Right-to-left shunt-associated brain functional changes in migraine: evidences from a resting-state FMRI study.

Background: Migraine, a neurological condition perpetually under investigation, remains shrouded in mystery regarding its underlying causes. While a potential link to Right-to-Left Shunt (RLS) has been postulated, the exact nature of this association remains elusive, necessitating further exploration. Methods: The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo) and functional connectivity (FC) were employed to investigate functional segregation and functional integration across distinct brain regions. Graph theory-based network analysis was utilized to assess functional networks in migraine patients with RLS. Pearson correlation analysis further explored the relationship between RLS severity and various functional metrics. Results: Compared with migraine patients without RLS, patients with RLS exhibited a significant increase in the ALFF within left middle occipital and superior occipital gyrus; In migraine patients with RLS, significantly reduced brain functional connectivity was found, including the connectivity between default mode network and visual network, ventral attention network, as well as the intra-functional connectivity of somatomotor network and its connection with the limbic network, and also the connectivity between the left rolandic operculum and the right middle cingulate gyrus. Notably, a significantly enhanced functional connectivity between the frontoparietal network and the ventral attention network was found in migraine with RLS; Patients with RLS displayed higher values of the normalized clustering coefficient and greater betweenness centrality in specific regions, including the left precuneus, right insula, and right inferior temporal gyrus. Additionally, these patients displayed a diminished nodal degree in the occipital lobe and reduced nodal efficiency within the fusiform gyrus; Further, the study found positive correlations between ALFF in the temporal lobes, thalamus, left middle occipital, and superior occipital gyrus and RLS severity. Conversely, negative correlations emerged between ALFF in the right inferior frontal gyrus, middle frontal gyrus, and insula and RLS grading. Finally, the study identified a positive correlation between angular gyrus betweenness centrality and RLS severity. Conclusion: RLS-associated brain functional alterations in migraine consisted of local brain regions, connectivity, and networks involved in pain conduction and regulation did exist in migraine with RLS.

Artificial Photosynthetic Cell with Molecular Biomimetic Thylakoid.

The construction of solar-to-chemical conversion system by mimicking the photosynthetic network of the chloroplast holds great promise on efficient solar energy utilization. We developed an artificial photosynthetic cell (APC) based on molecular biomimetic thylakoid (CoTPP-FePy) to split water into hydrogen and oxygen (H2 and O2) at low driving voltage (1.1 V) and neutral condition (pH≈7). The CoTPP-FePy can emulate the light reaction in thylakoids to produce O2 by coupling light harvesting, photocatalysis, and electron/energy storage (FeIII/FeII-Py). Subsequently, a membrane electrode assembly (MEA) were employed to simulate the dark reaction, wherein the proton, electron and energy generated by the light reaction can drive the H2 producing process. By a temporally and spatially coupling of the light and dark reactions, the resulting APC achieved a solar conversion efficiency of 3.1%, exceeding that of natural photosynthetic systems and demonstrating the potential of artificial photosynthesis.

Overestimated Halogen Atom Transfer Reactivity of α-Aminoalkyl Radicals.

Halogen atom transfer (XAT) is a versatile method for generating carbon radicals. Recent interest has focused on α-aminoalkyl radicals as potential XAT reagents, previously reported to exhibit reactivity comparable to tin radicals. Utilizing an advanced time-resolved EPR technique, the XAT reactions between α-aminoalkyl radicals and organic halides were examined, allowing direct observation of the process through EPR spectroscopy and analysis of radical kinetics. Second-order rate constants for these reactions were determined, with some validated using transient absorption spectroscopy. The key finding is that the reactivity of α-aminoalkyl radicals in XAT reactions is 103 to 105 times lower than that of tin and silicon radicals and only slightly higher than alkyl radicals. This challenges the belief that α-aminoalkyl radicals are as reactive as tin radicals. The study on the solvent effect indicates that the XAT reaction of α-aminoalkyl radicals does not involve a highly polarized transition state, suggesting that the kinetic polar effect in this XAT process is not as significant as previously believed. The present study provides a reliable XAT reactivity scale for α-aminoalkyl radicals, which is crucial for designing XAT reactions and understanding their mechanisms.

