High-performance pyrite nano-catalyst driven photothermal/chemodynamic synergistic therapy for Osteosarcoma.

Osteosarcoma (OS) is an aggressive bone tumor with strong invasiveness, rapid metastasis, and dreadful mortality. Chemotherapy is a commonly used approach for OS treatment but is limited by the development of drug resistance and long-term adverse effects. To date, OS still lacks the curative treatment. Herein, we fabricated pyrite-based nanoparticles (FeS2@CP NPs) as synergetic therapeutic platform by integrating photothermal therapy (PTT) and chemo-dynamic therapy (CDT) into one system. The synthetic FeS2@CP NPs showed superior Fenton reaction catalytic activity. FeS2@CP NPs-based CDT efficaciously eradicated the tumor cells by initiating dual-effect of killing of apoptosis and ferroptosis. Furthermore, the generated heat from FeS2@CP under near-infrared region II (NIR-II) laser irradiation could not only inhibit tumor's growth, but also promote tumor cell apoptosis and ferroptosis by accelerating •OH production and GSH depletion. Finally, the photothermal/NIR II-enhanced CDT synergistic therapy showed excellent osteosarcoma treatment effects both in vitro and in vivo with negligible side effects. Overall, this work provided a high-performance and multifunctional Fenton catalyst for osteosarcoma synergistic therapy, which provided a pathway for the clinical application of PTT augmented CDT.

Exploring the clinical features and risk factors for children tinea capitis complicated with allergic diseases.

BACKGROUND: Tinea capitis, atopic dermatitis and allergic rhinitis are the most common disorders endured by prepubescent children. Dermatophyte infections have been linked to allergic disorders, such as increased sensitivity to dermatophytes in patients with atopic dermatitis. OBJECTIVES: To explore the correlation between tinea capitis and allergic diseases in children and to analyse their risk factors. METHODS: This study monitored epidemiological changes in childhood tinea capitis and risk factors for whom with allergic disease in a single centre in three consecutive five-year intervals by reviewing clinical data and multivariate logistic data analysis. RESULTS: Between 2007 and 2022, there were 127 children patients with tinea capitis, the mean age was 4.83 years, and the male-to-female ratio was 1.76:1. Zoophilic Microsporum canis and Trichophyton mentagrophytes were the most prevalent pathogens, and the proportions remained relatively constant every 5 years. There were 34 (26.8%) children with tinea capitis complicated with allergic disease, among them 14 children with atopic dermatitis/eczema, 13 with allergic rhinitis, 8 urticaria, 6 food allergies and 1 allergic asthma. Male, kerion, zoophilic species infections and animal contact history were prevalent features in allergic disease combined with tinea capitis. Patients with tinea capitis plus allergic disease mostly had a family history with similar complications. CONCLUSION: M. canis and T. mentagrophytes were the most prevalent pathogens of tinea capitis in the last 15 years; atopic dermatitis/eczema and allergic rhinitis were the most frequently associated allergic diseases. Male, kerion, zoophilic pathogen and animal contact history are risk factors.

In Situ Visualization on Surface Oxidative Corrosion with Free Radicals: Black Phosphorus Nanoflake as an Example.

Free radicals exert a significant impact on the fate of redox-active substances and play a crucial role in the surface corrosion of solid in environment. Dynamic visualization on the response of the surface to the free radicals at nanoscale is essential to explore the mechanism. Environmental transmission electron microscopy will be a powerful tool for dynamic changes of the interface redox process of solid surface with electron beams induced free radicals, to simulate the redox process of a solid in the environment. Black phosphorus (BP), an environment-sensitive material, is selected as an example to visualize the degradation pathways with environmental transmission electron microscopy. The distribution of the corrosion initiation points, formation and growth of corrosion areas, and the eventual splintering and disappearance of BP nanoflakes are recorded vividly. In situ results are substantiated by the ex situ experiments and density functional theory (DFT) calculations. Results show that degradation originates at the edges and defect structures when the humidity reaches high enough. The microscopic structural oxidative etching of solid surface with radicals in natural light is simulated with radicals produced by electron beam irradiation on suspending medium O2 and H2O for the first time. This method will offer unprecedented details and valuable insights into the mechanism involved in the oxidative etching with natural light.

