Enantioselective Nickel-Electrocatalyzed Reductive Propargylic Carboxylation with CO2.

The exploitation of carbon dioxide (CO2) as a sustainable, plentiful, and harmless C1 source for the catalytic synthesis of enantioenriched carboxylic acids has long been acknowledged as a pivotal task in synthetic chemistry. Herein, we present a current-driven nickel-catalyzed reductive carboxylation reaction with CO2 fixation, facilitating the formation of C(sp3)-C(sp2) bonds by circumventing the handling of moisture-sensitive organometallic reagents. This electroreductive protocol serves as a practical platform, paving the way for the synthesis of enantioenriched propargylic carboxylic acids (up to 98% enantiomeric excess) from racemic propargylic carbonates and CO2. The efficacy of this transformation is exemplified by its successful utilization in the asymmetric total synthesis of (S)-arundic acid, (R)-PIA, (S)-chizhine D, (S)-cochlearin G, and (S,S)-alexidine, thereby underscoring the potential of asymmetric electrosynthesis to achieve complex molecular architectures sustainably.

Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits.

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

The Potential of FOXP3 in Predicting Survival and Treatment Response in Breast Cancer.

Background: Breast cancer (BC) continues to pose a substantial challenge to global health, necessitating an enhanced understanding of its fundamental mechanisms. Among its various pathological classifications, breast invasive carcinoma (BRCA) is the most prevalent. The role of the transcription factor forkhead box P3 (FOXP3), associated with regulatory T cells, in BRCA's diagnosis and prognosis remains insufficiently explored, despite its recognized importance. Methods: We examined the mRNA expression profile of FOXP3 in BRCA patients, assessing its correlation with disease detection, patient survival, immune checkpoint alterations, and response to anticancer drugs. Results: Our analysis revealed significantly elevated FOXP3 mRNA levels in BRCA patients, with a 95.7% accuracy for BRCA detection based on the area under the curve. High FOXP3 mRNA levels were positively correlated with overall survival and showed significant associations with CTLA4, CD274, PDCD1, TMB, and immune cell infiltration status. Furthermore, FOXP3 mRNA expression was linked to the efficacy of anticancer drugs and the tumor inflammation signature. Discussion: These findings suggest that FOXP3 serves as a promising biomarker for BRCA, offering valuable insights into its diagnosis and prognosis. The correlation between FOXP3 expression and immune checkpoint alterations, along with its predictive value for treatment response, underscores its potential in guiding therapeutic strategies. Conclusion: FOXP3 stands out as an influential factor in BRCA, highlighting its diagnostic accuracy and prognostic value. Its association with immune responses and treatment efficacy opens new avenues for research and clinical applications, positioning FOXP3 as a vital target for further investigation in BRCA management.

Atropisomeric Carboxylic Acids Synthesis via Nickel-Catalyzed Enantioconvergent Carboxylation of Aza-Biaryl Triflates with CO2.

Upgrading CO2 to value-added chiral molecules via catalytic asymmetric C-C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel-catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza-biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale-up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis.

Early warning indicators via latent stochastic dynamical systems.

Detecting early warning indicators for abrupt dynamical transitions in complex systems or high-dimensional observation data are essential in many real-world applications, such as brain diseases, natural disasters, and engineering reliability. To this end, we develop a novel approach: the directed anisotropic diffusion map that captures the latent evolutionary dynamics in the low-dimensional manifold. Then three effective warning signals (Onsager-Machlup indicator, sample entropy indicator, and transition probability indicator) are derived through the latent coordinates and the latent stochastic dynamical systems. To validate our framework, we apply this methodology to authentic electroencephalogram data. We find that our early warning indicators are capable of detecting the tipping point during state transition. This framework not only bridges the latent dynamics with real-world data but also shows the potential ability for automatic labeling on complex high-dimensional time series.

Structural and functional changes of anterior cingulate cortex subregions in migraine without aura: relationships with pain sensation and pain emotion.

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine.

Cu-Catalyzed Asymmetric Dicarboxylation of 1,3-Dienes with CO2.

