Neutralizing antibody responses against contemporary and future influenza A(H3N2) viruses in paradoxical clades elicited by repeated and single vaccinations.

As one of the most effective measures to prevent seasonal influenza viruses, annual influenza vaccination is globally recommended. Nevertheless, evidence regarding the impact of repeated vaccination to contemporary and future influenza has been inconclusive. A total of 100 subjects singly or repeatedly immunized with influenza vaccines including 3C.2a1 or 3C.3a1 A(H3N2) during 2018-2019 and 2019-2020 influenza season were recruited. We investigated neutralization antibody by microneutralization assay using four antigenically distinct A(H3N2) viruses circulating from 2018 to 2023, and tracked the dynamics of B cell receptor (BCR) repertoire for consecutive vaccinations. We found that vaccination elicited cross-reactive antibody responses against future emerging strains. Broader neutralizing antibodies to A(H3N2) viruses and more diverse BCR repertoires were observed in the repeated vaccination. Meanwhile, a higher frequency of BCR sequences shared among the repeated-vaccinated individuals with consistently boosting antibody response was found than those with a reduced antibody response. Our findings suggest that repeated seasonal vaccination could broaden the breadth of antibody responses, which may improve vaccine protection against future emerging viruses.

R229I substitution from oseltamivir induction in HA1 region significantly increased the fitness of a H7N9 virus bearing NA 292K.

The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was as high as 13%. These drug-resistant strains showed good replication capacity without serious loss of fitness. At the presence of oseltamivir, R229I substitution were found in HA1 region of the HPAI H7N9 virus before NA R292 K appeared. HPAI H7N9 or H7N9/PR8 recombinant viruses were developed to study whether HA R229I could increase the fitness of the H7N9 virus bearing NA 292 K. Replication efficiency was assessed in MDCK or A549 cells. Neuraminidase enzyme activity and receptor-binding ability were analyzed. The pathogenicity in C57 mice was evaluated. Antigenicity analysis was conducted through a two-way HI test, in which the antiserum was obtained from immunized ferrets. Transcriptomic analysis of MDCK infected with HPAI H7N9 24hpi was done. It turned out that HA R229I substitution from oseltamivir induction in HA1 region increased 1)replication ability in MDCK(P < 0.05) and A549(P < 0.05), 2)neuraminidase enzyme activity, 3)binding ability to both α2,3 and α2,6 receptor, 4)pathogenicity to mice(more weight loss; shorter mean survival day; viral titer in respiratory tract, P < 0.05; Pathological changes in pneumonia), 5) transcriptome response of MDCK, of the H7N9 virus bearing NA 292 K. Besides, HA R229I substitution changed the antigenicity of H7N9/PR8 virus (＞4-fold difference of HI titer). It indicated that through the fine-tuning of the HA-NA balance, R229I increased the fitness and change the antigenicity of a H7N9 virus bearing NA 292 K. Public health attention of this mechanism needs to be drawn.

Carboxymethyl chitosan and dialdehyde cellulose nanocrystal based injectable self-healing emulsion gel.

The study aims to demonstrate a general method for producing emulsion gels with self-healing properties. Specifically, the self-healing emulsion gels were fabricated by crosslinking carboxymethyl chitosan (CMC) stabilized emulsion with dialdehyde cellulose nanocrystal (DACNC). The reversible imine bonds between primary amino groups from CMC and aldehyde groups from DACNC endow the emulsion gel with self-healing properties. The compressive strength of the emulsion gels was greatly increased from 37.43 kPa 83.7 kPa by encapsulating emulsion droplets (φ = 0 %-40 %.) in the gel matrix. Moreover, the emulsion gels exhibited much better self-healing and injectability ability compared to hydrogel because the emulsion droplets interacted with the 3D gel matrix, which were observed by cryo-SEM and CLSM. The emulsion droplets distributed in the gel matrix improved the mobility and interfacial contact area of CMC and DACNC. Water contact measurement confirmed that the CMC/DACNC self-healing emulsion gels showed a hydrophilic surface. The CMC/DACNC emulsion gels could maintain a good structural stability as the oil loss was <1 % after centrifugation. This research provides a method to keep the structural stability of emulsion gels by inducing self-healing ability and modified cellulose nanocrystals, which could extend the shelf life and application area of emulsion gels.

