Single-nucleus chromatin landscape dataset of mouse brain development and aging.

The development and aging of the brain constitute a lifelong dynamic process, marked by structural and functional changes that entail highly coordinated cellular differentiation and epigenetic regulatory mechanisms. Chromatin accessibility serves as the foundational basis for genetic activity. However, the holistic and dynamic chromatin landscape that spans various brain regions throughout development and ageing remains predominantly unexplored. In this study, we employed single-nucleus ATAC-seq to generate comprehensive chromatin accessibility maps, incorporating data from 69,178 cells obtained from four distinct brain regions - namely, the olfactory bulb (OB), cerebellum (CB), prefrontal cortex (PFC), and hippocampus (HP) - across key developmental time points at 7 P, 3 M, 12 M, and 18 M. We delineated the distribution of cell types across different age stages and brain regions, providing insight into chromatin accessible regions and key transcription factors specific to different cell types. Our data contribute to understanding the epigenetic basis of the formation of different brain regions, providing a dynamic landscape and comprehensive resource for revealing gene regulatory programs during brain development and aging.

A spatiotemporal atlas of cholestatic injury and repair in mice.

Cholestatic liver injuries, characterized by regional damage around the bile ductular region, lack curative therapies and cause considerable mortality. Here we generated a high-definition spatiotemporal atlas of gene expression during cholestatic injury and repair in mice by integrating spatial enhanced resolution omics sequencing and single-cell transcriptomics. Spatiotemporal analyses revealed a key role of cholangiocyte-driven signaling correlating with the periportal damage-repair response. Cholangiocytes express genes related to recruitment and differentiation of lipid-associated macrophages, which generate feedback signals enhancing ductular reaction. Moreover, cholangiocytes express high TGFß in association with the conversion of liver progenitor-like cells into cholangiocytes during injury and the dampened proliferation of periportal hepatocytes during recovery. Notably, Atoh8 restricts hepatocyte proliferation during 3,5-diethoxycarbonyl-1,4-dihydro-collidin damage and is quickly downregulated after injury withdrawal, allowing hepatocytes to respond to growth signals. Our findings lay a keystone for in-depth studies of cellular dynamics and molecular mechanisms of cholestatic injuries, which may further develop into therapies for cholangiopathies.

Highly Stable Lithium Metal Batteries Enabled by Tuning the Molecular Polarity of Diluents in Localized High-Concentration Electrolytes.

Electrolyte plays a crucial role in ensuring stable operation of lithium metal batteries (LMBs). Localized high-concentration electrolytes (LHCEs) have the potential to form a robust solid-electrolyte interphase (SEI) and mitigate Li dendrite growth, making them a highly promising electrolyte option. However, the principles governing the selection of diluents, a crucial component in LHCE, have not been clearly determined, hampering the advancement of such a type of electrolyte systems. Herein, the diluents from the perspective of molecular polarity are rationally designed and developed. A moderately fluorinated solvent, 1-(1,1,2,2-tetrafluoroethoxy)propane (TNE), is employed as a diluent to create a novel LHCE. The unique molecular structure of TNE enhances the intrinsic dipole moment, thereby altering solvent interactions and the coordination environment of Li-ions in LHCE. The achieved solvation structure not only enhances the bulk properties of LHCE, but also facilitates the formation of more stable anion-derived SEIs featured with a higher proportion of inorganic species. Consequently, the corresponding full cells of both Li||LiFePO4 and Li||LiNi0.8 Co0.1 Mn0.1 O2 cells utilizing Li thin-film anodes exhibit extended long-term stability with significantly improved average Coulombic efficiency. This work offers new insights into the functions of diluents in LHCEs and provides direction for further optimizing the LHCEs for LMBs.

The value of TDI combined with myocardial strain parameters in quantitative evaluation of left heart function in parturient with pregnancy-induced hypertension.

