Validating the reproducibility of a low-cost single-channel fNIRS device across hierarchical cognitive tasks.

This study evaluates a low-cost, single-channel fNIRS device in cognitive neuroscience, aiming to overcome the financial barriers of commercial systems by testing its efficacy in tasks of varying complexity. Twenty-six participants engaged in motor control (finger-tapping), working memory (n-back), and creativity (AUT) tasks while their prefrontal cortex activity was monitored using the device, with behavioral and cerebral blood flow changes recorded. Results showed the device's capability to detect significant blood flow variations across different tasks, thereby supporting its use in cognitive research. The study confirms the potential of single-channel fNIRS as a cost-effective tool for diverse cognitive assessments, from simple motor actions to complex creative thinking.

The positivity rates and drug resistance patterns of Mycobacterium tuberculosis using nucleotide MALDI-TOF MS assay among suspected tuberculosis patients in Shandong, China: a multi-center prospective study.

Objective: To investigate the positivity rates and drug resistance characteristics of Mycobacterium tuberculosis (MTB) among suspected tuberculosis (TB) patients in Shandong Province, the second-largest population province in China. Methods: A prospective, multi-center study was conducted from April 2022 to June 2023. Pathogen and drug resistance were identified using nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS). Results: Of 940 suspected TB patients included in this study, 552 cases were found to be infected with MTB giving an overall positivity rate of 58.72%. Total of 346 cases were resistant to arbitrary anti-TB drug (62.68%), with Zibo (76.47%), Liaocheng and Weihai (both 69.23%) ranking top three and TB treatment history might be a related factor. Monoresistance was the most common pattern (33.53%), with isoniazid the highest at 12.43%, followed by rifampicin at 9.54%. Further analysis of gene mutations conferring resistance revealed diverse types with high heteroresistance rate found in multiple anti-TB drugs. Conclusion: A relatively high rate of MTB positivity and drug resistance was found in Shandong Province during and after the COVID-19 pandemic, indicating the need for strengthening rapid identification of species and drug resistance among suspected TB patients to guide better medication and minimize the occurrence of drug resistance.

Carbohydrate-DNA Conjugation Enabled by Glycosyl Radicals Generated from Glycosyl Sulfinates.

Herein, we report a method that enables the synthesis of carbohydrate-DNA conjugates by radical addition. Key to the success is the use of readily available, bench-stable, and unprotected glycosyl sulfinates as precursors to glycosyl radicals. The redox neutral reaction proceeds under mild and simple conditions and tolerates a broad substrate scope. A small library of carbohydrate-DNA conjugates was prepared.

Palladium catalysis enables cross-coupling-like SN2-glycosylation of phenols.

Despite their importance in life and material sciences, the efficient construction of stereo-defined glycosides remains a challenge. Studies of carbohydrate functions would be advanced if glycosylation methods were as reliable and modular as palladium (Pd)-catalyzed cross-coupling. However, Pd-catalysis excels in forming sp2-hybridized carbon centers whereas glycosylation mostly builds sp3-hybridized C-O linkages. We report a glycosylation platform through Pd-catalyzed SN2 displacement from phenols toward bench-stable, aryl-iodide-containing glycosyl sulfides. The key Pd(II) oxidative addition intermediate diverges from an arylating agent (Csp2 electrophile) to a glycosylating agent (Csp3 electrophile). This method inherits many merits of cross-coupling reactions, including operational simplicity and functional group tolerance. It preserves the SN2 mechanism for various substrates and is amenable to late-stage glycosylation of commercial drugs and natural products.

Discovery of Aminoratjadone Derivatives as Potent Noncovalent CRM1 Inhibitors.

Cancer cells frequently utilize elevated nuclear export to escape tumor suppression and gain proliferative advantage. Chromosome Region Maintenance 1 (CRM1/XPO1) mediates macromolecule nuclear export and plays an important role in tumorigenesis and progression. The clinical approval of its covalent inhibitor KPT-330 (Selinexor) validates the feasibility of targeting CRM1 to treat cancers. Here, we synthesized four aminoratjadone derivatives and found that two of them, KL1 and KL2, are noncovalent CRM1 inhibitors. The two compounds underwent spontaneous hydrolysis in aqueous buffers, and the resulting products were more active against CRM1. High-resolution crystal structures revealed the CRM1-binding mode of these compounds and explained the observed structure-activity relationships. In cells, KL1 and KL2 localized CRM1 in the nuclear periphery and led to depletion of nuclear CRM1, thereby inhibiting the nuclear export and growth of colorectal cancer cells at submicromolar concentrations. This work lays the foundation for further development of aminoratjadone-based noncovalent CRM1 inhibitors.

