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This study aimed to clarify the role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes and the role of voltage-dependent anion channel 1 (VDAC1) in the PINK1/Parkin signaling pathway in mouse glomerular podocytes. For this purpose, podocytes were cultured with rapamycin and observed using microscopy. The apoptosis rate of podocytes was detected by flow cytometry. Changes in the mitochondrial membrane potential were measured. The autophagy-related proteins VDAC1, PINK1, Parkin, and LC3 were detected, and mitochondrial autophagosomes were observed via transmission electron microscopy. In the present study, we demonstrated that the number of podocytes treated with rapamycin was significantly reduced. Compared with those in the control group, the apoptosis rate of podocytes and the degree of mitochondrial membrane potential depolarization were significantly higher. We also found the expression levels of VDAC1, PINK1, Parkin, and LC3 were significantly increased. In the rapamycin-treated group, the numbers of swollen mitochondria and mitochondrial autophagosomes were significantly higher. Finally, we showed that rapamycin can upregulate the expression of VDAC1, PINK1, Parkin, and LC3 in glomerular podocytes, which is correlated with mitophagy. VDAC1 is involved in mitophagy and is related to the PINK1/Parkin signaling pathway, serving as an indicator of mitophagy in podocytes.

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BACKGROUND: Allergen testing has emerged as a pivotal component in prevention and treatment strategies for allergic diseases among children and the utilization of specific IgE (sIgE) through a fully automated chemiluminescent microarray immunoassay (CLMIA) has emerged as a promising trend in the simultaneous detection of multiple allergenic components of children. METHODS: The accuracy and reliability of CLMIA were verified using children's serum samples that concentrated on allergens. the allergens. The clinical diagnostic practicability of CLMIA was assessed through comprehensive evaluations including measurements of the limit of detection (LOD), intra-batch, and inter-batch precision, linearity analysis, the cross-contamination rate, and the concordance rate with the Phadia system. RESULTS: After the optimization process of CLMIA, the LODs for allergens were calculated to be below 0.01 kU/L, demonstrating the high sensitivity of CLMIA. All components exhibited good linearity within the range of 0.1-100.0 kU/L and the coefficient of determinations (R2 > 0.99). The data of intra-batch precision (<10 %) and inter-batch data (<15 %) illustrated the high reproducibility of CLMIA. The cross-contamination rates for allergens (<0.5 %) showed the high accuracy of CLMIA without interfering. The positive concordance rate between CLMIA and the Phadia system exceeds 90 % with a good negative concordance rate (>85 %) and the Kappa coefficients (>0.8), suggesting the close alignment of CLMIA and the Phadia system and showing the satisfactory clinical potential of CLMIA in children's allergy disease. CONCLUSIONS: The application of CLMIA has been promising in allergen testing, especially for detecting multiple allergenic components in children.

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As global population ageing accelerates, cancer emerges as a predominant cause of mortality. Long non-coding RNAs (lncRNAs) play crucial roles in cancer cell growth and death, given their involvement in regulating downstream gene expression levels and numerous cellular processes. Cell death, especially non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis and necroptosis, significantly impacts cancer proliferation, invasion and metastasis. Understanding the interplay between lncRNAs and the diverse forms of cell death in cancer is imperative. Modulating lncRNA expression can regulate cancer onset and progression, offering promising therapeutic avenues. This review discusses the mechanisms by which lncRNAs modulate non-apoptotic RCDs in cancer, highlighting their potential as biomarkers for various cancer types. Elucidating the role of lncRNAs in cell death pathways provides valuable insights for personalised cancer interventions.

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Exosomes, which are extracellular vesicles secreted and released from specific cells, exist widely in cell culture supernatants and various body fluids. This study aimed to analyze the research status of exosomes in stroke, and predict developmental trends via bibliometric analyses. The related literature from January 1, 2008 to January 1, 2024 was searched in the Web of Science Core Collection and 943 articles were retrieved. VOSviewer was used to visualize national cooperation and institutional cooperation. Cluster analysis of keywords and Citespace were applied for mutation analysis. Results: The analysis of 943 works of literature showed that the number of published articles has been steadily increasing since 2015. It is predicted that nearly 211 articles will be published in 2024 and 220 annually by 2028. China has the largest number of publications (473), followed by the United States (234), and Germany (61). The institution with the most publications is Henry Ford Hospital (Detroit, MI). In the keyword cluster "Exosomes and the Mechanism of Stroke: Inflammation and Apoptosis," exosomes and inflammation were identified as hotspots. "Functional recovery" was a new trend in the keyword cluster of "Angiogenesis and Functional Recovery after Stroke." China and the United States are the main forces in this field, and both countries focusing on drug treatments. The studies have been published mainly in China and United States. The findings of our bibliometric analyses of the literature may enable researchers to choose appropriate institutions, collaborators, and journals.

