ABSTRACT
Here, we report a silver carbene-enabled single-carbon insertion reaction of indoles via a one-pot, two-step sequence to deliver a dearomative quaternary center quinoline scaffold in a modular fashion. Specifically, we used N-triftosylhydrazones as masked donor-donor carbene precursors that facilitate the insertion of carbon atoms bearing various functional groups to the library of functionalized quinoline. Experimental and DFT evidence support the transient presence of a cyclopropane species and removal of protecting groups.
ABSTRACT
Gestational diabetes mellitus (GDM) presents varied manifestations throughout pregnancy and poses a complex clinical challenge. High-depth cell-free DNA (cfDNA) sequencing analysis holds promise in advancing our understanding of GDM pathogenesis and prediction. In 299 women with GDM and 299 matched healthy pregnant women, distinct cfDNA fragment characteristics associated with GDM are identified throughout pregnancy. Integrating cfDNA profiles with lipidomic and single-cell transcriptomic data elucidates functional changes linked to altered lipid metabolism processes in GDM. Transcription start site (TSS) scores in 50 feature genes are used as the cfDNA signature to distinguish GDM cases from controls effectively. Notably, differential coverage of the islet acinar marker gene PRSS1 emerges as a valuable biomarker for GDM. A specialized neural network model is developed, predicting GDM occurrence and validated across two independent cohorts. This research underscores the high-depth cfDNA early prediction and characterization of GDM, offering insights into its molecular underpinnings and potential clinical applications.
Subject(s)
Cell-Free Nucleic Acids , Diabetes, Gestational , Humans , Diabetes, Gestational/genetics , Diabetes, Gestational/diagnosis , Diabetes, Gestational/blood , Female , Pregnancy , Cell-Free Nucleic Acids/genetics , Cell-Free Nucleic Acids/blood , Adult , Biomarkers/metabolism , Biomarkers/blood , Case-Control Studies , Longitudinal Studies , Transcriptome/geneticsABSTRACT
The chemical constituents from the stems and leaves of Artocarpus tonkinensis in Artocarpus of Moraceae were systematically studied by means of silica gel, octadecylsilyl(ODS), and Sephadex LH-20 gel column chromatographies, as well as preparative high-performance liquid chromatography(Pre-HPLC) and a variety of chromatographic separation techniques. The spectral data and physicochemical properties of the compounds were obtained from separation and compared with those of the compounds reported in the literature. As a result, 11 compounds isolated from the 90% ethanol extract of the stems and leaves of A. tonkinensis were identified as artocatonkine(1), 5,6,7,4'-tetramethoxyflavone(2), apigenin-4'-O-ß-D-glucoside(3), rayalinol(4), psorachalcone A(5), 4-ketopinoresinol(6), ficusesquilignan B(7), pinnatifidanin AI(8), pinnatifidanin A(9), O-methylmellein(10), and trans-4-hydroxymellein(11). Among these compounds, compound 1 was a new prenylated flavone, and compounds 2-11 were isolated from the plants belonging to the genus Artocarpus for the first time. Furthermore, all compounds 1-11 were evaluated for their anti-rheumatoid arthritis activities, and the MTS method was used to measure their inhibitory effects on the proliferation of synovioblasts in vitro. The results of activity evaluation showed that flavonoid compounds 1-3, 5, and lignan compounds 8 and 9 displayed significant anti-rheumatoid arthritis activities, showing the IC_(50) values in inhibiting the proliferation of synovioblasts MH7A from(6.38±0.06) µmol·L~(-1) to(168.58±0.28)µmol·L~(-1).
