METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.

Designing 3d Transition Metal Cation-Doped MRuOx As Durable Acidic Oxygen Evolution Electrocatalysts for PEM Water Electrolyzers.

The continuous dissolution and oxidation of active sites in Ru-based electrocatalysts have greatly hindered their practical application in proton exchange membrane water electrolyzers (PEMWE). In this work, we first used density functional theory (DFT) to calculate the dissolution energy of Ru in the 3d transition metal-doped MRuOx (M = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn) to evaluate their stability for acidic oxygen evolution reaction (OER) and screen out ZnRuOx as the best candidate. To confirm the theoretical predictions, we experimentally synthesized these MRuOx materials and found that ZnRuOx indeed displays robust acidic OER stability with a negligible decay of η10 after 15 000 CV cycles. Of importance, using ZnRuOx as the anode, the PEMWE can run stably for 120 h at 200 mA cm-2. We also further uncover the stability mechanism of ZnRuOx, i.e., Zn atoms doped in the outside of ZnRuOx nanocrystal would form a "Zn-rich" shell, which effectively shortened average Ru-O bond lengths in ZnRuOx to strengthen the Ru-O interaction and therefore boosted intrinsic stability of ZnRuOx in acidic OER. In short, this work not only provides a new study paradigm of using DFT calculations to guide the experimental synthesis but also offers a proof-of-concept with 3d metal dopants as RuO2 stabilizer as a universal principle to develop high-durability Ru-based catalysts for PEMWE.

Gadolinium Retention and Nephrotoxicity in a Mouse Model of Acute Ischemic Stroke: Linear Versus Macrocyclic Agents.

BACKGROUND: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used for acute ischemic stroke (AIS) patients. GBCAs or AIS alone may cause the adverse effects on kidney tissue, respectively. However, whether GBCAs and AIS would generate a synergistic negative effect remains undefined. PURPOSE: To evaluate synergistic negative effects of AIS and GBCAs on renal tissues in a mouse model of AIS, and to compare the differences of these negative effects between linear and macrocyclic GBCAs. STUDY TYPE: Animal study. ANIMAL MODEL: Seventy-two healthy mice underwent transient middle cerebral artery occlusion (tMCAO) and sham operation to establish AIS and sham model (N = 36/model). 5.0 mmol/kg GBCAs (gadopentetate or gadobutrol) or 250 µL saline were performed at 4.5 hours and 1 day after model establishing (N = 12/group). ASSESSMENT: Inductively coupled plasma mass spectrometry (ICP-MS) was performed to detect Gd concentrations. Serum biochemical analyzer was performed to measure the serum creatinine (Scr), uric acid (UA), and blood urea nitrogen (BUN). Pathological staining was performed to observe tubular injury, cell apoptosis, mesangial hyperplasia, and interstitial fibrosis. STATISTICAL TESTS: Two-way analysis of variances with post hoc Sidak's tests and independent-samples t-tests were performed. A P-value <0.05 was considered statistically significant. RESULTS: AIS groups showed higher Gd concentration than sham group on day 1 p.i. regardless of gadopentetate or gadobutrol used. Increased total Gd concentration was also found in AIS + gadopentetate group compared with the sham group on day 28 p.i. Significantly higher rates for renal dysfunction, higher tubular injury scores, and higher numbers of apoptotic cells on days 1 or 28 p.i. were found for AIS mice injected with GBCA. AIS + gadopentetate group displayed more severe renal damage than the AIS + gadobutrol group. DATA CONCLUSION: AIS and GBCAs may cause increased total Gd accumulation and nephrotoxicity in a mouse, especially linear GBCAs were used. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

A General Descriptor for Single-Atom Catalysts with Axial Ligands.

Decoration of an axial coordination ligand (ACL) on the active metal site is a highly effective and versatile strategy to tune activity of single-atom catalysts (SACs). However, the regulation mechanism of ACLs on SACs is still incompletely known. Herein, we investigate diversified combinations of ACL-SACs, including all 3d-5d transition metals and ten prototype ACLs. We identify that ACLs can weaken the adsorption capability of the metal atom (M) by raising the bonding energy levels of the M-O bond while enhancing dispersity of the d orbital of M. Through examination of various local configurations and intrinsic parameters of ACL-SACs, a general structure descriptor σ is constructed to quantify the structure-activity relationship of ACL-SACs which solely based on a few key intrinsic features. Importantly, we also identified the axial ligand descriptor σACL, as a part of σ, which can serve as a potential descriptor to determine the rate-limiting steps (RLS) of ACL-SACs in experiment. And we predicted several ACL-SACs, namely, CrN4-, FeN4-, CoN4-, RuN4-, RhN4-, OsN4-, IrN4- and PtN4-ACLs, that entail markedly higher activities than the benchmark catalysts of Pt and IrO2 for oxygen reduction reaction and oxygen evolution reaction, respectively, thereby supporting that the general descriptor σ can provide a simple and cost-effective method to assess efficient electrocatalysts.

Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits.

PURPOSE: To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke. METHODS: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. RESULTS: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p &lt; 0.05; gadopentetate, p &lt; 0.001) and 28 p. i of gadopentetate. (p &lt; 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p &gt; 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p &lt; 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p &lt; 0.05). CONCLUSIONS: Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

The endorsement of general and artificial intelligence reporting guidelines in radiological journals: a meta-research study.

BACKGROUND: Complete reporting is essential for clinical research. However, the endorsement of reporting guidelines in radiological journals is still unclear. Further, as a field extensively utilizing artificial intelligence (AI), the adoption of both general and AI reporting guidelines would be necessary for enhancing quality and transparency of radiological research. This study aims to investigate the endorsement of general reporting guidelines and those for AI applications in medical imaging in radiological journals, and explore associated journal characteristic variables. METHODS: This meta-research study screened journals from the Radiology, Nuclear Medicine & Medical Imaging category, Science Citation Index Expanded of the 2022 Journal Citation Reports, and excluded journals not publishing original research, in non-English languages, and instructions for authors unavailable. The endorsement of fifteen general reporting guidelines and ten AI reporting guidelines was rated using a five-level tool: "active strong", "active weak", "passive moderate", "passive weak", and "none". The association between endorsement and journal characteristic variables was evaluated by logistic regression analysis. RESULTS: We included 117 journals. The top-five endorsed reporting guidelines were CONSORT (Consolidated Standards of Reporting Trials, 58.1%, 68/117), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 54.7%, 64/117), STROBE (STrengthening the Reporting of Observational Studies in Epidemiology, 51.3%, 60/117), STARD (Standards for Reporting of Diagnostic Accuracy, 50.4%, 59/117), and ARRIVE (Animal Research Reporting of In Vivo Experiments, 35.9%, 42/117). The most implemented AI reporting guideline was CLAIM (Checklist for Artificial Intelligence in Medical Imaging, 1.7%, 2/117), while other nine AI reporting guidelines were not mentioned. The Journal Impact Factor quartile and publisher were associated with endorsement of reporting guidelines in radiological journals. CONCLUSIONS: The general reporting guideline endorsement was suboptimal in radiological journals. The implementation of reporting guidelines for AI applications in medical imaging was extremely low. Their adoption should be strengthened to facilitate quality and transparency of radiological study reporting.

Ischemic Stroke Increased Gadolinium Deposition in the Brain and Aggravated Astrocyte Injury After Gadolinium-Based Contrast Agent Administration: Linear Versus Macrocyclic Agents.

