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Parkinson's disease (PD) is the second most common chronic neurodegenerative disease globally; however, it lacks effective treatment at present. Focused ultrasound (FUS) combined with microbubbles could increase the efficacy of drug delivery to specific brain regions and is becoming a promising technology for the treatment of central nervous system diseases. In this study, we explored the therapeutic potential of FUS-mediated blood-brain barrier (BBB) opening of the left striatum to deliver gastrodin (GAS) in a subacute PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration of GAS in the left hemisphere was detected by ultra-high performance liquid chromatography electrospray Q-Orbitrap mass spectrometry (UHPLC/ESI Q-Orbitrap) and the distribution of tyrosine hydroxylase (TH) neurons was detected by immunohistochemical staining. The expression of TH, Dopamine transporter (DAT), cleaved-caspase-3, B-cell lymphoma 2 (Bcl-2), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYN) protein were detected by western blotting. Analysis showed that the concentration of GAS in the left hemisphere of PD mice increased by approximately 1.8-fold after the BBB was opened. FUS-mediated GAS delivery provided optimal neuroprotective effects and was superior to the GAS or FUS control group. In addition, FUS enhanced GAS delivery significantly increased the expression of Bcl-2, BDNF, PSD-95, and SYN protein in the left striatum ( P < 0.05) and reduced the levels of cleaved-caspase-3 remarkably ( P = 0.001). In conclusion, the enhanced delivery by FUS effectively strengthened the protective effect of GAS on dopaminergic neurons which may be related to the reinforcement of the anti-apoptotic activity and the expression of synaptic-related proteins in the striatum. Data suggests that FUS-enhanced GAS delivery may represent a new strategy for PD treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Luo, Li, Liao, Liao, Chen, Chen and Ao.)

Direct deoxygenation of long-chain fatty acids can produce both saturated alkanes (C n H 2n+2 ) and unsaturated olefins (C n H 2n ). However, the selectivity for the production of olefins via the decarbonylation route is relatively low because of the more favorable decarboxylation pathway. We present an atomically ordered intermetallic PtZn alloy on carbon catalyst (PtZn/C) with a record-high total selectivity (97 %) for undecane (C 11 H 24 ) and undecene (C 11 H 22 ) in the deoxygenation of lauric acid (C 12 H 24 O 2 ). Interestingly, the selectivity for C 11 H 22 is as high as 67.0 % on PtZn/C, which is significantly higher than that of 27.5 % obtained on the Pt/C counterpart under the same reaction conditions. Characterization and theoretical calculation results reveal that the intermetallic PtZn alloy not only inhibits the decarboxylation route by increasing the energy barrier of -COO* cleavage, but also facilitates the decarbonylation route by decreasing CO desorption energy, and therefore the major product is switched from alkanes to olefins., (© 2022 Wiley-VCH GmbH.)

Among metals used for CO 2 electroreduction in water, Cu appears to be unique in its ability to produce C2+ products like ethylene. Bimetallic combinations of Cu with other metals have been investigated with the goal of steering selectivity via creating a tandem pathway through the CO intermediate or by changing the surface electronic structure. Here, we demonstrate a facile cation exchange method to synthesize Ag/Cu electrocatalysts for CO 2 reduction using Cu sulfides as a growth template. Beginning with Cu 2- x S nanosheets (C-nano-0, 100 nm lateral dimension, 14 nm thick), varying the Ag + concentration in the exchange solution produces a gradual change in crystal structure from Cu 7 S 4 to Ag 2 S, as the Ag/Cu mass ratio varies from 0.3 to 25 (CA-nano- x , x indicating increasing Ag fraction). After cation exchange, the nanosheet morphology remains but with increased shape distortion as the Ag fraction is increased. Interestingly, the control (C-nano-0) and cation exchanged nanosheets have very high faradaic efficiency for producing formate at low overpotential (-0.2 V vs. RHE). The primary effect of Ag incorporation is increased production of C2+ products at -1.0 V vs. RHE compared with C-nano-0, which primarily produces formate. Cation exchange can also be used to modify the surface of Cu foils. A two-step electro-oxidation/sulfurization process was used to form Cu sulfides on Cu foil (C-foil- x ) to a depth of a few 10 s of microns. With lower Ag + concentrations, cation exchange produces uniformly dispersed Ag; however, at higher concentrations, Ag particles nucleate on the surface. During CO 2 electroreduction testing, the product distribution for Ag/Cu sulfides on Cu foil (CA-foil- x-y ) changes in time with an initial increase in ethylene and methane production followed by a decrease as more H 2 is produced. The catalysts undergo a morphology evolution towards a nest-like structure which could be responsible for the change in selectivity. For cation-exchanged nanosheets (CA-nano- x ), pre-reduction at negative potentials increases the CO 2 reduction selectivity compared to tests of as-synthesized material, although this led to the aggregation of nanosheets into filaments. Both types of bimetallic catalysts are capable of selective reduction of CO 2 to multi-carbon products, although the optimal configurations appear to be metastable., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Tuning the performance of nanoparticle (NP) catalysts by controlling the NP surface strain has evolved as an important strategy to optimize NP catalysis in many energy conversion reactions. Here, we present our new study on using an eigenforce model to predict and experiments to verify the strain-induced catalysis enhancement of the oxygen reduction reaction (ORR) in the presence of L1 0 -CoMPt NPs (M = Mn, Fe, Ni, Cu, Ni). The eigenforce model allowed us to predict anisotropic (that is, two-dimensional) strain levels on distorted Pt(111) surfaces. Experimentally, by preparing a series of 5 nm L1 0 -CoMPt NPs, we could push the ORR catalytic activity of these NPs toward the optimum region of the theoretical two-dimensional volcano plot predicted for L1 0 -CoMPt. The best ORR catalyst in the alloy NP series we studied is L1 0 -CoNiPt, which has a mass activity of 3.1 A/mg Pt and a specific activity of 9.3 mA/cm 2 at room temperature with only 15.9% loss of mass activity after 30 000 cycles at 60 °C in 0.1 M HClO 4 .

Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium (CM) and fluid flow-treated conditioned medium (FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition (MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition (EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer (FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumor-induced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFβ levels and the composition of tumor-associated volatile organic compounds in the urine. Collectively, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteopontin in tumor-osteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Understanding the Cu-catalyzed electrochemical CO 2 reduction reaction (CO 2 RR) under ambient conditions is both fundamentally interesting and technologically important for selective CO 2 RR to hydrocarbons. Current Cu catalysts studied for the CO 2 RR can show high activity but tend to yield a mixture of different hydrocarbons, posing a serious challenge on using any of these catalysts for selective CO 2 RR. Here, we report a new perovskite-type copper(I) nitride (Cu 3 N) nanocube (NC) catalyst for selective CO 2 RR. The 25 nm Cu 3 N NCs show high CO 2 RR selectivity and stability to ethylene (C 2 H 4 ) at -1.6 V (vs reversible hydrogen electrode (RHE)) with the Faradaic efficiency of 60%, mass activity of 34 A/g, and C 2 H 4 /CH 4 molar ratio of >2000. More detailed electrochemical characterization, X-ray photon spectroscopy, and density functional theory calculations suggest that the high CO 2 RR selectivity is likely a result of (100) Cu(I) stabilization by the Cu 3 N structure, which favors CO-CHO coupling on the (100) Cu 3 N surface, leading to selective formation of C 2 H 4 . Our study presents a good example of utilizing metal nitrides as highly efficient nanocatalysts for selective CO 2 RR to hydrocarbons that will be important for sustainable chemistry/energy applications.

Circulating cell-free tumor DNA (ctDNA) is a promising biomarker in cancer. Ultrasensitive technologies enable detection of low (< 0.1%) mutant allele frequencies, a pre-requisite to fully utilize the potential of ctDNA in cancer diagnostics. In addition, the entire liquid biopsy workflow needs to be carefully optimized to enable reliable ctDNA analysis. Here, we discuss important considerations for ctDNA detection in plasma. We show how each experimental step can easily be evaluated using simple quantitative PCR assays, including detection of cellular DNA contamination and PCR inhibition. Furthermore, ctDNA assay performance is also demonstrated to be affected by both DNA fragmentation and target sequence. Finally, we show that quantitative PCR is useful to estimate the required sequencing depth and to monitor DNA losses throughout the workflow. The use of quality control assays enables the development of robust and standardized workflows that facilitate the implementation of ctDNA analysis into clinical routine.

We report a general chemical approach to synthesize strongly ferromagnetic rare-earth metal (REM) based SmCo and SmFeN nanoparticles (NPs) with ultra-large coercivity. The synthesis started with the preparation of hexagonal CoO+Sm 2 O 3 (denoted as SmCo-O) multipods via decomposition of Sm(acac) 3 and Co(acac) 3 in oleylamine. These multipods were further reduced with Ca at 850 °C to form SmCo 5 NPs with sizes tunable from 50 to 200 nm. The 200 nm SmCo 5 NPs were dispersed in ethanol, and magnetically aligned in polyethylene glycol (PEG) matrix, yielding a PEG-SmCo 5 NP composite with the room temperature coercivity (H c ) of 49.2 kOe, the largest H c among all ferromagnetic NPs ever reported, and saturated magnetic moment (M s ) of 88.7 emu g -1 , the highest value reported for SmCo 5 NPs. The method was extended to synthesize other ferromagnetic NPs of Sm 2 Co 17 , and, for the first time, of Sm 2 Fe 17 N 3 NPs with H c over 15 kOe and M s reaching 127.9 emu g -1 . These REM based NPs are important magnetic building blocks for fabrication of high-performance permanent magnets, flexible magnets, and printable magnetic inks for energy and sensing applications., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report a simple strategy to synthesize anisotropic SmCo5 nanoplates. The strategy involves the pre-synthesis of 125 × 12 nm Sm(OH)3 nanorods and 10 nm Co nanoparticles followed by the self-assembly of these nanorods and nanoparticles into Sm(OH)3-Co nanocomposites. Once embedded in a CaO matrix, the nanocomposite is subjected to high temperature (850 °C) annealing in the presence of Ca, leading to the formation of 125 × 10 nm SmCo5 nanoplates, which are dispersible in ethanol, allowing the alignment in epoxy resin under a 20 kOe magnetic field. The aligned SmCo5 nanoplates show a square hysteresis behavior with room temperature coercivity reaching 30.1 kOe, which is among the highest values ever reported for SmCo5 made from chemical methods. This work provides a new approach to high-performance anisotropic SmCo5 for permanent magnetic applications.