Subject(s)
Artocarpus , Cell Proliferation , Plant Leaves , Plant Stems , Artocarpus/chemistry , Plant Leaves/chemistry , Plant Stems/chemistry , Cell Proliferation/drug effects , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Cell Line , Molecular Structure , Chromatography, High Pressure LiquidABSTRACT
In order to develop a highly efficient H2S gas sensor at low working temperature, in this work, a kind of novel Ce-doped ZnCo2O4 hollow microspheres (Ce/ZnCo2O4 HMSs) were successfully synthesized using a template-free one-pot method, showing a sensitive response toward H2S. The microstructure and morphology of the material were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The gas-sensing performance of the composite was investigated, showing that the ZnCo2O4 doped with 6 mol% Ce had the highest response to 20 ppm H2S at a low operating temperature of 160 °C with a response value of 67.42, which was about 2 times higher than that of original ZnCo2O4. The prepared Ce/ZnCo2O4 HMS sensor in response to H2S exhibited a linear range of 0.1-200 ppm with a low detection limit of 0.1 ppm under the conditions of ambient humidity of 45% and ambient temperature of 20 °C. Meanwhile, it also possessed good selectivity, repeatability and reproducibility. The response value of the sensor decreased by 5.32% after 7 months of continuous monitoring of H2S in an atmospheric environment of a pig farm, indicating that the sensor had a long-term stability and continuous service life with important application prospects.
ABSTRACT
High aerosol loadings are observed not only in megacities on continents but also in oceanic regions like the Bohai Sea. This work provides a comprehensive analysis of the spatial and temporal variations in Aerosol Optical Depth (AOD) across different ocean regions worldwide over the past four decades, using remote sensing reanalysis data. The mean AOD value across all oceanic grids is approximately 0.112, with higher levels recorded in the Central Atlantic (~0.206), followed by the North Indian Ocean (~0.201), and the Western North Pacific (~0.197). A latitudinal analysis reveals that high AOD values are predominantly found in the Northern Hemisphere's oceanic regions, especially between latitudes 0° and 70° N. Except for the Gulf of California and Hudson Bay, AOD values in the other fourteen surveyed inland seas surpass the mean levels found at similar latitudes in oceanic regions. Among which, the Bohai Sea stands out as the most polluted oceanic region with AOD value of 0.35. Over the last four decades, AOD trends have revealed a significant decrease across about 89.5 % of global oceanic grids, while an increase in AOD is observed in low-latitude oceanic areas (30° S-30° N). Investigation into inland seas shows that nearly two-thirds have experienced a declining AOD trend, while sharply upward trends in AOD are primarily found in Asia. The Bohai Sea shows the largest increase in AOD, with an annual growth rate of 1.4 %. The turning-points of the AOD in each inland sea confirm the success of regional emission control policies initiated on the adjacent continents. To improve air quality in inland seas like the Bohai Sea, adjusting industrial layouts, such as relocating heavy industries from the surrounding coastal cities' proximities to areas near open seas, could significantly benefit public health.
ABSTRACT
Non-invasive prenatal testing (NIPT) is a quite popular approach for detecting fetal genomic aneuploidies. However, due to the limitations on sequencing read length and coverage, NIPT suffers a bottleneck on further improving performance and conducting earlier detection. The errors mainly come from reference biases and population polymorphism. To break this bottleneck, we proposed NIPT-PG, which enables the NIPT algorithm to learn from population data. A pan-genome model is introduced to incorporate variant and polymorphic loci information from tested population. Subsequently, we proposed a sequence-to-graph alignment method, which considers the read mis-match rates during the mapping process, and an indexing method using hash indexing and adjacency lists to accelerate the read alignment process. Finally, by integrating multi-source aligned read and polymorphic sites across the pan-genome, NIPT-PG obtains a more accurate z-score, thereby improving the accuracy of chromosomal aneuploidy detection. We tested NIPT-PG on two simulated datasets and 745 real-world cell-free DNA sequencing data sets from pregnant women. Results demonstrate that NIPT-PG outperforms the standard z-score test. Furthermore, combining experimental and theoretical analyses, we demonstrate the probably approximately correct learnability of NIPT-PG. In summary, NIPT-PG provides a new perspective for fetal chromosomal aneuploidies detection. NIPT-PG may have broad applications in clinical testing, and its detection results can serve as a reference for false positive samples approaching the critical threshold.