Recent advances in exosome-mediated nucleic acid delivery for cancer therapy.

Cancer is a leading public health problem worldwide. Its treatment remains a daunting challenge, although significant progress has been made in existing treatments in recent years. A large concern is the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy has recently emerged as a powerful tool for cancer therapy. However, delivery methods limit its therapeutic effects. Exosomes, a subset of extracellular vesicles secreted by most cells, have the characteristics of good biocompatibility, low toxicity and immunogenicity, and great designability. In the past decades, as therapeutic carriers and diagnostic markers, they have caught extensive attention. This review introduced the characteristics of exosomes, and focused on their applications as delivery carriers in DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), circular RNA (circRNA) and other nucleic acids. Meanwhile, their application in cancer therapy and exosome-based clinical trials were presented and discussed. Through systematic summarization and analysis, the recent advances and current challenges of exosome-mediated nucleic acid delivery for cancer therapy are introduced, which will provide a theoretical basis for the development of nucleic acid drugs.

A New Target of the Four-Herb Chinese Medicine for Wound Repair Promoted by Mitochondrial Metabolism Using Protein Acetylation Analysis.

BACKGROUND Wound healing is a dynamic and complex process that is regulated by a variety of factors and pathways. This study sought to identify the mechanisms of the four-herb Chinese medicine ANBP in enhancing wound repair. MATERIAL AND METHODS By comparing the group treated with ANBP for 6 h (Z6h) with the corresponding control group (C6h), we used the new high-throughput differential acetylation proteomics method to explore the mechanism of ANBP treatment and analyse and identify new targets of ANBP for promoting wound healing. RESULTS ANBP promoted skin wound healing in mice; the wound healing process was accelerated and the wound healing time was shortened (P<0.05). The upregulated proteins were distributed mostly in the mitochondria to nuclear respiratory chain complexes and cytoplasmic vesicles. The dominant pathways for upregulated proteins were fatty acid metabolism, pyruvate metabolism, and tricarboxylic acid cycle. Pdha1 was upregulated with the most acetylation sites, while the downregulated Ncl, and Pfkm were most acetylated. CONCLUSIONS The findings from our study showed that ANBP improved cell aerobic respiration through enhanced glycolysis, pyruvic acid oxidative decarboxylation, and the Krebs cycle to produce more ATP for energy consumption, thus accelerating wound repair of skin.

Chitin-rich heteroglycan from Sporothrix schenckii sensu stricto potentiates fungal clearance in a mouse model of sporotrichosis and promotes macrophages phagocytosis.

BACKGROUND: Fungal cell wall polysaccharides maintain the integrity of fungi and interact with host immune cells. The immunomodulation of fungal polysaccharides has been demonstrated in previous studies. However, the effect of chitin-rich heteroglycan extracted from Sporothrix schenckii sensu stricto on the immune response has not been investigated. RESULTS: In this study, chitin-rich heteroglycan was extracted from S. schenckii sensu stricto, and immunomodulation was investigated via histopathological analysis of skin lesions in a mouse model of sporotrichosis and evaluation of the phagocytic function and cytokine secretion of macrophages in vitro. The results showed that the skin lesions regressed and granulomatous inflammation was reduced in infected mice within 5 weeks. Moreover, heteroglycan promoted the fungal phagocytosis by macrophages and modulated the cytokine secretion. Heteroglycan upregulated TNF-α expression early at 24 h and IL-12 expression late at 72 h after incubation, which might result from moderate activation of macrophages and contribute to the subsequent adaptive immune response. CONCLUSIONS: Chitin-rich heteroglycan extracted from S. schenckii sensu stricto potentiated fungal clearance in a mouse model of sporotrichosis. Moreover, chitin-rich heteroglycan promoted fungus phagocytosis by macrophages and modulated cytokines secretion. These results might indicate that chitin-rich heteroglycan could be considered as an immunomodulator used in the treatment of sporotrichosis.

One-step construction of a food-grade expression system based on the URA3 gene in Kluyveromyces lactis.

