The Transcription Factor T-Bet Is Required for Optimal Type I Follicular Helper T Cell Maintenance During Acute Viral Infection

Follicular helper T cells (TFH cells), known as the primary “helpers” of the germinal center (GC) reaction, promote the humoral immune response to defend against various pathogens. Under conditions of infection by different types of pathogens, many shared transcription factors (TFs), such as Bcl-6, TCF-1, and Maf, are selectively enriched in pathogen-specific TFH cells, orchestrating TFH cell differentiation and function. In addition, TFH cells also coexpress environmentally associated TFs as their conventional T cell counterparts (such as T-bet, GATA-3, or ROR-γt, which are expressed in Th1, Th2, or Th17 cells, respectively). These features likely indicate both the lineage-specificity and environmental adaption of the TFH cell responses. However, the extent to which the TFH cell response relies on these environmentally specific TFs is not completely understood. Here, we found that T-bet was specifically expressed in Type I TFH cells but not Type II TFH cells. While dispensable for the early fate commitment of TFH cells, T-bet was essential for the maintenance of differentiated TFH cells, promoting their proliferation, and inhibiting their apoptosis during acute viral infection. Microarray analysis showed both similarities and differences in transcriptome dependency on T-bet in TFH and TH1 cells, suggesting the distinctive role of T-bet in TFH cells. Collectively, our findings reveal an important and specific supporting role for T-bet in type I TFH cell response, which can help us gain a deeper understanding of TFH cell subsets

Sex-Based Differences in the Association between Serum Copper and Kidney Function: Evidence from NHANES 2011–2016

Epidemiological evidence on the relationship between copper (Cu) and kidney function is rare, and few studies examine the sex differences in this association. We aimed to explore the overall and sex-based relationship between exposure to Cu and biomarkers of kidney function among 4331 participants of the 2011–2016 National Health and Nutrition Examination Survey. Multiple linear regression models were fitted to examine the overall and sex-specific associations between serum Cu and the kidney function indicator-estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio (UACR). Restricted cubic spline models (RCS) stratified by sex were performed to explore the sex-based dose–response associations. Serum Cu in the highest quartile was associated with higher levels of UACR (β = 0.203, 95% CI: 0.100 to 0.306) among overall participants. In males, there was an association of the highest Cu quartile with decreased eGFR (β = −0.023, 95% CI: −0.042 to −0.003) and increased UACR (β = 0.349, 95% CI: 0.171 to 0.527); serum Cu levels also demonstrated a negative nonlinear dose–response association with eGFR and a positive linear dose–response association with UACR in males, whereas females showed a marginally significant nonlinear positive association of eGFR with serum Cu levels. In conclusion, there were sex-specific and dose–response relationships between serum Cu and kidney function indicators. Further prospective and mechanistic studies are warranted

Air pressure measurement of circular thin plate using optical fiber multimode interferometer

In this paper, a simple singlemode-multimode-singlemode (SMS) optical fiber sensor is proposed and investigated for measuring the air pressure of a circular thin plate. Theoretical analysis and experimental demonstration are presents in this paper. The air pressure changes the strain and bending radius of the SMS sensor directly attached to the thin plate, and hence leads to shifts and intensity variation of the transmission spectrum. The relationship between transmission spectrum and pressure has studied by finite element method and optical simulation analysis. Experimental results show that the intensity-pressure and wavelength-pressure are − 0.2718 dB/kPa and −106.7 pm/kPa in a pressure range of 70–130 kPa, respectively. The repeatability of the sensor is good, and the hysteresis rate is low. The key features of the proposed sensor are its simple structure and manufacturing process, low manufacturing cost. It can be used for high-precision pressure measurement

Rare earth separations by selective borate crystallization

Lanthanides possess similar chemical properties rendering their separation from one another a challenge of fundamental chemical and global importance given their incorporation into many advanced technologies. New separation strategies combining green chemistry with low cost and high efficiency remain highly desirable. We demonstrate that the subtle bonding differences among trivalent lanthanides can be amplified during the crystallization of borates, providing chemical recognition of specific lanthanides that originates from Ln(3+) coordination alterations, borate polymerization diversity and soft ligand coordination selectivity. Six distinct phases are obtained under identical reaction conditions across lanthanide series, further leading to an efficient and cost-effective separation strategy via selective crystallization. As proof of concept, Nd/Sm and Nd/Dy are used as binary models to demonstrate solid/aqueous and solid/solid separation processes. Controlling the reaction kinetics gives rise to enhanced separation efficiency of Nd/Sm system and a one-step quantitative separation of Nd/Dy with the aid of selective density-based flotation

Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation

Abstract One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research

Multi-omics analysis reveals the chemoresistance mechanism of proliferating tissue-resident macrophages in PDAC via metabolic adaptation

Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer that typically demonstrates resistance to chemotherapy. Tumor-associated macrophages (TAMs) are essential in tumor microenvironment (TME) regulation, including promoting chemoresistance. However, the specific TAM subset and mechanisms behind this promotion remain unclear. We employ multi-omics strategies, including single-cell RNA sequencing (scRNA-seq), transcriptomics, multicolor immunohistochemistry (mIHC), flow cytometry, and metabolomics, to analyze chemotherapy-treated samples from both humans and mice. We identify four major TAM subsets within PDAC, among which proliferating resident macrophages (proliferating rMφs) are strongly associated with poor clinical outcomes. These macrophages are able to survive chemotherapy by producing more deoxycytidine (dC) and fewer dC kinases (dCKs) to decrease the absorption of gemcitabine. Moreover, proliferating rMφs promote fibrosis and immunosuppression in PDAC. Eliminating them in the transgenic mouse model alleviates fibrosis and immunosuppression, thereby re-sensitizing PDAC to chemotherapy. Consequently, targeting proliferating rMφs may become a potential treatment strategy for PDAC to enhance chemotherapy

