Development and validation of a risk prediction model for physical frailty in older adults who are disabled.

Physical frailty is highly prevalent among the older adults who are disabled. The aim of this study was to explore the risk factors for physical frailty in older adults who are disabled and construct a nomogram prediction model. The data source was the China Health and Retirement Longitudinal Study (CHARLS). The prediction model was validated with a cohort of 1183 older adults who are disabled. The results showed that sleep quality, depression, fatigue, and chronic disease were the best predictive factors. These factors were used to construct the nomogram model, which showed good concordance and accuracy. The prediction model yielded an Area under the curve (AUC) value of 0.760. Calibration curves showed significant agreement between the nomogram model and actual observations. Receiver operating characteristic (ROC) and Decision curve analysis (DCA) showed that the nomogram had good predictive performance. The nomogram is contributed to the screening of specific populations by clinicians.

Three methods of behavioural testing to measure anxiety - A review.

Behavioural test is very useful to assess the anxiety activity, screen new anxiolytic drugs, explore the pathogenesis of anxiety disorders. Methods of behavioural testing that reflects different aspects of anxiety emotionality simultaneously have always been a critical issue for academics. In this paper, we reviewed previous methods to use behavioural test to evaluate the anxiety activity. A single test was used to measure only one aspect of anxiety emotionality. A battery of behavioural tests could get a comprehensive information of anxiety profile. In one single trial, open field test, elevated plus maze and light/dark box are integrated to assess different types of emotional behaviours. This new paradigm is useful for evaluating multiple dimensions of behaviours simultaneously, minimizing general concerns about previous test experience and inter-test intervals between tests. It is proposed as a promising alternative to using test battery.

Nickel doping of ferrous disulfide nanocubes exhibits enhanced oxidase-like activity for In vitro detection of total antioxidant capacity.

The development of nanomaterials that mimic oxidase-like activities has recently attracted an increasing amount of attention. Obtaining highly active and cost-effective oxidase mimics has posed a significant challenge in this area of research. In this study, we successfully synthesized nickel-doped ferrous disulfide nanocubes (Ni-FeS2) via a facile one-step method. Characterization by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that Ni was predominantly distributed within the surface layer of the Ni-FeS2 nanocubes. The incorporation of nickel in density functional theory (DFT) calculations effectively reduced the d-band center of Fe, resulting in weakened adsorption to intermediates and thereby enhancing its catalytic efficiency. Moreover, we developed a novel approach based on Ni-FeS2 (the Ni-FeS2 method) for detecting reducing substances, which exhibited good sensitivity toward ascorbic acid (AA), glutathione (GSH), and cysteine (Cys). Remarkably, the established Ni-FeS2 method was successfully employed for in vitro assessment of total antioxidant capacity (TAC) in cellular and organ samples, thereby enabling discrimination between normal, senescent, and malignant cells as well as distinguishing among healthy liver tissue, cancerous liver tissue, and metastatic organs.

Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow.

Flow patterns exert significant effects on vascular endothelial cells (ECs) to lead to the focal nature of atherosclerosis. Using a step flow chamber to investigate the effects of disturbed shear (DS) and pulsatile shear (PS) on ECs in the same flow channel, we conducted single-cell RNA sequencing analyses to explore the distinct transcriptomic profiles regulated by DS vs. PS. Integrated analysis identified eight cell clusters and demonstrated that DS induces EC transition from atheroprotective to proatherogenic phenotypes. Using an automated cell type annotation algorithm (SingleR), we showed that DS promoted endothelial-to-mesenchymal transition (EndMT) by inducing the transcriptional phenotypes for inflammation, hypoxia responses, transforming growth factor-beta (TGF-ß) signaling, glycolysis, and fatty acid synthesis. Enolase 1 (ENO1), a key gene in glycolysis, was one of the top-ranked genes in the DS-induced EndMT cluster. Pseudotime trajectory analysis revealed that the kinetic expression of ENO1 was significantly associated with EndMT and that ENO1 silencing repressed the DS- and TGF-ß-induced EC inflammation and EndMT. Consistent with these findings, ENO1 was highly expressed in ECs at the inner curvature of the mouse aortic arch (which is exposed to DS) and atherosclerotic lesions, suggesting its proatherogenic role in vivo. In summary, we present a comprehensive single-cell atlas of ECs in response to different flow patterns within the same flow channel. Among the DS-regulated genes, ENO1 plays an important role in DS-induced EC inflammation and EndMT. These results provide insights into how hemodynamic forces regulate vascular endothelium in health and disease.

SlMYB7, an AtMYB4-Like R2R3-MYB Transcription Factor, Inhibits Anthocyanin Accumulation in Solanum lycopersicum Fruits.

