COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas.

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.

Foxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasis.

The liver plays a crucial role in maintaining systemic iron homeostasis by secreting hepcidin, which is essential for coordinating iron levels in the body. Imbalances in iron homeostasis are associated with various clinical disorders related to iron deficiency or iron overload. Despite the clinical significance, the mechanisms underlying how hepatocytes sense extracellular iron levels to regulate hepcidin synthesis and iron storage are not fully understood. In this study, we identified Foxo1, a well-known regulator of macronutrient metabolism, that translocates to the nucleus of hepatocytes in response to high-iron feeding, holo-transferrin, and BMP6 treatment. Furthermore, Foxo1 plays a crucial role in mediating hepcidin induction in response to both iron and BMP signals by directly interacting with evolutionally conserved Foxo binding sites within the hepcidin promoter region. These binding sites were found to colocalize with Smad-binding sites. To investigate the physiological relevance of Foxo1 in iron metabolism, we generated mice with hepatocyte-specific deletion of Foxo1. These mice exhibited reduced hepatic hepcidin expression and serum hepcidin levels, accompanied by elevated serum iron and liver non-heme iron concentrations. Moreover, high-iron diet further exacerbated these abnormalities in iron metabolism in mice lacking hepatic Foxo1. Conversely, hepatocyte-specific Foxo1 overexpression increased hepatic hepcidin expression and serum hepcidin levels, thereby ameliorating iron overload in a murine model of hereditary hemochromatosis (Hfe-/- mice). In summary, our study identifies Foxo1 is a critical regulator of hepcidin and systemic iron homeostasis. Targeting Foxo1 may offer therapeutic opportunities for managing conditions associated with aberrant iron metabolism.

How plants manage pathogen infection.

To combat microbial pathogens, plants have evolved specific immune responses that can be divided into three essential steps: microbial recognition by immune receptors, signal transduction within plant cells, and immune execution directly suppressing pathogens. During the past three decades, many plant immune receptors and signaling components and their mode of action have been revealed, markedly advancing our understanding of the first two steps. Activation of immune signaling results in physical and chemical actions that actually stop pathogen infection. Nevertheless, this third step of plant immunity is under explored. In addition to immune execution by plants, recent evidence suggests that the plant microbiota, which is considered an additional layer of the plant immune system, also plays a critical role in direct pathogen suppression. In this review, we summarize the current understanding of how plant immunity as well as microbiota control pathogen growth and behavior and highlight outstanding questions that need to be answered.

A developmental landscape of 3D-cultured human pre-gastrulation embryos.

Our understanding of how human embryos develop before gastrulation, including spatial self-organization and cell type ontogeny, remains limited by available two-dimensional technological platforms1,2 that do not recapitulate the in vivo conditions3-5. Here we report a three-dimensional (3D) blastocyst-culture system that enables human blastocyst development up to the primitive streak anlage stage. These 3D embryos mimic developmental landmarks and 3D architectures in vivo, including the embryonic disc, amnion, basement membrane, primary and primate unique secondary yolk sac, formation of anterior-posterior polarity and primitive streak anlage. Using single-cell transcriptome profiling, we delineate ontology and regulatory networks that underlie the segregation of epiblast, primitive endoderm and trophoblast. Compared with epiblasts, the amniotic epithelium shows unique and characteristic phenotypes. After implantation, specific pathways and transcription factors trigger the differentiation of cytotrophoblasts, extravillous cytotrophoblasts and syncytiotrophoblasts. Epiblasts undergo a transition to pluripotency upon implantation, and the transcriptome of these cells is maintained until the generation of the primitive streak anlage. These developmental processes are driven by different pluripotency factors. Together, findings from our 3D-culture approach help to determine the molecular and morphogenetic developmental landscape that occurs during human embryogenesis.

Lead Bromide Complex in Tri-n-octylphosphine Oxide Matrix with Bright Photoluminance and Exceptional Thermoplasticity.

Metal halide materials have recently drawn increasing research interest for their excellent opto-electronic properties and structural diversity, but their resulting rigid structures render them brittle and poor formability during manufacturing. Here we demonstrate a thermoplastic luminant hybrid lead halide solid by integrating lead bromide complex into tri-n-octylphosphine oxide (TOPO) matrix. The construction of the hybrid materials can be achieved by a simple dissolution process, in which TOPO molecules act as the solvents and ligands to yield the monodispersed clusters. The combination of these functional units enables the near-room-temperature melt-processing of the materials into targeted geometry by simple molding or printing techniques, which offer possibilities for fluorescent writing inks with outstanding self-healing capacity to physical damage. The intermarriage between metal halide clusters with functional molecules expands the range of practical applications for hybrid metal halide materials.

