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In this study, a novel dextrin-based micelle (OSAD-SH), dual-modified with octenyl succinic anhydride (OSA) and cysteamine, was developed to address the acid instability issues of micelle modified only by OSA and designed for curcumin delivery. Three amphiphilic OSAD-SH polymers with different free sulfhydryl content were first synthesized. The study demonstrated that OSAD-SH micelles exhibited strong self-assembly properties, appearing as spheres with diameters ranging from 92.41 to 194.20 nm. Blank micelles showed good dilution resistance, as well as stability against acid, thermal, and ionic strength. The curcumin encapsulated by the micelles was in an amorphous state. In vitro release experiment demonstrated that curcumin released from OSAD-SH micelles exhibited pH responsiveness. The Ritger-Peppas model effectively predicted the release behavior of curcumin, which followed a super case-II transport. The OSAD-SH micelle will be a promising nanocarrier for improving the physicochemical properties of curcumin in food fields.
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In this study, biotin esterified debranched starch (Bio-DBS) nanoparticles with different molecular weights were prepared to improve the stability and antioxidant activity of resveratrol. The molecular weights of branched starch (DBS3, DBS9 and DBSp) determined by high-performance size-exclusion chromatography (HPSEC) were 3306, 3696, and 4688, respectively. Biotin was covalently coupled to DBS through the esterification reaction as a new material to prepare nanoparticles. The morphology, particle size, and loading capacity of Bio-DBS nanoparticles were all related to the molecular weights of DBS. The 1H NMR results indicated that there was a hydrogen bonding interaction between Bio-DBS and resveratrol, which contributed to the photochemical and antioxidant activity of resveratrol in the nanoparticles. The highest encapsulation efficiency (78.9 %) and loading capacity (15.78 %) of resveratrol were observed in Bio-DBS3 nanoparticles. Additionally, the cell viability was over 80 % when the concentration of Bio-DBS3 reached to 200 µg/mL. The Bio-DBS nanoparticles significantly improved the thermal stability, photostability, and antioxidant properties of resveratrol. Therefore, the Bio-DBS nanoparticles prepared in this study can be used as a promising carrier to improve the stability and antioxidant activity of resveratrol and may have potential applications in oral delivery.
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Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.
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With the aim of effectively improving the performance of bio-friendly food packaging and circumventing the hazards associated with petroleum-based plastic food packaging, composite films of corn starch and polyvinyl alcohol were prepared using a new method that involved chemical cross-linking of glutaraldehyde and blending with cinnamon essential oil nanoemulsion (CNE). Glutaraldehyde and CNE enhance the film's network structure by chemical bonding and hydrogen bonding, respectively. This results in improved surface smoothness, mechanical properties, and UV shielding ability of the film. However, the films' surface hydrophilicity increased as a result of CNE, which is harmful for food preservation in high humidity. Overall, glutaraldehyde and CNE have a synergistic effect on some of the properties of the film which is mainly attributed to the films' structure improvement. The films have great potential for preparing flexible and UV-shielding films and offer new ideas for developing biodegradable films.
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Reagentes de Ligações Cruzadas , Embalagem de Alimentos , Álcool de Polivinil , Amido , Raios Ultravioleta , Álcool de Polivinil/química , Embalagem de Alimentos/instrumentação , Amido/química , Reagentes de Ligações Cruzadas/química , Zea mays/química , Óleos Voláteis/química , Interações Hidrofóbicas e Hidrofílicas , Cinnamomum zeylanicum/químicaRESUMO
Rice contains abundant starch and contributes to a rapid rise in postprandial blood glucose levels. Hence, it is crucial to directly modify rice grains for resistant starch (RS) content elevation while preserving their morphology. In this study, rice grains were treated with 6%-18% concentrations of oleic acid (OA) and 8-20 h of soaking time to promote the formation of starch-lipid complexes, thereby reducing rice digestibility. In OA-treated rice, the OA molecules exist in three binding states. OA-treated rice exhibited a significantly higher complexation index and OA content than natural rice. RS content increased from 20.50% to 32.46%. X-ray diffraction and NMR spectroscopy revealed the development of amylose-OA complexes within the rice grains and a V-crystalline structure of up to 3.62%. Raman spectroscopy and thermogravimetric analysis showed enhanced molecular ordering and structural stability of rice starch. Overall, OA treatment effectively promotes RS formation within rice grains, consequently reducing rice digestibility.
