Spatially resolved epigenomic profiling of single cells in complex tissues.

The recent development of spatial omics methods has enabled single-cell profiling of the transcriptome and 3D genome organization with high spatial resolution. Expanding the repertoire of spatial omics tools, a spatially resolved single-cell epigenomics method will accelerate understanding of the spatial regulation of cell and tissue functions. Here, we report a method for spatially resolved epigenomic profiling of single cells using in situ tagmentation and transcription followed by multiplexed imaging. We demonstrated the ability to profile histone modifications marking active promoters, putative enhancers, and silent promoters in individual cells, and generated high-resolution spatial atlas of hundreds of active promoters and putative enhancers in embryonic and adult mouse brains. Our results suggested putative promoter-enhancer pairs and enhancer hubs regulating developmentally important genes. We envision this approach will be generally applicable to spatial profiling of epigenetic modifications and DNA-binding proteins, advancing our understanding of how gene expression is spatiotemporally regulated by the epigenome.

Multi-organ proteomic landscape of COVID-19 autopsies.

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

CYCLOIDEA-like genes control floral symmetry, floral orientation, and nectar guide patterning.

Actinomorphic flowers usually orient vertically (relative to the horizon) and possess symmetric nectar guides, while zygomorphic flowers often face horizontally and have asymmetric nectar guides, indicating that floral symmetry, floral orientation, and nectar guide patterning are correlated. The origin of floral zygomorphy is dependent on the dorsoventrally asymmetric expression of CYCLOIDEA (CYC)-like genes. However, how horizontal orientation and asymmetric nectar guides are achieved remains poorly understood. Here, we selected Chirita pumila (Gesneriaceae) as a model plant to explore the molecular bases for these traits. By analyzing gene expression patterns, protein-DNA and protein-protein interactions, and encoded protein functions, we identified multiple roles and functional divergence of 2 CYC-like genes, i.e. CpCYC1 and CpCYC2, in controlling floral symmetry, floral orientation, and nectar guide patterning. CpCYC1 positively regulates its own expression, whereas CpCYC2 does not regulate itself. In addition, CpCYC2 upregulates CpCYC1, while CpCYC1 downregulates CpCYC2. This asymmetric auto-regulation and cross-regulation mechanism might explain the high expression levels of only 1 of these genes. We show that CpCYC1 and CpCYC2 determine asymmetric nectar guide formation, likely by directly repressing the flavonoid synthesis-related gene CpF3'5'H. We further suggest that CYC-like genes play multiple conserved roles in Gesneriaceae. These findings shed light on the repeated origins of zygomorphic flowers in angiosperms.

Multi-field-driven optomechanical entanglement.

Cavity optomechanical (COM) entanglement, playing an essential role in building quantum networks and enhancing quantum sensors, is usually weak and easily destroyed by noises. As feasible and effective ways to overcome this obstacle, optical or mechanical parametric modulations have been used to improve the quality of quantum squeezing or entanglement in various COM systems. However, the possibility of combining these powerful means to enhance COM entanglement has yet to be explored. Here, we fill this gap by studying a COM system containing an intra-cavity optical parametric amplifier (OPA), driven optically and mechanically. By tuning the relative strength and the frequency mismatch of optical and mechanical driving fields, we find that constructive interference can emerge and significantly improve the strength of COM entanglement and its robustness to thermal noises. This work sheds what we believe to be a new light on preparing and protecting quantum states with multi-field driven COM systems for diverse applications.

Theoretical Prediction and Comprehensive Characterization of an All-Nitrogenatomic Ring, Cyclo[18]Nitrogen (N18).

The cyclic molecule cyclo[18]carbon composed of 18 carbon atoms has been observed in condensed phase experiment in recent years and has attracted great attention. Through state-of-art quantum chemistry calculation, this study found that 18 nitrogen atoms can also form a macrocyclic system, cyclo[18]nitrogen (N18), though its lifetime is very short at room temperature and can only exist for a relatively long time at very low temperatures. We comprehensively theoretically studied properties of N18, including geometric configurations, thermal decomposition mechanism and rate, molecular dynamics behavior, energetic properties, vibrational and electronic spectra. We also discussed in depth the electronic structure of N18, including nature of the N-N bonds, lone-pairs, charge distribution characteristics, electronic delocalization, and aromaticity. This work is not only the first exploration of the macrocyclic N18 molecule, but also the first time to systematically examine a very long-chain substance fully composed of nitrogen atoms in isolated state.

