Search

Abstract To realize room temperature ferromagnetic (FM) semiconductors is still a challenge in spintronics. Many antiferromagnetic (AFM) insulators and semiconductors with high Neel temperature T N are obtained in experiments, such as LaFeO3, BiFeO3, etc. High concentrations of magnetic impurities can be doped into these AFM materials, but AFM state with very tiny net magnetic moments was obtained in experiments because the magnetic impurities were equally doped into the spin up and down sublattices of the AFM materials. Here, we propose that the effective magnetic field provided by a FM substrate could guarantee the spin-dependent doping in AFM materials, where the doped magnetic impurities prefer one sublattice of spins, and the ferrimagnetic (FIM) materials are obtained. To demonstrate this proposal, we study the Mn-doped AFM insulator LaFeO3 with FM substrate of Fe metal by the density functional theory (DFT) calculations. It is shown that the doped magnetic Mn impurities prefer to occupy one sublattice of the AFM insulator and introduce large magnetic moments in La(Fe, Mn)O3. For the AFM insulator LaFeO3 with high T N = 740 K, several FIM semiconductors with high Curie temperature T C > 300 K and the band gap less than 2 eV are obtained by DFT calculations when 1/8 or 1/4 Fe atoms in LaFeO3 are replaced by the other 3d, 4d transition metal elements. The large magneto-optical Kerr effect (MOKE) is obtained in these LaFeO3-based FIM semiconductors. In addition, the FIM semiconductors with high T C are also obtained by spin-dependent doping in some other AFM materials with high T N, including BiFeO3, SrTcO3, CaTcO3, etc. Our theoretical results propose a way to obtain high T C FIM semiconductors by spin-dependent doping in high T N AFM insulators and semiconductors.

Abstract Background Glioblastoma (GBM) is an immunosuppressive, universally lethal cancer driven by glioblastoma stem cells (GSCs). The interplay between GSCs and immunosuppressive microglia plays crucial roles in promoting the malignant growth of GBM; however, the molecular mechanisms underlying this crosstalk are unclear. This study aimed to investigate the role of POSTN in maintaining GSCs and the immunosuppressive phenotype of microglia. Methods The expression of POSTN in GBM was identified via immunohistochemistry, quantitative real-time PCR, and immunoblotting. Tumorsphere formation assay, Cell Counting Kit-8 assay and immunofluorescence were used to determine the key role of POSTN in GSC maintenance. ChIP-seq and ChIP-PCR were conducted to confirm the binding sequences of β-catenin in the promoter region of FOSL1. Transwell migration assays, developmental and functional analyses of CD4+ T cells, CFSE staining and analysis, enzyme-linked immunosorbent assays and apoptosis detection tests were used to determine the key role of POSTN in maintaining the immunosuppressive phenotype of microglia and thereby promoting the immunosuppressive tumor microenvironment. Furthermore, the effects of POSTN on GSC maintenance and the immunosuppressive phenotype of microglia were investigated in a patient-derived xenograft model and orthotopic glioma mouse model, respectively. Results Our findings revealed that POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway. In addition to its intrinsic effects on GSCs, POSTN can recruit microglia and upregulate CD70 expression in microglia through the αVβ3/PI3K/AKT/NFκB pathway, which in turn promotes Treg development and functionality and supports the formation of an immunosuppressive tumor microenvironment. In both in vitro models and orthotopic mouse models of GBM, POSTN depletion disrupted GSC maintenance, decreased the recruitment of immunosuppressive microglia and suppressed GBM growth. Conclusion Our findings reveal that POSTN plays critical roles in maintaining GSCs and the immunosuppressive phenotype of microglia and provide a new therapeutic target for treating GBM.

