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Abstract A pressing challenge in spatially resolved transcriptomics (SRT) is to benchmark the computational methods. A widely-used approach involves utilizing simulated data. However, biases exist in terms of the currently available simulated SRT data, which seriously affects the accuracy of method evaluation and validation. Herein, we present scCube ( https://github.com/ZJUFanLab/scCube ), a Python package for independent, reproducible, and technology-diverse simulation of SRT data. scCube not only enables the preservation of spatial expression patterns of genes in reference-based simulations, but also generates simulated data with different spatial variability (covering the spatial pattern type, the resolution, the spot arrangement, the targeted gene type, and the tissue slice dimension, etc.) in reference-free simulations. We comprehensively benchmark scCube with existing single-cell or SRT simulators, and demonstrate the utility of scCube in benchmarking spot deconvolution, gene imputation, and resolution enhancement methods in detail through three applications.

Liver transplantation (LT) is the standard therapy for individuals afflicted with end-stage liver disease. Despite notable advancements in LT technology, the incidence of early allograft dysfunction (EAD) remains a critical concern, exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients. Unfortunately, the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD. Herein, we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients, with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages. Comparison of the 75 231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells, granzyme B+ (GZMB+) granzyme K+ (GZMK+) natural killer cells, and S100 calcium binding protein A12+ (S100A12+) neutrophils. Moreover, we verified this immune niche and its association with EAD occurrence in two independent cohorts. Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level, thus, offering valuable insights into EAD onset.

The utilization of vanadium titano-magnetite concentrate (VTM) for pellet preparation poses challenges in terms of low consolidation strength and high energy consumption during the thermal process. The effect and function mechanism of high-pressure grinding roll (HPGR) pretreatment on the preparation of VTM pellets were investigated. The results indicate that HPGR pretreatment increased the strength of the pellets prepared by VTM and decreased the thermal processing temperature and time. The main reason can be attributed to the reduced particle size of VTM, accompanied by an increase in specific surface area, iron-bearing mineral liberation, and improved interfacial hydrophilicity and particle ballability. Moreover, HPGR pretreatment reduced the crystallite size of VTM and increased lattice microstrain and amorphousness, leading to a 13.21 kJ/mol improvement in the mechanical energy storage of titanomagnetite. The increased specific surface area was a crucial factor in strengthening the preparation of VTM pellets, which increased the contacting points participated in interface physicochemical reactions. The enhanced hydrophilicity and ballability were beneficial to improving the strength of green pellets, while the increased strength of roasted pellets was primarily attributed to the iron-containing mineral liberation and crystal mechanical activation, which promoted the oxidation of iron-bearing minerals and the microcrystalline diffusion and connection. Compared with the untreated VTM, the compressive strength of roasted pellets increased from 2168 N P−1 (Newton per pellet) to 2813 N P−1 when the roller pressure intensity was 12 MPa, and the proper roasting temperature could be reduced by more than 50 °C.

Abstract Background Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. Methods SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. Results SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. Conclusions SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.

Backgroud: Thymic atrophy marks the onset of immune aging, precipitating developmental anomalies in T cells. Numerous clinical and preclinical investigations have underscored the regulatory role of Ganoderma lucidum spores (GLS) in T cell development. However, the precise mechanisms underlying this regulation remain elusive.Methods: In this study, a mice model of estradiol benzoate (EB)-induced thymic atrophy was constructed, and the improvement effect of GLS on thymic atrophy was evaluated. Then, we employs multi-omics techniques to elucidate how GLS modulates T cell development amidst EB-induced thymic atrophy in mice.Results: GLS effectively mitigates EB-induced thymic damage by attenuating apoptotic thymic epithelial cells (TECs) and enhancing the output of CD4+ T cells into peripheral blood. During thymic T cell development, sporoderm-removed GLS (RGLS) promotes T cell receptor (TCR) α rearrangement by augmenting V-J fragment rearrangement frequency and efficiency. Notably, biased Vα14-Jα18 rearrangement fosters double-positive (DP) to invariant natural killer T (iNKT) cell differentiation, partially contingent on RGLS-mediated restriction of peptide-major histocompatibility complex I (pMHCⅠ)-CD8 interaction and augmented CD1d expression in DP thymocytes, thereby promoting DP to CD4+ iNKT cell development. Furthermore, RGLS amplifies interaction between a DP subpopulation, termed DPsel-7, and plasmacytoid dendritic cells (pDCs), likely facilitating the subsequent development of double-negative iNKT1 cells. Lastly, RGLS suppresses EB-induced upregulation of Abpob and Apoa4, curbing the clearance of CD4+Abpob+ and CD4+Apoa4+ T cells by mTECs, resulting in enhanced CD4+ T cell output.Discussion: These findings indicate that the RGLS effectively mitigates EB-induced TEC apoptosis and compromised double-positive thymocyte development. These insights into RGLS’s immunoregulatory role pave the way for its potential as a T-cell regeneration inducer.

Abstract Background Cross-species transmission of zoonotic IAVs to humans is potentially widespread and lethal, posing a great threat to human health, and their cross-species transmission mechanism has attracted much attention. miRNAs have been shown to be involved in the regulation of IAVs infection and immunity, however, few studies have focused on the molecular mechanisms underlying miRNAs and mRNAs expression after IAVs cross-species infection. Methods We used tree shrews, a close relative of primates, as a model and used RNA-Seq and bioinformatics tools to analyze the expression profiles of DEMs and DEGs in the nasal turbinate tissue at different time points after the newly emerged swine influenza A virus SW2783 cross-species infection with tree shrews, and miRNA-mRNA interaction maps were constructed and verified by RT-qPCR, miRNA transfection and luciferase reporter assay. Results 14 DEMs were screened based on functional analysis and interaction map, miR-760-3p, miR-449b-2, miR-30e-3p, and miR-429 were involved in the signal transduction process of replication and proliferation after infection, miR-324-3p, miR-1301-1, miR-103-1, miR-134-5p, miR-29a, miR-31, miR-16b, miR-34a, and miR-125b participate in negative feedback regulation of genes related to the immune function of the body to activate the antiviral immune response, and miR-106b-3p may be related to the cross-species infection potential of SW2783, and the expression level of these miRNAs varies in different days after infection. Conclusions The miRNA regulatory networks were constructed and 14 DEMs were identified, some of them can affect the replication and proliferation of viruses by regulating signal transduction, while others can play an antiviral role by regulating the immune response. It indicates that abnormal expression of miRNAs plays a crucial role in the regulation of cross-species IAVs infection, which lays a solid foundation for further exploration of the molecular regulatory mechanism of miRNAs in IAVs cross-species infection and anti-influenza virus targets.

Abstract The use of exogenous mitochondria to replenish damaged mitochondria has been proposed as a strategy for the treatment of pulmonary fibrosis. However, the success of this strategy is partially restricted by the difficulty of supplying sufficient mitochondria to diseased cells. Herein, we report the generation of high-powered mesenchymal stem cells with promoted mitochondrial biogenesis and facilitated mitochondrial transfer to injured lung cells by the sequential treatment of pioglitazone and iron oxide nanoparticles. This highly efficient mitochondrial transfer is shown to not only restore mitochondrial homeostasis but also reactivate inhibited mitophagy, consequently recovering impaired cellular functions. We perform studies in mouse to show that these high-powered mesenchymal stem cells successfully mitigate fibrotic progression in a progressive fibrosis model, which was further verified in a humanized multicellular lung spheroid model. The present findings provide a potential strategy to overcome the current limitations in mitochondrial replenishment therapy, thereby promoting therapeutic applications for fibrotic intervention.

