Vascular cognitive impairment caused by chronic cerebral hypoperfusion (CCH) seriously affects the quality of life of elderly patients. However, there is no effective treatment to control this disease. This study investigated the potential neuroprotective effect of the 40 Hz light flicker in a mouse model of CCH. CCH was induced in male C57 mice by right unilateral common carotid artery occlusion (rUCCAO), leading to chronic brain injury. The mice underwent 40 Hz light flicker stimulation for 30 days after surgery. The results showed that 40 Hz light flicker treatment ameliorated memory deficits after rUCCAO and alleviated the damage to neurons in the frontal lobe and hippocampus. Light flicker administration at 40 Hz decreased IL-1ß and TNF-α levels in the frontal lobe and hippocampus, but immunohistochemistry showed that it did not induce angiogenesis in mice with rUCCAO. Gene expression profiling revealed that the induction of genes was mainly enriched in inflammatory-related pathways. Our findings demonstrate that 40 Hz light flicker can suppress cognitive impairment caused by rUCCAO and that this effect may be involved in the attenuation of neuroinflammation.
Brain Ischemia , Carotid Artery Diseases , Cognitive Dysfunction , Humans , Mice , Male , Animals , Aged , Transcriptome , Quality of Life , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Brain Ischemia/metabolism , Hippocampus/metabolism , Carotid Artery Diseases/metabolism , Disease Models, Animal , Carotid Artery, Common/surgery , Maze Learning
Recent studies have shown that neuropeptides and neurotrophic factors may be involved in the pathophysiological mechanisms of suicide. However, the current research on this aspect is still insufficient. Our study aimed to explore the biological patterns of suicide deaths, including levels of BDNF, proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2. The researchers selected 25 normal control patients matched by age with 30 suicide deaths. We used enzyme-linked immunosorbent assays to detect the levels of BDNF, proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2 in the plasma of suicide and control subjects. proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2 levels are shown as the median (25th-75th percentile). BDNF levels are shown as the mean (standard error of the mean). (1) The levels of plasma TPH2 and proBDNF in people who died by suicide were significantly higher than those in the control group. (2) The plasma levels of GDNF and BDNF/proBDNF in the suicide group were obviously lower than those in the control group. (3) There was no significant difference in plasma BDNF or Trk-b concentrations between the suicide group and the control group.Plasma TPH2, GDNF, and proBDNF levels are related to suicide. Plasma neurotrophic factor markers may predict suicide risk.
Metal molecular rings are a class of compounds with aesthetically pleasing symmetry and fundamentally useful properties. The reported work generally focuses on the ring center cavity, and there is little known about those on the ring waist. Herein, we report the discovery of porous aluminum molecular rings and their performance and contribution to the cyanosilylation reaction. We develop a facile ligand induced aggregation and solvent regulation strategy towards AlOC-58NC and AlOC-59NT with high purity, high yield (75% and 70%, respectively) and gram-level scale-up. These molecular rings exhibit a "two-tier" pore feature involving the general central cavity and newly observed equatorial semi-open cavities. AlOC-59NT with two types of one-dimensional channels showed good catalytic activity. The interaction of the aluminum molecular ring catalyst with the substrate has been crystallographically characterized and theoretically confirmed, showing a ring adaptability process that involves the capture and binding of the substrate. This work provides new ideas for the assembly of porous metal molecular rings and to understand the overall reaction pathway involving aldehydes and is expected to inspire the design of low-cost catalysts through structural modifications.
Isodesmic reactions represent mild alternatives to other chemical transformations that require harsh oxidizing agents or highly reactive intermediates. However, enantioselective isodesmic C-H functionalization is unknown and enantioselective direct iodination of inert C-H bond is very rare. Rapid synthesis of chiral aromatic iodides is of significant importance for synthetic chemistry. Herein, we report an unprecedented highly enantioselective isodesmic C-H functionalization to access chiral iodinated phenylacetic Weinreb amides via desymmetrization and kinetic resolution with PdII catalysis. Importantly, further transformations of the enantioenriched products are readily available at the iodinated or the Weinreb amide position, paving the way of related studies for synthetic and medicinal chemists.