Dual Ligand Enabled Pd-Catalyzed Ortho-Alkylation of Iodoarenes.

The synthesis of complex polysubstituted aromatic molecules from simple precursors is a central goal in organic chemistry. In this study, we developed an approach for the ortho-alkylation of iodoarenes utilizing a dual ligand catalytic system. By combining Pd/olefin ligand cooperative catalysis with bulky trialkylphosphine ligand-promoted C(sp2)-I reductive elimination, we have established an ortho-alkylative Catellani-type reaction with the aryl-iodine bond reconstruction as the final step, which opens new synthetic opportunities within the Catellani-type reactions. Through in-depth mechanistic investigations, we have isolated and characterized key organopalladium intermediates, revealing the synergistic interaction of the dual ligands in merging the Catellani-type process with C(sp2)-I reductive elimination. The present study showcases the unique advantages of Pd/olefin ligand catalysis and emphasizes the effectiveness of the dual ligand system in expanding the chemical space of the Catellani chemistry.

Oxygen-bridged W-Pd atomic pairs enable H2O2 activation for sensitive immunoassays.

Regulating the performance of peroxidase (POD)-like nanozymes is a prerequisite for achieving highly sensitive and accurate immunoassays. Inspired by natural enzyme catalysis, we design a highly active and selective nanozyme by loading atomically dispersed tungsten (W) sites on Pd metallene (W-O-Pdene) to construct an artificial three-dimensional (3D) catalytic center. The 3D asymmetric W-O-Pd atomic pairs can effectively stretch the O-O bonds in H2O2 and further promote the desorption of H2O to enhance POD-like activity. Moreover, the W-O-Pd sites with unique spatial structures demonstrate satisfactory specificity for H2O2 activation, effectively preventing the interference of dissolved oxygen. Accordingly, the highly active and specific W-O-Pdene nanozymes are utilized for sensitive and accurate prostate-specific antigen (PSA) immunoassay with a low detection limit of 1.92 pg mL-1, superior to commercial enzyme-linked immunosorbent assay.

Biomimetic Electronic Communication of Iodine Doped Single-Atom Fe Site for Highly Active and Stable Dopamine Oxidation.

Rational design of highly active and stable catalysts for dopamine oxidation is still a great challenge. Herein, inspired by the catalytic pocket of natural enzymes, an iodine (I)-doped single Fe-site catalyst (I/FeSANC) is synthesized to mimic the catalytic center of heme enzymes in both geometrical and electronic structures, aiming to enhance dopamine (DA) oxidation. Experimental studies and theoretical calculations show that electronic communication between I and FeN5 effectively modulates the electronic structure of the active site, greatly optimizing the overlap of Fe 3d and O 2p orbitals, thereby enhancing OH adsorption. In addition, the electronic communication induced by iodine doping attenuates the attack of proton hydrogen on the active center, thereby enhancing the stability of I/FeSANC. This work provides new insights into the design of highly active and stable single-atom catalysts and enhances the understanding of catalytic mechanisms for DA oxidation at the atomic scale.

Evaluation of human antibodies from vaccinated volunteers for protection against Yersinia pestis infection.

