Skin Mast Cells Contribute to Sporothrix schenckii Infection

Background: Sporothrix schenckii (S. schenckii), a dimorphic fungus, causes sporotrichosis. Mast cells (MCs) have been described to be involved in skin fungal infections. The role of MCs in cutaneous sporotrichosis remains largely unknown. Objectives: To characterize the role and relevance of MCs in cutaneous sporotrichosis. Methods: We analyzed cutaneous sporotrichosis in wild-type (WT) mice and two different MC-deficient strains. In vitro, MCs were assessed for S. schenckii-induced cytokine production and degranulation after incubation with S. schenckii. We also explored the role of MCs in human cutaneous sporotrichosis. Results: WT mice developed markedly larger skin lesions than MC-deficient mice (> 1.5 fold) after infection with S. schenckii, with significantly increased fungal burden. S. schenckii induced the release of tumor necrosis factor alpha (TNF), interleukin (IL)-6, IL-10, and IL-1β by MCs, but not degranulation. S. schenckii induced larger skin lesions and higher release of IL-6 and TNF by MCs as compared to the less virulent S. albicans. In patients with sporotrichosis, TNF and IL-6 were increased in skin lesions, and markedly elevated levels in the serum were linked to disease activity. Conclusions: These findings suggest that cutaneous MCs contribute to skin sporotrichosis by releasing cytokines such as TNF and IL-6

Chymase-Cre; Mcl-1fl/fl Mice Exhibit Reduced Numbers of Mucosal Mast Cells

Mast cells (MCs) are considered as key effector cells in the elicitation of allergic symptoms, and they are essential players in innate and adaptive immune responses. In mice, two main types of MCs have been described: connective tissue MCs (CTMCs) and mucosal MCs (MMCs). However, little is known about the biological functions of MMCs, which is due to the lack of suitable models to investigate MMCs in vivo. Here, we aimed to generate a mouse model selectively deficient in MMCs. It has been previously described that Cre expressed under the control of the baboon α-chymase promotor is predominantly localized in MMCs. Therefore, we mated α-chymase-Cre transgenic mice with mice bearing a floxed allele of the myeloid cell leukemia sequence 1 (Mcl-1). Mcl-1 encodes for an intracellular antiapoptotic factor in MCs; hence, a selective reduction in MMCs was expected. Our results show that this new mouse model contains markedly reduced numbers of MMCs in mucosal tissues, whereas numbers of CTMCs are normal. Thus, Chm-Cre; Mcl-1fl/fl mice are a useful tool for the investigation of the pathophysiological functions of MMCs in vivo

The Number of MRGPRX2-Expressing Cells Is Increased in Skin Lesions of Patients With Indolent Systemic Mastocytosis, But Is Not Linked to Symptom Severity

BackgroundRecently, the expression of the mast cell (MC) receptor Mas-related G protein–coupled receptor X2 (MRGPRX2) has been detected in lesional skin of adult patients with cutaneous mastocytosis. As of yet, little is known about the clinical relevance of MRGPRX2 and its agonists in patients with mastocytosis, including indolent systemic mastocytosis (ISM).MethodsMRGPRX2 and MRGPRX2 agonists, cortistatin (CST), and major basic protein (MBP) were analyzed in lesional and non-lesional skin of patients with ISM and skin of healthy controls by immunohistochemistry. Co-localization of MRGPRX2 and MRGPRX2-mRNA with the MC marker tryptase was assessed by immunofluorescence microscopy and in situ hybridization, respectively. We assessed clinical, demographic, and laboratory data, including mastocytosis activity score (MAS), serum tryptase, and KIT D816V allele burden.ResultsThe number of MRGPRX2-expressing (MRGPRX2+) cells, MRGPRX2-mRNA+ MCs, and CST-expressing (CST+) and MBP-expressing (MBP+) cells was significantly higher in lesional skin as compared to non-lesional skin and/or skin of healthy controls (all p < 0.05). Increased numbers of MRGPRX2+ cells, MRGPRX2-mRNA+ MCs, and CST+ and MBP+ cells were not associated with clinical and laboratory features of ISM, including disease burden, symptom severity, evidence of anaphylaxis, and tryptase levels.ConclusionsSkin lesions of patients with ISM showed high numbers of MRGPRX2+ cells, although they were not linked to symptom severity. Clinical relevance of the MRGPRX2-mediated pathway of MC activation in ISM remains unclear and should be investigated in further studies