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Digestão , Ácido Oleico , Oryza , Amido , Oryza/química , Oryza/metabolismo , Amido/química , Amido/metabolismo , Ácido Oleico/química , Ácido Oleico/metabolismo , Amilose/química , Amilose/metabolismo , Lipídeos/química , Difração de Raios X , Sementes/química , Sementes/metabolismoRESUMO
Population ageing is a significant trend in social development and will remain a fundamental national condition in China for the foreseeable future. Socialized older adults care has become a crucial strategy for China to address population ageing. However, the current levels of acceptance and willingness to seek socialized older adults care among older adults are relatively low. This study focuses on examining how the community environment and services influence older adults people's willingness to engage in social activities related to older adults care. Using data from the China Longitudinal Ageing Social Survey (CLASS) (N = 9,657), this study investigated the impact of the community service environment on older adults people's willingness to participate in social activities related to older adults care through a logit model. The study revealed that 9.15% of older adults (N = 9,657) in China are willing to engage in social activities related to older adults care. Furthermore, the individual characteristics and family support of older adults play a significant role in shaping their willingness to engage in older adults care. The provision of medical services, daily care services, and entertainment venues by the community positively influence older adults people's willingness to participate in social activities related to older adults care (p < 0.01), whereas psychological counselling services have a negative impact (p < 0.01). The impact of community services on older adults people's willingness to engage in social activities related to older adults care varies due to factors such as smoking and chronic diseases. These findings provide valuable insights for improving older adults' social engagement in China.
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Apoio Social , Humanos , Idoso , Masculino , Feminino , China , Pessoa de Meia-Idade , Estudos Longitudinais , Idoso de 80 Anos ou mais , Inquéritos e QuestionáriosRESUMO
Due to advances in methods for site-specific incorporation of unnatural amino acids (UAAs) into proteins, a large number of UAAs with tailored chemical and/or physical properties have been developed and used in a wide array of biological applications. In particular, UAAs with specific spectroscopic characteristics can be used as external reporters to produce additional signals, hence increasing the information content obtainable in protein spectroscopic and/or imaging measurements. In this Review, we summarize the progress in the past two decades in the development of such UAAs and their applications in biological spectroscopy and microscopy, with a focus on UAAs that can be used as site-specific vibrational, fluorescence, electron paramagnetic resonance (EPR), or nuclear magnetic resonance (NMR) probes. Wherever applicable, we also discuss future directions.
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Aminoácidos , Aminoácidos/química , Proteínas/química , Proteínas/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Microscopia/métodos , Espectroscopia de Ressonância Magnética/métodos , HumanosRESUMO
This study aimed to evaluate the potential of the bilayer emulsions stabilized with casein/butyrylated dextrin nanoparticles and chitosan as fat substitutes in preparing low-calorie sponge cakes. Among the different cake groups, the substitution of bilayer emulsions at 60% exhibited comparable baking properties, appearance, texture characteristics and stable secondary structure to fat. The specific volume and height were increased by 36.94% and 22%, respectively, while the cake showed higher lightness (L*) in the cores and softer hardness in the crumb. In addition, the moisture content of cakes was increased while the water activity remained unchanged. These results showed that casein/butyrylated dextrin bilayer emulsion was a potential fat substitute for cake products at the ratio of 60% with the desirable characteristics.