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, and the polymer industry. Although catalytic dicarboxylation with CO2 represents a straightforward and sustainable route to dicarboxylic acids, it is still highly challenging and limited to generation of achiral or racemic dicarboxylic acids. To date, catalytic asymmetric dicarboxylation with CO2 to give chiral dicarboxylic acids has not been reported. Herein, we report the first asymmetric dicarboxylation of 1,3-dienes with CO2 via Cu catalysis. This strategy provides an efficient and environmentally benign route to chiral dicarboxylic acids with high regio-, chemo-, and enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation of 1,3-dienes to give carboxylated allyl boronic ester intermediates and subsequent carboxylation of C-B bonds to give dicarboxylates, is key to the success of this dicarboxylation. Moreover, this protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, and facile synthesis of chiral liquid crystalline polyester and drug-like scaffolds.

SARS-CoV-2 antibody level one month after COVID-19 infection in healthcare workers in Pudong New Area of Shanghai / 上海预防医学

ObjectiveTo investigate the levels of serum antibodies against novel coronavirus （SARS-CoV-2） in healthcare workers after one month of natural infection， to explore the influencing factors and their correlations with the levels of antibodies， and to provide reference for strengthening the protection of healthcare workers and preventive intervention in Pudong New Area in Shanghai. MethodsVenous blood samples were collected from 1 102 medical staff in Pudong hospitals one month after infection. The serum levels of new coronavirus specific antibodies IgM， IgG and neutralizing antibodies were detected by chemiluminescent immunoassay. The information of gender， age， position， infection severity， vaccination， basic diseases and use of immunosuppressants were obtained by questionnaire to explore the influencing factors and their correlation with the antibody level. ResultsOne month after natural infection， 99.00% （1 091/1 102） of the subjects were found to be positive for IgG antibody against the new coronavirus， 17.79% （196/1 102） of the subjects were IgM antibody positive， and 99.00% （1 091/1 102） of the samples were positive for the neutralizing antibody. The level of antibody might be influenced by the severity of infection， the time of the last dose of vaccination， and the long-term use of immunosuppressants. The more severe the disease， the stronger the neutralizing antibody response. The antibody level in the people who received the final dose of vaccine within 6 months was higher than that of the people who received the vaccine 6 months ago， and the difference was statistically significant. The antibody levels were low in the subjects who received long-term immunosuppressants. ConclusionThe specific IgM， IgG and neutralizing antibody were found， one month after infection， in the medical workers in Pudong New Area， Shanghai， and the antibody titers were high， which had a good protective effect. The antibody level of the people who were vaccinated within 6 months was higher， it is recommended that people who receive the last vacination more than 6 months should be re-vaccinated with the booster vaccine， to improve the autoimmunity against the novel coronavirus.

Association of agression and angry expression category perception under social exclusion among male students in reform school / 中国学校卫生