BACKGROUND: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used in MRI. However, several studies have reported Gd deposition in the brain, which has raised concerns about safety. PURPOSE: To investigate the effects of ischemic stroke on Gd deposition in the brain after repeated administration of linear or macrocyclic GBCAs and to determine whether GBCAs aggravate astrocyte injury after stroke. STUDY TYPE: Animal study. ANIMAL MODEL: Twenty-seven male Sprague-Dawley rats were randomized to an exposure group (n = 24) and a healthy control group (n = 3). Half of the exposure group (n = 12) underwent transient middle cerebral artery occlusion (tMCAO) and half (n = 12) had a sham procedure. In each subgroup (tMCAO or sham), the rats had repeated gadopentetate (n = 6) or gadobutrol (n = 6) injections. Oxygen-glucose deprivation and reoxygenation (OGD/R) was used as an in vitro model of stroke. ASSESSMENT: On day 3 and day 28 after the last injection (p.i.), the Gd concentration in the cerebrum was quantified by inductively coupled plasma mass spectrometry. Cell viability, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were analyzed in vitro. STATISTICAL TESTS: One-way analysis of variance and two-sample t-tests were performed. RESULTS: The Gd concentration in the ipsilateral hemisphere homogenates of tMCAO group was significantly higher than that in the brain homogenates of the sham group on day 3 p.i. of either gadobutrol (0.065 ± 0.006 vs. 0.042 ± 0.007 µg/g, P < 0.05) or gadopentetate (0.093 ± 0.010 vs. 0.069 ± 0.008 µg/g, P < 0.05). Increased Gd deposition was also found in the ipsilateral hemisphere homogenates of the tMCAO group compared with the brain homogenates of the sham group on day 28 p.i. of gadopentetate (0.075 ± 0.012 vs. 0.044 ± 0.003 µg/g, P < 0.05), but not gadobutrol (0.012 ± 0.007 vs. 0.010 ± 0.001 µg/g, P = 0.80). The Gd concentration in the ipsilateral hemisphere in the tMCAO group was significantly higher for gadopentetate than gadobutrol on both day 3 p.i. (0.085 ± 0.006 vs. 0.049 ± 0.005 µg/g, P < 0.05) and day 28 p.i (0.075 ± 0.012 vs. 0.012 ± 0.007 µg/g, P < 0.05). Additionally, compared with gadobutrol, gadopentetate decreased viability, increased ROS accumulation, and decreased MMP in OGD/R-induced astrocytes (all P < 0.05). DATA CONCLUSION: Administration of GBCAs after an animal model of ischemic stroke increased Gd deposition in the brain and aggravated astrocyte injury. The effect of gadopentetate appeared to be more pronounced than that of gadobutrol.

Longitudinal Multiparametric MRI Assessment of Irradiated Salivary Gland in a Rat Model: Correlated With Histological Findings.

BACKGROUND: Several magnetic resonance imaging (MRI) sequences have been applied to assess injured glands but without histological validation. PURPOSE: To evaluate longitudinal changes in multiparametric MRI (mp-MRI) of irradiated salivary glands in a rat model and investigate correlations between mp-MRI and histological findings. STUDY TYPE: Prospective. ANIMAL MODEL: Submandibular glands of 36 rats were radiated using a single dose of 15 Gy X-ray (irradiation [IR] group), and 6 other rats were enrolled into sham-IR group. mp-MRI were scanned 1 day after sham-IR (n = 6), or 1, 2, 4, 8, 12, 24 weeks after IR (n = 36, 6 per subgroup). FIELD STRENGTH/SEQUENCE: A 3.0-T/Diffusion-weighted imaging (DWI), readout-segmented echo-planar imaging (EPI) sequence; intravoxel incoherent motion DWI, single-shot EPI sequence; T1 mapping, dual-flip-angle gradient-echo sequence with volumetric interpolated breath-hold examination; T2 mapping, turbo spin-echo sequence. ASSESSMENT: Parameters including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D* ), perfusion fraction (f), T1 and T2 value were obtained. Histological examinations, including hematoxylin and eosin staining (for acinar cell fraction [AC%] detection), Masson's trichrome staining (for degree of fibrosis [F%] determination) and CD34-immunohistochemical staining (for microvessel density [MVD] calculation), were performed at corresponding time points. STATISTICAL TESTS: One-way analysis of variance was used to compare the mp-MRI and histological parameters among different groups. Spearman correlation analysis was applied to determine the correlation between mp-MRI and histological parameters. Two-sided P ≤ 0.05 was considered statistically significant. RESULTS: Changes of mp-MRI parameters (ADC, D, D* , f, T1, T2) and histological results (AC%, F%, MVD) among the seven groups were all significant. ADC, D, and T2 values negatively correlated with AC% (ADC, r = -0.728; D, r = -0.773; T2, r = -0.600), f positively correlated with MVD (r = 0.496), and T1 values positively correlated with F% (r = 0.714). DATA CONCLUSION: mp-MRI might be able to noninvasively and quantitatively evaluate the dynamic pathological changes within the irradiated salivary glands. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Controlling the chirality and number of strands of helices self-assembled from achiral block copolymers confined inside a nanopore: a simulation study.

Achiral block copolymers can self-assemble into helical structures when confined inside a cylindrical nanopore. However, controlling the chirality and the number of strands of helices is challenging. We present our simulation results of the influence of a chiral patch added to the confining nanopore on the structures and chirality of helices self-assembled from achiral cylinder-forming diblock copolymers under the confinement. Our results indicate that, when the designed patch is of proper geometry, it can induce the formation of helical structures and exhibit good control over their chirality. The bottom surface of the patch can induce the formation of a characteristic local structure near and parallel to it. It is the characteristic local structure that directs the formation of helices and of their chirality consistent with that of the patch. A large patch angle or the top/bottom surface of a weakly selective pore promotes the formation of double-helices compared to single-helices by enlarging the pitch of the helices near the patch or through the entropic attraction of the top surface of the pore to the minority blocks.

