C–H Bond Functionalization via [1,5]-Hydride Shift/Cyclization Sequence: Approach to Spiroindolenines

A concise synthesis of spiroindolenines from 2-substituted (Me, Et) indoles and 2-(pyrrolidin-1-yl)­benzaldehydes has been developed via a [1,5]-hydride shift/cyclization sequence. This method features a wide substrate scope and an operationally simple procedure, affording the spiroindolenines in good to excellent yields and moderate diastereoselectivity (3.5/1 dr). When the inseparable mixture of spiroindolenine isomers were washed with isopropyl ether after flash chromatography, the major isomers could be obtained in up to >20/1 dr

Stereoselective Synthesis of Arylglycine Derivatives via Palladium-Catalyzed α‑Arylation of a Chiral Nickel(II) Glycinate

A practical and efficient stereoselective synthesis of arylglycine derivatives was realized via palladium-catalyzed α-arylation of a chiral nickel­(II) glycinate complex with aryl bromides. The structurally diverse arylglycine products were obtained in excellent isolated yields and with good diastereoselectivity. A simple acidic hydrolysis furnished optically pure arylglycines in high yield, and the chiral ligand (S)-BPB could be efficiently recovered and reused

Nanosheet-Assembled ZnFe₂O₄ Hollow Microspheres for High-Sensitive Acetone Sensor

Semiconductor oxides with hierarchically hollow architecture can provide significant advantages as sensing materials for gas sensors by facilitating the diffusion of target gases. Herein, we develop a facile template-free solvothermal strategy combined with the subsequent thermal treatment process toward the successful synthesis of novel ZnFe₂O₄ hollow flower-like microspheres. The images of electron microscopy unambiguously indicated that the ZnFe₂O₄ nanosheets with thickness of around 20 nm assembled hierarchically to form the unique flower-like architecture. As a proof-of-concept demonstration of the function, the as-prepared product was utilized as sensing material for gas sensor. Significantly, in virtue of the porous shell structure, hollow interior, and large surface area, ZnFe₂O₄ hierarchical microspheres exhibited high response, excellent cyclability, and long-term stability to acetone at the operating temperature of 215 °C

Synthesis and Molecular Structures of BINOL Complexes: An STM Investigation of 2D Self-Assembly

Three new (R)-BINOL complexes have been prepared. 2D self-assembly has been observed in the system consisting of crystalline (R)-BINOL derivatives (guest) and 1,3,5-tris­(10-carboxydecyloxy)-benzene (host) by means of the scanning tunneling microscopy (STM) technique. Density functional theory (DFT) calculations help to reveal the assembly on the HOPG surface

Construction of Oxadiazepines via Lewis Acid-Catalyzed Tandem 1,5-Hydride Shift/Cyclization

Expeditious access to oxadiazepines via 1,5-hydride shift/cyclization of pyrrolidine- or tetrahydroisoquinoline-containing nitrones has been developed. With 1,3-dipole nitrones serving as the hydride acceptors, this transformation was promoted by a Lewis acid, providing access to structurally diverse oxadiazepines in good yields. A one-pot process for in situ nitrone formation, a 1,5-hydride shift, and ring cyclization was also realized

A Collaborative Assembly Strategy for Tumor-Targeted siRNA Delivery

A novel “collaborative assembly” approach was reported for the synthesis of an siRNA delivery system via a combination of an electrostatically driven physical assembly and a facile click reaction-mediated chemical assembly, which showed various advantages of more safety, efficiency, and flexibility over the conventional approach that is only based on the physical assembly. This strategy remained a high cationic property of lipid-based complex for high siRNA loading capacity. The direct chemical modification of a model polyanion, hyaluronic acid (HA) on the cationic complex via click chemistry shielded the positive charge of complex without affecting the siRNA binding, which reduced the toxicity and enhanced the blood stability of the complex. In addition, the incorporated polyanion might be prefunctionalized, which endued the carrier with better biological characteristics such as long circulating or tumor targeting. We demonstrated that the obtained lipid-polymer hybrid nanoparticle (RSC-HA) using collaborative assembly presented greater <i>in vivo</i> stability in the blood for efficient tumor targeting than the physically assembled RSC/HA in which HA was physically adsorbed on the complex. After endocytosis into the cells, the protection of RSC-HA on siRNA turned off, while the release of siRNA induced by the intracellular signals for enhanced gene-silencing capacity. This combination of physical and chemical assemblies provides an efficient strategy for the exploitation of safe, stable, and functionalized siRNA delivery systems

