An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors.

Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved >80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.

GammaGateR: semi-automated marker gating for single-cell multiplexed imaging.

MOTIVATION: Multiplexed immunofluorescence (mIF) is an emerging assay for multichannel protein imaging that can decipher cell-level spatial features in tissues. However, existing automated cell phenotyping methods, such as clustering, face challenges in achieving consistency across experiments and often require subjective evaluation. As a result, mIF analyses often revert to marker gating based on manual thresholding of raw imaging data. RESULTS: To address the need for an evaluable semi-automated algorithm, we developed GammaGateR, an R package for interactive marker gating designed specifically for segmented cell-level data from mIF images. Based on a novel closed-form gamma mixture model, GammaGateR provides estimates of marker-positive cell proportions and soft clustering of marker-positive cells. The model incorporates user-specified constraints that provide a consistent but slide-specific model fit. We compared GammaGateR against the newest unsupervised approach for annotating mIF data, employing two colon datasets and one ovarian cancer dataset for the evaluation. We showed that GammaGateR produces highly similar results to a silver standard established through manual annotation. Furthermore, we demonstrated its effectiveness in identifying biological signals, achieved by mapping known spatial interactions between CD68 and MUC5AC cells in the colon and by accurately predicting survival in ovarian cancer patients using the phenotype probabilities as input for machine learning methods. GammaGateR is a highly efficient tool that can improve the replicability of marker gating results, while reducing the time of manual segmentation. AVAILABILITY AND IMPLEMENTATION: The R package is available at https://github.com/JiangmeiRubyXiong/GammaGateR.

Age-related mitophagy regulates orthodontic tooth movement by affecting PDLSCs mitochondrial function and RANKL/OPG.

A thorough comprehension of age-related variances in orthodontic tooth movement (OTM) and bone remodeling response to mechanical force holds significant implications for enhancing orthodontic treatment. Mitophagy plays a crucial role in bone metabolism and various age-related diseases. However, the impact of mitophagy on the bone remodeling process during OTM remains elusive. Using adolescent (6 weeks old) and adult (12 months old) rats, we established OTM models and observed that orthodontic force increased the expression of the mitophagy proteins PTEN-induced putative kinase 1 (PINK1) and Parkin, as well as the number of tartrate-resistant acid phosphatase-positive osteoclasts and osteocalcin-positive osteoblasts. These biological changes were found to be age-related. In vitro, compression force loading promoted PINK1/Parkin-dependent mitophagy in periodontal ligament stem cells (PDLSCs) derived from adolescents (12-16 years old) and adults (25-35 years old). Furthermore, adult PDLSCs exhibited lower levels of mitophagy, impaired mitochondrial function, and a decreased ratio of RANKL/OPG compared to young PDLSCs after compression. Transfection of siRNA confirmed that inhibition of mitophagy in PDLSC resulted in decreased mitochondrial function and reduced RANKL/OPG ratio. Application of mitophagy inducer Urolithin A enhanced bone remodeling and accelerated OTM in rats, while the mitophagy inhibitor Mdivi-1 had the opposite effect. These findings indicate that force-stimulated PDLSC mitophagy contributes to alveolar bone remodeling during OTM, and age-related impairment of mitophagy negatively impacts the PDLSC response to mechanical stimulus. Our findings enhance the understanding of mitochondrial mechanotransduction and offer new targets to tackle current clinical challenges in orthodontic therapy.

MiR-519e-5p regulates malignant phenotype of breast cancer cells through binding to CTPS1.

MiR-519e-5p and CTPS1 are aberrantly expressed in breast cancer (BC). However, the molecular mechanisms underlying tumorigenesis and development are unknown, and their potential as therapeutic targets needs to be explored. The molecular biology was explored through in vitro cellular experiments, tumor xenograft assay, and analysis of gene expression in human tissue and serum samples. We found that miR-519e-5p expression was much lower and CTPS1 expression was much higher in BC tissues and cells than in the normal tissues and cells. BC cells overexpressing miR-519e-5p or CTPS1 knockdown demonstrated decreased proliferation, migration, and invasion, whereas miR-519e-5p knockdown had the opposite effect. Further studies showed that there is a binding site between miR-519e-5p and CTPS1, leading to their interaction, CTPS1 overexpression and could partially reverse the inhibitory effects of miR-519e-5p overexpression on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). CTPS1 serum levels were higher in patients with BC, and these levels were associated with some highly correlated clinical indicators, including age, HER-2 index, and T and N staging. Overall, miR-519e-5p slows the proliferation, invasion, migration, and EMT of BC by binding to CTPS1. This study offers a new direction for BC treatment.

