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7 months. Overall survival (OS) was 82% at 4 years, with a significantly shorter OS in patients who relapsed within 1 year of initial treatment with vemurafenib. Higher cumulative doses or a longer duration of treatment did not lengthen the durability of response. All adverse events in the retreatment cohort were grade 1/2 except for 1 case of a grade 3 rash and 1 grade 3 fever/pneumonia. Our data suggest that vemurafenib retreatment is a safe and effective option for patients with R/R HCL.The MAPK-interacting kinase (Mnk) family includes Mnk1 and Mnk2, which are phosphorylated and activated in response to extracellular stimuli. Mnk1 contributes to cellular responses by regulating messenger RNA (mRNA) translation, and mRNA translation influences platelet production and function. However, the role of Mnk1 in megakaryocytes and platelets has not previously been studied. The present study investigated Mnk1 in megakaryocytes and platelets using both pharmacological and genetic approaches. We demonstrate that Mnk1, but not Mnk2, is expressed and active in human and murine megakaryocytes and platelets. Stimulating human and murine megakaryocytes and platelets induced Mnk1 activation and phosphorylation of eIF4E, a downstream target of activated Mnk1 that triggers mRNA translation. Mnk1 inhibition or deletion significantly diminished protein synthesis in megakaryocytes as measured by polysome profiling and [35S]-methionine incorporation assays. Depletion of Mnk1 also reduced megakaryocyte ploidy and proplatelet forming megakaryocytes in vitro and resulted in thrombocytopenia. However, Mnk1 deletion did not affect the half-life of circulating platelets. https://www.selleckchem.com/products/scutellarin.html Platelets from Mnk1 knockout mice exhibited reduced platelet aggregation, α granule secretion, and integrin αIIbβ3 activation. Ribosomal footprint sequencing indicated that Mnk1 regulates the translation of Pla2g4a mRNA (which encodes cPLA2) in megakaryocytes. Consistent with this, Mnk1 ablation reduced cPLA2 activity and thromboxane generation in platelets and megakaryocytes. In vivo, Mnk1 ablation protected against platelet-dependent thromboembolism. These results provide previously unrecognized evidence that Mnk1 regulates mRNA translation and cellular activation in platelets and megakaryocytes, endomitosis and thrombopoiesis, and thrombosis.Acquired hemophilia A (AHA) is a rare severe autoimmune bleeding disorder with significant morbidity and mortality. Although critical for disease control, there is no consensus for the best immunosuppressive regimen. Most authors use steroids first line, followed by other agents for steroid failures. Upfront combined regimens offer the advantage of reduced steroid exposure and toxicity as well as increased efficacy. We retrospectively analyzed data from 32 patients with AHA treated on an identical such institutional protocol cyclophosphamide 1000 mg on days 1 and 22, dexamethasone 40 mg on days 1, 8, 15, and 22, and rituximab 100 mg on days 1, 8, 15, and 22 (the regimen was termed CyDRi). All patients received at least 1 cycle of CyDRi. If necessary, CyDRi was repeated until remission, no sooner than day 43 of the previous cycle. Bleeding control was rapidly achieved. The median time for bleeding control was 15.5 days (range, 0-429 days; interquartile range, 2.5-29.5 days). Thirty-one (96.8%) of 32 patients achieved durable complete remission (CR); 29 (90.6%) of 32 patients were alive at last follow-up, all of them in CR. The median time to reach first CR was 77 days (range, 19-939 days; interquartile range, 31-115 days). Toxicity and side effects were acceptable and milder than those of commonly used, prolonged steroid therapies. In conclusion, the CyDRi regimen produced markedly higher CR rates and overall survival than currently used sequential regimens. Taken together, CyDRi proved to be an attractive option for the immunosuppression of elderly patients with AHA.Electronic textiles, inherited with the wearability of conventional clothes, are deemed fundamental for emerging wearable electronics, particularly in the Internet of Things era. However, the electronic waste produced by electronic textiles will further exacerbate the severe pollution in traditional textiles. Here, we develop a large-scale green electronic textile using renewable bio-based polylactic acid and sustainable eutectic gallium-indium alloys. The green electronic textile is extremely abrasion resistant and can degrade naturally in the environment even if abrasion produces infinitesimal amounts of microplastics. The mass loss and performance change rates of the reconstituted green electronic textiles are all below 5.4% after going through the full-cycle recycling procedure. This green electronic textile delivers high physiological comfort (including electronic comfort and thermal-moisture comfort), enables wireless power supply (without constraints by, e.g., wires and ports), has 2 orders of magnitude better air and moisture permeability than the body requires, and can lower skin temperature by 5.2 °C.Accurate, onsite detection of pathogenic bacteria from food matrices is required to rapidly respond to pathogen outbreaks. However, accurately detecting whole-cell bacteria in large sample volumes without an enrichment step remains a challenge. Therefore, bacterial samples must be concentrated, identified, and quantified. We developed a tunable magnetic capturing cartridge (TMCC) and combined it with a portable digital fluorescence reader for quick, onsite, quantitative detection of Staphylococcus aureus. The TMCC platform integrates an absorption pad impregnated with water-soluble polyvinyl alcohol (PVA) with an injection-molded polycarbonate (PC) plate that has a hard magnet on its back and an acrylonitrile-butadiene-styrene case. An S. aureus-specific antibody conjugated with magnetic nanoparticles was used to concentrate bacteria from a large-volume sample and capture bacteria within the TMCC. The retention time for capturing bacteria on the TMCC was adjusted by controlling the concentration and volume of the PVA solution. Concentrated bacterial samples bound to