Interspecific evolutionary associations of alphaglucuronidase in the genus Aspergillus

Extended-release gastrointestinal (GI) luminal delivery substantially increases the ease of administration of drugs and consequently the adherence to therapeutic regimens. However, because of clearance by intrinsic GI motility, device gastroretention and extended drug release over a prolonged duration are very challenging. Here, we report that GI parasite-inspired active mechanochemical therapeutic grippers, or theragrippers, can reside within the GI tract of live animals for 24 hours by autonomously latching onto the mucosal tissue. We also observe a notable sixfold increase in the elimination half-life using theragripper-mediated delivery of a model analgesic ketorolac tromethamine. These results provide first-in-class evidence that shape-changing and self-latching microdevices enhance the efficacy of extended drug delivery.We report a microresonator platform that allows room temperature detection of electron spins in volumes on the order of 100 pl, and demonstrate its utility to study low levels of dopants in perovskite oxides. We exploit the toroidal moment in a planar anapole, using a single unit of an anapole metamaterial architecture to produce a microwave resonance exhibiting a spatially confined magnetic field hotspot and simultaneously high quality-factor (Q-factor). To demonstrate the broad implementability of this design and its scalability to higher frequencies, we deploy the microresonators in a commercial electron paramagnetic resonance (EPR) spectrometer operating at 10 GHz and a NIST-built EPR spectrometer operating at 35 GHz. We report continuous-wave (CW) EPR spectra for various samples, including a dilute Mn2+-doped perovskite oxide, CaTiO3, and a transition metal complex, CuCl22H2O. The anapole microresonator presented here is expected to enable multifrequency EPR characterization of dopants and defects in perovskite oxide microcrystals and other volume-limited materials of technological importance.Aberrant number and/or dysfunction of CD4+Foxp3+ Regulatory T cells (Tregs) are associated with the pathogenesis of rheumatoid arthritis (RA). A previous study has demonstrated that thymus-derived, natural Tregs (nTregs) prefer to accumulate in inflamed joints and transdifferentiate to TH17 cells under the stimulation of inflamed synovial fibroblasts (SFs). In this study, we made a head-to-head comparison of both Treg subsets and demonstrated that induced Tregs (iTregs), but not nTregs, retained Foxp3 expression and regulatory function on T effector cells (Teffs) after being primed with inflamed SFs. In addition, iTregs inhibited proliferation, inflammatory cytokine production, migration, and invasion ability of collagen-induced arthritis (CIA)-SFs in vitro and in vivo. Moreover, we noted that iTregs directly targeted inflamed SFs to treat autoimmune arthritis, while nTregs failed to do this. Thus, manipulation of the iTreg subset may have a greater potential for prevention or treatment of patients with RA.Bacterial infection and infection-induced immune response have been a life-threatening risk for patients having orthopedic implant surgeries. Conventional biomaterials are vulnerable to biocontamination, which causes bacterial invasion in wounded areas, leading to postoperative infection. Therefore, development of anti-infection and immune-evasive coating for orthopedic implants is urgently needed. AZ-33 Here, we developed an advanced surface modification technique for orthopedic implants termed lubricated orthopedic implant surface (LOIS), which was inspired by slippery surface of Nepenthes pitcher plant. LOIS presents a long-lasting, extreme liquid repellency against diverse liquids and biosubstances including cells, proteins, calcium, and bacteria. In addition, we confirmed mechanical durability against scratches and fixation force by simulating inevitable damages during surgical procedure ex vivo. The antibiofouling and anti-infection capability of LOIS were thoroughly investigated using an osteomyelitis femoral fracture model of rabbits. We envision that the LOIS with antibiofouling properties and mechanical durability is a step forward in infection-free orthopedic surgeries.Residential contribution to air pollution-associated health impacts is critical, but inadequately addressed because of data gaps. Here, we fully model the effects of residential energy use on emissions, outdoor and indoor PM2.5 concentrations, exposure, and premature deaths using updated energy data. We show that the residential sector contributed only 7.5% of total energy consumption but contributed 27% of primary PM2.5 emissions; 23 and 71% of the outdoor and indoor PM2.5 concentrations, respectively; 68% of PM2.5 exposure; and 67% of PM2.5-induced premature deaths in 2014 in China, with a progressive order of magnitude increase from sources to receptors. Biomass fuels and coal provided similar contributions to health impacts. These findings are particularly true for rural populations, which contribute more to emissions and face higher premature death risks than urban populations. The impacts of both residential and nonresidential emissions are interconnected, and efforts are necessary to simultaneously mitigate both emission types.Endogenous DNA double-strand breaks (DSBs) formation and repair in neural stem/progenitor cells (NSPCs) play fundamental roles in neurogenesis and neurodevelopmental disorders. NSPCs exhibit heterogeneity in terms of lineage fates and neurogenesis activity. Whether NSPCs also have heterogeneous regulations on DSB formation and repair to accommodate region-specific neurogenesis has not been explored. Here, we identified a regional regulator Filia, which is predominantly expressed in mouse hippocampal NSPCs after birth and regulates DNA DSB formation and repair. On one hand, Filia protects stalling replication forks and prevents the replication stress-associated DNA DSB formation. On the other hand, Filia facilitates the homologous recombination-mediated DNA DSB repair. Consequently, Filia-/- mice had impaired hippocampal NSPC proliferation and neurogenesis and were deficient in learning, memory, and mood regulations. Thus, our study provided the first proof of concept demonstrating the region-specific regulations of DSB formation and repair in subtypes of NSPCs.