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Neural cell adhesion molecule (NCAM), a common mammalian cell surface glycoprotein, is the major substrate of polysialic acid (polySia). Polysialylated NCAM occurs in many types of cancer, but rarely in normal adult tissues. The functional role of NCAM hypersialylation in the epithelial-mesenchymal transition (EMT) process remains unclear. The present study indicates that NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways. NCAM and polysialylated NCAM are aberrantly regulated in breast cancer cells. They are both upregulated in normal breast epithelial cells undergoing EMT. Western blot analysis demonstrates that NCAM-140 overexpression induces EMT in breast epithelial cells and promotes cell proliferation and migration through activation of the β-catenin/slug signaling pathway. Modification of polySia attached to NCAM modulates cell adhesion and promotes cell motility through activation of the EGFR/STAT3 pathway. These observations contribute to clarifying the molecular mechanisms by which polysialic acid and its major substrate, NCAM, modulate cell behaviors, and highlight the significance of increased polysialylated expression on NCAM during EMT and tumor development.

Background: This study aims to analyze potential differences in clinicopathology, efficacy of neoadjuvant therapy (NAT), and clinical outcome among HER2-null, HER2-ultralow and HER2-low breast cancers., Methods: Consecutive cases of HER2-negative breast cancer that received NAT were included. They were classified as HER2-null (no staining), HER2-ultralow (incomplete faint staining in ≤ 10% of tumour cells) and HER2-low (HER2-1 + or HER2-2+, in situ hybridisation negative). Subgroup analysis was performed based on the HER2 expression level., Results: Out of 302 patients, 215 (71.19%) were HER2-low, 59 (19.54%) were HER2-ultralow, and 28 (9.27%) were HER2-null. In comparison to the HER2-ultralow group, the HER2-low group exhibited higher expression frequencies of ER (p < 0.001), PR (p < 0.001), and AR (p = 0.004), along with a greater prevalence of the luminal subtype (p < 0.001). The HER2-ultralow group also demonstrated a higher prevalence of lymph node metastasis compared to the HER2-null group (p = 0.026). Varied rates of pathologic complete response (pCR) were observed among the three subgroups: HER2-null, HER2-ultralow, and HER2-low, with rates of 35.71%, 22.03%, and 12.56%, respectively. Only the HER2-low subgroup exhibited a significant difference compared to HER2-null (p = 0.001). Despite variations in pCR rates, the three subgroups exhibited comparable disease-free survival (DFS) (p = 0.571). Importantly, we found HER2-low patients with better treatment response (RCB-0/I) exhibited significantly better DFS than those with significant residual disease (RCB-II/III) (P = 0.036). The overall rate of HER2 immunohistochemical score discordance was 45.24%, mostly driven by the conversion between HER2-0 and HER2-low phenotype. Notably, 32.19% of cases initially classified as HER2-0 phenotype on baseline biopsy were later reclassified as HER2-low after neoadjuvant therapy, and it is noteworthy that 22 out of these cases (78.57%) originally had an HER2-ultralow status in the pretreatment biopsy sample., Conclusions: Our results demonstrate the distinct clinicopathological features of HER2-low and HER2-ultralow breast tumors and confirm that RCB is an effective predictor of prognosis in HER2-low populations for the first time. Notably, our findings demonstrate high instability in both HER2-low and HER2-ultralow expression from the primary baseline biopsy to residual disease after NAT. Furthermore, this study is the first to investigate the clinicopathological feature and the effectiveness of NAT for HER2-ultralow breast cancer., (© 2024. The Author(s).)

The permeability of blood vessels plays a crucial role in the spread of cancer cells, facilitating their metastasis at distant sites. Small extracellular vesicles (sEVs) are known to contribute to the metastasis of various cancers by crossing the blood vessel wall. However, the role of abnormal glycoconjugates on sEVs in tumor blood vessels remains unclear. Our study found elevated levels of fucosyltransferase VII (FUT7) and its product sialyl Lewis X (sLeX) in muscle-invasive bladder cancer (BLCA), with high levels of sLeX promoting the growth and invasion of BLCA cells. Further investigation revealed that sLeX was enriched in sEVs derived from BLCA. sLeX-decorated sEVs increased blood vessel permeability by disrupting the tight junctions of human umbilical vein endothelial cells (HUVECs). Using the glycoproteomics approach, we identified integrin α3 (ITGA3) as a sLeX-bearing glycoprotein in BLCA cells and their sEVs. Mechanically, sLeX modification stabilized ITGA3 by preventing its degradation in lysosomes. sEVs carrying sLeX-modified ITGA3 can be effectively internalized by HUVECs, leading to a decrease in the expression of tight junction protein. Conversely, silencing ITGA3 in sLeX-decorated sEVs restored tight junction proteins and reduced blood vessel permeability by inhibiting the MAPK pathway. Moreover, sLeX-modification of ITGA3 at Asn 265 in HUVECs promoted occludin dephosphorylation at Ser/Thr residues, followed by inducing its importin α1-mediated nuclear translocation, which resulted in the disruption of tight junctions. Our findings suggest a potential strategy for disrupting the formation of a metastatic microenvironment and preventing the spread of malignant bladder cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS-based magnetic beads (Mag-CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV-HCC patients. Leveraging data-independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV-HCC from CHB, LC, and non-HCC conditions. Collectively, our findings highlight the utility of Mag-CS-based sEV isolation for identifying early detection biomarkers in HBV-HCC., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