A chiral metal-organic cage (MOC) was extended and fixed into a porous framework using a post-assembly modification strategy, which made it easier to study the host-guest chemistry of the solid-state MOC using a single-crystal diffraction technique. Anionic Ti4 L6 (L=embonate) cage can be used as a 4-connecting crystal engineering tecton, and its optical resolution was achieved, thus homochiral ΔΔΔΔ- and ΛΛΛΛ-[Ti4 L6 ] cages were obtained. Accordingly, a pair of homochiral cage-based microporous frameworks (PTC-236(Δ) and PTC-236(Λ)) were easily prepared by a post-assembly reaction. PTC-236 has rich recognition sites provided by the Ti4 L6 moieties, chiral channels and high framework stability, affording a single-crystal-to-single-crystal transformation for guest structure analyses. Thus it was successfully utilized for the recognition and separation of isomeric molecules. This study provides a new approach for the orderly combination of well-defined MOCs into functional porous frameworks.
Aims: This intervention study evaluates the effect of a virtual reality cognition training system (VRCTS) on improving cognitive function and clinical symptoms in Han Chinese patients with schizophrenia in the remission stage. Methods: Sixty-eight patients with schizophrenia in the remission stage were recruited for this study and were randomly allocated to either the virtual reality training (VRT) group or the treatment-as-usual (TAU) group. For the VRT group, patients received training with the VRCTS for two weeks and antipsychotic treatment as usual, while the TAU group only received antipsychotic treatment as usual. Cognitive function and clinical symptoms before and after the two-week treatment were assessed by the MATRICS consensus cognitive battery (MCCB), positive and negative syndrome scale (PANSS), and personal and social performance scale (PSP). Results: The results showed that (1) VRCTS could improve MCCB composite scores and scores on 2 out of 7 cognitive domains: visual learning as well as reasoning and problem solving. It was also observed that (2) VRCTS could alleviate general psychopathology symptoms of PANSS, but did not exert effects on positive and negative symptoms among patients with schizophrenia in the remission stage. Conclusions: A therapeutic effect of VRCTS was observed in patients with schizophrenia in the remission stage. This may improve cognitive function and general psychopathological symptoms. Trial registration: China Clinical Trial Registry, ChiVTR1800016121.
Functional group metathesis has the potential to render mild reaction conditions for C-H functionalization. Protocols for the meta- and ortho-C-H iodination of aniline derivatives via formal C(sp2)-H/C(sp2)-I metathesis using 2-nitrophenyl iodides as mild iodinating reagents are reported herein. These protocols led to the production of a range of valuable iodinated aniline derivatives. These results demonstrate the potential of developing novel site-selective C-H activation reactions with electron-rich compounds, since mild reagents can often been utilized in functional group metathesis reactions.
C-H functionalization via functional group metathesis is extremely rare. A protocol of remote site-selective C-H iodination of 2-aryl benzoic acid derivatives via formal C(sp2)-H/C(sp2)-I metathesis using readily available 1-iodo-4-methoxy-2-nitrobenzene as the mild iodinating reagent was reported herein. A range of 2-aryl benzoic acid derivatives including 2-(naphthalen-1-yl)benzoic acids and [1,1'-binaphthalene]-2-carboxylic acids were iodinated under mild conditions to give valuable iodinated products in a site- and chemo-selective fashion.
