Palladium-Catalyzed Enantioselective Isodesmic C-H Iodination of Phenylacetic Weinreb Amides.

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.

Post-Assembly Modification of Homochiral Titanium-Organic Cages for Recognition and Separation of Molecular Isomers.

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.

Encoding biological recognition in a bicomponent cell-membrane mimic.

Self-assembling dendrimers have facilitated the discovery of periodic and quasiperiodic arrays of supramolecular architectures and the diverse functions derived from them. Examples are liquid quasicrystals and their approximants plus helical columns and spheres, including some that disregard chirality. The same periodic and quasiperiodic arrays were subsequently found in block copolymers, surfactants, lipids, glycolipids, and other complex molecules. Here we report the discovery of lamellar and hexagonal periodic arrays on the surface of vesicles generated from sequence-defined bicomponent monodisperse oligomers containing lipid and glycolipid mimics. These vesicles, known as glycodendrimersomes, act as cell-membrane mimics with hierarchical morphologies resembling bicomponent rafts. These nanosegregated morphologies diminish sugar-sugar interactions enabling stronger binding to sugar-binding proteins than densely packed arrangements of sugars. Importantly, this provides a mechanism to encode the reactivity of sugars via their interaction with sugar-binding proteins. The observed sugar phase-separated hierarchical arrays with lamellar and hexagonal morphologies that encode biological recognition are among the most complex architectures yet discovered in soft matter. The enhanced reactivity of the sugar displays likely has applications in material science and nanomedicine, with potential to evolve into related technologies.

Verification of using virtual reality to evaluate deficiencies in cognitive function among patients with schizophrenia in the remission stage: a cross-sectional study.

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.

Screening Libraries of Amphiphilic Janus Dendrimers Based on Natural Phenolic Acids to Discover Monodisperse Unilamellar Dendrimersomes.

Natural, including plant, and synthetic phenolic acids are employed as building blocks for the synthesis of constitutional isomeric libraries of self-assembling dendrons and dendrimers that are the simplest examples of programmed synthetic macromolecules. Amphiphilic Janus dendrimers are synthesized from a diversity of building blocks including natural phenolic acids. They self-assemble in water or buffer into vesicular dendrimersomes employed as biological membrane mimics, hybrid and synthetic cells. These dendrimersomes are predominantly uni- or multilamellar vesicles with size and polydispersity that is predicted by their primary structure. However, in numerous cases, unilamellar dendrimersomes completely free of multilamellar assemblies are desirable. Here, we report the synthesis and structural analysis of a library containing 13 amphiphilic Janus dendrimers containing linear and branched alkyl chains on their hydrophobic part. They were prepared by an optimized iterative modular synthesis starting from natural phenolic acids. Monodisperse dendrimersomes were prepared by injection and giant polydisperse by hydration. Both were structurally characterized to select the molecular design principles that provide unilamellar dendrimersomes in higher yields and shorter reaction times than under previously used reaction conditions. These dendrimersomes are expected to provide important tools for synthetic cell biology, encapsulation, and delivery.

Palladium-Catalyzed C(sp2)-H Olefination of Free Primary and Secondary 2-Phenylethylamines: Access to Tetrahydroisoquinolines.

A rapid construction of THIQs by a Pd(II)-catalyzed C(sp2)-H olefination of free primary and secondary 2-phenylethylamines with high step- and atom-economy was reported. Notably, no substituent was required at the α-position to the amino group of the 2-phenylethylamines. The substrate scope was broad, and the reaction could also be applied to generate THIQs from the biologically active molecules such as the drug molecule baclofen and phenylalanine ester.

Altered coupling of spontaneous brain activities and brain temperature in patients with adolescent-onset, first-episode, drug-naïve schizophrenia.