Generation and Use of Glycosyl Radicals under Acidic Conditions: Glycosyl Sulfinates as Precursors.

We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to the success is the design and use of glycosyl sulfinates as radical precursors, which are bench-stable solids and can be readily prepared from commercial starting materials. This development allows the installation of glycosyl units onto pyridine rings directly by the Minisci reaction. We further demonstrate the utility of this method in the late-stage modification of complex drug molecules, including the anticancer agent camptothecin. Experimental studies provide insight into the reaction mechanism.

Characterizing microbiota and metabolomics analysis to identify candidate biomarkers in lung cancer.

Background: Lung cancer is the leading malignant disease and cause of cancer-related death worldwide. Most patients with lung cancer had insignificant early symptoms so that most of them were diagnosed at an advanced stage. In addition to factors such as smoking, pollution, lung microbiome and its metabolites play vital roles in the development of lung cancer. However, the interaction between lung microbiota and carcinogenesis is lack of systematically characterized and controversial. Therefore, the purpose of this study was to excavate the features of the lung microbiota and metabolites in patients and verify potential biomarkers for lung cancer diagnosis. Methods: Lung tissue flushing solutions and bronchoalveolar lavage fluid samples came from patients with lung cancer and non-lung cancer. The composition and variations of the microbiota and metabolites in samples were explored using muti-omics technologies including 16S rRNA amplicon sequencing, metagenomics and metabolomics. Results: The metabolomics analysis indicated that 40 different metabolites, such as 9,10-DHOME, sphingosine, and cysteinyl-valine, were statistically significant between two groups (VIP > 1 and P < 0.05). These metabolites were significantly enriched into 11 signal pathways including sphingolipid, autophagy and apoptosis signaling pathway (P < 0.05). The analysis of lung microbiota showed that significant changes reflected the decrease of microbial diversity, changes of distribution of microbial taxa, and variability of the correlation networks of lung microbiota in lung cancer patients. In particular, we found that oral commensal microbiota and multiple probiotics might be connected with the occurrence and progression of lung cancer. Moreover, our study found 3 metabolites and 9 species with significantly differences, which might be regarded as the potential clinical diagnostic markers associated with lung cancer. Conclusions: Lung microbiota and metabolites might play important roles in the pathogenesis of lung cancer, and the altered metabolites and microbiota might have the potential to be clinical diagnostic markers and therapeutic targets associated with lung cancer.

Rh(I)-Catalyzed Coupling of Azides with Boronic Acids Under Neutral Conditions.

Because of the importance of polyfunctional amines, C-N bond formation is important in synthetic organic chemistry. Here we present a neutral amination reaction using azides as the nitrogen source and arylboronic acids with a rhodium(I) catalyst to afford alkyl-aryl and aryl-aryl secondary amines. Natural products and pharmaceutical derivatives were applied, and gram-scale reactions were performed, which demonstrated the utility. Mechanistic experiments and DFT calculations suggested that the reaction involves a metal-nitrene intermediate.

Selective synthesis of enol ethers via nickel-catalyzed cross coupling of α-oxy-vinylsulfones with alkylzinc reagents.

We describe here a Ni-catalyzed Negishi coupling reaction to prepare 1,2-dialkyl enol ethers in a stereoconvergent fashion. This method employs readily available and bench-stable α-oxy-vinylsulfones as electrophiles. The C-sulfone bond in the α-oxy-vinylsulfone motif is cleaved chemoselectively in these reactions. The mild conditions are tolerant of a variety of functional groups on both partners, thus representing a general strategy for enol ether synthesis. This unique reactivity of α-oxy-vinylsulfones indicates their further application as electrophilic partners in cross-coupling reactions.