Benzoic Acid , Halogenation , Benzoates , Catalysis , Iodides
As hypocretin can markedly affect neurophysiological and behavioural processes in mood disorders. However, few studies have measured changes in hypocretin levels in patients with mood disorders. We estimated the hypocretin-1 plasma levels in mood disorder patients and controls (CON) using an enzyme-linked immunosorbent assay. Results: (i) The hypocretin-1 plasma level was significantly higher in major depressive disorder (MDD) patients [59.04 (35.78-80.12) pg/ml, P < 0.001] and bipolar disorder (BD) patients [65.50 (58.46-74.57) pg/ml, P < 0.001] patients than in CON [49.25 (28.51-80.40) pg/ml]. Moreover, the plasma hypocretin-1 levels in the BD group were significantly higher than those in the MDD group (P < 0.001). (ii). In the MDD group, patients with higher suicidal ideation had higher hypocretin-1 levels [62.09 (38.23-80.12) pg/ml] than those with lower suicidal ideation [59.63 (35.79-77.37) pg/ml), P = 0.032]. (iii). Plasma hypocretin-1 levels were increased in both female and male mood disorder patients compared to CON [male: MDD 60.51 (35.79-80.12) pg/ml; BD 65.40 (58.76-74.14) pg/ml; CON 45.63 (28.51-62.05) pg/ml; all P < 0.016; female: MDD 57.37 (34.59-80.40) pg/ml; BD 65.61 (58.46-74.57) pg/ml; CON 52.92 (38.23-78.89) pg/ml; all P < 0.015]. (iv). In CON, we found a significant negative correlation between plasma hypocretin-1 levels and age (rho = -0.251, P = 0.032), while this negative correlation was absent in the MDD and BD groups. Limitations may partly arise from the relatively small sample size and the medication history of patients participating in our research. We concluded that the clear changes found in plasma hypocretin-1 levels might be applied in the diagnosis of depression and the differential diagnosis of MDD and BD. The clear suicidal-ideation-related change found in hypocretin-1 levels in depression might be taken into account in the prevention of suicidal behaviour and further study of hypocretin-targeted therapies.
Direct para-selective C-H functionalization of arenes remains a daunting challenge and is still significantly restricted to a few scaffolds. Herein, we report an unprecedented pyridine-based para-directing template (DT) assisted, Pd-catalyzed para-C-H alkenylation of three classes of arenes, i.e. phenylpropanoic acids, 2-phenyl benzoic acids and benzyl alcohols, with a series of alkenes including perfluoroalkenes. Notably, the pyridine-based para-DT could be easily synthesized and readily recycled under mild conditions. These results may find application in rapid construction of para-substituted arenes and stimulate the exploration of novel methods for para-C-H functionalization of arenes.
BACKGROUND: Schizophrenia is associated with widespread cognitive impairment. The MATRICS Consensus Cognitive Battery (MCCB) is most frequently used to assess cognitive function. However, the MCCB test is time consuming for the clinician. Virtual reality (VR) has emerged as an adjunctive tool to overcome this limitation and provides a new means to assess cognitive function. METHODS: The present study examined the validity and safety of using VR technology to assess cognitive function in Han Chinese patients with schizophrenia (SZs). The VR cognition training system (VRCTS) was used to simulate real-life supermarkets and assess cognitive function. Thirty-two SZs and 25 healthy controls (HCs) underwent VRCTS and MCCB assessments. An auxiliary diagnosis model was created based on the outcomes of the VRCTS to classify SZs and HCs by cognitive impairment. RESULTS: Significant differences in completion time between the SZs and HCs were detected using the VRCTS. SZs spent more time completing tasks than HCs. The outcome of VRCTS significantly correlated with the MCCB. The auxiliary diagnosis model had a sensitivity of 88.89% and a specificity of 88.89%. CONCLUSIONS: These results support the use of VR technology in the assessment of cognitive impairment in Han Chinese schizophrenia patients. TRIAL REGISTRATION: China Clinical Trial Registry, ChiVTR1800016121. Registered 13 May 2018, http://www.chictr.org.cn/showproj.aspx?proj=27233.