We report a facile method for assembly of a monolayer array of nitrogen-doped graphene (NG) and nanoparticles (NPs) and the subsequent transfer of two layers onto a solid substrate (S). Using 3 nm NiPd NPs as an example, we demonstrate that NiPd-NG-Si (Si=silicon wafer) can function as a catalyst and show maximum NiPd catalysis for the hydrolysis of ammonia borane (H 3 NBH 3 , AB) with a turnover frequency (TOF) of 4896.8 h -1 and an activation energy (E a ) of 18.8 kJ mol -1 . The NiPd-NG-S catalyst is also highly active for catalyzing the transfer hydrogenation from AB to nitro compounds, leading to the green synthesis of quinazolines in water. Our assembly method can be extended to other graphene and NP catalyst materials, providing a new 2D NP catalyst platform for catalyzing multiple reactions in one pot with maximum efficiency., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Stabilizing a 3d-transition metal component M from an MPd alloy structure in an acidic environment is key to the enhancement of MPd catalysis for various reactions. Here we demonstrate a strategy to stabilize Cu in 5 nm CuPd nanoparticles (NPs) by coupling the CuPd NPs with perovskite-type WO 2.72 nanorods (NRs). The CuPd NPs are prepared by controlled diffusion of Cu into Pd NPs, and the coupled CuPd/WO 2.72 are synthesized by growing WO 2.72 NRs in the presence of CuPd NPs. The CuPd/WO 2.72 can stabilize Cu in 0.1 M HClO 4 solution and, as a result, they show Cu, Pd composition dependent activity for the electrochemical oxidation of formic acid in 0.1 M HClO 4 + 0.1 M HCOOH. Among three different CuPd/WO 2.72 studied, the Cu 48 Pd 52 /WO 2.72 is the most efficient catalyst, with its mass activity reaching 2086 mA/mg Pd in a broad potential range of 0.40 to 0.80 V (vs RHE) and staying at this value after the 12 h chronoamperometry test at 0.40 V. The synthesis can be extended to obtain other MPd/WO 2.72 (M = Fe, Co, Ni), making it possible to study MPd-WO 2.72 interactions and MPd stabilization on enhancing MPd catalysis for various chemical reactions.

We report a seed-mediated growth of 2.3 nm AgPd nanoparticles (NPs) in the presence of 40 × 5 nm WO 2.72 nanorods (NRs) for the synthesis of AgPd/WO 2.72 composites. The strong interactions between AgPd NPs and WO 2.72 NRs make the composites, especially the Ag 48 Pd 52 /WO 2.72 , catalytically active for dehydrogenation of formic acid (TOF = 1718 h -1 and E a = 31 kJ/mol) and one-pot reactions of formic acid, 2-nitrophenol, and aldehydes into benzoxazoles in near quantitative yields under mild conditions. The catalysis can also be extended to the one-pot reactions of ammonium formate, 2-nitroacetophenone, and aldehyde for high yield syntheses of quinazolines. Our studies demonstrate a new catalyst design to achieve a green chemistry approach to one-pot reactions for the syntheses of benzoxazoles and quinazolines.

We synthesize a new type of hybrid Pd/WO 2.72 structure with 5 nm Pd nanoparticles (NPs) anchored on 50 × 5 nm WO 2.72 nanorods. The strong Pd/WO 2.72 coupling results in the lattice expansion of Pd from 0.23 to 0.27 nm and the decrease of Pd surface electron density. As a result, the Pd/WO 2.72 shows much enhanced catalysis toward electrochemical oxidation of formic acid in 0.1 M HClO 4 ; it has a mass activity of ∼1600 mA/mg Pd in a broad potential range of 0.4-0.85 V (vs RHE) and shows no obvious activity loss after a 12 h chronoamperometry test at 0.4 V. Our work demonstrates an important strategy to enhance Pd NP catalyst efficiency for energy conversion reactions.