hDPCs and human hair follicles in vitro and in a murine alopecia model in vivo, revealed the potential mechanism of htSKP-EVs in hair growth and identified a new therapeutic target for alopecia in regenerative medicine.
Root hairs are specialized extensions of root epidermal cells that allow plants to explore and attach to the soil. They exhibit polar growth under the influence of isotropic turgor pressure thanks to the anisotropic nature of their cell walls. This unidirectional growth is regulated by myriad subcellular factors such as microtubule and actin dynamics, a tip-focused calcium gradient, and the interplays between gradients of apoplastic and cytosolic pH and reactive oxygen species. All these players also influence cell wall dynamics by forming feedback loops that modulate cell wall assembly and modification, which are essential processes for root hair morphogenesis. In this review we discuss the functions of cell wall polysaccharides and proteins and their impacts on the biomechanics of root hair growth at each developmental stage. We also discuss important open questions and technical advancements in studying root hair mechanobiology. Despite significant progress, many of the spatiotemporal changes that occur in the cell walls of root hairs remain undiscovered. Therefore, we highlight ongoing research and exciting future avenues that will shed light on cell wall dynamics, biomechanics, and mechanobiology of root hair morphogenesis.
Instrumental methods for measuring hair volume can detect physical differences that are not perceptible to consumers, creating a disconnect between in-vitro measurements and real-world perception. This study aimed to establish the Just-Noticeable Difference (JND) for hair volume and to develop a predictive model incorporating hair waviness to better align instrumental data with sensory evaluation. Bulk volume and waviness were quantified from hair swatches using a custom image-analysis framework. Volume was determined via pixel intensity-based fibre density classification, while waviness was derived from an amplitude-frequency analysis of the detrended medial axis. Sensory evaluation was conducted by an expert panel across controlled four-swatch sets with defined volume differences (ΔV ≈ 5, 3 and 2 cm2). Mean sensory rank was used as the primary perceptual metric. A multivariable Ordinary Least Squares regression model was developed and validated using Leave-One-Group-Out Cross-Validation across 35 independent sets. A perceptual threshold of ΔV ≈ 3 cm2 was identified as the JND for hair volume. At ΔV ≈ 5 cm2, instrumental and sensory rankings were in strong agreement, whereas at ΔV ≈ 2 cm2, perceptual discrimination failed. Regression analysis confirmed bulk volume as the dominant predictor of perceived volume (β = 0.798, p < 0.001), with waviness providing a significant secondary contribution (β = 0.135, p = 0.005; Adjusted R2 = 0.660). A waviness correction factor (k ≈ 0.169) was derived, and cross-validation demonstrated robust predictive performance (66.67% top-rank accuracy; 94.87% top-two accuracy). This study establishes the quantitative perceptual threshold for hair volume and introduces a morphology-aware correction model that aligns instrumental measurements with human perception. Together, these tools provide a practical framework for ensuring that volumising product claims are both physically measurable and perceptually meaningful. Les méthodes instrumentales de mesure du volume capillaire peuvent détecter des différences physiques non perceptibles pour les consommateurs, créant ainsi un décalage entre les mesures in vitro et la perception en conditions réelles. Cette étude visait à établir la différence juste perceptible (Just‐Noticeable Difference, JND) pour le volume capillaire et à développer un modèle prédictif intégrant l'ondulation des cheveux afin d'assurer une meilleure correspondance entre les données instrumentales et l'évaluation sensorielle. MÉTHODES: Le volume global et l'ondulation ont été quantifiés à partir de mèches de cheveux à l'aide d'un cadre d'analyse d'images personnalisé. Le volume a été déterminé au moyen d'une classification de la densité des fibres basée sur l'intensité des pixels, tandis que l'ondulation a été dérivée d'une analyse