Tomato is a horticultural crop with an incomplete flavonoid metabolic pathway that does not typically accumulate anthocyanins in the fruit. In recent years, intensive studies of the loci Anthocyanin fruit (Aft) and atroviolacium (atv) have clarified the functions of positive regulators (R2R3-MYBs) and a negative regulator (CPC-MYB) in anthocyanin biosynthesis in the fruits. However, little is known about the R2R3-MYB repressors. Here, we used transient overexpression analysis to show that SlMYB7, a subgroup 4 AtMYB4-like R2R3-MYB, inhibited anthocyanin accumulation and reduced expression of anthocyanin synthase genes in the 'black pearl' tomato fruits, which usually accumulate high concentrations of anthocyanins. These findings revealed that SlMYB7 served as a repressor of anthocyanin production. Furthermore, SlMYB7 actively repressed SlANS expression by binding its promoter and passively inhibited anthocyanin synthesis by interacting with the basic helix-loop-helix (bHLH) proteins SlJAF13 and SlAN1, which are involved in the formation of MBW complexes. Thus, SlMYB7 and the MBW complex may coregulate the anthocyanin content of 'black pearl' tomato fruits via a negative feedback loop. These findings provide a theoretical basis for the future enhancement of tomato anthocyanin contents through genetic manipulation of the biosynthetic regulatory network.

The Effect of Moringa Isothiocyanate-1 on Renal Damage in Diabetic Nephropathy.

INTRODUCTION: Diabetic nephropathy (DN) is the most common clinical complication of diabetes mellitus. Moringa isothiocyanate-1 (MIC-1) is effective in the treatment of diabetes mellitus, but its mechanism of action in DN remains obscure. This research specifically probed the role of MIC-1 in modulating renal injury in DN. METHODS: Six db/m mice were assigned to control group and twelve db/db mice were randomly allocated to the db/db and db/db + MIC-1 groups. The body and kidney weights of the mice were monitored. Renal function indicators and oxidative stress-related markers were assessed by automatic biochemical analyzer and ELISA method. The pathological changes, apoptosis of renal tissues, extracellular regulated protein kinases (ERK) 1/2/ Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related markers, and the positive expressions of podocalyxin (Pod) and synaptopodin (Syn) were measured by H&E, PAS, and TUNEL staining, Western blot, and IHC assay. RESULTS: MIC-1 reduced the body and kidney weights, and increased the kidney organ index (calculated as 100*kidney weight/ body weight) in db/db mice. In addition, MIC-1 improved renal function, kidney tissue injury, and apoptosis of db/db mice. MIC1 noticeably repressed the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) and enhanced the contents of (glutathione) GSH, superoxide dismutase (SOD), and catalase (CAT) in db/db mice. At molecular level, db/db mice showed a decrease in p-ERK/ERK, Nrf2, SOD-1, heme oxygenase 1 (HO-1), and CAT and an increase in p- inhibitor kappa B alpha (IKBα) and p-Nuclear factor-kappa B (P65/P65), which were reversed when MIC-1 was administered. Furthermore, MIC-1 facilitated the positive expressions of Pod and Syn of the kidney tissues in db/db mice. CONCLUSION: MIC-1 reduces oxidative stress and renal injury by activating the ERK/Nrf2/HO-1 signaling and repressing the NFκB signaling in db/db mice.  DOI: 10.52547/ijkd.7515.

PLA2G12B Mediates Arachidonic Acid Metabolism through Activation of the NF-κB Pathway to Promote Membrane Nephropathy.

INTRODUCTION: The disruption of podocyte structure and function are the main pathological mechanism of membranous nephropathy (MN). Phospholipases A2, Group XII B (PLA2G12B) was reported involved in the regulation of MN by interfering with arachidonic acid (AA) metabolism, but there is a lack of sufficient evidence. In this study, we investigated the role and molecular mechanism of PLA2G12B in MN. METHODS: C57BL/6 mice were used to establish MN model to extract primary podocytes, then divided into control, model, si-phospholipases A2 receptor (PLA2R), PLA2G12B, PLA2G12B + si-PLA2R, PLA2G12B + nuclear factor kappa-B (NF-κB) inhibitor, PLA2G12B + NF-κB inhibitor + si-PLA2R groups. Hematoxylin-eosin staining and immunofluorescence were used to detect kidney histological arrangement, serum levels of cholesterol-related indices, and AA. Genes and proteins associated with metabolism and inflammatory factors were detected by quantitative real-time PCR and Western blot. RESULTS: The results revealed that AA metabolites were activated in the MN model mice, and the expression of PLA2G12B and NF-κB pathway levels were elevated. Besides, cellular experiments demonstrated that prostaglandin I2 (PGI2), thromboxane A2 (TXA2), leukotriene B4 (LTB4), and NF-κB pathway were significantly increased in the PLA2G12B group. Also, PLA2G12B promotes apoptosis and suppresses cell activity in podocytes, and these effects could be antagonized by NF-κB inhibitors. Furthermore, with the inference of si-PLA2R, the NF-κB inhibitors' effects were reversed. CONCLUSION: Promotional effects of PLA2G12B in primary MN are associated with the regulation of AA metabolism and NF-κB pathway.

Biological functions of endophytic bacteria in Robinia pseudoacacia 'Hongsen'.

