[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective:To investigate the role of Ym2 in olfactory epithelium homeostasis and olfactory behavior.Methods:Differential expression of Ym2 in the olfactory epithelium of young and aged mice was analyzed using single-cell RNA sequencing. Ym2 and related genes in the aged olfactory epithelium were identified, and their biological function was analyzed by GO enrichment analysis. The expression of Ym2 and Ym2-related genes in the young and aged olfactory epithelium was detected by immunostaining and RNAscope in situ hybridization. Buried food pullet test was used to assess the impact of Ym2 knockout on olfactory function, while immunostaining was used to evalute the effect of Ym2 knockout of on the homeostasis of olfactory epithelium. Statistical analysis was performed using GraphPad Prism 8.0.1 software.Results:Single-cell RNA sequencing revealed that Ym2 was highly expressed in multiple cell types, including horizontal basal cells and respiratory ciliated cells of the olfactory epithelium in aged mice compared to young animals. In situ hybridization and immunostaining data showed that Ym2 mRNA level were higher in the aged olfactory epithelium than that in the young tissue ( t=4.50, P<0.001). At the protein level, Ym2 expression was higher in horizontal basal cells ( t=3.03, P<0.05) and supporting cells ( t=7.76, P<0.001) of the aged epithelium compared to the young tissue. Additionally, the mRNA levels of the two Ym2-related genes, Alox15 and Cxcl5, were also higher in the aged olfactory epithelium ( t=2.72 and 2.68, respectively, both P<0.05). Behavioral testing showed that Ym2-/- mice took significantly longer to find buried food pellets compared to wild-type (WT) mice ( t=2.35, P<0.05). Histological analysis revealed a significant reduction in the number of olfactory sensory neurons and supporting cells in the olfactory epithelium of Ym2-/- mice compared to WT mice ( t=5.86 and 3.69, respectively, both P<0.01). Conclusions:Ym2 plays a critical role in smell perception. Ym2 knockout leads to reduction in the number of olfactory epithelial cell and impairs olfactory behavior of food-searching in young mice.

In the field of oral medicine, 3D-printed individualized titanium mesh technology is gradually becoming an important means for the treatment of severe alveolar bone defect augmentation. This article provides a comprehensive analysis of the advantages of this technology, the evaluation of osteogenic effects, and the progress of research in clinical applications. In response to the current issue of variability in bone augmentation outcomes, this paper delves into multiple factors affecting bone augmentation effects, including individualized titanium mesh design (involving the thickness, pore size, pore shape, porosity, contour shape, selection of titanium alloy materials, and 3D printing technology), intraoperative procedures (the accuracy of placement during 3D-printed individualized titanium mesh surgery), and postoperative care (including the prevention of complications, formation of pseudoperiosteum, and stability of the titanium mesh). By integrating the clinical experience and research findings of our team, we propose a series of targeted optimization strategies, including designing, manufacturing, and clinically applying self-positioning individualized titanium meshs (positioning wings + individualized titanium meshs) to improve the positioning accuracy of the titanium mesh; propose individualized treatment processes and titanium mesh design schemes based on specific conditions of alveolar bone defects and soft tissue status; and emphasize the importance of long-term stable fixation of the titanium mesh to reduce the risk of postoperative mesh loosening and displacement. In addition, we appropriately summarize the evaluation methods for the bone augmentation effects of 3D-printed individualized titanium meshes, covering the following key indicators: (1) vertical bone augmentation and horizontal bone augmentation; (2) changes in bone contour morphology; (3) bone volume increase; (4) clinical indicators (surgical success rate, titanium mesh exposure, infection rate, and postoperative recovery); (5) aesthetic effect evaluation; (6) long-term stability; (7) radiological assessment; (8) patient satisfaction; and (9) precision of surgical operation, aiming to assist doctors in comprehensively assessing and in-depth analyzing the surgical outcomes to achieve the best therapeutic effects. The purpose of this article is to provide a reference for the optimization and clinical application of 3D-printed individualized titanium mesh technology and to lay a theoretical foundation for achieving the best osteogenic effects.