Schizophrenia , Virtual Reality , China , Cognition , Cross-Sectional Studies , Humans , Neuropsychological Tests , Schizophrenia/complications , Schizophrenia/diagnosis , Schizophrenic Psychology
OBJECTIVE: Currently, an efficient method for improving cognitive impairment due to sleep deprivation (SD) is lacking. The aim of this study is to evaluate the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) during SD on reversing the adverse effects of SD. METHODS: A total of 66 healthy people were randomized into the rTMS group and sham group. Both groups were deprived of sleep for 24 h. During SD, participants were asked to complete several cognitive tasks and underwent mood assessments. Saliva cortisol levels, plasma concentrations of brain-derived neurotrophic factor (BDNF), precursor BDNF (proBDNF), and tissue-type plasminogen activator (tPA), and frontal blood activation were detected before and after SD. The rTMS group received real rTMS stimulation for 2 sessions of 10 Hz rTMS (40 trains of 50 pulses with a 20-second intertrain interval) to the left dorsolateral prefrontal cortex and the sham group received sham stimulation during SD. RESULTS: Twenty-four hours of SD induced a reduced accuracy in the n-back task, increases in both anxiety and depression, increased cortisol levels, decreased frontal blood activation and decreased BDNF levels in healthy people. Notably, rTMS improved the hyperactivity of the hypothalamic-pituitary-adrenal axis and decreased frontal blood activation induced by SD, and reduced the consumption of plasma proBDNF. CONCLUSIONS: Twenty-four hours of SD induced a cognitive impairment. The administration of high-frequency rTMS during sleep deprivation exerted positive effects on HPA axis and frontal activation and might help alleviate cognitive impairment in the long term.
Cognitive Dysfunction , Hypothalamo-Hypophyseal System , Cognitive Dysfunction/etiology , Cognitive Dysfunction/therapy , Humans , Pituitary-Adrenal System , Prefrontal Cortex , Sleep Deprivation , Transcranial Magnetic Stimulation
Objective: Patients with hypochondriasis hold unexplainable beliefs and a fear of having a lethal disease, with poor compliances and treatment response to psychotropic drugs. Although several studies have demonstrated that patients with hypochondriasis demonstrate abnormalities in brain structure and function, gray matter volume (GMV) and functional connectivity (FC) in hypochondriasis still remain unclear. Methods: The present study collected T1-weighted and resting-state functional magnetic resonance images from 21 hypochondriasis patients and 22 well-matched healthy controls (HCs). We first analyzed the difference in the GMV between the two groups. We then used the regions showing a difference in GMV between two groups as seeds to perform functional connectivity (FC) analysis. Finally, a support vector machine (SVM) was applied to the imaging data to distinguish hypochondriasis patients from HCs. Results: Compared with the HCs, the hypochondriasis group showed decreased GMV in the left precuneus, and increased GMV in the left medial frontal gyrus. FC analyses revealed decreased FC between the left medial frontal gyrus and cuneus, and between the left precuneus and cuneus. A combination of both GMV and FC in the left precuneus, medial frontal gyrus, and cuneus was able to discriminate the hypochondriasis patients from HCs with a sensitivity of 0.98, specificity of 0.93, and accuracy of 0.95. Conclusion: Our study suggests that smaller left precuneus volumes and decreased FC between the left precuneus and cuneus seem to play an important role of hypochondriasis. Future studies are needed to confirm whether this finding is generalizable to patients with hypochondriasis.
A protocol of carboxyl-group-assisted, Pd(II)-catalyzed remote meta-C(sp2)-H olefination and arylation of benzylsulfonamides has been developed. It was supposed to proceed through a κ2 coordination of the carboxyl group to the Pd center. These findings demonstrated the versatility of carboxyl-assisted remote meta-C-H activation strategy and might stimulate the exploration of novel reactivity and selectivity of other traditional chelating groups in different contexts.