Proteins from food-grade expression systems can be used in food products and medical applications. Herein, we describe a one-step method of constructing an expression vector in Kluyveromyces lactis by combining a URA3-deficient strain and a plasmid vector with no drug-resistant selection. Adjacent DNA elements of the vector were assembled in a targeted manner through a reaction with a special recombinase to form a plasmid vector using a one-step reaction. The unnecessary fragments containing the pUC origin and the ampicillin resistance gene were removed, and the vector was isolated and purified before transformation. A single transformation of the vector can produce a URA3-deficient strain. PCR assay, sequencing, and western blot analysis all indicated that the method of vector construction and target protein expression (mCherry and human serum albumin) were successful. This method may potentially be applied to any species containing the URA3 gene; this system has the potential to become a safe and powerful tool for promoting protein expression in food-safe species.

The design and application of an automated microscope developed based on deep learning for fungal detection in dermatology.

BACKGROUND: Light microscopy to study the infection of fungi in skin specimens is time-consuming and requires automation. OBJECTIVE: We aimed to design and explore the application of an automated microscope for fungal detection in skin specimens. METHODS: An automated microscope was designed, and a deep learning model was selected. Skin, nail and hair samples were collected. The sensitivity and the specificity of the automated microscope for fungal detection were calculated by taking the results of human inspectors as the gold standard. RESULTS: An automated microscope was built, and an image processing model based on the ResNet-50 was trained. A total of 292 samples were collected including 236 skin samples, 50 nail samples and six hair samples. The sensitivities of the automated microscope for fungal detection in skin, nails and hair were 99.5%, 95.2% and 60%, respectively, and the specificities were 91.4%, 100% and 100%, respectively. CONCLUSION: The automated microscope we developed is as skilful as human inspectors for fungal detection in skin and nail samples; however, its performance in hair samples needs to be improved.

Molecular mechanism of myofibroblast formation and strategies for clinical drugs treatments in hypertrophic scars.

Hypertrophic scars (HTS) commonly occurred after burn and trauma. It was characterized by the excessive deposition of extracellular matrix with the inadequate remodeling, which could result in severe physiological and psychological problems. However, the effective available prevention and treatment measures were still limited. The main pathological feature of HTS was the excessive formation of myofibroblasts, and they persist in the repaired tissue. To better understand the mechanics of this process, this review focused on the characteristics and formation of myofibroblasts, the main effector cells in HTS. We summarized the present theories and opinions on myofibroblasts formation from the perspective of related signaling pathways and epigenetic regulation, such as DNA methylation, miRNA/lncRNA/ceRNA action, histone modification, and so forth for a better understanding on the development of HTS. This information might assist in developing effective experimental and clinical treatment strategies. Additionally, we also summarized currently known clinical strategies for HTS treatment, including traditional drugs, molecular medicine, stem cells, and exosomes.

The Role of Semantic Gender in Name Comprehension: An Event-Related Potentials Study.

It is well known that the semantic features of gender associated with peoples' names are represented in the conceptual semantic system. However, there is scant evidence that such knowledge plays a role in name comprehension, and if so, in which processing stage this occurs. The aim of this study was to provide evidence concerning the time course of the activation of semantic gender in the processing of people's names. We recorded event-related potentials when participants saw picture-name pairs. Compared with the gender congruent condition in which the priming picture and Chinese name were matched on gender, names in the gender incongruent condition showed a mismatch effect in the time windows of 300-500 ms and 500-700 ms. These findings illustrate for the first time the activation of semantic gender when processing people's names, and further specify that this access occurs in the stage of name recognition rather than person identification.

Arsenic trioxide inhibits the differentiation of fibroblasts to myofibroblasts through nuclear factor erythroid 2-like 2 (NFE2L2) protein and the Smad2/3 pathway.