We characterize the multiphase circumgalactic medium (CGM) and galaxy properties at z = 6.0–6.5 in four quasar fields from the James Webb Space Telescope A SPectroscopic survey of biased halos In the Reionization Era (ASPIRE) program. We use the Very Large Telescope/X-shooter spectra of quasar J0305–3150 to identify one new metal absorber at z = 6.2713 with multiple transitions (O i , Mg ii , Fe ii, and C ii ). They are combined with the published absorbing systems in Davies et al. at the same redshift range to form a sample of nine metal absorbers at z = 6.03–6.49. We identify eight galaxies within 1000 km s ^−1 and 350 kpc around the absorbing gas from the ASPIRE spectroscopic data, with their redshifts secured by [O iii ] ( λ λ 4959, 5007) doublets and H β emission lines. Our spectral energy distribution fitting indicates that the absorbing galaxies have stellar masses ranging from 10 ^7.2 to 10 ^8.8 M _⊙ and metallicity between 0.02 and 0.4 solar. Notably, the z = 6.2713 system in the J0305–3150 field resides in a galaxy overdensity region, which contains two (tentatively) merging galaxies within 350 kpc and seven galaxies within 1 Mpc. We measure the relative abundances of α elements to iron ([ α /Fe]) and find that the CGM gas in the most overdense region exhibits a lower [ α /Fe] ratio. Our modeling of the galaxy’s chemical abundance favors a top-heavy stellar initial mass function and hints that we may be witnessing the contribution of the first generation of Population III stars to the CGM at the end of the reionization epoch.

Protoclusters, the progenitors of galaxy clusters, trace large scale structures in the early Universe and are important to our understanding of structure formation and galaxy evolution. To date, only a handful of protoclusters have been identified in the Epoch of Reionization. As one of the rarest populations in the early Universe, distant quasars that host active supermassive black holes are thought to reside in the most massive dark matter halos at that cosmic epoch and could thus potentially pinpoint some of the earliest protoclusters. In this Letter, we report the discovery of a massive protocluster around a luminous quasar at z = 6.63. This protocluster is anchored by the quasar and includes three [C ii ] emitters at z ∼ 6.63, 12 spectroscopically confirmed Ly α emitters (LAEs) at 6.54 < z ≤ 6.64, and a large number of narrow-band-imaging selected LAE candidates at the same redshift. This structure has an overall overdensity of $\delta ={3.3}_{-0.9}^{+1.1}$ within ∼35 × 74 cMpc ^2 on the sky and an extreme overdensity of δ > 30 in its central region (i.e., R ≲ 2 cMpc). We estimate that this protocluster will collapse into a galaxy cluster with a mass of ${6.9}_{-1.4}^{+1.2}\times {10}^{15}\,{M}_{\odot }$ at the current epoch, more massive than the most massive clusters known in the local Universe such as Coma. In the quasar vicinity, we discover a double-peaked LAE, which implies that the quasar has a UV lifetime greater than 0.8 Myrs and has already ionized its surrounding intergalactic medium.

Gaining a better understanding of autoprotection against drug-induced liver injury (DILI) may provide new strategies for its prevention and therapy. However, little is known about the underlying mechanisms of this phenomenon. We used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells (NPCs) in autoprotection against DILI, using acetaminophen (APAP) as a model drug. Autoprotection was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice, followed by a higher dose in a secondary challenge. NPC subsets and dynamic changes were identified in the APAP (hepatotoxicity-sensitive) and APAP-resistant (hepatotoxicity-resistant) groups. A chemokine (C-C motif) ligand 2+ endothelial cell subset almost disappeared in the APAP-resistant group, and an R-spondin 3+ endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP autoprotection. Moreover, the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of inflammation. DC-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant group. In addition, the natural killer cell subsets NK-3 and NK-4 and the Sca-1–CD62L+ natural killer T cell subset may promote autoprotection through interferon-γ-dependent pathways. Furthermore, macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP hepatotoxicity. Overall, this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.

Abstract Background Immune checkpoint inhibitors (ICIs) have altered the clinical management of non-small cell lung cancer (NSCLC). However, the low response rate, severe immune-related adverse events (irAEs), and hyperprogressive disease following ICIs monotherapy require attention. Combination therapy may overcome these limitations and traditional Chinese medicine with immunomodulatory effects provides a promising approach. Shenmai injection (SMI) is a clinically effective adjuvant treatment for cancer with chemotherapy and radiotherapy. Therefore, the combined effects and mechanisms of SMI and programmed death-1 (PD-1) inhibitor against NSCLC was focused on this study. Methods A Lewis lung carcinoma mouse model and a lung squamous cell carcinoma humanized mouse model were used to investigate the combined efficacy and safety of SMI and PD-1 inhibitor. The synergistic mechanisms of the combination therapy against NSCLC were explored using single-cell RNA sequencing. Validation experiments were performed using immunofluorescence analysis, in vitro experiment, and bulk transcriptomic datasets. Results In both models, combination therapy alleviated tumor growth and prolonged survival without increasing irAEs. The GZMA high and XCL1 high natural killer (NK) cell subclusters with cytotoxic and chemokine signatures increased in the combination therapy, while malignant cells from combination therapy were mainly in the apoptotic state, suggesting that mediating tumor cell apoptosis through NK cells is the main synergistic mechanisms of combination therapy. In vitro experiment confirmed that combination therapy increased secretion of Granzyme A by NK cells. Moreover, we discovered that PD-1 inhibitor and SMI combination blocked inhibitory receptors on NK and T cells and restores their antitumoral activity in NSCLC better than PD-1 inhibitor monotherapy, and immune and stromal cells exhibited a decrease of angiogenic features and attenuated cancer metabolism reprogramming in microenvironment of combination therapy. Conclusions This study demonstrated that SMI reprograms tumor immune microenvironment mainly by inducing NK cells infiltration and synergizes with PD-1 inhibitor against NSCLC, suggested that targeting NK cells may be an important strategy for combining with ICIs. Video Abstract

Panax ginseng (PG) and Panax notoginseng (PN) are highly valuable Chinese medicines (CM). Although both CMs have similar active constituents, their clinical applications are clearly different. Over the past decade, RNA sequencing (RNA-seq) analysis has been employed to investigate the molecular mechanisms of extracts or monomers. However, owing to the limited number of samples in standard RNA-seq, few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level. Here, we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq (TCM-seq), a high-throughput, low-cost workflow to molecularly evaluate CM perturbations. A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq. Transcriptomes from repeated samples were used to verify the robustness of TCM-seq. We then focused on the primary active components, Panax notoginseng saponins (PNS) and Panax ginseng saponins (PGS) extracted from PN and PG, respectively. We also characterized the transcriptome changes of 10 cell lines, treated with four different doses of PNS and PGS, using TCM-seq to compare the differences in their perturbing effects on genes, functional pathways, gene modules, and molecular networks. The results of transcriptional data analysis showed that the transcriptional patterns of various cell lines were significantly distinct. PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease, whereas PNS resulted in a greater coagulation effect on vascular endothelial cells. This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Abstract Tissues are highly complicated with spatial heterogeneity in gene expression. However, the cutting-edge single-cell RNA-seq technology eliminates the spatial information of individual cells, which contributes to the characterization of cell identities. Herein, we propose single-cell spatial position associated co-embeddings (scSpace), an integrative method to identify spatially variable cell subpopulations by reconstructing cells onto a pseudo-space with spatial transcriptome references (Visium, STARmap, Slide-seq, etc.). We benchmark scSpace with both simulated and biological datasets, and demonstrate that scSpace can accurately and robustly identify spatially variated cell subpopulations. When employed to reconstruct the spatial architectures of complex tissue such as the brain cortex, the small intestinal villus, the liver lobule, the kidney, the embryonic heart, and others, scSpace shows promising performance on revealing the pairwise cellular spatial association within single-cell data. The application of scSpace in melanoma and COVID-19 exhibits a broad prospect in the discovery of spatial therapeutic markers.