Purple rice starch in wheat: Effect on retrogradation dependent on addition amount.

While individual starch types may not possess the ideal gelatinization and retrogradation properties for specific applications, the amalgamation of multiple starch varieties might bestow desirable physicochemical properties upon resulting starch-based products. This study explored the impact of incorporating purple rice starch (PRS), as a novel starch variant (up to 15 % PRS), on the gelatinization and retrogradation (within 14 days) of regular wheat starch (WS). Rheological and texture assessments demonstrated that the introduction of PRS diminished the viscoelasticity and hardness of fresh WS paste. Additionally, in the case of retrograded WS pastes stored at 4 °C for 1-14 days, the incorporation of 10 % or 15 % PRS effectively retarded the reduction in transparency and significantly reduced hardness, retrogradation degree, the ratio of absorbance at 1047/1017 cm-1, and relative crystallinity. Notably, 10 % PRS results in a more pronounced effect. Conversely, 5 % PRS induced an opposing impact on retrograded WS post-storage. Moreover, scanning electron microscopy revealed that as the proportion of PRS increased, the microstructure of gelatinized WS-PRS closely resembled that of pure PRS. In conclusion, the diverse effects of varying PRS proportions on WS alter the texture and characteristics of starch-based foods, underscoring the potential of starch blending for improved applications.

Global research hotspots, development trends and prospect discoveries of phase separation in cancer: a decade-long informatics investigation.

Liquid-liquid phase separation (LLPS) is a complex and subtle phenomenon whose formation and regulation take essential roles in cancer initiation, growth, progression, invasion, and metastasis. This domain holds a wealth of underutilized unstructured data that needs further excavation for potentially valuable information. Therefore, we retrospectively analyzed the global scientific knowledge in the field over the last decade by using informatics methods (such as hierarchical clustering, regression statistics, hotspot burst, and Walktrap algorithm analysis). Over the past decade, this area enjoyed a favorable development trend (Annual Growth Rate: 34.98%) and global collaboration (International Co-authorship: 27.31%). Through unsupervised hierarchical clustering based on machine learning, the global research hotspots were divided into five dominant research clusters: Cluster 1 (Effects and Mechanisms of Phase Separation in Drug Delivery), Cluster 2 (Phase Separation in Gene Expression Regulation), Cluster 3 (Phase Separation in RNA-Protein Interaction), Cluster 4 (Reference Value of Phase Separation in Neurodegenerative Diseases for Cancer Research), and Cluster 5 (Roles and Mechanisms of Phase Separation). And further time-series analysis revealed that Cluster 5 is the emerging research cluster. In addition, results from the regression curve and hotspot burst analysis point in unison to super-enhancer (a=0.5515, R2=0.6586, p=0.0044) and stress granule (a=0.8000, R2=0.6000, p=0.0085) as the most potential star molecule in this field. More interestingly, the Random-Walk-Strategy-based Walktrap algorithm further revealed that "phase separation, cancer, transcription, super-enhancer, epigenetics"(Relevance Percentage[RP]=100%, Development Percentage[DP]=29.2%), "stress granule, immunotherapy, tumor microenvironment, RNA binding protein"(RP=79.2%, DP=33.3%) and "nanoparticle, apoptosis"(RP=70.8%, DP=25.0%) are closely associated with this field, but are still under-developed and worthy of further exploration. In conclusion, this study profiled the global scientific landscape, discovered a crucial emerging research cluster, identified several pivotal research molecules, and predicted several crucial but still under-developed directions that deserve further research, providing an important reference value for subsequent basic and clinical research of phase separation in cancer.

Comparative investigation of neoadjuvant immunotherapy versus adjuvant immunotherapy in perioperative patients with cancer: a global-scale, cross-sectional, large-sample informatics study.