Yersinia pestis has a broad host range and has caused lethal bubonic and pneumonic plague in humans. With the emergence of multiple resistant strains and the potential for biothreat use, there is an urgent need for new therapeutic strategies that can protect populations from natural or deliberate infection. Targeting F1 has been proven to be the main strategy for developing vaccines and therapeutic antibodies, but data on anti-F1 antibodies, especially in humans, are scarce. To date, three human anti-F1 monoclonal antibodies (m252, αF1Ig2, and αF1Ig8) from naive populations have been reported. Here, we constructed an antibody library from vaccinees immunized with the plague subunit vaccine IIa by phage display. The genetic basis, epitopes, and biological functions of the obtained mAbs were assessed and evaluated in plague-challenged mice. Three human mAbs, namely, F3, F19, and F23, were identified. Their biolayer responses were 0.4, 0.6, and 0.6 nm, respectively. The dissociation constants (KD) of the F1 antigen were 1 pM, 0.165 nM, and 1 pM, respectively. Although derived from distinct Ab lineages, that is, VH3-30-D3-10-JH4 (F3&F23) and VH3-43-D6-19-JH4 (F19), these mAbs share similar binding sites in F1 with some overlap with αF1Ig8 but are distinct from αF1Ig2. Each of them provided a significant protective effect for Balb/c mice against a 100 median lethal dose (MLD) challenge of a virulent Y. pestis strain when administered at a dose of 100 µg. No synergistic or antagonistic effects were observed among them. These mAbs are novel and excellent candidates for further drug development and use in clinical practice.IMPORTANCEIn this study, we identified three human monoclonal antibodies with a high affinity to F1 protein of Yersinia pestis. We discovered that they have relatively lower somatic hypermutations compared with antibodies, m252, αF1Ig2, and αF1Ig8, derived from the naive library reported previously. We also observed that these mAbs share similar binding sites in F1 with some overlapping with αF1Ig8 but distinct from that of αF1Ig2. Furthermore, each of them could provide complete protection for mice against a lethal dose of Yersinia pestis challenge. Our data provided new insights into the anti-F1 Ab repertories and their associated epitopes during vaccination in humans. The findings support the additional novel protective human anti-F1Abs for potential therapeutics against plaque.

Facile, green and scalable synthesis of single-layer manganese dioxide nanosheets and its application for GSH and cTnI colorimetric detection.

Manganese dioxide (MnO2) nanosheets possess unique physical and chemical properties, making them widely applicable in various fields, such as chemistry and biomedicine. Although MnO2 nanosheets are produced using bottom-up wet chemistry synthesis methods, their scale is below the gram level and requires a long processing time, restricting their effective scale-up from laboratory to market. We report a facile, green and scalable synthesis of MnO2 nanosheets by mixing Shiranui mandarin orange juice and KMnO4 for 30 minutes. We produced more than one gram (1.095) of MnO2 nanosheets with a 0.65 nm mean thickness and a 50 nm mean lateral size. Furthermore, we established a visual colorimetric biosensing strategy based on MnO2 nanosheets for the assay of glutathione (GSH) and cardiac troponin I (cTnI), offering high sensitivity and feasibility in clinical samples. For GSH, the limit of detection was 0.08 nM, and for cTnI, it was 0.70 pg mL-1. Meanwhile, the strategy can be used for real-time analysis by applying a smartphone-enabled biosensing strategy, which can provide point-of-care testing in remote areas.

Molecular Engineering of Methylated Sulfone-Based Covalent Organic Frameworks for Back-Reaction Inhibited Photocatalytic Overall Water Splitting.

Solar-to-hydrogen (H2) and oxygen (O2) conversion via photocatalytic overall water splitting (OWS) holds great promise for a sustainable fuel economy, but has been challenged by the backward O2 reduction reaction (ORR) with favored proton-coupled electron transfer (PCET) dynamics. Here, we report that molecular engineering by methylation inhibits the backward ORR of molecular photocatalysts and enables efficient OWS process. As demonstrated by a benchmark sulfone-based covalent organic framework (COF) photocatalyst, the precise methylation of its O2 adsorption sites effectively blocks electron transfer and increases the barrier for hydrogen intermediate desorption that cooperatively obstructs the PCET process of ORR. Methylation also repels electrons to the neighboring photocatalytic sulfone group that promotes the forward H2 evolution. The resultant DS-COF achieves an impressive inhibition of about 70 % of the backward reaction and a three-fold enhancement of the OWS performance with a H2 evolution rate of 124.7 µmol h-1 g-1, ranking among the highest reported for organic-based photocatalysts. This work provides insights for engineering photocatalysts at the molecular level for efficient solar-to-fuel conversion.

Inhibition effect of p-d orbital hybridized PtSn nanozymes for colorimetric sensor array of antioxidants.