BACKGROUND: Tissue contraction and the extracellular matrix deposition are part of the pathogenesis of hypertrophic scars. The transcriptional factor NFE2L2 inhibits fibroblast differentiation in idiopathic pulmonary fibrosis and promotes myofibroblast dedifferentiation. Our previous study showed that the transcription factor NFE2L2 was strongly induced on treatment with arsenic trioxide (ATO). OBJECTIVE: The present study sought to investigate the effect of ATO on myofibroblast formation to determine its potential role in hypertrophic scar treatment. METHODS: Small interfering RNA against NFE2L2 was used on treatment with ATO in human skin myofibroblasts. The expression levels of fibrosis markers were assessed by reverse transcription polymerase chain reaction, western blot, and immunofluorescence staining. The transforming growth factor-ß1 (TGF-ß1)/Smad2/3 signaling was detected by western blot. A rabbit ear model was used to evaluate the antifibrotic role of ATO. RESULTS: At the cellular level, ATO abolished fibroblast differentiation in response to TGF-ß1. ATO reduced TGF-ß1-induced reactive oxygen species accumulation through increased expression of the antioxidant gene HO-1 in fibroblasts. In addition, ATO promoted the nuclear translocation of NFE2L2 and inhibited the phosphorylation of Smad2/3. In the rabbit ear model, ATO prevented the progression of hypertrophic scar formation. CONCLUSIONS: This study provides the first evidence implying that ATO inhibits the formation of myofibroblasts in vivo and in vitro and provides a possible treatment for hypertrophic scars.

Prevalence of low inflammatory tinea genitalis in southern China.

BACKGROUND: Emergence of highly inflammatory genital dermatophyte infections has been reported from Southeast Asia. In view of this, knowledge of the non-outbreak fungal flora of the genitals is required as a baseline study. OBJECTIVES: We present our 12-year experience in a tertiary clinic with the diagnosis of scrotal fungal infections. METHODS: A retrospective review was performed of patients with a diagnosis of scrotal fungal infections proven by direct microscopy and culture. Clinical, mycological and treatment data were collected. RESULTS: In total, 35 male patients were identified, of which 27 concerned dermatophyte infections and eight were yeasts. Nannizzia gypsea was the most common agent (48.6%), presenting as thick pseudomembraneous lesions limited to the scrotum. Trichophyton rubrum (22.9%) and Epidermophyton floccosum (5.7%) mainly presented erythematous, dry and scaly lesions and involving more sites besides the scrotum. Candida albicans (n = 3), C. glabrata (n = 2), C. guilliermondii (n = 1) and Trichosporon asteroides (n = 1), presented various lesions. Sports, sweating and concurrent tineas are hypothesised as predisposing factors. CONCLUSIONS: The prevalent causative agent of scrotum infections is N. gypsea, but wide species diversity is observed. All infections show mild skin inflammation. It is suggested that this genital fungal flora represents the current situation prior to clonal dermatophyte outbreaks.

Neuroticism and depression: a moderated mediation model of secure peer attachment and blindness.

Background: Prior studies have shown strong pairwise relationships between neuroticism, peer attachment, and depression but very little was found on the questions of how neuroticism is associated with depression through secure peer attachment, and what role individual difference played in these relations (i.e., the moderating mechanism of being visually impaired or not). Objective: The present study investigated the relationship between neuroticism and depression with secure peer attachment as the mediator and being visually impaired or not as the moderator among visually impaired and sighted adolescents. Methods: The sample consisted of 67 visually impaired adolescents from a special education school, and 160 sighted adolescents from an elementary school and a middle school in Guangzhou, China. All of the adolescents completed a battery of questionnaires that measured secure peer attachment, neuroticism, and depression. Results: The results suggested that neuroticism and depression were negatively associated with secure peer attachment. Moreover, it was found that secure peer attachment partially mediated the relationship between neuroticism and depression and that this link was stronger in visually impaired adolescents than in sighted adolescents. Conclusions: The findings highlighted the importance of secure peer attachment for visually impaired adolescents, and results were interpreted in terms of implications for future studies.

Umbilical cord-derived mesenchymal stromal cell-conditioned medium exerts in vitro antiaging effects in human fibroblasts.