The Kinase Complex mTOR Complex 2 Promotes the Follicular Migration and Functional Maturation of Differentiated Follicular Helper CD4+ T Cells During Viral Infection

Follicular helper CD4+ T (TFH) cells are critical for optimal B-cell-mediated humoral immunity by initiating, fueling, and sustaining germinal center reactions. The differentiation of TFH cells relies on multiple intrinsic and extrinsic factors; however, the details by which these factors are integrated to coordinate TFH differentiation are largely unknown. In this study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) viral infection, we demonstrate that mTOR complex 2 (mTORC2) kinase integrates TCR signaling and ICOS-mediated co-stimulation to promote late differentiation and functional maturation of virus-specific TFH cells. Specifically, mTORC2 functions to maintain TFH lineage specifications, including phenotypes, migratory characteristics, and functional properties. Thus, our results highlight the importance of mTORC2 in guarding TFH phenotypic and functional maturation

Hydrolytically Stable Luminescent Cationic Metal Organic Framework for Highly Sensitive and Selective Sensing of Chromate Anions in Natural Water Systems

Effective detection of chromate anions in aqueous solution is highly desirable because of their high solubility, environmental mobility, carcinogenicity, and bioaccumulation effect. A new strategy for precise detection of chromate anions in the presence of a large excess of other anions, such as Cl^–, NO₃^–, and HCO₃^–, in drinking water and natural water systems remains a challenge. Herein, a hydrolytically stable cationic luminescent europium­(III)-based metal organic framework (MOF), <b>1</b>, was successfully synthesized and investigated as a luminescent sensor that exhibits instant and selective luminescence quenching properties toward chromate ions in aqueous solutions. Moreover, <b>1</b> can be introduced into high-ionic-strength water system (e.g., seawater) for chromate detection as a consequence of the excellent sensing selectivity. The real environmental application of <b>1</b> as a chromate probe is studied in deionized water, lake water, and seawater. The detection limits in these aqueous media are calculated to be 0.56, 2.88, and 1.75 ppb, respectively. All of these values are far below the maximum contamination standard of Cr­(VI) in drinking water of 100 ppb, defined by the U.S. Environmental Protection Agency. This excellent chromate sensing capability originates from the fast enrichment of chromate ions in solids of <b>1</b> from solutions, followed by efficient energy transfer from the MOF skeleton to the chromate anion, as demonstrated by solution absorption spectroscopy, X-ray diffraction, and chromate uptake kinetics and isotherm investigations. To the best of our knowledge, <b>1</b> possesses the lowest chromate detection limit among all reported MOFs up to date and is the only MOF material reported for chromate sensing application under environmentally relevant conditions with high ionic strengths

CREB1-driven CXCR4hi neutrophils promote skin inflammation in mouse models and human patients

Abstract Neutrophils have a pathogenic function in inflammation via releasing pro-inflammatory mediators or neutrophil extracellular traps (NETs). However, their heterogeneity and pro-inflammatory mechanisms remain unclear. Here, we demonstrate that CXCR4hi neutrophils accumulate in the blood and inflamed skin in human psoriasis, and correlate with disease severity. Compared to CXCR4lo neutrophils, CXCR4hi neutrophils have enhanced NETs formation, phagocytic function, neutrophil degranulation, and overexpression of pro-inflammatory cytokines and chemokines in vitro. This is accompanied by a metabolic shift in CXCR4hi neutrophils toward glycolysis and lactate release, thereby promoting vascular permeability and remodeling. CXCR4 expression in neutrophils is dependent on CREB1, a transcription factor activated by TNF and CXCL12, and regulated by de novo synthesis. In vivo, CXCR4hi neutrophil infiltration amplifies skin inflammation, whereas blockade of CXCR4hi neutrophils through CXCR4 or CXCL12 inhibition leads to suppression of immune responses. In this work, our study identifies CREB1 as a critical regulator of CXCR4hi neutrophil development and characterizes the contribution of CXCR4hi neutrophils to vascular remodeling and inflammatory responses in skin

Facile and Efficient Decontamination of Thorium from Rare Earths Based on Selective Selenite Crystallization

The coexistence of radioactive contaminants (e.g., thorium, uranium, and their daughters) in rare earth minerals introduces significant environmental, economic, and technological hurdles in modern rare earth production. Efficient, low cost, and green decontamination strategies are therefore desired to ameliorate this problem. We report here a single-step and quantitative decontamination strategy of thorium from rare earths based on a unique periodic trend in the formation of crystalline selenite compounds across the lanthanide series, where Ce­(III) is fully oxidized in situ to Ce­(IV). This gives rise to a crystallization system that is highly selective to trap tetravalent f-blocks while all other trivalent lanthanides completely remain in solution when coexist. These results are bolstered by first-principles calculations of lattice energies and an examination of bonding in these compounds. This system is contrasted with typical natural and synthetic systems, where trivalent and tetravalent f-block elements often cocrystallize. The separation factors after one round of crystallization were determined from binary systems of Th­(IV)/La­(III), Th­(IV)/Eu­(III), and Th­(IV)/Yb­(III) to reach 2.1 × 10⁵, 1.2 × 10⁵, and 9 × 10⁴, respectively. Selective crystallization of thorium from a simulated monazite composite yields a separation factor of 1.9 × 10³ with nearly quantitative removal of thorium