Objective@#To explore the relationship between aggression and category perception of angry expression in reform school students under social exclusion, so as to provide reference for the reform school students mental health promotion.@*Methods@#In May 2023, 144 students were randomly selected from a reform school in Guizhou Province, and were divided into high and low aggression groups(77 and 67 students) by Aggression Questionnaire. Cyberball game was used to induce social exclusion and acceptance, subjects were divided into high aggressive exclusion group ( n =42), high aggressive acceptance group ( n =35), low aggressive exclusion group ( n =37) and low aggressive acceptance group ( n =30). All the participants completed the discrimination and identification tasks of category perception paradigm, and the relationship between aggression and category perception of angry expression of reform school students under social exclusion was analyzed by using category turning point, identification curve and analysis of variance.@*Results@#The total score of aggression(97.34±8.00) and four dimensions (physical aggression: 29.75± 4.61, verbal aggression:17.19±2.58, anger:22.29±3.66, hostility:28.10±3.54) in the high aggression group were higher than those in the low aggression group(74.10±9.02，21.09±4.98，14.30±2.66，17.16±3.83，21.55±3.88), and the differences were statistically significant ( t =16.38, 10.85, 6.62, 8.20, 10.59, P <0.01). For identifying the turning point of the fear anger continuum, the social exclusion group（2.58±0.07）was significantly smaller than the social acceptance group（2.79±0.07）( F =4.85, η 2=0.07, P < 0.05 ）, and the social exclusion group had a tendency to shift the category boundary to the fear side. For identifying the slope at the angry happiness continuum category boundary curve, the high aggression group (0.63±0.03) was significantly higher than the low aggression group (0.53±0.03)( F =5.38, η 2=0.08, P <0.05). In the fear anger continuum,the high aggression group[(694.86± 78.29 )ms] reacted more quickly than the low aggression group[(660.70±79.86)ms]( F =5.08, η 2=0.05， P <0.05) In the angry happiness continuum, there was no statistical significance of social exclusion and aggression( P >0.05).@*Conclusions@#The suggests that social exclusion can lead to hostility attribution bias in individuals, while aggression can make individuals more sensitive to angry expression. The mechanisms by which social exclusion and aggression affect expression category perception are independent rather than interactive. The society should give tolerance and acceptance to reform school students, reduce exclusion and discrimination, and the reform education department should correct the aggressive behavior of reform school students and promote their mental health.

Risk factors and predictive models for early recurrent intussusception in children: a retrospective cohort study.

Background: Early recurrent intussusception (ERI) in children is common and seriously affects the physical and mental health of the children. There are few reports discussing risk factors for ERI in children, and this study aims to identify risk factors for ERI in children and build predictive models. Methods: We conducted a retrospective study of 787 children with no relapse intussusception (NRI) and 82 children with ERI between January 2011 and December 2021. Univariate and multifactorial stepwise logistic regression analysis was used to analyze the correlation between 11 factors and ERI, to determine the independent risk factors for ERI in children. The prediction model was established by independent risk factors and then verified. Results: Age, vomiting, bloody stools, and monocyte ratios were independently correlated with the composite endpoint (P<0.05). A nomogram was constructed and a calibration curve was plotted, using independent risk factors. Based on the disease's diagnostic score, the predictive model's performance was validated by using logistic regression receiver operating characteristic (ROC) curve detection, with area under the curve (AUC) value of 0.883 [95% confidence interval (CI): 0.846-0.920], and the calibration curve was close to the ideal diagonal line. In addition, the decision curve analysis (DCA) showed that the model had significant net benefits. Conclusions: Independent risk factors for ERI in children are age, vomiting, bloody stool, and monocyte ratio. Children older than 1 year in age, who lacked vomiting and bloody stool symptoms, and who exhibited an elevated ratio of monocytes were more likely to relapse early. The predictive model constructed herein can predict the early recurrence of children with ERI, providing a reference for clinicians' individualized judgments.

Magnetic Bistability in an Organic Radical-Based Charge Transfer Cocrystal.

We report herein an organic charge transfer cocrystal complex, consisting of a stable radical TPVr and an electron acceptor TCNQF4, as a rare sort of all-organic-based magnetic bistable materials with a thermally activated magnetic hysteresis loop over the temperature range from 170 to 260 K. Detailed X-ray crystallographic studies and theoretical calculations revealed that while a π-associated radical anion dimer was formed upon an integer charge transfer process from TPVr to the TCNQF4 molecules within the cocrystal lattice, the resulting TCNQF4·- π-dimers were found to exhibit varied intradimer π-stacking distances and singly occupied molecular orbital overlaps at different temperatures, thus yielding two different singlet states with distinct singlet-triplet gaps above and below the loop, which eventually contributed to the thermally excited molecular magnetic bistability.

Human umbilical cord mesenchymal stem cell-derived exosomal miR-214-3p regulates the progression of gallbladder cancer by regulating ACLY/GLUT1.

