No abstract

Emerging data indicate that gut dysbiosis contributes to many human diseases, including several comorbidities that develop after traumatic spinal cord injury (SCI). To date, all analyses of SCI-induced gut dysbiosis have used 16S rRNA amplicon sequencing. This technique has several limitations, including being susceptible to taxonomic “blind spots,” primer bias, and an inability to profile microbiota functions or identify viruses. Here, SCI-induced gut dysbiosis was assessed by applying genome- and gene-resolved metagenomic analysis of murine stool samples collected 21 days after an experimental SCI at the 4th thoracic spine (T4) or 10th thoracic spine (T10) spinal level. These distinct injuries partially (T10) or completely (T4) abolish sympathetic tone in the gut. Among bacteria, 105 medium- to high-quality metagenome-assembled genomes (MAGs) were recovered, with most (n = 96) representing new bacterial species. Read mapping revealed that after SCI, the relative abundance of beneficial commensals (Lactobacillus johnsonii and CAG-1031 spp.) decreased, while potentially pathogenic bacteria (Weissella cibaria, Lactococcus lactis_A, Bacteroides thetaiotaomicron) increased. Functionally, microbial genes encoding proteins for tryptophan, vitamin B6, and folate biosynthesis, essential pathways for central nervous system function, were reduced after SCI. Among viruses, 1,028 mostly novel viral populations were recovered, expanding known murine gut viral species sequence space ∼3-fold compared to that of public databases. Phages of beneficial commensal hosts (CAG-1031, Lactobacillus, and Turicibacter) decreased, while phages of pathogenic hosts (Weissella, Lactococcus, and class Clostridia) increased after SCI. Although the microbiomes and viromes were changed in all SCI mice, some of these changes varied as a function of spinal injury level, implicating loss of sympathetic tone as a mechanism underlying gut dysbiosis. IMPORTANCE To our knowledge, this is the first article to apply metagenomics to characterize changes in gut microbial population dynamics caused by a clinically relevant model of central nervous system (CNS) trauma. It also utilizes the most current approaches in genome-resolved metagenomics and viromics to maximize the biological inferences that can be made from these data. Overall, this article highlights the importance of autonomic nervous system regulation of a distal organ (gut) and its microbiome inhabitants after traumatic spinal cord injury (SCI). By providing information on taxonomy, function, and viruses, metagenomic data may better predict how SCI-induced gut dysbiosis influences systemic and neurological outcomes after SCI.

No abstract

Our study demonstrates that miR-509-3p could sensitize ovarian cancer cells to cisplatin treatment by targeting multiple anti-apoptosis genes including BCL2.

Contrary to dogma, the human urinary bladder possesses its own unique bacterial community with alteration of composition associated with disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease often characterized by kidney impairment.

Aim: miR-137 is downregulated in various cancers; however, its function in ovarian cancer remains unclear. Methods: The roles of miR-137 in apoptosis were accessed through IC50 values and DAPI assay. The regulation of MCL1 by miR-137 was investigated through luciferase reporter assay and immunoblot. Results: miR-137 mimic could decrease the IC50 value of cisplatin and promote apoptosis in OVCAR3 ovarian cancer cells. Using luciferase assay, results on a panel of anti-apoptotic proteins, we identified MCL1 as a target for miR-137 and the results were confirmed using immunoblot. Finally, the underlying pathway in which miR-137 may be involved was investigated by transcriptome sequencing. Conclusion: These results suggest that miR-137 downregulates MCL1 in ovarian cancer cells and mediates cisplatin-induced apoptosis.

Development of flexible thermoelectric devices offers exciting opportunities for wearable applications in consumer electronics, healthcare, human–machine interface, etc. Despite the increased interests and efforts in nanotechnology‐enabled flexible thermoelectrics, translating the superior properties of thermoelectric materials from nanoscale to macroscale and reducing the manufacturing costs at the device level remain a major challenge. Here, an economic and scalable inkjet printing method is reported to fabricate high‐performance flexible thermoelectric devices. A general templated‐directed chemical transformation process is employed to synthesize several types of 1D metal chalcogenide nanowires (e.g., Ag2Te, Cu7Te4, and Bi2Te2.7Se0.3). These nanowires are made into inks suitable for inkjet printing by dispersing them in ethanol without any additives. As a showcase for thermoelectric applications, fully inkjet‐printed Ag2Te‐based flexible films and devices are prepared. The printed films exhibit a power factor of 493.8 µW m−1 K−2 at 400 K and the printed devices demonstrate a maximum power density of 0.9 µW cm−2 K−2, both of which are significantly higher than those reported in state‐of‐the‐art inkjet‐printed thermoelectrics. The protocols of metal chalcogenide ink formulations, as well as printing are general and extendable to a wider range of material systems, suggesting the great potential of this printing platform for scalable manufacturing of next‐generation, high‐performance flexible thermoelectric devices.

In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 mice and compared four clinical isolates of A. urinae isolated from patients with UTI, urgency urinary incontinence, and overactive bladder. Our data demonstrate that host genetic background modulates A. urinae UTI. Female C57BL/6 female mice rapidly cleared the infection. Female C3H/HeN mice, which have inherent vesicoureteral reflux that flushes urine from the bladder up into the kidneys, were susceptible to prolonged bacteriuria. This result is consistent with the fact that A. urinae infections most frequently occur in patients with underlying urinary tract abnormalities or disorders that make them susceptible to bacterial infection. Unlike uropathogens such as E. coli, which cause infection and inflammation both of the bladder and kidneys in C3H/HeN mice, A. urinae displayed tropism for the kidney, persisting in kidney tissue even after clearance of bacteria from the bladder. Aerococcus urinae strains from different genetic clades displayed varying propensities to cause persistent kidney infection. Aerococcus urinae infected kidneys displayed histological inflammation, neutrophil recruitment and increased pro-inflammatory cytokines. These results set the stage for future research that interrogates host-pathogen interactions between A. urinae and the urinary tract.