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Hygromycin B is an aminoglycoside antibiotic widely used in industry and biological research. However, most of its biosynthetic pathway has not been completely identified due to the immense difficulty in genetic manipulation of the producing strain. To address this problem, we developed an efficient system that combines clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-associated base editing and site-specific recombination instead of conventional double-crossover-based homologous recombination. This strategy was successfully applied to the in vivo inactivation of five candidate genes involved in the biosynthesis of hygromycin B by generating stop codons or mutating conserved residues within the encoding region. The results revealed that HygJ, HygL, and HygD are responsible for successive dehydrogenation, transamination, and transglycosylation of nucleoside diphosphate (NDP)-heptose. Notably, HygY acts as an unusual radical S-adenosylmethionine (SAM)-dependent epimerase for hydroxyl carbons, and HygM serves as a versatile methyltransferase in multiple parallel metabolic networks. Based on in vivo and in vitro evidence, the biosynthetic pathway for hygromycin B is proposed.The human serotonin transporter (hSERT) termi-nates serotonergic signaling through reuptake of neurotransmitter into presynaptic neurons and is a target for many antidepressant drugs. We describe here the development of a photoswitchable hSERT inhibitor, termed azo-escitalopram, that can be re-versibly switched between trans and cis configura-tions using light of different wavelengths. The dark-adapted trans isomer, was found to be signifi-cantly less active than the cis isomer, formed upon irradiation.Nanopores are promising for many applications including DNA sequencing and molecular filtration. Solid-state nanopores are preferable over their biological counterparts for applications requiring durability and operation under a wider range of external parameters yet few studies have focused on optimizing their robustness. We report the lifetime and durability of pores and porous arrays in 10 to 100 nm thick, low-stress silicon nitride (SiNx) membranes. Pores are fabricated using a transmission electron microscope (TEM) and/or electron-beam lithography (EBL) and reactive ion etching (RIE), with diameters from 2 to 80 nm. We store them in various electrolyte solutions (KCl, LiCl, MgCl2) and record open pore conductance over months to quantify pore stability. Pore diameters increase with time and diameter etch rate increases with electrolyte concentration from Δd/Δt ~ 0.2 to ~ 3 nm/day for 0.01 to 3 M KCl, respectively. TEM confirms the range of diameter etch rates from ionic measurements. Using electron energy loss spectroscopy (EELS), we observe that a N-deficient region around the edges of TEM-drilled pores. Pore expansion is caused by etching of the Si/SiO2 pore walls, which resembles the dissolution of silicon found in minerals such as silica (SiO2) in salty ocean water. The etching process occurs where the membrane was exposed to the electron beam and can result in pore formation. However, coating pores with a conformal 1-nm-thick hafnium oxide layer prevents expansion in 1M KCl, in stark contrast to bare SiNx pores (~ 1.7 nm/day). EELS data reveal the atomic composition of bare and HfO2-coated pores. Keywords Solid-state nanopore, silicon nitride, nanoporous membranes, nanopore array, electron beam lithography, electron energy loss spectroscopy.At present, pressure sensor textiles are of great significance in the area of wearable electronics, especially for making smart or intelligent textiles. However, the design of these textile-based devices with sensitive ability, simple fabrication, and low cost is still challenging. In this study, we developed a triboelectric sensing textile constructed with core-shell yarns. Nylon filament and polytetrafluoroethylene filament were selected as the positive and negative layers, respectively, in the woven structure while the built-in helical stainless steel yarn was serving as the inner electrode layer. The sensitivity of the sensing textile can reach up to 1.33 V·kPa-1 and 0.32 V·kPa-1 in the pressure range of 1.95-3.13 kPa and 3.20-4.61 kPa, respectively. This sensing textile presented good mechanical stability and sensing capability even after 4200 cycles of continuous operation or after 4 h continuous water washing. Benefiting from the favorable merits of being highly flexible, breathable, lightweight, and even dyeable, the fabricated device was capable of being placed on any desired body parts for quantifying the dynamic human motions. [https://www.selleckchem.com/products/gsk591-epz015866-gsk3203591.html GSK591 concentration] It can be effectively used to measure and monitor various human movements associated with different joints, such as the hand, elbow, knee, and underarm. Moreover, the sensing textile was able to capture real-time pulse signals and reflect the current health status for human beings. This study affords an innovative and promising track for multifunctional pressure sensor textiles with wide applications in smart textiles and personalized healthcare.The indication of bloodletting therapy was determined based on the multi-dimensional evidence assessment, which could provide guidance for the clinical application of bloodletting therapy. The literature of bloodletting therapy was comprehensively collected by retrieval in CNKI, Wanfang and VIP databases (until February 23, 2019), modern books in Library of Tianjing University of TCM and the Chinese Medical Code (Fifth Edition). The disease spectrum of bloodletting therapy was determined by self-designed questionnaire survey e-mailed to relevant experts. The indication of bloodletting therapy was determined by Delphi expert meeting. As a result, 746 pieces of ancient literature and 32 775 modern literature were included. The indications of bloodletting therapy based on the multi-dimensional evidence assessment include herpes zoster, acne, acute tonsillitis, vascular headache, varicose veins of lower extremities, acute lumbar sprain, early erysipelas, wheat swelling, exogenous fever of children, stroke, which are mainly the syndromes of blood stasis, toxin, excess and heat.