Subject(s)
Aneuploidy , Noninvasive Prenatal Testing , Humans , Female , Pregnancy , Noninvasive Prenatal Testing/methods , Algorithms , Genomics/methods , Prenatal Diagnosis/methods , Sequence Analysis, DNA/methodsABSTRACT
Layered or chain materials have received significant research attention owing to their interesting physical properties, which can dramatically change when the material is thinned from bulk (three-dimensional) to thin two-dimensional sheet or one-dimensional (1D) chain form. Materials with the stoichiometry AX2 with A = Si or Ge and X = S or Se form an especially intriguing semiconducting class. For example, bulk silicon dichalcogenides (SiX2) consist of 1D chains held together by van der Waals forces. Although this structural configuration has the potential to reveal interesting physical phenomena within the 1D limit, obtaining SiX2 single chains has been challenging. We here examine experimentally and theoretically SiX2 materials in the low chain number limit. Carbon nanotubes serve as growth templates and stabilize and protect the structures, and atomic-resolution scanning transmission electron microscopy directly identifies the atomic structure. Two distinct chain structures are observed for SiX2. SixGe1-xS2(1-y)Se2y quaternary alloy chains are also synthesized and characterized, demonstrating tunable semiconducting properties at the atomic-chain level. Density functional theory calculations reveal that the band gap of these alloy chains can be widely tuned through composition engineering. This work offers the possibilities for synthesizing and controlling semiconductor compositions at the single-chain limit to tailor material properties.
ABSTRACT
Van der Waals (vdW) ferromagnetic materials have emerged as a promising platform for the development of 2D spintronic devices. However, studies to date are restricted to vdW ferromagnetic materials with low Curie temperature (Tc) and small magnetic anisotropy. Here, a chemical vapor transport method is developed to synthesize a high-quality room-temperature ferromagnet, Fe3GaTe2 (c-Fe3GaTe2), which boasts a high Tc = 356 K and large perpendicular magnetic anisotropy. Due to the planar symmetry breaking, an unconventional room-temperature antisymmetric magnetoresistance (MR) is first observed in c-Fe3GaTe2 devices with step features, manifesting as three distinctive states of high, intermediate, and low resistance with the sweeping magnetic field. Moreover, the modulation of the antisymmetric MR is demonstrated by controlling the height of the surface steps. This work provides new routes to achieve magnetic random storage and logic devices by utilizing the room-temperature thickness-controlled antisymmetric MR and further design room-temperature 2D spintronic devices based on the vdW ferromagnet c-Fe3GaTe2.
ABSTRACT
Epoxides, as a prominent small ring O-heterocyclic and the privileged pharmacophores for medicinal chemistry, have recently represented an ideal substrate for the development of single-atom replacements. The previous O-to-C replacement strategy for epoxides to date typically requires high temperatures to achieve low yields and lacks substrate range and functional group tolerance, so achieving this oxygen-carbon exchange remains a formidable challenge. Here, we report a silver-catalyzed direct conversion of epoxides into trifluoromethylcyclopropanes in a single step using trifluoromethyl N-triftosylhydrazones as carbene precursors, thereby achieving oxygen-carbon exchange via a tandem deoxygenation/[2 + 1] cycloaddition. The reaction shows broad tolerance of functional groups, allowing routine cheletropic olefin synthesis in a strategy for the net oxygen-carbon exchange reaction. The utility of this method is further showcased with the late-stage diversification of epoxides derived from bioactive natural products and drugs. Mechanistic experiments and DFT calculations elucidate the reaction mechanism and the origin of the chemo- and stereoselectivity.
ABSTRACT
Understanding tissue architecture and niche-specific microenvironments in spatially resolved transcriptomics (SRT) requires in situ annotation and labeling of cells. Effective spatial visualization of these data demands appropriate colorization of numerous cell types. However, current colorization frameworks often inadequately account for the spatial relationships between cell types. This results in perceptual ambiguity in neighboring cells of biological distinct types, particularly in complex environments such as brain or tumor. To address this, we introduce Spaco, a potent tool for spatially aware colorization. Spaco utilizes the Degree of Interlacement metric to construct a weighted graph that evaluates the spatial relationships among different cell types, refining color assignments. Furthermore, Spaco incorporates an adaptive palette selection approach to amplify chromatic distinctions. When benchmarked on four diverse datasets, Spaco outperforms existing solutions, capturing complex spatial relationships and boosting visual clarity. Spaco ensures broad accessibility by accommodating color vision deficiency and offering open-accessible code in both Python and R.
