Development of a nomogram to predict the risk of secondary failure of platelet recovery in patients with ß-thalassemia major after hematopoietic stem cell transplantation: a retrospective study.

Background: Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with ß-thalassemia major (ß-TM) after hematopoietic stem cell transplantation (HSCT). Objectives: A model to predict the risk of SFPR in ß-TM patients after HSCT was developed. Design: A retrospective study was used to develop the prediction model. Methods: The clinical data for 218 ß-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model. Results: The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%. Conclusion: We constructed a nomogram model to predict the risk of SFPR in patients with ß-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.

Bulk Photovoltaic Effect Induced by Non-Covalent Interactions in Bilayered Hybrid Perovskite for Efficient Passive X-Ray Detection.

Hydrogen bonding as a multifunctional tool has always influenced the structure of hybrid perovskites. Compared with the research on hydrogen bonding, the study of halogen-halogen interactions on the structure and properties of hybrid perovskites is still in its early stages. Herein, a polar bilayered hybrid perovskite (IEA)2FAPb2I7 (IEA+ is 2-iodoethyl-1-ammonium, FA is formamidinium) with iodine-substituted spacer is successfully constructed by changing the configuration of interlayer cations and regulating non-covalent interactions at the organic-inorganic interface, which shows a shorter interlayer spacing and higher density (ρ = 3.862 g cm-3). The generation of structure polarity in (IEA)2FAPb2I7 is caused by the synergistic effect of hydrogen bonding and halogen-halogen interactions. Especially, as the length of the carbon chain in organic cations decreases, the I---I interaction in the system gradually strengthens, which may be the main reason for the symmetry-breaking. Polarity-induced bulk photovoltaics (Voc = 1.0 V) and higher density endow the device based on (I-EA)2FAPb2I7 exhibit a high sensitivity of 175.6 µC Gy-1 cm-2 and an ultralow detection limit of 60.4 nGy s-1 at 0 V bias under X-ray irradiation. The results present a facile approach for designing polar multifunctional hybrid perovskites, also providing useful assistance for future research on halogen-halogen interactions.

Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans.

The prevalence of COVID-19 critical illness varies across ethnicities, with recent studies suggesting that genetic factors may contribute to this variation. The aim of this study was to investigate natural selection signals of genes associated with critically-ill COVID-19 in sub-Saharan Africans. Severe COVID-19 SNPs were obtained from the HGI website. Selection signals were assessed in 661 sub-Sahara Africans from 1000 Genomes Project using integrated haplotype score (iHS), cross-population extended haplotype homozygosity (XP-EHH), and fixation index (Fst). Allele frequency trajectory analysis of ancient DNA samples were used to validate the existing of selection in sub-Sahara Africans. We also used Mendelian randomization to decipher the correlation between natural selection and critically-ill COVID-19. We identified that CCR3 exhibited significant natural selection signals in sub-Sahara Africans. Within the CCR3 gene, rs17217831-A showed both high iHS (Standardized iHS = 2) and high XP-EHH (Standardized XP-EHH = 2.5) in sub-Sahara Africans. Allele frequency trajectory of CCR3 rs17217831-A revealed natural selection occurring in the recent 1,500 years. Natural selection resulted in increased CCR3 expression in sub-Sahara Africans. Mendelian Randomization provided evidence that increased blood CCR3 expression and eosinophil counts lowered the risk of critically ill COVID-19. Our findings suggest that sub-Saharan Africans are resistant to critically ill COVID-19 due to natural selection and identify CCR3 as a potential novel therapeutic target.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

Comparative Pharmacokinetics and Safety Assessment of 1st- and 2nd-Generation Zinpentraxin Alfa Drug Products in Healthy Volunteers: A Randomized Crossover Study.

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterize and compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs). In a phase 1 randomized, double-blind, 2-sequence crossover, sequential 2-stage study (ISRCTN59409907), single intravenous (IV) doses of 1st- and 2nd-generation zinpentraxin alfa at 10 mg/kg were studied with a blinded interim analysis (IA) at the end of stage 1. Bioequivalence (BE) was achieved for the maximum observed plasma concentration (Cmax), but the overall exposure was higher for the 2nd- compared to the 1st-generation zinpentraxin alfa. The study was stopped after stage 1 as the gating criteria were met based on the result of the blinded IA. Safety profiles were similar for the 1st- and 2nd-generation drug products, and antidrug antibody (ADA) was not observed in this study.