BACKGROUND: Neoadjuvant and adjuvant immunotherapies for cancer have evolved through a series of remarkable and critical research advances; however, addressing their similarities and differences is imperative in clinical practice. Therefore, this study aimed to examine their similarities and differences from the perspective of informatics analysis. METHODS: This cross-sectional study retrospectively analyzed extensive relevant studies published between 2014 and 2023 using stringent search criteria, excluding non-peer-reviewed and non-English documents. The main outcome variables are publication volume, citation volume, connection strength, occurrence frequency, relevance percentage, and development percentage. Furthermore, an integrated comparative analysis was conducted using unsupervised hierarchical clustering, spatiotemporal analysis, regression statistics, and Walktrap algorithm analysis. RESULTS: This analysis included 1,373 relevant studies. Advancements in neoadjuvant and adjuvant immunotherapies have been promising over the last decade, with an annual growth rate of 25.18% vs. 6.52% and global collaboration (International Co-authorships) of 19.93% vs. 19.84%. Respectively, five dominant research clusters were identified through unsupervised hierarchical clustering based on machine learning, among which Cluster 4 (Balance of neoadjuvant immunotherapy efficacy and safety) and Cluster 2 (Adjuvant immunotherapy clinical trials) (Average Publication Year [APY]: 2021.70±0.70 vs. 2017.54±4.59) are emerging research populations. Burst and regression curve analyses uncovered domain pivotal research signatures, including microsatellite instability (R2=0.7500, P=0.0025) and biomarkers (R2=0.6505, P=0.0086) in neoadjuvant scenarios, and the tumor microenvironment (R2=0.5571, P=0.0209) in adjuvant scenarios. The Walktrap algorithm further revealed that "neoadjuvant immunotherapy, non-small cell lung cancer (NSCLC), immune checkpoint inhibitors, melanoma" and "adjuvant immunotherapy, melanoma, hepatocellular carcinoma, dendritic cells" (Relevance Percentage: 100% vs. 100%, Development Percentage: 37.5% vs. 17.1%) are extremely relevant to this field but remain underdeveloped, highlighting the need for further investigation. CONCLUSION: This study identified pivotal research signatures and provided substantial predictions for neoadjuvant and adjuvant cancer immunotherapies. In addition, comprehensive quantitative comparisons revealed a notable shift in focus within this field, with neoadjuvant immunotherapy taking precedence over adjuvant immunotherapy after 2020; such a qualitative finding facilitate proper decision-making for subsequent research and mitigate the wastage of healthcare resources.

Isolation, structural, biological activity and application of Gleditsia species seeds galactomannans.

Gleditsia fruits have been known as a valuable traditional Chinese herb for tens of centuries. Previous studies showed that the galactomannans are considered as one of the major bioactive components in Gleditsia fruits seeds (GSGs). Here, we systematically review the major studies of GSGs in recent years to promote their better understanding. The extraction methods of GSGs mainly include hot water extraction, microwave-assisted extraction, ultrasonic extraction, acid extraction, and alkali extraction. The analysis revealed that GGSs exhibited in the form of semi-flexible coils, and its molecular weight ranged from 0.018 × 103 to 2.778 × 103 KDa. GSGs are composed of various monosaccharide constituents such as mannose, galactose, glucose, and arabinose. In terms of pharmacological effects, GSGs exhibit excellent activity in antioxidation, hypoglycemic, hypolipidemic, anti-inflammation. Moreover, GSGs have excellent bioavailability, biocompatibility, and biodegradability, which make them used in food additives, food packaging, pharmaceutical field, industry and agriculture. Of cause, the shortcomings of the current research and the potential development and future research are also highlighted. We believe our work provides comprehensive knowledge and underpinnings for further research and development of GSGs.

Effect of soybean polysaccharide and soybean oil on gelatinization and retrogradation properties of corn starch.

This investigation stems from the wide interest in mitigating starch retrogradation, which profoundly impacts the quality of starch-based food, garnering significant attention in the contemporary food industry. Our study delves into the intricate dynamics of soluble soybean polysaccharide (SSPS) and soybean oil (SO) when added individually or in combination to native corn starch (NCS), offering insights into the gelatinization and retrogradation phenomena. We observed that SSPS (0.5 %, w/w) hindered starch swelling, leading to an elevated gelatinization enthalpy change (∆H) value, while SO (0.5 %, w/w) increased ∆H due to its hydrophobicity. Adding SSPS and/or SO concurrently reduced the viscosity and storage modulus (G') of starch matrix. For the starch gel (8 %, w/v) after refrigeration, SSPS magnified water-holding capacity (WHC) and decreased hardness through hydrogen bonding with starch, while SO increased hardness with limited water retention. Crucially, the combination of SSPS and SO maximized WHC, minimized hardness, and significantly inhibited starch retrogradation. The specific ratio of SSPS to SO was found to significantly influence the starch properties, with a 1:1 ratio resulting in the most desirable quality for application in starch-based foods. This study offers insights for utilizing polysaccharides and lipids in starch-based food products to extend shelf life.