Organoids are three-dimensional cell accusations generated from pluripotent stem cells or adult stem cells in vitro. With many advantages over cell and animal models, organoids have been increasingly used in drug and clinical medical research in recent years. Chinese herbal medicine (CHM) is characterized by multi-target and multi-pathway treatment methods; however, there is no commonly accepted study method regarding efficacy and underlying mechanisms. In this review we summarized the important applications of organoid models in pharmacodynamic mechanism studies, efficacy and safety evaluations, and CHM personalized medicine, thus providing the theoretical basis for its development and innovation.

Abstract Unidirectional SiCf/SiC minicomposite with a scheelite (CaWO4) interphase coating was fabricated through the precursor infiltration and pyrolysis method. Fractography of the SiCf/SiC minicomposites indicated that weak fiber/matrix bonding can be provided by the CaWO4 interphase. Furthermore, interfacial debonding stress of SiCf/CaWO4/SiC minicomposite was evaluated through the fiber push-out test, and estimated to be 80.7 ± 4.6 MPa. In-situ tensile SEM observation of SiCf/CaWO4/SiC minicomposite after oxidation at 1000–1100 °C was carried out, and thermal compatibility between CaWO4 interphase coating and SiC fiber or matrix after heat treatment at 1300 °C was investigated.

Abstract Background Polyhalite fertilizer application is an effective way to alleviate a shortage of potassium. This study explored the effects of polyhalite fertilizer application as a total or partial replacement for conventional potassium fertilizer to improve peanut growth and soil quality. Results The index of peanut yield and its economic benefits, the content and distribution of mineral nutrients in different organs, soil chemical properties, and rhizosphere microbial diversity in response to the treatments were examined. The results show that the M4P6T treatment (60% polyhalite fertilizer replacing potassium chloride as the base fertilizer, and 40% potassium chloride fertilizer applied as a topdressing) increased profit by 7.2% without affecting the yield. The M4P6T treatment significantly improved the accumulation and distribution of potassium, calcium and magnesium in the kernels compared with the M10B treatment (no polyhalite fertilizer; potassium chloride fertilizer only as the base fertilizer). Soil treated with polyhalite fertilizer had higher alpha-diversity values and greater relative abundance of microbes at the phylum and genus levels. Conclusions Partial substitution of polyhalite for potassium chloride improved soil quality and peanut growth more than did single applications of polyhalite and potassium chloride. Graphical Abstract

We study the environment of the z = 6.33 ultraluminous quasar SDSS J010013.02+280225.8 (J0100) to understand its association with large-scale structure. Theoretical models propose high-redshift quasars as markers of galaxy overdensities residing in the most massive dark matter halos (DMHs) in the early Universe. J0100 is an ultraluminous quasar with the most massive black hole known at z ≳ 6, suggesting a high likelihood of residing in a massive DMH. We present wide-field (∼522 arcmin ^2 ) imaging in the r , i , and z bands from the Large Binocular Cameras on the Large Binocular Telescope, with Y- and J -band imaging from the Wide-field Infrared Camera on the Canada–France–Hawaii Telescope, centered on J0100. Applying color selections, we identify 23 objects as i -dropout Lyman break galaxy (LBG) candidates in the J0100 field. We use the deep photometric catalog in the 1.27 deg ^2 COSMOS field to calculate the density of LBGs in a blank field, and to estimate the selection completeness and purity. The observed surface density of LBG candidates in the J0100 field corresponds to a galaxy overdensity of δ = 4 (at 8.4 σ ). This large-scale overdensity suggests that the ∼22 arcmin ^2 overdensity found by Kashino et al. using JWST data extends out to much larger scales. We calculate the angular autocorrelation function of the candidates and find a positive correlation on ≲10′ scales as well as evidence of asymmetries in their spatial distribution, further suggesting the direct detection of large-scale structure in the field of the ultraluminous quasar J0100.

The [C ii ] 158 μ m emission line and the underlying far-infrared (FIR) dust continuum are important tracers for studying star formation and kinematic properties of early galaxies. We present a survey of the [C ii ] emission lines and FIR continua of 31 luminous quasars at z > 6.5 using the Atacama Large Millimeter Array (ALMA) and the NOrthern Extended Millimeter Array at sub-arcsec resolution. This survey more than doubles the number of quasars with [C ii ] and FIR observations at these redshifts and enables statistical studies of quasar host galaxies deep into the epoch of reionization. We detect [C ii ] emission in 27 quasar hosts with a luminosity range of L _[C _II _] = (0.3–5.5) × 10 ^9 L _⊙ and detect the FIR continuum of 28 quasar hosts with a luminosity range of L _FIR = (0.5–13.0) × 10 ^12 L _⊙ . Both L _[C _II _] and L _FIR are correlated ( ρ ≃ 0.4) with the quasar bolometric luminosity, albeit with substantial scatter. The quasar hosts detected by ALMA are clearly resolved with a median diameter of ∼5 kpc. About 40% of the quasar host galaxies show a velocity gradient in [C ii ] emission, while the rest show either dispersion-dominated or disturbed kinematics. Basic estimates of the dynamical masses of the rotation-dominated host galaxies yield M _dyn = (0.1–7.5) × 10 ^11 M _⊙ . Considering our findings alongside those of literature studies, we found that the ratio between M _BH and M _dyn is about 10 times higher than that of local M _BH – M _dyn relation on average but with substantial scatter (the ratio difference ranging from ∼0.6 to 60) and large uncertainties.

The James Webb Space Telescope provides an unprecedented opportunity for unbiased surveys of H α -emitting galaxies at z > 4 with the NIRCam's wide-field slitless spectroscopy (WFSS). In this work, we present a census of Ly α escape fraction ( f _esc,Ly _α ) of 165 star-forming galaxies at z = 4.9–6.3, utilizing their H α emission directly measured from FRESCO NIRCam/WFSS data. We search for Ly α emission of each H α -emitting galaxy in the Very Large Telescope/MUSE data. The overall f _esc,Ly _α measured by stacking is 0.090 ± 0.006. We find that f _esc,Ly _α displays a strong dependence on the observed UV slope ( β _obs ) and E ( B − V ), such that the bluest galaxies ( β _obs ∼ −2.5) have the largest escape fractions ( f _esc,Ly _α ≈ 0.6), indicative of the crucial role of dust and gas in modulating the escape of Ly α photons. f _esc,Ly _α is less well related to other parameters, including the UV luminosity and stellar mass, and the variation in f _esc,Ly _α with them can be explained by their underlying coupling with E ( B − V ) or β _obs . Our results suggest a tentative decline in f _esc,Ly _α at z ≳ 5, implying increasing intergalactic medium attenuation toward higher redshift. Furthermore, the dependence of f _esc,Ly _α on β _obs is proportional to that of the ionizing photon escape fraction ( f _esc,LyC ), indicating that the escape of Ly α and ionizing photon may be regulated by similar physical processes. With f _esc,Ly _α as a proxy to f _esc,LyC , we infer that UV-faint ( M _UV > −16) galaxies contribute >70% of the total ionizing emissivity at z = 5–6. If these relations hold during the epoch of reionization, UV-faint galaxies can contribute the majority of UV photon budget to reionize the Universe.

