The Phylogeny and Taxonomy of Cryptothecia (Arthoniaceae, Ascomycota) and Myriostigma (Arthoniaceae, Ascomycota), including Three New Species and Two New Records from China.

Cryptothecia and Myriostigma are important elements of crustose lichen communities in tropical to subtropical forests, but little research has been done on these two genera in China. Morphological and molecular phylogenetic approaches to investigate species diversity of Cryptothecia and Myriostigma from Southern China were carried out in this study. We find five species of Cryptothecia and Myriostigma in our study, including three new species (M. flavescens, M. hainana and M. laxipunctata) and two new records (C. bartlettii and C. inexspectata). In addition, a phylogenetic tree based on mtSSU, RPB2 and nLSU illustrates the placement of the five species and supports the delimitation of the three new taxa. Detailed descriptions of morphological, ecological and chemical characteristics and illustrations are provided for every species. A key to all known Chinese Cryptothecia and Myriostigma species is also provided.

MDA5 Enhances Invasive Candida albicans Infection by Regulating Macrophage Apoptosis and Phagocytosis/Killing Functions.

Candida albicans is a common opportunistic pathogenic fungus. The innate immune system provides the first-line host defense against fungal infection. Innate immune receptors and downstream molecules have been shown to play various roles during fungal infection. The innate immune receptor MDA5, encoded by the gene Ifih1, enhances host resistance against viral and Aspergillus fumigatus infection by inducing the production of interferons (IFNs). However, the role of MDA5 in C. albicans infection is still unclear. Here, we found that the gene expression levels of IFIH1 were significantly increased in innate immune cells after C. albicans stimulation through human bioinformatics analysis or mouse experiments. Through in vivo study, MDA5 was shown to enhance host susceptibility to C. albicans infection independent of IFN production. Instead, MDA5 exerted its influence on macrophages and kidneys by modulating the expression of Noxa, Bcl2, and Bax, thereby promoting apoptosis. Additionally, MDA5 compromised killing capabilities of macrophage by inhibition iNOS expression. The introduction of the apoptosis inducer PAC1 further impaired macrophage functions, mimicking the enhancing effect of MDA5 on C. albicans infection. Furthermore, the administration of macrophage scavengers increased the susceptibility of Ifih1-/- mice to C. albicans. The founding suggests that MDA5 promote host susceptibility to invasive C. albicans by enhancing cell apoptosis and compromising macrophage functions, making MDA5 a target to treat candidiasis.

Intestinal epithelial SNAI1 promotes the occurrence of colorectal cancer by enhancing EMT and Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is a prevalent cause of cancer and mortality on a global scale. SNAI1, a member of the zinc finger transcription superfamily, is a significant contributor to embryonic development and carcinogenesis through the process of epithelial-mesenchymal transition (EMT). While prior research utilizing CRC cells and clinical data has demonstrated that SNAI1 facilitates CRC progression through diverse mechanisms, the precise manner in which epithelial SNAI1 regulates CRC development in vivo remains unclear. In this study, colitis and colitis-associated CRC were induced through the use of intestinal epithelium-specific Snai1 knockout (Snai1 cKO) mice. Our findings indicate that Snai1 cKO mice exhibit a reduced susceptibility to acute colitis and colitis-associated CRC compared to control mice. Western-blot analysis of colon tissues revealed that Snai1 cKO mice exhibited a higher overall apoptosis level during tumor formation than control mice. No significant differences were observed in the activation of the classical p53 signaling pathway. However, Snai1 cKO mice exhibited weakened EMT and Wnt/ß-catenin pathway activation. In summary, our study has provided evidence in vivo that the intestinal epithelial SNAI1 protein suppresses apoptosis, amplifies the EMT, and activates the Wnt/ß-catenin signaling pathways in both early and late phases of CRC formation, thus promoting the development and progression of colitis-associated CRC.

Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels.