BACKGROUND: Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes have been reported to be effective in the treatment of cancer. The miR-214-3p is a suppressor miRNA that has been extensively studied and has been proposed as a diagnostic and prognostic biomarker in some cancers. OBJECTIVES: The aim of this study was to investigate whether the regulatory mechanism of hucMSC-derived exosomal miR-214-3p with GLUT1 and ACLY affects the proliferation and apoptosis of gallbladder cancer (GBC) cells. MATERIAL AND METHODS: We found that the target genes of miR-214-3p on the TargetScan website contain GLUT1 and ACLY, and the targeting relationship was verified using luciferases. The GBC-SD cells overexpressing GLUT1 and ACLY were constructed to determine proliferation, apoptosis, migration, and other cellular activities. RESULTS: We identified hucMSCs and exosomes, and found that the exosomes contained miR-214-3p. Furthermore, TargetScan predicted that miR-214-3p had base interactions with ACLY. Dual luciferase assays showed that miR-214-3p could inhibit ACLY (p < 0.05). The results of quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot showed that exosomal miR-214-3p could inhibit the expression of ACLY and GLUT1 (p < 0.05). Exosomal miR-214-3p can inhibit the proliferation, cloning and migration of GBC-SD cells (p < 0.05). The apoptosis of GBC-SD cells was increased (p < 0.05). The GBC-SD cells overexpressing ACLY and GLUT1 could reverse the efficacy of miR-214-3p. CONCLUSIONS: Exosomal miR-214-3p can inhibit the downstream expression of ACLY and GLUT1. The ACLY and GLUT1 could affect the proliferation and apoptosis of GBC-SD cells.

Joint polarization detection and degradation mechanisms for underwater image enhancement.

Light absorption and scattering exist in the underwater environment, which can lead to blurring, reduced brightness, and color distortion in underwater images. Polarized images have the advantages of eliminating underwater scattering interference, enhancing contrast, and detecting material information of the object in underwater detection. In this paper, from the perspective of polarization imaging, different concentrations (0.15 g/ml, 0.30 g/ml, and 0.50 g/ml), different wave bands (red, green, and blue), different materials (copper, wood, high-density PVC, aluminum, cloth, foam, cloth sheet, low-density PVC, rubber, and porcelain tile), and different depths (10 cm, 20 cm, 30 cm, and 40 cm) are set up in a chamber for the experimental environment. By combining the degradation mechanism of underwater images and the analysis of polarization detection results, it is proved that the degree of polarization images have greater advantages than degree of linear polarization images, degree of circular polarization images, S1, S2, and S3 images, and visible images underwater. Finally, a fusion algorithm of underwater visible images and polarization images based on compressed sensing is proposed to enhance underwater degraded images. To improve the quality of fused images, we introduce orthogonal matching pursuit (OMP) in the high-frequency part to improve image sparsity and consistency detection in the low-frequency part to improve the image mutation phenomenon. The fusion results show that the peak SNR values of the fusion result maps using OMP in this paper are improved by 32.19% and 22.14% on average over those using backpropagation and subspace pursuit methods. With different materials and concentrations, the underwater image enhancement algorithm proposed in this paper improves information entropy, average gradient, and standard deviation by 7.76%, 18.12%, and 40.8%, respectively, on average over previous algorithms. The image NIQE value shows that the image quality obtained by this paper's algorithm is improved by about 69.26% over the original S0 image.

Sleep Traits Causally Affect the Brain Cortical Structure: A Mendelian Randomization Study.

Background: Brain imaging results in sleep deprived patients showed structural changes in the cerebral cortex; however, the reasons for this phenomenon need to be further explored. Methods: This MR study evaluated causal associations between morningness, ease of getting up, insomnia, long sleep, short sleep, and the cortex structure. Results: At the functional level, morningness increased the surface area (SA) of cuneus with global weighted (beta(b) (95% CI): 32.63 (10.35, 54.90), p = 0.004). Short sleep increased SA of the lateral occipital with global weighted (b (95% CI): 394.37(107.89, 680.85), p = 0.007. Short sleep reduced cortical thickness (TH) of paracentral with global weighted (OR (95% CI): -0.11 (-0.19, -0.03), p = 0.006). Short sleep reduced TH of parahippocampal with global weighted (b (95% CI): -0.25 (-0.42, -0.07), p = 0.006). No pleiotropy was detected. However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and the five types of sleep traits met the threshold. Conclusions: Our results potentially show evidence of a higher risk association between neuropsychiatric disorders and not only paracentral and parahippocampal brain areas atrophy, but also an increase in the middle temporal zone. Our findings shed light on the associations of cortical structure with the occurrence of five types of sleep traits.