A Phase 1a Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7303509, an Anti-TGFß3 Antibody, in Healthy Volunteers.

INTRODUCTION: Transforming growth factor beta (TGFß) cytokines (TGFß1, TGFß2, and TGFß3) play critical roles in tissue fibrosis. However, treatment with systemic pan-TGFß inhibitors have demonstrated unacceptable toxicities. In this study, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7303509, a high-affinity, TGFß3-specific, humanized immunoglobulin G1 monoclonal antibody, in healthy adult volunteers (HVs). METHODS: This phase 1a, randomized, double-blind trial included six cohorts for evaluation, with each cohort receiving single doses of placebo or RO7303509, administered intravenously (IV; 50 mg, 150 mg, 240 mg) or subcutaneously (SC; 240 mg, 675 mg, 1200 mg). The frequency and severity of adverse events (AEs) and RO7303509 serum concentrations were monitored throughout the study. We also measured serum periostin and cartilage oligomeric matrix protein (COMP) by immunoassay and developed a population pharmacokinetics model to characterize RO7303509 serum concentrations. RESULTS: The study enrolled 49 HVs, with a median age of 39 (range 18-73) years. Ten (27.8%) RO7303509-treated subjects reported 24 AEs, and six (30.8%) placebo-treated subjects reported six AEs. The most frequent AEs related to the study drug were injection site reactions and infusion-related reactions. Maximum serum concentrations (Cmax) and area under the concentration-time curve from time 0 to infinity (AUC0-inf) values for RO7303509 appeared to increase dose-proportionally across all doses tested. Serum concentrations across cohorts were best characterized by a two-compartment model plus a depot compartment with first-order SC absorption kinetics. No subjects tested positive for anti-drug antibodies (ADAs) at baseline; one subject (2.8%; 50 mg IV) tested positive for ADAs at a single time point (day 15). No clear pharmacodynamic effects were observed for periostin or COMP upon TGFß3 inhibition. CONCLUSION: RO7303509 was well tolerated at single SC doses up to 1200 mg in HVs with favorable pharmacokinetic data that appeared to increase dose-proportionally. TGFß3-specific inhibition may be suitable for development as a chronic antifibrotic therapy. TRIAL REGISTRATION: ISRCTN13175485.

A Two-Step Regional Ionospheric Modeling Approach for PPP-RTK.

In the precise point positioning/real-time kinematic (PPP-RTK) technique, high-precision ionospheric delay correction information is an important prerequisite for rapid PPP convergence. The commonly used ionospheric modeling approaches in the PPP-RTKs only take the trend term of the ionospheric total electron content (TEC) variations into account. As a result, the residual ionospheric delay still affects the positioning solutions. In this study, we propose a two-step regional ionospheric modeling approach that involves combining a polynomial fitting model (PFM) and a Kriging interpolation (KI) model. In the first step, a polynomial fitting method is used to model the trend term of the ionospheric TEC variations. In the second step, a KI method is used to compensate for the residual term of the ionospheric TEC variations. Datasets collected from continuously operating reference stations (CORSs) in Hunan Province, China, are used to validate the PFM/KI method by comparing with a single PFM method and a combined PFM and inverse distance weighting interpolation (IDWI) method. The experimental results show that the two-step PFM/KI modeled ionospheric delay achieves an average root mean square (RMS) error of 1.8 cm, which is improved by about 48% and 23% when compared with the PFM and PFM/IDWI methods, respectively. Regarding the positioning performance, the PPP-RTK with the PFM/KI method takes an average of 1.8 min or 4.0 min to converge to a positioning accuracy of 1.3 cm or 2.5 cm in the horizontal and vertical directions, respectively. The convergence times are decreased by about 18% and 14% in the horizontal direction and 9% and 5% in the vertical direction over the PFM and the PFM/IDWI methods, respectively.