A simulation study of the self-assembly of ABC star terpolymers confined between two parallel surfaces.

The phase behavior of ABC star terpolymers confined between two identical parallel surfaces is systematically studied using a simulated annealing method. Several phase diagrams are constructed for systems with different bulk phases or with different interfacial interaction strength ratios in the space of surface distance (D) and surface preference for different arms, or in the space of D and the arm-length ratio x. Phases, including tiling patterns [6.6.6], [8.8.4], [8.6.6; 8.6.4], [8.6.6; 8.6.4; 10.6.6; 10.6.4] and hierarchical lamellar structures of lamella + cylinders and lamella + rods, are identified both in the bulk and in the films. Our results suggest that the self-assembled structure of a phase is largely controlled by x, while an increase of the interfacial interaction strength ratio shifts the x-window for each phase to the smaller x side. The orientation of a confined phase depends on the "effective surface preference" which is a combined effect of the interfacial interaction strength ratio, the surface preference, and the entropic preference. In the case of neutral or weak "effective surface preference", phases with a perpendicular orientation are usually observed, while in the case of strong "effective surface preference" phases with a perpendicular orientation or also with outermost wetting-layers can be frequently observed under some circumstances.

Dual Nickel/Ruthenium Strategy for Photoinduced Decarboxylative Cross-Coupling of α,ß-Unsaturated Carboxylic Acids with Cycloketone Oxime Esters.

Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,ß-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,ß-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.

Signalling pathway of U46619-induced vascular smooth muscle contraction in mouse coronary artery.

BACKGROUND: Thromboxane A2 (TXA2 ) participates in many pathophysiological processes of coronary artery disease. However, its mechanism of TXA2 -induced contraction in the coronary artery remains to be clarified. A multi myograph system was used to measure the isometric tension of the mouse coronary arteries and identify the effect and pathway of TXA2 analogues U46619. Confocal laser scanning microscopy was used to measure the intracellular calcium concentration ([Ca2+ ]i ) in mouse coronary artery smooth muscle cells. Results from the experiment had shown that contraction in coronary artery was generated by U46619 in a concentration-dependent manner, which was completely abolished by a specific TXA2 receptor blocker, GR32191. PI-PLC inhibitors U73122 and D609 and Rho-Kinase inhibitor Y-27632 can block the U46619 elicited coronary artery contraction in a dose-dependent manner. Then, the vasoconstriction response to U46619 was obviously inhibited by two pan-PKC inhibitors chelerythrine or GÓ§6983, and a selective PKCδ inhibitor rottlerin, but was not blocked by a selective PKCζ inhibitor PKC-PS or a selective PKCß inhibitor hispidin. Meanwhile, the PKC activator PDBu-induced vasoconstriction was significantly inhibited by 1 µmol/L nifedipine, then mostly inhibited by 100 µmol/L 2-APB and 10 µmol/L Y27632. We further found that the response to U46619 was inhibited, respectively, by three calcium channel blockers nifedipine, SKF96356 or 2-APB in a concentration-dependent manner. Although Store-operated Ca2+ (SOC) channels generated the increase of [Ca2+ ]i in mouse coronary artery smooth muscle cells, SOC channels did not contribute to the vasoconstriction in mouse coronary arteries. Caffeine-induced sarcoplasmic reticulum (SR) Ca2+ release could obviously induce coronal vasoconstriction. In addition, NPPB, a cell membrane Ca2+ activated C1- channel blocker, could obviously inhibit the U46619-induced vasoconstriction. The U46619-induced mouse coronary artery contraction was involved in the increase in [Ca2+ ]i mediated by Cav1.2, TRPC channels and SR release through the activation of G-protein-coupled TP receptors and the kinases signalling pathway in TP downstream proteins, while SOC channels did not participate in the vasoconstriction.

Phase behavior of ABC cyclic terpolymer melts: a simulation study.