Short-Process Regeneration of Highly Stable Spherical LiCoO2 Cathode Materials from Spent Lithium-Ion Batteries through Carbonate Precipitation.

High-efficacy recycling of spent lithium cobalt oxide (LiCoO2 ) batteries is one of the key tasks in realizing a global resource security strategy due to the rareness of lithium (Li) and cobalt (Co) resources. However, it is of great significance to develop the innovative recycle methods for spent LiCoO2 , simultaneously realizing the efficient recovery of valuable elements and the regeneration of high-performance LiCoO2 . Herein, a novel strategy of regenerating LiCoO2 cathode is proposed, which involves the preparation of micro-spherical aluminum (Al)-doped lithium-lacked precursor (Li2x Co1-x-y Al2/3y CO3, remarked as "PLCAC") via ammonium bicarbonate coprecipitation. The comprehensive conditions affecting particle growth kinetics, morphology and particle size the has been investigated in detail by physical characterizations and electrochemical measurements. And the optimized Al-doped LiCoO2 materials with high-density sphericity (LiCo1-z Alz O2 , remarked as "LCAO") shows a high initial specific capacity of 161 mAh g-1 at 0.1 C and excellent capacity retention of 99.5 % within 100 cycles at 1 C in the voltage range of 2.8 to 4.3 V. Our work provides valuable insights into the featured design of LiCoO2 precursors and cathode materials from spent LiCoO2 batteries, potentially guaranteeing the high-efficacy recycling and utilization of strategic resources.

Residual networks without pooling layers improve the accuracy of genomic predictions.

KEY MESSAGE: Residual neural network genomic selection is the first GS algorithm to reach 35 layers, and its prediction accuracy surpasses previous algorithms. With the decrease in DNA sequencing costs and the development of deep learning, phenotype prediction accuracy by genomic selection (GS) continues to improve. Residual networks, a widely validated deep learning technique, are introduced to deep learning for GS. Since each locus has a different weighted impact on the phenotype, strided convolutions are more suitable for GS problems than pooling layers. Through the above technological innovations, we propose a GS deep learning algorithm, residual neural network for genomic selection (ResGS). ResGS is the first neural network to reach 35 layers in GS. In 15 cases from four public data, the prediction accuracy of ResGS is higher than that of ridge-regression best linear unbiased prediction, support vector regression, random forest, gradient boosting regressor, and deep neural network genomic prediction in most cases. ResGS performs well in dealing with gene-environment interaction. Phenotypes from other environments are imported into ResGS along with genetic data. The prediction results are much better than just providing genetic data as input, which demonstrates the effectiveness of GS multi-modal learning. Standard deviation is recommended as an auxiliary GS evaluation metric, which could improve the distribution of predicted results. Deep learning for GS, such as ResGS, is becoming more accurate in phenotype prediction.

Enhancement and modulation of valley polarization in Janus CrSSe with internal and external electric fields.

The valley polarization, induced by the magnetic proximity effect, in monolayer transition metal dichalcogenides (TMDCs), has attracted significant attention due to the intriguing fundamental physics. However, the enhancement and modulation of valley polarization for real device applications is still a challenge. Here, using first-principles calculations we investigate the valley polarization properties of monolayer TMDCs CrS2 and CrSe2 and how to enhance the valley polarization by constructing Janus CrSSe (with an internal electric field) and modulate the polarization in CrSSe by applying external electric fields. Janus CrSSe exhibits inversion symmetry breaking, internal electric field, spin-orbit coupling, and compelling spin-valley coupling. A magnetic substrate of the MnO2 monolayer can induce a modest magnetic moment in CrSe2, CrSe2, and CrSSe. Notably, the Janus structure with an internal electric field has a much larger valley p compared with its non-Janus counterparts. Moreover, the strength of valley polarization can be further modulated by applying external electric fields. These findings suggest that Janus materials hold promise for designing and developing advanced valleytronic devices.

Correlation between TCF7L2 and CAPN10 gene polymorphisms and gestational diabetes mellitus in different geographical regions: a meta-analysis.

