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ese injuries should continue to be prioritized.Pseudogymnoascus destructans, the fungal pathogen that causes white-nose syndrome, has killed millions of bats across eastern North America and continues to threaten new bat populations. The spread and persistence of P. selleck chemical destructans has likely been worsened by the ability of this fungus to grow as a saprotroph in the hibernaculum environment. Reducing the environmental growth of P. destructans may improve bat survival. Volatile organic compounds (VOCs) are attractive candidates to target environmental P. destructans, as they can permeate through textured environments that may be difficult to thoroughly contact with other control mechanisms. We tested in hibernaculum sediment the performance of VOCs that were previously shown to inhibit P. destructans growth in agar cultures and examined the inhibition kinetics and specificity of these compounds. Three VOCs, 2-methyl-1-butanol, 2-methyl-1-propanol, and 1-pentanol, were fungicidal towards P. destructans in hibernaculum sediment, fast-acting, and had greater effects against P. destructans than other Pseudogymnoascus species. Our results suggest that use of these VOCs may be considered further as an effective management strategy to reduce the environmental exposure of bats to P. destructans in hibernacula.Background An acute Achilles tendon rupture (ATR) is a long-lasting and devastating injury. Possible biological augmentation to promote and strengthen tendon healing after an ATR would be desirable. Purpose To determine whether the application of a platelet-rich plasma (PRP) injection in nonsurgically treated ATRs may promote healing and thereby improve functional outcomes. Study design Randomized controlled trial; Level of evidence, 2. Methods A total of 40 men (aged 18-60 years) with an ATR incurred within 72 hours were included, and 38 were followed for 12 months. All patients were treated with an orthosis with 3 wedges for 8 weeks; full weightbearing from day 1 was allowed, combined with either 4 PRP or 4 placebo injections (a few drops of saline, less then 0.5 mL, under the skin) 14 days apart. All patients received the same instructions on an exercise program starting from week 9. Outcomes included the self-reported Achilles tendon Total Rupture Score (ATRS) as well as heel-rise work, heel-rise height, tendon elongation, calf circumference, and ankle dorsiflexion range of motion. Results The mean ATRS score improved in both groups at all time points (P less then .001), but there was no difference between the groups at any time points (12 months 90.1 points in PRP group and 88.8 points in placebo group). No differences in all functional outcomes at any time points were seen between the groups. At 12 months, the injured leg did not reach normal functional values compared with the uninjured leg. Conclusion The application of PRP in nonsurgically treated ATRs did not appear to show any superior clinical and functional improvement. Registration NCT02417922 (ClinicalTrials.gov identifier).Rationale While centrilobular (CLE) and paraseptal (PSE) emphysema are commonly identified on multi-detector computed tomography (MDCT), little is known about the pathology associated with PSE compared to CLE. Objective To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD). Methods Air-inflated frozen lung specimens (n=6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. Frozen tissue cores were taken from central (n=8) and peripheral (n=8) regions of each lung, scanned with microCT, and processed for histology. The core locations were registered to the MDCT and a percentage of PSE or CLE was assigned by radiologists to each of the regions. MicroCT scans were used to measure number and structural change of terminal bronchioles. Further, microCT based volume fractions of centrilobular (CLE%) and paraseptal (PSE%) emphysema allowed classifying cores into mild emphysema, CLE-dominant, and PSE-dominant. Measurements and main results PSE% measured on MDCT and microCT were positively associated (p=0.015). Number of terminal bronchioles per ml of lung and cross-sectional lumen area were significantly lower while wall area percent was significantly higher in CLE-dominant compared to mild emphysema and PSE-dominant regions (all p0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (p=0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared to CLE regions. Conclusions The terminal bronchioles are relatively preserved while neutrophilic inflammation is increased in PSE-dominant regions compared to CLE-dominant regions in patents with COPD.We introduced the oriented-external-electric-field-induced modification of bowl-shaped corannulene using density functional theory calculations. The results show that the electric field is capable of significantly modulating the polarization and electrostatic characteristics of the concave and convex surfaces of buckybowls. The structure-energy-reactivity relation can be precisely controlled, leading to a variety of unconventional properties for practical applications.Biosystems such as enzymes, pathways, and whole cells have been increasingly explored for biotechnological applications. However, the intricate connectivity and resulting complexity of biosystems poses a major hurdle in designing biosystems with desirable features. As -omics and other high throughput technologies have been rapidly developed, the promise of applying machine learning (ML) techniques in biosystems design has started to become a reality. ML models enable the identification of patterns within complicated biological data across multiple scales of