The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and tuf2 gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, P = 0.201), but distinct microbial communities were identified at the class (R2 = 0.104, P = 0.023) and order (R2 = 0.0904, P = 0.038) levels. Increased relative abundance of the genera Catenococcus, Vibrio, Roseomonas, Acinetobacter, and unclassified Clostridiales was associated with increased skin disease burden (P < 0.005, q < 0.05). Performed to accurately resolve nasal Staphylococcus at the species level, tuf2 gene amplicon sequencing revealed no significant differences between mycosis fungoides/Sézary syndrome and healthy controls. Although S. aureus has been shown to worsen CTCL through its toxins, no increase in the relative abundance of this taxon was observed in nasal samples. Despite the lack of differences in Staphylococcus, the CTCL nasal microbiome was characterized by shifts in numerous other bacterial taxa. These data add to our understanding of the greater CTCL microbiome and provide context for comprehending nasal-skin and host‒tumor‒microbial relationships.

UNASSIGNED: Hepatic encephalopathy (HE) is a major complication after transjugular intrahepatic portosystemic shunt (TIPS) and is primarily influenced by the gut microbiota. We aimed to evaluate alterations in the microbiota after TIPS and the association between such alterations and HE.
UNASSIGNED: We conducted a prospective longitudinal study of 106 patients with cirrhosis receiving TIPS. Faecal samples were collected before and after TIPS, and the gut microbiota was analysed by 16S ribosomal RNA sequencing.
UNASSIGNED: Among all patients, 33 developed HE (HE+ group) within 6 months after TIPS and 73 did not (HE- group), and 18 died during follow-up. After TIPS, the autochthonous taxa increased, whereas the potential pathogenic taxa decreased in the HE- group, and the autochthonous taxon Lachnospiraceae decreased in the HE+ group. Furthermore, synergism among harmful bacteria was observed in all patients, which was weakened in the HE- group (p <0.001) but enhanced in the HE+ group (p <0.01) after TIPS. Variations of 5 autochthonous taxa, namely, Coprococcus, Ruminococcus, Blautia, Ruminococcaceae_uncultured, and Roseburia, were negatively correlated with the severity of HE. Notably, increased abundances of Coprococcus and Ruminococcus were protective factors against HE, and the incidences of HE in patients with improved, stable, and deteriorated microbiota after TIPS were 13.3, 25.9, and 68.2%, respectively. Higher total bilirubin level, Child-Pugh score, model for end-stage liver disease score, Granulicatella, and Alistipes and lower Subdoligranulum before TIPS were the independent risk factors for death.
UNASSIGNED: Alterations in gut dysbiosis were negatively related to the occurrence and severity of post-TIPS HE, and the pre-TIPS microbiota were associated with death, suggesting the gut microbiota could be a promising potential biological target for screening suitable patients receiving TIPS and prevention and treatment of post-TIPS HE.
UNASSIGNED: Alterations in the gut microbiota after transjugular intrahepatic portosystemic shunt (TIPS) and the relationship between such alterations and post-TIPS hepatic encephalopathy (HE) remain unclear. We therefore performed this study and found that after TIPS, restoration of the gut microbiota, mainly characterised by expansion of autochthonous taxa, depletion of harmful taxa, and weakening of synergism among harmful bacteria, was inversely related to the occurrence and severity of post-TIPS HE.

Cutaneous T-cell lymphoma (CTCL) is a life-debilitating malignancy of lymphocytes homing to the skin. Although CTCL is thought to arise from a combination of genetic, epigenetic, and environmental factors, specific triggers are unclear. The skin is colonized by a unique microbiota and is heavily influenced by its interactions. We hypothesized that adaptive immune responses to skin commensals lead to clonal T-cell proliferation and transformation in the appropriate genetic background. We therefore collected lesional and nonlesional skin microbiota from patients with CTCL to study T cell interactions using skin T cell explants and peripheral, skin-homing CD4+ T cells. By various methods, we identified Bacillus safensis in CTCL lesions, a rare human commensal in healthy skin, and showed that it can induce malignant T cell activation and cytokine secretion. Taken together, our data suggest microbial triggers in the skin microbiota of patients with CTCL as potential instigators of tumorigenesis.