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Caseínas , Quitosana , Dextrinas , Emulsões , Substitutos da Gordura , Nanopartículas , Quitosana/química , Nanopartículas/química , Caseínas/química , Dextrinas/química , Emulsões/química , Substitutos da Gordura/química , CulináriaRESUMO
BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) in advanced gastric cancer (GC) is still a controversial issue. AIM: To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC. METHODS: The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020. Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors. A nomogram model was employed to predict the response to NAC. RESULTS: In total 230 patients were finally included in this study, including 154 males (67.0%) and 76 females (33.0%). The mean age was (59.37 ± 10.60) years, ranging from 24 years to 80 years. According to the tumor regression grade standard, there were 95 cases in the obvious response group (grade 0 or grade 1) and 135 cases in the poor response group (grade 2 or grade 3). The obvious response rate was 41.3%. Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location (P < 0.001), histological differentiation (P = 0.001), clinical T stage (P = 0.008), and carbohydrate antigen 724 (P = 0.008). The C-index for the prediction nomogram was 0.806. The calibration curve revealed that the predicted value exhibited good agreement with the actual value. Decision curve analysis showed that the nomogram had a good value in clinical application. CONCLUSION: A nomogram combining tumor location, histological differentiation, clinical T stage, and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.
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Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein-protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase (PhBPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID. In particular, we found that the lysosomal V-ATPase subunit ATP6AP1 could dynamically interact with Rheb. ATP6AP1 could directly bind to Rheb through its last 12 amino acids and utilizes a tri-aspartate motif in its highly conserved C-tail to enhance Rheb GTP loading. In fact, targeting the ATP6AP1 C-tail could block Rheb activation and inhibit cancer cell proliferation and migration. Our findings highlight the versatility of PhastID in mapping transient PPIs in live cells, reveal ATP6AP1's role as an unconventional GEF for Rheb, and underscore the importance of ATP6AP1 in integrating mTORC1 activation signals through Rheb, filling in the missing link in Rheb/mTORC1 activation.
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Proteína Enriquecida em Homólogo de Ras do Encéfalo , Humanos , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Células HEK293 , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Ligação Proteica , Transdução de Sinais , Linhagem Celular TumoralRESUMO
In present study, bilayer emulsions with different interfacial structures stabilized by casein/butyrylated dextrin nanoparticles (CDNP), chitosan (CS) and chitosan nanoparticles (CSNP) were prepared to overcome the limitations of conventional emulsions. The effects of chitosan morphology and incorporation sequences on the bilayer emulsions were examined. Bilayer emulsions prepared with CDNP as the inner layer and CS/CSNP as the outer layer were observed to have smaller droplet sizes (1.39 ± 86.74 um and 1.45 ± 7.87 um). Bilayer emulsions prepared with CDNP as the inner layer and CS as the outer layer exhibited the lowest creaming index (2.38 %) after 14 days of storage, indicating excellent stability. Furthermore, bilayer emulsion prepared with CDNP as the inner layer and CS as the outer layer also exhibited a uniform water distribution, excellent protein oxidative stability, and uniformly distributed droplets by the measurement of Low-field NMR, intrinsic tryptophan fluorescence and laser confocal laser scanning microscopy. These results indicated that the study provided a theoretical basis for the development and design of bilayer emulsions with different interfacial structures. This study also provides a new material for the preparation of delivery systems that protect biologically active compounds. Bilayer emulsions are promising for applications in traditional and manufactured food products.
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Caseínas , Quitosana , Dextrinas , Emulsões , Nanopartículas , Quitosana/química , Caseínas/química , Emulsões/química , Nanopartículas/química , Dextrinas/química , Tamanho da PartículaRESUMO
Appropriate Ca2+ concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca2+ signal, serves significant roles in physiological function of pancreatic ß cells. To maintaining ER homeostasis, Ca2+ movement across the ER membrane is always accompanied by a simultaneous K+ flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca2+ influx. Meanwhile, the specific function of KCNH6 in pancreatic ß-cells remains unclear. In this study, we found that KCNH6 exhibited mainly ER localization and Kcnh6 ß-cell-specific knockout (ßKO) mice suffered from abnormal glucose tolerance and impaired insulin secretion in adulthood. ER Ca2+ store was overloaded in islets of ßKO mice, which contributed to ER stress and ER stress-induced apoptosis in ß cells. Next, we verified that ethanol treatment induced increases in ER Ca2+ store and apoptosis in pancreatic ß cells, whereas adenovirus-mediated KCNH6 overexpression in islets attenuated ethanol-induced ER stress and apoptosis. In addition, tail-vein injections of KCNH6 lentivirus rescued KCNH6 expression in ßKO mice, restored ER Ca2+ overload and attenuated ER stress in ß cells, which further confirms that KCNH6 protects islets from ER stress and apoptosis. These data suggest that KCNH6 on the ER membrane may help to stabilize intracellular ER Ca2+ stores and protect ß cells from ER stress and apoptosis. In conclusion, our study reveals the protective potential of KCNH6-targeting drugs in ER stress-induced diabetes.