analysis and can augment biosystems design applications by predicting new candidates for optimized performance. ML is being used at every stage of biosystems design to help find nonobvious engineering solutions with fewer design iterations. In this review, we first describe commonly used models and modeling paradigms within ML. We then discuss some applications of these models that have already shown success in biotechnological applications. Moreover, we discuss successful applications at all scales of biosystems design, including nucleic acids, genetic circuits, proteins, pathways, genomes, and bioprocesses. Finally, we discuss some limitations of these methods and potential solutions as well as prospects of the combination of ML and biosystems design.Triple-negative breast cancer (TNBC) has high rate of metastasis, which is associated with breast cancer stem-like cells (CSCs). Although Taxol (micelle formulation of paclitaxel) is the first line chemotherapy to treat TNBC, it increases CSCs in residual tumors. Abraxane, albumin nanoparticle of paclitaxel, showed lower plasma concentration compared to Taxol in both human and animal models, but it is not clear why Abraxane showed superior efficacy to Taxol in treatment of metastatic breast cancer in human. In this study, we intend to investigate if Abraxane decreases CSCs for its better efficacy. The results showed that Abraxane showed similar cytotoxicity in SUM149 cells in comparison with Taxol. Although Abraxane showed 3 to 5-fold lower blood drug concentration compared to Taxol, it achieved similar tumor drug concentration and 10-fold higher tumor/plasma ratio in SUM149 xenograft NOD/SCID mouse model. In addition, Abraxane and Taxol showed similar efficacy to shrink the tumor size in orthotopic breast cancer NOD/SCID mouse model. However, Abraxane decreased breast CSCs frequency by 3 to 9-fold, while Taxol increased breast CSCs frequency in orthotopic breast cancer NOD/SCID mouse model. Furthermore, Abraxane increased 3 to 15-fold higher intracellular uptake in both ALDH+ CSCs and differentiated ALDH- cells in comparison with Taxol, which provides a mechanism for Abraxane's superior efficacy to eliminate CSCs in comparison with Taxol. Our data suggest albumin nanoparticle Abraxane may have a broad implication to enhance drug's efficacy by eliminating breast cancer stem cells for treatment of metastatic diseases.Synthetic biology is enabling rapid advances in the areas of biomanufacturing and live therapeutics. Dynamic circuits that can be used to regulate cellular resources and microbial community behavior represent a defining focus of synthetic biology, and have attracted tremendous interest. However, the existing dynamic circuits are mostly gene editing-dependent or cell lysis-based, which limits their broad and convenient application, and in some cases, such lysis-based circuits can suffer from genetic instability due to evolution. There is limited research in quorum sensing-assisted CRISPRi, which can function in a gene editing-independent manner. Here, we constructed a series of quorum sensing controlled CRISPRi systems (Q-CRISPRi), which can dynamically program bacteria by using customized sgRNA without introducing cell lysis. We successfully applied Q-CRISPRi circuits to dynamically program gene expression, population density, phenotype, physical property, and community composition of microbial consortia. The strategies reported here represent methods for dynamic cell programming and could be effective in programming industrially and medically important microorganisms to offer better control of their metabolism and behavior.New technologies to target nucleotide diversification in vivo are promising enabling strategies to perform directed evolution for engineering applications and forward genetics for addressing biological questions. Recently, we reported EvolvR-a system that employs CRISPR-guided Cas9 nickases fused to nick-translating, error-prone DNA polymerases to diversify targeted genomic loci-in E. coli. As CRISPR-Cas9 has shown activity across diverse cell types, EvolvR has the potential to be ported into other organisms, including eukaryotes, if nick-translating polymerases can be active across species. Here, we implement and characterize EvolvR's function in Saccharomyces cerevisiae, representing a key first step to enable EvolvR-mediated mutagenesis in eukaryotes. This advance will be useful for mutagenesis of user-defined loci in the yeast chromosomes for both engineering and basic research applications, and it furthermore provides a platform to develop the EvolvR technology for performance in higher eukaryotes.Tilimycin is an enterotoxin produced by the opportunistic pathogen Klebsiella oxytoca that causes antibiotic-associated hemorrhagic colitis (AAHC). This pyrrolobenzodiazepine (PBD) natural product is synthesized by a bimodular nonribosomal peptide synthetase (NRPS) pathway composed of three proteins NpsA, ThdA, and NpsB. We describe the functional and structural characterization of the fully reconstituted NRPS system and report the steady-state kinetic analysis of all natural substrates and cofactors as well as the structural characterization of both NpsA and ThdA. The mechanism of action of tilimycin was confirmed using DNA adductomics techniques through the detection of putative N-2 guanine alkylation after tilimycin exposure to eukaryotic cells, providing the first structural characterization of a PBD-DNA adduct formed in cells. Finally, we report the rational design of small-molecule inhibitors that block tilimycin biosynthesis in whole cell K. oxytoca (IC50 = 29 ± 4 μM) through the inhibition of NpsA (KD = 29 ± 4 nM).