Nonenzymatic Stereoselective S-Glycosylation of Polypeptides and Proteins.

Here we report a nonenzymatic glycosylation reaction that builds axial S-glycosidic bonds under biorelevant conditions. This strategy is enabled by the design and use of allyl glycosyl sulfones as precursors to glycosyl radicals and exploits the exceptional functional group tolerance of radical processes. Our method introduces a variety of unprotected glycosyl units to the cysteine residues of peptides in a highly selective fashion. Through developing the second-generation protocol, we applied our method in the direct glycosylation of complex polypeptides and proteins. Computational studies were performed to elucidate the reaction mechanism.

Assembly and annotation of whole-genome sequence of Fusarium equiseti.

Fusarium equiseti is a plant pathogen with a wide range of hosts and diverse effects, including probiotic effects. However, the molecular mechanisms underlying these effects remain unclear, hindering its effective utilization. The final assembly included 16 scaffolds of contiguous sequence without gaps. The total sequence length was 40,776,005 bp, and the GC content of 48.01%. In total, we annotated the putative function of 13,134 genes, accounting for 94.97% of the candidate genes. We identified two and 23 candidate genes that are likely involved in the production of mycotoxins zearalenone and trichothecene, respectively. A comparative genomic analysis supported the high quality of the F. equiseti assembly. Our comprehensive analysis of whole-genome sequence will serve as a valuable resource for future studies of expression, regulation, function and evolution of the genes of F. equiseti as well as studies into disease prevention and control.

Task Difficulty Regulates How Conscious and Unconscious Monetary Rewards Boost the Performance of Working Memory: An Event-Related Potential Study.

The performance of working memory can be improved by the corresponding high-value vs. low-value rewards consciously or unconsciously. However, whether conscious and unconscious monetary rewards boosting the performance of working memory is regulated by the difficulty level of working memory task is unknown. In this study, a novel paradigm that consists of a reward-priming procedure and N-back task with differing levels of difficulty was designed to inspect this complex process. In particular, both high-value and low-value coins were presented consciously or unconsciously as the reward cues, followed by the N-back task, during which electroencephalogram signals were recorded. It was discovered that the high-value reward elicited larger event-related potential (ERP) component P3 along the parietal area (reflecting the working memory load) as compared to the low-value reward for the less difficult 1-back task, no matter whether the reward was unconsciously or consciously presented. In contrast, this is not the case for the more difficult 2-back task, in which the difference in P3 amplitude between the high-value and low-value rewards was not significant for the unconscious reward case, yet manifested significance for the conscious reward processing. Interestingly, the results of the behavioral analysis also exhibited very similar patterns as ERP patterns. Therefore, this study demonstrated that the difficulty level of a task can modulate the influence of unconscious reward on the performance of working memory.

Relationship between circadian rhythm and brain cognitive functions.

Circadian rhythms are considered a masterstroke of natural selection, which gradually increase the adaptability of species to the Earth's rotation. Importantly, the nervous system plays a key role in allowing organisms to maintain circadian rhythmicity. Circadian rhythms affect multiple aspects of cognitive functions (mainly via arousal), particularly those needed for effort-intensive cognitive tasks, which require considerable top-down executive control. These include inhibitory control, working memory, task switching, and psychomotor vigilance. This mini review highlights the recent advances in cognitive functioning in the optical and multimodal neuroimaging fields; it discusses the processing of brain cognitive functions during the circadian rhythm phase and the effects of the circadian rhythm on the cognitive component of the brain and the brain circuit supporting cognition.

Decreased interhemispheric resting-state functional connectivity in male adolescents with conduct disorder.

