Disseminated Coinfection by Mycobacterium fortuitum and Talaromyces marneffei in a Non-HIV Case.

BACKGROUND: Mycobacterium fortuitum is a rapidly growing non-tuberculous mycobacterium (NTM) with weak pathogenicity. Here, we present a rare case of disseminated M. fortuitum and Talaromyces marneffei coinfection in a human immunodeficiency virus (HIV) negative patient. CASE PRESENTATION: A 28-year-old female was admitted to our hospital due to 2 months of swelling of lymph nodes on the right side of her cervix, accompanied by repeated low fever for more than 1 month. Biopsy of the right cervical lymph node and endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) both suggested granulomatous inflammation. The bacterial culture and mycobacteria examination of the lesion as well as HIV antibody test were all negative. Disseminated T. marneffei infection was diagnosed by the quantitative polymerase chain reaction (qPCR) results from the blood showing 1798 copies/ul. In the meantime, treatment with amphotericin B combined with cefoxitin was administered for suspected NTM infection. However, the once-dropped fever recurred and the lymph nodes continued to swell. Metagenomics next-generation sequencing (mNGS) detection of the lymph nodes indicated M. fortuitum. After combination treatment with amphotericin B, voriconazole, linazolamide, and imipenem, the patient's body temperature returned to normal, the lymph node swelling was gradually reduced, and the lung lesion was absorbed. CONCLUSION: We report the first case of an HIV-negative patient diagnosed with disseminated M. fortuitum and T. marneffei coinfection with nonspecific clinical manifestation, in order to heighten awareness of these infections.

[Mutual Influence Between Microbial Community, Wastewater Characteristics, and Antibiotic Resistance Genes During Spiramycin Production Wastewater Treatment].

Wastewater from antibiotic production usually contains a huge amount of antibiotic resistance genes (ARG). Therefore, it is essential to study the dissemination and control of antibiotic resistance during the treatment of antibiotic production wastewater. The mutual influence between microbial community evolution, wastewater characteristics, and ARG was investigated using high-throughput sequencing and a variety of statistical analysis methods. Results showed that the influent characteristics had only a marginal influence on the microbial community of each treatment section. Methanogenic bacteria and sulfate-reducing bacteria were the dominant microbes in the anaerobic and anoxic tank. Chemical oxygen demand (COD), NO2--N, and PO43--P exhibited an intimate relationship with the microbial community, whereas biomass, NH4+-N, and COD showed a strong correlation with ARG and mobile genetic elements (MGE). In the sludge, more genera (including pathogenic bacteria) were significantly correlated with ARG and MGE than that in the wastewater, indicating that bacteria in the sludge had a greater chance of acquiring pathogenicity and resistance. Therefore, more attnetion should be given to waste sludge from the treatment plants of antibiotic production wastewater. This research could provide further understanding of antibiotic resistance dissemination and control during wastewater treatment, especially for antibiotic production wastewater.

Distinct multilevel misregulations of Parkin and PINK1 revealed in cell and animal models of TDP-43 proteinopathy.

Parkin and PINK1 play an important role in mitochondrial quality control, whose malfunction may also be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Excessive TDP-43 accumulation is a pathological hallmark of ALS and is associated with Parkin protein reduction in spinal cord neurons from sporadic ALS patients. In this study, we reveal that Parkin and PINK1 are differentially misregulated in TDP-43 proteinopathy at RNA and protein levels. Using knock-in flies, mouse primary neurons, and TDP-43Q331K transgenic mice, we further unveil that TDP-43 downregulates Parkin mRNA, which involves an unidentified, intron-independent mechanism and requires the RNA-binding and the protein-protein interaction functions of TDP-43. Unlike Parkin, TDP-43 does not regulate PINK1 at an RNA level. Instead, excess of TDP-43 causes cytosolic accumulation of cleaved PINK1 due to impaired proteasomal activity, leading to compromised mitochondrial functions. Consistent with the alterations at the molecular and cellular levels, we show that transgenic upregulation of Parkin but downregulation of PINK1 suppresses TDP-43-induced degenerative phenotypes in a Drosophila model of ALS. Together, these findings highlight the challenge associated with the heterogeneity and complexity of ALS pathogenesis, while pointing to Parkin-PINK1 as a common pathway that may be differentially misregulated in TDP-43 proteinopathy.

Integrin ß3/Akt signaling contributes to platelet-induced hemangioendothelioma growth.

Hemangioendothelioma (HE) is a type of angiomatous lesions that features endothelial cell proliferation. Understanding the mechanisms orchestrating HE angiogenesis can provide therapeutic insights. It has been shown that platelets can support normal and malignant endothelial cells during angiogenesis. Using the mouse endothelial-derived EOMA cell line as a model of HE, we explored the regulatory effect of platelets. We found that platelets stimulated EOMA proliferation but did not mitigate apoptosis. Furthermore, direct platelet-EOMA cell contact was required and the proliferation was mediated via integrin ß3/Akt signaling in EOMA cells. SiRNA knockdown of integrin ß3 and inhibition of Akt activity significantly abolished platelet-induced EOMA cell proliferation in vitro and tumor development in vivo. These results provide a new mechanism by which platelets support HE progression and suggest integrin ß3 as a potential target to treat HE.

[Fate of ARB and ARGs During Wastewater Treatment Process of Spiramycin Production].

Antibiotic resistant bacteria (ARB) and antibiotic resistance gene(ARG) pose great risk to both environment and human health. This study aimed to investigate the fate of macrolide resistant bacteria, six macrolide resistance genes ermB, ermF, ermX, mefA, ereA, mphB and three transfer elements ISCR1, intIl and Tn916/1545 during wastewater biological treatment processes of spiramycin production. Samples were collected from an antibiotic wastewater treatment station in different seasons. Results showed that the total heterotrophs and Enterococci were mostly removed during wastewater biological treatment, with the reduction of 1. 6-2. 1 logs for total heterotrophs and of 3. 7 logs for Enterococci, respectively. For 94 antibiotic resistant Enterococci individually isolated from four different treatment units including adjusting tank, anaerobic tank, anoxic tank, and aerobic tank, all of these strains showed resistance to spiramycin, azithromycin, erythromycin, and clarithromycin; moreover, the antibiotic resistance rates was not reduced in the effluent. Results of PCR and quantitative PCR showed that 80% of antibiotic resistant Enterococci were positive for PCR amplification of erAB, but negative for PCR amplification of other genes. Concentrations of ermB and ermF were peaked in the spring and autumn samples. Resistance genes of ermB, ermF, mefA, ereA, mphB and transfer element of Tn916/1545 were reduced to some degree during antibiotic production wastewater treatment, but concentrations of ermX, intIl, ISCRl in the effluent were higher than those in the influent. The abundance of mefA, ereA and Tn916/1545 were reduced during wastewater treatment process, and the better removal performance for mefA, ereA, Tn916/1545 occurred in spring than in autumn; however, the abundance of ermX, intI1 and ISCR1 were increased.