B regulatory cells in allergy.

B cells have classically been recognized for their unique and indispensable role in the production of antibodies. Their potential as immunoregulatory cells with anti-inflammatory functions has received increasing attention during the last two decades. Herein, we highlight pioneering studies in the field of regulatory B cell (Breg) research. We will review the literature on Bregs with a particular focus on their role in the regulation of allergic inflammation.

Influence of Sex on Respiratory Syncytial Virus Genotype Infection Frequency and Nasopharyngeal Microbiome.

Respiratory syncytial virus (RSV) has a significant health burden in children, older adults, and the immunocompromised. However, limited effort has been made to identify emergence of new RSV genotypes' frequency of infection and how the combination of nasopharyngeal microbiome and viral genotypes impact RSV disease outcomes. In an observational cohort designed to capture the first infant RSV infection, we employed multi-omics approaches to sequence 349 RSV complete genomes and matched nasopharyngeal microbiomes, during which the 2012/2013 season was dominated by RSV-A, whereas 2013 and 2014 was dominated by RSV-B. We found non-G-72nt-duplicated RSV-A strains were more frequent in male infants (P = 0.02), whereas G-72nt-duplicated genotypes (which is ON1 lineage) were seen equally in both males and females. DESeq2 testing of the nasal microbiome showed Haemophilus was significantly more abundant in infants with RSV-A infection compared to infants with RSV-B infection (adjusted P = 0.002). In addition, the broad microbial clustering of the abundant genera was significantly associated with infant sex (P = 0.03). Overall, we show sex differences in infection by RSV genotype and host nasopharyngeal microbiome, suggesting an interaction between host genetics, virus genotype, and associated nasopharyngeal microbiome. IMPORTANCE Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infections in young children and is responsible for high hospitalization rates and morbidity in infants and the elderly. To understand how the emergence of RSV viral genotypes and viral-respiratory microbiome interactions contribute to infection frequency and severity, we utilized an observational cohort designed to capture the first infant RSV infection we employed multi-omics approaches to sequence 349 RSV complete genomes and matched nasopharyngeal microbiomes. We found non-G-72nt-duplicated RSV-A genotypes were more frequent in male infants, whereas G-72nt-duplicated RSV-A strains (ON1 lineage) were seen equally in both males and females. Microbiome analysis show Haemophilus was significantly more abundant in infants with RSV-A compared to infants with RSV-B infection and the microbial clustering of the abundant genera was associated with infant sex. Overall, we show sex differences in RSV genotype-nasopharyngeal microbiome, suggesting an interaction host genetics-virus-microbiome interaction.

Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses.

Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.

The downregulation of Tapasin in dendritic cell regulates CD8+ T cell autophagy to hamper hepatitis B viral clearance in the induced pluripotent stem cell-derived hepatocyte organoid.

Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO.

Children with eosinophilic esophagitis non-responsive to combination therapy have distinct esophageal transcriptomic and microbiome profile.

BACKGROUND: A combination of proton-pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non-responders (EoE-PPI-TSnr; n = 7) and responders (EoE-PPI-TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics. METHODS: Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. RESULTS: In all, 3164 upregulated and 3154 downregulated genes distinguished EoE-PPI-TSnr from EoE-PPI-TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE-PPI-TSnr. There was a 56% overlap in dysregulated genes between EoE-PPI-TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic-erythroid progenitors, and T helper type 1 cells were significantly higher in EoE-PPI-TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE-PPI-TSnr and correlated with the key pathways. CONCLUSION: Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.

A case report of prolonged viral shedding of SARS-CoV-2 in a patient who receive ibrutinib for CLL therapy.

Patients on B cell immunosuppressive treatments have been shown to have persistent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, a woman treated with ibrutinib for chronic lymphocytic leukemia experienced more than 40 days of coronavirus disease 2019 (COVID-19) infection. Unexpectedly, her peripheral blood experiments showed a normal SARS-CoV-2-specific antibody level and a relatively elevated percentage of CD19 + B cells, while an obvious decrease in the percentages of NK cells, CD4 + T cells and CD8 + T cells. Further SARS-CoV-2-specific T cell analysis in this patient indicated a significant decrease in the percentage of SARS-CoV-2-specific IFN-γ, TNF-α or IL-2 producing CD4 + T or CD8 + T cells. Most notably, ten days after the cease of ibrutinib, the PCR for SARS-CoV-2 turned negative and the reduced proportions of peripheral CD4 + T cells and CD8 + T cells recovered. Our research predicted that the depleted B-cell function therapies may play considerable role in the development of long COVID-19 and the abnormal T-cell subset distribution might be the underlying mechanism.

