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Due largely to the high stability and the potential ozone‐depleting, the transformation of greenhouse gas nitrous oxide has gained much attentions. In present paper, a new insight into the deoxygenation of nitrous oxide with silane was reported by using oriented external electric field (OEEF) as a catalytic strategy. When the OEEF was employed, the reaction barrier of deoxygenation was marvelously decreased as it was oriented along the positive NO/OSi bond‐axis. Especially the field strength is 300 × 10−4 a.u., the differences are up to 22.4/18.3 kcal mol−1 as compared with that of nonfield. In addition, once the H atom in SiH4 was replaced by methyl, two reaction modes were obtained, in which the deoxygenation process was easier when the N2O captured the H atom attached to the Si atom, not attached to the C atom. Further, the solvent effects of deoxygenation reaction were also considered, but with a weak influence were obtained. [ABSTRACT FROM AUTHOR]

Background: Cyclin‐dependent kinases 4 and 6 inhibitors (CDK4/6i) have been shown to improve progression‐free survival (PFS) in patients with metastatic breast cancer (MBC) in randomized control trials. This study aimed to evaluate the efficacy and safety of CDK4/6i in patients with advanced breast cancer (ABC) in a clinical setting. Methods: Consecutive patients with ABC were treated between October 2019 and March 2023 at Taipei Tzu Chi Hospital, Taiwan. Patients who had received at least one dose of CDK4/6i were included in this retrospective study. The main outcome of this study was efficacy based on the treating physicians' assessments in terms of PFS, and overall survival (OS), as well as the factors associated with patient outcome. The secondary outcome was safety. Results: A total of 85 patients were included in the analysis, with a mean age of 66.8 years. After a median follow‐up of 16.1 months, the median PFS was 28.4 months (95% CI: 22.5–33.6) and the median OS could not yet be estimated. The most common adverse events (AE) were fatigue (50.8%), anorexia (45.9%), and leukopenia (44.7%). In multivariable analysis, treatment with CDK4/6i with any grade AE or response to treatment effect (CR/PR) was an independent predictor for longer PFS (hazard ratio [HR] = 0.27, 95% CI: 0.11–0.68; HR = 0.21, 95% CI: 0.06–0.67; p < 0.05). Conclusion: CDK4/6i administered in a real‐world setting exhibits a similar survival benefit with the clinical trials. [ABSTRACT FROM AUTHOR]

Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission. Mitochondria are in a constant balance of fusion and fission, but how the cell prevents excessive fission is unclear. This study shows that the evolutionarily conserved AAA-ATPase Yta4 interacts with the mitochondrial divisome (Fis1, Mdv1 and Dnm1) to inhibit mitochondrial fission. [ABSTRACT FROM AUTHOR]

Aims: Synaptic strength depends strongly on the subsynaptic organisation of presynaptic transmitter release and postsynaptic receptor densities, and their alterations are expected to underlie pathologies. Although synaptic dysfunctions are common pathogenic traits of Alzheimer's disease (AD), it remains unknown whether synaptic protein nano‐organisation is altered in AD. Here, we systematically characterised the alterations in the subsynaptic organisation in cellular and mouse models of AD. Methods: We used immunostaining and super‐resolution stochastic optical reconstruction microscopy imaging to quantitatively examine the synaptic protein nano‐organisation in both Aβ1–42‐treated neuronal cultures and cortical sections from a mouse model of AD, APP23 mice. Results: We found that Aβ1–42‐treatment of cultured hippocampal neurons decreased the synaptic retention of postsynaptic scaffolds and receptors and disrupted their nanoscale alignment to presynaptic transmitter release sites. In cortical sections, we found that while GluA1 receptors in wild‐type mice were organised in subsynaptic nanoclusters with high local densities, receptors in APP23 mice distributed more homogeneously within synapses. This reorganisation, together with the reduced overall receptor density, led to reduced glutamatergic synaptic transmission. Meanwhile, the transsynaptic alignment between presynaptic release‐guiding RIM1/2 and postsynaptic scaffolding protein PSD‐95 was reduced in APP23 mice. Importantly, these reorganisations were progressive with age and were more pronounced in synapses in close vicinity of Aβ plaques with dense cores. Conclusions: Our study revealed a spatiotemporal‐specific reorganisation of synaptic nanostructures in AD and identifies dense‐core amyloid plaques as the major local inductor in APP23 mice. [ABSTRACT FROM AUTHOR]