Experimental method for optimizing the molding conditions of hot-pressed briquette

In response to the problems of low strength and high permeability of coal materials in the current physical simulation test of coal mine gas dynamics, a set of experimental research methods for optimizing the molding conditions of hot-pressed briquette. Firstly, a hot-pressed briquette test system was independently established and the advantages and future improvement directions of the test system were summarized. At the same time, based on the Horsfield dense stacking theory, the optimal preparation plan for coal briquette materials was formulated. Finally, a molding condition optimization method was developed that combines the Markov distance measurement method and the golden section method. To verify the effectiveness of the experimental method, the secondary carbonization experiments of briquette were conducted under different molding pressure conditions by controlling the molding temperature to 311.8 ℃, heating rate to 5 ℃/min, and holding time to 5.3 h. The response characteristics of the microstructure, physical and mechanical properties, and permeability characteristics of the hot-pressed briquette under different molding pressure conditions were studied. The results show that with the increase of molding pressure, the total porosity gradually decreases, and the uniaxial compressive strength shows a trend of first increasing and then decreasing. The main forms of failure are block spalling and longitudinal fracture. The initial permeability shows a trend of first decreasing and then increasing, while the minimum permeability shows a trend of first decreasing, then increasing and then decreasing. Using the specific values of each molding condition as the test points, and the key parameters of hot-pressed coal and raw coal as the evaluation parameters, a sample matrix was constructed to calculate the Mahalanobis distance between hot-pressed briquette and raw coal under each molding condition, and then optimize the experimental interval using the golden section method. The optimized final molding pressure is 80 MPa. Under these molding conditions, the density, uniaxial compressive strength, and initial permeability of the hot-pressed briquette produced are 1.137 g/cm3, 12.21 MPa, and 1.32 × 10−15 m2, respectively. They are highly similar to the 1.132 g/cm3, 12.83 MPa, and 1.08 × 10−15 m2 of the raw coal, achieving the goal of improving the strength of the briquette and reducing the permeability of the briquette

Galectin-9 contributes to the pathogenesis of atopic dermatitis via T cell immunoglobulin mucin-3

BackgroundAtopic dermatitis (AD), a common type 2 inflammatory disease, is driven by T helper (TH) 2/TH22polarization and cytokines.Galectin-9 (Gal-9), via its receptor T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3), can promote TH2/TH22 immunity. The relevance of this in AD is largely unclear.ObjectivesTo characterize the role of TIM-3 and Gal-9 in the pathogenesis of AD and underlying mechanisms.MethodsWe assessed the expression of Gal-9 and TIM-3 in 30 AD patients, to compare them with those of 30 healthy controls (HC) and to explore possible links with disease features including AD activity (SCORAD), IgE levels, and circulating eosinophils and B cells. We also determined the effects of Gal-9 on T cells from the AD patients.ResultsOur AD patients had markedly higher levels of serum Gal-9 and circulating TIM-3-expressing TH1 and TH17 cells than HC. Gal-9 and TIM-3 were linked to high disease activity, IgE levels, and circulating eosinophils and/or B cells. The rates of circulating TIM-3-positive CD4+ cells were positively correlated with rates of TH2/TH22 cells and negatively correlated with rates of TH1/TH17 cells. Gal-9 inhibited the proliferation and induced the apoptosis of T cells in patients with AD, especially in those with severe AD.ConclusionOur findings suggest thatGal-9, via TIM-3, contributes to the pathogenesis of AD by augmenting TH2/TH22 polarization through the downregulation of TH1/TH17immunity. This makes Gal-9 and TIM-3 interesting to explore further, as possible drivers of disease and targets of novel AD treatment

Omics-based interpretation of synergism in a soil-derived cellulose-degrading microbial community

