Effectiveness of portable HEPA air cleaners on reducing indoor PM2.5 and NH3 in an agricultural cohort of children with asthma: A randomized intervention trial

We conducted a randomized trial of portable HEPA air cleaners with pre-filters designed to also reduce NH₃ in non-smoking homes of children age 6-12 with asthma in Yakima Valley (Washington, USA). Participants were recruited through the Yakima Valley Farm Workers Clinic asthma education program. All participants received education on home triggers while intervention families additionally received two HEPA cleaners (child's sleeping area, main living area). Fourteen-day integrated samples of PM_2.5 and NH₃ were measured at baseline and one-year follow-up. We fit ANCOVA models to compare follow-up concentrations in HEPA vs control homes, adjusting for baseline concentrations. Seventy-one households (36 HEPA, 35 control) completed the study. Most were single-family homes, with electric heat and stove, A/C, dogs/cats, and mean (SD) 5.3 (1.8) occupants. In the sleeping area, baseline geometric mean (GSD) PM_2.5 was 10.7 (2.3) μg/m³ (HEPA) vs 11.2 (1.9) μg/m³ (control); in the living area, it was 12.5 (2.3) μg/m³ (HEPA) vs 13.6 (1.9) μg/m³ (control). Baseline sleeping area NH₃ was 62.4 (1.6) μg/m³ (HEPA) vs 65.2 (1.8) μg/m³ (control). At follow-up, HEPA families had 60% (95% CI, 41%-72%; p < .0001) and 42% (19%-58%; p = .002) lower sleeping and living area PM_2.5, respectively, consistent with prior studies. NH₃ reductions were not observed.     

Profiling hot isostatically pressed canister–wasteform interaction for Pu-bearing zirconolite-rich wasteforms

Zirconolite-rich full ceramic wasteforms designed to immobilize Pu-bearing wastes were produced via hot isostatic pressing (HIP) using stainless steel (SS) and nickel (Ni) HIP canisters. A detailed profiling of the elemental compositions of the major and minor phases over the canister–wasteform interaction zone was performed using scanning electron microscopy combined with energy-dispersive X-ray spectroscopy (SEM-EDS) characterization. Bulk sample analyses from regions near the center of the HIP canister were also conducted for both samples using X-ray diffraction and SEM-EDS. The sample with the Ni HIP canister showed almost no interaction zone with only minor diffusion of Ni from the inner wall of the canister into the near-surface region of the wasteform. The sample with the SS HIP canister showed ∼100–120 μm of interaction zone dominated by high-temperature Cr diffusion from canister materials to the wasteform with the Cr predominantly incorporated into the durable zirconolite phase. We also examined, for the first time, changes to the HIP canister wall thickness caused by HIPing and demonstrated that no canister wall thinning occurred. Instead, in the areas examined, the canister wall thickness was observed to increase (up to ∼20%) due to the compression occurring during the HIP cycle. Further, only sparse formation of (Cr, Mn)-rich oxide particles were noted within the HIP canister inner wall area immediately adjacent to the ceramic material, with no evidence for reverse diffusion of ceramic materials. Though the HIP canister–wasteform interaction extends to ∼120 μm when using an SS HIP canister for the system investigated, this translates to <<1 vol.% for an industrial scale HIPed wasteform. Importantly, the HIP canister–wasteform interactions did not produce any obviously less durable phases in the wasteform or had any detrimental impact on the HIP canister properties.     

Rheokinematics for product development—Formulation screening in rotational rheometers

Product formulations for industrial processes are typically developed at laboratory scale. However, the mixing conditions are not easily mimicked in the laboratory. A rotational device is proposed in this study as a fast laboratory-scale formulation development, which enables mimicking the mixing conditions in the industrial process. The geometrical configurations of the rotational device are from rheometry devices (plate-plate and cone-plate). The main advantages of this method are the small amounts of raw materials and shorter testing times. This methodology is applied to an industrial case study, the reaction injection molding (RIM) process. The mixing length scales evolution in the rotational rheometer were matched to those in RIM machines. The main novelty of this study is the introduction of a protocol that bridges the processing conditions at laboratory using small amounts of raw materials to high throughput continuous flow reactors.     

Applications of analytical electron microscopy to guide the design of boron carbide

Compositional analysis of boron carbide on nanometer length scales to examine or interpret atomic mechanisms, for example, solid-state amorphization or grain-boundary segregation, is challenging. This work reviews advancements in high-resolution microanalysis to characterize multiple generations of boron carbide. First, ζ-factor microanalysis will be introduced as a powerful (scanning) transmission electron microscopy ((S)TEM) analytical framework to accurately characterize boron carbide. Three case studies involving the application of ζ-factor microanalysis will then be presented: (1) accurate stoichiometry determination of B-doped boron carbide using ζ-factor microanalysis and electron energy loss spectroscopy, (2) normalized quantification of silicon grain-boundary segregation in Si-doped boron carbide, and (3) calibration of a scanning electron microscope X-ray energy-dispersive spectroscopy (XEDS) system to measure compositional homogeneity differences of B/Si-doped arc-melted boron carbides in the as-melted and annealed conditions. Overall, the improvement and application of advanced analytical tools have helped better understand processing–microstructure–property relationships and successfully manufacture high-performance ceramics.     

Aluminium-doped TiO2 nanotubes with enhanced light-harvesting properties

Titanium dioxide (TiO₂) application in light-harvesting processes is hindered by its wide band gap. Strategies such as morphology shifts from nanoparticles to nanotubes and doping of fabricated nanostructures are widely used to address this issue. Combining both approaches, this work successfully synthesizes, for the first time, aluminium-doped TiO₂ nanotubes via a single-step anodization method at three distinct potentials (20, 40 and 60 V). SEM images revealed the successful formation of remarkably thin layers of TiO₂ nanotubes produced at 40 and 60 V. X-ray diffractograms and Raman spectra suggest the successful insertion of aluminium into the anatase lattice. Diffuse reflectance confirmed the doping process through a marked effect on the absorbance of visible light for the higher voltages, as well as through a reduction in the optical band gap. For utilization purposes, the photoelectrochemical performance of 40 V Al–TiO₂ was able to deliver a comparable response to that of a compact TiO₂ layer of the same thickness. The current density developed by the 60 V sample was increased by 120% in comparison to the undoped material, despite having an absorbance much lower than that of the latter. Overall, synthesizing an Al-doped TiO₂ nanotubular structure has proven to be a great strategy in the development of materials for application in advanced light-harvesting electrodes.     

The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2)

Here we present the rational design and synthetic methodologies towards proteolysis-targeting chimeras (PROTACs) for the recently-emerged target leucine-rich repeat kinase 2 (LRRK2). Two highly potent, selective, brain-penetrating kinase inhibitors were selected, and their structure was appropriately modified to assemble a cereblon-targeting PROTAC. Biological data show strong kinase inhibition and the ability of the synthesized compounds to enter the cells. However, data regarding the degradation of the target protein are inconclusive. The reasons for the inefficient degradation of the target are further discussed.     

Design,Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2–5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.     

Correction to: Two New Co(II) Complexes of Picolinate: Synthesis,Crystal Structure,Spectral Characterization, α-Glucosidase İnhibition and TD/DFT Study

Journal of Inorganic and Organometallic Polymers and Materials -     

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.     

Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.