Fabrication and characterization of complex coacervates utilizing gelatin and carboxymethyl starch.

BACKGROUND: Modified polysaccharides have greatly expanded applications in comparison with native polysaccharides due to their improved compatibility and interactions with proteins and active compounds in food-related areas. Nonetheless, there is a noticeable dearth of research concerning the utilization of carboxymethyl starch (CMS) as a microcapsule wall material in food processing, despite its common use in pharmaceutical delivery. The development of an economical and safe embedding carrier using CMS and gelatin (GE) holds immense importance within the food-processing industry. In this work, the potential of innovative coacervates formed by the combination of GE and CMS as a reliable, stable, and biodegradable embedding carrier is evaluated by turbidity measurements, thermogravimetric analysis (TGA), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and rheological measurements. RESULTS: The results indicate that GE-CMS coacervates primarily resulted from electrostatic interactions and hydrogen bonding. The optimal coacervation was observed at pH 4.6 and with a GE/CMS blend ratio of 3:1 (w/w). However, the addition of NaCl reduced coacervation and made it less sensitive to temperature changes (35-55 °C). In comparison with individual GE or CMS, the coacervates exhibited higher thermal stability, as shown by TGA. X-ray diffraction analysis shows that the GE-CMS coacervates maintained an amorphous structure. Rheological testing reveals that the GE-CMS coacervates exhibited shear-thinning behavior and gel-like properties. CONCLUSION: Overall, attaining electroneutrality in the mixture boosts the formation of a denser structure and enhances rheological properties, leading to promising applications in food, biomaterials, cosmetics, and pharmaceutical products. © 2023 Society of Chemical Industry.

Comprehensive scientometrics and visualization study profiles lymphoma metabolism and identifies its significant research signatures.

Background: There is a wealth of poorly utilized unstructured data on lymphoma metabolism, and scientometrics and visualization study could serve as a robust tool to address this issue. Hence, it was implemented. Methods: After strict quality control, numerous data regarding the lymphoma metabolism were mined, quantified, cleaned, fused, and visualized from documents (n = 2925) limited from 2013 to 2022 using R packages, VOSviewer, and GraphPad Prism. Results: The linear fitting analysis generated functions predicting the annual publication number (y = 31.685x - 63628, R² = 0.93614, Prediction in 2027: 598) and citation number (y = 1363.7x - 2746019, R² = 0.94956, Prediction in 2027: 18201). In the last decade, the most academically performing author, journal, country, and affiliation were Meignan Michel (n = 35), European Journal of Nuclear Medicine and Molecular Imaging (n = 1653), USA (n = 3114), and University of Pennsylvania (n = 86), respectively. The hierarchical clustering based on unsupervised learning further divided research signatures into five clusters, including the basic study cluster (Cluster 1, Total Link Strength [TLS] = 1670, Total Occurrence [TO] = 832) and clinical study cluster (Cluster 3, TLS = 3496, TO = 1328). The timeline distribution indicated that radiomics and artificial intelligence (Cluster 4, Average Publication Year = 2019.39 ± 0.21) is a relatively new research cluster, and more endeavors deserve. Research signature burst and linear regression analysis further confirmed the findings above and revealed additional important results, such as tumor microenvironment (a = 0.6848, R² = 0.5194, p = 0.019) and immunotherapy (a = 1.036, R² = 0.6687, p = 0.004). More interestingly, by performing a "Walktrap" algorithm, the community map indicated that the "apoptosis, metabolism, chemotherapy" (Centrality = 12, Density = 6), "lymphoma, pet/ct, prognosis" (Centrality = 11, Density = 1), and "genotoxicity, mutagenicity" (Centrality = 9, Density = 4) are crucial but still under-explored, illustrating the potentiality of these research signatures in the field of the lymphoma metabolism. Conclusion: This study comprehensively mines valuable information and offers significant predictions about lymphoma metabolism for its clinical and experimental practice.