The phase behavior of ABC cyclic terpolymer melts is investigated using a simulated annealing technique. A ternary phase diagram is constructed by tuning the volume fractions of the three blocks (fA, fB, and fC) in the case of symmetric interactions. 11 phases are predicted, including lamellae with spheres at the interfaces, lamellae with spheres inside a domain, lamellae with spheres inside domains, cylinders in perforated lamellae, [6.6.6] tiling patterns, lamella + cylinder, hierarchical double-gyroid, columnar piled disk, patched spheres, cylinders with spheres at the interfaces and double gyroid with spheres at the interfaces. In these structures, the end segments of the three blocks tend to distribute uniformly on the A/B, B/C, or A/C interfaces, which may result in superior mechanical properties of the structures in cyclic terpolymer systems than those of the same structures formed in star or linear terpolymer systems. The physical reason for the similarities and differences between the phases formed in ABC cyclic and star terpolymer systems is investigated. Our simulation results are compared with related experimental observations and theoretical calculations.

Lattice self-consistent field calculations of confined symmetric block copolymers of various chain architectures.

The effects of chain architecture and confinement on the structure and orientation of lamellae formed by incompressible and symmetric AB-type block copolymer melts confined between two parallel and identical surfaces are investigated using self-consistent field calculations on a simple cubic lattice. Five systems of various chain architectures (linear, ring, and star) and lengths are studied, with their bulk lamellar period L0 chosen such that they have comparable L0/Rg, where Rg denotes the ideal-chain radius of gyration. For thin films of thickness D = L0 confined between two neutral surfaces, we define the rescaled volume fraction profiles of A, B, chain end, and joint segments in the parallel and perpendicular lamellae such that these profiles can be directly compared among the five systems to quantitatively reveal the interplay between the chain-end enrichment near confining surfaces and the surface-induced A-B compatibilization, and how such interplay is affected by the chain architectures (for example, the chain-crowding effects in the star block copolymers). The effects of D and surface preference for one of the blocks are also investigated.

Structure-Property Effects in the Generation of Transient Aqueous Benzoic Acid Anhydrides by Carbodiimide Fuels.

The design of dissipative systems, which operate out-of-equilibrium by consuming chemical fuels, is challenging. As yet, there are a few examples of privileged fuel chemistries that can be broadly applied in abiotic systems in the same way that ATP hydrolysis is exploited throughout biochemistry. The key issue is that designing nonequilibrium systems is inherently about balancing the relative rates of coupled reactions. The use of carbodiimides as fuels to generate transient aqueous carboxylic anhydrides has recently been used in examples of new nonequilibrium materials and supramolecular assemblies. Here, we explore the kinetics of formation and decomposition of a series of benzoic anhydrides generated from the corresponding acids and EDC under typical conditions (EDC = N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride). The reactions can be described by a simple mechanism that merges known behavior for the two processes independently. Structure-property effects in these systems are dominated by differences in the anhydride decomposition rate. The kinetic parameters allow trends in concentration-dependent properties to be simulated, such as reaction lifetimes, peak anhydride concentrations, and yields. For key properties, there are diminishing returns with the addition of increasing amounts of fuel. These results should provide useful guidelines for the design of functional systems making use of this chemistry.

Synthesis of gem-difluoroalkenes via nickel-catalyzed allylic defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides.

A nickel-catalyzed defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides has been developed. Various substituted trifluoromethyl alkenes and epoxides were found to be suitable reaction substrates. This reaction enabled C(sp3)-C(sp3) bond construction through allylic defluorinative cross-coupling of trifluoromethyl alkenes under mild reaction conditions. This methodology was highly compatible with various sensitive functional groups, providing access to a diverse array of functionalized gem-difluoroalkene-containing alcohol compounds.

Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats.

In recent years, studies have shown that the secretome of bone marrow mesenchymal stromal cells (BMSCs) contains many growth factors, cytokines, and antioxidants, which may provide novel approaches to treat ischemic diseases. Furthermore, the secretome may be modulated by hypoxic preconditioning. We hypothesized that conditioned medium (CM) derived from BMSCs plays a crucial role in reducing tissue damage and improving neurological recovery after ischemic stroke and that hypoxic preconditioning of BMSCs robustly improves these activities. Rats were subjected to ischemic stroke by middle cerebral artery occlusion and then intravenously administered hypoxic CM, normoxic CM, or Dulbecco modified Eagle medium (DMEM, control). Cytokine antibody arrays and label-free quantitative proteomics analysis were used to compare the differences between hypoxic CM and normoxic CM. Injection of normoxic CM significantly reduced the infarct area and improved neurological recovery after stroke compared with administering DMEM. These outcomes may be associated with the attenuation of apoptosis and promotion of angiogenesis. Hypoxic preconditioning significantly enhanced these therapeutic effects. Fourteen proteins were significantly increased in hypoxic CM compared with normoxic CM as measured by cytokine arrays. The label-free quantitative proteomics analysis revealed 163 proteins that were differentially expressed between the two groups, including 107 upregulated proteins and 56 downregulated proteins. Collectively, our results demonstrate that hypoxic CM protected brain tissue from ischemic injury and promoted functional recovery after stroke in rats and that hypoxic CM may be the basis of a potential therapy for stroke patients.