PURPOSE: A recent study has reported that schizophrenia patients show an uncoupled association between intraventricular brain temperature (BT) and cerebral blood flow (CBF). CBF has been found to be closely coupled with spontaneous brain activities (SBAs) derived from resting-state BOLD fMRI metrics. Yet, it is unclear so far whether the relationship between the intraventricular BT and the SBAs may change in patients with adolescent-onset schizophrenia (AOS) compared with that in healthy controls (HCs). METHODS: The present study recruited 28 first-episode, drug-naïve AOS patients and 22 matched HCs. We measured the temperature of the lateral ventricles (LV) using diffusion-weighted imaging thermometry and measured SBAs using both regional homogeneity and amplitude of low-frequency fluctuation methods. A nonparametric Wilcoxon rank sum test was used to detect the difference in intraventricular BT between AOS patients and HCs with LV volume, age, and sex as covariates. We also evaluated the relationship between the intraventricular BT and the SBAs using partial correlation analysis controlling for LV volume, age, and sex. RESULTS: We found that HCs showed a significant negative correlation between the intraventricular BT and the local SBAs in the bilateral putamina and left superior temporal gyrus, while such a correlation was absent in AOS patients. Additionally, no significant difference between the two groups was found in the intraventricular BT. CONCLUSION: These findings suggest that AOS patients may experience an uncoupling between intraventricular BT and SBAs in several schizophrenia-related brain areas, which may be associated with the altered relationships among intraventricular BT, CBF, and metabolism.

Carboxy Group as a Remote and Selective Chelating Group for C-H Activation of Arenes.

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.

Phase-Pure α-Sn Quantum Material on Si Seeded by a 2 nm-Thick Ge Layer.

α-Sn, a new elemental topological quantum material, has drawn substantial attention lately. Unique transport properties and intriguing spintronics applications of α-Sn are demonstrated, resurrecting this material from its notorious "tin pest" infamy. With a diamond cubic crystal structure, group-IV α-Sn holds the potential for integrated topological quantum devices on Si. However, directly growing α-Sn on Si is still challenging due to the ≈20% lattice mismatch. Here, a new method is demonstrated to grow 200 nm-thick α-Sn microstructures on a 2 nm-thick Ge seed layer on Si substrate by physical vapor deposition. In situ Raman spectroscopy reveals that the as-deposited ß-Sn melts upon rapid thermal annealing at 350-450 °C and solidifies to α-Sn after cooling back to room temperature, seeded by heterogeneous nucleation on the Ge layer. Cooling condition and HCl etching are tuned to achieve phase-pure α-Sn microstructures toward quantum devices. Approximately 1 at.% Ge is alloyed into α-Sn due to diffusion from the Ge seed layer, which helps stabilize α-Sn thermodynamically to facilitate device processing. A compressive strain is incorporated into these α-Sn microstructures, making them 3D topological Dirac semimetals for integrated quantum devices on Si.

Changes in Plasma TPH2, GDNF, Trk-b, BDNF, and proBDNF in People Who Died by Suicide.

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.

Effect of 40 Hz light flicker on cognitive impairment and transcriptome of hippocampus in right unilateral common carotid artery occlusion mice.

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.

Accurate binding of porous aluminum molecular ring catalysts with the substrate.

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.

Formal C-H/C-I Metathesis: Site-Selective C-H Iodination of 2-Aryl Benzoic Acid Derivatives Using Aryl Iodide.

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.

Formal C-H/C-I Metathesis: Site-Selective C-H Iodination of Anilines Using Aryl Iodides.

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.

Effect of Virtual Reality on Cognitive Impairment and Clinical Symptoms among Patients with Schizophrenia in the Remission Stage: A Randomized Controlled Trial.

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.

Palladium-catalyzed remote para-C-H activation of arenes assisted by a recyclable pyridine-based template.

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.

Increased Hypocretin (Orexin) Plasma Level in Depression, Bipolar Disorder Patients.

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.

Effect of repetitive transcranial magnetic stimulation on the cognitive impairment induced by sleep deprivation: a randomized trial.

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.

Carboxyl-Assisted meta-Selective C-H Functionalizations of Benzylsulfonamides.

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.

Gray Matter Volume and Functional Connectivity in Hypochondriasis: A Magnetic Resonance Imaging and Support Vector Machine Analysis.

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.