Ultrafast Axial Freezing in a Liquid-Filled Capillary Tube.

Liquid-filled capillary tubes are a kind of standard component in life science (e.g., blood vessels, interstitial pores, and plant vessels) and engineering (e.g., MEMS microchannel resonators, heat pipe wicks, and water-saturated soils). Under sufficiently low temperatures, the liquid in a capillary tube undergoes phase transition, forming an ice nucleus randomly on its inner wall. However, how an ice layer forms from the nucleus and then expands, either axially or radially to the tube inner wall, remains obscure. We demonstrated, both experimentally and theoretically, that axial freezing along the inner wall of a water-filled capillary tube occurs way ahead of radial freezing, at a nearly constant velocity 3 orders in magnitude faster than the latter. Rapid release of latent heat during axial freezing was identified as the determining factor for the short duration of recalescence, resulting in an exponential rise of the supercooling temperature from ice nucleation via axial freezing to radial freezing. The profile of the ice-water interface is strongly dependent upon the length-to-radius ratio of the capillary tube and the supercooling degree at ice nucleation. The results obtained in this study bridge the knowledge gap between the classical nucleation theory and the Stefan solution of phase transition.

Characteristics of intestinal bacteriophages and their relationship with Bacteria and serum metabolites during quail sexual maturity transition.

BACKGROUND: Bacteriophages are prokaryotic viruses that rank among the most abundant microbes in the gut but remain among the least understood, especially in quails. In this study, we surveyed the gut bacteriophage communities in 22 quails at different ages (days 20 and 70) using shotgun metagenomic sequencing. We then systematically evaluated the relationships with gut bacteria and host serum metabolites. RESULTS: We discovered that Myoviridae and Siphoviridae were the dominant bacteriophage families in quails. Through a random forest and LEfSe analysis, we identified 23 differential bacteriophages with overlapping presence. Of these, 21 bacteriophages (e.g., Enterococcus phage IME-EFm5 and Enterococcus phage IME-EFm1) showed higher abundances in the day 20 group, while two bacteriophages (Bacillus phage Silence and Bacillus virus WPh) were enriched in the day 70 group. These key bacteriophages can serve as biomarkers for quail sexual maturity. Additionally, the differential bacteriophages significantly correlated with specific bacterial species and shifts in the functional capacities of the gut microbiome. For example, Enterococcus phages (e.g., Enterococcus phage EFP01, Enterococcus phage IME-EFm5, and Enterococcus phage IME-EFm1) were significantly (P < 0.001, FDR) and positively correlated with Enterococcus faecalis. However, the relationships between the host serum metabolites and either bacteriophages or bacterial species varied. None of the bacteriophages significantly (P > 0.05, FDR) correlated with nicotinamide riboside and triacetate lactone. In contrast, some differential bacterial species (e.g., Christensenella massiliensis and Bacteroides neonati) significantly (P < 0.05, FDR) correlated with nicotinamide riboside and triacetate lactone. Furthermore, characteristic successional alterations in gut bacteriophages, bacteria, and host serum metabolites across different ages highlighted a sexual maturity transition coexpression network. CONCLUSION: This study improves our understanding of the gut bacteriophage characteristics in quails and offers profound insights into the interactions among gut bacteriophages, bacteria, and host serum metabolites during the quail's sexual maturity transition.

Tissue-Characteristic Expression of Mouse Proteome.