A novel heteropolysaccharide isolated from custard apple pulp and its immunomodulatory activity in mouse macrophages and dendritic cells.

In this study, a novel heteropolysaccharide (ASPA80-1) with an average molecular weight of 5.48 × 104 Da was isolated and structurally elucidated from custard apple pulp (Annona squamosa) through DEAE-cellulose, Sephadex G-100 and Sephacryl S-300 HR chromatography and spectral analysis. ASPA80-1 is a water-soluble polysaccharide and it is a polymer consisting of predominant amounts of (1 â†’ 3)-linked-L-arabinose (Ara) residues, small amounts of (1 â†’ 6)-linked-D-galactose (Gal), (1 â†’ 3,5)-linked-L-arabinose (Ara) residues and terminal linked-L-arabinose (Ara) residues, trace amount of (1 â†’ 4)-linked-D-glucose (Glc) residues and (1 â†’ 2)-linked-L-rhamnose (Rham) residues. ASPA80-1 showed significant effect on antigen-presenting cells (APCs) activation. On the one hand, ASPA80-1 activated RAW264.7 macrophage cells by inducing morphology change, enhancing phagocytic ability, increasing nitric oxide (NO) secretion and promoting expression of major histocompatibility complex class II (MHC II) and cluster of differentiation 86 (CD 86). On the other hand, ASPA80-1 promoted the maturation of dendritic cells (DCs) by inducing longer dendrites, decreasing phagocytic ability and increasing MHC II and CD86 expression. Furthermore, mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways were activated after the intervention of ASPA80-1 on RAW264.7 cells or DCs. Thus, the novel heteropolysaccharide ASPA80-1 has the potential to be used as an immunoenhancing component in functional foods.

Comparative effectiveness and acceptability of HIF prolyl-hydroxylase inhibitors versus for anemia patients with chronic kidney disease undergoing dialysis: a systematic review and network meta-analysis.

Background: The comparative benefits and acceptability of HIF-PHIs for treating anemia have not been well researched to date. We sought to compare the effectiveness of 6 HIF-PHIs and 3 ESAs for the treatment of renal anemia patients undergoing dialysis. Data sources: Cochrane Central Register of Controlled Trials, PubMed, Embase, Cochrane Library, MEDLINE, Web of Science, and clinicaltrials.gov databases. Results: Twenty-five RCTs (involving 17,204 participants) were included, all of which were designed to achieve target Hb levels by adjusting thee dose of HIF-PHIs. Regarding the efficacy in achieving target Hb levels, no significant differences were found between HIF-PHIs and ESAs in Hb response at the dose-adjusted designed RCTs selected for comparison. Intervention with roxadustat showed a significantly lower risk of RBC transfusion than rhEPO, with an OR and 95% CI of 0.76 (0.56-0.93). Roxadustat and vadadustat had higher risks of increasing the discontinuation rate than ESAs; the former had ORs and 95% CIs of 1.58 (95% CI: 1.21-2.06) for rhEPO, 1.66 (1.16-2.38) for DPO (darbepoetin alfa), and 1.76 (1.70-4.49) for MPG-EPO, and the latter had ORs and 95% CIs of 1.71 (1.09-2.67) for rhEPO, 1.79 (1.29-2.49) for DPO, and 2.97 (1.62-5.46) for MPG-EPO. No differences were observed in the AEs and SAEs among patients who received the studied drugs. Results of a meta-analysis of gastrointestinal disorders among AEs revealed that vadadustat was less effect on causing diarrea than DPO, with an OR of 0.97 (95% CI, 0.9-0.99). Included HIF-PHIs, were proven to be more effective than ESAs in reducing hepcidin levels and increasing TIBC and serum iron level with OR of -0.17 (95% CI, -0.21 to -0.12), OR of 0.79 (95% CI, 0.63-0.95), and OR of 0.39 (95% CI, 0.33-0.45), respectively. Conclusion: HIF-PHIs and ESAs have their characteristics and advantages in treating anemia undergoing dialysis. With the selected dose-adjusted mode, some HIF-PHIs appeared to be a potential treatment for DD-CKD patients when ompared with rhEPO, due to its effectiveness in decreasing the risk of RBC transfusion rate or regulating iron or lipid metabolism while achieving target Hb levels. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=306511; Identifier: CRD42022306511.