The tumor microenvironment (TME) consists of tumor cells, non-tumor cells, extracellular matrix, and signaling molecules, which can contribute to tumor initiation, progression, and therapy resistance. In response to starvation, hypoxia, and drug treatments, tumor cells undergo a variety of deleterious endogenous stresses, such as hypoxia, DNA damage, and oxidative stress. In this context, to survive the difficult situation, tumor cells evolve multiple conserved adaptive responses, including metabolic reprogramming, DNA damage checkpoints, homologous recombination, up-regulated antioxidant pathways, and activated unfolded protein responses. In the last decades, the protein O-GlcNAcylation has emerged as a crucial causative link between glucose metabolism and tumor progression. Here, we discuss the relevant pathways that regulate the above responses. These pathways are adaptive adjustments induced by endogenous stresses in cells. In addition, we systematically discuss the role of O-GlcNAcylation-regulated stress-induced adaptive response pathways (SARPs) in TME remodeling, tumor progression, and treatment resistance. We also emphasize targeting O-GlcNAcylation through compounds that modulate OGT or OGA activity to inhibit tumor progression. It seems that targeting O-GlcNAcylated proteins to intervene in TME may be a novel approach to improve tumor prognosis., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The aberrant up-regulation of meiotic nuclear division 1 (MND1) in somatic cells is considered as one of the driving factors of oncogenesis, whereas its expression and role in breast invasive cancer (BRCA) remain unclear. Hence, this study embarked on a comprehensive evaluation of MND1 across various cancers and identified its roles in BRCA., Methods: Based on publicly available databases, including but not limited to UCSC Xena, TCGA, GTEx, GEO, STRING, GeneMANIA, and CancerSEA, we evaluated the expression patterns, genomic features, and biological functions of MND1 from a pan-cancer viewpoint and delved into the implications of MND1 in the prognosis and treatment of BRCA. Further molecular biology experiments were undertaken to identify the role of MND1 in proliferation, migration, and apoptosis in BRCA cells., Results: Elevated levels of MND1 were notably observed in a wide array of tumor types, especially in BRCA, COAD, HNSC, LIHC, LUAD, LUSC, STAD, and UCEC. Elevated MND1 expression was markedly associated with shortened OS in several tumors, including BRCA (HR = 1.52 [95%CI, 1.10-2.09], P = 0.011). The up-regulation of MND1 in BRCA was validated in external cohorts and clinical samples. Survival analyses demonstrated that elevated MND1 expression was associated with decreased survival for patients with BRCA. Co-expressed genes of MND1 were identified, and subsequent pathway analyses based on significantly associated genes indicated that MND1 plays key roles in DNA replication, cell cycle regulation, and DNA damage repair. The observed abnormal elevation and activation of MND1 led to increased proliferation and migration, along with decreased apoptosis in BRCA cells., Conclusions: MND1 emerges as a promising biomarker for diagnostic and therapeutic targeting in various cancers, including BRCA. The abnormal up-regulation and activation of MND1 are linked to carcinogenesis and poor prognosis among BRCA patients, which may be attributed to its involvement in HR-dependent ALT, warranting further scrutiny., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Chemoresistance is a key factor contributing to the failure of anti-breast cancer chemotherapy. Although abnormal glycosylation is closely correlated with breast cancer progression, the function of glycoconjugates in chemoresistance remains poorly understood. Methods: Levels and regulatory roles of bisecting N-acetylglucosamine (GlcNAc) in chemoresistant breast cancer cells were determined in vitro and in vivo. Glycoproteomics guided identification of site-specific bisecting GlcNAc on P-glycoprotein (P-gp). Co-immunoprecipitation coupled mass spectrometry (Co-IP-MS) and proximity labelling MS identified the interactome of P-gp, and the biological function of site-specific bisecting GlcNAc was investigated by site/truncation mutation and structural simulations. Results: Bisecting GlcNAc levels were reduced in chemoresistant breast cancer cells, accompanied by an enhanced expression of P-gp. Enhanced bisecting GlcNAc effectively reversed chemoresistance. Mechanical study revealed that bisecting GlcNAc impaired the association between Ezrin and P-gp, leading to a decreased expression of membrane P-gp. Bisecting GlcNAc suppressed VPS4A-mediated P-gp recruitment into microvesicles, and chemoresistance transmission. Structural dynamics analysis suggested that bisecting GlcNAc at Asn494 introduced structural constraints that rigidified the conformation and suppressed the activity of P-gp. Conclusion: Our findings highlight the crucial role of bisecting GlcNAc in chemoresistance and suggest the possibility of reversing chemoresistance by modulating the specific glycosylation in breast cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Protein glycosylation is a type of protein post-translational modification. One specific example is the modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) and O-linked α-N-acetylgalactosamine (O-GalNAc). Enhanced levels of both O-GalNAc and O-GlcNAc in bladder cancer (BlCa) have been reported previously. However, the interplay between O-GalNAc and O-GlcNAc has yet to be explored. Herein, we find that the expression level of core1 β-1,3-galactosyltransferase (C1GalT1), which is responsible for extending and maturing mucin-type O-glycans, is increased in BlCa. This increase is accompanied by O-GlcNAc modification of C1GalT1. This modification stabilizes C1GalT1 expression and strengthens its interaction with its chaperone Cosmc. Mutation at Thr229 or Thr233 attenuates C1GalT1 stability and facilitates its degradation via the proteasome pathway. Furthermore, a decrease in C1GalT1 inhibits the pro-tumorigenic effect on bladder cancer cells by suppressing glycolysis.

Ruminants are one of the world's economically important species, and their reproductive health is critical to the economic development of the livestock industry. In recent years, research on the relationship between microbiota and reproductive health has received much attention. Microbiota disruption affects the developmental health of the testes and epididymis, the male reproductive organs of the host, which in turn is related to sperm quality. Maintaining a stable microbiota protects the host from pathogens and increases breeding performance, which in turn promotes the economic development of animal husbandry. In addition, the effects and mechanisms of microbiota on reproduction were further explored. These findings support new approaches to improving and managing reproductive health in ruminants through the microbiota and facilitate further systematic exploration of microbiota-mediated reproductive impacts., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Hirudo nipponia is an important medicinal animal in China. Its salivary gland secretions contain a variety of protein bioactive substances. Investigations of its salivary glands are of great significance in the study of the medicinal value and mechanism of leech secretions. Illumina RNA-Seq technology was used to perform transcriptome sequencing of salivary gland tissue of H. nipponia under starvation (D30) and fed (D0) states. A total of 2,650 differentially expressed genes (DEGs) were screened. Using the label-free protein quantification technique and bioinformatics analysis, the expression of differentially expressed proteins (DEPs) in the salivary gland tissue of H. nipponia was compared. A total of 2,021 proteins were identified, among which 181 proteins were differentially expressed between the starvation and fed states, with 72 significantly upregulated and 109 significantly downregulated. The salivary glands of H. nipponia synthesized protein-based active substances after 30 days of starvation and adapted to the starvation environment by weakening respiratory activity and reducing metabolic activity to reduce energy expenditure. Energy was produced by glycolysis and the tricarboxylic acid cycle for the synthesis of substances such as antibiotics. This study combined transcriptome and proteome sequencing data to provide a data reference for an in-depth study of the regulatory mechanism of salivary gland secretions of H. nipponia under starvation stress by analyzing DEGs and DEPs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to examine the feasibility of utilizing radiomics models derived from 18 F-FDG PET/CT imaging to screen for T-cell lymphoma in children with lymphoma. All patients had undergone 18 F-FDG PET/CT scans. Lesions were extracted from PET/CT and randomly divided into training and validation sets. Two different types of models were constructed as follows: features that are extracted from standardized uptake values (SUV)-associated parameters, and CT images were used to build SUV/CT-based model. Features that are derived from PET and CT images were used to build PET/CT-based model. Logistic regression (LR), linear support vector machine, support vector machine with the radial basis function kernel, neural networks, and adaptive boosting were performed as classifiers in each model. In the training sets, 77 patients, and 247 lesions were selected for building the models. In the validation sets, PET/CT-based model demonstrated better performance than that of SUV/CT-based model in the prediction of T-cell lymphoma. LR showed highest accuracy with 0.779 [0.697, 0.860], area under the receiver operating characteristic curve (AUC) with 0.863 [0.762, 0.963], and preferable goodness-of-fit in PET/CT-based model at the patient level. LR also showed best performance with accuracy of 0.838 [0.741, 0.936], AUC of 0.907 [0.839, 0.976], and preferable goodness-of-fit in PET/CT-based model at the lesion level. 18 F-FDG PET/CT-based radiomics models with different machine learning classifiers were able to screen T-cell lymphoma in children with high accuracy, AUC, and preferable goodness-of-fit, providing incremental value compared with SUV-associated features., (© 2024. The Author(s).)