We present the final data from the Sloan Digital Sky Survey (SDSS) Reverberation Mapping (RM) project, a precursor to the SDSS-V Black Hole Mapper RM program. This data set includes 11 yr photometric and 7 yr spectroscopic light curves for 849 broad-line quasars over a redshift range of 0.1 < z < 4.5 and a luminosity range of L _bol = 10 ^44−47.5 erg s ^−1 , along with spectral and variability measurements. We report 23, 81, 125, and 110 RM lags (relative to optical continuum variability) for broad H α , H β , Mg ii , and C iv using the SDSS-RM sample, spanning much of the luminosity and redshift ranges of the sample. Using 30 low-redshift RM active galactic nuclei with dynamical-modeling black hole masses, we derive a new estimate of the average virial factor of $\left\langle \mathrm{log}f\right\rangle =0.62\pm 0.07$ for the line dispersion measured from the rms spectrum. The intrinsic scatter of individual virial factors is 0.31 ± 0.07 dex, indicating a factor of 2 systematic uncertainty in RM black hole masses. Our lag measurements reveal significant R – L relations for H β and Mg ii at high redshift, consistent with the latest measurements based on heterogeneous samples. While we are unable to robustly constrain the slope of the R – L relation for C iv given the limited dynamic range in luminosity, we found substantially larger scatter in C iv lags at fixed L _1350 . Using the SDSS-RM lag sample, we derive improved single-epoch (SE) mass recipes for H β , Mg ii , and C iv , which are consistent with their respective RM masses as well as between the SE recipes from two different lines, over the luminosity range probed by our sample. The new H β and Mg ii recipes are approximately unbiased estimators at given RM masses, but there are systematic biases in the C iv recipe. The intrinsic scatter of SE masses around RM masses is ∼0.45 dex for H β and Mg ii , increasing to ∼0.58 dex for C iv .

We report the detection of a pair of massive quiescent galaxies likely in the process of merging at the center of the spectroscopically confirmed, extremely massive protocluster BOSS1244 at z = 2.24 ± 0.02. These galaxies, BOSS1244-QG1 and BOSS1244-QG2, were detected with Hubble Space Telescope grism slitless spectroscopic observations. These two quiescent galaxies are among the brightest member galaxies, with z = 2.223–2.255 in BOSS1244, and reside at redshifts z = 2.244 and z = 2.242, with a half-light radius of 6.76 ± 0.50 kpc and 2.72 ± 0.16 kpc, respectively. BOSS1244-QG1 and BOSS1244-QG2 are separated by a projected distance of about 70 physical kpc, implying that the two galaxies likely merge to form a massive brightest cluster galaxy (BCG) with size and mass similar to the most massive BCGs in the local Universe. We thus infer that BCG formation through dry major mergers may happen earlier than the full assembly of a cluster core, which broadens our previous understanding of the coevolution of mature galaxy clusters and BCGs in the nearby Universe. Moreover, we find a strong density–star formation relation over a scale of ∼18 comoving Mpc in BOSS1244, i.e., star formation activity decreases as density increases, implying that the quenching of star formation in BCGs and their progenitors is likely governed by environment-related processes before the virialization of the cluster core.

We present observations using the Northern Extended Millimetre Array (NOEMA) of CO and H _2 O emission lines and the underlying dust continuum in two quasars at z ∼ 6, i.e., P215−16 at z = 5.78 and J1429+5447 at z = 6.18. Notably, among all published CO spectral line energy distributions (SLEDs) of quasars at z ∼ 6, the two systems reveal the highest and the lowest CO levels of excitation, respectively. Our radiative transfer modeling of the CO SLED of P215−16 suggests that the molecular gas heated by active galactic nuclei could be a plausible origin for the high CO excitation. For J1429+5447, we obtain the first well-sampled CO SLED (from transitions from 2−1 to 10−9) of a radio-loud quasar at z ≳ 6. Analysis of the CO SLED suggests that a component from a single photodissociation region could explain the CO excitation in the radio-loud quasar J1429+5447. This work highlights the utility of the CO SLED in uncovering the properties of the interstellar medium in these young quasar–starburst systems at the highest redshift. The diversity of the CO SLEDs reveals the complexities in gas conditions and excitation mechanisms at their early evolutionary stage.

Cosmic variance introduces significant uncertainties into galaxy number density properties when surveying the high-redshift Universe with a small volume. Such uncertainties produce the field-to-field variance σ _g of galaxy numbers in observational astronomy, which significantly affects the luminosity function (LF) measurement of Ly α emitters (LAEs). For most previous Ly α LF studies, σ _g is often adopted from predictions by cosmological simulations, but barely confirmed by observations. Measuring cosmic variance requires a huge sample over a large volume, exceeding the capabilities of most astronomical instruments. In this study, we demonstrate an observational approach for measuring the cosmic variance contribution for z ≈ 2.2 Ly α LFs. The LAE candidates are observed using the narrow band and broad band of the Subaru/Hyper Suprime-Cam in eight independent fields, making the total survey area ≃11.62 deg ^2 and a comoving volume of ≃8.71 × 10 ^6 Mpc ^3 . We report a best-fit Schechter function with parameters α = −1.75 (fixed), ${L}_{\mathrm{Ly}\alpha }^{* }={5.95}_{-0.96}^{+1.22}\times {10}^{42}$ erg s ^−1 , and ${\phi }_{\mathrm{Ly}\alpha }^{* }={5.26}_{-1.27}^{+1.65}$ × 10 ^−4 Mpc ^−3 for the overall Ly α LFs. After clipping out the regions that may bias the cosmic variance measurements, we calculate σ _g by sampling LAEs within multiple pointings on the field image. We investigate the relation between σ _g and survey volume V , and fit a simple power-law ${\sigma }_{g}=k\times {\left(\tfrac{V}{{10}^{5}\,{\mathrm{Mpc}}^{3}}\right)}^{\beta }$ . We find best-fit values of $-{1.399}_{-0.156}^{+0.160}$ for β and ${1.249}_{-0.193}^{+0.213}$ for k . We compare our measurements with predictions from simulations and find that the cosmic variance of LAEs is likely larger than that of general star-forming galaxies.

In this paper, we present a Ly α halo (LAH) identified by stacking ∼3300 Ly α emitters (LAEs) at z = 2.2–2.3. We carry out imaging observations and data reduction with Subaru/Hyper Suprime-Cam. Our total survey area is ∼12 deg ^2 and the imaging depths are 25.5–27.0 mag. Using the imaging data, we select 1240 and 2101 LAE candidates at z = 2.2 and 2.3, respectively. We carry out spectroscopic observations of our LAE candidates and data reduction with Magellan/IMACS to estimate the contamination rate of our LAE candidates. We find that the contamination rate of our sample is low (8%). We stack our LAE candidates with a median stacking method to identify the LAH at z = 2. We show that our LAH is detected until ∼100 kpc at the 2 σ significance level and likely extended to ∼200 kpc at a surface brightness level of ∼10 ^−20 erg s ^−1 cm ^−2 arcsec ^−2 . Compared to those of previous studies, our LAH is brighter at radii of ∼25–100 kpc, which is not likely caused by the contamination in our sample but by the different redshifts, fields, and selection methods instead. To investigate how central galaxies affect surrounding LAHs, we divide our LAEs into subsamples based on the Ly α luminosity ( L _Ly _α ), rest-frame Ly α equivalent width (EW _0 ), and UV magnitude ( M _uv ). We stack the subsamples and find that higher L _Ly _α , smaller EW _0 , and brighter M _uv cause more extended halos. Our results suggest that more massive LAEs generally have more extended LAHs.

