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Introduction: Cutibacterium acnes (C. acnes) resides in various organs such as the skin, prostate, eye, nose, stomach, and intestine, indicating the possibility of extensive crosstalk between this bacterium and the human body. C. acnes strains are classified into three subspecies based on phylogenetics and distinguishable phenotypes. Among them, C. acnes subsp. defendens strains are characterized by anti-inflammatory features, raising expectations for their potential as future microbiome therapeutics. However, the heterogeneity of C. acnes subsp. defendens and its corresponding immunological functions have not been clearly addressed. Methods: The genetic diversity of the strains was assessed using single- and multi-locus sequence typing. Their immune-modulatory functions were evaluated in vitro using 2D and 3D assays with immune and epithelial cells. The anti-inflammatory effects were further confirmed in vivo using a rosacea-like mouse model. Comparative genomic and transcriptomic analyses were conducted to uncover mechanisms underlying the immunosuppressive activity of the strains. Results: We demonstrated that the newly isolated C. acnes subsp. defendens strains, exhibiting phenotypic heterogeneity, are distinctly clustered using single- and multi-locus sequence typing methods. These strains showed strong immune-regulatory functions in immune and epithelial cell-based 2D and 3D in vitro assays. Furthermore, their anti-inflammatory role was functionally confirmed in vivo using a rosacea-like mouse model, where they alleviated skin lesions characterized by hyperplasia and dermal inflammation. Comparative transcriptomics revealed that these strains may exert their immunosuppressive effects through the enhanced expression of acnecins and transcriptional variation in envelope stress regulators (specifically the two-component systems, CesSR homologs). Additionally, we propose that these C. acnes type II strains produce anti-inflammatory metabolites or peptides smaller than 3 kDa, which are associated with elevated pyrimidine and reduced L-arginine biosynthesis. Discussion: The newly isolated C. acnes subsp. defendens strains demonstrate significant anti-inflammatory properties both in vitro and in vivo , suggesting their potential as microbiome-based therapeutics. Their unique genomic and transcriptomic profiles, including the production of small bioactive compounds and specific transcriptomic patterns, underpin their immunosuppressive capabilities. These findings provide a foundation for developing novel treatments for inflammatory skin conditions, such as rosacea. [ABSTRACT FROM AUTHOR]

According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.

Background and Objective: Although extracorporeal membrane oxygenation (ECMO) is an essential life-saving technique for patients with refractory cardiopulmonary shock, it can be fatal in certain cases. Case Presentation: A 19-year-old girl treated with ECMO presented with acute limb ischemia 2 days after cannula removal. The decannulation was performed percutaneously by an interventional cardiologist, and the vascular surgery department was consulted after the patient developed symptoms. The first suspected diagnosis was thrombosis due to incorrect use of the closure device. However, the artery had ruptured due to the insertion of a catheter with a cannula that was larger than the patient's artery. Management and Outcome: Fortunately, excessive bleeding due to the size-mismatched cannula was prevented by an unintentional complication of the closing device, which saved the patient's life. She underwent a right common femoral artery thrombectomy and patch angioplasty. Hospital guidelines have changed regarding the surgical removal of ECMO cannulas. Discussion: This report aims to highlight the importance of two aspects that are critical to a successful outcome: individualized cannula selection followed by precise insertion and removal and postoperative evaluation of a patient's final status. [ABSTRACT FROM AUTHOR]