BACKGROUND: The association between TCF7L2 and CAPN10 gene polymorphisms and gestational diabetes mellitus (GDM) has been explored in diverse populations across different geographical regions. Yet, most of these studies have been confined to a limited number of loci, resulting in inconsistent findings. In this study, we conducted a comprehensive review of published literature to identify studies examining the relationship between TCF7L2 and CAPN10 gene polymorphisms and the incidence of GDM in various populations. We specifically focused on five loci that were extensively reported in a large number of publications and performed a meta-analysis. METHODS: We prioritized the selection of SNPs with well-documented correlations established in existing literature on GDM. We searched eight Chinese and English databases: Cochrane, Elton B. Stephens. Company (EBSCO), Embase, Scopus, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database and retrieved all relevant articles published between the inception of the database and July 2022. The Newcastle Ottawa Scale (NOS) was used to evaluate the selected articles, and the odds ratio (OR) was used as the combined effect size index to determine the association between genotypes, alleles, and GDM using different genetic models. Heterogeneity between the studies was quantified and the I2 value calculated. Due to large heterogeneities between different ethnic groups, subgroup analysis was used to explore the correlation between genetic polymorphisms and the incidence of GDM in the different populations. The stability of the results was assessed using sensitivity analysis. Begg's and Egger's tests were used to assess publication bias. RESULTS: A total of 39 articles reporting data on 8,795 cases and 16,290 controls were included in the analysis. The frequency of the rs7901695 genotype was statistically significant between cases and controls in the European population (OR = 0.72, 95% CI: 0.65-0.86) and the American population (OR = 0.61, 95% CI: 0.48-0.77). The frequencies of rs12255372, rs7901695, rs290487, and rs2975760 alleles were also considerably different between the cases and controls in the populations analyzed. CONCLUSIONS: rs7903146, rs12255372, rs7901695, rs290487, and rs2975760 were associated with the incidence of GDM in different populations.

High mobility group AT-hook 1 (HMGA1) is an important positive regulator of hepatitis B virus (HBV) that is reciprocally upregulated by HBV X protein.

Chronic infection with hepatitis B virus (HBV) is associated with liver cirrhosis and hepatocellular carcinoma. Upon infection of hepatocytes, HBV covalently closed circular DNA (cccDNA) exists as histone-bound mini-chromosome, subjected to transcriptional regulation similar to chromosomal DNA. Here we identify high mobility group AT-hook 1 (HMGA1) protein as a positive regulator of HBV transcription that binds to a conserved ATTGG site within enhancer II/core promoter (EII/Cp) and recruits transcription factors FOXO3α and PGC1α. HMGA1-mediated upregulation of EII/Cp results in enhanced viral gene expression and genome replication. Notably, expression of endogenous HMGA1 was also demonstrated to be upregulated by HBV, which involves HBV X protein (HBx) interacting with SP1 transcription factor to activate HMGA1 promoter. Consistent with these in vitro results, chronic hepatitis B patients in immune tolerant phase display both higher intrahepatic HMGA1 protein levels and higher serum HBV markers compared to patients in inactive carrier phase. Finally, using a mouse model of HBV persistence, we show that targeting endogenous HMGA1 through RNA interference facilitated HBV clearance. These data establish HMGA1 as an important positive regulator of HBV that is reciprocally upregulated by HBV via HBx and also suggest the HMGA1-HBV positive feedback loop as a potential therapeutic target.

Environmental enrichment improves behaviors rather than the growth and physiology of rock bream Oplegnathus fasciatus.

Environmental enrichment has the potential to improve the welfare and post-release survival of hatchery fish stocked for conservation purposes. However, the effectiveness of environmental enrichment is partly dependent on the fish species, life stage, and specific enrichment structure used. To enhance the effectiveness of environmental enrichment, it is crucial to focus on characteristic differences in enrichment structures, such as type and level. This study investigated how differences in enrichment type and level affected physiological and behavioral aspects of the welfare of pre-release juvenile rock bream Oplegnathus fasciatus by evaluating growth performance, basal and stressed cortisol levels, antioxidant enzyme activities, and exploratory behaviors regarding anxiety and flexibility. Fish were reared for 4 weeks in different enrichment treatments: barren, low-level cover structure, high-level cover structure, low-level interference structure (LI), and high-level interference structure (HI). The results revealed that fish reared with the LI treatment showed less anxiety and greater flexibility with respect to exploratory behaviors, without oxidative damage being detected. Despite exhibiting less anxiety as well, fish reared in the HI treatment had oxidative damage, indicated by lower superoxide dismutase activity, compared to those in the barren treatment. In addition, none of these enrichment structures enhanced growth performance or mitigate chronic and acute stress responses. Overall, the low-level interference structure may be more favorable in promoting the behavioral welfare of the fish. Application of this type and level of enrichment may increase the survival of the hatchery fish after release, which is critical to stocking success.

