Shell cross-linked micelles (SCMs) containing Co(III)-salen cores were prepared from amphiphilic poly(2-oxazoline) triblock copolymers. The catalytic activity of these nanoreactors for the hydrolytic kinetic resolution of various terminal epoxides was investigated. The SCM catalysts showed high catalytic efficiency and, more significantly, substrate selectivity based on the hydrophobic nature of the epoxide. Moreover, because of the nanoscale particle size and the high stability, the catalyst could be recovered easily by ultrafiltration and reused with high activity for eight cycles.

Daratumumab and its use in combination with other agents is becoming a new standard of care for the treatment of multiple myeloma. We mechanistically studied how daratumumab acts on natural killer (NK) cells. Quantities of NK cells in peripheral blood and/or bone marrow of patients with multiple myeloma or healthy donors were examined by flow cytometry. NK-cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded using feeder cells. Combination treatment of daratumumab and expanded NK cells was performed using an MM.1S xenograft animal model. CD38 NK cells survived, whereas CD38 NK cells were almost completely eliminated, in peripheral blood and bone marrow of daratumumab-treated multiple myeloma patients. NK-cell depletion occurred due to daratumumab-induced NK-cell fratricide via antibody-dependent cellular cytotoxicity. Consequently, CD38 NK cells were more effective for eradicating multiple myeloma cells than were CD38 NK cells in the presence of daratumumab. Blockade of CD38 with the F(ab) fragments of daratumumab inhibited the antibody-mediated NK-cell fratricide. CD38 NK cells displayed a significantly better potential for expansion than CD38 NK cells, and the expanded NK cells derived from the former population were more cytotoxic than those derived from the latter against multiple myeloma cells. Therefore, infusion of -expanded autologous NK cells from daratumumab-treated patients may improve the antibody therapy. We unravel a fratricide mechanism for daratumumab-mediated NK-cell depletion and provide a potential therapeutic strategy to overcome this side effect in daratumumab-treated patients with multiple myeloma. .

b Rifampin (RIF) susceptibility is a key factor in determining the treatment effectiveness of the standardized treatment regimens. In Mycobacterium tuberculosis, both target gene mutation and the efflux pump play major roles in the resistance to antituberculosis drugs. By eliminating RIF-resistant strains with rpoB mutation, the choice of RIF-monoresistant strains may allow us to identify the RIF-specific efflux pump genes. This study explored the RIF monoresistance mechanism in M. tuberculosis. Data from DNA sequencing and MIC measurements revealed that specific mutations, including Ser531Leu and His526Asp in RpoB, show high-level drug resistance. Three-dimensional structure modeling provided further evidence that the affinity between RIF and RpoB mutants was in accordance with the drug resistance level of the corresponding isolates. Furthermore, transcriptionlevel analysis among the nonmutated isolates indicated that three efflux pumps (Rv0783, Rv2936, and Rv0933) might be involved in exporting RIF from the cell. Compared to 8 g/ml for wild-type Escherichia coli, the MICs for the transgenic E. coli strains with either Rv0783 or Rv2936 were 32 and 16 g/ml, respectively. In conclusion, our study indicated that several RpoB mutant types, including Ser531Leu and His526Asp, show high-level RIF resistance attributed to low affinity between RpoB mutant proteins and RIF. In addition, this work demonstrates that Rv2936 and Rv0783 may be responsible for low-level resistance to RIF by exporting RIF from cells. The predicted structure of RpoB and the newly identified efflux pumps in this study will provide a novel approach to design new drugs and develop novel diagnosis technologies.

Studies on the phase segregation of unimolecular block copolymers (BCPs) are limited by a lack of reliable, versatile methods for the synthesis of such polymers on the preparative scale. Herein, we describe an advancement of Iterative Exponential Growth (IEG) wherein chiral allyl-based IEG oligomers are subjected to thiol-ene reactions and converted into unimolecular BCPs. With this strategy we have synthesized uniform BCPs with molar masses up to 12.1 kDa on ∼1 g scale. BCPs composed of decane-based side chains and either triethyleneglycol- or thioglycerol-based side chains phase-segregate into hexagonal cylinder morphologies. The assembly is not driven by side-chain crystallization, but is instead the result of amorphous BCP assembly.