Synthesis, characterization, and efficacy evaluation of a PH-responsive Fe-MOF@GO composite drug delivery system for the treating colorectal cancer.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

Morphological control and performance engineering of Co-based materials for supercapacitors.

As one of the most promising energy storage devices, supercapacitors exhibit a higher power density than batteries. However, its low energy density usually requires high-performance electrode materials. Although the RuO2 material shows desirable properties, its high cost and toxicity significantly limit its application in supercapacitors. Recent developments demonstrated that Co-based materials have emerged as a promising alternative to RuO2 for supercapacitors due to their low cost, favorable redox reversibility and environmental friendliness. In this paper, the morphological control and performance engineering of Co-based materials are systematically reviewed. Firstly, the principle of supercapacitors is briefly introduced, and the characteristics and advantages of pseudocapacitors are emphasized. The special forms of cobalt-based materials are introduced, including 1D, 2D and 3D nanomaterials. After that, the ways to enhance the properties of cobalt-based materials are discussed, including adding conductive materials, constructing heterostructures and doping heteroatoms. Particularly, the influence of morphological control and modification methods on the electrochemical performances of materials is highlighted. Finally, the application prospect and development direction of Co-based materials are proposed.

Organic Fluorophores with Large Stokes Shift for the Visualization of Rapid Protein and Nucleic Acid Assays.

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).

Deciphering ACE2-RBD binding affinity through peptide scanning: A molecular dynamics simulation approach.

Rapid discovery of target information for protein-protein interactions (PPIs) is significant in drug design, diagnostics, vaccine development, antibody therapy, etc. Peptide microarray is an ideal tool for revealing epitope information of PPIs. In this work, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) and the host cell receptor angiotensin-converting enzyme 2 (ACE2) were introduced as a model to study the epitope information of RBD-specific binding to ACE2 via a combination of theoretical calculations and experimental validation. Through dock and molecular dynamics simulations, it was found that among the 22 peptide fragments that consist of RBD, #14 (YNYLYRLFRKSNLKP) has the highest binding strength. Subsequently, the experiments of peptide microarray constructed based on plasmonic materials chip also confirmed the theoretical calculation data. Compared to other methods, such as phage display technology and surface plasmon resonance (SPR), this method is rapid and cost-effective, providing insights into the investigation of pathogen invasion processes and the timely development of peptide drugs and other fields.

Modulating Thermal Conductivity and Flame Retardancy of Polyolefin Composites via Distributed Structures of Magnesium Hydroxide and Hexagonal Boron Nitride.

Thermally conductive and flame-retardant polyolefin composites are facing great challenges in meeting the increasing demands for fire safety and thermal management. Aiming at simultaneously enhancing thermal conductivity and flame retardancy, hexagonal boron nitride (hBN) and magnesium hydroxide (MH) were adopted in ethylene-vinyl acetate copolymer/polyolefin elastomer (EVA/POE) blends to design composites with selective filler distributions and co-continuous networks via different processing schemes. The thermal conductivity and flame retardancy show strong dependence on the distributed structure of hBN and MH. The composites with hBN-rich centers and MH-rich edges in the filled POE phase show a thermal conductivity of 0.70 W/(m·K) and an LOI of 27.7%, which are very close to the thermal conductivity of EVA/POE/hBN and the LOI of EVA/POE/MH at the same total filler content. The composites with MH-rich centers and hBN-rich edges show pHRR, THR and TSP values of 169 kW/m2, 49.8 MJ/m2 and 1.8 m2, which are decreased by 40%, 33% and 62% in comparison with EVA/POE/MH, respectively. Modulating the filler structure distribution provides a strategy to co-enhance thermal conductivity and flame retardancy.

Agronomic, physiological and transcriptional characteristics provide insights into fatty acid biosynthesis in yellowhorn (Xanthoceras sorbifolium Bunge) during fruit ripening.