Follicle Architects in the Colonic Mucosa Experimental Salmonella infections in the colon of mice are associated with a heterogeneous infiltrate of inflammatory myeloid cells including a predominance of cells expressing the CX3CR1 chemokine receptor. Koscsó et al. used a fluorescent reporter mouse strain to separate the inflammatory myeloid infiltrate into subsets of cells with low, intermediate, and high levels of CX3CR1 expression. RNA sequencing analysis provided clues to the functional roles of each subset. The CX3CR1hi macrophages were enriched within tertiary lymphoid structures that developed at mucosal sites of Salmonella invasion and contributed to induction of localized IgA antibody responses to Salmonella through expression of CXCL13, TGF-β1, and IL-10. These findings enhance our understanding of the functional diversification of the macrophage subsets associated with colonic inflammation. Intestinal mononuclear phagocytes (MPs) are composed of heterogeneous dendritic cell (DC) and macrophage subsets necessary for the initiation of immune response and control of inflammation. Although MPs in the normal intestine have been extensively studied, the heterogeneity and function of inflammatory MPs remain poorly defined. We performed phenotypical, transcriptional, and functional analyses of inflammatory MPs in infectious Salmonella colitis and identified CX3CR1+ MPs as the most prevalent inflammatory cell type. CX3CR1+ MPs were further divided into three distinct populations, namely, Nos2+CX3CR1lo, Ccr7+CX3CR1int (lymph migratory), and Cxcl13+CX3CR1hi (mucosa resident), all of which were transcriptionally aligned with macrophages and derived from monocytes. In follow-up experiments in vivo, intestinal CX3CR1+ macrophages were superior to conventional DC1 (cDC1) and cDC2 in inducing Salmonella-specific mucosal IgA. We next examined spatial organization of the immune response induced by CX3CR1+ macrophage subsets and identified mucosa-resident Cxcl13+CX3CR1hi macrophages as the antigen-presenting cells responsible for recruitment and activation of CD4+ T and B cells to the sites of Salmonella invasion, followed by tertiary lymphoid structure formation and the local pathogen-specific IgA response. Using mice we developed with a floxed Ccr7 allele, we showed that this local IgA response developed independently of migration of the Ccr7+CX3CR1int population to the mesenteric lymph nodes and contributed to the total mucosal IgA response to infection. The differential activity of intestinal macrophage subsets in promoting mucosal IgA responses should be considered in the development of vaccines to prevent Salmonella infection and in the design of anti-inflammatory therapies aimed at modulating macrophage function in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background and Objectives: Proteome analysis of periodontal ligament stem cells (PDLSCs) could be used to study the function of PDL tissue. We used a label‐free quantitative proteomic technique to investigate differentially expressed proteins (DEPs) in human PDLSCs (hPDLSCs) compared to human bone marrow mesenchymal stem cells (hBMSCs) and identify proteins specific to hPDLSCs. Material and Methods: hPDLSCs (n = 3) and hBMSCs (n = 3) were cultured and harvested for protein extraction and trypsin digestion. The proteomes of both cell types were analyzed by nano‐liquid chromatography/tandem mass spectrometry. DEPs in hPDLSCs compared to hBMSCs were detected by label‐free quantification and evaluated through signal transduction pathway and gene ontology (GO) analysis. Results: In total, 690 and 771 proteins were identified from hPDLSCs and hBMSCs, of which 561 proteins were in common and 124 DEPs were found between hPDLSCs and hBMSCs. Fifty‐eight proteins were expressed at significantly higher levels in hPDLSCs, whereas 66 proteins were expressed at lower levels compared to hBMSCs. The more highly expressed proteins were associated with translation and initiating protein synthesis, and lower expressed proteins were related to cell aging and metabolic processes. Proteins unique to hPDLSCs and hBMSCs were associated with translation and metabolic processes, respectively. Conclusion: Our results demonstrate evidence of distinct differences in protein expression between hPDLSCs and hBMSCs by using label‐free quantitative proteomic analysis which was the first attempt in this field. DEPs included previously reported hPDLSC marker proteins and novel marker candidates, such as microtubule‐associated protein, CTP synthase 1 and stathmin, which could be the markers for developing periodontal disease diagnostics and therapies. [ABSTRACT FROM AUTHOR]

A high-signal-to-noise ratio (SNR) inductor-free 3-D hover sensor is presented. This paper solved the low-signal component issue, which is the biggest problem in 3-D hover sensing. For this purpose, we propose a power- and cost-effective high-voltage driving technique in the self-capacitance sensing scheme (SCSS) and lateral resolution optimization of a touch panel. In addition, the huge panel offsets in the SCSS from both vertical panel capacitance (CSV) and horizontal panel capacitance (CSH) can effectively be eliminated by exploiting the panel’s natural characteristics, without using other costly resources. Therefore, in the proposed design, the total calibration block is minimized only for parasitic capacitance mismatches. Last, by adopting new driving scheme, two-phase simultaneous sensing is enabled to increase the SNR further. The proposed hover sensing system achieved a 39-dB SNR at a 1-cm hover point under a 240-Hz scan rate condition in noise experiments, while consuming 183 \mu \textW /electrode and 0.73 mm2/sensor, which are the lowest power per electrode performance and the smallest die-area per sensor performance, respectively, in comparison to the state-of-the-art 3-D hover systems. [ABSTRACT FROM AUTHOR]