Maize (Zea mays) smut is a common biotrophic fungal disease caused by Ustilago maydis and leads to low maize yield. Maize resistance to U. maydis is a quantitative trait. However, the molecular mechanism underlying the resistance of maize to U. maydis is poorly understood. Here, we reported that a maize mutant caused by a single gene mutation exhibited defects in both fungal resistance and plant development. maize mutant highly susceptible to U. maydis (mmsu) with a dwarf phenotype forms tumors in the ear. A map-based cloning and allelism test demonstrated that 1 gene encoding a putative arogenate dehydratase/prephenate dehydratase (ADT/PDT) is responsible for the phenotypes of the mmsu and was designated as ZmADT2. Combined transcriptomic and metabolomic analyses revealed that mmsu had substantial differences in multiple metabolic pathways in response to U. maydis infection compared with the wild type. Disruption of ZmADT2 caused damage to the chloroplast ultrastructure and function, metabolic flux redirection, and reduced the amounts of salicylic acid (SA) and lignin, leading to susceptibility to U. maydis and dwarf phenotype. These results suggested that ZmADT2 is required for maintaining metabolic flux, as well as resistance to U. maydis and plant development in maize. Meanwhile, our findings provided insights into the maize response mechanism to U. maydis infection., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Milk and dairy products represent important sources of nutrition in our daily lives. The identification of species within dairy products holds importance for monitoring food adulteration and ensuring traceability. This study presented a method that integrated double-tube and duplex real-time polymerase chain reaction (PCR) with multiplex TaqMan probes to enable the high-throughput detection of animal-derived ingredients in milk and dairy products. The detection system utilized one pair of universal primers, two pairs of specific primers, and eight animal-derived specific probes for cow, buffalo, goat, sheep, camel, yak, horse, and donkey. These components were optimized within a double-tube and four-probe PCR multiplex system. The developed double-tube detection system could simultaneously identify the above eight targets with a detection limit of 10-0.1 pg/μL. Validation using simulated adulterated milk samples demonstrated a detection limit of 0.1%. The primary advantage of this method lies in the simplification of the multiplex quantitative real-time PCR (qPCR) system through the use of universal primers. This method provides an efficient approach for detecting ingredients in dairy products, providing powerful technical support for market supervision.

Goupi plaster, a representative preparation of black plaster, has demonstrated promising effects in treating knee osteoarthritis. However, high temperature used in traditional frying extraction may cause decomposition of its effective components, thus limiting the efficacy. This study aimed to explore the scientific nature of the traditional preparation technology of Goupi plaster, and to compare the effects of different extraction methods on the types of chemical components and the content of index components. The UPLC-Q-Exactive-MS and UPLC-MS/MS technologies which have high efficiency, sensitivity and accuracy, were used to qualitatively and quantitatively analyze the chemical components of Goupi plaster under different preparation processes. The results show that the extraction solvent approach is different from the traditional frying extraction method, and has a positive effect. However, the mechanism of action of Goupi plaster is complex and its pharmacological effects are diverse. Future studies should explore whether it necessary to change the frying extraction method. This experiment provides a theoretical basis that will guide further scientific discussion and research into the frying extraction of Goupi plaster., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: We aim to assess the association between smoking behavior and intracranial aneurysms (IAs) and the effect of smoking cessation medications on IAs at the genetic level., Methods: Causal effects of four phenotypes: 1) age at initiation of regular smoking, 2) cigarettes smoked per day, 3) smoking cessation, and 4) smoking initiation on IAs, were analyzed using two-sample inverse-variance weighted Mendelian randomization analyses. The effects of genes interacting with the smoking cessation medications were analyzed using cis-expression quantitative trait loci genetic instruments on IAs using summary statistics-based Mendelian randomization analyses. Colocalization analyses were then used to test whether the genes shared causal variants with IAs. The role of confounding phenotypes as potential causative mechanisms of IAs at these gene loci was tested., Results: Cigarettes smoked per day (OR=2.89; 95% CI:1.85-4.51) and smoking initiation on IAs (OR=4.64; 95% CI: 2.64-8.15) were significantly associated with IA risk. However, age at initiation of regular smoking (OR=0.54; 95% CI: 0.10-2.8) and smoking cessation (OR=6.80; 95% CI: 0.01-4812) had no overall effect on IAs. Of 88 genes that interacted with smoking cessation medications, two had a causal effect on IA risk. Genetic variants affecting HYKK levels showed strong evidence of colocalization with IA risk. Higher HYKK levels in the blood were associated with a lower IA risk. Gene target analyses revealed that cigarettes/day could be a main mediator of HYKK's effect on IA risk., Conclusions: This study provides evidence supporting that smoking initiation on IAs and cigarettes/day may increase IA risk. Increased HYKK gene expression may reduce IA risk. This can be explained by the increased number of cigarettes consumed daily. HYKK could also reduce IA risk due to the positive effect of continuous abstinence and varenicline therapy on smoking cessation., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Liang X. et al.)

Immunotherapy has shown great potential in cancer treatment. However, even with the intervention of techniques such as immune checkpoint inhibitor therapy, tumors can still achieve immune escape, leading to a low response rate. Abnormal glycosylation is a widely recognized hallmark of cancer. The development of a complex "glyco-code" on the surface of tumor cells can potentially influence the immune system's ability to monitor tumors and can impact the anti-tumor immune response. Therefore, abnormal glycosylation has emerged as a promising target for immunotherapy. Many recent studies have shown that targeted glycosylation can reshape the tumor microenvironment (TME) and promote the immune response, thereby improving the response to immunotherapy. This review summarizes how glycosylation affects anti-tumor immune function in the TME and synthesizes the latest research progress on targeted glycosylation in immunotherapy. It is hoped that by elucidating the basic laws and biological connotations of glycosylation, this review will enable researcher to thoroughly analyze the mechanism of its influence on the immune metabolic regulation network, which will provide a theoretical tool for promoting the clinical application of glycosylation codes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Anisakiasis is a food-borne parasitic disease mainly caused by the third stage of Anisakis simplex (s. s.) and Anisakis pegreffii. Traditional methods for detecting of Anisakis involve morphology identification such as visual inspection, enzyme digestion, and molecular methods based on PCR, but they have certain limitations. In this study, the internal transcribed spacer 1 (ITS 1) regions of Anisakis were targeted to develop a visual screening method for detecting A. simplex (s. s.) and A. pegreffii in fish meat based on recombinase polymerase amplification (RPA) combined with lateral flow dipstick (LFD). Specific primers and probes were designed and optimized for temperature, reaction time, and detection threshold. LFD produced clear visual results that were easily identifiable after a consistent incubation of 10-20 min at 37 °C. The whole process of DNA amplification by RPA and readout by LFD did not exceed 30 min. In addition, the detection limit is up to 9.5 × 10 -4  ng/μL, and the detection of the artificially contaminated samples showed that the developed assay can effectively and specifically detect A. simplex (s. s.) and A. pegreffii , which fully meet the market's requirements for fish food safety supervision., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Fusarium wilt fungus infection of bitter gourd, a major melon vegetable crop, results in massive yield reduction. Through extensive testing, some Fusarium wilt-resistant bitter melon varieties have been produced, but the molecular mechanism of their resistance to the fungus remains unknown. Importantly, after bitter melon plants are infected with Fusarium oxysporum f. sp. momordicae (FOM), apart from altering their gene expression levels, numerous metabolites are produced because of the interaction with the fungus. In the current study, an untargeted metabolomics analysis was performed to investigate the metabolic difference between resistant and susceptible bitter gourd varieties at various timepoints postinoculation with FOM based on liquid chromatography with mass spectrometry. A total of 1,595 positive ion mode and 922 negative ion mode metabolites were identified. Between the resistant and susceptible bitter gourd varieties, 213 unique differentially abundant metabolites (DAMs) were identified, and they were mainly enriched in the alpha-linolenic acid metabolism pathway. By comparing the postinoculation with preinoculation timepoints in the resistant and susceptible bitter gourd varieties, 93 and 159 DAMs were identified, respectively. These DAMs were mainly related to beta-alanine metabolism, among others. Multiple metabolites in the biosynthesis of the phenylpropanoid pathway showed greater variability in the susceptible than the resistant varieties, which may be related to senescence and mortality in the susceptible variety. These results provide new insights into the understanding of metabolite changes after FOM infection and a theoretical foundation for the elucidation of the bitter gourd disease resistance mechanism., Competing Interests: The author(s) declare no conflict of interest.