Amantadine (AMD) is an antiviral drug that is prohibited for use in livestock and poultry. In this study, carboxyl-modified magnetic nanoparticles (MNPs) were synthesized using the solvothermal method in one step with harmless and inexpensive regents, and they were used to label monoclonal antibodies (mAbs) of AMD in microwells with electrostatic adsorption. Then, a magnetic immunochromatography assay (MICA) method was successfully established. Under optimal conditions, the MICA showed a good performance, with a linear range of 0.2~10.0 µg/L. The limit of detection (LOD) was 0.068 µg/L with the instrument, and the visual LOD (vLOD) was 0.5 µg/L. There was no cross-reaction with rimantadine and ribavirin. The vLOD in real samples was 1.0 µg/kg. The developed MICA has the advantages of convenience, speed, and sensitivity, which make it suitable for the on-site rapid detection of AMD residues in chicken tissues and eggs.

Highlights Shenmai injection attenuates 5-FU-induced myelotoxicity in tumor-bearing mice. Both carbohydrates and ginsenosides in Shenmai injection promote hematopoiesis. Carbohydrates may regulate Glutathione metabolism and B cell receptor pathway.

With the modernization and internationalization of traditional Chinese medicine (TCM), the requirement for quality control has increased. The quality marker (Q-marker) is an important standard in this field and has been implemented with remarkable success in recent years. However, the establishment of Q-markers remains fragmented and the process lacks systematicity, resulting in inconsistent quality control and insufficient correlation with clinical efficacy and safety of TCM. This review introduces four multimodal integrated approaches that contribute to the discovery of more comprehensive and accurate Q-markers, thus aiding in the establishment of new quality control patterns based on the characteristics and principles of TCM. These include the whole-process quality control strategy, chemical-activity-based screening method, efficacy, safety, and consistent combination strategy, and TCM theory-guided approach. Furthermore, methodologies and representative examples of these strategies are described, and important future directions and questions in this field are also proposed.

Current methods to reanalyze bulk RNA-seq at spatially resolved single-cell resolution have limitations. Here, the authors develop Bulk2Space, a spatial deconvolution algorithm using single-cell and spatial transcriptomics as references, providing new insights into spatial heterogeneity within bulk tissue.

Co-processing of municipal solid waste incineration fly ash (MSWI-FA) during iron ore sintering is a potentially feasible path for harmless and resourceful utilization. In this paper, the mineralization behavior of high calcium water-washed municipal solid waste incineration fly ash (WM-FA) during iron ore sintering was studied through high temperature in-situ, diffusion couple and sintering experiments, and the corresponding regulation technology was put forward. When adding 1.0 wt.% WM-FA, the tumbler index of sinter was slightly reduced from 69.20% to 68.82%. This index dropped to 62.43% with increasing the proportion of WM-FA to 2.0 wt.%. Potential reason indicated that WM-FA showed higher soft melting temperature than that of sintering mixture, resulted in its insufficient mineralization property. By adding 20 wt.% iron ore into the WM-FA pellets, the mineralization reaction inside and outside WM-FA was significantly improved, and a large amount of CaO·Fe2O3 liquid phase was formed. The tumbler index of sinter increased from 62.43% to 68.35%. Research findings provides a certain theoretical basis for the treatment of municipal solid waste incineration fly ash in the sintering process, and is of great significance to the green and sustainable development of iron and steel industry and cities.

The grate bars are a critical and easily consumable component of the sintering machine, and the control of their corrosion is of great importance to reduce their consumption. This investigation focused on revealing the physicochemical profile of the failure sintering grate bar and the potential corrosion mechanism. The results showed that the superficial area of the failure grate bar consisted of the adhesive layer, corrosion layer, and metal layer from outside to inside. The adhesion layer is characterised by a loose structure, consisting of higher contents of alkali chloride salts and sulphate, which were the typical corrosive substances. The main components of the corrosion layer were Fe2O3 and Cr2O3; the metal layer structure was dense, which remained the original composition of the grate bar. Based on the characteristics of sintering flue gas, the potential corrosion mechanism was summarised into three main types: (a) high-temperature oxidation, due to the periodic exposure of the grate bars to the high-temperature sintering flue; (b) chlorine corrosion, due to the existence of HCl, alkali (heavy) metal chloride salts (KCl, NaCl, PbCl2) in sintering flue gas, which formed the adhesive layer of grate bars; (c) sulphate corrosion, due to the existence of high SO2 contents and sulphate in the flue gas. The research findings are important to guide the development of grate bar corrosion control technologies.

Cell-cell communication is a vital feature involving numerous biological processes. Here, the authors develop SpaTalk, a cell-cell communication inference method using knowledge graph for spatially resolved transcriptomic data, providing valuable insights into spatial intercellular tissue dynamics.

Abstract Objective To systematically review the clinical efficacy and safety of Chinese herbal medicine (CHM) with and without Western medicine (WM) for different severity of COVID-19. Methods CNKI, PubMed, Wanfang Database, ClinicalTrails.gov, Embase, ChiCTR and ICTRP were searched from 01 Jan, 2020 to 30 Jun, 2021. Two authors independently assessed all the randomized clinical trials (RCTs) for trial inclusion, data extraction and quality assessment. Meta-analysis was conducted using Review Manager software (RevMan 5.4.1). Evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Primary outcomes included total effectiveness rate. Secondary outcomes included improvements in symptom improvement and total adverse event rate. Different severity of COVID-19 patients was assessed in subgroup analysis. This study was registered with INPLASY, INPLASY202210072. Results 22 high quality RCTs involving 1789 participants were included. There were no trial used CHM alone nor compare placebo or no treatment. Compared with WM, combined CHM and WM (CHM-WM) treatment showed higher total effectiveness rate, lower symptom scores of fever, cough, fatigue, dry throat and pharyngalgia, shorter mean time to viral conversion, better Computerized Tomography (CT) image and blood results, fewer total adverse events and worse conditions (P

With the deepening of exploration and development, due to the limitation of the resolution of the conventional seismic data, it is difficult to meet the needs of exploration and development. Since the attenuation degree of different frequency components of seismic signals is different, the frequency decomposing technology can be applied to perform differential compensation on each frequency component to improve the resolution of seismic data. However, the conventional frequency division technology generally not only holds low frequency division accuracy but also shows modal aliasing, thus it cannot be well applied to seismic data processing. To solve these problems, this paper proposes a high-resolution processing method for seismic data based on adaptive variational modal decomposition (VMD). The multi-objective bat algorithm is applied to the variational modal decomposition, and the VMD parameters are optimized by the fitness function constructed using power spectrum entropy, energy difference, and sample entropy. The model test results show that the optimized VMD method holds high frequency division accuracy and strong anti-noise ability, and also can avoids modal aliasing, When the optimized VMD method is applied to high-resolution processing of seismic data, the model and actual data test results show that the resolution of processed seismic data is effectively improved.

