1,4-Bis(imidazol-1-yl)benzene–terephthalic acid (1/1)

In the title compound, C12H10N4·C8H6O4, 1,4-bis­(imidazol-1-yl)benzene and terephthalic acid mol­ecules are joined via strong O—H⋯N hydrogen bonds to form infinite zigzag chains. Both mol­ecules are located on crystallographic inversion centers. The O—H⋯N hydrogen-bonded chains are assembled into two-dimensional layers through weak C—H⋯O and strong π–π stacking inter­actions [centroid–centroid distance = 3.818 (2) Å], leading to the formation of a three-dimensional supra­molecular structure

Direct numerical simulation of Taylor-Couette flow with vertical asymmetric rough walls

Direct numerical simulations are performed to explore the effects of rotating direction of the vertical asymmetric rough wall on the transport properties of Taylor-Couette (TC) flow up to a Taylor number of $\textit{Ta} = 2.39 \times 10^7$. It is shown that compared to the smooth wall, the rough wall with vertical asymmetric strips can enhance the dimensionless torque \textit{Nu}$_\omega$, and more importantly, at high \textit{Ta} clockwise rotation of the inner rough wall (the fluid is sheared by the steeper slope side of the strips) results in a significantly bigger torque enhancement as compared to the counter-clockwise rotation (the fluid is sheared by the smaller slope side of the strips) due to the larger convective contribution to the angular velocity flux, although the rotating direction has a negligible effect on the torque at low \textit{Ta}. The larger torque enhancement caused by the clockwise rotation of vertical asymmetric rough wall at high \textit{Ta} is then explained by the stronger coupling between the rough wall and the bulk due to the larger biased azimuthal velocity towards the rough wall at the mid-gap of TC system, the increased intensity of turbulence manifesting by larger Reynolds stress and thinner boundary layer, and the more significant contribution of the pressure force on the surface of rough wall to the torque.Comment: 17 pages,11 figure

DeepBouton: Automated Identification of Single-Neuron Axonal Boutons at the Brain-Wide Scale

Fine morphological reconstruction of individual neurons across the entire brain is essential for mapping brain circuits. Inference of presynaptic axonal boutons, as a key part of single-neuron fine reconstruction, is critical for interpreting the patterns of neural circuit wiring schemes. However, automated bouton identification remains challenging for current neuron reconstruction tools, as they focus mainly on neurite skeleton drawing and have difficulties accurately quantifying bouton morphology. Here, we developed an automated method for recognizing single-neuron axonal boutons in whole-brain fluorescence microscopy datasets. The method is based on deep convolutional neural networks and density-peak clustering. High-dimensional feature representations of bouton morphology can be learned adaptively through convolutional networks and used for bouton recognition and subtype classification. We demonstrate that the approach is effective for detecting single-neuron boutons at the brain-wide scale for both long-range pyramidal projection neurons and local interneurons

Progress and perspectives of perioperative immunotherapy in non-small cell lung cancer

Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC

Design, Synthesis and Structural Analysis of Glucocerebrosidase Imaging Agents

Gaucher disease (GD) is a lysosomal storage disorder caused by inherited deficiencies in β-glucocerebrosidase (GBA). Current treatments require rapid disease diagnosis and a means of monitoring therapeutic efficacy, both of which may be supported by the use of GBA-targeting activity-based probes (ABPs). Here, we report the synthesis and structural analysis of a range of cyclophellitol epoxide and aziridine inhibitors and ABPs for GBA. We demonstrate their covalent mechanism-based mode of action and uncover binding of the new N- functionalised aziridines to the ligand binding cleft. These inhibitors became scaffolds for the development of ABPs; the O6-fluorescent tags of which bind in an allosteric site at the dimer interface. Considering GBA’s preference for O6- and N -functionalised reagents, we synthesised a bi-functional aziridine ABP which we hoped would offer a more powerful imaging agent. Whilst this ABP binds to two unique active site clefts of GBA, no further benefit in potency was achieved over our first generation ABPs. Nevertheless, such ABPs should serve useful in the study of GBA in relation to GD and inform the design of future probes