Facile Recycling of Waste Biomass for Preparation of Hierarchical Porous Carbon with High-Performance Electromagnetic Wave Absorption.

Hierarchical-porous-structured materials have been widely used in the field of electromagnetic wave (EMW) absorption, playing a critical role in minimizing EMW interference and pollution. High-quality EMW absorbers, characterized by a lower thickness, lighter weight, wider absorption band, and stronger absorption capacity, have been instrumental in reducing damage and preventing malfunctions in the automotive and aviation industries. The utilization of discarded nut shells through recycling can not only alleviate environmental problems but relieve resource constraints. Herein, a facile method for the preparation of hierarchical porous biomass carbon derived from abandoned Xanthoceras Sorbifolium Bunge Shell (XSS) biomass was developed for high-performance EMW absorption. The porous structures of XSS biochar were studied by using different levels of the K2CO3 activator and simple carbonization. The effect of K2CO3 on the EMW parameters, including the complex permittivity, complex permeability, polarization relaxation, and impedance matching, was analyzed. The best EMW absorption performance of the XSS biochar was observed at a mass ratio of activator-to-biomass of 2:1. A minimum reflection loss (RLmin) of -38.9 dB was achieved at 9.12 GHz, and a maximum effective absorption bandwidth (EABmax) of up to 3.28 GHz (14.72~18.0 GHz) could be obtained at a 1.8 mm thickness. These results demonstrated that hierarchical porous XSS carbon was prepared successfully. Simultaneously, the prepared XSS biochar was confirmed as a potential and powerfully attractive EMW-absorbing material. The proposal also provided a simple strategy for the development of a green, low-cost, and sustainable biochar as a lightweight high-performance absorbing material.

Effect of Lacticaseibacillus paracasei K56 with galactooligosaccharide synbiotics on obese individuals: an in vitro fermentation model.

BACKGROUND: The use of synbiotics is emerging as a promising intervention strategy for regulating the gut microbiota and for preventing or reducing obesity, in comparison with the use of probiotics or prebiotics alone. A previous in vivo study revealed that Lacticaseibacillus paracasei K56 (L. paracasei K56) could alleviate obesity induced in high-fat-diet mice; however, the effect of the synbiotic combination of L. paracasei K56 and prebiotics in obese individuals has not been explored fully. RESULTS: The effect of prebiotics on the proliferation of L. paracasei K56 was determined by spectrophotometry. The results showed that polydextrose (PG), xylooligosaccharide (XOS), and galactooligosaccharide (GOS) had a greater potential to be used as substrates for L. paracasei K56 than three other prebiotics (melitose, stachyose, and mannan-oligosaccharide). An in vitro fermentation model based on the feces of ten obese female volunteers was then established. The results revealed that K56_GOS showed a significant increase in GOS degradation rate and short-chain fatty acid (SCFA) content, and a decrease in gas levels, compared with PG, XOS, GOS, K56_PG, and K56_XOS. Changes in these microbial biomarkers, including a significant increase in Bacteroidota, Bifidobacterium, Lactobacillus, Faecalibacterium, and Blautia and a decrease in the Firmicutes/Bacteroidota ratio and Escherichia-Shigella in the K56_GOS group, were associated with increased SCFA content and decreased gas levels. CONCLUSION: This study demonstrates the effect of the synbiotic combination of L. paracasei K56 and GOS on obese individuals and indicates its potential therapeutic role in obesity treatment. © 2024 Society of Chemical Industry.

Lower frequency of MDSCs was significantly related to functional cure in CHB patients treated with peginterferon.

BACKGROUND AND AIMS: Myeloid-derived suppressor cells (MDSCs) and CD4+ regulatory T cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity. However, the relationship between antiviral effect and the frequencies of those immune suppressive cells after pegylated interferon α-2a (PegIFNα-2a) therapy is not clearly understood. This study aimed to investigate the contribution of monocytic MDSCs (mMDSCs) and CD4+ Tregs to functional cure (HBsAg seroclearance) after PegIFNα-2a therapy and evaluate the effect of PegIFNα-2a therapy on these cells. METHODS: Flow cytometry analysis was performed along with longitudinal immune monitoring of 97 hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) patients receiving PegIFNα-2a weekly for 48 weeks. RESULTS: The frequencies of mMDSCs and CD4+ Tregs increased in all HBV patients, and they were higher in the HBsAg persistence group than in the HBsAg seroclearance group. A significant decline in the frequency of mMDSCs was found in patients who realized functional cure after PegIFNα-2a treatment. In contrast, the frequency of CD4+ Tregs in both the HBsAg seroclearance and persistence groups significantly increased. Multivariate analyses indicated that the baseline serum HBsAg levels (p < .001) and mMDSCs frequency (p = .027) were independently associated with the HBsAg clearance, and the combined marker (HBsAg plus mMDSCs) displayed the highest specificity (93.1%) than any other markers in predicting HBsAg seroclearance. CONCLUSIONS: These results suggest that a poor response to PegIFNα-2a treatment in CHB patients may be related to the frequencies of immune suppressive cells, while the therapeutic targeting of these cells might be effective in boosting anti-HBV immunity.