Background and Purpose: Piezo1 channels are mechanosensitive cationic channels that are activated by mechanical stretch or shear stress. Endothelial Piezo1 activation by shear stress caused by blood flow induces ATP release from endothelial cells; however, the link between shear stress and endothelial ATP production is unclear. Experimental Approach: The mitochondrial respiratory function of cells was measured by using high‐resolution respirometry system Oxygraph‐2k. The intracellular Ca2+ concentration was evaluated by using Fluo‐4/AM and mitochondrial Ca2+ concentration by Rhod‐2/AM. Key Results: The specific Piezo1 channel activator Yoda1 or its analogue Dooku1 increased [Ca2+]i in human umbilical vein endothelial cells (HUVECs), and both Yoda1 and Dooku1 increased mitochondrial oxygen consumption rates (OCRs) and mitochondrial ATP production in HUVECs and primary cultured rat aortic endothelial cells (RAECs). Knockdown of Piezo1 inhibited Yoda1‐ and Dooku1‐induced increases of mitochondrial OCRs and mitochondrial ATP production in HUVECs. The shear stress mimetics, Yoda1 and Dooku1, and the Piezo1 knock‐down technique also demonstrated that Piezo1 activation increased glycolysis in HUVECs. Chelating extracellular Ca2+ with EGTA or chelating cytosolic Ca2+ with BAPTA‐AM did not affect Yoda1‐ and Dooku1‐induced increases of mitochondrial OCRs and ATP production, but chelating cytosolic Ca2+ inhibited Yoda1‐ and Dooku1‐induced increase of glycolysis. Confocal microscopy showed that Piezo1 channels are present in mitochondria of endothelial cells, and Yoda1 and Dooku1 increased mitochondrial Ca2+ in endothelial cells. Conclusion and Implications: Piezo1 channel activation stimulates ATP production through enhancing mitochondrial respiration and glycolysis in vascular endothelial cells, suggesting a novel role of Piezo1 channel in endothelial ATP production. [ABSTRACT FROM AUTHOR]

Herein we report a two‐directional cyclization strategy for the synthesis of highly strained depth‐expanded oxygen‐doped chiral molecular belts of the zigzag‐type. From the easily accessible resorcin[4]arenes, an unprecedented cyclization cascade generating fused 2,3‐dihydro‐1H‐phenalenes has been developed to access expanded molecular belts. Stitching up the fjords through intramolecular nucleophilic aromatic substitution and ring‐closing olefin metathesis reactions furnished a highly strained O‐doped C2‐symmetric belt. The enantiomers of the acquired compounds exhibited excellent chiroptical properties. The calculated parallelly aligned electric (μ) and magnetic (m) transition dipole moments are translated to the high dissymmetry factor (|glum| up to 0.022). This study provides not only an appealing and useful strategy for the synthesis of strained molecular belts but also a new paradigm for the fabrication of belt‐derived chiroptical materials with high CPL activities. [ABSTRACT FROM AUTHOR]

A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world's population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood–brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently. [ABSTRACT FROM AUTHOR]

The preparation of fire-safe and high-performance carbon fiber reinforced composites with reprocessable resin matrix and recyclable reinforced fibers is of great importance and particularly urgent to solve the current overreliance on petrochemical resources for composite raw materials. Herein, we propose an effective strategy to simultaneously solve the flammability and nonrecyclability of the epoxy resin-based composites, in the form of fire-safe and catalyst-free dynamic transesterification networks by introducing a phosphaphenanthrene-derived diol as a multifunctional modifier for transesterification without using any toxic catalysts. In this strategy, the phosphaphenanthrene moieties enhanced the fire safety; while the hydroxy groups promoted the construction of catalyst-free dynamic transesterification networks. To our delight, the generated epoxy resin and its composite exhibit excellent mechanical properties, high thermal stability, fire safety, fast repairability and malleability. Furthermore, the resin matrix can be dissolved as the low-mass diol molecules participate in bond exchange reactions to achieve CFs with nearly 100% recyclability. [ABSTRACT FROM AUTHOR]

Objectives: Circulating microRNAs (miRNAs) have been discovered to play a novel role in intercellular communication and cancer biology. They are emerging candidates for noninvasive molecular biomarkers of cancer and other diseases. However, current translational researches have been limited by the lack of consensus on the optimal endogenous control of circulating miRNAs quantitation. In this study, we compared two promising miRNAs, miR-1228 and miR-16, as an endogenous control. The effects of normalizers on the relative quantification of circulating miR-31 in plasma samples of colorectal cancer (CRC) were also assessed. Materials and Methods: The cel-miR-39 was a spiked-in RNA used as an external control and added to plasma samples before RNA extraction. Quantitative real-time polymerase chain reaction technology was used to analyze the expression levels of circulating miRNAs in plasma samples of 4 healthy controls and 14 CRC patients. The expression stability of the candidate controls was compared by Ct analysis and NormFinder algorithms. Results: There was no significant difference in expression level of miR-16 and miR-1228 between healthy control group and before or after therapy of CRC patient groups. The expression of miR-1228 has smaller the range Ct values (28.25-25.64) compared with those of miR-16 (24.91-20.34). The stability value of miR-1228 (0.102) is lower than that of miR-16 (0.350). The expression of miR-1228 endogenous reference candidate has lower stability value and smaller the range Ct values compared with those in miR-16. According to the range Ct values and stability value, miR-1228 is better than miR-16 as endogenous control in CRC patients. There are significant differences in circulating miR-31 expression between healthy control and CRC patients when miR-1228 was used to standardize miR-31 expression. Conclusions: miR-1228 is recommended as a better endogenous control in quantification of circulating miRNAs in CRC patients. [ABSTRACT FROM AUTHOR]