Clogging of the submerged entry nozzle (SEN) is a serious problem during the continuous casting of steel, due to its influence on the casting operations and product quality. Fluid-flow-related phenomena in the continuous casting mold region with the SEN clogging are investigated in the current article, including the quantitative evaluation of inclusion removal, slag entrainment, heat transfer, and the prediction of breakouts. The calculations indicate that, in order to accurately simulate the fluid flow in the mold region, the SEN should be connected with the mold region and the two should be calculated together. In addition, the whole mold region has to be calculated. Clogging at the SEN at one side induces asymmetrical jets from the two outports; thus, the fluid flow in the mold is asymmetrical. In addition, more inclusions are carried by the flow to the top surface of the nonclogged side, and the slab at the nonclogged side has a lower quality. With SEN one-sided clogging, inclusions travel a much larger distance, on average, before they escape from the top or move to the bottom. The overall inclusion entrainment fraction from the entire top surface for inclusions of any size is less than 10 pct. A higher turbulence energy and a larger surface velocity induce more inclusion entrainment from the top surface. Smaller inclusions are more easily entrained into the steel than are larger ones. More >200-lm inclusions can be entrained into the molten steel from the top slag with SEN clogging than without clogging. The SEN one-sided clogging generates an asymmetrical temperature distribution in the mold; it also generates temperatures higher than the liquidus temperature at some locations of the solidified shell, which increases the risk of breakouts. The SEN clogging should be minimized in order to achieve a uniform steel cleanliness, a cleaner steel, and a safe continuous casting operation.

No abstract

China is one of the countries with the highest burdens of multidrug-resistant (MDR) and fluoroquinolone (FQ)-resistant tuberculosis (TB) globally. Nevertheless, knowledge about the prevalence and molecular characterization of FQ-resistant Mycobacterium tuberculosis isolates from this region remains scant. In this study, 138 M. tuberculosis isolates determined by the agar proportion susceptibility method to be resistant to ofloxacin (OFX) were enrolled from a national drug resistance survey of China. All these strains were tested for susceptibility to ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, and sparfloxacin using liquid Middlebrook 7H9 medium. The entire gyrA and gyrB genes conferring FQ resistance were sequenced, and spoligotyping was performed to distinguish different genotypes. Overall, the prevalence of resistance in China was highest for ofloxacin (3.76%), intermediate for levofloxacin (3.18%) and moxifloxacin (3.12%), and lowest for sparfloxacin (1.91%) and gatifloxacin (1.33%). Mutations in the gyrA gene were observed in 89 (64.5%) out of the 138 OFX-resistant M. tuberculosis strains. Positions 94 and 90 were the most frequent sites of mutation conferring FQ resistance on these strains, accounting for high-level FQ resistance. Furthermore, the Beijing genotype showed no association with high-level FQ resistance or distribution in hot spots in the quinolone resistance-determining region (QRDR) of gyrA. Our findings provide essential implications for the feasibility of genotypic tests relying on detection of mutations in the QRDR of gyrA and the shorter first-line treatment regimens based on FQs in China.

The development of ionic conductors with extreme stretchability, superior ionic conductivity, and harsh‐environment resistance is urgent while challenging because the tailoring of these performances is mutually exclusive. Herein, a hydrophobicity‐constrained association strategy is presented for fabricating a liquid‐free ion‐conducting fluorinated elastomer (ICFE) with microphase‐separated structures. Hydrophilic nanodomains with long‐range ordering and selectively enriched Li ions provided high‐efficient conductive pathways, yielding impressive room‐temperature ionic conductivity of 3.5 × 10–3 S m–1. Hydrophobic nanodomains with abundant and reversible hydrogen bonds endow the ICFE with superior damage‐tolerant performances including ultrastretchability (>6000%), large toughness (17.1 MJ m–3) with notch insensitivity, antifatigue ability, and high‐efficiency self‐healability. Due to its liquid‐free characteristic and surface‐enriched hydrophobic nanodomains, the ICFE demonstrates an extreme temperature tolerance (−20 to 300 °C) and unique underwater resistance. The resultant ICFE is assembled into a proof‐of‐concept skin‐inspired sensor, showing impressive capacitive sensing performance with high sensitivity and wide‐strain‐range linearity (gauge factor to 1.0 in a strain range of 0–350%), excellent durability (>1000 cycles), and unique waterproofness in monitoring of complex human motions. It is believed that the hydrophobicity‐constrained association method boosts the fabrication of stretchable ionic conductors holding a great promise in skin‐inspired ionotronics with harsh‐environment tolerance.