This study aimed to investigate the value of tissue doppler imaging (TDI) and 4D myocardial strain parameters in evaluating left heart function of pregnant women with hypertension and the association between these parameters and relevant factors. Forty-five pregnant women with hypertensive disorder, including 20 with hypertension, 15 with mild preeclampsia, and 10 with severe preeclampsia, were recruited, and their cardiac functions were compared with those of 30 healthy pregnant women as controls. High Left ventricular end-systolic volume (LVESV), Left atrial volume index (LAVI), E/e were observed in hypertensive disorder, while Mitral peak diastolic velocity(E), Early diastolic peak velocity(e), E/A, Left ventricularglobal longitudinal strain (LVGLS), Left ventricularglobal area strain (LVGAS), and Left atrialglobal longitudinal strain (LAGLS) were decreased; for pre-eclampsia, Left ventricular end-systolic diameter (LVESD), Left atrial anteroposterior diameter (LAD-ap), LVESV, LAVI were significantly increased, LVGLS, LAGLS were significantly decreased, Left ventricular end-diastolic diameter (LVEDD), Left ventricular end-diastolic volume (LVEDV), A peak, E/e were increased, while E peak, E/A, e, Left ventricle global radial strain (LVGRS), Left ventricle global circumferential strain (LVGCS), LVGAS were decreased but not significantly; for severe preeclampsia, Left ventricular end diastolic diameter (LVEDD), LVESD, LAD-ap, Left ventricular end-diastolic volume (LVEDV), LVESV, LAVI, A, and E/e were significantly increased, while LVGLS, LVGRS, LVGCS, LVGAS, LAGLS, E peak, E/A, and e were significantly reduced. TDI combined with 4D myocardial strain parameters can detect early changes in cardiac function of hypertensive disorders in pregnancy, with LVGLS, LVGAS, and LAGLS being the most sensitive indicators for early changes. Such findings provide a basis for effective clinical treatment of these symptoms.

A scATAC-seq atlas of chromatin accessibility in axolotl brain regions.

Axolotl (Ambystoma mexicanum) is an excellent model for investigating regeneration, the interaction between regenerative and developmental processes, comparative genomics, and evolution. The brain, which serves as the material basis of consciousness, learning, memory, and behavior, is the most complex and advanced organ in axolotl. The modulation of transcription factors is a crucial aspect in determining the function of diverse regions within the brain. There is, however, no comprehensive understanding of the gene regulatory network of axolotl brain regions. Here, we utilized single-cell ATAC sequencing to generate the chromatin accessibility landscapes of 81,199 cells from the olfactory bulb, telencephalon, diencephalon and mesencephalon, hypothalamus and pituitary, and the rhombencephalon. Based on these data, we identified key transcription factors specific to distinct cell types and compared cell type functions across brain regions. Our results provide a foundation for comprehensive analysis of gene regulatory programs, which are valuable for future studies of axolotl brain development, regeneration, and evolution, as well as on the mechanisms underlying cell-type diversity in vertebrate brains.

Revealing the role of interfacial water and key intermediates at ruthenium surfaces in the alkaline hydrogen evolution reaction.

Ruthenium exhibits comparable or even better alkaline hydrogen evolution reaction activity than platinum, however, the mechanistic aspects are yet to be settled, which are elucidated by combining in situ Raman spectroscopy and theoretical calculations herein. We simultaneously capture dynamic spectral evidence of Ru surfaces, interfacial water, *H and *OH intermediates. Ru surfaces exist in different valence states in the reaction potential range, dissociating interfacial water differently and generating two distinct *H, resulting in different activities. The local cation tuning effect of hydrated Na+ ion water and the large work function of high-valence Ru(n+) surfaces promote interfacial water dissociation. Moreover, compared to low-valence Ru(0) surfaces, high-valence Ru(n+) surfaces have more moderate adsorption energies for interfacial water, *H, and *OH. They, therefore, facilitate the activity. Our findings demonstrate the regulation of valence state on interfacial water, intermediates, and finally the catalytic activity, which provide guidelines for the rational design of high-efficiency catalysts.

Single-nucleus chromatin landscapes during zebrafish early embryogenesis.

Vertebrate embryogenesis is a remarkable process, during which numerous cell types of different lineages arise within a short time frame. An overwhelming challenge to understand this process is the lack of dynamic chromatin accessibility information to correlate cis-regulatory elements (CREs) and gene expression within the hierarchy of cell fate decisions. Here, we employed single-nucleus ATAC-seq to generate a chromatin accessibility dataset on the first day of zebrafish embryogenesis, including 3.3 hpf, 5.25 hpf, 6 hpf, 10 hpf, 12 hpf, 18 hpf and 24 hpf, obtained 51,620 high-quality nuclei and 23 clusters. Furthermore, by integrating snATAC-seq data with single-cell RNA-seq data, we described the dynamics of chromatin accessibility and gene expression across developmental time points, which validates the accuracy of the chromatin landscape data. Together, our data could serve as a fundamental resource for revealing the epigenetic regulatory mechanisms of zebrafish embryogenesis.