Background: Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types of mammalian cancer. Glycoconjugates are highly expressed on sEV and play important roles in sEV biogenesis and their interaction with other cells. However, the study on vesicular glycoconjugates are far behind proteins and nucleic acids. Especially, the functions of sialic acids which are the terminal components of glycoconjugates, are poorly understood in sEV., Methods: Sialic acid levels on sEV from plasma and bladder cancer cells were determined by ELISA and lectin blotting. Effects of sialylation on sEV uptake were determined by flow cytometry. Vesicular glycoproteins bearing sialic acids responsible for sEV uptake was identified by proteomics and density gradient centrifugation, and their site-specific sialylation functions were assayed by N-glycosylation site mutation. Effects of integrin β1 bearing sialic acids on the pro-metastatic function of sEV in vivo were explored using Balb/c nu/nu mice., Results: (1) Increased sialic acid levels were observed in sEV from malignant bladder cancer cells. (2) Elimination of sialic acids on sEV impaired sEV uptake by recipient cells. (3) Vesicular integrin β1 bearing sialic acids was identified to play a key role in sEV uptake. (4) Desialylation of the hybrid domain of vesicular integrin β1 inhibited its binding to matrix fibronectin, and reduced sEV entry into recipient cells. (5) Sialylation on integrin β1 affected pro-metastatic function of sEV in Balb/c nu/nu mice., Conclusions: Taken together, our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker., Methods: An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC., Results: Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis., Conclusions: The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression., (© 2024. The Author(s).)

The aim of this study was to investigate the functional mechanism of Wuniuzao dark tea polysaccharide (WDTP) that protect against hyperlipidemia in mice induced by high-fat diet. WDTP was extracted by hot water, isolated and purified by DEAE-52 chromatography and characterized by high-performance liquid chromatograph (HPLC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). Different doses (200 or 800 mg/kg/day) of WDTP were orally administered to mice induced by high-fat diet to evaluate the mechanism of WDTP regulating lipid metabolism. And these results showed that average molecular weight of WDTP was nearly 63,869 Da. And WDTP intervention significantly reduced body weight, lipid accumulation, and modulated blood lipid levels. The mechanism of WDTP ameliorating lipid metabolism was associated with regulating the expression of lipid metabolism-related genes and serum exosomes miR-19b-3p, and modulating the community structure of gut microbiota in mice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The application of plasma proteomics is a reliable approach for the discovery of biomarkers. However, the utilization of mass spectrometry-based proteomics in plasma encounters limitations due to the presence of high-abundant proteins (HAPs) and the vast dynamic range. To address this issue, we conducted an optimization and integration of depletion and precipitation strategies eliminating interference from HAPs. The optimized procedure involved utilizing 40 µL of beads for the removal of 1 µL of plasma, and maintaining a ratio of 1:1:1 between plasma, urea, and trichloroacetic acid for the precipitation of 50 µL of plasma. To facilitate high-throughput processing, experimental procedures were carried out utilizing 96-well plates. The depletion method identified a total of 1510 proteins, whereas the precipitated method yielded a total of 802 proteins. The integration of these methods yielded a total of 1794 proteins, including a wide concentration range spanning over 8 orders of magnitude. Furthermore, these approaches exhibited a commendable level of reproducibility, as indicated by median coefficients of variation of 14.7 % and 21.1 % for protein intensities, respectively. The integrative method was found to be effective in precisely quantifying yeast proteins that were intentionally spiked in plasma at predetermined rations of 5, 2, 0.5, and 0.2 with a high genuine positive recovery with a range of 71 % to 91 % of all yeast proteins. The use of a complementary and finely tuned approach involving depletion and precipitation demonstrates tremendous potential in the field of discovering protein biomarkers from large-scale cohort studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The functions of macrophages are governed by distinct polarization phenotypes, which can be categorized as either anti-tumor/M1 type or pro-tumor/M2 type. Glycosylation is known to play a crucial role in various cellular processes, but its influence on macrophage polarization is not well-studied. In this study, we observed a significant decrease in bisecting GlcNAc during M0-M1 polarization, and impaired bisecting GlcNAc was found to drive M0-M1 polarization. Using a glycoproteomics strategy, we identified Lgals3bp as a specific glycoprotein carrying bisecting GlcNAc. A high level of bisecting GlcNAc modification facilitated the degradation of Lgals3bp, while a low level of bisecting GlcNAc stabilized Lgals3bp. Elevated levels of Lgals3bp promoted M1 polarization through the activation of the NF-кB pathway. Conversely, the activated NF-кB pathway significantly repressed the transcription of MGAT3, leading to reduced levels of bisecting GlcNAc modification on Lgals3bp. Overall, our study highlights the impact of glycosylation on macrophage polarization and suggests the potential of engineered macrophages via glycosylated modification. Video Abstract., (© 2024. The Author(s).)

This study aimed to enhance the stability and bioavailability of lycopene (LYC) and nicotinamide mononucleotide (NMN) by incorporating them into porous microgels after loading LYC into liposomes. The particle size, zeta potential, encapsulation rate (%), scanning electron microscopy images, and stability and release kinetics characteristics in simulating digestion confirmed that the microgels had high LYC and NMN encapsulation rates (99.11% ± 0.12% and 68.98% ± 0.26%, respectively) and good stability and release characteristics. The protective effect and potential mechanism of microgels loaded with LYC and NMN on lipopolysaccharide (LPS)-induced acute liver injury in C57BL/6 mice were investigated by intragastric administration for 28 days prior to LPS exposure. The results showed that the microgels loaded with LYC and NMN significantly ameliorated LPS-induced liver injury and reduced the inflammatory response and oxidative stress. In addition, LYC and NMN can not only act on the Toll-like receptor 4 (TLR4)/MD2 complex but also regulate TLR4-related miRNAs (miR-145a-5p and miR-217-5p) in serum extracellular vesicles, thereby synergistically inhibiting the TLR4/NF-κB signaling pathway. In addition, the microgels loaded with LYC and NMN were able to enrich beneficial bacteria that produced short-chain fatty acids and reduce harmful bacteria. In conclusion, LYC and NMN protected against LPS-induced acute liver injury via inhibition of oxidative stress and inflammation, as well as regulating the gut microbiota.