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Renal fibrosis (RF) is a common endpoint of various chronic kidney diseases, leading to functional impairment and ultimately progressing to end-stage renal failure. Glycolytic reprogramming plays a critical role in the pathogenesis of fibrosis, which maybe a potential therapeutic target for treating renal fibrosis. Here, we revealed the novel role of ZEB1 in renal fibrosis, and whether targeting ZEB1 is the underlying mechanism for the anti-fibrotic effects of ethyl caffeate (EC) to regulate the glycolytic process. Treatment of EC attenuated the renal fibrosis and inhibited ZEB1 expression in vivo and in vitro, reducing the upregulated expression of glycolytic enzymes (HK2, PKM2, PFKP) and key metabolites (lactic acid, pyruvate). ZEB1 overexpression promoted the renal fibrosis and glycolysis, whereas knockout of ZEB1 apparently attenuated renal fibrosis in vivo and in vitro. EC interacted with ZEB1 to modulate the glycolytic enzymes for suppressing the elevated glycolytic reprogramming during renal fibrosis. In summary, our study reveals that ZEB1 plays an important role in regulating glycolytic reprogramming during the renal tubular epithelial cell fibrosis, suggesting inhibition of ZEB1 may be a potential strategy for treating renal fibrosis. Additionally, EC is a potential new drug candidate for the treatment of renal fibrosis and CKD.

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BACKGROUND: Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome (ARDS) patients. Mesenchymal stromal cell-derived microvesicles (MSC-MVs) have been shown to exert antifibrotic effects in lung diseases. AIM: To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models. METHODS: MSC-MVs with low hepatocyte growth factor (HGF) expression (siHGF-MSC-MVs) were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model. Following intubation, respiratory mechanics-related indicators were measured via an experimental small animal lung function tester. Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging. Immunohistochemical, western blotting, ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators. RESULTS: The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice. Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores. However, low expression of HGF (siHGF-MSC-MVs) significantly inhibited the effects of MSC-MVs (P < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expression of type I collagen antigen, type III collagen antigen, and the proteins transforming growth factor-ß and α-smooth muscle actin, whereas the siHGF-MVs group exhibited significantly increased expression of these proteins. In addition, pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group, and the effects of the MSC-MVs were significantly inhibited by low HGF expression (all P < 0.05). CONCLUSION: MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

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It has been recognized that oxidative stress (OS) is implicated in the etiology of recurrent pregnancy loss (RPL), yet the biomarkers reflecting oxidative stress in association with RPL remain scarce. The dataset GSE165004 was retrieved from the Gene Expression Omnibus (GEO) database. From the GeneCards database, a compendium of 789 genes related to oxidative stress-related genes (OSRGs) was compiled. By intersecting differentially expressed genes (DEGs) in normal and RPL samples with OSRGs, differentially expressed OSRGs (DE-OSRGs) were identified. In addition, four machine learning algorithms were employed for the selection of diagnostic markers for RPL. The Receiver Operating Characteristic (ROC) curves for these genes were generated and a predictive nomogram for the diagnostic markers was established. The functions and pathways associated with the diagnostic markers were elucidated, and the correlations between immune cells and diagnostic markers were examined. Potential therapeutics targeting the diagnostic markers were proposed based on data from the Comparative Toxicogenomics Database and ClinicalTrials.gov. The candidate biomarker genes from the four models were further validated in RPL tissue samples using RT-PCR and immunohistochemistry. A set of 20 DE-OSRGs was identified, with 4 genes (KRAS, C2orf69, CYP17A1, and UCP3) being recognized by machine learning algorithms as diagnostic markers exhibiting robust diagnostic capabilities. The nomogram constructed demonstrated favorable predictive accuracy. Pathways including ribosome, peroxisome, Parkinson's disease, oxidative phosphorylation, Huntington's disease, and Alzheimer's disease were co-enriched by KRAS, C2orf69, and CYP17A1. Cell chemotaxis terms were commonly enriched by all four diagnostic markers. Significant differences in the abundance of five cell types, namely eosinophils, monocytes, natural killer cells, regulatory T cells, and T follicular helper cells, were observed between normal and RPL samples. A total of 180 drugs were predicted to target the diagnostic markers, including C544151, D014635, and CYP17A1. In the validation cohort of RPL patients, the LASSO model demonstrated superiority over other models. The expression levels of KRAS, C2orf69, and CYP17A1 were significantly reduced in RPL, while UCP3 levels were elevated, indicating their suitability as molecular markers for RPL. Four oxidative stress-related diagnostic markers (KRAS, C2orf69, CYP17A1, and UCP3) have been proposed to diagnose and potentially treat RPL.

