The anterior cingulate cortex (ACC) and visual cortex are integral components of the neurophysiological mechanisms underlying migraine, yet the impact of altered connectivity patterns between these ...regions on migraine treatment remains unknown. To elucidate this issue, we investigated the abnormal causal connectivity between the ACC and visual cortex in patients with migraine without aura (MwoA), based on the resting‐state functional magnetic resonance imaging data, and its predictive ability for the efficacy of nonsteroidal anti‐inflammatory drugs (NSAIDs). The results revealed increased causal connectivity from the bilateral ACC to the lingual gyrus (LG) and decreased connectivity in the opposite direction in nonresponders compared with the responders. Moreover, compared with the healthy controls, nonresponders exhibited heightened causal connectivity from the ACC to the LG, right inferior occipital gyrus (IOG) and left superior occipital gyrus, while connectivity patterns from the LG and right IOG to the ACC were diminished. Based on the observed abnormal connectivity patterns, the support vector machine (SVM) models showed that the area under the receiver operator characteristic curves for the ACC to LG, LG to ACC and bidirectional models were 0.857, 0.898, and 0.939, respectively. These findings indicate that neuroimaging markers of abnormal causal connectivity in the ACC‐visual cortex circuit may facilitate clinical decision‐making regarding NSAIDs administration for migraine management.
This article explored the abnormal causal connectivity of the anterior cingulate cortex‐visual cortex circuit between migraine without aura (MwoA) with and without response to nonsteroidal anti‐inflammatory drugs (NSAIDs) and its ability to predict the efficacy of NSAIDs based on the machine learning models. The relationship between the causal connectivity patterns and treatment outcomes can provide new insights into clinical decision‐making to improve the efficacy of individual migraine management.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC ...intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.
The ester-amide exchange reaction enables spontaneous formation of prebiotic proto-peptides under mild conditions. However, this reaction also leads to oligomers with a vast sequence diversity of ...ester and amide linkages. Here, we demonstrate using deep eutectic solvents as a universal strategy to regulate the reaction pathways and promote the formation of amino acid-enriched oligomers with peptide backbones.
Deep eutectic solvents enable efficient growth of proto-peptides with low sequence complexity.
The recent discovery of magnetism within the family of exfoliatable van der Waals (vdW) compounds has attracted considerable interest in these materials for both fundamental research and ...technological applications. However, current vdW magnets are limited by their extreme sensitivity to air, low ordering temperatures, and poor charge transport properties. Here the magnetic and electronic properties of CrSBr are reported, an air‐stable vdW antiferromagnetic semiconductor that readily cleaves perpendicular to the stacking axis. Below its Néel temperature, TN = 132 ± 1 K, CrSBr adopts an A‐type antiferromagnetic structure with each individual layer ferromagnetically ordered internally and the layers coupled antiferromagnetically along the stacking direction. Scanning tunneling spectroscopy and photoluminescence (PL) reveal that the electronic gap is ΔE = 1.5 ± 0.2 eV with a corresponding PL peak centered at 1.25 ± 0.07 eV. Using magnetotransport measurements, strong coupling between magnetic order and transport properties in CrSBr is demonstrated, leading to a large negative magnetoresistance response that is unique among vdW materials. These findings establish CrSBr as a promising material platform for increasing the applicability of vdW magnets to the field of spin‐based electronics.
CrSBr is an air‐stable, intrinsically magnetic, van der Waals semiconductor with an electronic bandgap ∆E = 1.5 ± 0.2 eV and photoluminescence peak centered at 1.25 ± 0.07 eV. Magnetometry and magnetotransport measurements demonstrate that CrSBr exhibits intraplanar ferromagnetic ordering and interplanar antiferromagnetic ordering below TN ≈ 132 ± 1 K, producing a large intrinsic negative magnetoresistance.
Crystal engineering of the nbo metal–organic framework (MOF) platform MOF‐505 with a custom‐designed azamacrocycle ligand (1,4,7,10‐tetrazazcyclododecane‐N,N′,N′′,N′′′‐tetra‐p‐methylbenzoic acid) ...leads to a high density of well‐oriented Lewis active sites within the cuboctahedral cage in MMCF‐2, Cu2(Cu‐tactmb)(H2O)3(NO3)2. This MOF demonstrates high catalytic activity for the chemical fixation of CO2 into cyclic carbonates at room temperature under 1 atm pressure.