Objective: The widespread use of antibiotics has inevitably led to the emergence of multidrug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making treatment of this infection a serious challenge. This study aimed to explore new treatment strategies for MRSA infection. Methods: The structure of Fe3O4 NPs with limited antibacterial activity was optimized, and the Fe2+ ↔ Fe3+ electronic coupling was eliminated by replacing 1/2 Fe2+ with Cu2+. A new type of copper-containing ferrite nanoparticles (hereinafter referred to as Cu@Fe NPs) that fully retained oxidation-reduction activity was synthesized. First, the ultrastructure of Cu@Fe NPs was examined. Then, antibacterial activity was determined by testing the minimum inhibitory concentration (MIC) and safety for use as an antibiotic agent. Next, the mechanisms underlying the antibacterial effects of Cu@Fe NPs were investigated. Finally, mice models of systemic and localized MRSA infections was established for in vivo validation. Results: It was found that Cu@Fe NPs exhibited excellent antibacterial activity against MRSA with MIC of 1 µg/mL. It effectively inhibited the development of MRSA resistance and disrupted the bacterial biofilms. More importantly, the cell membranes of MRSA exposed to Cu@Fe NPs underwent significant rupture and leakage of the cell contents. Cu@Fe NPs also significantly reduced the iron ions required for bacterial growth and contributed to excessive intracellular accumulation of exogenous reactive oxygen species (ROS). Therefore, these findings may important for its antibacterial effect. Furthermore, Cu@Fe NPs treatment led to a significant reduction in colony forming units within intra-abdominal organs, such as the liver, spleen, kidney, and lung, in mice with systemic MRSA infection, but not for damaged skin in those with localized MRSA infection. Conclusion: The synthesized nanoparticles has an excellent drug safety profile, confers high resistant to MRSA, and can effectively inhibit the progression of drug resistance. It also has the potential to exert anti-MRSA infection effects systemically in vivo. In addition, our study revealed a unique multifaceted antibacterial mode of Cu@Fe NPs: (1) an increase in cell membrane permeability, (2) depletion of Fe ions in cells, (3) generation of ROS in cells. Overall, Cu@Fe NPs may be potential therapeutic agents for MRSA infections.

Retrospective comparison of stereotactic body radiotherapy versus intensity-modulated radiotherapy for stage III ultra-central squamous non-small-cell lung cancer.

Aim: To analyze the efficacy and toxicity of stereotactic body radiotherapy (SBRT) versus intensity-modulated radiotherapy (IMRT) in stage III patients with ultra-central squamous non-small-cell lung cancer (sqNSCLC). Methods: Forty-four stage III patients with ultra-central sqNSCLC receiving SBRT (n = 15) or IMRT (n = 29) between December 2014 and August 2017 were reviewed. Results: At a median follow-up of 16.5 months, the 1-year local control rate of SBRT and IMRT was 60.8 and 37.5%, respectively (p = 0.23); the median overall survival was 17 versus 18 months (p = 0.48); ≥3 grade toxicity was 20 versus 24.1% (p = 0.83). Conclusion: SBRT is effective and patient friendly for stage III patients with ultra-central sqNSCLC. Toxicity might be tolerable with a moderate dose five to six fraction regimen. However, more prospective studies are warranted.

Stereotactic gamma-ray body radiation therapy for asynchronous bilateral renal cell carcinoma.

PURPOSE: To preliminarily evaluate the feasibility, therapeutic effect and toxicity of stereotactic gamma-ray body radiation therapy (γ-SBRT) for asynchronous bilateral renal cell carcinoma (bRCC). MATERIALS AND METHODS: A retrospective analysis was performed on the clinical data of nine patients with asynchronous bRCC who were unable to undergo surgery and received γ-SBRT between February 2002 and May 2012. A total dose of 36-51 Gy was delivered to the 50 % isodose line covering the planning target volume at 3-5 Gy/fraction, whereas a total dose of 60-85 Gy was delivered at 5-7 Gy/fraction to the gross target volume. The local control rate (LC) and overall survival rate (OS) were calculated using the Kaplan-Meier method. RESULTS: Patient follow-up ended in March 2013 and the follow-up rate was 100 %. Of the nine patients, none presented with complete remission and five (55.6 %) achieved partial remission. The objective response rate was 55.6 %. The 1-, 3- and 5-year LC rates were 64.8, 43.2 and 43.2 %, respectively. The 1-, 3- and 5-year OS rates were 66.7, 53.3 and 35.6 %, respectively. Four (44.4 %) patients had an acute radiation reaction; there were two cases of grade I leukocytopenia and two cases of grade I gastrointestinal reactions. Late radiation-induced toxicity consisted of grade II gastrointestinal reactions in two patients. CONCLUSION: Stereotactic gamma-ray body radiation therapy was found to be safe and effective in the treatment of asynchronous bRCC. Improved prognosis will require individualised treatment and a combination of multiple therapeutic approaches; this will be a primary research trend in the future.