A scientometrics and visualization analysis of oxidative stress modulator Nrf2 in cancer profiles its characteristics and reveals its association with immune response.

Background: Nrf2, an essential and fascinating transcription factor, enjoys a dual property in the occurrence and development of inflammation and cancer. For over two decades, numerous studies regarding Nrf2 in cancer have been reported, whereas there is still a lack of a scientometrics and visualization analysis of Nrf2 in cancer. Hence, a scientometric study regarding the oxidative stress modulator Nrf2 was implemented. Methods: After the quality screening, we defined 7168 relevant studies from 2000 to 2021. CiteSpace, VOSviewer, R software, and GraphPad Prism were used for the following scientometric study and visualization analysis, including field profiles, research hotspots, and future predictions. Results: The total number of publications and citations are 1058 and 54,690, respectively. After polynomial fitting curve analysis, two prediction functions of the annual publication number (y = 3.3909x2 - 13585x + 1 E+07) and citation number (185.45x2 - 743669x + 7 E+08) were generated. After scientometric analysis, we found that Biochemistry Molecular Biology correlates with Nrf2 in cancer highly, and Free Radical Biology and Medicine is a good choice for submitting Nrf2-related manuscripts. The current research hotspots of Nrf2 in cancer mainly focus on cancer therapy and its cellular and molecular mechanisms. "antioxidant response element (87.5)", "gene expression (43.98)", "antioxidant responsive element (21.14)", "chemoprevention (20.05)", "carcinogenesis (19.2)", "cancer chemoprevention (18.45)", "free radical (17.15)", "response element (14.17)", and "chemopreventive agent (14.04)" are important for cancer therapy study. In addition, "glutathione-S-transferase (47)", "keap1 (15.39)", and "heme oxygenase 1 gene (24.35)" are important for inflammation and cell fate study. More interestingly, by performing an "InfoMap" algorithm, the thematic map showed that the "immune response" is essential to oxidative stress modulator Nrf2 but not well developed, indicating it deserves further exploration. Conclusion: This study revealed field profiles, research hotspots, and future directions of oxidative stress modulator Nrf2 in inflammation and cancer research, and our findings will offer a vigorous roadmap for further studies in this field.

Isolation, structures and biological activities of medicinal glycoproteins from natural resources: A review.

In recent years, natural resources have proven to be tremendous sources of glycoproteins. As biological macromolecules, glycoproteins are essential to the growth and development of organisms, and have attracted increasing attention around the world. This review summarized and discussed the development of glycoproteins from natural resources, including isolation methods, purification processes, structural features and biological activities. Generally, the vast majority of glycoproteins can be isolated by hot water extraction followed by purification through gel filtration chromatography. Combined with component analysis, the physicochemical properties of glycoproteins are studied by using several spectroscopic techniques such as ultraviolet-visible (UV-visible), Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR). Moreover, natural glycoproteins possess various remarkable biological activities, including anti-tumor, anti-oxidant, anti-coagulant and anti-microbial activities. The content of this review will provide a theoretical basis for the research on related glycoproteins and give a perspective on the use of these medical resources.

PHB promotes bladder cancer cell epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway.

As a member of PHB (prohibitin1) family, PHB plays important roles in many cancers, but its property in bladder carcinoma aggressiveness is unknown. This research was to explore the function and potential mechanism of PHB in bladder carcinoma in vivo and in vitro. The invasive abilities of cancer cell were determined by transwell and wound-healing assays. The function of PHB was confirmed by gene knockdown and overexpression methods. Further in vivo confirmation was performed in a nude mouse model with lung metastasis. The relationship of PHB and ß-catenin was confirmed by immunoprecipitation and immunofluorescence staining assays. The protein expression of epithelial-mescenchymal transition (EMT) and Wnt/ß-catenin signaling pathway was tested by immunofluorescence staining and western blotting assay. The depletion of PHB prevented bladder cancer cell invasiveness and inhibited EMT. Contrarily，the abilities of bladder carcinoma cells migration and invasion in vitro as well as metastasis in vivo were enhanced when the PHB overexpressed unnormally. Importantly, the ß-catenin was identified to be bound by PHB and ß-catenin knockdown reduced the cancer cell migration, invasion and EMT in PHB overexpressing cells. In addition, PHB stabilized ß-catenin by inhibiting its ubiqutin-mediated degradation thus leading to increased Wnt/ß-catenin signaling. These observations indicate that PHB could promote bladder cancer aggressiveness by binding with ß-catenin to prevent the degradation of ß-catenin and the localized invasive bladder cancer patients with PHB overexpression should take more aggressive postsurgical adjuvant anticancer therapies.