The mouse is a valuable model organism for biomedical research. Here, we established a comprehensive spectral library and the data-independent acquisition-based quantitative proteome maps for 41 mouse organs, including some rarely reported organs such as the cornea, retina, and nine paired organs. The mouse spectral library contained 178,304 peptides from 12,320 proteins, including 1678 proteins not reported in previous mouse spectral libraries. Our data suggested that organs from the nervous system and immune system expressed the most distinct proteome compared with other organs. We also found characteristic protein expression of immune-privileged organs, which may help understanding possible immune rejection after organ transplantation. Each tissue type expressed characteristic high-abundance proteins related to its physiological functions. We also uncovered some tissue-specific proteins which have not been reported previously. The testis expressed highest number of tissue-specific proteins. By comparison of nine paired organs including kidneys, testes, and adrenal glands, we found left organs exhibited higher levels of antioxidant enzymes. We also observed expression asymmetry for proteins related to the apoptotic process, tumor suppression, and organ functions between the left and right sides. This study provides a comprehensive spectral library and a quantitative proteome resource for mouse studies.

Locking Patterned Carbon Nanotube Cages by Nanofibrous Mats to Construct Cucurbituril[n]-Based Ultrapermselective Dye/Salt Separation Membranes.

Surface patterning is a promising strategy to overcome the trade-off effect of separation membranes. Herein, a bottom-up patterning strategy of locking micron-sized carbon nanotube cages (CNCs) onto a nanofibrous substrate is developed. The strongly enhanced capillary force triggered by the abundant narrow channels in CNCs endows the precisely patterned substrate with excellent wettability and antigravity water transport. Both are crucial for the preloading of cucurbit[n]uril (CB6)-embeded amine solution to form an ultrathin (∼20 nm) polyamide selective layer clinging to CNCs-patterned substrate. The CNCs-patterning and CB6 modification result in a 40.2% increased transmission area, a reduced thickness, and a lowered cross-linking degree of selective layer, leading to a high water permeability of 124.9 L·m-2 h-1 bar-1 and a rejection of 99.9% for Janus Green B (511.07 Da), an order of magnitude higher than that of commercial membranes. The new patterning strategy provides technical and theoretical guidance for designing next-generation dye/salt separation membranes.

[Mechanism of ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix regulates HIF-1α signaling pathway mediated by renal hypoxia to ameliorate renal fibrosis in DKD rats].

This study explored the mechanism of the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix in ameliorating renal fibrosis in the rat model of diabetic kidney disease(DKD) based on the expression of hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) and HIF-1α/platelet-derived growth factor(PDGF)/platelet-derived growth factor receptor(PDGFR) signaling pathways in the DKD rats. After 1 week of adaptive feeding, 50 male SPF-grade Wistar rats were randomized into a blank group(n=7) and a modeling group. After 24 h of fasting, the rats in the modeling group were subjected to intraperitoneal injection of streptozocin and fed with a high-sugar and high-fat diet to establish a DKD model. After modeling, the rats were randomly assigned into model(n=7), low-dose ultrafiltration extract(n=7), medium-dose ultrafiltration extract(n=7), irbesartan(n=8), and high-dose ultrafiltration extract(n=8) groups. After intervention by corresponding drugs for 12 weeks, the general conditions of the rats were observed. The body weights and blood glucose levels of the rats were measured weekly, and the 24 h urinary protein(24hUP) was measured at the 6th and 12th weeks of drug administration. After the last drug administration, the renal function indicators were determined. Masson staining was employed to observe the pathological changes of the renal tissue. The expression of prolyl hydroxylase domain 2(PHD2) and HIF-1α in the renal tissue was detected by immunohistochemistry(IHC). Real-time qPCR was employed to determine the mRNA levels of PHD2, VEGF, PDGF, and PDGFR in the renal tissue. Western blot was employed to determine the protein levels of HIF-1α, VEGF, PDGF, and PDGFR in the renal tissue. The results showed that compared with the model group, drug administration lowered the levels of glycosylated serum protein(GSP), aerum creatinine(Scr), and blood urea nitrogen(BUN) in a dose-dependent manner(P<0.05 or P<0.01) and mitigated the pathological changes in the renal tissue. Furthermore, drug administration up-regulated mRNA level of PHD2(P<0.05 or P<0.01), down-regulated the mRNA levels of VEGF, PDGF, and PDGFR(P<0.05 or P<0.01) and the protein levels of HIF-1α, VEGF, PDGF, and PDGFR(P<0.01) in the renal tissue, and increased the rate of PHD2-positive cells(P<0.01). In conclusion, the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix effectively alleviated the renal fibrosis in DKD rats by inhibiting the expression of key proteins in the HIF-1α signaling pathway mediated by renal hypoxia and reducing extracellular matrix(ECM) deposition.