ABSTRACT
Given the prevalence of heterocyclic scaffolds in drug-related molecules, converting these highly modular heterocyclic scaffolds into structural diversified and dearomatized analogs is an ideal strategy for improving their physicochemical and pharmacokinetic properties. Here, we described an efficient method for silver carbene-mediated dearomative N-N bond cleavage leading to skeletal hopping between indazole and 1,2-dihydroquinazoline via a highly selective single-carbon insertion procedure. Using this methodology, a series of dihydroquinazoline analogues with diarylmethylene-substituted quaternary carbon centers were constructed with excellent yields and good functional group compatibility, which was further illustrated by the late-stage diversification of important pharmaceutically active ingredients. DFT calculations indicated that the silver catalyst not only induces the formation of the silver carbene, but also activates the diazahexatriene intermediate, which plays a crucial role in the formation of the C-N bond.
ABSTRACT
The skeletal ring expansion of heteroarenes through carbene insertion is gaining popularity in synthetic chemistry. Efficient strategies for heterocyclic ring expansion to access heterocycles containing a fluoroalkyl quaternary carbon center through fluoroalkyl carbene insertion are highly desirable because of their broad applications in medicinal chemistry. Herein, we report a general strategy for the dearomative one-carbon insertion of azoles using fluoroalkyl N-triftosylhydrazones as fluoroalkyl carbene precursors, resulting in ring-expanded heterocycles in excellent yields with good functional-group compatibility. The broad generality of this methodology in the late-stage diversification of pharmaceutically interesting bioactive molecules and versatile transformations of the products has been demonstrated.
ABSTRACT
Air pollution over the oceans has received less attention compared to densely populated urban areas of continents. The Bohai Sea, a semi-enclosed sea in northern China, is surrounded by thirteen industrial cities that have experienced significant improvements in air quality over the past decade. However, the changes in air pollution over the Bohai Sea and its impacts on surrounding cities remain poorly understood. To address this, this study investigated the evolution of air pollution and its chemical composition in the Bohai Sea over four decades, utilizing satellite remote sensing data, reanalysis datasets, emissions inventories, and statistical modeling. Historically, the region has suffered from severe air pollution, resulting from a combination of continental emissions and marine inputs (e.g., sea salt, ports and maritime vessel activities). The aerosol optical depth (AOD) over the sea was higher than the mean levels observed in its surrounding coastal cities. Statistically, 45% of the air masses reaching the Bohai Sea are associated with natural sources (dust- and marine-rich), while the remainder carry anthropogenic pollutants from continental regions. With the exception of Cangzhou city, these coastal cities suffer from air pollutants originating from the Bohai Sea. Cities in the northern region of the sea, spanning from Tianjin to Yingkou, are particularly impacted. The majority of the surrounding cities are affected by a large proportion of anthropogenic aerosol types transported through air masses from the Bohai Sea, including those from biomass burning and industrial activities. These findings emphasize the considerable influence of human-induced sources in the Bohai Sea on neighboring urban areas. Furthermore, being a maritime region, natural sources like sea salt and dust from the sea may also exert a discernible impact on the neighboring environment.
Subject(s)
Air Pollutants , Air Pollution , Humans , Cities , Air Pollutants/analysis , Dust/analysis , Air Pollution/analysis , China , Aerosols/analysis , Environmental Monitoring/methodsABSTRACT
Precision medicine depends on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is still not suitable for gigantic studies due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we used 10 000 samples with medium-depth WGS to construct a reference panel that we named the CKB reference panel. By imputing microarray datasets, it showed that the CKB panel outperformed compared panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of 100 706 microarrays with the CKB panel, and the after-imputed data is the hitherto largest whole genome data of the Chinese population. Furthermore, in the GWAS analysis of real phenotype height, the number of tested SNPs tripled and the number of significant SNPs doubled after imputation. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the CKB panel is of great value for imputing microarray or low-coverage genotype data of Chinese population, and potentially mixed populations. The imputation-completed 100 706 microarray data are enormous and precious resources of population genetic studies for complex traits and diseases.