Currently, polylactic acid (PLA) is an attractive alternative to polypropylene (PP) because of its biodegradability. This study introduces a novel modification strategy for PLA by creating a multifunctional ionization layer with ionic salts. This approach achieves humidity sensing, reliable antibacterial properties, and excellent degradability simultaneously. The modified PLA textile sensor exhibits high sensitivity to respiratory humidity (0.92 at 90% RH), with ultrafast response (0.12 s) and recovery times (0.16 s). Additionally, the textile demonstrates excellent antibacterial performance against both E. coli (99.9%) and S. aureus (99.9%) after 1 h of contact. It also shows notable biodegradability with a weight loss rate of 60.38% after 30 days. Also, the ionic salt mechanism is explained through dynamic ionization interactions attributed to the modified ionic salts, which feature both long-chain alkanes and active ions. This work presents a new method to enhance the respiratory detection and antibacterial performance of biodegradable masks.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Peri-implant diseases, characterized by inflammatory conditions affecting peri-implant tissues, encompass peri-implant mucositis and peri-implantitis. Peri-implant mucositis is an inflammatory lesion limited to the mucosa around an implant, while peri-implantitis extends from the mucosa to the supporting bone, causing a loss of osseointegration. For non-surgical treatments, we tested the null hypothesis that the presence or absence of air-polishing made no difference. The study focused on randomized controlled trials (RCTs) comparing air-polishing with mechanical or ultrasonic debridement, evaluating outcomes such as bleeding on probing (BOP), probing depth (PD), plaque index/plaque score (PI/PS), clinical attachment level (CAL), bone loss, and mucosal recession (MR). Two independent reviewers conducted data extraction and quality assessments, considering short-term (

AbstractContext Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown.Objective This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota.Materials and methods 120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (n = 56) or RAAS inhibitor (n = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics.Results Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium, and Sutterella increased significantly, while pathogenic bacteria such as the Eggerthella and Clostridium innocuum group decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as Lachnospiraceae and the Lachnoclostridium genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism.Discussion and conclusion The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored.Trial registration ChiCTR2300076136, retrospectively registered.

ABSTRACTBackground Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials.Research design and methods Study-1 involved subjects were randomized (1:1:1) to receive 20 μg ReCOV, 40 μg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 μg ReCOV (pilot batch, ReCOV HA), 20 μg ReCOV (commercial batch, ReCOV TC), or 30 μg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster.Results Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence.Conclusions Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV’s potential for enhanced protection, supported by strong cross-neutralization and immune persistence.Clinical Trial Registration Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Analyzing the vast amount of omics data generated comprehensively by high-throughput sequencing technology is of utmost importance for scientists. In this context, we propose HiOmics, a cloud-based platform equipped with nearly 300 plugins designed for the comprehensive analysis and visualization of omics data. HiOmics utilizes the Element Plus framework to craft a user-friendly interface and harnesses Docker container technology to ensure the reliability and reproducibility of data analysis results. Furthermore, HiOmics employs the Workflow Description Language and Cromwell engine to construct workflows, ensuring the portability of data analysis and simplifying the examination of intricate data. Additionally, HiOmics has developed DataCheck, a tool based on Golang, which verifies and converts data formats. Finally, by leveraging the object storage technology and batch computing capabilities of public cloud platforms, HiOmics enables the storage and processing of large-scale data while maintaining resource independence among users.