Background: We aimed to develop a machine-learning model for predicting treatment response to radioiodine (131I) therapy and thyrotropin (TSH) suppression therapy in patients with differentiated thyroid cancer (DTC) but without structural disease, based on pre-treatment information., Patients and Methods: Overall, 597 and 326 patients with DTC but without structural disease were randomly assigned to "training" cohorts for predicting treatment response to 131I therapy and TSH suppression therapy, respectively. Six supervised algorithms, including Logistic Regression, Support Vector Machine, Random Forest (RF), Neural Networks, Adaptive Boosting, and Gradient Boost, were used to predict effective response (ER) to 131I therapy and biochemical remission (BR) to TSH suppression therapy., Results: Stimulated and suppressed thyroglobulin (Tg) and radioiodine uptake before the current course of 131I therapy were mostly attributed to ER to 131I therapy, while thyroid remnant available on the post-therapeutic whole-body scan at the last course of 131I therapy and TSH were greatly contributed to Tg decline under TSH suppression therapy. RF showed the best performance among all models. The accuracy and area under the receiver operating characteristic curve (AUC) for segregating ER from non-ER during 131I therapy with RF were 81.3% and 0.896, respectively. The accuracy and AUC for predicting BR to TSH suppression therapy with RF were 78.7% and 0.857, respectively., Conclusion: This study demonstrates that machine learning models, especially the RF algorithm are useful tools that may predict treatment response to 131I therapy and TSH suppression therapy in DTC patients without structural disease based on pre-treatment routine clinical variables and biochemical markers., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Cuproptosis plays a crucial role in the biological function of cells. The subject of this work was to analyze the effects of cuproptosis-related genes (CRGs) on the prognosis and biological function in lung adenocarcinoma (LUAD)., Methods: In this study, RNA sequencing and clinical data of LUAD samples were screened from public databases and our institution. A CRG signature was identified by least absolute shrinkage and selection operator and Cox regression. In addition, this study analyzed the correlation between prognostic CRGs and clinicopathological features. Finally, this study studied the effect of inhibiting dihydrolipoamide dehydrogenase ( DLD ) expression on cell biological function., Results: There were 10 CRGs that showed differential expression between LUAD and normal tissues (p<0.05). A prognostic signature ( DLD and lipoyltransferase 1 [ LIPT1 ]) was constructed. Survival analysis suggested that patients with LUAD in the high-risk group had shorter overall survival (OS) (p<0.05). High expression of DLD and low expression of LIPT1 were significantly associated with shorter OS (p<0.05). Immunohistochemical analysis revealed that, in LUAD tissues, DLD was highly expressed, whereas LIPT1 was not detected. Finally, inhibition of DLD expression could significantly restrain cell proliferation, invasion and migration., Conclusion: Overall, this prognostic CRG signature may play a pivotal role in LUAD outcome, while oncogene DLD may be a future therapeutic candidate for LUAD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Using diammonium hydrogen phosphate as an activator and N and P source and and bamboo chips as the carbon source, N, P co-doped activated carbon was prepared by one-step pyrolysis and used to efficiently remove La 3+ in aqueous solutions. The effects of activation temperature and pH value on the adsorption performance of La 3+ were analyzed, and the activation and adsorption mechanisms were explored using TG-IR, SEM-EDX, pore structure, XPS, and hydrophilicity. The results showed that diammonium hydrogen phosphate easily decomposed at a high temperature to produce ammonia and phosphoric acid, which activated the material and promoted the increase in the specific surface area and pore volume of the activated carbon. As an N and P source, the addition of diammonium hydrogen phosphate successfully achieved the N, P co-doping of activated carbon, and the introduction of N- and P-containing functional groups was the key to enhance the adsorption of La 3+ . Among them, graphitic nitrogen could provide interactions between La 3+ -π bonds, and C-P=O and C/P-O-P could provide active sites for the adsorption of La 3+ through complexation and electrostatic interaction. The adsorption of La 3+ on N, P co-doped activated carbons was endothermic and spontaneous, and the adsorption process conformed to the Langmuir isotherm and secondary kinetic model. Under the process conditions of an activation temperature of 900℃ and pH=6, the adsorption capacity of the N, P co-doped activated carbon was as high as 55.18 mg·g -1 , which was 2.53 times higher than that of the undoped sample, and its adsorption selectivity for La 3+ in the La 3+ /Na + and La 3+ /Ca 2+ coexistence systems reached 93.49% and 82.49%, respectively. Additionally, the removal efficiency remained above 54% after five successive adsorption-desorption cycle experiments.

Cold coagulation and blood stasis (CCBS) syndrome is one of the common traditional Chinese medicine (TCM) syndromes of gynecological diseases. However, the molecular mechanism of CCBS syndrome is still unclear. Thus, there is a need to reveal the occurrence and regulation mechanism of CCBS syndrome, in order to provide a theoretical basis for the treatment of CCBS syndrome in gynecological diseases. The plasma proteins in primary dysmenorrhea (PD) patients with CCBS syndrome, endometriosis (EMS) patients with CCBS syndrome, and healthy women were screened using Label-free quantitative proteomics. Based on the TCM theory of "same TCM syndrome in different diseases," the differentially expressed proteins (DEPs) identified in each group were subjected to intersection mapping to obtain common DEPs in CCBS syndrome. The DEPs of gynecological CCBS syndrome in the intersection part were again cross-mapped with the DEPs of gynecological CCBS syndrome obtained by the research group according to the TCM theory of "different TCM syndromes in same disease" theory in the early stage, so as to obtain the DEPs of gynecological CCBS syndrome that were shared by the two parts. The common DEPs were subjected to bioinformatics analysis, and were verified by enzyme-linked immunosorbent assay (ELISA). A total of 67 common DEPs were identified in CCBS syndrome, of which 33 DEPs were upregulated and 34 DEPs were downregulated. The functional classification of DEPs involved in metabolic process, energy production and conversion, immune system process, antioxidant activity, response to stimulus, and biological adhesion. The subcellular location mainly located in the cytoplasm, nucleus, and extracellular. Gene ontology (GO) enrichment analysis showed that the upregulated DEPs mainly concentrated in lipid transport, cell migration, and inflammatory reaction, and the downregulated DEPs mostly related to cell junction, metabolism, and energy response. Protein domain enrichment analysis and clustering analysis revealed that the DEPs mainly related to cell proliferation and differentiation, cell morphology, metabolism, and immunity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis clustering analysis showed that the upregulated DEPs were involved in inflammation and oxidative damage, while the downregulated DEPs were involved in inflammation, cell adhesion, cell apoptosis, and metabolism. The results of ELISA showed significantly increased levels of Cell surface glycoprotein MUC18 (MCAM) and Apolipoprotein C1 (APOC1), and significantly decreased levels of Vasodilator-stimulated phosphoprotein (VASP), Fatty acid-binding protein 5 (FABP5), and Vinculin (VCL) in patients with CCBS syndrome compared with healthy women. We speculated that cold evil may affect the immune process, inflammatory response, metabolic process, energy production and conversion, oxidative damage, endothelial cell dysfunction, and other differential proteins expression to cause CCBS syndrome in gynecological diseases., (© 2022 American Association for Anatomy.)

Methyl-CpG (mCpG) binding domain (MBD) proteins especially bind with methylated DNA, and are involved in many important biological processes; however, the binding mechanism between insect MBD2/3 and mCpG remains unclear. In this study, we identified 2 isoforms of the MBD2/3 gene in Bombyx mori, MBD2/3-S and MBD2/3-L. Binding analysis of MBD2/3-L, MBD2/3-S, and 7 mutant MBD2/3-L proteins deficient in β1-β6 or α1 in the MBD showed that β2-β3-turns in the β-sheet of the MBD are necessary for the formation of the MBD2/3-mCpG complex; furthermore, other secondary structures, namely, β4-β6 and an α-helix, play a role in stabilizing the β-sheet structure to ensure that the MBD is able to bind mCpG. In addition, sequence alignment and binding analyses of different insect MBD2/3s indicated that insect MBD2/3s have an intact and conserved MBD that binds to the mCpG of target genes. Furthermore, MBD2/3 RNA interference results showed that MBD2/3-L plays a role in regulating B. mori embryonic development, similar to that of DNA methylation; however, MBD2/3-S without β4-β6 and α-helix does not alter embryonic development. These results suggest that MBD2/3-L recognizes and binds to mCpG through the intact β-sheet structure in its MBD, thus ensuring silkworm embryonic development., (© 2023 Institute of Zoology, Chinese Academy of Sciences.)