amplitude–fréquence de l'axe médian corrigé de la tendance. L'évaluation sensorielle a été réalisée par un panel d'experts sur des ensembles contrôlés de quatre mèches présentant des différences de volume définies (ΔV ≈ 5, 3 et 2 cm²). Le rang sensoriel moyen a été utilisé comme principal indicateur perceptif. Un modèle de régression multivariée par moindres carrés ordinaires a été élaboré et validé à l'aide d'une validation croisée de type Leave‐One‐Group‐Out sur 35 ensembles indépendants. RÉSULTATS: Un seuil perceptif de ΔV ≈ 3 cm² a été identifié comme correspondant à la JND pour le volume capillaire. À ΔV ≈ 5 cm², les classements instrumentaux et sensoriels présentaient une forte concordance, tandis qu'à ΔV ≈ 2 cm², la discrimination perceptive n'était plus possible. L'analyse de régression a confirmé que le volume global constituait le principal facteur prédictif du volume perçu (β = 0,798 ; p < 0,001), l'ondulation apportant une contribution secondaire significative (β = 0,135 ; p = 0,005 ; R² ajusté = 0,660). Un facteur de correction de l'ondulation (k ≈ 0,169) a été dérivé, et la validation croisée a démontré de solides performances prédictives (exactitude de 66,67 % pour le classement au premier range; 94,87 % pour le classement parmi les deux premiers rangs). Cette étude établit le seuil perceptif quantitatif du volume capillaire et introduit un modèle de correction tenant compte de la morphologie, permettant d'aligner les mesures instrumentales sur la perception humaine. Ensemble, ces outils fournissent un cadre pratique permettant de garantir que les allégations relatives aux produits volumateurs sont à la fois physiquement mesurables et perceptiblement significatives.
Hair graying, often linked to aging (oxidative stress), has gained significant attention due to its social implications and the desire for a youthful appearance. Currently, there is no effective solution. The objective of this study was to determine whether Gynostemma pentaphyllum (Thunb.) Makino extract (GP) can mitigate the effects of H2O2-induced oxidative stress in melanocytes and evaluate its potential as a treatment for hair graying. Oxidative stress models were established using B16 melanoma cells and C57BL/6 mice. GP treatment's effects on cell viability, melanocyte apoptosis, intracellular reactive oxygen species (ROS) levels, melanin production, tyrosinase activity, total superoxide dismutase (SOD) activity, and the Wnt/β-catenin signaling pathway were assessed. In animal experiments, the protective effects of GP on mouse hair follicles were evaluated. GP treatment enhanced cell viability, decreased melanocyte apoptosis, reduced intracellular ROS levels, increased melanin production, boosted tyrosinase and SOD activity, and potentially modulated the Wnt/β-catenin signaling pathway. In animal experiments, GP significantly protected mouse hair follicles from H2O2-induced damage. The findings suggest that GP has potential as a treatment for hair graying by mitigating H2O2-induced oxidative stress in melanocytes, highlighting its therapeutic potential in addressing oxidative stress-related hair graying.
As a cutaneous appendage, the hair follicle is tightly associated with the skin during growth, pigmentation, and aging. These two interconnected tissues share evolutionarily conserved regulatory mechanisms-including stem cell niche signaling, inflammatory cascades, and oxidative stress-and collectively function as hallmarks of systemic organismal aging. Hair abnormalities are well-established concomitant manifestations of aged skin. The crosstalk between skin aging and hair aging is particularly pronounced in several hereditary progeroid disorders, which are typified by concurrent premature aging in both tissues. Notably, multiple intervention strategies have shown promising therapeutic efficacy against both aging processes. To date, numerous molecular cascades have been implicated in skin aging, including DNA damage accumulation, telomere attrition, oxidative stress, chronic low-grade inflammation, and stem cell exhaustion. Given the intricate interplay among these pathways, this review systematically dissects the contributions of each mechanism to hair follicle aging and further clarifies the mechanistic links underlying skin and hair aging.