Conduct disorder (CD) is a common psychiatric disorder defined by a repetitive and persistent pattern of aggressive and antisocial behaviors. Although numerous task-based and resting-state functional magnetic resonance imaging (rsfMRI) studies have emphasized the disrupted functional connectivity in CD, the CD-related alterations in functional interactions between the bilateral cerebral hemispheres are rarely investigated directly. In this study, a voxel-mirrored homotopic connectivity (VMHC) method based on rsfMRI was employed for the first time to examine the abnormalities of interhemispheric functional connectivity in patients with CD. The VMHC was compared between eighteen pure CD patients and eighteen typically developing (TD) healthy controls. In CD patients, reduced homotopic connectivity was observed relative to TDs in the middle occipital gyrus (MOG), pre- and postcentral gyrus, rolandic operculum and paracentral lobe (PCL) which were the components of visual and motor networks. Furthermore, the VMHC of the MOG and PCL was found to be negatively correlated with clinical scores in the CD group. Moreover, the regions with altered VMHC exhibited a relative good and robust ability to discriminate CD patients from TDs. This study provided a novel angle to identify the important role of interhemispheric coordination in the pathophysiology underlying CD and further indicated that the aberrant homotopic connectivity could be a potential clinical neural marker for CD diagnosis.

Effective Connectivity Study Guiding the Neuromodulation Intervention in Figurative Language Comprehension Using Optical Neuroimaging.

The current study is aimed at establishing links between brain network examination and neural plasticity studies measured by optical neuroimaging. Sixteen healthy subjects were recruited from the University of Macau to test the Granger Prediction Estimation (GPE) method to investigate brain network connectivity during figurative language comprehension. The method is aimed at mapping significant causal relationships across language brain networks, captured by functional near-infrared spectroscopy measurements (fNIRS): (i) definition of regions of interest (ROIs) based on significant channels extracted from spatial activation maps; (ii) inspection of significant causal relationships in temporal resolution, exploring the experimental task agreement; and (iii) early identification of stronger causal relationships that guide neuromodulation intervention, targeting impaired connectivity pathways. Our results propose top-down mechanisms responsible for perceptive-attention engagement in the left anterior frontal cortex and bottom-up mechanism in the right hemispheres during the semantic integration of figurative language. Moreover, the interhemispheric directional flow suggests a right hemisphere engagement in decoding unfamiliar literal sentences and fine-grained integration guided by the left hemisphere to reduce ambiguity in meaningless words. Finally, bottom-up mechanisms seem activated by logographic-semantic processing in literal meanings and memory storage centres in meaningless comprehension. To sum up, our main findings reveal that the Granger Prediction Estimation (GPE) integrated strategy proposes an effective link between assessment and intervention, capable of enhancing the efficiency of the treatment in language disorders and reducing the neuromodulation side effects.

More than just statics: Abnormal dynamic amplitude of low-frequency fluctuation in adolescent patients with pure conduct disorder.

BACKGROUND: The human brain activity is inherently dynamic over time. Conventional neuroimaging studies have reported abnormalities of static intrinsic brain activity or connectivity in adolescent patients with conduct disorder (CD). Little is known, however, regarding the temporal dynamics alterations of brain activity in CD. METHODS: In this study, resting-state functional magnetic resonance imaging examinations were performed on adolescent patients with pure CD and age-matched typically developing (TD) controls. The dynamic amplitude of low-frequency fluctuation (dALFF) was first measured using a sliding-window method. The temporal variability (TV) was then quantified as the variance of dALFF over time and compared between the two groups. Further, the relationships between aberrant TV of dALFF and clinical features were evaluated. RESULTS: CD patients showed reduced brain dynamics (less temporal variability) in the default-mode network, frontal-limbic cortices, sensorimotor areas, and visual regions which are involved in cognitive, emotional and perceptional processes. Importantly, receiver operating characteristic curve analysis revealed that regions with altered TV of dALFF exhibited a better ability to distinguish CD patients than the results from static ALFF in the current data set. CONCLUSIONS: Our findings extended previous work by providing a novel perspective on the neural mechanisms underlying adolescent patients with CD and demonstrated that the altered dynamic local brain activity may be a potential biomarker for CD diagnosis.

A Monoclinic V1-x-yTixRuyO2 Thin Film with Enhanced Thermal-Sensitive Performance.