target-specific aptamer probes conjugated with quantum dots were loaded into the TMCC for a controlled time, followed by attachment of the bacteria to the PC plate and removal of unbound aptamer probes with wash buffer. The captured bacteria were quantified using a digital fluorescence reader equipped with an embedded program that automatically counts fluorescently tagged bacteria. The bacterial count made using the TMCC was comparable to a standard plate count (R2 = 0.9898), with assay sensitivity and specificity of 94.3 and 100%, respectively.Peracetic acid (PAA) serves as a potent and low-toxic oxidant for contaminant removal. Radical-mediated catalytic PAA oxidation processes are typically non-selective, rendering weakened oxidation efficacy under complex water matrices. Herein, we explored the usage of reduced graphene oxide (rGO) for PAA activation via a non-radical pathway. Outperforming the most catalytic PAA oxidation systems, the rGO-PAA system exhibits near-complete removal of typical micropollutants (MPs) within a short time ( less then 2 min). Non-radical direct electron transfer (DET) from MPs to PAA plays a decisive role in the MP degradation, where accelerated DET is achieved by a higher potential of the rGO-PAA reactive surface complexes. Benefitting from DET, the rGO-PAA system shows robust removal of multiple MPs under complex water matrices and with low toxicity. Notably, in the DET regime, the electrostatic attraction of rGO to both PAA and target MP is a critical prerequisite for achieving efficient oxidation, depending on the conditions of solution pH and MP pKa. A heatmap model building on such an electrostatic interaction is further established as guidance for regulating the performance of the DET-mediated PAA oxidation systems. Overall, our work unveils the imperative role of DET for rGO-activated PAA oxidation, expanding the knowledge of PAA-based water treatment strategies.The Tc-99m nucleus is the most used nuclide in radiopharmaceuticals designed for imaging diagnosis. The metal can exist in nine distinct oxidation states and forms distinct coordination complexes with a variety of chelating agents and geometries. These complexes are usually characterized through Tc-99 NMR that is very sensitive to the Tc coordination sphere. Therefore, predicting Tc-99 NMR might be useful to assist experimentalists in structural characterization. In the present study, we propose three computational protocols for predicting Tc-99 NMR chemical shifts based on density functional theory calculations using relativistic and nonrelativistic Hamiltonians the relativistic Model 1, the nonrelativistic Model 2, and the empirical nonrelativistic Model 3. In Models 2 and 3, the NMR-DKH basis set was used for all atoms, including the Tc, for which it was developed here. All models were applied for a set of 41 Tc-complexes with metal oxidation states 0, I, and V, for which the Tc-99 chemical shift was available experimentally. The mean absolute deviation and the mean relative deviation were 67 ppm and 4.8% (Model 1), 92 ppm and 6.2% (Model 2), and 65 ppm and 4.9% (Model 3), respectively. Last, the effect of the explicit solvent was evaluated for the [TcO2(en)2]+─Tc(V) complex. The calculated results for the Tc-99 NMR chemical shift at SO-ZORA-SSB-D/TZ2P-ZORA/COSMO//TPSS/def2-SVP/IEF-PCM(UFF) show that the inclusion of 14 water molecules (first solvation shell) together with the implicit solvation model leads to an absolute deviation of only 7 ppm (0.3%) from the experimental value, indicating that the solvent effects play a key role in predicting Tc-99 NMR.Superhydrophobic (SH) polylactic acid (PLA) surfaces were previously produced by various methods and used especially in biomedical applications and oil/water separation processes after 2008. However, the wettability of SH-PLA patterns containing micropillars has not been investigated before. In this study, PLA patterns having regular microstructured pillars with 12 different pillar diameters and pillar-to-pillar distances were prepared by hot pressing pre-flattened PLA sheets onto preformed polydimethylsiloxane (PDMS) soft molds having micro-sized pits. PDMS templates were previously prepared by photolithography using SU-8 molds. Apparent, advancing, and receding water contact angle measurements were carried out on the PLA patterns containing micropillars, and the morphology of the patterns was examined by optical and SEM microscopy. The largest contact angle obtained without the surface modification of the pure PLA pattern was 139°. Then, PLA micropatterns were hydrophobized using three types of silanes via chemical vapor deposition method, and SH-PLA patterns were obtained having θs of up to 167°. It was found that the highest θ values could be obtained when PLA pattern samples were coated with a silane containing a fluorine atom in its chemical structure. Washing and service life stability tests were also performed on the coated pattern samples and all of the silane coatings on the PLA patterns were found to be resistant over a 6 month period.Cellulose nanofibers functionalized with multiple aldehyde group were synthesized as the crosslinker to produce composite self-healing hydrogel and shape memory cryogel from chitosan. The hydrogel possessed effective self-healing (∼100% efficiency) and shear-thinning properties. The cryogel had macroporous structure, large water absorption (>4300%), and high compressibility. Both hydrogel and cryogel were injectable. In particular, the cryogel (nanocellulose/chitosan 16) revealed thermally induced shape memory, the mechanism of which was elucidated by in situ small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS) as changes in orientation of the induced crystalline structure during the shape memory program. The shape memory cryogel with a large size (15 mm × 10 mm × 1.1 mm) injected through a 16 G syringe needle was recoverable in 37 °C water. Moreover, the cryogel was cytocompatible and promoted cell growth. The nanocellulose-chitosan composite hydrogel and cryogel are injectable and degradable biomaterials with adjustable mechanical properties for potential medical applications.
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