High catalytic activity for chemical fixation of CO2 into cyclic carbonates under ambient conditions has been demonstrated in the metal–organic framework (MOF) MMCF‐2 (see picture; C gray, O red, N blue, Cu pale blue). This MOF features a high density of well‐oriented Lewis acid active sites within the cuboctahedral cage.
Realization of ideal molecular sieves, in which the larger gas molecules are completely blocked without sacrificing high adsorption capacities of the preferred smaller gas molecules, can ...significantly reduce energy costs for gas separation and purification and thus facilitate a possible technological transformation from the traditional energy‐intensive cryogenic distillation to the energy‐efficient, adsorbent‐based separation and purification in the future. Although extensive research endeavors are pursued to target ideal molecular sieves among diverse porous materials, over the past several decades, ideal molecular sieves for the separation and purification of light hydrocarbons are rarely realized. Herein, an ideal porous material, SIFSIX‐14‐Cu‐i (also termed as UTSA‐200), is reported with ultrafine tuning of pore size (3.4 Å) to effectively block ethylene (C2H4) molecules but to take up a record‐high amount of acetylene (C2H2, 58 cm3 cm−3 under 0.01 bar and 298 K). The material therefore sets up new benchmarks for both the adsorption capacity and selectivity, and thus provides a record purification capacity for the removal of trace C2H2 from C2H4 with 1.18 mmol g−1 C2H2 uptake capacity from a 1/99 C2H2/C2H4 mixture to produce 99.9999% pure C2H4 (much higher than the acceptable purity of 99.996% for polymer‐grade C2H4), as demonstrated by experimental breakthrough curves.
An ideal molecular sieve is realized for the highly efficient removal of C2H2 from C2H2/C2H4 (1:99) mixture, attributed to the optimized pore sizes to efficiently block C2H4 molecules, and strong binding sites to take up a record‐high amount of C2H2, thus simultaneously producing high purity C2H4 (99.9999%) with record C2H4 productivity of 87.5 mmol g−1 per cycle and recovery of C2H2 (97%).
Although 5-methylcytosine (m
C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the ...single-nucleotide resolution landscape of messenger RNA m
C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m
C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m
C 'reader' recognizing m
C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m
C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m
C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.
Understanding the electronic structures of high‐valent metal complexes aids the advancement of metal‐catalyzed cross coupling methodologies. A prototypical complex with formally high valency is ...Cu(CF3)4− (1), which has a formal Cu(III) oxidation state but whose physical analysis has led some to a Cu(I) assignment in an inverted ligand field model. Recent examinations of 1 by X‐ray spectroscopies have led previous authors to contradictory conclusions, motivating the re‐examination of its X‐ray absorption profile here by a complementary method, resonant diffraction anomalous fine structure (DAFS). From analysis of DAFS measurements for a series of seven mononuclear Cu complexes including 1, here it is shown that there is a systematic trifluoromethyl effect on X‐ray absorption that blue shifts the resonant Cu K‐edge energy by 2–3 eV per CF3, completely accounting for observed changes in DAFS profiles between formally Cu(III) complexes like 1 and formally Cu(I) complexes like (Ph3P)3CuCF3 (3). Thus, in agreement with the inverted ligand field model, the data presented herein imply that 1 is best described as containing a Cu(I) ion with dn count approaching 10.
The electronic structures of Cu(CF3)4− and other Cu−CF3 complexes are (re−)evaluated using resonant X‐ray diffraction methods. A systematic trend was identified by which each additional CF3 ligand shifts the resonant Cu K‐edge energy by 2–3 eV, completely accounting for observed differences between complexes with different formal oxidation states. The recently debated assignment of Cu(CF3)4− as containing a Cu(I) ion is, thus, verified.
Metal-organic frameworks (MOFs) have recently garnered consideration as an attractive solid substrate because the highly tunable MOF framework can not only serve as an inert host but also enhance the ...selectivity, stability, and/or activity of the enzymes. Herein, we demonstrate the advantages of using a mechanochemical strategy to encapsulate enzymes into robust MOFs. A range of enzymes, namely β-glucosidase, invertase, β-galactosidase, and catalase, are encapsulated in ZIF-8, UiO-66-NH
, or Zn-MOF-74 via a ball milling process. The solid-state mechanochemical strategy is rapid and minimizes the use of organic solvents and strong acids during synthesis, allowing the encapsulation of enzymes into three prototypical robust MOFs while maintaining enzymatic biological activity. The activity of encapsulated enzyme is demonstrated and shows increased resistance to proteases, even under acidic conditions. This work represents a step toward the creation of a suite of biomolecule-in-MOF composites for application in a variety of industrial processes.
PDF