Pulmonary arterial hypertension (PAH) is a disease of abnormal pulmonary vascular remodeling whose medical therapies are thought to primarily act as vasodilators but also may have effects on pulmonary vascular remodeling. The angiotensin II type 1 receptor (AT1R) is a G protein-coupled receptor that promotes vasoconstriction through heterotrimeric G proteins but also signals via β-arrestins, which promote cardioprotective effects and vasodilation through promoting cell survival. We found that an AT1R β-arrestin-biased agonist promoted vascular remodeling and worsened PAH, suggesting that the primary benefit of current PAH therapies is through pulmonary vascular reverse remodeling in addition to their vasodilation.

The entrenched dogma of a sterile middle ear mucosa in health is incongruent with its periodic aeration and seeding with saliva aerosols. To test this, we sequenced 16S rRNA-V4 amplicons from otic secretions collected at the nasopharyngeal orifice of the tympanic tube and, as controls, oropharyngeal and buccal samples. The otic samples harbored a rich diversity of oral keystone genera and similar functional traits but were enriched in anaerobic genera in the Bacteroidetes (Prevotella and Alloprevotella), Fusobacteria (Fusobacterium and Leptotrichia) and Firmicutes (Veillonella) phyla. Facultative anaerobes in the Streptococcus genus were also abundant in the otic and oral samples but corresponded to distinct, and sometimes novel, cultivars, consistent with the ecological diversification of the oral migrants once in the middle ear microenvironment. Neutral community models also predicted a large contribution of oral dispersal to the otic communities and the positive selection of taxa better adapted to growth and reproduction under limited aeration. These results challenge the traditional view of a sterile middle ear in health and highlight hitherto unknown roles for oral dispersal and episodic ventilation in seeding and diversifying otic biofilms.

Circular RNAs (circRNAs) are a very interesting class of conserved single-stranded RNA molecules derived from exonic or intronic sequences by precursor mRNA back-splicing. Unlike canonical linear RNAs, circRNAs form covalently closed, continuous stable loops without a 5\'end cap and 3\'end poly(A) tail, and therefore are resistant to exonuclease digestion. The majority of circRNAs are highly abundant, and conserved across different species with a tissue or developmental-stage-specific expression. circRNAs have been shown to play important roles as microRNA sponges, regulators of gene splicing and transcription, RNA-binding protein sponges and protein/peptide translators. Emerging evidence reveals that circRNAs function in various human diseases, particularly cancers, and may function as better predictive biomarkers and therapeutic targets for cancer treatment. In consideration of their potential clinical relevance, circRNAs have become a new research hotspot in the field of tumor pathology. In the present study, the current understanding of the biogenesis, characteristics, databases, research methods, biological functions subcellular distribution, epigenetic regulation, extracellular transport and degradation of circRNAs was discussed. In particular, the multiple databases and methods involved in circRNA research were first summarized, and the recent advances in determining the potential roles of circRNAs in tumor growth, migration and invasion, which render circRNAs better predictive biomarkers, were described. Furthermore, future perspectives for the clinical application of circRNAs in the management of patients with cancer were proposed, which could provide new insights into circRNAs in the future.

Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease begins as an infection of lungs, which is self-limiting in the majority of infections; however, some develop severe respiratory distress and organ failures. Lung microbiome, though neglected previously have received interest recently because of its association with several respiratory diseases and immunity. Lung microbiome can modify the risk and consequences of COVID-19 disease by activating an innate and adaptive immune response. In this review, we examine the current evidence on COVID-19 disease and lung microbiome, and how lung microbiome can affect SARS-CoV-2 infection and the outcomes of this disease. To date there is no direct evidence from human or animal studies on the role of lung microbiome in modifying COVID-19 disease; however, related studies support that microbiome can play an essential role in developing immunity against viral infections. Future studies need to be undertaken to find the relationship between lung microbiome and COVID-19 disease.