Bone marrow-derived mesenchymal stem cells (BMMSCs) derived from myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients often show a shift in the balance between osteoblastogenesis and adipogenesis. It was suggested that BMMSCs can potentially undergo reprogramming or educational processes. However, the results of reprogrammed differentiation have been inconclusive. In this study, clinical samples, co-culture models and mouse models were employed to explore the association of MDS/AML clonal cells and BMMSCs differentiation. We found that clonal MDS/AML cells promoted adipogenic differentiation and inhibited osteogenic differentiation of BMMSCs, which in turn promoted MDS expansion. Mass spectrometry and cytokine array were used to identify the molecules to drive the BMMSCs differentiation in MDS/AML. Mechanistically, highly expressed transcription factor TWIST1 in clonal MDS/AML cells induces MDS/AML cells to secrete more IFN-γ, which can induce oxidative stress through STAT1-dependent manner, ultimately causing enhanced adipogenic differentiation and inhibited osteogenic differentiation in BMMSCs. Overall, our findings suggest that targeting the driving oncogenes in malignant clonal cells, such as TWIST1, may offer new therapeutic strategies by remodeling the surrounding bone marrow microenvironment in the treatment of MDS/AML and other hematopoietic malignancies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Microvascular decompression (MVD) is already the preferred surgical treatment for medically refractory neurovascular compression syndromes (NVC) such as hemifacial spasm (HFS), trigeminal neuralgia (TN), and glossopharyngeal neuralgia (GPN). Endoscopy has significantly advanced surgery and provides enhanced visualization of MVD. The aim of this study is to analyze the efficacy and safety of fully endoscopic microvascular decompression (E-MVD) for the treatment of HFS, TN, and GPN, as well as to present our initial experience., Materials and Methods: This retrospective case series investigated fully E-MVD performed in 248 patients (123 patients with HFS, 115 patients with TN, and 10 patients with GPN ) from December 2008 to October 2021 at a single institution. The operation duration, clinical outcomes, responsible vessels, intra- and postoperative complications, and recurrences were recorded. Preoperative and immediate postoperative magnetic resonance imaging (MRI) and computerized tomography (CT) were performed for imageological evaluation. The Shorr grading and Barrow Neurological Institute (BNI) pain score were used to evaluate clinical outcomes. The efficacy, safety, and risk factors related to the recurrence of the operation were retrospectively analysed, and the surgical techniques of fully E-MVD were summarised., Results: A total of 248 patients (103 males) met the inclusion criteria and underwent fully E-MVD were retrospectively studied. The effective rate of 123 patients with HFS was 99.1%, of which 113 cases were completely relieved and 9 cases were significantly relieved. The effective rate of 115 patients with TN was 98.9%, of which 105 cases had completely pain relieved after surgery, 5 cases had significant pain relieved, 4 cases had partial pain relieved but still needed to be controlled by medication. The effective rate of 10 patients with GPN was 100%, 10 cases of GPN were completely relieved after surgery. As for complications, temporary facial numbness occurred in 4 cases, temporary hearing loss in 5 cases, dizziness with frequent nausea and vomiting in 8 cases, headache in 12 cases, and no cerebral hemorrhage, intracranial infection, and other complications occurred. Follow-up ranged from 3 to 42 months, with a mean of 18.6 ± 3.3 months. There were 4 cases of recurrence of HFS and 11 cases of recurrence of TN. The other effective patients had no recurrence or worsening of postoperative symptoms. The cerebellopontine angle (CPA) area ratio (healthy/affected side), the length of disease duration, and the type of responsible vessels are the risk factors related to the recurrence of HFS, TN, and GPN treated by fully E-MVD., Conclusions: In this retrospective study, our results suggest that the fully E-MVD for the treatment of NVC such as HFS, TN, and GPN, is a safe and effective surgical method. Fully E-MVD for the treatment of NVC has advantages and techniques not available with microscopic MVD, which may reduce the incidence of surgical complications while improving the curative effect and reducing the recurrence rate., (© 2023. The Author(s).)

Chemoresistance poses a significant impediment to effective treatment strategies for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our previous study unveiled that oncogene TWIST1 interacted with DNA methyltransferase 3a (DNMT3a) to regulate the decitabine (DAC) resistance in MDS/AML. However, the underlying mechanism of TWIST1 dysregulation in DAC resistance remained enigmatic. Here, we found that O-GlcNAc modification was upregulated in CD34 + cells from MDS/AML patients who do not respond to DAC treatment. Functional study revealed that O-GlcNAcylation could stabilize TWIST1 by impeding its interaction with ubiquitin E3 ligase CBLC. In addition, as one typical transcription factor, TWIST1 could bind to the promoter of O-GlcNAc transferase (OGT) gene and activate its transcription. Collectively, we highlighted the crucial role of the O-GlcNAcylated TWIST1 in the chemoresistance capacity of MDS/AML clonal cells, which may pave the way for the development of a new therapeutic strategy targeting O-GlcNAcylated proteins and reducing the ratio of MDS/AML relapse. Video Abstract., (© 2023. BioMed Central Ltd., part of Springer Nature.)

One of the highly attractive research directions in the electrochemiluminescence (ECL) field is how to regulate and improve ECL efficiency. Quantum dots (QDs) are highly promising ECL materials due to their adjustable luminescence size and strong luminous efficiency. MoS 2 NSs@QDs, an ECL emitter, is synthesized via hydrothermal methods, and its ECL mechanism is investigated using cyclic voltammetry and ECL-potential curves. Then, a stable and vertical attachment of a triplex DNA (tsDNA) probe to the MoS 2 nanosheets (NSs) is applied to the electrode. Next, an innovative ECL sensor is courageously empoldered for precise and ultrasensitive detection of target miRNA-199a through the agency of ECL-resonance energy transfer (RET) strategy and a dextrous target-initiated catalytic three-arm DNA junction assembly (CTDJA) based on a toehold strand displacement reaction (TSDR) signal amplification approach. Impressively, the ingenious system not only precisely regulates the distance between energy donor-acceptor pairs leave energy less loss and more ECL-RET efficiency, but also simplifies the operational procedure and verifies the feasibility of this self-assembly process without human intervention. This study can expand MoS 2 NSs@QDs utilization in ECL biosensing applications, and the proposed nucleic acid amplification strategy can become a miracle cure for ultrasensitive detecting diverse biomarkers, which helps researchers to better study the tumor mechanism, thereby unambiguously increasing cancer cure rates and reducing the risk of recurrence.

Dysregulation of clusterin (CLU) has been demonstrated in many cancers and has been proposed as a regulator of carcinogenesis. However, the roles of CLU in gliomas remain unclear. The expression of CLU was assessed using TIMER2.0, GEPIA2, and R package 4.2.1 software, leveraging data from TCGA and/or GTEx databases. Survival analysis and Cox regression were employed to investigate the prognostic significance of CLU. Immune infiltration was evaluated utilizing TIMER2.0, ESTIMATE, and CIBERSORT. The findings reveal the dysregulated expression of CLU in many cancers, with a marked increase observed in glioblastoma and lower-grade glioma (LGG). High CLU expression indicated worse survival outcomes and was an independent risk factor for the prognosis in LGG patients. CLU was involved in immune status as evidenced by its strong correlations with immune and stromal scores and the infiltration levels of multiple immune cells. Additionally, CLU was co-expressed with multiple immune-related genes, and high CLU expression was associated with the activation of immune-related pathways, such as binding to the antigen/immunoglobulin receptor and aiding the cytokine and cytokine receptor interaction. In conclusion, CLU appears to play crucial roles in tumor immunity within gliomas, highlighting its potential as a biomarker or target in glioma immunotherapy.

Natural polysaccharides are macromolecular substances with great potential owing to their wide biological activity and low toxicity. However, not all polysaccharides have significant pharmacodynamic activity; hence, appropriate chemical modification methods can be selected according to the unique structural characteristics of polysaccharides to assist in enhancing and promoting the presentation of their biological activities. This review summarizes research progress on modified polysaccharides, including common chemical modification methods, the change in biological activity following modification, and the factors affecting the biological activity of chemically modified polysaccharides. At the same time, the difficulties and challenges associated with the structural modification of natural polysaccharides are also outlined in this review. Thus, research on polysaccharide structure modification is critical for improving the development and utilization of sugar products.