Rational design of peroxidase (POD)-like nanozymes with high activity and specificity still faces a great challenge. Besides, the investigations of nanozymes inhibitors commonly focus on inhibition efficiency, the interaction between nanozymes-involved catalytic reactions and inhibitors is rarely reported. In this work, we design a p-block metal Sn-doped Pt (p-d/PtSn) nanozymes with the selective enhancement of POD-like activity. The p-d orbital hybridization interaction between Pt and Sn can effectively optimize the electronic structure of PtSn nanozymes and thus selectively enhance POD-like activity. In addition, the antioxidants as nanozymes inhibitors can effectively inhibit the POD-like activity of p-d/PtSn nanozymes, which results in the fact that antioxidants absorbed on the p-d/PtSn surface can hinder the adsorption of hydrogen peroxide. The inhibition type (glutathione as a model molecule) is reversible mixed-inhibition with inhibition constants (Ki' and Ki) of 0.21 mM and 0.03 mM. Finally, based on the varying inhibition levels of antioxidant molecules, a colorimetric sensor array is constructed to distinguish and simultaneously detect five antioxidants. This work is expected to design highly active and specific nanozymes through p-d orbital hybrid engineering, and also provides insights into the interaction between nanozymes and inhibitors.

Molecular Photoelectrochemical Energy Storage Materials for Coupled Solar Batteries.

ConspectusSolar-to-electrochemical energy storage is one of the essential solar energy utilization pathways alongside solar-to-electricity and solar-to-chemical conversion. A coupled solar battery enables direct solar-to-electrochemical energy storage via photocoupled ion transfer using photoelectrochemical materials with light absorption/charge transfer and redox capabilities. Common photoelectrochemical materials face challenges due to insufficient solar spectrum utilization, which restricts their redox potential window and constrains energy conversion efficiency. In contrast, molecular photoelectrochemical energy storage materials are promising for their mechanism of exciton-involved redox reaction that allows for extra energy utilization from hot excitons generated by superbandgap excitation and localized heat after absorption of sub-bandgap photons. This enables more efficient redox reactions with a less restricted redox potentials window and, thus, better utilization of the full solar spectrum. Despite these advantages, practical application remains elusive due to the mismatch between the short lifetime of the charge separation state (µs). This mismatch results in a significant portion of the photogenerated charges recombining before participating in desired electrochemical energy storage reactions, leading to diminished overall efficiency. It is therefore highly important to develop molecular materials with intrinsic prolonged charge separation state and extrinsic effective mass-electron transfer to enable efficient coupled solar batteries for practical applications.In this Account, we begin with an introduction of the general solar-to-electrochemical energy storage concept based on molecular photoelectrochemical energy storage materials, highlighting the advantages of periodic oxidative donor-reductive acceptor porous aggregate structures that have synergistic implications on charge separation state lifetime extension and mass-electron transfer. We then present our earliest trial on the design and application of molecular photoelectrochemical energy storage materials, which stimulated our subsequent studies on tuning electron donor and acceptor structures for enhanced charge separation and diverse photoelectrochemical redox reactions. Moreover, we introduce the best practices in the design and assembly of various coupled solar battery devices, along with our literature contributions and progresses in solar-to-electrochemical energy storage efficiency (ηSES) over nearly the past decade. Finally, we conclude by highlighting the universality of our strategies as essential design principles, spanning from regulating long-lived charge separation states and photocoupled ion transfer processes in molecular materials to the construction of efficient coupled solar batteries. We offer perspectives on the synergy between photovoltage and redox potentials and the practical significance of 3D printing, providing key evaluation indicators for large-scale application. This Account provides molecular level insights for the construction of high-efficiency photoelectrochemical energy storage materials and guidance for practical solar-to-electrochemical energy storage applications.

Catalase-like Fe Nanoparticles and Single Atoms Catalysts with Boosted Activity and Stability of Oxygen Reduction for Pesticide Detection.