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OBJECTIVE: To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) and radical surgery for non-metastatic pancreatic cancer (PC). MATERIALS AND METHODS: We retrospectively analyzed 89 stage I/II/III PC patients who underwent HIFU (n = 43) or surgery (n = 46) at the Third Xiangya Hospital from January 2020 to December 2021. Pain relief, Karnofsky Performance Scale (KPS), overall survival (OS), treatment-related complications and risk factors for OS were assessed. RESULTS: There was no significant difference in the pain relief rate at 30 days post-treatment between the two groups. However, compared with the surgery group, the HIFU group showed significantly lower post-treatment VAS scores (p = 0.019). In the surgery group, the KPS at 30 days post-treatment was lower than pretreatment KPS (70 vs 80; p = 0.015). This relationship was reversed in the HIFU group (80 vs 70; p = 0.024). Median OS favored surgery over HIFU (23 vs 10 months; p < 0.001), with a higher 1-year OS rate (69.57% vs 32.6%; p < 0.001). However, there was no significant difference in OS between the two groups for stage III patients (p = 0.177). Complications rated ≥ grade III were 2.33% in the HIFU group and 32.6% in the surgery group. Multivariate analyses showed that age, KPS, and treatment methods were independent prognostic factors for OS. CONCLUSION: HIFU demonstrates advantages over surgery in terms of early KPS, VAS improvements, and safety for pancreatic cancer; however, long-term outcomes favor surgery. For III-stage disease, HIFU was noninferior to surgery in overall survival.

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Microbial degradation plays a crucial role in removing sulfonamides from soil, enhancing sulfamethoxazole (SMX) remediation. To further augment SMX removal efficiency and mitigate the transmission risk associated with antibiotic resistance genes (ARGs), this study proposes a novel approach that integrates micro-animals, microorganisms, and microbial fuel cell (MFC) technology. The results showed that earthworm-MFC synergy substantially reduces SMX content and ARGs abundance in soil. The introduction of earthworms enhances humus content, facilitating electron transfer within MFC and consequently improving current generation. Furthermore, electrical stimulation applied to earthworms led to increased protein secretion and enhanced antioxidant system activity, thereby accelerating SMX degradation. Earthworms also foster MFC-associated bacterial growth and SMX-degrading bacteria proliferation, augmenting MFC treatment efficacy. This synergistic effect significantly augmented the overall efficacy of MFC treatment for antibiotics. Overall, integrating earthworm activity with MFC technology effectively optimizes electricity generation and enhances pollutant removal.

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Cardiovascular disease (CVD) has now become the leading cause of death worldwide, and its high morbidity and mortality rates pose a great threat to society. Although numerous studies have reported the pathophysiology of CVD, the exact pathogenesis of all types of CVD is not fully understood. Therefore, much more research is still needed to explore the pathogenesis of CVD. With the development of proteomics, many studies have successfully identified the role of posttranslational modifications in the pathogenesis of CVD, including key processes such as apoptosis, cell metabolism, and oxidative stress. In this review, we summarize the progress in the understanding of posttranslational modifications in cardiovascular diseases, including novel protein posttranslational modifications such as succinylation and nitrosylation. Furthermore, we summarize the currently identified histone deacetylase (HDAC) inhibitors used to treat CVD, providing new perspectives on CVD treatment modalities. We critically analyze the roles of posttranslational modifications in the pathogenesis of CVD-related diseases and explore future research directions related to posttranslational modifications in cardiovascular diseases.