Release of cargo molecules from cell-like nanocarriers can be achieved by chemical perturbations, including changes to pH and redox state and via optical modulation of membrane properties. However, little is known about the kinetics or products of vesicle breakdown due to limitations in real-time imaging at nanometer length scales. Using a library of 12 single-single type photocleavable amphiphilic Janus dendrimers, we developed a self-assembling light-responsive dendrimersome vesicle platform. A photocleavable ortho-nitrobenzyl inserted between the hydrophobic and hydrophilic dendrons of amphiphilic Janus dendrimers allowed for photocleavage and disassembly of their supramolecular assemblies. Distinct methods used to self-assemble amphiphilic Janus dendrimers produced either nanometer size small unilamellar vesicles or micron size giant multilamellar and onion-like dendrimersomes. In situ observation of giant photosensitive dendrimersomes via confocal microscopy elucidated rapid morphological transitions that accompany vesicle breakdown upon 405 nm laser illumination. Giant dendrimersomes displayed light-induced cleavage, disassembling and reassembling into much smaller vesicles at millisecond time scales. Additionally, photocleavable vesicles demonstrated rapid release of molecular and macromolecular cargos. These results guided our design of multilamellar particles to photorelease surface-attached proteins, photoinduce cargo recruitment, and photoconvert vesicle morphology. Real-time characterization of the breakdown and reassembly of lamellar structures provides insights on partial cargo retention and informs the design of versatile, optically regulated carriers for applications in nanoscience and synthetic biology.
Our recent study reported that adolescent-onset schizophrenia showed an uncoupling between intraventricular brain temperature (iBT) and local spontaneous brain activity (SBA). While auditory verbal hallucinations (AVH) are common in schizophrenia, the role of AVH in the iBT-SBA relationship is unclear. The current study recruited 24 drug-naïve schizophrenia patients with AVH, 20 patients without AVH and 30 matched healthy controls (HC). We used a diffusion-weighted imaging (DWI) based thermometry method to calculate the iBT for each participant and used both regional homogeneity and amplitude of low-frequency fluctuation methods to assess the SBA. One-way ANOVA was used to detect group differences in iBT, and a partial correlation analysis controlling for lateral ventricles volume, sex and age was applied to detect the relationships between iBT and SBA across the three groups. The results demonstrated that the AVH group showed a significant coupling between iBT and SBA in the bilateral lingual gyrus, left superior occipital gyrus and caudate compared with the other two groups, and no uncoupling was found in the two patients groups relative to HCs. These findings suggest that AVH may modulate the relationship between iBT and SBA in schizophrenia-related regions.
Brain/physiopathology , Hallucinations/physiopathology , Schizophrenia/physiopathology , Temperature , Adolescent , Adult , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Magnetic Resonance Imaging/methods , Male , Pharmaceutical Preparations/metabolism , Young Adult
During the last decade, the problem of suicide has become more serious in individuals with depression. Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD). This study aims to investigate the efficacy of magnetic resonance imaging (MRI)-based neuronavigation-guided daily high-dose rTMS for rapidly improving suicidal ideation in treatment-naive patients with MDD. In the present 1-week double-blind study, 42 treatment-naive patients with MDD with suicidal ideation were randomly assigned to the treatment of escitalopram oxalate tablets (10 mg/d) in combination with either active (n = 21) or sham (n = 21) rTMS. The TMS coil was positioned over a specified target location (-44, 40, and 29) in left dorsolateral prefrontal cortex based on MRI data. The severity of suicidal ideation was measured by the Beck Scale for Suicide Ideation (BSI). The 24-item Hamilton Depression Rating Scale (HAMD-24) and Montgomery-Åsberg Depression Rating Scale (MADRS) were utilized to assess the severity of depression. The Wisconsin Card Sorting Test, Continuous Performance Test, and Stroop Color-Word Test were adopted to assess executive function. In contrast to the sham group, the active rTMS group showed a significantly greater BSI score reduction at the third day and the seventh day (P < 0.001). Moreover, the active rTMS group showed a significantly greater HAMD (P < 0.001) and MADRS (P < 0.001) score reduction at the seventh day in comparison to the sham group. The present findings suggested that the neuronavigation-guided high-dose rTMS may be a novel method to rapidly reduce suicidal ideation and mitigate depressive symptoms.
