The subthalamic nucleus (STN) controls basal ganglia outputs via the substantia nigra pars reticulata (SNr) and the globus pallidus internus (GPi). However, the synaptic properties of these ...projections and their roles in motor control remain unclear. We show that the STN-SNr and STN-GPi projections differ markedly in magnitude and activity-dependent plasticity despite the existence of collateral STN neurons projecting to both the SNr and GPi. Stimulation of either STN projection reduces locomotion; in contrast, inhibition of either the STN-SNr projection or collateral STN neurons facilitates locomotion. In 6-OHDA-hemiparkinsonian mice, the STN-SNr projection is dramatically attenuated, but the STN-GPi projection is robustly enhanced; apomorphine inhibition of the STN-GPi projection through D2 receptors is significantly augmented and improves locomotion. Optogenetic inhibition of either the STN-SNr or STN-GPi projection improves parkinsonian bradykinesia. These results suggest that the STN-GPi and STN-SNr projections are differentially involved in motor control in physiological and parkinsonian conditions.
Display omitted
•Subthalamic neurons differentially control nigral and pallidal neurons and movement•Subthalamonigral and subthalamopallidal pathways are modified in parkinsonian mice•Inhibition of subthalamic projections restores parkinsonian locomotor deficit
Ji et al. report that subthalamic neurons project to two basal ganglia output nuclei with different strength and activity dependence. These projections differ in movement control in normal mice and are subjected to opposite modifications and different dopamine-receptor-agonist-modulation in parkinsonian mice. Inhibition of these projections restores parkinsonian bradykinesia.
Thiophene‐based rings are one of the most widely used building blocks for the synthesis of sulfur‐containing molecules. Inspired by the redox diversity of these features in nature, we demonstrate ...herein a redox‐divergent construction of dihydrothiophenes, thiophenes, and bromothiophenes from the respective readily available allylic alcohols, dimethyl sulfoxide (DMSO), and HBr. The redox‐divergent selectivity could be manipulated mainly by controlling the dosage of DMSO and HBr. Mechanistic studies suggest that DMSO simultaneously acts as an oxidant and a sulfur donor. The synthetic potentials of the products as platform molecules were also demonstrated by various derivatizations, including the preparation of bioactive and functional molecules.
We report herein a redox‐divergent construction of dihydrothiophenes, thiophenes, and bromothiophenes from readily available allylic alcohols, dimethyl sulfoxide (DMSO), and HBr, respectively. This strategy can serve for the programmable and concise synthesis of bioactive and functional molecules.
In nature, prenylation and geranylation are two important metabolic processes for the creation of hemiterpenoids and monoterpenoids under enzyme catalysis. Herein, we have demonstrated bioinspired ...unnatural prenylation and geranylation of oxindoles using the basic industrial feedstock isoprene through ligand regulation under Pd catalysis. Pentenylated oxindoles (with C5 added) were attained with high selectivity when using a bisphosphine ligand, whereas upon switching to a monophosphine ligand, selectivity toward geranylated oxindoles (with C10 added) was achieved. Moreover, the head‐to‐head product could be further isomerized to an internal skipped diene under Pd−H catalysis. No stoichiometric by‐product was formed in the process.
A practical strategy has been developed for the bioinspired and ligand‐regulated chemoselective unnatural prenylation and geranylation of oxindoles with isoprene under Pd catalysis. The selectivity was governed by modulating the coordination geometry of the Pd catalyst.
An efficient and synthetically convenient method for the synthesis of 3,3-difluoro-2-oxindole through a visible-light-induced photoredox difluoromethylation−amidation is described. The process can ...generate a broad range of difluorooxindoles using bromodifluoroacetate and broadly available free anilines. The wide range of substrate tolerance and mild reaction conditions make this transformation a highly valuable method in applications for drug discovery and development.
We introduce an interferometric single-molecule localization method for super-resolution fluorescence microscopy. Fluorescence molecules are located by the intensities of multiple excitation patterns ...of an interference fringe, providing around a twofold improvement in the localization precision compared with the conventional imaging with the same photon budget. We demonstrate this technique by resolving nanostructures down to 5 nm in size over a large 25 × 25 μm
field of view.