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OBJECTIVE: To investigate potential mechanisms of anti-atherosclerosis by berberine (BBR) using ApoE-/- mice. METHODS: Eight 8-week-old C57BL/6J mice were used as a blank control group (normal), and 56 8-week-old AopE-/- mice were fed a high-fat diet for 12 weeks, according to a completely random method, and were divided into the model group, BBR low-dose group (50 mg/kg, BBRL), BBR medium-dose group (100 mg/kg, BBRM), BBR high-dose group (150 mg/kg, BBRH), BBR+nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor group (100 mg/kg BBR+30 mg/kg ML385, BBRM+ML385), NRF2 inhibitor group (30 mg/kg, ML385), and positive control group (2.5 mg/kg, atorvastatin), 8 in each group. After 4 weeks of intragastric administration, samples were collected and serum, aorta, heart and liver tissues were isolated. Biochemical kits were used to detect serum lipid content and the expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in all experimental groups. The pathological changes of atherosclerosis (AS) were observed by aorta gross Oil Red O, aortic sinus hematoxylin-eosin (HE) and Masson staining. Liver lipopathy was observed in mice by HE staining. The morphology of mitochondria in aorta cells was observed under transmission electron microscope. Flow cytometry was used to detect reactive oxygen species (ROS) expression in aorta of mice in each group. The content of ferrous ion Fe2+ in serum of mice was detected by biochemical kit. The mRNA and protein relative expression levels of NRF2, glutathione peroxidase 4 (GPX4) and recombinant solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real time polymerase chain reaction (RT-qPCR) and Western blot, respectively. RESULTS: BBRM and BBRH groups delayed the progression of AS and reduced the plaque area (P<0.01). The characteristic morphological changes of ferroptosis were rarely observed in BBR-treated AS mice, and the content of Fe2+ in BBR group was significantly lower than that in the model group (P<0.01). BBR decreased ROS and MDA levels in mouse aorta, increased SOD activity (P<0.01), significantly up-regulated NRF2/SLC7A11/GPX4 protein and mRNA expression levels (P<0.01), and inhibited lipid peroxidation. Compared with the model group, the body weight, blood lipid level and aortic plaque area of ML385 group increased (P<0.01); the morphology of mitochondria showed significant ferroptosis characteristics; the serum Fe2+, MDA and ROS levels increased (P<0.05 or P<0.01), and the activity of SOD decreased (P<0.01). Compared with BBRM group, the iron inhibition effect of BBRM+ML385 group was significantly weakened, and the plaque area significantly increased (P<0.01). CONCLUSION: Through NRF2/SLC7A11/GPX4 pathway, BBR can resist oxidative stress, inhibit ferroptosis, reduce plaque area, stabilize plaque, and exert anti-AS effects.

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Research on the microbiome and resistome in polar environments, such as the Arctic, is crucial for understanding the emergence and spread of antibiotic resistance genes (ARGs) in the environment. In this study, soil and reindeer faeces samples collected from Ny-Ålesund (Svalbard, High Arctic) were examined to analyze the microbiome, ARGs, and biocide/metal resistance genes (BMRGs). The dominant phyla in both soil and faeces were Pseudomonadota, Actinomycetota, and Bacteroidota. A total of 2618 predicted Open Reading Frames (ORFs) containing antibiotic resistance genes (ARGs) were detected. These ARGs belong to 162 different genes across 17 antibiotic classes, with rifamycin and multidrug resistance genes being the most prevalent. We focused on investigating antibiotic resistance mechanisms in the Ny-Ålesund environment by analyzing the resistance genes and their biological pathways. Procrustes analysis demonstrated a significant correlation between bacterial communities and ARG/BMRG profiles in soil and faeces samples. Correlation analysis revealed that Pseudomonadota contributed most to multidrug and triclosan resistance, while Actinomycetota were predominant contributors to rifamycin and aminoglycoside resistance. The geochemical factors, SiO42- and NH4+, were found to significantly influence the microbial composition and ARG distribution in the soil samples. Analysis of ARGs, BMRGs, virulence factors (VFs), and pathogens identified potential health risks associated with certain bacteria, such as Cryobacterium and Pseudomonas, due to the presence of different genetic elements. This study provided valuable insights into the molecular mechanisms and geochemical factors contributing to antibiotic resistance and enhanced our understanding of the evolution of antibiotic resistance genes in the environment.