In recent years, the analysis and identification of benzodiazepines and Z-drugs have presented significant challenges in forensic medicine and pharmaceutical analysis due to their widespread use. Notably, some of these substances are classified as new psychoactive substances (NPS) by the UNODC. Hair was chosen as a biological matrix for monitoring long-term drug intake in this study. We aimed to develop and validate a rapid and sensitive method for simultaneous determination of 40 benzodiazepines and Z-drugs in hair using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). All the analytes were detected within 11 min. The method was validated with linear calibration curves over the range of 5-500 pg mg-1 (coefficient of determination, r2 > 0.99). The limits of detection (LOD) were 1-3 pg mg-1, and the limits of quantification (LOQ) were 5 pg mg-1. The method demonstrated acceptable selectivity, accuracy, and precision (< 20%). Matrix effects ranged from -29.8-23.5%, and recoveries ranged from 77.9% to 119.9%. The method was successfully applied to six authentic hair samples, detecting nine substances: Nitrazepam, Temazepam, Lorazepam, 7-Aminoflunitrazepam, Clobazam, Lormetazepam, α-Hydroxyalprazolam, 7-Aminoclonazepam, and Zolpidem. Benzodiazepines concentrations ranged from 5.6 to 436.1 pg mg-1, while zolpidem concentrations ranged from 11.1 to 113.8 pg mg-1. This method provided a reliable tool for detecting benzodiazepines and Z-drugs in hair and addresses the requirements of routine forensic practice.
In humans, microorganisms within hair follicles differ from those on the skin surface and may contribute to autoimmune skin diseases such as alopecia areata and vitiligo. Owing to the low biomass of hair follicle microorganisms, precise sample acquisition and strategies to avoid contamination with genetic material are critical. To address this, we developed and evaluated a sampling methodology using a nonhuman wildlife proxy model - the wild roe deer (Capreolus capreolus) - to identify effective approaches for minimizing skin contamination prior to biopsy. Animal was obtained during licenced hunts and frozen at -20°C shortly postmortem. Four sets of biopsy and skin surface swab samples were collected from the right front leg: 1) untreated skin; 2) skin cleaned with isopropyl alcohol (IPA) wipes; 3) skin treated with cyanoacrylate glue (CAG); and 4) skin treated with CAG followed by IPA wipes. Swabs were collected via Copan FLOQSwabs, whereas biopsies were obtained with single-use 1 mm biopsy punches. Nucleic acids were subjected to droplet digital PCR (ddPCR) for 16S rRNA and 18S rRNA gene copy number quantification. Additionally, the swab samples were subjected to 16S rRNA V3-4 region and ITS-1 sequencing. ddPCR analysis revealed greater bacterial presence on the skin surface (11,661±5,181 copies/±L) than fungal presence (87±35 copies/μL), and the microbial load was greater in the swab samples (16S: 11,661±5,181; 18S: 87±35 copies/μL) than in the biopsy samples (16S: 76±56; 18S: 8±5 copies/μL). Notably, the use of CAG reduced the microbial load in biopsy samples by 3.7-fold. 16S and ITS sequencing analysis revealed slightly greater alpha diversity in swab samples than in biopsy samples, particularly in areas treated with CAG. Beta diversity revealed distinct clustering of swab and biopsy samples, with shorter distances between CAG-treated samples and untreated samples. Fewer bacterial (n = 8) and fungal (n = 1) genera were detected in CAG-treated biopsies compared with untreated (n = 21, n = 9, resp.) and IPA-treated (n = 45, n = 7, resp.) biopsies. These results demonstrate a high probability of biopsy contamination with microbial DNA originating from the skin surface. They also confirmed that CAG effectively reduces such contamination and can serve as a practical decontamination step before biopsy. Although based on a nonhuman wildlife model, this feasibility study provides methodological insights that can inform the design of future human hair follicle microbiome investigations.
Collagen XVIIα1, encoded by COL17A1 and historically known as BP180/BPAG2, is a type II transmembrane collagen enriched in hemidesmosomes of basal keratinocytes. Through interactions with integrin α6β4, laminin-332 and other dermal-epidermal junction (DEJ) components, collagen XVIIα1 links the keratin cytoskeleton to the basement membrane. Recent studies indicate that this junctional anchorage supports epidermal homeostasis by preserving stem cell adhesion, polarity and regenerative capacity. During aging, collagen XVIIα1 levels decline and proteolytic processing increases, including ADAM9/ADAM10-dependent ectodomain shedding and cleavage by inflammatory proteases. These changes weaken DEJ integrity and are associated with photoaging and impaired repair. In hair follicles, collagen XVIIα1 is also required for hair follicle stem cell (HFSC) maintenance, and its reduction is linked to HFSC exhaustion, hair aging phenotypes and altered niche signals that may influence melanocyte stem cell-dependent pigmentation. This review summarizes translational approaches targeting collagen XVIIα1 and proposes practical in vivo readouts for target engagement. Key gaps include mechanism attribution, durable functional restoration at the DEJ, persistence within the epidermal-follicular niche and a shortage of rigorous human studies.