Objective To analyze the levels and functions of CD4+T cell subsets in mouse spleen and lung tissues after Streptococcus pneumoniae(S.P.)infection,and to explore the immune regulatory mechanisms S.P.infection.Methods Flow cytometry was used to detect the proportions of CD4+T cell subsets(Th1,Th2,Th17,and Treg cells)in mouse spleen tissues from control group(n=4),S.P.infection at 12 h(n=4),and 24 h(n=4).H&E staining was used to examine lung tissue pathological characteristics.Differential gene sets and functional changes in lung tissues were analyzed after S.P.infection for 2 and 5 days,and immune cell abundance was predicted.Results Significant inflammatory pathological features were observed in the lung tissues of mice after S.P.infection.The proportions of Th1 and Treg cells in the spleen tissues gradually increased after S.P.infection,with Th1 and Treg cell proportions significantly higher than the control group at 24 h post-infection(P<0.05).At 5 d post-infection,only Treg cell proportion was significantly higher than the control group(P<0.05).Functional analysis revealed abnormal activation of IL6,IL10,and IL4/IL13 signaling pathways 2 days after infection,and abnormal enrichment of IL-2 and IL-6/TGF-β pathways 5 days after infection.Conclusion Treg and Th1 cells are key immune regulatory cells in mice following S.P.infection.Modulating Treg cell function mediated by IL-10 and Th1 cell function mediated by IL-2 can improve immune responses after S.P.infection.

The liver,as the core metabolic organ of the human body,undertakes multiple critical physiological functions such as protein synthesis,xenobiotic metabolism,and immune regulation.Liver failure represents a major disease process in patients with end-stage liver disease,characterized clinically by coagulopathy,abnormal bilirubin metabolism,and multiple organ dysfunction.Depending on the disease course,liver failure can be classified into four types:acute,subacute,acute-on-chronic,and chronic.The pathogenic mechanisms are complex,involving interactions among various factors such as pathogen infections,dysregulation of the immune microenvironment,and gut microbiota disturbances,which pose significant challenges for clinical diagnosis and treatment.This review summarizes the abnormalities in innate and adaptive immune responses,as well as the molecular mechanisms of immune metabolic dysregulation during the occurrence and progression of liver failure.It further explores the pivotal role of immune cell dysfunction in the disease process,aiming to provide a theoretical basis for targeted immune therapies in liver failure.

Objective:To establish a quality control method for the standard decoction of Polygoni Avicularis Herba.Methods:Totally 12 batches of decoction pieces from different origins were collected, the standard decoction was prepared and the quality evaluation method was established, the content of index components in the decoction pieces and the standard decoction was determined with HPLC, the index components, solution pH and other parameters were calculated, and the similarity analysis was carried out against the fingerprints.Results:The total content of myricetin in 12 batches of decoction pieces was >0.12%, and the content of myricetin in the standard decoction was >0.03%, which met the standard of the 2020 edition of the Chinese Pharmacopoeia. The pH value was 5.1-5.5, the transfer rate of myricetin components ranged from 50.0%-106.3%, and the fingerprint study showed that there were 7 common peaks. The similarity analysis results indicated that the standard decoction of 12 batches of decoction pieces of Polygoni Avicularis Herba had good consistency.Conclusion:The preparation process is stable and feasible in line with the traditional decoction preparation method, and can be used for the research and quality evaluation of the standard decoction.

Energy metabolism regulation plays a pivotal role in metabolic engineering. It mainly achieves the balance of material and energy metabolism or maximizes the utilization of materials and energy by regulating the supply intensity and mode of ATP and reducing electron carriers in cells. On the one hand, the production efficiency can be increased by changing the distribution of material metabolic flow. On the other hand, the thermodynamic parameters of enzyme-catalyzed reactions can be altered to affect the reaction balance, and thus the production costs are reduced. Therefore, energy metabolism regulation is expected to become a favorable tool for the modification of microbial cell factories, thereby increasing the production of target metabolites and reducing production costs. This article introduces the commonly used energy metabolism regulation methods and their effects on cell factories, aiming to provide a reference for the efficient construction of microbial cell factories.
Energy Metabolism/physiology* ; Metabolic Engineering/methods* ; Adenosine Triphosphate/metabolism* ; Industrial Microbiology/methods*

Cognitive impairment is the main clinical manifestation of many nervous system diseases such as stroke,multiple sclerosis,and neurodegeneration,and neuroinflammation is one of the key mechanisms for the onset of cognitive disorders.Chemokines are a class of highly conserved small-molecule secretory proteins that bind to the corresponding chemokine receptors located on cell mem-brane,activating downstream signaling pathways and playing an important role in cell migration,proliferation,differentiation,and sur-vival.In the central nervous system,chemokines and their receptors are involved in immune response and can exert a certain regulatory effect on neuroinflammation.This article reviews the research advances in chemokines and their receptors in cognitive disorders,in or-der to provide new insights and targets for the early diagnosis and treatment of related diseases.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*