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Diabetes Mellitus , Células Secretoras de Insulina , Camundongos , Animais , Secreção de Insulina , Diabetes Mellitus/metabolismo , Células Secretoras de Insulina/metabolismo , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Cálcio/metabolismo , Etanol , Insulina/metabolismoRESUMO
OBJECTIVE: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of KATP depolarization and K+ repolarization. It is well known that glucose stimulates insulin secretion from pancreatic ß-cells, mainly via the KATP depolarization channel, but whether other nutrients directly regulate the repolarization K+ channel to promote insulin secretion is unknown. METHODS: We used a system involving CRISPR-Cas9-mediated knockout of all 83 K+ channels and scRNA-seq in a pancreatic ß cell line to identify genes associated with insulin secretion. RESULTS: The expression levels of insulin genes were significantly increased after all-K+ channel knockout. Furthermore, Kcnb1 and Kcnh6 were the two most important repolarization K+ channels for the increase in high-glucose-dependent insulin secretion that occurred upon application of specific inhibitors of the channels. Kcnh6 currents, but not Kcnb1 currents, were reduced by one of the amino acids, lysine, in both transfected cells, primary cells and mice with ß-cell-specific deletion of Kcnh6. CONCLUSIONS: Our function-related CRISPR screen with scRNA-seq identifies Kcnh6 as a lysine-specific channel.
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Insulina , Lisina , Camundongos , Animais , Secreção de Insulina , Lisina/metabolismo , Insulina/metabolismo , Glucose/farmacologia , Trifosfato de Adenosina/metabolismoRESUMO
Ribonucleic acids (RNA) play active roles within cells or viruses by catalyzing biological reactions, controlling gene expression, and communicating responses to cellular signals. Rapid monitoring RNA variation has become extremely important for appropriate clinical decisions and frontier biological research. However, the most widely used method for RNA detection, nucleic acid amplification, is restricted by a mandatory temperature cycling period of ≈1 h required to reach target detection criteria. Herein, a direct detection approach via single-atom site integrated surface-enhanced Raman scattering (SERS) monitoring nucleic acid pairing reaction, can be completed within 3 min and reaches high sensitivity and extreme reproducibility for COVID-19 and two other influenza viruses' detection. The mechanism is that a single-atom site on SERS chip, enabled by positioning a single-atom oxide coordinated with a specific complementary RNA probe on chip nanostructure hotspots, can effectively bind target RNA analytes to enrich them at designed sites so that the binding reaction can be detected through Raman signal variation. This ultrafast, sensitive, and reproducible single-atom site SERS chip approach paves the route for an alternative technique of immediate RNA detection. Moreover, single-atom site SERS is a novel surface enrichment strategy for SERS active sites for other analytes at ultralow concentrations.
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Nanopartículas Metálicas , Ácidos Nucleicos , Reprodutibilidade dos Testes , Limite de Detecção , Nanopartículas Metálicas/química , RNA , Análise Espectral Raman/métodos , Ouro/químicaRESUMO
HPV vaccine hesitancy in Asia is unique compared to western countries. Concerning whether social media promotion about HPV vaccine will be related with parental support for Chinese adolescent girls, we investigated the correlation among social media promotion, risk perception of HPV vaccine and parental support. Through the theoretical lens of Health Action Process Approach model (HAPA), we found that social media promotion could reduce the risk perception of HPV vaccine and promoted parental supportive decision, and risk perception played a mediation role between social media information exposure to vaccine and parental support. Consideration of future consequences has been found to play a moderating role between social media promotion and risk perception, and parents' sexual attitudes moderated the effect of social media promotion on parental support. Implications of the findings are discussed.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Mídias Sociais , Feminino , Humanos , Adolescente , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus/prevenção & controle , Pais , Aceitação pelo Paciente de Cuidados de Saúde , Vacinação , PercepçãoRESUMO
Triple bonds, such as that formed between two carbon atoms (i.e., C≡C) or that formed between one carbon atom and one nitrogen atom (i.e., C≡N), afford unique chemical bonding and hence vibrational characteristics. As such, they are not only frequently used to construct molecules with tailored chemical and/or physical properties but also employed as vibrational probes to provide site-specific chemical and/or physical information at the molecular level. Herein, we offer our perspective on the emerging applications of various triple-bond vibrations in energy and biological sciences with a focus on C≡C and C≡N triple bonds.