BACKGROUND AIMS: Chronic wounds are a common complication of diabetes. Fibroblast-myofibroblast differentiation is important for wound repair, which is commonly impaired in non-healing wounds, and the underlying mechanisms need to be further elucidated. METHODS: We used high glucose (HG) to simulated the diabetes microenvironment and explored its effects on the biological features of fibroblasts in vitro. RESULTS: The results showed that prolonged HG induced senescence in fibroblasts through activation of p21 and p16 in a reactive oxygen species (ROS)-dependent manner, further delayed the viability and migration in fibroblasts and also depressed fibroblast differentiation through the TGF-ß/Smad signaling pathway. However, mesenchymal stromal cell-conditioned medium (MSC-CM) counteracts the effects of HG. Treatment of fibroblasts with MSC-CM decreased HG-induced ROS overproduction, ameliorated HG-induced senescence in fibroblasts and reversed the defects in myofibroblast formation. Our results may provide clues for the pathogenesis of chronic wounds and a theoretical basis to develop MSC-CM as an alternative therapeutic method to treatment of chronic wounds.

A new putative deltapartitivirus recovered from Dianthus amurensis.

Two double stranded RNAs (dsRNA), likely representing the genome of a novel deltapartitivirus, provisionally named carnation cryptic virus 3 (CCV3), were recovered from Dianthus amurensis. The two dsRNAs were 1,573 (dsRNA1) and 1,561 (dsRNA2) bp in size, each containing a single open reading frame (ORF) encoding a 475- and 411-aa protein, respectively. The 475-aa protein contains a conserved RNA dependent RNA polymerase (RdRp) domain which shows significant homology to RdRps of established or putative partitiviruses, particularly those belonging to the genus Deltapartitivirus. However, it shares an amino acid identity of 75% with its closest relative, the RdRp of the deltapartitivirus beet cryptic virus 2 (BCV2), and is <62% identical to the RdRps of other partitiviruses. In a phylogenetic tree constructed with RdRps of selected partitiviruses, CCV3 clustered with BCV2 and formed a well-supported monophyletic clade with known or putative deltapartitiviruses.

Mapping the Reactions in a Single Zero-Valent Iron Nanoparticle.

Nanoscale zerovalent iron (nZVI) possesses unique functionalities for metal-metalloid removal and sequestration. So far, direct evidence on the heavy metal-nZVI reactions in the solid phase is still limited due to low concentration of heavy metals and small size of nanoparticles. In this work, angstrom-resolution spectral mappings on the reactions of nZVI with chromate, arsenate, nickel, silver, cesium, and zinc ions are presented. This work was achieved with spherical aberration-corrected scanning transmission electron microscopy integrated with high-sensitivity X-ray energy-dispersive spectroscopy-scanning transmission electron microscopy (XEDS-STEM). Results confirm that iron nanoparticles have a core-shell structure. In addition, the removal mechanism significantly depends on the standard potential E0 (E0 is standard potential w.r.t. standard hydrogen electrode at 25 °C when free ion activity is 1.). For strong oxidizing agents, such as Cr(VI), the removal mechanism is diffusion and encapsulation in the core area of the nZVI particle. For moderate oxidizers, such as As(V) with E0 more positive than that of iron, the removal mechanism is adsorption at the surface, followed by diffusion and encapsulation into the particle between the core and the shell. For metal cations with an E0 close to or more negative than that of iron, such as Cs(I) and Zn(II), the removal mechanism is sorption or surface-complex formation. For metal cations with E0 much more positive than that of iron, such as Ag(I), the removal mechanism is rapid reduction on the surface of nZVI. Meanwhile, metals with E0 slightly more positive than that of iron, such as Ni(II), can be immobilized at the nanoparticle surface via sorption and reduction. The synergetic effects of sorption, reduction, and encapsulation mechanisms of nZVI lead to rapid reactions and high efficiency for treatment and immobilization of many toxic heavy metals. Results also demonstrate that the XEDS-STEM technique is a powerful tool for studying reactions in individual nanoparticles and is particularly valuable for mapping trace-level elements in environmental media.

Onychomycosis secondary to onychomadesis: an underdiagnosed manifestation.

