Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.

Syphilis remains a global public health threat and can lead to severe complications. In addition to resolution of clinical manifestations, a reduction in nontreponemal antibody titers after treatment is regarded as “proof of cure.” However, some patients manifest < 4-fold decline (“serological non-response”) or persistently positive nontreponemal titers despite an appropriate decline (“serofast”) that may represent treatment failure, reinfection, or a benign immune response. To delineate these treatment phenomena, we conducted a systematic review of the literature regarding serological outcomes and associated factors among HIV-infected and -uninfected subjects. Six databases (PubMed, Embase, CINAHL, Web of Science, Scopus, and BIOSIS) were searched with no date restrictions. Relevant articles that evaluated serological treatment responses and correlates of serological cure (≥ four-fold decline in nontreponemal titers) were included. We identified 1693 reports in the literature, of which 20 studies met selection criteria. The median proportion of patients who had serological non-response was 12.1 % overall (interquartile range, 4.9–25.6), but varied depending on the time points after therapy. The serofast proportion could only be estimated from 2 studies, which ranged from 35.2–44.4 %. Serological cure was primarily associated with younger age, higher baseline nontreponemal titers, and earlier syphilis stage. The relationship between serological cure and HIV status was inconsistent; among HIV-infected patients, CD4 count and HIV viral load was not associated with serological cure. Serological non-response and the serofast state are common syphilis treatment outcomes, highlighting the importance of determining the immunological and clinical significance of persistent nontreponemal antibody titers after therapy.

Hesperidin is a bioflavonoid, with high concentration in citrus fruits. In addition to its well-known benefits for cardiovascular function, type II diabetes, and anti-inflammation, recent studies have demonstrated multiple benefits of hesperidin for cutaneous functions, including wound healing, UV protection, anti-inflammation, antimicrobial, antiskin cancer, and skin lightening. In addition, hesperidin enhances epidermal permeability barrier homeostasis in both normal young and aged skin. The mechanisms by which hesperidin benefits cutaneous functions are attributable to its antioxidant properties, inhibition of MAPK-dependent signaling pathways, and stimulation of epidermal proliferation, differentiation, and lipid production. Because of its low cost, wide availability, and superior safety, hesperidin could prove useful for the management of a variety of cutaneous conditions.

Dual‐mode readout platforms with colorimetric and electrochemiluminescence (ECL) signal enhancement are proposed for the ultrasensitive and flexible detection of the monkeypox virus (MPXV) in different scenes. A new nanotag, Ru@U6‐Ru/Pt NPs is constructed for dual‐mode platforms by integrating double‐layered ECL luminophores and the nanozyme using Zr‐MOF (UiO‐66‐NH₂) as the carrier, which not only generates enhanced ECL and colorimetric signals but also provide greater stability than that of commonly used nanotags. Dual‐mode platforms are used within 15 min from the “sample in” to the “result out” steps, without nucleic acid amplification. The colorimetric mode allows the screening of MPXV with the visual limit of detection (vLOD) of 0.1 pM (6 × 10⁸ copies µL⁻¹) and the ECL mode supports quantitative detection of MPXV with an LOD as low as 10 aM (6 copies·µL⁻¹), resulting in a broad sensing range of 60 to 3 × 10¹¹ copies·µL⁻¹ (10 orders of magnitude). Validation is conducted using 50 clinical samples, which is 100% concordant to those of quantitative polymerase chain reaction (qPCR), indicating that Ru@U6‐Ru/Pt NPs‐based dual‐mode sensing platforms showed great promise as rapid, sensitive, and accurate tools for diagnosis of the nucleic acid of MPXV and other infectious pathogens.

Zika virus (ZIKV) is a re-emerging flavivirus that leads to devastating consequences for fetal development. It is crucial to visualize the pathogenicity activities of ZIKV ranging from infection pathways to immunity processes, but the accurate labeling of ZIKV remains challenging due to the lack of a reliable labeling technique. We introduce the photo-activated bio-orthogonal cycloaddition to construct a fluorogenic probe for the labeling and visualizing of ZIKV. Via a simple UV photoirradiation, the fluorogenic probes could be effectively labeled on the ZIKV. We demonstrated that it can be used for investigating the interaction between ZIKV and diverse cells and avoiding the autofluorescence phenomenon in traditional immunofluorescence assay. Thus, this bioorthogonal-enabled labeling strategy can serve as a promising approach to monitor and understand the interaction between the ZIKV and host cells.

Fungal biofilms, as self-produced extracellular polymeric substances that resist antifungal agents and immune defense, represent a major cause of treatment failure and recurrent infections. Therefore, it is of great importance to eradicate fungal biofilms to achieve efficient therapy. This study develops a synergistic reactive oxygen species (ROS)-enhanced strategy to eradicate Candida albicans biofilms by designing ultrasound-light dual-responsive nanohybrids (UCNP@CR). The system integrates thulium-doped upconversion nanoparticles (UCNPs) with carbon nitride-coated surfaces (g-C₃N₄) and polypyridine ruthenium complex (Ru) photosensitizers. In treatment, the dense fungal biofilm can be effectively loosened under ultrasound stimulation while ultrasound simultaneously triggers ROS production of UCNP@CR, collectively promoting irreversible destruction of biofilm and inward penetration of photosensitizer. Moreover, UCNP@CR exhibits strong fungal adhesion, while its g-C₃N₄-mediated enhanced metal-to-ligand charge transfer (MLCT) process of Ru under near-infrared light irradiation amplifies ROS generation, which leads to efficient eradication of fungal biofilms. As in vivo experimental evidence, UCNP@CR exhibits excellent antifungal efficacy in treating fungal biofilm-infected wounds in immunosuppressed male mice under ultrasound-light stimulation. These findings establish the ultrasound-assisted, ROS-enhanced synergistic strategy as a promising approach against fungal biofilm infections and provide diverse perspective for managing other biofilm-related infectious diseases.