Atmospheric organic aerosols consist of both gas-phase organic compounds and particle-phase organic compounds. The components of aerosol particles (solid or liquid droplets) can undergo exchange or chemical reactions with gas-phase components, influencing atmospheric physical and chemical processes and potentially impacting atmospheric environment, climate, and human health. Methods for detecting organic compounds in aerosol particle phase are classified into offline and online detection. Offline detection methods involve collecting aerosol samples for analysis using chromatography-mass spectrometry, which is time-consuming and limited sensitivity. Online detection methods involve enriching aerosols through aerodynamic lens and then detecting them using laser ablation or electron impact ionization techniques. However, these methods usually generate a large number of ion fragments, making mass spectrum analysis difficult. Therefore, it is necessary to develop an online detection method for aerosol particle-phase organic compounds with soft ionization and high sampling efficiency. In the present work, a set of aerodynamic lens sampling systems was designed and developed for online detection and analysis of organic compounds in aerosol particle phase. This sampling system consists of a gas-phase stripping module for removing gas-phase organic compounds, an aerodynamic lens module for particle focusing and enrichment, and a thermal desorption module for extracting particle-phase organic compounds. The efficiency of gas-phase organic compound removal and the particle transmission rate of the gas-phase stripping module were firstly investigated. The results showed that gas-phase stripping module achieves a removal efficiency of 98.89% for gas-phase organic compounds, and the particle transmission rate ranges from 75.16% to 91.15% for particles with the diameters between 295 and 375 nm. Subsequently, the effectiveness of the aerodynamic lens was studied through theoretical simulations. The simulation results indicated that the transmission rate of particles in the diameters of 0.36-6.0 μm is above 90% in the designed aerodynamic lens. Finally, The designed aerodynamic lens sampling system with a homemade proton transfer reaction mass spectrometer (PTR-MS) was integrated to develop an aerodynamic lens-PTR-MS device. This device was tested by detecting simulated aerosol samples containing reaction products of α-pinene and ozone. The mass spectrometry results demonstrated that the intensity changes of the examined ten ions are closely related to the presence of α-pinene, confirming that the device can achieve online detection of organic compounds in aerosols ranging from submicron to several micrometers.

Abstract To establish a population pharmacokinetic (PopPK) model of posaconazole suspension in Chinese hematopoietic stem cell transplantation (HSCT) patients and to recommend an optimal dosing regimen. A single-center, retrospective, model-based study was conducted in 62 Chinese patients, including 103 with posaconazole plasma concentrations. PopPK analysis using NONMEM software. A one-compartment model of first-order elimination and absorption was in good agreement with the experimental data. Analysis of covariance showed that body weight (WT), creatinine clearance (CCR), and proton pump inhibitor (PPI) had a significant effect on the pharmacokinetics of posaconazole. The dose simulation results show that patients with CCR ≥ 90 mL/min require at least 3 mg/kg TID and 7 mg/kg BID dosing regimens for prevention and treatment, respectively. However, when combined with PPI, at least 5 mg/kg BID and 5 mg/kg TID dosing regimens are required for prevention and treatment, respectively. Regardless of whether it is used in combination with PPI or not, patients with a CCR of 60–90 mL/min can achieve PTA goals by using a 4 mg/kg BID and 4 mg/kg TID regimen for prevention and treatment, respectively. A dosing regimen of 3 mg/kg BID in patients with a CCR of 30–60 mL/min is sufficient to meet the PTA goal of prophylaxis, and the dose needs to be elevated to 4 mg/kg BID for the treatment of fungal infections, and there is no need to change the dose according to the coadministration of PPI. When the patient's CCR is less than 30 mL/min, whether or not combined with PPI, the administration regimen of 2 mg/kg BID and 3 mg/kg BID can meet the PTA goals for prevention and treatment, respectively.

Abstract Eosinophils, traditionally associated with allergic phenomena, play a pivotal role in inflammatory responses. Despite accumulating evidence suggesting their pro-inflammatory function upon activation, the underlying mechanisms governing eosinophil activation remain incompletely characterized. In this study, we investigate the local activation of pulmonary and colon eosinophils within the inflammatory microenvironment. Leveraging transcriptional sequencing, we identify TGF-β as a putative regulator of eosinophil activation, leading to the secretion of granule proteins, including peroxidase. Genetic deletion of TGF-β receptors on eosinophils resulted in the inhibition of peroxidase synthesis, affirming the significance of TGF-β signaling in eosinophil activation. Using models of HDM-induced asthma and DSS-induced colitis, we demonstrate the indispensability of TGF-β-driven eosinophil activation in both disease contexts. Notably, while TGF-β signaling did not significantly influence asthmatic inflammation, its knockout conferred protection against experimental colitis. This study delineates a distinct pattern of eosinophil activation within inflammatory responses, highlighting the pivotal role of TGF-β signaling in regulating eosinophil behavior. These findings deepen our comprehension of eosinophil-related pathophysiology and may pave the way for targeted therapeutic approaches in allergic and inflammatory diseases.