Although oxygen reduction reaction (ORR) as an effective signal amplification strategy has been extensively investigated for the improvement of sensitivity of electrochemical sensors, their activity and stability are still a great challenge. Herein, single-atom Fe (FeSA) and Fe nanoparticles (FeNP) on nitrogen-doped carbon (FeSA/FeNP) catalysts demonstrate a highly active and stable ORR performance, thus achieving the sensitive and stable electrochemical sensing of organophosphorus pesticides (OPs). Experimental investigations indicate that FeNP in FeSA/FeNP can improve the ORR activity by adjusting the electronic structure of FeSA active sites. Besides, owing to the excellent catalase-like activity, FeSA/FeNP can rapidly consume in situ generated H2O2 in the ORR process and avoid the leakage of active sites, thereby improving the stability of ORR. Utilizing the excellent ORR performance of FeSA/FeNP, an electrochemical sensor for OPs is established based on the thiocholine-induced poison of the active sites, demonstrating satisfactory sensitivity and stability. This work provides new insight into the design of high performance ORR catalysts for sensitive and stable electrochemical sensing.

LncRNA CCRR maintains Ca2+ homeostasis against myocardial infarction through the FTO-SERCA2a pathway.

Cardiac conduction regulatory RNA (CCRR) has been documented as an antiarrhythmic lncRNA in our earlier investigation. This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca2+ homeostasis in myocardial infarction (MI). Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca2+ homeostasis and reduced the heightened methylation level of SERCA2a following MI. These effects were also observed in CCRR over-expressing transgenic mice. A conserved sequence domain of CCRR mimicked the protective function observed with the full length. Furthermore, silencing CCRR in healthy mice led to intracellular Ca2+ overloading of cardiomyocytes. CCRR increased SERCA2a protein stability by upregulating FTO expression. The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation (RIP) analysis and RNA pulldown experiments. Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI. This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO, thereby reducing the m6A RNA methylation level of SERCA2a, ultimately preserving calcium homeostasis for myocardial contractile function in MI. Therefore, CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

Unveiling the Mechanistic Role of Chiral Palladacycles in Pd(II)-Catalyzed Enantioselective C(sp3)-H Functionalization.

Palladium-catalyzed enantioselective C(sp3)-H functionalization reactions has attracted considerable attention due to its ability for the synthesis of enantiomerically enriched molecules and stimulation of novel retrosynthetic disconnections. Understanding the reaction mechanism, especially the stereochemical process of the reaction, is crucial for the rational design of more efficient catalytic systems. Previously, we developed a Pd(II)/sulfoxide-2-hydroxypridine (SOHP) catalytic system for asymmetric C(sp3)-H functionalization reactions. In this study, we focused on unraveling the chemistry of chiral palladacycles involved in the Pd(II)-catalyzed enantioselective C(sp3)-H functionalization. We have isolated key palladacycle intermediates involved in the enantioselective ß-C(sp3)-H arylation of carboxylic acids catalyzed by the Pd(II)/SOHP system. These palladacycles, exhibiting ligand-induced chirality, provided a significant opportunity to investigate the stereochemical process and the ligand effect in this asymmetric C-H functionalization. Our investigation provided direct evidence for the C-H palladation step as the enantioselectivity-determining step, which forms diastereomeric palladacycles that exhibited preservation of chirality in the functionalization step. DFT calculations provided insights into the chiral induction in palladacycle formation. This work highlights the value of chiral palladacycle chemistry in offering mechanistic insights into the Pd(II)-catalyzed asymmetric C(sp3)-H functionalization reactions.

Determination of pulmonary vessel alteration in Chinese male smokers by quantitative computed tomography measurements: a retrospective study.