Defects usually play an important role in tailoring various properties of two-dimensional materials. Defects in two-dimensional monolayer molybdenum disulphide may be responsible for large variation ...of electric and optical properties. Here we present a comprehensive joint experiment-theory investigation of point defects in monolayer molybdenum disulphide prepared by mechanical exfoliation, physical and chemical vapour deposition. Defect species are systematically identified and their concentrations determined by aberration-corrected scanning transmission electron microscopy, and also studied by ab-initio calculation. Defect density up to 3.5 × 10(13) cm(-2) is found and the dominant category of defects changes from sulphur vacancy in mechanical exfoliation and chemical vapour deposition samples to molybdenum antisite in physical vapour deposition samples. Influence of defects on electronic structure and charge-carrier mobility are predicted by calculation and observed by electric transport measurement. In light of these results, the growth of ultra-high-quality monolayer molybdenum disulphide appears a primary task for the community pursuing high-performance electronic devices.
In the letter, a new frequency offset generation method based on polynomial fitting is proposed. The frequency offset can be obtained by sampling the fitted curve. By adjusting the coefficients of ...the polynomial, different forms of frequency offset can be generated. Different from existing window-based frequency diverse arrays (FDAs), which adopt traditional window functions to generate frequency offset and suffer from high sidelobe levels (SLLs) and low range resolution, the performance of Poly-FDA can be more flexibly regulated by fitting different forms of polynomial curves. Moreover, the particle swarm optimization (PSO) algorithm is exploited in the coefficient optimization process to obtain the optimal polynomial curve and enhanced beampattern property. Numerical examples demonstrate the superiority and effectiveness of the proposed Poly-FDA with lower SLL and narrower beamwidth other than the existing window-based FDAs and FDA of other frequency offset forms.
Frequency diverse array (FDA) has received much attention due to its capability of forming range-angle-dependent beampatterns. However, the standard FDA can only provide S-shaped beampatterns, ...leading to weakening the signal-to-interference-plus-noise ratio (SINR). Several window-based FDAs have been proposed to remove the coupling. However, the performance of these FDAs is limited by the use of conventional window functions, hindering further improvements. In this article, the "window-shaped" Sinc function (Sinc-FDA) is innovatively exploited into the frequency offset form to decouple the beampattern rather than using traditional window functions. Moreover, the sidelobe performance of existing window-based FDAs degrades in higher frequency offset bandwidth and wider observation area and is limited by the sidelobes near the main lobe. A weighted function is introduced to further flexibly suppress sidelobes, which forms a new weighted Sinc-FDA (W-Sinc-FDA). Simulation results compared with other optimization algorithm and function-based FDAs further demonstrate the effectiveness of the proposed Sinc-FDA and W-Sinc-FDA.
A regiospecific allyl-allyl coupling reaction between 1,3-dienes and allylboronates has been demonstrated under nickel catalysis. Salient features of this method include the earth-abundant metal ...catalyst, excellent regioselectivity and good functional group tolerance. Notably, even congested allyl substrates can also be applied to this protocol, thus allowing for the rapid preparation of a series of valuable 1,5-dienes.
A nickel-hydride catalysis has been developed to facilitate the allyl-allyl cross-coupling reactions between 1,3-dienes and allyl-B(pin) in excellent regioselectivity.
Accurate prognosis assessment is essential for surgically resected intrahepatic cholangiocarcinoma (ICC) while published prognostic tools are limited by modest performance. We therefore aimed to ...establish a novel model to predict survival in resected ICC based on readily-available clinical parameters using machine learning technique.
A gradient boosting machine (GBM) was trained and validated to predict the likelihood of cancer-specific survival (CSS) on data from a Chinese hospital-based database using nested cross-validation, and then tested on the Surveillance, Epidemiology, and End Results (SEER) database. The performance of GBM model was compared with that of proposed prognostic score and staging system.
A total of 1050 ICC patients (401 from China and 649 from SEER) treated with resection were included. Seven covariates were identified and entered into the GBM model: age, tumor size, tumor number, vascular invasion, number of regional lymph node metastasis, histological grade, and type of surgery. The GBM model predicted CSS with C-Statistics ≥ 0.72 and outperformed proposed prognostic score or system across study cohorts, even in sub-cohort with missing data. Calibration plots of predicted probabilities against observed survival rates indicated excellent concordance. Decision curve analysis demonstrated that the model had high clinical utility. The GBM model was able to stratify 5-year CSS ranging from over 54% in low-risk subset to 0% in high-risk subset.
We trained and validated a GBM model that allows a more accurate estimation of patient survival after resection compared with other prognostic indices. Such a model is readily integrated into a decision-support electronic health record system, and may improve therapeutic strategies for patients with resected ICC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