MicroRNAs (miRNAs) are short non-coding RNA species that play key roles in post-transcriptional regulation of gene expression. MiRNAs also serve as a promising source of early biomarkers for different environmental exposures and health effects, although there is limited information linking miRNA changes to specific target pathways. In this study, we measured liver miRNAs in male B6C3F1 mice exposed to a known chemical activator of the peroxisome proliferator-activated receptor alpha (PPARα) pathway, di(2-ethylhexyl) phthalate (DEHP), for 7 and 28 days at concentrations of 0, 750, 1500, 3000, or 6000 ppm in feed. At the highest dose tested, DEHP altered 61 miRNAs after 7 days and 171 miRNAs after 28 days of exposure, with 48 overlapping miRNAs between timepoints. Analysis of these 48 common miRNAs indicated enrichment in PPARα-related targets and other pathways related to liver injury and cancer. Four of the 10 miRNAs exhibiting a clear dose trend were linked to the PPARα pathway: mmu-miRs-125a-5p, -182-5p, -20a-5p, and -378a-3p. mmu-miRs-182-5p and -378a-3p were subsequently measured using digital drop PCR across a dose range for DEHP and two related phthalates with weaker PPARα activity, di-n-octyl phthalate and n-butyl benzyl phthalate, following 7-day exposures. Analysis of mmu-miRs-182-5p and -378a-3p by transcriptional benchmark dose analysis correctly identified DEHP as having the greatest potency. However, benchmark dose estimates for DEHP based on these miRNAs (average 163; range 126-202 mg/kg-day) were higher on average than values for PPARα target genes (average 74; range 29-183 mg/kg-day). These findings identify putative miRNA biomarkers of PPARα pathway activity and suggest that early miRNA changes may be used to stratify chemical potency.

A 72-year-old man, healthy, smoker, with long-standing cough, was referred to our hospital and his chest X-ray (CXR) revealed a cavity lesion in the right upper lobe. Direct sputum smears, but not culture in solid medium, were positive for acid-fast bacilli (AFB) without tuberculosis DNA. The preliminary diagnosis was of a non-tuberculosis infection that progressed slowly, and the CXR showed the condition to worsen daily. Four years later, a commercialized mycobacteria growth indicator tube system was used to culture the colonies of AFB successfully in liquid medium, and the species Mycobacterium heckeshornense was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The patient responded well to triple therapy with rifampicin, ethambutol, and clarithromycin, the sputum cultures remained negative and the roentgenogram showed minor improvement over the following 6 months.

Guanidinylated bioresponsive poly(amido amine)s polymers, CAR-CBA and CHL-CBA, were synthesized by Michael-type addition reaction between guanidine hydrochloride (CAR) or chlorhexidine (CHL) and N,N\'-cystaminebisacrylamide (CBA). Previous studies have shown that both polymers had high transfection efficiencies as gene delivery carriers. In this study, we investigated the nucleolus localization abilities and cellular internalization pathways of these two polymers in gene delivery. Each polymer condensed plasmid DNA (pDNA) and formed nanoparticle complexes, and then their transfection studies were performed in MCF-7 cells. Both complexes were found enriched in nucleolus after cellular transfection, and their transfection efficiencies were significantly improved when transfection was performed on MCF-7 cells arrested at M phase. The transfection efficiency of CAR-CBA-pDNA was inhibited by chlorpromazine, and cell endosomes were disrupted after being exposed to CAR-CBA-pDNA. In regards to CHL-CBA-pDNA, its transfection efficiency was not affected by three types of endocytosis inhibitors used in the study, and CHL-CBA-pDNA showed no effect on endosomes. Cellular lactate dehydrogenase release and membrane morphology were changed after cells were transfected by the two complexes. The results indicated that both CAR-CBA and CHL-CBA polymers demonstrated good nucleolus localization abilities. It was beneficial for transfection when cells were arrested at M phase. CAR-CBA-pDNA cellular internalization was involved with clathrin-mediated endocytosis pathway, and escaping from endosomal entrapment, while the cellular uptake of CHL-CBA-pDNA occurs via clathrin- and caveolae-independent mechanism.