Single-cell chromatin accessibility profiling of cell-state-specific gene regulatory programs during mouse organogenesis.

In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations.

Translation and validation of chinese version of MDASI immunotherapy for early-phase trials module: a cross-sectional study.

BACKGROUND: During immunotherapy treatment and survival, identifying symptoms requires a standardized and validated assessment tool. The aim of this study was to translate, validate and use the Chinese version of the Immunotherapy of the M.D. Anderson Symptom Inventory for Early-Phase Trials module (MDASI-Immunotherapy EPT) to assess the symptom burden of cancer patients receiving immunotherapy in China. METHODS: The MDASI-Immunotherapy EPT was translated into Chinese using Brislin's translation model and the back-translation method. In total, 312 Chinese-speaking colorectal cancer patients receiving immunotherapy were enrolled in the trial from August 2021 to July 2022 after receiving definitive diagnoses in our cancer center. The reliability and validity of the translated version was evaluated. RESULTS: Cronbach's α values were 0.964 and 0.935 for the symptom severity and interference scales, respectively. Significant correlations were found between the MDASI-Immunotherapy EPT-C and FACT-G scores (-0.617-0.732, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by ECOG PS (all P < 0.01). The overall mean subscale scores for the core and interference subscales were 1.92 ± 1.75 and 1.46 ± 1.87, respectively. Fatigue, numbness/tingling, and disturbed sleep had the highest scores for the most serious symptoms. CONCLUSION: The MDASI-Immunotherapy EPT-C showed adequate reliability and validity for measuring symptoms among Chinese-speaking colorectal cancer patients receiving immunotherapy. The tool could be used in clinical practice and clinical trials to gather patients' health and quality of life data and manage their symptoms in a timely manner in the future.

Understanding the origin of the improved sodium ion storage performance of the transition metal oxide@carbon nanocomposite anodes.

Transition metal oxide (TMO) anodes show inferior sodium ion storage performance compared with that of lithium ion storage owing to the larger radium size and heavier elemental mass of Na+ than Li+. Effective strategies are highly desired to improve the Na+ storage performance of TMOs for applications. In this work, using ZnFe2O4@xC nanocomposites as model materials for investigation, we found that by manipulating the particle sizes of the inner TMOs core and the features of outer carbon coating, the Na+ storage performance can be significantly improved. The ZnFe2O4@1C with a diameter of the inner ZnFe2O4 core of around 200 nm coated by a thin carbon layer of around 3 nm shows a specific capacity of only 120 mA h g-1. The ZnFe2O4@6.5C with a diameter of the inner ZnFe2O4 core of around 110 nm embedding in a porous interconnected carbon matrix displays a significantly improved specific capacity of 420 mA h g-1 at the same specific current. Furthermore, the latter shows an excellent cycling stability of 1000 cycles with a capacity retention of 90% of the initial 220 mA h g-1 specific capacity at 1.0 A g-1. TEM, electrochemical impedance spectroscopy, and kinetic analysis show that the inner ZnFe2O4 core with reduced particle size and the outer thicker and interconnected carbon matrix synergistically improve the active reaction sites, integrity, electric conductivity, and pseudocapacitive-controlled contribution of ZnFe2O4@xC nanocomposites, thus leading to an overall enhanced Na+ storage performance. Our findings create a universal, facile, and effective method to enhance the Na+ storage performance of the TMO@C nanomaterials.

Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants.

SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies-YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.

Immune response and homeostasis mechanism following administration of BBIBP-CorV SARS-CoV-2 inactivated vaccine.

The BBIBP-CorV severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccine has been authorized for emergency use and widely distributed. We used single-cell transcriptome sequencing to characterize the dynamics of immune responses to the BBIBP-CorV inactivated vaccine. In addition to the expected induction of humoral immunity, we found that the inactivated vaccine induced multiple, comprehensive immune responses, including significantly increased proportions of CD16+ monocytes and activation of monocyte antigen presentation pathways; T cell activation pathway upregulation in CD8+ T cells, along with increased activation of CD4+ T cells; significant enhancement of cell-cell communications between innate and adaptive immunity; and the induction of regulatory CD4+ T cells and co-inhibitory interactions to maintain immune homeostasis after vaccination. Additionally, comparative analysis revealed higher neutralizing antibody levels, distinct expansion of naive T cells, a shared increased proportion of regulatory CD4+ T cells, and upregulated expression of functional genes in booster dose recipients with a longer interval after the second vaccination. Our research will support a comprehensive understanding of the systemic immune responses elicited by the BBIBP-CorV inactivated vaccine, which will facilitate the formulation of better vaccination strategies and the design of new vaccines.