Evolution and Potential Subfunctionalization of Duplicated fms-Related Class III Receptor Tyrosine Kinase flt3s and Their Ligands in the Allotetraploid Xenopus laevis.

The fms-related tyrosine kinase 3 (Flt3) and its ligand (Flt3lg) are important regulators of hematopoiesis and dendritic cell (DC) homeostasis with unsettled coevolution. Gene synteny and deduced amino acid sequence analyses identified conserved flt3 gene orthologs across all jawed vertebrates. In contrast, flt3lg orthologs were not retrieved in ray-finned fish, and the gene locus exhibited more variability among species. Interestingly, duplicated flt3/flt3lg genes were maintained in the allotetraploid Xenopus laevis Comparison of modeled structures of X. laevis Flt3 and Flt3lg homoeologs with the related diploid Xenopus tropicalis and with humans indicated a higher conformational divergence between the homoeologous pairs than their respective counterparts. The distinctive developmental and tissue expression patterns of Flt3 and Flt3lg homoeologs in tadpoles and adult frogs suggest a subfunctionalization of these homoeologs. To characterize Flt3 cell surface expression, X. laevis-tagged rFlt3lg.S and rFlt3lg.L were produced. Both rFlt3lg.S and rFlt3lg.L bind in vitro Flt3.S and Flt3.L and can trigger Erk1/2 signaling, which is consistent with a partial overlapping function between homoeologs. In spleen, Flt3.S/L cell surface expression was detected on a fraction of B cells and a population of MHC class IIhigh/CD8+ leukocytes phenotypically similar to the recently described dual follicular/conventional DC-like XL cells. Our result suggests that 1) Flt3lg.S and Flt3lg.L are both involved in XL cell homeostasis and that 2) XL cells have hematopoietic origin. Furthermore, we detected surface expression of the macrophage/monocyte marker Csf1r.S on XL cells as in mammalian and chicken DCs, which points to a common evolutionary origin in vertebrate DCs.

Pregnancy-induced physiological hypertrophic preconditioning attenuates pathological myocardial hypertrophy by activation of FoxO3a.

Previous studies show a woman's pregnancy is correlated with post-reproductive longevity, and nulliparity is associated with higher risk of incident heart failure, suggesting pregnancy likely exerts a cardioprotection. We previously reported a cardioprotective phenomenon termed myocardial hypertrophic preconditioning, but it is unknown whether pregnancy-induced physiological hypertrophic preconditioning (PHP) can also protect the heart against subsequent pathological hypertrophic stress. We aimed to clarify the phenomenon of PHP and its mechanisms. The pluripara mice whose pregnancy-induced physiological hypertrophy regressed and the nulliparous mice underwent angiotensin II (Ang II) infusion or transverse aortic constriction (TAC). Echocardiography, invasive left ventricular hemodynamic measurement and histological analysis were used to evaluate cardiac remodeling and function. Silencing or overexpression of Foxo3 by adeno-associated virus was used to investigate the role of FoxO3a involved in the antihypertrophic effect. Compared with nulliparous mice, pathological cardiac hypertrophy induced by Ang II infusion, or TAC was significantly attenuated and heart failure induced by TAC was markedly improved in mice with PHP. Activation of FoxO3a was significantly enhanced in the hearts of postpartum mice. FoxO3a inhibited myocardial hypertrophy by suppressing signaling pathway of phosphorylated glycogen synthase kinase-3ß (p-GSK3ß)/ß-catenin/Cyclin D1. Silencing or overexpression of Foxo3 attenuated or enhanced the anti-hypertrophic effect of PHP in mice with pathological stimulation. Our findings demonstrate that PHP confers resistance to subsequent hypertrophic stress and slows progression to heart failure through activation of FoxO3a/GSK3ß pathway.

Enhancing traumatic brain injury emergency care: the impact of grading and zoning nursing management.