Novel plant-derived exosome-like nanovesicles from Catharanthus roseus: preparation, characterization, and immunostimulatory effect via TNF-α/NF-κB/PU.1 axis.

BACKGROUND: Plant-derived exosomes-like nanovesicles (PDENs) have been found to be advantageous in disease treatment and drug delivery, but research on their biogenesis, compositional analysis, and key marker proteins is still in its infancy, which limits the standardized production of PDENs. Efficient preparation of PDENs continues to be a major challenge. RESULTS: Novel PDENs-based chemotherapeutic immune modulators, Catharanthus roseus (L.) Don leaves-derived exosome-like nanovesicles (CLDENs) were isolated from apoplastic fluid. CLDENs were membrane structured vesicles with a particle size of 75.51 ± 10.19 nm and a surface charge of -21.8 mV. CLDENs exhibited excellent stability, tolerating multiple enzymatic digestions, resisting extreme pH environments, and remaining stable in the gastrointestinal simulating fluid. Biodistribution experiments showed that CLDENs could be internalized by immune cells, and targeted at immune organs after intraperitoneal injection. The lipidomic analysis revealed CLDENs' special lipid composition, which contained 36.5% ether-phospholipids. Differential proteomics supported the origin of CLDENs in multivesicular bodies, and six marker proteins of CLDENs were identified for the first time. 60 ~ 240 µg/ml of CLDENs promoted the polarization and phagocytosis of macrophages as well as lymphocyte proliferation in vitro. Administration of 20 mg/kg and 60 mg/kg of CLDENs alleviated white blood cell reduction and bone marrow cell cycle arrest in immunosuppressive mice induced by cyclophosphamide. CLDENs strongly stimulated the secretion of TNF-α, activated NF-κB signal pathway and increased the expression of the hematopoietic function-related transcription factor PU.1 both in vitro and in vivo. To ensure a steady supply of CLDENs, plant cell culture systems of C. roseus were established to provide CLDENs-like nanovesicles which had similar physical properties and biological activities. Gram-level nanovesicles were successfully obtained from the culture medium, and the yield was three times as high as the original. CONCLUSIONS: Our research supports the use of CLDENs as a nano-biomaterial with excellent stability and biocompatibility, and for post-chemotherapy immune adjuvant therapy applications.

Factors affecting the immunogenicity of influenza vaccines in human.

BACKGROUND: The influenza viruses pose a threat to human health and medical services, and vaccination is an important way to prevent infection. However, the effectiveness of influenza vaccines is affected by various aspects. This study aimed to explore factors related to the immune response to influenza vaccines. METHODS: The study was conducted from September 2019 to September 2021, and a total of 593 volunteers were recruited from the Center for Disease Control and Prevention in 3 provinces in China. The hemagglutination inhibition assay was used to measure antibody levels. The Chi-square test, multivariable logistic regression analysis, and sum-rank test were used to analyze the factors associated with influenza vaccine immune response. RESULTS: The Chi-square test showed that seroconversion rates and response rate were associated with age group, vaccination history, chronic conditions, the frequency of colds, and region (P < 0.05). The multivariable logistic regression analysis showed that age was an important factor that affected participants' seroconversion rates for A/H1N1, A/H3N2, B/Victoria, and response status (18-64 vs. ≤5: OR = 2.77, P < 0.001; ≥65 vs. ≤5: OR = 0.38, P = 0.01; 18-64 vs. ≤5: OR = 2.64, P = 0.03). Vaccination history was also an affecting factor for A/H1N1, B/Victoria, and response status (yes vs. no: OR = 0.4 / 0.44 / 0.25, P < 0.001). The frequency of colds and chronic conditions were also affecting factors for participants' seroconversion rates and response levels to different degrees. The sum-rank test showed that the fold changes for A/H1N1, B/Victoria, and B/Yamagata were associated with age group and vaccination history (P < 0.01). The fold changes for A/H3N2 were associated with the frequency of colds (P < 0.05), and those for B/Victoria were associated with gender and chronic conditions (P < 0.05). CONCLUSIONS: Vaccination history, age, health condition, and frequency of colds were important factors affecting the seroconversion rate of the influenza vaccine in human. There is a need for developing optimized vaccination strategies for vulnerable groups to improve the efficacy of influenza vaccines in human.