Yellowhorn (Xanthoceras sorbifolium Bunge) is an oil-bearing tree species in northern China. In this study, we used yellowhorn from Heilongjiang to analyze the morphological and physiological changes of fruit development and conducted transcriptome sequencing. The results showed that the fruit experienced relatively slow growth from fertilization to DAF20 (20 days after flowering). From DAF40 to DAF60, the fruit entered an accelerated development stage, with a rapid increase in both transverse and longitudinal diameters, and the kernel contour developed completely at DAF40. From DAF60 to DAF80, the transverse and vertical diameters of the fruit developed slowly, and the overall measures remained stable until maturity. The soluble sugar, starch, and anthocyanin content gradually accumulated until reaching a peak at DAF80 and then rapidly decreased. RNA-seq analysis revealed differentially expressed genes (DEGs) in the seed coat and kernel, implying that seed components have different metabolite accumulation mechanisms. During the stages of seed kernel development, k-means clustering separated the DEGs into eight sub-classes, indicating gene expression shifts during the fruit ripening process. In subclass 8, the fatty acid biosynthesis pathway was enriched, suggesting that this class was responsible for lipid accumulation in the kernel. WGCNA revealed ten tissue-specific modules for the 12 samples among 20 modules. We identified 54 fatty acid biosynthesis pathway genes across the genome, of which 14 was quantified and confirmed by RT-qPCR. Most genes in the plastid synthesis stage showed high expression during the DAF40-DAF60 period, while genes in the endoplasmic reticulum synthesis stage showed diverse expression patterns. EVM0012847 (KCS) and EVM0002968 (HCD) showed similar high expression in the early stages and low expression in the late stages. EVM0022385 (HCD) exhibited decreased expression from DAF40 to DAF60 and then increased from DAF60 to DAF100. EVM0000575 (KCS) was increasingly expressed from DAF40 to DAF60 and then decreased from DAF60 to DAF100. Finally, we identified transcription factors (TFs) (HB-other, bHLH and ARF) that were predicted to bind to fatty acid biosynthesis pathway genes with significant correlations. These results are conducive to promoting the transcriptional regulation of lipid metabolism and the genetic improvement in terms of high lipid content of yellowhorn.

P129, a pyrazole ring-containing isolongifolanone-derivate: synthesis and investigation of anti-glioma action mechanism.

BACKGROUND: Cyclin-dependent kinase-2 (CDK-2) is an important regulatory factor in the G1/S phase transition. CDK-2 targeting has been shown to suppress the viability of multiple cancers. However, the exploration and application of a CDK-2 inhibitor in the treatment of glioblastoma are sparse. METHODS: We synthesized P129 based on isolongifolanone, a natural product with anti-tumor activity. Network pharmacology analysis was conducted to predict the structural stability, affinity, and pharmacological and toxicological properties of P129. Binding analysis and CETSA verified the ability of P129 to target CDK-2. The effect of P129 on the biological behavior of glioma cells was analyzed by the cell counting kit-8, colony formation, flow cytometry, and other experiments. Western blotting was used to detect the expression changes of proteins involved in the cell cycle, cell apoptosis, and epithelial-mesenchymal transition. RESULTS: Bioinformatics analysis and CETSA showed that P129 exhibited good intestinal absorption and blood-brain barrier penetrability together with high stability and affinity with CDK-2, with no developmental toxicity. The viability, proliferation, and migration of human glioma cells were significantly inhibited by P129 in a dose- and time-dependent manner. Flow cytometry and western blotting analyses showed G0/G1 arrest and lower CDK-2 expression in cells treated with P129 than in the controls. The apoptotic ratio of glioma cells increased significantly with increasing concentrations of P129 combined with karyopyknosis and karyorrhexis. Apoptosis occurred via the mitochondrial pathway. CONCLUSION: The pyrazole ring-containing isolongifolanone derivate P129 exhibited promising anti-glioma activity by targeting CDK-2 and promoting apoptosis, indicating its potential importance as a new chemotherapeutic option for glioma.

Unveiling the Remarkable Potential of Geopolymer-Based Materials by Harnessing Manganese Dioxide Incorporation.