The identification of the cancer cell of origin is a fundamental question in cancer biology. We used fluorescent lineage tracing of independent mouse skin stem cell populations, single cell transcriptomics, and Duplex sequencing, to identify the origin of chemically induced skin tumors. Tumors arose predominantly from Lgr6+ and / or Lrig1+ stem cells of the upper hair follicle, but only very rarely from the Lgr5+ and Krt19+ hair follicle bulge. Lgr6+ stem cells initiated by dimethylbenzanthracene responded to tumor promoter treatment resulting in clonal expansion of initiated cells carrying the canonical Hras Q61L mutation. Spontaneous mutations in Kras also clonally expanded, but did not generate tumors unless the Hras gene was deleted, thus revealing a competitive interaction between Hras and Kras pathways that influences clonal selection.
Aims and Backgrounds: Hair loss is a highly prevalent condition, and patients are increasingly seeking pre-junvination and restoration. This review evaluates contemporary non-surgical hair restoration modalities. Therapeutic strategies have evolved from topical vasodilators to targeted hormonal, regenerative, and device-based interventions reflecting advances in our understanding of follicular biology and technology. Hair follicle cycling is regulated by dermal papilla signaling, epithelial stem cells, and perifollicular vascular and inflammatory environments. Non-surgical therapies include oral and topical pharmacologics, hormonal therapies, platelet-rich plasma (PRP), microneedling, peptide-based treatments, exososomes, nutraceuticals, low-level laser therapy (LLLT), lasers, and transdermal delivery systems. Appropriate candidates include patients with androgenetic alopecia and other non-scarring alopecias; accurate diagnosis is critical. Combination therapy is increasingly utilized to target multiple biologic pathways. Post Operative Care: Minimal downtime is expected; long-term adherence is required. Current and Future Development: Emerging therapies include exosome-based treatments, peptides, and advanced drug delivery platforms. Non-surgical modalities are central to prejuvenation and can delay or complement surgical intervention when appropriately applied.
Noonan-like syndrome with loose anagen hair (NS/LAH) is a RASopathy caused by genetic variants in SHOC2. There are now several reports of moyamoya syndrome in association with this condition and with Noonan and other Noonan-like syndromes. We report the case of a young boy with NS/LAH secondary to the c.4A>G, p.Ser2Gly variant in SHOC2 who was subsequently diagnosed with growth hormone insufficiency. Although the pituitary appeared normal on brain magnetic resonance imaging, findings consistent with moyamoya syndrome were identified and subsequently confirmed by magnetic resonance angiography. He remains on growth hormone treatment, with ongoing close surveillance planned to monitor the progression of his moyamoya. Growth hormone insufficiency predominates as the cause of short stature in NS/LAH. We conducted a comprehensive review of published case reports to date on patients with Noonan and Noonan-like syndromes and moyamoya syndrome. From this review, we identified 13 clinically diagnosed cases. Genotype data was only available for 5 patients, 3 of whom had NS/LAH secondary to SHOC2 variants. To our knowledge, our patient represents the 4th reported case with NS/LAH and moyamoya. The possibility of moyamoya should be considered during follow-up of patients with Noonan and Noonan-like syndromes, including NS/LAH, to facilitate timely recognition and intervention.
Scalp follicular unit (FU) transplantation is a highly effective yet underutilised minimally invasive technique for promoting healing in chronic and recalcitrant cutaneous wounds. In this case series, five patients with long-standing nonhealing leg ulcers of mixed etiologies were treated exclusively with single FU grafts harvested from the scalp with a 0.9-1-mm punch. Complete re-epithelialization occurred in three cases by 6, 3 and 1 month, respectively, while the remaining two cases showed marked partial improvement at 6 months, with reduction in ulcer area and pain. Overall, all five patients experienced a favourable clinical outcome. Case reports suggest that the transplantation of a minimum of 4 FU grafts/cm2 is required to promote effective wound closure, with higher graft densities being associated with faster healing. However, the optimal graft density and placement, whether uniform distribution or targeting the wound edge to exploit an 'edge effect', require further investigation. Considered alongside prior reports, these results suggest that 1-mm single-FU grafting achieves wound healing comparable to, and often faster than, 2-3-mm punch grafts. Additionally, the technique is less invasive and causes less bleeding, overall supporting wider use as an adjunct in multidisciplinary wound care. Level of Evidence: IV.