Objective: To conduct an updated systematic review and meta-analysis on the efficacy and safety of Chinese herbal medicine (CHM) for threatened miscarriage.Data Sources: Electronic databases were searched from inception to 30 June 2022. Study Eligibility Criteria: Only randomized controlled trials (RCTs) that assessed the efficacy and safety of CHM or combined CHM and Western medicine (CHM-WM) and compared with other treatments for threatened miscarriage were included for analysis.Methods: Three review authors independently evaluated included studies, assessed the risk of bias and extracted data for meta-analysis (continuation of pregnancy after 28 gestational weeks, continuation of pregnancy after treatment, preterm birth, adverse maternal outcomes, neonatal death, TCM syndrome severity, β-hCG levels after treatment), sensitivity analysis (β-hCG level) and subgroup analysis (TCM syndrome severity, β-hCG level). The risk ratio and 95% confidence interval were calculated by RevMan. Certainty of the evidence was assessed according to GRADE.Results: Overall, 57 RCTs involving 5,881 patients met the inclusion criteria. Compared with WM alone, CHM alone showed significant higher incidence of continuation of pregnancy after 28 gestational weeks (Risk Ratio (RR) 1.11; 95% CI 1.02 to 1.21; n = 1; moderate quality of evidence), continuation of pregnancy after treatment (RR 1.30; 95% CI 1.21 to 1.38; n = 10; moderate quality of evidence), higher β-hCG level (Standardized Mean Difference (SMD) 6.88; 95% CI 1.74 to 12.03; n = 4) and lower Traditional Chinese medicine (TCM) syndrome severity (SMD −2.94; 95% CI −4.27 to −1.61; n = 2). Compared with WM alone, combined CHM-WM showed significant higher incidence of continuation of pregnancy after 28 gestational weeks (RR 1.21; 95% CI 1.16 to 1.27; n = 15; moderate quality of evidence), continuation of pregnancy after treatment (RR 1.19; 95% CI 1.16 to 1.23; n = 41; moderate quality of evidence), higher β-hCG level (SMD 2.27; 95% CI 1.72 to 2.83; n = 37) and lower TCM syndrome severity (SMD −1.74; 95% CI −2.21 to −1.27; n = 15). No significant differences in reducing the adverse maternal outcomes and neonatal death were found in combined CHM-WM compared with WM alone (RR 0.97; 95% CI 0.62 to 1.52; n = 8; RR 0.39; 95% CI 0.12 to 1.21; n = 2).Conclusion: Current evidence supported CHM could be a potential treatment for threatened miscarriage. However, results should be interpreted with caution considering the low to moderate quality of the available evidence.Systematic Review Registration: [https://inplasy.com/inplasy-2022-6-0107/], identifier [INPLASY20220107].

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR)‐based genetic screening has been demonstrated as a powerful approach for unbiased functional genomics research. Single‐cell CRISPR screening (scCRISPR) techniques, which result from the combination of single‐cell toolkits and CRISPR screening, allow dissecting regulatory networks in complex biological systems at unprecedented resolution. These methods allow cells to be perturbed en masse using a pooled CRISPR library, followed by high‐content phenotyping. This is technically accomplished by annotating cells with sgRNA‐specific barcodes or directly detectable sgRNAs. According to the integration of distinct single‐cell technologies, these methods principally fall into four categories: scCRISPR with RNA‐seq, scCRISPR with ATAC‐seq, scCRISPR with proteome probing, and imaging‐based scCRISPR. scCRISPR has deciphered genotype–phenotype relationships, genetic regulations, tumor biological issues, and neuropathological mechanisms. This review provides insight into the technical breakthrough of scCRISPR by systematically summarizing the advancements of various scCRISPR methodologies and analyzing their merits and limitations. In addition, an application‐oriented approach guide is offered to meet researchers’ individualized demands.

JWST is revolutionizing our understanding of the high- z Universe by expanding the black hole horizon, looking farther and to smaller masses, and revealing the stellar light of their hosts. By examining JWST galaxies at z = 4–7 that host H α -detected black holes, we investigate (i) the high- z M _• – M _⋆ relation and (ii) the black hole mass distribution, especially in its low-mass range ( M _• ≲ 10 ^6.5 M _⊙ ). With a detailed statistical analysis, our findings conclusively reveal a high- z M _• – M _⋆ relation that deviates at >3 σ confidence level from the local relation. The high- z relation is $\mathrm{log}({M}_{\bullet }/\,{M}_{\odot })=-{2.43}_{-0.83}^{+0.83}+{1.06}_{-0.09}^{+0.09}\mathrm{log}({M}_{\star }/\,{M}_{\odot })$ . Black holes are overmassive by ∼10–100× compared to their low- z counterparts in galactic hosts of the same stellar mass. This fact is not due to a selection effect in surveys. Moreover, our analysis predicts the possibility of detecting in high- z JWST surveys 5–15× more black holes with M _• ≲ 10 ^6.5 M _⊙ , and 10–30× more with M _• ≲ 10 ^8.5 M _⊙ , compared to local relation’s predictions. The lighter black holes preferentially occupy galaxies with a stellar mass of ∼10 ^7.5 –10 ^8 M _⊙ . We have yet to detect these sources because (i) they may be inactive (duty cycles 1%–10%), (ii) the host overshines the active galactic nucleus (AGN), or (iii) the AGN is obscured and not immediately recognizable by line diagnostics. A search of low-mass black holes in existing JWST surveys will further test the M _• – M _⋆ relation. Current JWST fields represent a treasure trove of black hole systems at z = 4–7; their detection will provide crucial insights into their early evolution and coevolution with their galactic hosts.

The launch of JWST opens a new window for studying the connection between metal-line absorbers and galaxies at the end of the Epoch of Reionization. Previous studies have detected absorber–galaxy pairs in limited quantities through ground-based observations. To enhance our understanding of the relationship between absorbers and their host galaxies at z > 5, we utilized the NIRCam wide-field slitless spectroscopy to search for absorber-associated galaxies by detecting their rest-frame optical emission lines (e.g., [O III ] + H β ). We report the discovery of a Mg ii -associated galaxy at z = 5.428 using data from the JWST ASPIRE program. The Mg ii absorber is detected on the spectrum of quasar J0305–3150 with a rest-frame equivalent width of 0.74 Å. The associated galaxy has an [O III ] luminosity of 10 ^42.5 erg s ^−1 with an impact parameter of 24.9 pkpc. The joint Hubble Space Telescope–JWST spectral energy distribution (SED) implies a stellar mass and star formation rate of M _* ≈ 10 ^8.8 M _⊙ , star-formation rate ≈ 10 M _⊙ yr ^−1 . Its [O III ] equivalent width and stellar mass are typical of [O III ] emitters at this redshift. Furthermore, connecting the outflow starting time to the SED-derived stellar age, the outflow velocity of this galaxy is ∼300 km s ^−1 , consistent with theoretical expectations. We identified six additional [O III ] emitters with impact parameters of up to ∼300 pkpc at similar redshifts (∣ dv ∣ < 1000 km s ^−1 ). The observed number is consistent with that in cosmological simulations. This pilot study suggests that systematically investigating the absorber–galaxy connection within the ASPIRE program will provide insights into the metal-enrichment history in the early Universe.