Highly Ordered 3D Porous Graphene Sponge for Wearable Piezoresistive Pressure Sensor Applications.

Wearable sensors with excellent flexibility and sensitivity have emerged as a promising field for healthcare, electronic skin, and so forth. Three-dimensional (3D) graphene sponges (GS) have emerged as high-performance piezoresistive sensors; however, problems, such as limited flexibility, high cost, and low sensitivity, remain. Meanwhile, device-level wearable pressure sensors with GS have rarely been demonstrated. In this work, highly ordered 3D porous graphene sponges (OPGSs) were first successfully prepared and controlled through an emulsion method, and then a device-level wearable pressure sensor with high flexibility and sensitivity was assembled with a gold electrode and polydimethylsiloxane into a reliable package. The pH values were carefully controlled to form a stable emulsion and the OPGSs showed a highly ordered 3D structure with ultralow density, high porosity, and conductivity; this resulted in a gauge factor of 0.79-1.46, with 50 % compression strain and excellent long-term reproducibility over 500 cycles of compression-relaxation. Moreover, the well-packaged pressure sensor devices exhibited ultrahigh sensitivity to detect human motions, such as wrist bending, elbow bending, finger bending, and palm flexing. Thus, the developed pressure sensors exhibited great potential in the fields of human-interactive applications, biomechanical systems, electronic skin, and so forth.

Formation Mechanisms of Porous Particles from Self-Assembly of Amphiphilic Diblock Copolymers inside an Oil-in-Water Emulsion Droplet upon Solvent Evaporation.

The formation mechanisms of porous particles from self-assembly of amphiphilic diblock copolymers inside an oil-in-water emulsion droplet upon evaporation of the organic solvent are investigated based on Monte Carlo simulations for the first time. A morphological diagram of particles is constructed as a function of the surfactant concentration (φ) and the copolymer composition characterized by the volume fraction of the hydrophilic B block ( fB). Particles with various morphologies are predicted. Morphological sequences from non-porosity to closed-porosity to capsules and finally to open-porosity particles are usually observed with increasing φ when fB ≤ 1/2, with the only exception that capsules do not occur when fB = 1/6. Furthermore, the critical φ value for a given morphological transition usually decreases with increasing fB. Micelles are always observed at higher φ regions when fB > 1/2. It is found that the specific surface area falls on almost the same regime for particles with the same kind of morphology, indicating that the morphology of a particle largely determines its specific surface area. The chain stretching varies with the particle morphology. It is the presence of the surfactant that makes the formation of porous particles possible, while when φ > 0, multiple morphological transitions can be induced by changing fB. In the process of organic solvent removal, the value of fB may affect the shape of pores inside the droplet and hence leads to the fB dependence of the morphological sequences. When the solvent evaporation is not too fast, the resulting morphological sequence does not depend on the evaporation rate. Our results are compared with related experiments.

A Novel Differential High-Frequency Current Transformer Sensor for Series Arc Fault Detection.

Fault arc detection is an important technology to ensure the safe operation of electrical equipment and prevent electrical fires. The high-frequency noise of the arc current is one of the typical arc characteristics of almost all loads. In order to accurately detect arc faults in a low-voltage alternating-current (AC) system, a novel differential high-frequency current transformer (D-HFCT) sensor for collecting high-frequency arc currents was proposed. The sensitivity and frequency band of the designed sensor were verified to ensure that the acquisition requirements of the high-frequency current were satisfied. A series arc fault simulation experiment system was built, and resistive, inductive, and non-linear load and high-power shielding load experiments were carried out. Experiments showed that the sensor output signal was close to zero in the non-arc state, and the sensor output response was a high-frequency glitch in the arc state. The results were consistent for different loads, and the discrimination between normal and fault states was obvious, which proved that the sensor is suitable for series arc fault detection.