In Situ Probe of the Hydrogen Oxidation Reaction Intermediates on PtRu a Bimetallic Catalyst Surface by Core-Shell Nanoparticle-Enhanced Raman Spectroscopy.

In situ monitoring of the evolution of intermediates and catalysts during hydrogen oxidation reaction (HOR) processes and elucidating the reaction mechanism are crucial in catalysis and energy science. However, spectroscopic information on trace intermediates on catalyst surfaces is challenging to obtain due to the complexity of interfacial environments and lack of in situ techniques. Herein, core-shell nanoparticle-enhanced Raman spectroscopy was employed to probe alkaline HOR processes on representative PtRu surfaces. Direct spectroscopic evidence of an OHad intermediate and RuOx (Ru(+3)/Ru(+4)) surface oxides is simultaneously obtained, verifying that Ru doping onto Pt promotes OHad adsorption on the RuOx surface to react with Had adsorption on the Pt surface to form H2O. In situ Raman, XPS, and DFT results reveal that RuOx coverage tunes the electronic structure of PtRuOx to optimize the adsorption energy of OHad on catalyst surfaces, leading to an improvement in HOR activity. Our findings provide mechanistic guidelines for the rational design of HOR catalysts with high activity.

Spatiotemporal mapping of gene expression landscapes and developmental trajectories during zebrafish embryogenesis.

A major challenge in understanding vertebrate embryogenesis is the lack of topographical transcriptomic information that can help correlate microenvironmental cues within the hierarchy of cell-fate decisions. Here, we employed Stereo-seq to profile 91 zebrafish embryo sections covering six critical time points during the first 24 h of development, obtaining a total of 152,977 spots at a resolution of 10 × 10 × 15 µm3 (close to cellular size) with spatial coordinates. Meanwhile, we identified spatial modules and co-varying genes for specific tissue organizations. By performing the integrated analysis of the Stereo-seq and scRNA-seq data from each time point, we reconstructed the spatially resolved developmental trajectories of cell-fate transitions and molecular changes during zebrafish embryogenesis. We further investigated the spatial distribution of ligand-receptor pairs and identified potentially important interactions during zebrafish embryo development. Our study constitutes a fundamental reference for further studies aiming to understand vertebrate development.

Label-free SERS strategy for rapid detection of capsaicin for identification of waste oils.

Identification of waste oils is challenging in the field of food safety due to the lack of common markers and straightforward analytical methods. Herein, we developed a novel label-free surface-enhanced Raman spectroscopy (SERS) strategy to identify waste oils using Ag nanoparticles solution (Ag NPs sol.) as a SERS substrate to significantly enhance the Raman signal of capsaicin marker molecule usually contained in the waste oils. The enhanced signal was directly detected by a portable Raman spectrometer with the limit of detection (LOD) of 2.9 µg L-1 within 10 min. Concentration-dependent SERS investigation showed the linear relationship between the SERS signal intensity of the characteristic peaks and the concentrations of capsaicin in the range of 10-2500 µg L-1 and the correlation coefficient was 0.9895. Our findings show the sensitivity, accessibility, and reliability of this method for the rapid identification of waste oils and furthermore for the practical applications in the field of food safety.

Single-cell transcriptional diversity of neonatal umbilical cord blood immune cells reveals neonatal immune tolerance.

The characteristics of neonatal immune cells display intrinsic differences compared with adult immune cells. Therefore, a comprehensive analysis of key gene expression regulation is required to understand the response of the human fetal immune system to infections. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) to systematically profile umbilical cord blood (UCB) nucleated cells and peripheral blood mononuclear cells (PBMCs) to identify their composition and differentially expressed genes. The immune cells in neonatal UCB demonstrated the expression of key genes, such as HBG2, NFKBIA, JUN, FOS, and TNFAIP3. In contrast, natural killer and T cells, which are constituents of adult PBMCs, exhibited high cytotoxic gene expression. Furthermore, we obtained similar results from the data of scATAC-seq by identifying the status of chromatin accessibility of key genes. Therefore, scRNA-seq and scATAC-seq of neonatal UCB nucleated cells and adult PBMCs could serve as an invaluable resource for elucidating the regulatory mechanisms of responses of distinct immune cell types and further identifying the differences between neonatal and adult immune responses to predict the potential underlying mechanism for neonatal immune tolerance.

