No abnormalities were found in DMN. In the motor networks, we identified reduced midbrain-pallidum FC in BGN and reduced motor and somatosensory cortex FC in SMN.
 
  We found abnormal ECN and normal DMN as a possible hallmark of cognitive dysfunctions in early α-synucleinopathies. We replicated abnormalities in BGN and SMN corresponding to subclinical movement disorder of RBD. RsfcMRI may provide an early biomarker of both cognitive and motor network dysfunctions of α-synucleinopathies.
 We found abnormal ECN and normal DMN as a possible hallmark of cognitive dysfunctions in early α-synucleinopathies. We replicated abnormalities in BGN and SMN corresponding to subclinical movement disorder of RBD. RsfcMRI may provide an early biomarker of both cognitive and motor network dysfunctions of α-synucleinopathies.
  To explore and quantify systematically the ocular abnormal movements present in progressive supranuclear palsy (PSP) from the early stages, to assess the ability of this standardized examination in the differential diagnosis of PSP from Parkinson's disease (PD), and to compare in more detail oculomotor disturbances between PSP variants.
 
  Sixty-five consecutive PSP patients with <5 years of disease duration diagnosed according to MDS-PSP criteria, 25 PD patients and 25 controls comparable in age, education and disease duration were explored using a bedside battery of tests for the quantitative evaluation of oculomotor dysfunction in clinical practice. Other accepted scales were used for measurement of motor (PSPRS), cognitive (FAB) and behavioral (FBI) impairment.
 
  Measurement of oculomotor dysfunction significantly differentiated PSP from PD and controls (p<0.001) and showed high accuracy in the differential diagnosis of early-to-mid stage PSP from PD. PSP-Parkinsonism and PSP-Progressive Gait Freezing phenotypes showed more preserved ocular motor function compared to PSP-Richardson Syndrome, although no differences were found between PSP subtypes in the number of square wave jerks, optokinetic nystagmus defects, degree of apraxia of eyelid opening, or presence of the "Round the Houses" sign.
 
  Using a bedside clinical instrument for quantifying oculomotor disturbances in PSP shows promising potential at differentiating PSP from PD, and it seems able to provide a qualitative and quantitative description of ocular motor function in parkinsonian disorders.
 Using a bedside clinical instrument for quantifying oculomotor disturbances in PSP shows promising potential at differentiating PSP from PD, and it seems able to provide a qualitative and quantitative description of ocular motor function in parkinsonian disorders.Hurdled and marred by the notorious nature of glioblastomas (GBM) in terms of resistance to therapy and limited drug delivery into the brain, the anti-GBM drug pipeline is required to be loaded with mechanistically diverse agents. The consideration of HDAC inhibition as a prudent approach to circumvent the resistance issue in GBM spurred us to pragmatically design and synthesizes hydroxamic acids endowed with CNS penetrating ability. By virtue of the blood brain barrier permeability (BBB), memantine was envisioned as an appropriate CAP component for the construction of the HDAC inhibitors. Diverse linkers were stapled for the tetheration of the zinc binding motif with the CAP group to pinpoint an appropriate combination (CAP and linker) that could confer inhibitory preference to HDAC6 isoform (overexpressed in GBM). Resultantly, hydroxamic acid 16 was identified as a promising compound that elicited striking antiproliferative effects against Human U87MG GBM cells as well as TMZ-resistant GBM cells and P1S cells, a concurrent chemo radiotherapy (CCRT)-resistant/patient-derived glioma cell line mediated through preferential HDAC6 inhibition (IC50 = 5.42 nM). Furthermore, 16 exerted cell cycle arrest at G2 phase, induced apoptosis in GBM cells at high concentration and exhibited high BBB permeability. To add on, in-vivo study revealed that the administration of compound 16 prolonged the survival of TMZ-resistant U87MG inoculated orthotopic mice. Overall, the cumulative results indicate that 16 is a tractable CNS penetrant preferential HDAC6 inhibitor that might emerge as a potent weapon against GBM.Diabetes mellitus is one of the most challenging threats to global public health. To improve the therapy efficacy of antidiabetic drugs, numerous drug delivery systems have been developed. Polyethylene glycol (PEG) is a polymeric family sharing the same skeleton but with different molecular weights which is considered as a promising material for drug delivery. In the delivery of antidiabetic drugs, PEG captures much attention in the designing and preparation of sustainable and controllable release systems due to its unique features including hydrophilicity, biocompatibility and biodegradability. Due to the unique architecture, PEG molecules are also able to shelter delivery systems to decrease their immunogenicity and avoid undesirable enzymolysis. PEG has been applied in plenty of delivery systems such as micelles, vesicles, nanoparticles and hydrogels. In this review, we summarized several commonly used PEG-contained antidiabetic drug delivery systems and emphasized the advantages of stimuli-responsive function in these sustainable and controllable formations.Presently, artemisinin-based combination therapy (ACT) is the first-line therapy of Plasmodium falciparum malaria. With the emergence of malaria parasites that are resistant to ACT, alternative antimalarial therapies are urgently needed.  https://www.selleckchem.com/products/dj4.html  In line with this, we designed and synthesised a series of novel N-(7-chloroquinolin-4-yl)-N'-(4,6-diphenylpyrimidin-2-yl)alkanediamine hybrids (6a-7c) and evaluated their inhibitory activity against the NF54 chloroquine-susceptible strain as a promising class of antimalarial compounds. The antiplasmodial screening revealed that seven analogues showed promising to good activity with half-maximal inhibitory concentration (IC50) = 0.32 μM-4.30 μM. Compound 7a with 1,4-diamine butyl linker and 4-hydroxyl phenyl on fourth and sixth position of pyrimidine core showed the most prominent activity with an IC50 value of 0.32 ± 0.06 μM, with a favourable safety profile of 9.79 to human kidney epithelial (HEK293) cells. The remaining six analogues showed moderate activity with IC50 values ranging from 7.