We present a study of the mass–metallicity relation (MZR) of 51 dwarf galaxies ( M _⋆ ≈ 10 ^6.5 –10 ^9.5 M _⊙ ) at z = 2–3 from the A2744 and SMACS J0723-3732 galaxy cluster fields. These dwarf galaxies are identified and confirmed by deep JWST/NIRISS imaging and slitless grism spectroscopic observations. By taking advantage of the superior performance of JWST and the gravitational lensing effect, we extend the previous MZR relation at z = 2–3 to a much lower-mass regime down by ≈2.5 orders of magnitude as compared with previous studies. We find that the MZR has a shallower slope at the low-mass end ( M _⋆ < 10 ^9 M _⊙ ), with a slope turnover point of ≈10 ^9 M _⊙ . This implies that the dominating feedback processes in dwarf galaxies may be different from that in massive galaxies. From z = 3, to z = 2, the metallicity of the dwarf galaxies is enhanced by ≈0.09 dex for a given stellar mass, consistent with the mild evolution found in galaxies with higher mass. Furthermore, we confirm the existence of a fundamental metallicity relation (FMR) between the gas-phase metallicity, stellar mass, and star formation rate in dwarf galaxies at z = 2–3. Our derived FMR, which has no significant redshift evolution, can be used as a benchmark to understand the origin of the anticorrelation between the star formation rate and metallicity of dwarf galaxies in the high- z Universe.

We present the first results from the JWST program A SPectroscopic survey of biased halos In the Reionization Era (ASPIRE). This program represents an imaging and spectroscopic survey of 25 reionization-era quasars and their environments by utilizing the unprecedented capabilities of NIRCam Wide Field Slitless Spectroscopy (WFSS) mode. ASPIRE will deliver the largest ( $\sim 280\,{\mathrm{arcmin}}^{2}$ ) galaxy redshift survey at 3–4 μ m among JWST Cycle 1 programs and provide extensive legacy values for studying the formation of the earliest supermassive black holes, the assembly of galaxies, early metal enrichment, and cosmic reionization. In this first ASPIRE paper, we report the discovery of a filamentary structure traced by the luminous quasar J0305–3150 and 10 [O iii ] emitters at z = 6.6. This structure has a 3D galaxy overdensity of δ _gal = 12.6 over 637 cMpc ^3 , one of the most overdense structures known in the early universe, and could eventually evolve into a massive galaxy cluster. Together with existing VLT/MUSE and ALMA observations of this field, our JWST observations reveal that J0305–3150 traces a complex environment where both UV-bright and dusty galaxies are present and indicate that the early evolution of galaxies around the quasar is not simultaneous. In addition, we discovered 31 [O iii ] emitters in this field at other redshifts, 5.3 < z < 6.7, with half of them situated at z ∼ 5.4 and 6.2. This indicates that star-forming galaxies, such as [O iii ] emitters, are generally clustered at high redshifts. These discoveries demonstrate the unparalleled redshift survey capabilities of NIRCam WFSS and the potential of the full ASPIRE survey data set.

Studies of rest-frame optical emission in quasars at z > 6 have historically been limited by the wavelengths accessible by ground-based telescopes. The James Webb Space Telescope (JWST) now offers the opportunity to probe this emission deep into the reionization epoch. We report the observations of eight quasars at z > 6.5 using the JWST/NIRCam Wide Field Slitless Spectroscopy as a part of the “A SPectroscopic survey of biased halos In the Reionization Era (ASPIRE)” program. Our JWST spectra cover the quasars’ emission between rest frame ∼4100 and 5100 Å. The profiles of these quasars’ broad H β emission lines span a full width at half maximum from 3000 to 6000 km s ^−1 . The H β -based virial black hole (BH) masses, ranging from 0.6 to 2.1 billion solar masses, are generally consistent with their Mg ii -based BH masses. The new measurements based on the more reliable H β tracer thus confirm the existence of a billion solar-mass BHs in the reionization epoch. In the observed [O iii ] λ λ 4960,5008 doublets of these luminous quasars, broad components are more common than narrow core components (≤ 1200 km s ^−1 ), and only one quasar shows stronger narrow components than broad. Two quasars exhibit significantly broad and blueshifted [O iii ] emission, thought to trace galactic-scale outflows, with median velocities of −610 and −1430 km s ^−1 relative to the [C ii ] 158 μ m line. All eight quasars show strong optical Fe ii emission and follow the eigenvector 1 relations defined by low-redshift quasars. The entire ASPIRE program will eventually cover 25 quasars and provide a statistical sample for the studies of the BHs and quasar spectral properties.

Direct observations of low-mass, low-metallicity galaxies at z ≳ 4 provide an indispensable opportunity for detailed inspection of the ionization radiation, gas flow, and metal enrichment in sources similar to those that reionized the universe. Combining the James Webb Space Telescope (JWST), Very Large Telescope/MUSE, and Atacama Large Millimeter/submillimeter Array, we present detailed observations of a strongly lensed, low-mass (≈10 ^7.6 M _⊙ ) galaxy at z = 3.98 (also see Vanzella et al.). We identify strong narrow nebular emission, including C iv λ λ 1548, 1550, He ii λ 1640, O iii ] λ λ 1661, 1666, [Ne iii ] λ 3868, [O ii ] λ 3727, and the Balmer series of hydrogen from this galaxy, indicating a metal-poor H ii region (≲0.12 Z _⊙ ) powered by massive stars. Further, we detect a metal-enriched damped Ly α system (DLA) associated with the galaxy with the H i column density of N _H I ≈ 10 ^21.8 cm ^−2 . The metallicity of the associated DLA may reach the supersolar metallicity (≳ Z _⊙ ). Moreover, thanks to JWST and gravitational lensing, we present the resolved UV slope ( β ) map at the spatial resolution of ≈100 pc at z = 4, with steep UV slopes reaching β ≈ −2.5 around three star-forming clumps. Combining with low-redshift analogs, our observations suggest that low-mass, low-metallicity galaxies, which dominate reionization, could be surrounded by a high covering fraction of the metal-enriched, neutral-gaseous clouds. This implies that the metal enrichment of low-mass galaxies is highly efficient, and further supports that in low-mass galaxies, only a small fraction of ionizing radiation can escape through the interstellar or circumgalactic channels with low-column-density neutral gas.

Abstract Background Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.

COVID-19 has caused severe threats to lives and damage to property worldwide. The immunopathology of the disease is of particular concern. Currently, researchers have used gene co-expression networks (GCNs) to deepen the study of molecular mechanisms of immune responses to COVID-19. However, most efforts have not fully explored dynamic changes of cell-type-specific molecular networks in the disease process. This study proposes a GCN construction pipeline named single-cell Disease Progression cellular module analysis (scDisProcema), which can trace dynamic changes of immune system response during disease progression using single-cell data. Here, scDisProcema considers changes in cell fate and expression patterns during disease development, identifying gene modules responsible for different immune cells. The hub genes are screened for each module by the specific expression level and the intercellular connectivity of modules. Based on functional items enriched by each gene module, we elucidate the biological processes of different cells involved in disease development and explain the molecular mechanisms underlying the process of cell depletion or proliferation caused by disease. Compared with traditional WGCNA methods, scDisProcema can make more convenient use of the heterogeneity information provided by scRNA-seq data and has great potential in exploring molecular changes during disease progression and organ development.