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A set of actinobacterial strains was isolated from the root nodules of Acacia gerrardii grown as part of an afforestation trial in the Khurais desert, Saudi Arabia. Among them, five clonal isolates could not be unambiguously assigned to any recognized type species, and two of them, designated AC027ST and AC027N, were selected as representatives for taxonomic characterization. Cells were Gram-stain-positive, aerobic, non-motile, non-spore-forming, with short rods to coccoid-like morphology. Growth occurred at 20-42 °C, pH 5.0-10.0 and in the presence of up to 3.0% (w/v) NaCl. The major whole-cell sugar was glucose, and the muramic acid residues of the peptidoglycan carried peptide subunits composed of alanine, glutamic acid and lysine. The predominant menaquinone was MK-9(H4). Major fatty acids were iso-C15:0 and anteiso-C15:0, and the polar lipid profile included diphosphatidylglycerol, phosphatidylglycerols and several unidentified glycophospholipids, glycolipids, phospholipids and lipids. Phylogenetic analysis based on 16S rRNA gene sequences placed AC027ST and AC027N within the genus Promicromonospora. Whole-genome sequence-based phylogenomic reconstruction and relatedness indices confirmed that these G+C-rich strains (72%) are distinct from all described Promicromonospora species, with Promicromonospora soli NEAU-GS50T as the closest described relative. Consistent with their nodule-associated niche, the strains were able to degrade and utilize plant-derived substrates, tolerate microaerophilic conditions and possessed genes for mobilizing essential metals, such as iron and molybdenum, suggesting a supportive role in the nodule microbial community and in sustaining rhizobial nitrogen fixation, as reflected in an enhanced nodulation by native rhizobia when inoculated in desert soil. Based on phenotypic, chemotaxonomic and genomic evidence, strains AC027ST and AC027N represent a novel species of the genus Promicromonospora, for which the name Promicromonospora noduliphila sp. nov. is proposed. The type strain is AC027ST (=KCTC 59476ᵀ, =JCM 37759ᵀ).
Alopecia areata (AA) is a chronic autoimmune disease characterized by sudden patchy hair loss and persistent inflammation. To date, only JAK inhibitors have been approved for AA treatment, but FDA-issued black box warnings highlight the need for alternative therapies. We previously reported that an anti-γc antibody, hC2, inhibits autoreactive B, T, and NK cells by selectively attenuating JAK/STAT signaling induced by six γc cytokines, without affecting off-target TEC kinase pathways. Here, we sought to define the mechanism of action and efficacy of hC2 in AA by using an ex-vivo T cell platform and a xenogeneic AA-like mouse model induced by human T cell engraftment. Analyses showed that hC2 could restore hair follicle homeostasis and suppress hair loss by inhibiting autoreactive T cell activity and proliferation of tissue-resident memory T cells. Although JAK3 inhibitor ritlecitinib could potentially protect hair follicles through T cell depletion strategy in-vitro, severe side effects were associated with ritlecitinib treatment while no significant safety issues were noted after hC2 treatment in the xenogeneic AA-like mouse model. These findings suggest that hC2 might offer a safer and more effective therapeutic approach for AA patients in the future.