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Disciplinas das Ciências Biológicas , Vibração , Nitrogênio/química , CarbonoRESUMO
Porcine reproductive and respiratory syndrome (PRRS) is a serious infectious disease and one of the major causes of death in the global pig industry. PRRS virus (PRRSV) strains have complex and diverse genetic characteristics and cross-protection between strains is low, which complicates vaccine selection; thus, the current vaccination strategy has been greatly compromised. Therefore, it is necessary to identify effective natural compounds for the clinical treatment of PRRS. A small molecule library composed of 720 natural compounds was screened in vitro, and we found that Sanggenon C (SC) was amongst the most effective natural compound inhibitors of PRRSV infection. Compared with ribavirin, SC more significantly inhibited PRRSV infection at both the gene and protein levels and reduced the viral titres and levels of protein expression and inflammatory cytokine secretion to more effectively protect cells from PRRSV infection and damage. Mechanistically, SC inhibits activation of the NF-κB signalling pathway by promoting TRAF2 expression, thereby reducing PRRSV replication. In conclusion, by screening natural compounds, we found that SC suppresses PRRSV infection by regulating the TRAF2/NF-κB signalling pathway. This study contributes to a deeper understanding of the therapeutic targets and pathogenesis of PRRSV infection. More importantly, our results demonstrate that SC has potential as a candidate for the treatment of PRRS.
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Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Doenças dos Suínos , Suínos , Animais , NF-kappa B/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Fator 2 Associado a Receptor de TNF/metabolismo , Linhagem Celular , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Photocatalytic two-electron oxygen reduction to produce high-value hydrogen peroxide (H2O2) is gaining popularity as a promising avenue of research. However, structural evolution mechanisms of catalytically active sites in the entire photosynthetic H2O2 system remains unclear and seriously hinders the development of highly-active and stable H2O2 photocatalysts. Herein, we report a high-loading Ni single-atom photocatalyst for efficient H2O2 synthesis in pure water, achieving an apparent quantum yield of 10.9% at 420 nm and a solar-to-chemical conversion efficiency of 0.82%. Importantly, using in situ synchrotron X-ray absorption spectroscopy and Raman spectroscopy we directly observe that initial Ni-N3 sites dynamically transform into high-valent O1-Ni-N2 sites after O2 adsorption and further evolve to form a key *OOH intermediate before finally forming HOO-Ni-N2. Theoretical calculations and experiments further reveal that the evolution of the active sites structure reduces the formation energy barrier of *OOH and suppresses the O=O bond dissociation, leading to improved H2O2 production activity and selectivity.
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Neoadjuvant chemotherapy (NAC) is a well-established treatment modality for locally advanced breast cancer (BC). However, it can also result in severe toxicities while controlling tumors. Therefore, reliable predictive biomarkers are urgently needed to objectively and accurately predict NAC response. In this study, we integrated single-cell and bulk RNA-seq data to identify nine genes associated with the prognostic response to NAC: NDRG1, CXCL14, HOXB2, NAT1, EVL, FBP1, MAGED2, AR and CIRBP. Furthermore, we constructed a prognostic risk model specifically linked to NAC. The clinical independence and generalizability of this model were effectively demonstrated. Additionally, we explore the underlying cancer hallmarks and microenvironment features of this NAC response-related risk score, and further assess the potential impact of risk score on drug response. In summary, our study constructed and validated a nine-gene signature associated with NAC prognosis, which was accomplished through the integration of single-cell and bulk RNA data. The results of our study are of crucial significance in the prediction of the efficacy of NAC in BC, and may have implications for the clinical management of this disease.