Hickory (Carya cathayensis) kernel is rich in powerful bioactive flavonoids, which can remove excess free radicals in the human body and play an important role in regulating the physiological metabolism of the plant. This study investigated the changes of flavonoids in hickory exocarp and embryo during development. In this study, 72 DEGs involved in the regulation of flavonoid biosynthesis in fruits were identified, and TT4 , CCoAOMT1 , UGT71D1 , C4H , F3H , TT8 , FLS1 , and LDOX were identified as the core genes of flavonoid biosynthesis. A total of 144 flavonoid-related metabolites were detected by metabolite analysis. Transcriptome and metabolome analysis combined to construct the flavonoid biosynthesis regulatory pathway in the development stage of hickory fruit. Our results provide a theoretical basis for the exploration and regulation of functional genes related to flavonoid biosynthesis and metabolism in hickory and other plants and the breeding of new walnut varieties. [ABSTRACT FROM AUTHOR]

Arbitrary control of photon flow is of fundamental significance in many applications of light. Here, we propose a new approach that can trap, store, and move the signal photons to arbitrary desired place, just like what optical tweezers do on micro particles. In addition, the trapped photons can also be released at a given direction. The mechanism is based on an ultrahigh- Q nanocavity formed by two dynamically-generated potential barriers in a photonic crystal (PC) waveguide. Different from the traditional fixed ultrahigh- Q nanocavities, this new-type cavity can be formed instantaneously at any moment and any position in a PC waveguide, and is completely movable while keeps ultrahigh Q factor simultaneously. These novel features make controlling the flow of light like an optical tweezer possible, and open up new opportunities for dynamic lightâ€"matter interactions and on-chip optical signal processing. [ABSTRACT FROM AUTHOR]

Auxin and auxin‐mediated signaling pathways are known to regulate lateral root development. Although exocytic vesicle trafficking plays an important role in recycling the PIN‐FORMED (PIN) auxin efflux carriers and in polar auxin transport during lateral root formation, the mechanistic details of these processes are not well understood. Here, we demonstrate that BYPASS1‐LIKE (B1L) regulates lateral root initiation via exocytic vesicular trafficking‐mediated PIN recycling in Arabidopsis thaliana. b1l mutants contained significantly more lateral roots than the wild type, primarily due to increased lateral root primordium initiation. Furthermore, the auxin signal was stronger in stage I lateral root primordia of b1l than in those of the wild type. Treatment with exogenous auxin and an auxin transport inhibitor indicated that the lateral root phenotype of b1l could be attributed to higher auxin levels and that B1L regulates auxin efflux. Indeed, compared to the wild type, C‐terminally green fluorescent protein‐tagged PIN1 and PIN3 accumulated at higher levels in b1l lateral root primordia. B1L interacted with the exocyst, and b1l showed defective PIN exocytosis. These observations indicate that B1L interacts with the exocyst to regulate PIN‐mediated polar auxin transport and lateral root initiation in Arabidopsis. [ABSTRACT FROM AUTHOR]

Mutations of fibrillin‐1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as "type I fibrillinopathy". However, few genotype–phenotype correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received panel‐based next‐generation sequencing, complemented with multiplex ligation‐dependent probe amplification. In a total of 125 probands, the ocular phenotypes were compared for different types of FBN1 mutations. Premature termination codons were associated with less severe EL and a thinner central corneal thickness (CCT) than the inframe mutations. The eyes of patients with mutations in the C‐terminal region had a higher incidence of posterior staphyloma than those in the middle and N‐terminal regions. Mutations in the TGF‐β‐regulating sequence had larger horizontal corneal diameters (white‐to‐white [WTW]), higher incidence of posterior staphyloma, but less severe EL than those with mutations in other regions. Mutations in the neonatal region were associated with thinner CCT. Longer axial length (AL) was associated with mutations in the C‐terminal region or TGF‐β regulating sequence after adjusting for age, EL severity, and corneal curvature radius. FBN1 genotype–phenotype correlations were established for some ocular features, including EL severity, AL, WTW, CCT, and so forth, providing novel perspectives and directions for further mechanistic studies. [ABSTRACT FROM AUTHOR]