The ß-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 axis promotes adult T-cell lymphoblastic lymphoma progression and chemoresistance.

BACKGROUND: High-intensity chemotherapy regimens are often used in adult T-cell lymphoblastic lymphoma (T-LBL) patients. Nevertheless, the response rate remains unsatisfactory due to emergence of chemoresistance. Growing evidence has shown that long non-coding RNAs (lncRNAs) are involved in tumor progression and chemoresistance. Herein, we investigated the potential role of lncRNAs in T-LBLs. METHODS: RNAseq was used to screen and identify candidate lncRNAs associated with T-LBL progression and chemoresistance. Luciferase reporter assay was used to examine the binding of miR-371b-5p to the 3'UTR of Smad2 and LEF1, and the binding of TCF-4/LEF1 to the promoter of LINC00183. Chromatin immunoprecipitation assay was undertaken to analyze the connection between LEF1 and the LINC00183 promoter region. RNA immunoprecipitation assays were used to explore the mechanism whereby LINC00183 regulated miR-371b-5p. MTT and flow cytometry assays were used to measure apoptosis of T-LBL cells. RESULTS: LINC00183 was upregulated in T-LBL progression and chemoresistant tissues in both the Sun Yat-sen University Cancer Center dataset and the First Affiliated Hospital of Anhui Medical University dataset. High expression of LINC00183 was correlated with poorer overall survival and progression-free survival of T-LBL patients compared to those with low expression of LINC00183. Furthermore, miR-371b-5p was negatively regulated by LINC00183. In vivo and in vitro assays showed that LINC00183-mediated T-LBL chemoresistance depended on miR-371b-5p expression. The direct binding of miR-371b-5p to Smad2 and LEF1 was verified by luciferase assays. It was shown that TCF4/LEF1 could bind to the LINC00183 promoter site and increase its transcript level. Downregulation of miR-371b-5p led to increased expression of Smad2/LEF1, and in turn increased LINC00183 expression. Additionally, phospho-Smad2 promotes nuclear translocation of ß-catenin, LINC00183 downregulation decreased chemoresistance induced by ß-catenin and TGF-ß1 in T-LBL cells. CONCLUSION: We unraveled a ß-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 feedback loop that promotes T-LBL progression and chemoresistance, indicating that LINC00183 may serve as a potential therapeutic target in T-LBLs.

Effects of tea saponin on the foaming properties of pea protein.

Plant proteins are becoming increasingly important for foam formation as an alternative to animal proteins. Consumers, however, are unsatisfied with the foaming properties of pea protein isolates. Recent research on proteins and surfactants has primarily concentrated on chemically synthesized surfactants. In this study, foams were prepared by complexing pea protein isolates with a natural small molecule surfactant tea saponin. This study investigates the mechanisms responsible for the formation and stability of foams prepared from pea protein isolates (PPIs) complexed with tea saponins. Analyses of foaming performance were carried out by analyzing the morphology of foam, foaming properties, foam's rheological properties, and the microstructure of the pea protein-tea saponin complex system. Compared to the pea protein isolate alone, the pea protein-tea saponin complex significantly improved foaming capacity and foaming stability. As shown by light microscopy analysis, the size of the foam decreased and became more homogeneous, probably because of the altered aggregate state of the protein. In this study, natural surfactants and mixtures of plant proteins are studied in order to better understand their properties. The mixed system has excellent prospects for application in the industries related to foam.