Mean z-score matrices for the control and PNE groups.

<p>Each figure shows a 116×116 square matrix in which the x- and y-axes correspond to AAL regions. Each entry indicates the mean z-score representing functional connectivity between each pair of regions in the brain.</p

Design and Synthesis of Curcumin Analogues for in Vivo Fluorescence Imaging and Inhibiting Copper-Induced Cross-Linking of Amyloid Beta Species in Alzheimer’s Disease

In this article, we first designed and synthesized curcumin-based near-infrared (NIR) fluorescence imaging probes for detecting both soluble and insoluble amyloid beta (Aβ) species and then an inhibitor that could attenuate cross-linking of Aβ induced by copper. According to our previous results and the possible structural stereohindrance compatibility of the Aβ peptide and the hydrophobic/hydrophilic property of the Aβ13–20 (HHQKLVFF) fragment, NIR imaging probe CRANAD-58 was designed and synthesized. As expected CRANAD-58 showed significant fluorescence property changes upon mixing with both soluble and insoluble Aβ species in vitro. In vivo NIR imaging revealed that CRANAD-58 was capable of differentiating transgenic and wild-type mice as young as 4 months old, the age that lacks apparently visible Aβ plaques and Aβ is likely in its soluble forms. According to our limited studies on the interaction mechanism between CRANAD-58 and Aβ, we also designed CRANAD-17 to attenuate the cross-linking of Aβ42 induced by copper. It is well-known that the coordination of copper with imidazoles on Histidine-13 and 14 (H13, H14) of Aβ peptides could initialize covalent cross-linking of Aβ. In CRANAD-17, a curcumin scaffold was used as an anchoring moiety to usher the designed compound to the vicinity of H13 and H14 of Aβ, and imidazole rings were incorporated to compete with H13/H14 for copper binding. The results of SDS-PAGE gel and Western blot indicated that CRANAD-17 was capable of inhibiting Aβ42 cross-linking induced by copper. This raises a potential for CRANAD-17 to be considered for AD therapy

DataSheet_1_Deep learning based on 68Ga-PSMA-11 PET/CT for predicting pathological upgrading in patients with prostate cancer.docx

ObjectivesTo explore the feasibility and importance of deep learning (DL) based on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT in predicting pathological upgrading from biopsy to radical prostatectomy (RP) in patients with prostate cancer (PCa).MethodsIn this retrospective study, all patients underwent 68Ga-PSMA-11 PET/CT, transrectal ultrasound (TRUS)-guided systematic biopsy, and RP for PCa sequentially between January 2017 and December 2022. Two DL models (three-dimensional [3D] ResNet-18 and 3D DenseNet-121) based on 68Ga-PSMA-11 PET and support vector machine (SVM) models integrating clinical data with DL signature were constructed. The model performance was evaluated using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity.ResultsOf 109 patients, 87 (44 upgrading, 43 non-upgrading) were included in the training set and 22 (11 upgrading, 11 non-upgrading) in the test set. The combined SVM model, incorporating clinical features and signature of 3D ResNet-18 model, demonstrated satisfactory prediction in the test set with an AUC value of 0.628 (95% confidence interval [CI]: 0.365, 0.891) and accuracy of 0.727 (95% CI: 0.498, 0.893).ConclusionA DL method based on 68Ga-PSMA-11 PET may have a role in predicting pathological upgrading from biopsy to RP in patients with PCa.</p