Thermoelectric (TE) building materials have the potential to revolutionize sustainable architecture by converting temperature differences into electrical energy. This study introduces geopolymeric TE materials enhanced with manganese dioxide (MnO2 ) as a modifying agent. Calorimetric experiments examine the impact of MnO2 on geopolymerization. Mechanical tests show that adding MnO2 (up to 5% by weight) improves the geopolymer composite's strength, achieving a peak compressive strength of 36.8 MPa. The Seebeck effect of the MnO2 -modified geopolymeric composite is also studied. The inclusion of MnO2 boosts the Seebeck coefficient of the geopolymer, reaching a notable 4273 µV C-1 at a 5% MnO2 dosage. This enhancement is attributed to an increase in the density of states (DOS) and a reduction in relaxation time. However, excessive MnO2 or high alkali levels may adversely affect the Seebeck coefficient by lengthening the relaxation time.

Polyguluronate alleviates ulcerative colitis by targeting the gut commensal Lactobacillus murinus and its anti-inflammatory metabolites.

Polyguluronate (PG) is a fermentable polysaccharide from edible algae. The present study was designed to investigate the therapeutic effect of PG on ulcerative colitis (UC) and its underlying mechanisms. Our results suggest that oral intake of PG attenuates UC and improves gut microbiota dysbiosis by promoting the growth of Lactobacillus spp. in dextran sulfate sodium-fed mice. Five different species of Lactobacillus were isolated from the feces of PG-treated mice and L. murinus was identified to have the best anti-colitis effect, suggesting a critical role for L. murinus in mediating the therapeutic effect of PG. Furthermore, PG was degraded potentially by the beta-glucuronidase from L. murinus and adding PG to the culture medium of L. murinus remarkably increased its production of anti-inflammatory metabolites, including itaconic acid, cis-11,14-eicosadienoic acid, and 3-amino-3-(2-chlorophenyl)-propionic acid. Additionally, L. salivarius, a human intestine-derived PG-utilizing species that is closely related to L. murinus, was also demonstrated to have potent anti-colitis effects, suggesting that it is a candidate target of PG in the human gut. Altogether, our study illustrates an unprecedented application of PG in the treatment of UC and establishes the basis for understanding its therapeutic effect from the perspective of L. murinus and its metabolites.

Multi-Source Domain Adaptation for Medical Image Segmentation.

Unsupervised domain adaptation(UDA) aims to mitigate the performance drop of models tested on the target domain, due to the domain shift from the target to sources. Most UDA segmentation methods focus on the scenario of solely single source domain. However, in practical situations data with gold standard could be available from multiple sources (domains), and the multi-source training data could provide more information for knowledge transfer. How to utilize them to achieve better domain adaptation yet remains to be further explored. This work investigates multi-source UDA and proposes a new framework for medical image segmentation. Firstly, we employ a multi-level adversarial learning scheme to adapt features at different levels between each of the source domains and the target, to improve the segmentation performance. Then, we propose a multi-model consistency loss to transfer the learned multi-source knowledge to the target domain simultaneously. Finally, we validated the proposed framework on two applications, i.e., multi-modality cardiac segmentation and cross-modality liver segmentation. The results showed our method delivered promising performance and compared favorably to state-of-the-art approaches.

Association between viral infections and glioma risk: a two-sample bidirectional Mendelian randomization analysis.

BACKGROUND: Glioma is one of the leading types of brain tumor, but few etiologic factors of primary glioma have been identified. Previous observational research has shown an association between viral infection and glioma risk. In this study, we used Mendelian randomization (MR) analysis to explore the direction and magnitude of the causal relationship between viral infection and glioma. METHODS: We conducted a two-sample bidirectional MR analysis using genome-wide association study (GWAS) data. Summary statistics data of glioma were collected from the largest meta-analysis GWAS, involving 12,488 cases and 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures were used as instrumental variables to estimate the causal relationship between glioma and twelve types of viral infections from corresponding GWAS data. In addition, sensitivity analyses were performed. RESULTS: After correcting for multiple tests and sensitivity analysis, we detected that genetically predicted herpes zoster (caused by Varicella zoster virus (VZV) infection) significantly decreased risk of low-grade glioma (LGG) development (OR = 0.85, 95% CI: 0.76-0.96, P = 0.01, FDR = 0.04). No causal effects of the other eleven viral infections on glioma and reverse causality were detected. CONCLUSIONS: This is one of the first and largest studies in this field. We show robust evidence supporting that genetically predicted herpes zoster caused by VZV infection reduces risk of LGG. The findings of our research advance understanding of the etiology of glioma.

Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution.

Background: Diffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of aggressive non-Hodgkin lymphoma. Despite receiving standard treatment, a subset of patients undergoes refractory or recurrent cases, wherein the involvement of cancer stem cells (CSCs) could be significant. Methods: We comprehensively characterized B cell subpopulations using single-cell RNA sequencing data from three DLBCL samples and one normal lymph tissue. The CopyKat R package was employed to assess the malignancy of B cell subpopulations based on chromosomal copy number variations. CIBERSORTx software was utilized to estimate the proportions of B cell subpopulations in 230 DLBCL tissues. Furthermore, we employed the pySCENIC to identify key transcription factors that regulate the functionality of B cell subpopulations. By employing CellphoneDB, we elucidated the interplay among tumor microenvironment components within the B cell subpopulations. Finally, we validated our findings through immunofluorescence experiments. Results: Our analysis revealed a specific cancer stem cell-like B cell subpopulation exhibiting self-renewal and multilineage differentiation capabilities based on the exploration of B cell subpopulations in DLBCL and normal lymph tissues at the single-cell level. Notably, a high infiltration of cancer stem cell-like B cells correlated with a poor prognosis, potentially due to immune evasion mediated by low expression of major histocompatibility complex molecules. Furthermore, we identified key transcription factor regulatory networks regulated by HMGB3, SAP30, and E2F8, which likely played crucial roles in the functional characterization of the cancer stem cell-like B cell subpopulation. The existence of cancer stem cell-like B cells in DLBCL was validated through immunofluorescent staining. Finally, cell communication between B cells and tumor-infiltrating T cell subgroups provided further insights into the functional characterization of the cancer stem cell-like B cell subpopulation. Conclusions: Our research provides a systematic description of a specific cancer stem cell-like B cell subpopulation associated with a poor prognosis in DLBCL. This study enhances our understanding of CSCs and identifies potential therapeutic targets for refractory or recurrent DLBCL patients.

Phosphate-Solubilizing Bacteria: Advances in Their Physiology, Molecular Mechanisms and Microbial Community Effects.

Phosphorus is an essential nutrient for all life on earth and has a major impact on plant growth and crop yield. The forms of phosphorus that can be directly absorbed and utilized by plants are mainly HPO42- and H2PO4-, which are known as usable phosphorus. At present, the total phosphorus content of soils worldwide is 400-1000 mg/kg, of which only 1.00-2.50% is plant-available, which seriously affects the growth of plants and the development of agriculture, resulting in a high level of total phosphorus in soils and a scarcity of available phosphorus. Traditional methods of applying phosphorus fertilizer cannot address phosphorus deficiency problems; they harm the environment and the ore material is a nonrenewable natural resource. Therefore, it is imperative to find alternative environmentally compatible and economically viable strategies to address phosphorus scarcity. Phosphorus-solubilizing bacteria (PSB) can convert insoluble phosphorus in the soil into usable phosphorus that can be directly absorbed by plants, thus improving the uptake and utilization of phosphorus by plants. However, there is no clear and systematic report on the mechanism of action of PSB. Therefore, this paper summarizes the discovery process, species, and distribution of PSB, focusing on the physiological mechanisms outlining the processes of acidolysis, enzymolysis, chelation and complexation reactions of PSB. The related genes regulating PSB acidolysis and enzymatic action as well as genes related to phosphate transport and the molecular direction mechanism of its pathway are examined. The effects of PSB on the structure and abundance of microbial communities in soil are also described, illustrating the mechanism of how PSB interact with microorganisms in soil and indirectly increase the amount of available phosphorus in soil. And three perspectives are considered in further exploring the PSB mechanism in utilizing a synergistic multi-omics approach, exploring PSB-related regulatory genes in different phosphorus levels and investigating the application of PSB as a microbial fungicide. This paper aims to provide theoretical support for improving the utilization of soil insoluble phosphorus and providing optimal management of elemental phosphorus in the future.