Directed cell migration towards softer environments.

How cells sense tissue stiffness to guide cell migration is a fundamental question in development, fibrosis and cancer. Although durotaxis-cell migration towards increasing substrate stiffness-is well established, it remains unknown whether individual cells can migrate towards softer environments. Here, using microfabricated stiffness gradients, we describe the directed migration of U-251MG glioma cells towards less stiff regions. This 'negative durotaxis' does not coincide with changes in canonical mechanosensitive signalling or actomyosin contractility. Instead, as predicted by the motor-clutch-based model, migration occurs towards areas of 'optimal stiffness', where cells can generate maximal traction. In agreement with this model, negative durotaxis is selectively disrupted and even reversed by the partial inhibition of actomyosin contractility. Conversely, positive durotaxis can be switched to negative by lowering the optimal stiffness by the downregulation of talin-a key clutch component. Our results identify the molecular mechanism driving context-dependent positive or negative durotaxis, determined by a cell's contractile and adhesive machinery.

Electronic Structure and Aromaticity of an Unusual Cyclo[18]carbon Precursor, C18 Br6.

Herein, the electronic structure and bonding character of the stable cyclo[18]carbon (C18 ) precursor, C18 Br6 , are thoroughly characterized by molecular orbital (MO), density of states (DOS), bond order (BO), and interaction region indicator (IRI) analyses. The delocalization characters of out-of-plane and in-plane π-electrons (labeled as πout - and πin -electrons, respectively) in bonding regions were examined using localized orbital locator (LOL) and electron localization function (ELF). The aromaticity was investigated, studying the molecular magnetic response to external magnetic field by computing the magnetically induced current density (Jind ), iso-chemical shielding surface (ICSS), anisotropy of the induced current density (AICD), and the induced magnetic field (Bind ). All these analyses indicate that C18 Br6 is a globally aromatic species with lower aromaticity than C18 , and the blocking of in-plane π-conjugation (labeled as πin -conjugation) by the presence of -Br substituents in it is the underlying cause for the weakening of molecular aromaticity.

Endovascular Treatment of Superior Mesenteric Artery Pseudoaneurysm Due to Infective Endocarditis With Stent-Graft.

PURPOSE: To report a successful case of pseudoaneurysm of the superior mesenteric artery (SMA) caused by infected endocarditis treated with a covered stent. CASE REPORT: A patient was diagnosed with infective endocarditis and 2 months later a proximal SMA pseudoaneurysm was identified on computed tomography. Daptomycin was started on admission and continued for approximately 4 months until the inflammatory markers normalized, and then the SMA pseudoaneurysm was successfully excluded with a stent-graft and antibiotics were continued for 1 year after the procedure. There were no associated complications or recurrences at the 3-year follow-up. CONCLUSION: Placing a covered stent with a full course of antibiotics before and after surgery may be a successful alternative to open surgery in the treatment of pseudoaneurysms of the SMA due to infective endocarditis. CLINICAL IMPACT: This case report reports a rare case of pseudoaneurysm of the superior mesenteric artery due to infective endocarditis, which was successfully treated with an overlapping stent and confirmed by complete imaging data at a three-year follow-up. This report suggests that endovascular treatment may be an alternative to open surgery in the treatment of pseudoaneurysms of the superior mesenteric artery caused by infective endocarditis.

Exploring the Aromaticity Differences of Isoelectronic Species of Cyclo[18]carbon (C18), B6C6N6, and B9N9: The Role of Carbon Atoms as Connecting Bridges.