Applications and Challenges of Bacteriostatic Aptamers in the Treatment of Common Pathogenic Bacteria Infections.

The continuous evolution and spread of common pathogenic bacteria is a major challenge in diagnosis and treatment with current biotechnology and modern molecular medicine. To confront this challenge, scientists urgently need to find alternatives for traditional antimicrobial agents. Various bacteriostatic aptamers obtained through SELEX screening are one of the most promising strategies. These bacteriostatic aptamers can reduce bacterial infection by blocking bacterial toxin infiltration, inhibiting biofilm formation, preventing bacterial invasion of immune cells, interfering with essential biochemical processes, and other mechanisms. In addition, aptamers may also help enhance the function of other antibacterial materials/drugs when used in combination. This paper has reviewed the bacteriostatic aptamers in the treatment of common pathogenic bacteria infections. For this aspect, first, bacteriostatic aptamers and their screening strategies are summarized. Then, the effect of molecular tailoring and modification on the performance of the bacteriostatic aptamer is analyzed, and the antibacterial mechanism and antibacterial strategy based on aptamers are introduced. Finally, the key technical challenges and their development prospects in clinical treatment are also carefully discussed.

Solvent-free base-controlled addition reaction of H-phosphonates and H-phosphine oxides to α-CF3 styrenes: facile synthesis of ß-CF3-substituted phosphonates and phosphine oxides.

A practical and efficient solvent-free synthesis of ß-trifluoromethyl-substituted phosphonates and phosphine oxides via hydrophosphonylation and hydrophosphinylation of α-(trifluoromethyl)styrenes with H-phosphonates and H-phosphine oxides, respectively, was developed. The reaction proceeded smoothly within 2 h at room temperature without the cleavage of the rather fragile C-F bond in α-(trifluoromethyl)styrenes and afforded a wide variety of structurally diverse and valuable ß-trifluoromethyl-containing phosphonates and phosphine oxides in moderate to good yields. This protocol features mild conditions, wide substrate scope, simple manipulation, and excellent functional group compatibility.

Dietary intakes of total, nonheme, and heme iron and hypertension risk: a longitudinal study from the China Health and Nutrition Survey.

AIMS: Evidence is limited regarding the long-term impact of dietary iron intake on the development of hypertension. We investigated the association between dietary intakes of total, nonheme, and heme iron and hypertension risk in a large prospective cohort of Chinese populations over 26 years. METHODS: A total of 16,122 adults (7810 men and 8312 women) who participated in the China Health and Nutrition Survey (1989-2015) were included. Dietary intake was repeatedly assessed by combining three consecutive 24­h individual dietary recalls with household food inventory weighing at each survey round. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, diagnosis by physicians, or current use of anti-hypertensive drugs. RESULTS: During a median follow­up of 11.1 years, 2863 men and 2532 women developed hypertension. After adjustment for non-dietary and dietary factors, a lower risk of hypertension was found in men and women with higher intakes of total, nonheme, or heme iron. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest vs. lowest quartiles were 0.76 (0.67, 0.87) in men and 0.85 (0.74, 0.97) in women for total iron intake, 0.77 (0.67, 0.87) in men and 0.85 (0.74, 0.98) in women for nonheme iron intake, and 0.73 (0.62, 0.87) in men and 0.69 (0.58, 0.82) in women for heme iron intake. Dose-response analyses further revealed a U-shaped association of total and nonheme iron intake and an L-shaped association of heme iron intake with hypertension risk in both men and women (all P for non-linearity < 0.001). CONCLUSIONS: Our findings emphasize the importance of maintaining moderate iron intake in the prevention of hypertension. Both insufficient and excess intake of iron might increase the risk of hypertension.

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

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

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

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