Two Extracellular Poly(ε-caprolactone)-Degrading Enzymes From Pseudomonas hydrolytica sp. DSWY01T: Purification, Characterization, and Gene Analysis.

Poly(ε-caprolactone) (PCL) is an artificial polyester with commercially promising application. In this study, two novel PCL-degrading enzymes named PCLase I and PCLase II were purified to homogeneity from the culture supernatant of an effective polyester-degrading bacterium, Pseudomonas hydrolytica sp. DSWY01T. The molecular masses of PCLase I and PCLase II were determined to be 27.5 and 30.0 kDa, respectively. The optimum temperatures for the enzyme activities were 50 and 40°C, and the optimum pH values were 9.0 and 10.0, respectively. The two enzymes exhibited different physical and chemical properties, but both enzymes could degrade PCL substrates into monomers and oligomers. Weight loss detection and scanning electron microscopy revealed that PCLase I had more effective degradation ability than PCLase II. The genes of the two enzymes were cloned on the basis of the peptide fingerprint analysis results. The sequence analysis and substrate specificity analysis results showed that PCLase I and PCLase II were cutinase and lipase, respectively. Interface activation experiment also confirmed this conclusion. Structural analysis and modeling were further performed to obtain possible insights on the mechanism.

Rapid and Simple Analysis of the Human Pepsin Secondary Structure Using a Portable Raman Spectrometer.

Human pepsin is a digestive protease that plays an important role in the human digestive system. The secondary structure of human pepsin determines its bioactivity. Therefore, an in-depth understanding of human pepsin secondary structure changes is particularly important for the further improvement of the efficiency of human pepsin biological function. However, the complexity and diversity of the human pepsin secondary structure make its analysis difficult. Herein, a convenient method has been developed to quickly detect the secondary structure of human pepsin using a portable Raman spectrometer. According to the change of surface-enhanced Raman spectroscopy (SERS) signal intensity and activity of human pepsin at different pH values, we analyze the change of the human pepsin secondary structure. The results show that the content of the ß-sheet gradually increased with the increase in the pH in the active range, which is in good agreement with circular dichroism (CD) measurements. The change of the secondary structure improves the sensitivity of human pepsin SERS detection. Meanwhile, human pepsin is a commonly used disease marker for the noninvasive diagnosis of gastroesophageal reflux disease (GERD); the detection limit of human pepsin we obtained is 2 µg/mL by the abovementioned method. The real clinical detection scenario is also simulated by spiking pepsin solution in saliva, and the standard recovery rate is 80.7-92.3%. These results show the great prospect of our method in studying the protein secondary structure and furthermore promote the application of SERS in clinical diagnosis.

Single-cell brain atlas of Parkinson's disease mouse model.

Parkinson's disease (PD) is a neurodegenerative disease, leading to the impairment of movement execution. PD pathogenesis has been largely investigated, either limited to bulk transcriptomic levels or at certain cell types, which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types. Here, we report the application of single-nucleus RNA-seq on midbrain, striatum, and cerebellum of the α-syn-A53T mouse, a well-established PD mouse model, and matched controls, generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells. Additionally, we comprehensively depicte the dysfunctions in PD pathology, covering the elevation of NF-κB activity, the alteration of ion channel components, the perturbation of protein homeostasis network, and the dysregulation of glutamatergic signaling. Notably, we identify a variety of cell types closely associated with PD risk genes. Taken together, our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution, which facilitates the development of novel approaches for diagnosis and therapies against PD.

Single-cell atlas of domestic pig cerebral cortex and hypothalamus.

The brain of the domestic pig (Sus scrofa domesticus) has drawn considerable attention due to its high similarities to that of humans. However, the cellular compositions of the pig brain (PB) remain elusive. Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB (frontal lobe, parietal lobe, temporal lobe, occipital lobe, and hypothalamus) and identified 21 cell subpopulations. The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution. Furthermore, we identified cell types and molecular pathways closely associated with neurological disorders, bridging the gap between gene mutations and pathogenesis. We reported, to our knowledge, the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species, providing extensive resources for future research regarding neural science, evolutionary developmental biology, and regenerative medicine.