Subject(s)
Biological Specimen Banks , Genome , Humans , Haplotypes , Genotype , Genome-Wide Association Study , Polymorphism, Single Nucleotide , ChinaABSTRACT
Spider silk is biocompatible, biodegradable, and rivals some of the best synthetic materials in terms of strength and toughness. Despite extensive research, comprehensive experimental evidence of the formation and morphology of its internal structure is still limited and controversially discussed. Here, we report the complete mechanical decomposition of natural silk fibers from the golden silk orb-weaver Trichonephila clavipes into ≈10 nm-diameter nanofibrils, the material's apparent fundamental building blocks. Furthermore, we produced nanofibrils of virtually identical morphology by triggering an intrinsic self-assembly mechanism of the silk proteins. Independent physico-chemical fibrillation triggers were revealed, enabling fiber assembly from stored precursors "at-will". This knowledge furthers the understanding of this exceptional material's fundamentals, and ultimately, leads toward the realization of silk-based high-performance materials. STATEMENT OF SIGNIFICANCE: Spider silk is one of the strongest and toughest biomaterials, rivaling the best man-made materials. The origins of these traits are still under debate but are mostly attributed to the material's intriguing hierarchical structure. Here we fully disassembled spider silk into 10 nm-diameter nanofibrils for the first time and showed that nanofibrils of the same appearance can be produced via molecular self-assembly of spider silk proteins under certain conditions. This shows that nanofibrils are the key structural elements in silk and leads toward the production of high-performance future materials inspired by spider silk.
Subject(s)
Silk , Spiders , Animals , Silk/chemistry , Biocompatible Materials/metabolism , Spiders/metabolismABSTRACT
Ligusticum chuanxiong Hort. (Chuanxiong) is an important Chinese medicinal herb, whose rhizomes are widely used as raw materials for treating various diseases caused by blood stasis. The fresh tender stems and leaves of Chuanxiong are also consumed and have the potential as microgreens. Here, we investigated the effect of light spectra on yield and total flavonoid content of Chuanxiong microgreens by treatment with LED-based white light (WL), red light (RL), blue light (BL), and continuous darkness (DD). The results showed that WL and BL reduced biomass accumulation but significantly increased total flavonoid content compared to RL or DD treatments. Widely targeted metabolomics analysis confirmed that BL promoted the accumulation of flavones and flavonols in Chuanxiong microgreens. Further integration of transcriptomics and metabolomics analysis revealed the mechanism by which BL induces the up-regulation of transcription factors such as HY5 and MYBs, promotes the expression of key genes targeted for flavonoid biosynthesis, and ultimately leads to the accumulation of flavones and flavonols. This study suggests that blue light is a proper light spectra to improve the quality of Chuanxiong microgreens, and the research results lay a foundation for guiding the de-etiolation of Chuanxiong microgreens to obtain both yield and quality in production practice.
Subject(s)
Flavones , Ligusticum , Flavonols , Transcriptome , Flavonoids , MetabolomicsABSTRACT
In this work, a new type of H2S sensor was fabricated by means of drop-coating of an Au/SnO-SnO2 nanosheet material, which was prepared by a one-pot hydrothermal reaction, onto a gold electrode in an alumina ceramic tube with the formation of a thin nanocomposite film. The microstructure and morphology of the nanosheet composites were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A gas-sensitivity study presented good H2S-sensing performance of such Au/SnO-SnO2 nanosheet composites. At an optimal operating temperature of 240 °C and ambient temperature of 25 °C, the resulting sensor showed a good linear response to H2S in a range of 1.0 to 100 ppm with a low detection limit of 0.7 ppm, and a very fast response-recovery time of 22 s for response and 63 s for recovery, respectively. The sensor was also unaffected by ambient humidity and had good reproducibility and selectivity. When being applied to the monitoring of H2S in an atmospheric environment in a pig farm, the response signal to H2S was only attenuated by 4.69% within 90 days, proving that the sensor had a long and stable service lifetime for continuous running and showing its important practical application prospects.