Onychomycosis is a rare nail disorder in early childhood, while onychomadesis is a periodic idiopathic, non-inflammatory disease that affects the nail matrix and is common in children especially in those who suffer from viral infections. In this study, we investigated recent cases of onychomycosis subsequent to periods of onychomadesis in children. Sixteen young children (six males, 10 females) with a mean age of 36.5 months were diagnosed with onychomadesis, and 13 of the patients had a history of viral infection prior to nail changes. Direct microscopy of nail scaling was positive in 11 cases (68.8%), and culture was positive in the same number of cases. Four Candida species were isolated: Candida glabrata was the most frequent, found in eight cases (72.7%), while C. albicans, C. parapsilosis and C. tropicalis, each were encountered in a single case. All children were treated successfully with or without topical bifonazole therapy.

Mesenchymal stem cell-conditioned medium accelerates wound healing with fewer scars.

Mesenchymal stem cells (MSCs) derived from umbilical cords (UC-MSCs) have been shown to enhance cutaneous wound healing by means of the paracrine activity. Fibroblasts are the primary cells involved in wound repair. The paracrine effects of UC-MSCs on dermal fibroblasts have not been fully explored in vitro or in vivo. Dermal fibroblasts were treated with conditioned media from UC-MSCs (UC-MSC-CM). In this model, UC-MSC-CM increased the proliferation and migration of dermal fibroblasts. Moreover, adult dermal fibroblasts transitioned into a phenotype with a low myofibroblast formation capacity, a decreased ratio of transforming growth factor-ß1,3 (TGF-ß1/3) and an increased ratio of matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMP/TIMP). Additionally, UC-MSC-CM-treated wounds showed accelerated healing with fewer scars compared with control groups. These observations suggest that UC-MSC-CM may be a feasible strategy to promote cutaneous repair and a potential means to realise scarless healing.

A case of chromoblastomycosis by Fonsecaea nubica indicating a possible insect route of transmission.

A first auricular case of chromoblastomycosis due to Fonsecaea nubica is reported in a 42-year-old Chinese male. He presented a slightly verrucous, erythematous plaque on his right auricle which had gradually extended over a 10-year period, and the patient reported a history of dog flea sting before onset of the lesions. Diagnosis was based on histopathological and mycological examination of clinical samples, which revealed muriform cells. Identification of the aetiological agent was assessed by morphological characteristics and confirmed at species level by sequencing of the rDNA internal transcribed spacer (ITS). The patient showed marked clinical improvement after 3 months combination therapy with itraconazole and terbinafine. The possible mode of transmission of auricular chromoblastomycosis is discussed.

Spatial dynamics of the bacterial community structure in the gastrointestinal tract of red kangaroo (Macropus rufus).

The quantification and community of bacteria in the gastrointestinal (GI) tract (stomach, jejunum, ileum, cecum, colon and rectum) of red kangaroos (Macropus rufus) were examined by using real-time PCR and paired-end Illumina sequencing. The quantification of bacteria showed that the number of bacteria in jejunum and rectum was significantly lower than that in colon and cecum (P < 0.05). A total of 1,872,590 sequences was remained after quality-filtering and 50,948 OTUs were identified at the 97 % similarity level. The dominant phyla in the GI tract of red kangaroos were identified as Actinobacteria, Bacteroidetes and Firmicutes. At the level of genus, the samples from different parts of GI tract clustered into three groups: stomach, small intestine (jejunum and ileum) and large intestine (cecum and rectum). Prevotella (29.81 %) was the most dominant genus in the stomach and significantly (P < 0.05) higher than that in other parts of GI tract. In the small intestine, Bifidobacterium (33.04, 12.14 %) and Streptococcus (22.90, 19.16 %) were dominant genera. Unclassified Ruminococcaceae was the most dominant family in large intestine and the total relative abundance of unclassified bacteria was above 50 %. In identified genera, Dorea was the most important variable to discriminate large intestine and it was significantly higher in cecum than in stomach, small intestine and colon (P < 0.05). Bifidobacterium (21.89 %) was the only dominant genus in colon. Future work on culture in vitro and genome sequencing of those unidentified bacteria might give us insight into the function of these microorganisms in the GI tract. In addition, the comparison of the bacterial community in the foregut of kangaroos and other herbivores and the rumen might give us insight into the mechanism of fiber degradation and help us exploit approaches to improve the feed efficiency and subsequently, reduce the methane emission from herbivores.