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OBJECTIVE: Facial paralysis (FP), which resulted from head and neck cancer resection, significantly impacts patients' quality of life. Traditional assessments rely on subjective evaluations and electromyography, whereas functional magnetic resonance imaging offers a noninvasive alternative for enhanced rehabilitation. Acupuncture has shown promise in promoting cerebral cortex reorganization, yet the precise relationship between acupuncture-induced structural and functional changes remains unclear, necessitating further investigation into therapeutic mechanisms. METHODS: Fifty-five patients afflicted with FP underwent evaluations using voxel-mirrored homotopic connectivity (VMHC) and tract-based spatial statistics and were divided into the acupuncture intervention group (n = 35) and pseudo intervention group (n = 20). Comparative analyses of metrics pre and postintervention were conducted to delineate therapy-induced modifications in acupuncture intervention. The postacupuncture effect between groups to verify the necessity of accurate positioning for the rehabilitation of FP. RESULTS: Patients with FP showed deficits in VMHC in regions of the postcentral, precentral, and parietal areas. Corpus callosum and internal capsule showed significantly increased fractional anisotropy of the white matter skeleton in tract-based spatial statistics after treatment. Comparison postintervention results between groups exhibited deficits in VMHC and increased fractional anisotropy in regions of the corpus callosum in the acupuncture intervention group. CONCLUSIONS: Early acupuncture intervention may suppress cortical hyperactivation and restore interhemispheric inhibition across the corpus callosum to inhibit maladaptive structural plasticity. Precise acupoint localization is crucial for effective therapy, highlighting the potential of postacupuncture cortical space data for refining therapeutic strategies.

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Aqueous emulsion polymerization is a robust technique for preparing nanoparticles of block copolymers; however, it typically yields spherical nanoassemblies. The scale preparation of nanoassemblies with nonspherical high-order morphologies is a challenge, particularly 2D core-shell nanosheets. In this study, the polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are combined to demonstrate the preparation of 2D nanosheets and their aggregates via aqueous reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. First, the crucial crystallizable component for CDSA, hydroxyethyl methacrylate polycaprolactone (HPCL) macromonomer is synthesized by ring opening polymerization (ROP). Subsequently, the RAFT emulsion polymerization of HPCL is conducted to generate crystallizable nanomicelles by a grafting-through approach. This PISA process simultaneously prepared spherical latices and bottlebrush block copolymers comprising poly(N',N'-dimethylacrylamide)-block-poly(hydroxyethyl methacrylate polycaprolactone) (PDMA-b-PHPCL). The latexes are now served as seeds for inducing the formation of 2D hexagonal nanosheets, bundle-shaped and flower-like aggregation via the CDSA of PHPCL segments and unreacted HPCL during cooling. Electron microscope analysis trace the morphology evolution of these 2D nanoparticles and reveal that an appropriate crystallized component of PHPCL blocks play a pivotal role in forming a hierarchical structure. This work demonstrates significant potential for large-scale production of 2D nanoassemblies through RAFT emulsion polymerization.

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Lilium brownii var. viridulum (Longya lily) is an edible vegetable and medicinal plant with the effects of moistening lungs, relieving coughs, and removing phlegm. In this study, a homogenous mannoglucan LLP11 was purified from Longya lily using membrane ultrafiltration followed by ion exchange chromatography. The M w of LLP11 was 12.0 kDa. LLP11 exhibited a backbone of →4)-α-D-Glcp-(1 â†’ and →4)-ß-D-Manp-(1 â†’ with a branch of T-α-D-Glcp-(1 â†’ substituted at C-6 of →4,6)-α-D-Glcp-(1→. During the simulated digestion, LLP11 remained indigestible to digestive enzymes. Furthermore, through its interaction with the gut microbiota, LLP11 was able to significantly boost Bifidobacterium and decrease the harmful bacteria Klebsiella, that was linked to pneumonia. Additionally, LLP11 promoted the growth of B. pseudocatenulatum and B. longum and was utilized to produce acetic acid. Our findings introduced an alternative approach for the investigation of microbiota-targeted polysaccharides and underscored the potential of LLP11 as a prebiotic for supplementary treatment in respiratory diseases.

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Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.