OBJECTIVE: This research aimed to evaluate the impact of grading and zoning nursing management on traumatic brain injury (TBI) patients' emergency treatment outcomes. METHODS: This randomized controlled trial included 200 TBI patients. They were treated with a conventional care (control group, n = 100) and a novel grading and zoning approach (study group, n = 100), respectively. This innovative model organized care into levels based on urgency and complexity, facilitating targeted medical response and resource allocation. Key metrics compared included demographic profiles, consultation efficiency (time metrics and emergency treatment rates), physiological parameters (HR, RR, MAP, SpO2, RBS), and patient outcomes (hospital and ICU stays, complication rates, and emergency outcomes). RESULTS: The study group demonstrated significantly improved consultation efficiency, with reduced times for physician visits, examinations, emergency stays, and specialist referrals (all p < 0.001), alongside a higher emergency treatment rate (93% vs. 79%, p = 0.004), notably better physiological stability, improved HR, RR, MAP, SpO2 and RBS (p < 0.001), shorter hospital and ICU stays, fewer complications, and superior emergency outcomes. CONCLUSION: Grading and zoning nursing management substantially enhances TBI patients' emergency care efficiency and clinical outcomes, suggesting a viable model for improving emergency treatment protocols.

Mechanical Behavior Monitoring and Load Inversion Analysis of Large-Diameter Underwater Shield Tunnel during Construction.

The construction of large-diameter shield tunnels underwater involves complex variations in water and earth load outside the tunnel segment, as well as intricate mechanical responses. This study analyzes the variation laws of external loads, axial forces, and bending moments acting on the segment ring during the shield assembly and removal from the shield tail. It accomplishes this through the establishment of an on-site monitoring system based on the Internet of Things (IoT) and proposes a Bayesian-genetic algorithm model to estimate the water and earth pressure. The fluctuation section exhibits a peak load twice as high as that in the stable section. These variations are influenced by Jack thrust, shield shell force, and grouting pressure. The peak load observed in the fluctuation section is twice as high as the load observed in the stable section. During the shield tail removal process, the internal forces undergo significant fluctuations due to changes in both load and boundary conditions, and the peak value of the axial force during the fluctuation section is eight times higher than that during the stable section, while the peak value of the bending moment during the fluctuation section is five times higher than that during the stable section. The earth and water pressure calculated using the inversion analysis method, which relies on the measured internal forces, closely matches the actual measured values. The results demonstrate that the accuracy of the water and earth pressure obtained through inversion analysis is twice as high as that obtained using the full coverage pressure method. These results can serve as a valuable reference for similar projects.

Triterpenoid Saponins and Flavonoid Glycosides from the Flower of Camellia flavida and Their Cytotoxic and α-Glycosidase Inhibitory Activities.

Camellia flavida var. flavida, commonly known as "Jinhua Tea", has its flowers and leaves traditionally utilized as tea and functional food sources. However, there is limited knowledge about its bioactive components and their biological activities. This study isolated ten previously unidentified glycoside compounds from the flowers of Camellia flavida, including three oleanane-type triterpenoid saponins (compounds 1-3) and seven flavonoid glycosides (compounds 4-10), collectively named flavidosides A-J. This study assessed the cytotoxicity of these compounds against a panel of human cancer cell lines and their α-glucosidase inhibitory activities. Notably, flavidoside C showed significant cytotoxicity against BEL-7402 and MCF-7 cell lines, with IC50 values of 4.94 ± 0.41 and 1.65 ± 0.39 µM, respectively. Flavidoside H exhibited potent α-glucosidase inhibitory activity, with an IC50 value of 1.17 ± 0.30 mM. These findings underscore the potential of Camellia flavida in the development of functional foods.

Populus euphratica GRP2 Interacts with Target mRNAs to Negatively Regulate Salt Tolerance by Interfering with Photosynthesis, Na+, and ROS Homeostasis.

The transcription of glycine-rich RNA-binding protein 2 (PeGRP2) transiently increased in the roots and shoots of Populus euphratica (a salt-resistant poplar) upon initial salt exposure and tended to decrease after long-term NaCl stress (100 mM, 12 days). PeGRP2 overexpression in the hybrid Populus tremula × P. alba '717-1B4' (P. × canescens) increased its salt sensitivity, which was reflected in the plant's growth and photosynthesis. PeGRP2 contains a conserved RNA recognition motif domain at the N-terminus, and RNA affinity purification (RAP) sequencing was developed to enrich the target mRNAs that physically interacted with PeGRP2 in P. × canescens. RAP sequencing combined with RT-qPCR revealed that NaCl decreased the transcripts of PeGRP2-interacting mRNAs encoding photosynthetic proteins, antioxidative enzymes, ATPases, and Na+/H+ antiporters in this transgenic poplar. Specifically, PeGRP2 negatively affected the stability of the target mRNAs encoding the photosynthetic proteins PETC and RBCMT; antioxidant enzymes SOD[Mn], CDSP32, and CYB1-2; ATPases AHA11, ACA8, and ACA9; and the Na+/H+ antiporter NHA1. This resulted in (i) a greater reduction in Fv/Fm, YII, ETR, and Pn; (ii) less pronounced activation of antioxidative enzymes; and (iii) a reduced ability to maintain Na+ homeostasis in the transgenic poplars during long-term salt stress, leading to their lowered ability to tolerate salinity stress.

Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia.

BACKGROUND: The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing. METHODS: The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2. RESULTS: Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and ß-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed. CONCLUSIONS: Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.

Direct Quantitative Analysis of Fluorine in Solid Samples by Cryogenic Laser Ablation and Ionization Time-of-Flight Mass Spectrometry.

The determination of fluorine, the lightest element in halogens, suffers from high ionization potential and spectral interference from water molecules in mass spectrometry. Herein, we introduced a liquid nitrogen cooling unit into the laser ablation and ionization source for the first time to construct a cryogenic laser ablation and ionization time-of-flight mass spectrometry (Cryo-LAI-TOFMS) system. With this system, the interference of water-related species at m/z 19 was effectively eliminated, and fluorine atomization and ionization efficiency could reach 6.3%. A direct quantitative analysis method was developed to determine fluorine contents in phosphate rock, copper ore, industrial byproduct gypsum, stream sediment, and soil. Considering the simplicity, high sensitivity, and low spectral interference of this technique, it can be extended to the determination of fluorine content as low as µg/g in complex solid samples.

Benchmarking the Effect of Particle Size on Silicon Anode Materials for Lithium-Ion Batteries.

High-capacity silicon has been regarded as one of the most promising anodes for high-energy lithium-ion batteries. However, it suffers from severe volume expansion, particle pulverization, and repeated solid electrolyte interphase (SEI) growth, which leads to rapid electrochemical failure, while the particle size also plays key role here and its effects remain elusive. In this paper, through multiple-physical, chemical, and synchrotron-based characterizations, the evolutions of the composition, structure, morphology, and surface chemistry of silicon anodes with the particle size ranging from 50 to 5 µm upon cycling are benchmarked, which greatly link to their electrochemical failure discrepancies. It is found that the nano- and micro-silicon anodes undergo similar crystal to amorphous phase transition, but quite different composition transition upon de-/lithiation; at the same time, the nano- and 1 µm-silicon samples present obviously different mechanochemical behaviors from the 5 µm-silicon sample, such as electrode crack, particle pulverization/crack as well as volume expansion; in addition, the micro-silicon samples possess much thinner SEI layer than the nano-silicon samples upon cycling, and also differences in SEI compositions. It is hoped this comprehensive study and understanding should offer critical insights into the exclusive and customized modification strategies to diverse silicon anodes ranging from nano to microscale.

Exosomes loading Tapasin enhance T cell immune response by autophagy to inhibit HBV replication.

Hepatitis B virus (HBV) specific T cell immune response plays a vital role in viral clearance. Dendritic cell derived exosomes (Dexs) can activate T cell immunity effectively. Tapasin (TPN) is involved in antigen processing and specific immune recognition. In the present study, we elucidated that Dexs loading TPN (TPN-Dexs) could enhance CD8+ T cell immune response and inhibit virus replication in HBV transgenic mice. T cell immune response and the ability of inhibiting HBV replication were measured in HBV transgenic mice immunized with TPN-Dexs. Meanwhile, CD8+ T cell autophagy and specific T cell immune responses were measured in vitro and vivo, and the mechanisms probably involved in were explored. Purified TPN-Dexs could be taken up into the cytoplasm of DCs and upregulate CD8+ T cell autophagy to enhance specific T cell immune response. In addition, TPN-Dexs could increase the expression of AKT and decrease the expression of mTOR in CD8+ T cells. Further research confirmed that TPN-Dexs could inhibit virus replication and decrease the expression of HBsAg in the liver of HBV transgenic mice. Nevertheless, those also could elicit mice hepatocytes damage. In conclusion, TPN-Dexs could enhance specific CD8+ T cell immune responses via the AKT/mTOR pathway to regulate the autophagy and exert the antiviral effect in HBV transgenic mice.