Preparing the thermal-sensitive thin films with high temperature coefficient of resistance (TCR) and low resistivity by a highly compatible process is favorable for increasing the sensitivity of microbolometers with small pixels. Here, we report an effective and process-compatible approach for preparing V1-x-yTixRuyO2 thermal-sensitive thin films with monoclinic structure, high TCR, and low resistivity through a reactive sputtering process followed by annealing in oxygen atmosphere at 400 °C. X-ray photoelectron spectroscopy demonstrates that Ti4+ and Ru4+ ions are combined into VO2. X-ray diffraction, Raman spectroscopy, and transmission electron microscopy reveal that V1-x-yTixRuyO2 thin films have a monoclinic lattice structure as undoped VO2. But V1-x-yTixRuyO2 thin films exhibit no-SMT feature from room temperature (RT) to 106 °C due to the pinning effect of high-concentration Ti in monoclinic lattice. Moreover, RT resistivity of the V0.8163Ti0.165Ru0.0187O2 thin film is only one-eighth of undoped VO2 thin film, and its TCR is as high as 3.47%/°C.

Altered Functional Connectivity in the Motor and Prefrontal Cortex for Children With Down's Syndrome: An fNIRS Study.

Children with Down's syndrome (DS) might exhibit disrupted brain functional connectivity in the motor and prefrontal cortex. To inspect the alterations in brain activation and functional connectivity for children with DS, the functional near-infrared spectroscopy (fNIRS) method was applied to examine the brain activation difference in the motor and prefrontal cortex between the DS and typically developing (TD) groups during a fine motor task. In addition, small-world analysis based on graph theory was also carried out to characterize the topological organization of functional brain networks. Interestingly, behavior data demonstrated that the DS group showed significantly long reaction time and low accuracy as compared to the TD group (p < 0.05). More importantly, significantly reduced brain activations in the frontopolar area, the pre-motor, and the supplementary motor cortex (p < 0.05) were identified in the DS group compared with the TD group. Meanwhile, significantly high global efficiency (E g ) and short average path length (L p ) were also detected for the DS group. This pilot study illustrated that the disrupted connectivity of frontopolar area, pre-motor, and supplementary motor cortex might be one of the core mechanisms associated with motor and cognitive impairments for children with DS. Therefore, the combination of the fNIRS technique with functional network analysis may pave a new avenue for improving our understanding of the neural mechanisms of DS.

Interrelated Pathogenesis? Neuronal Intranuclear Inclusion Disease Combining With Hemiplegic Migraine.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is considered a heterogeneous disease because of its highly variable clinical manifestations. To date, there are no reports of NIID patients presenting with hemiplegic migraine (HM)-like headache, or of HM and NIID co-occurring as comorbidity, and the connection between these 2 seemingly unrelated clinical conditions has yet to be established. METHOD: We present a patient with NIID who was previously diagnosed with HM. To determine the pathogenesis of HM in this NIID patient, we systematically reviewed published NIID and HM cases and cataloged them based on their clinical manifestations. RESULT: The clinical manifestations of NIID is highly various; however, there is no case reported to date that shows HM-like symptoms or cerebral edema. All documented symptomatic HM cases show vascular dysfunction to various degrees, but none of them has been shown to be correlated with NIID. CONCLUSION: Our patient is the first documented case in which HM and NIID occur simultaneously. Vascular dysfunctions that cause cerebral hypoperfusion and glucose hypometabolism, two of the dominant causes of symptomatic HM, may be associated with the accumulation of eosinophilic hyaline inclusions that cause NIID. However, the existence of inclusions may also alter neuronal behavior and indirectly cause cerebral hypoperfusion and glucose hypometabolism. Further research and observations are needed to examine the relationship between HM and NIID.

Pd-Catalyzed Carbonylation of Acyl Azides.

Pd-catalyzed reactions of azides with CO to access an isocynate intermediate have been developed extensively in recent years. However, the catalytic carbonylation of sensitive acyl azides has not been reported. Herein, we report a simple Pd-catalyzed carbonylation reaction of acyl azides with broad substrate scope, high efficiency, and simple operation under mild conditions, which provides facile access to acyl ureas. In addition, a mechanistic study was carried out by both experiment and DFT calculation. Control experiments and kinetic study revealed that the real active palladium species were Pd(0). The result of kinetic study suggested that palladium catalyst, azide, and CO were all involved in the turnover-limiting step except for amine. Further DFT study suggested that an unprecedented five-membered palladacycle intermediate was the key intermediate in the carbonylation reaction.