Chemotherapeutic drugs are used routinely for treatment for myelodysplastic syndrome (MDS) patients but are ineffective in a substantial proportion of patients. Abnormal hematopoietic microenvironments, in addition to spontaneous characteristics of malignant clones, contribute to ineffective hematopoiesis. In our study, we found expression of enzyme β1,4-galactosyltransferase 1 (β4GalT1), which regulates N-acetyllactosamine (LacNAc) modification of proteins, is elevated in bone marrow stromal cells (BMSCs) of MDS patients, and also contributes to drug ineffectiveness through a protective effect on malignant cells. Our investigation of the underlying molecular mechanism revealed that β4GalT1-overexpressing BMSCs promoted MDS clone cells resistant to chemotherapeutic drugs and also showed enhanced secretion of cytokine CXCL1 through degradation of tumor protein p53. Chemotherapeutic drug tolerance of myeloid cells was inhibited by application of exogenous LacNAc disaccharide and blocking of CXCL1. Our findings clarify the functional role of β4GalT1-catalyzed LacNAc modification in BMSCs of MDS. Clinical alteration of this process is a potential new strategy that may substantially enhance effectiveness of therapies for MDS and other malignancies, by targeting a niche interaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

DNA methylation and transcription factors play roles in gene expression and animal development. In insects, DNA methylation modifies gene bodies, but how DNA methylation and transcription factors regulate gene expression is unclear. In this study, we investigated the mechanism that regulates the expression of Bombyx mori Zinc finger protein 615 (ZnF 615), which is a downstream gene of DNA methyltransferase 1 (Dnmt1), and its effects on the regulation of embryonic development. By progressively truncating the ZnF 615 promoter, it was found that the -223 and -190 nt region, which contains homeobox (Hox) protein cis-regulatory elements (CREs), had the greatest impact on the transcription of ZnF 615. RNA interference (RNAi)-mediated knockdown and overexpression of Hox family genes showed that Hox A1-like can enhance the messenger RNA level of ZnF 615. Further studies showed that Hox A1-like regulates ZnF 615 expression by directly binding to the -223 and -190 nt region of its promoter. Simultaneous RNAi-mediated knockdown or overexpression of Hox A1-like and Dnmt1 significantly inhibited or enhanced the regulatory effect of either gene alone on ZnF 615 expression, suggesting that both DNA methylation of gene bodies and binding of transcription factors to promoters are essential for gene expression. RNAi-mediated knockdown of Hox A1-like and Dnmt1 showed that the embryonic development was retarded and the hatching rate was decreased. Taken together, these data suggest that Hox A1-like and DNA methylation enhance the expression of ZnF 615, thereby affecting the development of B. mori embryos., (© 2022 Institute of Zoology, Chinese Academy of Sciences.)

In this work, ultrasonic vibration treatment (UVT) was introduced to improve the interfacial microstructure and bonding strength of A356/AZ91D bimetal processed via lost foam compound casting (LFCC). The interfacial microstructure and mechanical properties of the Al/Mg bimetal processed via LFCC with different UVT durations were investigated. Results revealed the UVT did not change the composition of phases at the interface. The Al/Mg bimetallic interface consisted of an intermetallic compound area (β-Al 3 Mg 2 + γ-Al 12 Mg 17 + Mg 2 Si) and eutectic area (δ-Mg + γ-Al 12 Mg 17 + Mg 2 Si). When the duration of the UVT was increased, the gathered Mg 2 Si particles at the intermetallic compound area were refined to sizes of no more than 5 μm and became more homogeneously dispersed in the intermetallic compound area and diffused in the eutectic area, which could be attributed to the removal of oxide film and the acoustic cavitation and streaming flow effects induced by the UVT. The microhardness of the Al/Mg bimetallic interface was not obviously changed by the increase in UVT duration. The shear strength of the Al/Mg bimetal was increased with UVT and reached maximum with a UVT duration of 5 s, with a value of 56.7 MPa, which was increased by 70.3%, compared with Al/Mg bimetal without UVT. This could be attributed to the removal of the oxide film at the Al/Mg bimetallic interface, which improved the metallurgical bonding of the Al/Mg interface. Additionally, the refined and homogeneously dispersed Mg 2 Si particles played an important role in suppressing the propagation of cracks and enhancing the shear strength of the Al/Mg bimetal.

This study aimed to explore the applicability of DNA barcoding for assessing the authenticity of caviar on the Chinese market. A set of universal COI primers and two sets of designed primers based on COI and D-loop genes were used to identify maternal species of samples from 21 batches of caviar. The results showed that the PCR products from three sets of primers had more than 98% similarity to the sequences in database. The COI gene could not distinguish sturgeons with closed genetic relationships, while D-loop gene could effectively improve the accuracy of DNA barcoding and was more suitable to the identification of interspecific sturgeon than the COI gene. The neighbor-joining dendrogram further confirmed the applicability and accuracy of COI and D-loop genes in identifying maternal relatives of caviar ( Acipenser baerii / Acipenser gueldenstaedtii / Acipenser schrenckii / Huso dauricus / Huso huso) . Despite the limitations of mitochondrial DNA in identifying hybrid sturgeon species, the presence of counterfeit caviar of non-sturgeon ingredients could be excluded. All the caviar samples were identified successfully as sturgeon species, but the mislabeling rate of species was 33.4%, indicating that there were illegal phenomena such as disorderly labeling, mislabeling, and adulteration on the market.

Decitabine (5-aza-2-deoxycytidine, DAC), a DNA-hypomethylating agent, has been one of the frontline therapies for clonal hematopoietic stem cell disorders, such as myelodysplastic syndrome and acute myeloid leukemia, but DAC-resistance often occurs and leads to treatment failure. Therefore, elucidating the mechanisms of DAC resistance is important for improving its therapeutic efficacy. The extracellular vesicles and particles (EVPs) have been reported to be involved in mediating drug resistance by transporting diverse bioactive components. In this study, we established the DAC-resistant cell line (KG1a-DAC) from its parental human leukemia-derived cell line KG1a and observed that EVPs released from KG1a-DAC can promote DAC-resistant in KG1a cells. Moreover, treatment with KG1a-DAC EVPs reduced the expression of cyclin-dependent kinase inhibitor 2B (CDKN2B) in KG1a cells. miRNA-Seq analysis revealed that miR-4755-5p is overexpressed in EVPs from KG1a-DAC. Dual-luciferase reporter assay and flow cytometry analysis confirmed that miR-4755-5p rendered KG1a cells resistant to the DAC by targeting CDKN2B gene. Taken together, miR-4755-5p in EVPs released from the DAC-resistant cells plays an essential role in inducing DAC-resistance, and is a potential therapeutic target for suppression of DAC resistance., (© 2023 Wiley Periodicals LLC.)