Reaching a comprehensive understanding of how nature solves the problem of degrading recalcitrant biomass may eventually allow development of more efficient biorefining processes. Here we interpret genomic and proteomic information generated from a cellulolytic microbial consortium (termed F1RT) enriched from soil. Analyses of reconstructed bacterial draft genomes from all seven uncultured phylotypes in F1RT indicate that its constituent microbes cooperate in both cellulose-degrading and other important metabolic processes. Support for cellulolytic inter-species cooperation came from the discovery of F1RT microbes that encode and express complimentary enzymatic inventories that include both extracellular cellulosomes and secreted free-enzyme systems. Metabolic reconstruction of the seven F1RT phylotypes predicted a wider genomic rationale as to how this particular community functions as well as possible reasons as to why biomass conversion in nature relies on a structured and cooperative microbial community

Polar auxin transport modulates early leaf flattening

The flattened leaf form is an important adaptation for efficient photosynthesis, and the developmental process of flattened leaves has been intensively studied. Classic microsurgery studies in potato and tomato suggest that the shoot apical meristem (SAM) communicates with the leaf primordia to promote leaf blade formation. More recently, it was found that polar auxin transport (PAT) could mediate this communication. However, it is unclear how the expression of leaf patterning genes is tailored by PAT routes originating from SAM. By combining experimental observations and computer model simulations, we show that microsurgical incisions and local inhibition of PAT in tomato interfere with auxin transport toward the leaf margins, reducing auxin response levels and altering the leaf blade shape. Importantly, oval auxin responses result in the bipolar expression of SlLAM1 that determines leaf blade formation. Furthermore, wounding caused by incisions promotes degradation of SlREV, a known regulator of leaf polarity. Additionally, computer simulations suggest that local auxin biosynthesis in early leaf primordia could remove necessity for external auxin supply originating from SAM, potentially explaining differences between species. Together, our findings establish how PAT near emerging leaf primordia determines spatial auxin patterning and refines SlLAM1 expression in the leaf margins to guide leaf flattening.Peer reviewe

Data_Sheet_2_Hemoptysis caused by Parvimonas micra: case report and literature review.pdf

BackgroundParvimonas micra (P. micra), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated with diverse diseases. The diagnostic trajectory for P. micra-related diseases encounters delays, often with severe consequences, including fatality, attributed to the absence of symptom specificity and challenges in culture. The absence of a consensus on the diagnostic and therapeutic approaches to P. micra exacerbates the complexity of addressing associated conditions. This study aims to elucidate and scrutinize the clinical manifestations linked to P. micra, drawing insights from an extensive literature review of pertinent case reports.Case presentationA 53-year-old male sought medical attention at our institution presenting with recurrent hemoptysis. Empirical treatment was initiated while awaiting pathogen culture results; however, the patient’s symptoms persisted. Subsequent metagenomic next-generation sequencing (mNGS) analysis revealed a pulmonary infection attributable to P. micra. Resolution of symptoms occurred following treatment with piperacillin sulbactam sodium and moxifloxacin hydrochloride. A comprehensive literature review, utilizing the PubMed database, was conducted to assess case reports over the last decade where P. micra was identified as the causative agent.ConclusionThe literature analysis underscores the predilection of P. micra for immunocompromised populations afflicted by cardiovascular diseases, diabetes, orthopedic conditions, and tumors. Risk factors, including oral and periodontal hygiene, smoking, and alcohol consumption, were found to be associated with P. micra infections. Clinical manifestations encompassed fever, cough, sputum production, and back pain, potentially leading to severe outcomes such as Spondylodiscitis, septic arthritis, lung abscess, bacteremia, sepsis, and mortality. While conventional bacterial culture remains the primary diagnostic tool, emerging technologies like mNGS offer alternative considerations. In terms of treatment modalities, β-lactam antibiotics and nitroimidazoles predominated, exhibiting recovery rates of 56.10% (46/82) and 23.17% (19/82), respectively. This case report and literature review collectively aim to enhance awareness among clinicians and laboratory medicine professionals regarding the intricacies of P. micra-associated infections.</p