Corrigendum: Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis.

[This corrects the article DOI: 10.3389/fgene.2023.1124330.].

The role and application of fibroblast activating protein.

Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is rarely expressed in normal tissues but highly abundant in pathological diseases, including fibrosis, arthritis, and cancer. Ever since its discovery, we have deciphered its structure and biological properties and continue to investigate its roles in various diseases while attempting to utilize it for targeted therapy. To date, no significant breakthroughs have been made in terms of efficacy. However, in recent years, several practical applications in the realm of imaging diagnosis have been discovered. Given its unique expression in a diverse array of pathological tissues, the fundamental biological characteristics of FAP render it a crucial target for disease diagnosis and immunotherapy. To obtain a more comprehensive understanding of the research progress of FAP, its biological characteristics, involvement in diseases, and recent targeted application research have been reviewed. Moreover, we explored its development trend in the direction of clinical diagnoses and treatment.

Identification of key immune genes of osteoporosis based on bioinformatics and machine learning.

Introduction: Immunity is involved in a variety of bone metabolic processes, especially osteoporosis. The aim of this study is to explore new bone immune-related markers by bioinformatics method and evaluate their ability to predict osteoporosis. Methods: The mRNA expression profiles were obtained from GSE7158 in Gene expression Omnibus (GEO), and immune-related genes were obtained from ImmPort database (https://www.immport.org/shared/). immune genes related to bone mineral density(BMD) were screened out for differential analysis. protein-protein interaction (PPIs) networks were used to analyze the interrelationships between different immune-related genes (DIRGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DIRGs function were performed. A least absolute shrinkage and selection operation (LASSO) regression model and multiple Support Vector Machine-Recursive Feature Elimination (mSVM-RFE) model were constructed to identify the candidate genes for osteoporosis prediction The receiver operator characteristic (ROC) curves were used to validate the performances of predictive models and candidate genes in GEO database (GSE7158,GSE13850).Through the RT - qPCR verify the key genes differentially expressed in peripheral blood mononuclear cells Finally, we constructed a nomogram model for predicting osteoporosis based on five immune-related genes. CIBERSORT algorithm was used to calculate the relative proportion of 22 immune cells. Results: A total of 1158 DEGs and 66 DIRGs were identified between high-BMD and low-BMD women. These DIRGs were mainly enriched in cytokine-mediated signaling pathway, positive regulation of response to external stimulus and the cellular components of genes are mostly localized to external side of plasma membrane. And the KEGG enrichment analysis were mainly involved in Cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction,Natural killer cell mediated cytotoxicity. Then five key genes (CCR5, IAPP, IFNA4, IGHV3-73 and PTGER1) were identified and used as features to construct a predictive prognostic model for osteoporosis using the GSE7158 dataset. Conclusion: Immunity plays an important role in the development of osteoporosis.CCR5, IAPP, IFNA4, IGHV3-73 and PTGER1were play an important role in the occurrences and diagnosis of OP.

Secondary hierarchical complexity in double-stranded cluster helicates covered by NNNNN type pincer ligands.

We designed and synthesized a new tripyridine dipyrrolide pincer ligand, which could be doubly deprotonated to provide five-nitrogen-donor sites and then utilized to prepare a subnanometric chiral silver cluster. The cluster belongs to an S4 point group and shows a double-stranded helicate. DFT calculations were performed to analyze the electronic structure of the cluster. Interestingly, through hierarchical intercluster interactions, the cluster helicates evolve into complex secondary structures including a right-handed helix and a folded sheet, both of which are reminiscent of secondary structures of proteins, i.e., an α-helix and an antiparallel ß-sheet.