Dissecting cellulitis of the scalp is an uncommon chronic inflammatory disorder within the follicular occlusion spectrum and may progress to permanent cicatricial alopecia if not recognized early. We report a case of a 34-year-old male with androgenetic alopecia, two years of exogenous testosterone use, and a recent history of six-monthly sessions of scalp microinfusion of medication into the skin, who developed painful and pruritic inflammatory scalp nodules approximately 45 days after the last procedure. The procedure was performed using a Cheyenne Unlimited 4 dermograph fitted with a 2710MG cartridge, corresponding to a 27-needle magnum configuration with 0.30 mm diameter needles, operating at 6.1 V, with the needle depth set to 1.2 mm. Clinical examination showed focal inflammatory alopecic nodules over a background of patterned hair thinning. Trichoscopy demonstrated perifollicular erythema, reduced follicular density, broken hairs, black dots, white structureless areas, and partial preservation of follicular openings, without classic features of alopecia areata. Histopathology showed hypodermal granulation tissue, intense mixed leukocytic inflammation composed of lymphocytes, plasma cells, neutrophils, macrophages, and foreign body-type multinucleated giant cells, follicular involvement with miniaturization, negative periodic acid-Schiff staining for fungi, and bacterial colonization in the infundibular and isthmic portions of hair follicles. These findings were consistent with dissecting folliculitis of the scalp. The patient was treated with oral antibiotics, intralesional corticosteroid, and high-potency topical corticosteroid, with partial inflammatory improvement and stabilization. This case highlights the value of clinicotrichoscopic-pathologic correlation in early dissecting cellulitis and raises the possibility that repeated procedural microtrauma, barrier disruption, follicular injury, or secondary bacterial colonization may act as a local trigger in a predisposed patient. The long-term exogenous testosterone exposure should be interpreted as a possible modifying factor rather than proof of causality.
This study aimed to compare the clinical efficacy and safety of two rosacea treatment regimens: oral doxycycline plus the Shumin treatment instrument and oral doxycycline plus red light therapy. Objective assessments, including reflectance confocal microscopy, were used to evaluate both regimens. A total of 60 patients with rosacea were randomly divided into two groups, each containing 30 patients. The control group received doxycycline (100 mg/day) orally combined with red light therapy for 12 weeks (twice a week), whereas the experimental group received doxycycline (100 mg/day) orally combined with Shumin treatment instrument therapy for 12 weeks (twice a week). The efficacy rate was 93.3% in the experimental group and 80.0% in the control group. Following treatment, significant reductions in Dermatology Life Quality Index scores and Demodex counts were achieved in both groups (all p < 0.001). However, the experimental group exhibited superior improvements in Dermatology Life Quality Index scores and affected hair follicle counts compared with the control group (p < 0.05). No significant difference was observed in the reduction in the total Demodex count between the groups. Similarly, no significant difference was observed in the change in the total hair follicle number between the groups. Furthermore, the relapse rate was notably lower in the experimental group than in the control group (p = 0.026). When used as an adjunctive therapy with oral doxycycline, the Shumin device yields better clinical outcomes than red light therapy for treating rosacea and has a favorable safety profile. These preliminary results establish a basis for the use of adjuvant physical interventions for rosacea.
This study evaluated whether the complexity and temporal dynamics of environmental enrichment during the nursery phase are associated with piglets' threat-related responses and affective state using a multimodal approach. We combined an Attentional Bias Test (ABT) with bioacoustic measures, Qualitative Behavior Assessment (QBA), and biomarkers (hair cortisol and serum BDNF). In a commercial nursery setting, 675 piglets were allocated to three treatments: UNI (single continuous item: chains), ALT (chains plus an additional object rotated weekly), and SIM (continuous simultaneous provision of multiple objects). A subsample of 32 piglets underwent the ABT (UNI, n = 10; ALT, n = 11; SIM, n = 11). Most ABT measures related to threat-directed attention and space use showed no detectable treatment differences under the present protocol, and feeding latency was affected by stimulus exposure but not by treatment. In contrast, treatments differed in coping-related responses: UNI showed a higher frequency of excretions, ALT showed a longer standing-inactive duration, and SIM showed more escape attempts. Vocalizations were restricted to harsh grunts, with ALT showing longer harsh-grunt duration and higher total vocal output. QBA and biomarkers further differentiated treatments: SIM showed calmer/less tense expressive profiles, whereas UNI showed higher post-exposure hair cortisol and lower serum BDNF than the more complex conditions. Overall, enrichment-related differences were more consistently detected in coping-related behavior, QBA, and biomarkers than in ABT attentional measures, suggesting that enrichment implementation (stable vs. rotational) shapes partially dissociable behavioral and physiological adaptation profiles, and that both more complex strategies showed a more favorable biological profile than UNI.