A novel paper-based analytical device (PAD) was prepared and applied to determine the xanthine oxidase (XOD) inhibitory activity of Salvia miltiorrhiza extracts (SME). First, polycaprolactone was 3D printed on filter paper and heated to form hydrophobic barriers. Then the modified paper was cut according to the specific design. Necessary reagents including XOD for the colorimetric assay were immobilized on two separate pieces of paper. By simply adding phosphate buffer, the reaction was performed on the double-layer PAD. Quantitative results were obtained by analyzing the color intensity with the specialized device system (consisting of a smartphone, a detection box and sandwich plates). The 3D-printed detection box was small, with a size of 9.0 cm × 7.0 cm × 11.5 cm. Color component G performed well in terms of linearity and detection limits and thus was identified as the index. The reaction conditions were optimized using a definitive screening design. Moreover, a 10% glycerol solution was found to be a suitable stabilizer. When the stabilizer was added, the activity of XOD could be maintained for at least 15 days under 4 °C or −20 °C storage conditions. The inhibitory activity of SME was investigated and compared to that of allopurinol. The results obtained with the PAD showed agreement with those obtained with the microplate method. In conclusion, the proposed PAD method is simple, accurate and has a potential for point-of-care testing. It also holds promise for use in rapid quality testing of medicinal herbs, intermediate products, and preparations of traditional Chinese medicines.

Abstract Background Microbiome big data from population-scale cohorts holds the key to unleash the power of microbiomes to overcome critical challenges in disease control, treatment and precision medicine. However, variations introduced during data generation and processing limit the comparisons among independent studies in respect of interpretability. Although multiple databases have been constructed as platforms for data reuse, they are of limited value since only raw sequencing files are considered. Description Here, we present MetaGeneBank, a standardized database that provides details on sample collection and sequencing, and abundances of genes, microbiota and molecular functions for 4470 raw sequencing files (over 12 TB) collected from 16 studies covering over 10 types of diseases and 14 countries using a unified data-processing pipeline. The incorporation of tools that enable browsing and searching with descriptive attributes, gene sequences, microbiota and functions makes the database user-friendly. We found that the source of specimen contributes more than sequencing centers or platforms to the variations of microbiota. Special attention should be paid when re-analyzing sequencing files from different countries. Conclusions Collectively, MetaGeneBank provides a gateway to utilize the untapped potential of gut metagenomic data in helping fighting against human diseases. With the continuous updating of the database in terms of data volume, data types and sample types, MetaGeneBank would undoubtedly be the benchmarking database in the future in respect of data reuse, and would be valuable in translational science.

Abstract Non‐alcoholic fatty liver disease (NAFLD) with an increasing incidence is one of the leading causes for liver transplantation and cancer, whereas understandings on the onset and development of this disease are quite limited. Nowadays, gut microbial dysregulation has been proposed to play a critical role in the immune‐metabolic disorders in NAFLD patients via gut‐liver axis. Although definitive crosstalk between gut and liver has not been thoroughly depicted, the nanosized bacterial extracellular vesicles (bEVs) capable of transporting multiple kinds of molecules to distant organs of host in intact form via system circulation act as major mediators in host‐bacterial interactions. A recent review has confirmed the associations between bEVs and NAFLD features such as insulin resistance and liver inflammation, whereas the mechanisms involved have not been elucidated. Considering that gut‐liver crosstalk is the main pathway through which bEVs take part in NAFLD pathogenesis, we summarize the recent findings of bEVs in gut‐liver crosstalk by modulating the reshape of gut microbial system, host intestinal barrier integrity, host immune responses and metabolic homeostasis, as well as the potential roles of bEVs in regulating NAFLD progression.

The H6H6 subtype avian influenza virus (AIV) is currently prevalent in wild birds and poultry. Its host range has gradually expanded to mammals, such as swines. Some strains have even acquired the ability to bind to human-like SAα-2,6 Gal receptors, thus increasing the risk of animal to human transmission. To investigate whether the H6N6 AIV can overcome interspecies barriers from poultry to mammals and even to humans, we have assessed the molecular characteristics, receptor-binding preference, replication in mice and human lungs of three chicken-originated H6N6 strains. Among these, the A/CK/Zhangzhou/346/2014 (ZZ346) virus with the P186T, H156R, and S263G mutations of the hemagglutinin molecule showed the ability to bind to avian-like SAα-2,3 Gal and human-like SAα-2,6 Gal receptors. Moreover, H6N6 viruses, especially the ZZ346 strain, could replicate and infect mice and human lungs. Our study showed the H6N6 virus binding to both avian-like and human-like receptors, confirming its ability to cross the species barrier to infect mice and human lungs without prior adaptation. This study emphasizes the importance of continuous and intense monitoring of the H6N6 evolution in terrestrial birds.

Abstract Life is indeed continuously going through the irreversible and inevitable process of aging. The rate of aging process depends on various factors and varies individually. These factors include various environmental stimuli including exposure to toxic chemicals, psychological stress whereas suffering with various illnesses specially the chronic diseases serve as endogenous triggers. The basic underlying mechanism for all kinds of stresses is now known to be manifested as production of excessive ROS, exhaustion of ROS neutralizing antioxidant enzymes and proteins leading to imbalance in oxidation and antioxidant processes with subsequent oxidative stress induced inflammation affecting the cells, tissues, organs and the whole body. All these factors lead to conventional cell death either through necrosis, apoptosis, or autophagy. Currently, a newly identified mechanism of iron dependent regulated cell death called ferroptosis, is of special interest for its implication in pathogenesis of various diseases such as cardiovascular disease, neurological disorders, cancers, and various other age-related disorders (ARD). In ferroptosis, the cell death occur neither by conventional apoptosis, necrosis nor by autophagy, rather dysregulated iron in the cell mediates excessive lipid peroxidation of accumulated lethal lipids. It is not surprising to assume its role in aging as previous research have identified some solid cues on the subject. In this review, we will highlight the factual evidences to support the possible role and implication of ferroptosis in aging in order to declare the need to identify and explore the interventions to prevent excessive ferroptosis leading to accelerated aging and associated liabilities of aging.

The Pentose Phosphate Pathway (PPP), a metabolic offshoot of the glycolytic pathway, provides protective metabolites and molecules essential for cell redox balance and survival. Transketolase (TKT) is the critical enzyme that controls the extent of “traffic flow” through the PPP. Here, we explored the role of TKT in maintaining the health of the human retina. We found that Müller cells were the primary retinal cell type expressing TKT in the human retina. We further explored the role of TKT in human Müller cells by knocking down its expression in primary cultured Müller cells (huPMCs), isolated from the human retina (11 human donors in total), under light-induced oxidative stress. TKT knockdown and light stress reduced TKT enzymatic activities and the overall metabolic activities of huPMCs with no detectable cell death. TKT knockdown restrained the PPP traffic flow, reduced the expression of NAD(P)H Quinone Dehydrogenase 1 (NQO1), impaired the antioxidative response of NRF2 to light stress and aggravated the endoplasmic reticulum (ER) stress. TKT knockdown also inhibited overall glucose intake, reduced expression of Dihydrolipoamide dehydrogenase (DLD) and impaired the energy supply of the huPMCs. In summary, Müller cell-mediated TKT activity plays a critical protective role in the stressed retina. Knockdown of TKT disrupted the PPP and impaired overall glucose utilisation by huPMCs and rendered huPMCs more vulnerable to light stress by impairing energy supply and antioxidative NRF2 responses.