Plants often utilize nucleotide-binding leucine-rich repeat (NLR) proteins to perceive pathogen infections and trigger a hypersensitive response (HR). The endosomal sorting complex required for transport (ESCRT) machinery is a conserved multisubunit complex that is essential for the biogenesis of multivesicular bodies and cargo protein sorting. VPS23 is a key component of ESCRT-I and plays important roles in plant development and abiotic stresses. ZmVPS23L, a homolog of VPS23-like in maize (Zea mays), was previously identified as a candidate gene in modulating HR mediated by the autoactive NLR protein Rp1-D21 in different maize populations. Here, we demonstrate that ZmVPS23L suppresses Rp1-D21-mediated HR in maize and Nicotiana benthamiana. Variation in the suppressive effect of HR by different ZmVPS23L alleles was correlated with variation in their expression levels. ZmVPS23 also suppressed Rp1-D21-mediated HR. ZmVPS23L and ZmVPS23 predominantly localized to endosomes, and they physically interacted with the coiled-coil domain of Rp1-D21 and mediated the relocation of Rp1-D21 from the nucleo-cytoplasm to endosomes. In summary, we demonstrate that ZmVPS23L and ZmVPS23 are negative regulators of Rp1-D21-mediated HR, likely by sequestrating Rp1-D21 in endosomes via physical interaction. Our findings reveal the role of ESCRT components in controlling plant NLR-mediated defense responses., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Delayed wound healing is one of the major diabetes complications that occur in 25% of diabetic patients. Specific wound management and combination treatment are required to repair the wound, which still remains a challenge with few effective therapies available currently. In this work, a new H 2 S donor PRO-F , which is characterized by the capability to promote wound healing in diabetes, was designed. PRO-F can be activated by light without consuming endogenous substances and the accompanying fluorescent signal makes the real-time tracking of released H 2 S possible. PRO-F is able to deliver H 2 S in an intracellular environment with moderate release efficiency (50%), which presents cytoprotective effects against excessive reactive oxygen species (ROS) induced damage. Furthermore, the potential of PRO-F to enhance chronic wound healing was validated by employing diabetic models. This work provides new insights into the therapeutic role of H 2 S donors in complex wound conditions, which should advance the pathophysiological research associated with H 2 S.

Magnetic interferential compensation plays a vital role in geomagnetic vector measurement applications. Traditional compensation accounts for only the permanent interferences, induced field interferences, and eddy-current interferences. However, nonlinear magnetic interferences are found, which also have a great impact on measurement, and it cannot be fully characterized by a linear compensation model. This paper proposes a new compensation method based on a back propagation neural network, which can reduce the influence of the linear model on compensation accuracy due to its good nonlinear mapping capabilities. The high-quality network training requires representative datasets, yet it is a common problem in the engineering field. To provide adequate data, this paper adopts a 3D Helmholtz coil to restore the magnetic signal of a geomagnetic vector measurement system. A 3D Helmholtz coil is more flexible and practical than the geomagnetic vector measurement system itself when generating abundant data under different postures and applications. Simulations and experiments are both conducted to prove the superiority of the proposed method. According to the experiment, the proposed method can reduce the root mean square errors of north, east, and vertical components and the total intensity from 73.25, 68.54, 70.45, and 101.77 nT to 23.35, 23.58, 27.42, and 29.72 nT, respectively, compared with the traditional method.

Objectives: To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease., Methods: A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS ( n =20) and non-FRNS (NFRNS; n =15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed., Results: Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD + memory B cells, and IgE + memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group ( P <0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups ( P <0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM + IgD + memory B cells, IgM + memory B cells, IgE + memory B cells, IgD + memory B cells, and IgG + memory B cells ( P <0.05) and a significant increase in the percentage of class-switched memory B cells ( P <0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups ( P <0.05) and a significantly lower level of albumin than the control group ( P <0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE + memory B cells ( P <0.05)., Conclusions: Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE + memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Chronic endometritis (CE) has been considered to reduce uterine receptivity and negatively affect reproductive outcomes for in vitro fertilization-embryo transfer (IVF-ET) patients, especially for people undergoing recurrent implantation failure (RIF). To investigate the effects of antibiotic and platelet-rich plasma (PRP) therapy on pregnancy outcomes following frozen-thawed embryo transfer (FET) in RIF patients with CE, endometrial specimens of 327 patients with RIF obtained by endometrial scratching during mid-luteal phase were immunostained by multiple myeloma oncogene-1 (Mum-1)/syndecan-1 (CD138). RIF patients with CE were given antibiotics and PRP treatment. According to the Mum-1 + /CD138 + plasmacytes after treatment, patients were divided into persistent weak positive CE (+) group, CE (-) group and non-CE group. FET was performed and the basic characteristics and pregnancy outcomes of patients in three groups were compared. Among 327 RIF patients, 117 patients were complicated with CE, the prevalence was 35.78%. The prevalence of strong positive was 27.22% and that of weak positive was 8.56%. 70.94% patients with CE converted to negative after treatment. There was no significant difference in the basic characteristics, including age, BMI, AMH, AFC, infertility years, infertility types, number of previous transplant cycles, endometrial thickness on transplantation day and number of transplanted embryos ( p > 0.05); The positive rate of hCG, clinical pregnancy rate and implantation rate in CE (-) group were significantly increased compared with the weak CE (+) group and non-CE group ( p < .01), and the live birth rate also improved ( p < .05). Whereas, the rate of early abortion in CE (-) group was 12.70%, which was higher than that in weak CE (+) group and non-CE group ( p < .05). After multivariate analysis, number of previous failed cycles and CE remained independent factors associated with live birth rate, while only CE remained to be the independent factor of clinical pregnancy rate. It is recommended to perform CE-related examination for patients with RIF. Antibiotic and PRP treatment can significantly improve pregnancy outcomes of patients with CE negative conversion in FET cycle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Li, Ding, Zhao, Chen, Guan, Deng, Zhou, Han, Xiao and Yang.)

β1,4-galactosyltransferase-1 (β4GalT1) is a type II membrane protein that catalyzes the transfer of galactose (Gal) from UDP-Gal to N-acetylglucosamine (GlcNAc) and forms a LacNAc structure. β4GalT1 has a long form (termed β4GalT1-L) and a short form (termed β4GalT1-S) in mammalian cells. Although β4GalT1 has been proven to play an important role in many biological and pathological processes, such as differentiation, immune responses and cancer development, the different functions of the two β4GalT1 forms remain ambiguous. In this study, we demonstrated that total β4GalT1 was upregulated in bladder cancer. Overexpression of β4GalT1-S, but not β4GalT1-L, increased drug resistance in bladder epithelial cells by upregulating p53 expression. Glycoproteomic analysis revealed that the substrate specificities of the two β4GalT1 forms were different. Among the LacNAcylated proteins, the E3 ligase MDM2 could be preferentially modified by β4GalT1-L compared to β4GalT1-S, and this modification could increase the binding of MDM2 and p53 and further facilitate the degradation of p53. Our data proved that the two forms of β4GalT1 could synergistically regulate p53-mediated cell survival under chemotherapy treatment. These results provide insights into the role of β4GalT1-L and β4GalT1-S and suggest their differentially important implications in the development of bladder cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.

Bone marrow (BM) stroma plays key roles in supporting hematopoietic stem cell (HSC) growth. Glycosylation contributes to the interactions between HSC and surrounding microenvironment. We observed that bisecting N-acetylglucosamine (GlcNAc) structures, in BM stromal cells were significantly lower for MDS/AML patients than for healthy subjects. Malignant clonal cells delivered exosomal miR-188-5p to recipient stromal cells, where it suppressed bisecting GlcNAc by targeting MGAT3 gene. Proteomic analysis revealed reduced GlcNAc structures and enhanced expression of MCAM, a marker of BM niche. We characterized MCAM as a bisecting GlcNAc-bearing target protein, and identified Asn 56 as bisecting GlcNAc modification site on MCAM. MCAM on stromal cell surface with reduced bisecting GlcNAc bound strongly to CD13 on myeloid cells, activated responding ERK signaling, and thereby promoted myeloid cell growth. Our findings, taken together, suggest a novel mechanism whereby MDS/AML clonal cells generate a self-permissive niche by modifying glycosylation level of stromal cells., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)