Background: The blood volume of intraparenchymal vessels is reported to be increased in smokers. However, the blood volume can be affected by many confounders besides tobacco exposure. This study aimed to investigate the association between cigarette smoking and pulmonary blood volume after adjusting the related factors in a large cohort of Chinese males. Methods: In this retrospective study, male participants admitted to the First Affiliated Hospital of Xi'an Jiaotong University for annual health assessment between February 2017 and February 2018 were enrolled. All subjects underwent non-contrast chest computed tomography (CT) scans, and 152 subjects underwent a review CT scan 2-3 years later. A three-dimensional approach was employed to segment the lung and intrapulmonary vessels and quantitative CT (QCT) measurements, including lung volume (LV), intrapulmonary vessel volume (IPVV), low-attenuation area <-950 Hounsfield unit (LAA-950 and LAA-950%), and mean lung density (MLD). Linear regression was used to estimate the association between IPVV and the smoking index (SI). A paired t-test was used to compare the QCT parameters between the initial and follow-up CT scans. Results: A total of 656 male participants were enrolled and classified into three subgroups: non-smokers (n=311), current smokers (n=267), and former smokers (n=78). The IPVV of current smokers (134.62±23.96 vs. 120.76±25.52 mL) and former smokers (130.79±25.13 vs. 120.76±25.52 mL) were significantly larger than that of non-smokers (P<0.05). A higher SI was associated with greater IPVV [non-standardized coefficient: 0.167, 95% confidence interval (CI): 0.086-0.248]. For current smokers, the IPVV of the follow-up scan significantly increased compared to its baseline scan (135.49±28.60 vs. 129.73±29.75 mL, t=-2.326, P=0.02), but for the non-smokers and former smokers, the IPVV of the follow-up scan did not increase or decrease compared to the baseline scan (P>0.05). Conclusions: Pulmonary vascular volumes detectable on non-contrast CT are associated with cigarette exposure, and smoking cessation may prevent pulmonary vasculature remodeling.

Highly selective electroreduction of CO2 to CO with ZnO QDs/N-doped porous carbon catalysts.

ZnO quantum dots (QDs) supported on porous nitrogen-doped carbon (ZnOQDs/P-NC) exhibited excellent electrochemical performance for the electroreduction of CO2 to CO with a faradaic efficiency of 95.3% and a current density of 21.6 mA cm-2 at -2.2 V vs. Ag/Ag+.

A multicomponent triformylphoroglucinol-based covalent organic framework for overall hydrogen peroxide photosynthesis.

A multicomponent covalent organic framework (COF-Tfp-BpyDaaq) integrating bipyridine with diaminoanthraquinone through a triformylphoroglucinol linkage was synthesized for the first time as a photocatalyst for overall H2O2 photosynthesis. It exhibits enhanced photo-charge separation and H2O2 production rate over its two-component counterparts, demonstrating the pivotal role of multicomponent synthesis in designing efficient photocatalysts.

Direct Observation of All Open-Shell Intermediates in a Photocatalytic Cycle.

Molecular photocatalysis has shown tremendous success in sustainable energy and chemical synthesis. However, visualizing the transient open-shell intermediates in photocatalysis is a significant and long-standing challenge. By employing our recently developed innovative time-resolved electron paramagnetic resonance technique, we directly observed all radicals and radical ions involved in the photocatalytic addition of pempidine to tert-butyl acrylate. The full picture of the photocatalytic cycle is vividly illustrated by the fine structures, chemical kinetics, and dynamic spin polarization of all open-shell intermediates directly observed in this prototypical system. Given the universality of this methodology, we believe it greatly empowers the research paradigm of direct observation in both photocatalysis and radical chemistry.

p-d Orbital Hybridization-Engineered PdSn Nanozymes for a Sensitive Immunoassay.

Nanozymes with peroxidase-like activity have been extensively studied for colorimetric biosensing. However, their catalytic activity and specificity still lag far behind those of natural enzymes, which significantly affects the accuracy and sensitivity of colorimetric biosensing. To address this issue, we design PdSn nanozymes with selectively enhanced peroxidase-like activity, which improves the sensitivity and accuracy of a colorimetric immunoassay. The peroxidase-like activity of PdSn nanozymes is significantly higher than that of Pd nanozymes. Theoretical calculations reveal that the p-d orbital hybridization of Pd and Sn not only results in an upward shift of the d-band center to enhance hydrogen peroxide (H2O2) adsorption but also regulates the O-O bonding strength of H2O2 to achieve selective H2O2 activation. Ultimately, the nanozyme-linked immunosorbent assay has been successfully developed to sensitively and accurately detect the prostate-specific antigen (PSA), achieving a low detection limit of 1.696 pg mL-1. This work demonstrates a promising approach for detecting PSA in a clinical diagnosis.