The cyclo[18]carbon (C18) has piqued widespread interest in recent years for its geometrical aesthetic and unique electronic structure. Inspired by it, theoretical investigations of its isoelectronic B9N9 have been published occasionally; however, few studies considered their other companion B6C6N6. In this work, we study the geometric structure, charge distribution, bonding characteristic, aromaticity, and electron delocalization of B6C6N6 and B9N9 for the first time and compare the relevant results with those of C18. Based on the comprehensive analysis of aromaticity indicators such as AV1245, nucleus-independent chemical shifts, anisotropy of the induced current density, magnetically induced current density, iso-chemical shielding surface, and induced magnetic field (Bind), we found that B6C6N6 has definitely a double aromatic character similar to C18 and the aromaticities of the two are very close, while B9N9 is a nonaromatic species. In response to this novel finding, we delved into its nature from an electron delocalization perspective through a localized orbital locator, electron localization function, Fermi hole, and atomic remote delocalization index analyses. The C atom between B and N as an interconnecting bridge strengthens the electron delocalization of the conjugate path, which is the essence of the significant enhancement of the molecular aromaticity from B9N9 to B6C6N6. This work elucidates that within the framework of the isoelectronicity of C18, different methods of atomic doping can achieve molecules with completely different properties.

Molecular assembly with a figure-of-eight nanohoop as a strategy for the collection and stabilization of cyclo[18]carbon.

The recently synthesized novel figure-of-eight nanohoop with two strained oligoparaphenylenes (OPPs) was theoretically designed to collect and stabilize new allotropic carbon cyclo[18]carbon (C18) through molecular assembly. The size adaptability and shape complementarity of C18 to OPP make it possible for them to combine into extraordinary ring-in-ring supramolecules. Thermodynamic analysis of 2C18@OPP showed that the host-guest complex should spontaneously form below 404 K. Molecular dynamics (MD) simulations demonstrated that the assembly of C18 and OPP into host-guest complexes of up to 1 : 2 can occur at ambient temperature. Various real-space function analyses revealed that the nature of the non-covalent interaction between C18 and OPP is the van der Waals (vdW) attraction characterized by π-π stacking. Photoexcitation makes the host-guest complexes less stable in their S1 state by causing the central linker to flatten.

Size dependence of optical nonlinearity for H-capped carbon chains, H-(CC)n-H (n = 3-15): analysis of its nature and prediction for long chains.

Based on a computational approach that can accurately describe their geometric structures and electronic spectra, we have theoretically studied the nonlinear optical (NLO) properties of H-capped carbon chains, H-(CC)n-H (n = 3-15), for the first time. Special attention was paid to the size dependence of the molecular (hyper)polarizability of these species through the nonlinear fitting of the data, which formed two power-law formulas of αiso(∞) = -0.206 + 0.264n1.498 and γ‖(∞) = -0.624 + 0.006n3.368 and was thoroughly discussed at the electronic structure level by in-depth wavefunction analyses. The fundamental gap (ΔE) between vertical ionization energy (VIE) and vertical electron affinity (VEA) is found to be related to the molecular (hyper)polarizability. The calculated (hyper)polarizability of the carbon chains H-(CC)n-H (n = 3-15) is more sensitive to the density functional theory (DFT) applied than to the basis set selected. The results are expected to provide theoretical guidance for the property prediction of arbitrarily long carbon chains not yet synthesized.

Correction: Rich magnetic phase transitions and completely dual-spin polarization of zigzag PC3 nanoribbons under uniaxial strain.

Correction for 'Rich magnetic phase transitions and completely dual-spin polarization of zigzag PC3 nanoribbons under uniaxial strain' by Hui-Min Ni et al., Phys. Chem. Chem. Phys., 2023, https://doi.org/10.1039/d2cp05066h.

Rich magnetic phase transitions and completely dual-spin polarization of zigzag PC3 nanoribbons under uniaxial strain.

Among many modulation methods, strain engineering is often chosen for nanomaterials to produce tunable band gaps continuously. Inspired by the recently reported two-dimensional material PC3, we explore the tuning of strain on the spin-dependent transport properties of PC3 nanoribbons using the first-principle approach. Surprisingly, strain regulation achieves uninterrupted completely dual-spin polarization over a wide energy range near EF. Analysis reveals that the peculiar transmission spectra arise from the interesting evolution of the band structure, in which strain induces bands to shift and broaden/flatten. This results in triggering the transition of PC3NRs from bandgap-tunable bipolar magnetic semiconductors to spin-gapless semiconductors to ferromagnetic metals or half-metal magnets. Their unique performance demonstrates great potential in spintronics, and our study is expected to provide ideas and theoretical support for the design and application of novel PC3-based spintronic devices in the future.