ABSTRACT
INTRODUCTION: During the arms race between plants and pathogens, pathogenesis-related proteins (PR) in host plants play a crucial role in disease resistance, especially PR1. PR1 constitute a secretory peptide family, and their role in plant defense has been widely demonstrated in both hosts and in vitro. However, the mechanisms by which they control host-pathogen interactions and the nature of their targets within the pathogen remain poorly understood. OBJECTIVES: The present study was aimed to investigate the anti-oomycete activity of secretory PR1 proteins and elaborate their underlying mechanisms. METHODS: This study was conducted in the potato-Phytophthora infestans pathosystem. After being induced by the pathogen infection, the cross-kingdom translocation of secretory PR1 was demonstrated by histochemical assays and western blot, and their targets in P. infestans were identified by yeast-two-hybrid assays, bimolecular fluorescence complementation assays, and co-immunoprecipitation assay. RESULTS: The results showed that the expression of secretory PR1-encoding genes was induced during pathogen infection, and the host could deliver PR1 into P. infestans to inhibit its vegetative growth and pathogenicity. The translocated secretory PR1 targeted the subunits of the AMPK kinase complex in P. infestans, thus affecting the AMPK-driven phosphorylation of downstream target proteins, preventing ROS homeostasis, and down-regulating the expression of RxLR effectors. CONCLUSION: The results provide novel insights into the molecular function of PR1 in protecting plants against pathogen infection, and uncover a potential target for preventing pre- and post-harvest late blight.
Subject(s)
AMP-Activated Protein Kinase Kinases , Phytophthora infestans , Plants , Phytophthora infestans/genetics , Host-Pathogen Interactions , Disease Resistance/geneticsABSTRACT
The role of chloride in atmospheric chemistry received increased attention over recent years. Given the primary and chemical-active nature of PM2.5-bound chlorine (p-Cl-), it makes sense to get to know the sources and processes of p-Cl-. The temporal behavior of observed p-Cl- concentration based on 1-h high resolution exhibited seasonal variation of high in winter, low in summer and diurnal variation of high in the morning, low in afternoon. Meteorological normalization technique based on random forest was used to disentangle the effects of emission changes which affected the seasonal variation and meteorology which was related to diurnal variation on p-Cl-. Generalized additive model (GAM) identified RH and temperature as the key meteorological factors of p-Cl- generation, and p-Cl- pollution was serious under the condition of low temperature and high RH. Dispersion-normalized positive matrix factorization (DN-PMF) was used to apportion the p-Cl- to its sources, finding that coal combustion was the main source of p-Cl-, followed by biomass burning and industrial process emissions. Our results will provide the basis for further analysis the causes of p-Cl- pollution and composite air pollution control strategies.
Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , China , Chlorides , Chlorine/analysis , Coal/analysis , Environmental Monitoring , Meteorology , Particulate Matter/analysis , Seasons , Vehicle Emissions/analysisABSTRACT
Catalytic carbene transfer reactions are fundamental transformations in modern organic synthesis, which enable direct access to diverse structurally complex molecules. Despite diazo precursors playing a crucial role in catalytic carbene transfer reactions, most reported methodologies take into account only diazoacetates or related compounds. This is primarily because diazoalkanes, unless they contain a resonance stabilizing group, are more susceptible to violent exothermic decomposition. In this feature article, we present an alternative approach to carbene-transfer reactions based on the formation of highly electrophilic silver carbenes from N-sulfonylhydrazones, where the high electrophilicity of silver carbenes stems from the weak interaction between silver and the carbenic carbon. These precursors are readily accessible, stable, and environmentally sustainable. Using the strategy that employs highly electrophilic silver carbenes, it is possible to develop novel intermolecular transformations involving non-stabilized carbenes, including C(sp3)-H insertion, C(sp3)-C(O) insertion, cycloaddition, and defluorinative functionalization. The silver-catalyzed carbene transfer reactions described here have high efficiency, unusual reactivity, exceptional selectivity, and a reaction pathway that differs from typical transition metal-catalyzed reactions. Our research provided fundamental insight into silver carbene chemistry, and we hope to apply this mode of catalysis to other more general transformations, including asymmetric transformations.