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Protein therapeutics are essential in treating various diseases, but their inherent biological instability and short circulatory half-lives in vivo pose challenges. Herein, a quantitative one-pot iterative living polymerization technique is reported towards precision control over the molecular structure and monomer sequence of protein-polymer conjugates, aiming to maximize physicochemical properties and biological functions of proteins. Using this quantitative one-pot iterative living polymerization technique, we successfully develop a series of sequence-controlled protein-multiblock polymer conjugates, enhancing their biostability, pharmacokinetics, cellular uptake, and in vivo biodistribution. All-atom molecular dynamics simulations are performed to disclose the definite sequence-function relationship of the bioconjugates, further demonstrating their sequence-encoded cellular uptake behavior and in vivo biodistribution in mice. Overall, this work provides a robust approach for creating precision protein-polymer conjugates with defined sequences and advanced functions as a promising candidate in disease treatment.

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Macrocycles play vital roles in supramolecular chemistry and chromatography. 1,1'-Bi-2-naphthol (BINOL)-based chiral polyimine macrocycles are an emerging class of chiral macrocycles that can be constructed by one-step aldehyde-amine condensation of BINOL derivatives with other building blocks. These macrocycles exhibit good characteristics, such as facile preparation, rigid cyclic structures, multiple chiral centers, and defined molecular cavities, that make them good candidates as new chiral recognition materials for chromatographic enantioseparations. In this study, a BINOL-based [2+2] chiral polyimine macrocycle was synthesized by one-step condensation of enantiopure (S)-2,2'-dihydroxy-[1,1'-binaphthalene]-3,3'-dicarboxaldehyde with (1R,2R)-1,2-diaminocyclohexane. The product was modified with 5-bromo-1-pentene and then attached to thiolated silica using click chemistry to construct a new chiral stationary phase (CSP). The enantioselectivity of the new CSP was explored by separating various racemates under normal phase (NP) and reversed phase (RP) high performance liquid chromatography (HPLC). Thirteen racemates and eight racemates were enantioseparated under the two separation modes, respectively, including chiral alcohols, phenols, esters, ketones, amines, and organic acids. Among them, nine racemates achieved baseline separation under NP-HPLC and seven racemates achieved baseline separation under RP-HPLC. High resolution separation was observed with benzoin (Rs = 5.10), epinephrine (Rs = 4.98), 3-benzyloxy-1,2-propanediol (Rs = 4.42), and 4,4'-dimethylbenzoin (Rs = 4.52) in NP-HPLC, and with 4-methylbenzhydrol (Rs = 4.72), benzoin ethyl ether (Rs = 3.79), 1-phenyl-1-pentanol (Rs = 3.68), and 1-(3-bromophenyl)ethanol (Rs = 3.60) in RP-HPLC. Interestingly, the CSP complemented Chiralcel OD-H, Chiralpak AD-H, and CYCLOBOND I 2000 RSP columns for resolution of these test racemates, separating several racemic compounds that could not be well separated by the three commercially available columns. The influences of injected sample amount on separation were also evaluated. It was found that the column exhibited excellent stability and reproducibility after hundreds of injections, and the relative standard deviations (n = 5) of the retention time and resolution were less than 0.49% and 0.69%, respectively. This study indicates that the BINOL-based chiral macrocycle has great potential for HPLC enantioseparation.

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Macrocyclic compounds such as crown ethers and cyclodextrins play an important role in the field of chromatography and show excellent separation performance. The design of simple and convenient methods for the efficient synthesis of novel chiral macrocycles for chromatographic separation is of great significance. In this work, a novel chiral polyimine macrocycle (PIMC) was designed and synthesized by the simply one-step reaction of 2,6-diformyl-4-tert-butylphenol with (S)-(-)-1,2-propanediamine. Then, it was bonded onto silica by the thiol-ene click reaction to construct a new chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC). The chiral separation performance of the proposed CSP was examined by separating various racemates in the normal-phase (NP) and reversed-phase (RP) HPLC. In total, twelve and nine racemates, including ethers, esters, amines, alcohols, organic acids, ketones, and epoxides, were separated to varying degrees via NP-HPLC and RP-HPLC, respectively, Moreover, the CSP offered good chiral separation complementarity to Chiralcel OD-H and Chiralpak AD-H columns for resolution of these test racemates, and it can separate several racemic compounds that either cannot be separated or cannot be separated well be separated by the two commercially available columns. After the column was used for hundreds of injections, the relative standard deviations of the retention time and resolution were below 0.56 % and 0.45 %, respectively, showing the good reproducibility and stability of the CSP. This study provides a simple and convenient approach to synthesize a novel chiral macrocycle and CSP and also indicates the broad application prospects of such chiral PIMCs in HPLC chiral separation.