Depressive Disorder, Major/therapy , Magnetic Resonance Imaging , Neuronavigation , Prefrontal Cortex/physiopathology , Suicidal Ideation , Transcranial Direct Current Stimulation , Adolescent , Adult , Antidepressive Agents, Second-Generation/therapeutic use , China , Citalopram/therapeutic use , Combined Modality Therapy , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Double-Blind Method , Feasibility Studies , Female , Humans , Male , Neuronavigation/adverse effects , Neuropsychological Tests , Predictive Value of Tests , Prefrontal Cortex/diagnostic imaging , Transcranial Direct Current Stimulation/adverse effects , Treatment Outcome , Young Adult
The relationship between the cognitive impairment and the structural and functional abnormalities in the brains of patients with schizophrenia (SZ) is not yet clear. This study aims to investigate the relationship, thereby exploring the neuromechanism underlying SZ. We collected multimodal MRI data from 68 first-episode, drug-naïve patients with SZ, and 64 well-matched healthy controls, and used regional homogeneity (ReHo) and gray matter volume (GMV) to assess the functional and structural integrity of the brains, respectively. We then evaluated in the entire brain the correlations between ReHo/GMV and the participants' neuropsychological assessment scores for each group using a partial correlation analysis controlling for age and sex. We found significant uncoupling between attention performance and mean ReHo in the left middle frontal gyrus, right superior/inferior parietal lobe (IPL), right angular gyrus (AG) and right middle/inferior temporal lobe (ITG) in SZ compared with healthy controls. Moreover, we found that the SZ group showed decreased GMV in the right IPL and AG, and a significant coupling between ReHo and GMV in the right ITG. Our findings suggest that the attention dysfunction found in SZ may be associated with the structural and functional abnormalities as well as the structure-function interrelation in several SZ-related brain regions.
Attention/physiology , Brain/physiopathology , Schizophrenia/physiopathology , Adult , Brain Mapping , Cognitive Dysfunction/physiopathology , Female , Frontal Lobe/physiopathology , Gray Matter/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Parietal Lobe/physiopathology , Temporal Lobe/physiopathology , Young Adult
The first example of carboxy group assisted, remote-selective C(sp2 )-H activation with a PdII catalyst has been developed and proceeds through a possible κ2 coordination of the carboxy group, thus suppressing the ortho-C-H activation through κ1 coordination. Besides meta-C-H olefination, direct meta-arylation of hydrocinnamic acid derivatives with low-cost aryl iodides has been achieved for the first time. These findings may motivate the exploration of novel reactivities of the carboxy assisted C-H activation reactions with intriguing selectivities.
PURPOSE: There is growing evidence showing that inflammatory cytokines and neuropeptides may be involved in the pathophysiology of suicidal behavior. However, studies have yielded contradictory data, and no biological markers that help predict suicide have been identified. This study aimed to identify biological patterns, such as NPY, IL-1ß and hypocretin plasma levels, in people who died by suicide. PATIENTS AND METHODS: Twenty-two people who died by suicide compared with 22 controls matched for age and sex were studied. In suicide and control subjects, we estimated the levels of NPY, IL-1ß and hypocretin in plasma using enzyme-linked immunosorbent assay. The data are presented as the median (25th-75th percentile). RESULTS: We found (1) a significant elevation in plasma NPY levels in suicide subjects versus control subjects (suicide: 11.38 (9.380-16.55); controls: 8.95 (7.590-10.93); P=0.013), and plasma NPY concentrations were approximately 62% higher in suicide subjects than those in control subjects; (2) a significant decrease in plasma IL-1ß concentrations between suicide and control subjects (suicide: 121.1 (82.97-143.0); controls: 425.9 (233.1-835.3); P<0.001) as well as a decrease in IL-1ß concentrations by almost 80%; and (3) no significant difference in plasma hypocretin levels between suicide and control subjects (suicide: 16.62 (13.62-25.77); controls: 21.63 (14.97-29.72); P=0.356). CONCLUSION: Our results suggest that plasma NPY and IL-1ß were related with suicide behavior rather than to suicide causes or suicide method. Specific combinations of plasma biomarkers may discriminate between types of suicidal behaviors and indicate increased risk for future suicide attempts.