Introduction: Endophytes and their host plants have co-evolved for a very long time. This relationship has led to the general recognition of endophytes as a particular class of microbial resources. R. pseudoacacia 'Hongsen' is drought- and barren-resistant species that can be grown in both the north and south of China, efficiently addresses the ecological issues caused by China's 'southern eucalyptus and northern poplar. Up to date, cultured-dependent studies are available for the R. pseudoacacia nitrogen-fixing and other endophytes. Therefore, the present research studied the R. pseudoacacia 'Hongsen,' microbiome in detail by high-throughput sequencing and culture dependant. Methods: This study examined microbial species and functional diversity in Robinia pseudoacacia 'Hongsen' using culture-dependent (isolation) and culture-independent techniques. Results: A total of 210 isolates were isolated from R. pseudoacacia 'Hongsen.' These isolates were clustered into 16 groups by the In Situ PCR (IS-PCR) fingerprinting patterns. 16S rRNA gene sequence analysis of the representative strain of each group revealed that these groups belonged to 16 species of 8 genera, demonstrating the diversity of endophytes in R. pseudoacacia 'Hongsen'. 'Bacillus is the most prevalent genus among all the endophytic bacteria. High-throughput sequencing of endophytic bacteria from R. pseudoacacia 'Hongsen' of the plant and the rhizosphere soil bacteria showed that the bacterial populations of soil near the root, leaf, and rhizosphere differed significantly. The microbial abundance decreased in the endophytes as compared to the rhizosphere. We observed a similar community structure of roots and leaves. With and without root nodules, Mesorhizobium sp. was significantly different in R. pseudoacacia 'Hongsen' plant. Discussion: It was predicted that R. pseudoacacia 'Hongsen' plant endophytic bacteria would play a significant role in the metabolic process, such as carbohydrate metabolism, amino acid metabolism, membrane transport, and energy metabolism.

Cordycepin: A review of strategies to improve the bioavailability and efficacy.

Cordycepin is a bioactive compound extracted from Cordyceps militaris. As a natural antibiotic, cordycepin has a wide variety of pharmacological effects. Unfortunately, this highly effective natural antibiotic is proved to undergo rapid deamination by adenosine deaminase (ADA) in vivo and, as a consequence, its half-life is shortened and bioavailability is decreased. Therefore, it is of critical importance to work out ways to slow down the deamination so as to increase its bioavailability and efficacy. This study reviews recent researches on a series of aspects of cordycepin such as the bioactive molecule's pharmacological action, metabolism and transformation as well as the underlying mechanism, pharmacokinetics and, particularly, the methods for reducing the degradation to improve the bioavailability and efficacy. It is drawn that there are three methods that can be applied to improve the bioavailability and efficacy: to co-administrate an ADA inhibitor and cordycepin, to develop more effective derivatives via structural modification, and to apply new drug delivery systems. The new knowledge can help optimize the application of the highly potent natural antibiotic-cordycepin and develop novel therapeutic strategies.

Identification and Characterization of C-Mos in Pearl Mussel Hyriopsis cumingii and Its Role in Gonadal Development.

C-Mos, a proto-oncogene, regulates oocyte maturation by activating the classical MAPK pathway in cells. To examine the function of C-Mos in Hyriopsis cumingii, C-Mos was identified in this study. The full-length cDNA of C-Mos was 2213 bp, including 144 bp in the 5' UTR, 923 bp in 3' the UTR, and 1146 bp in the open reading frame (ORF) region. During early gonad development, the expression of C-Mos from 4 to 6 months of age in H. cumingii was significantly higher than that in other months, with the highest expression in 6-month-old H. cumingii, suggesting that C-Mos may be involved in early gonadal development in H. cumingii. Clear hybridization signals were found by in situ hybridization in the oocytes, oocyte nucleus and oogonium, and a small number of hybridization signals were found in the follicular wall of the male gonads. In addition, the C-Mos RNA interference (RNAi) assay results showed that the knockdown of C-Mos caused a down-regulation of ERK and P90rsk. In summary, these results indicate that C-Mos has a crucial part to play in gonadal development in H. cumingii.

RETN gene polymorphisms interact with alcohol dependence in association with depression.

BACKGROUND: Previous studies suggest that alcohol dependence is associated with increased risk of depression. The occurrence of depressive symptoms is related to polymorphisms in various genetic regions. This study aimed to investigate the interaction of RETN gene polymorphisms (rs1477341, rs3745368) with alcohol dependence on depressive symptoms in adult male during acute alcohol withdrawal. METHODS: A total of 429 male adults were recruited in this study. Alcohol dependence was assessed using the Michigan alcoholism screening test (MAST). Depression was assessed using the 20-item self-rating depression scale (SDS). Hierarchical regression analysis was used to evaluate the interaction between genes and alcohol dependence on depression. Region of significance (ROS) test was used to explain the interaction effect. The strong and weak forms of the differential susceptibility and diathesis models were used to determine which fits the data better. RESULTS: Our results showed that MAST scores were significantly positively associated with SDS scores (r = 0.23, p < 0.01) in alcohol-dependent patients during alcohol withdrawal. The interaction between genotype and alcohol dependence was significant (ß = -0.14, p < 0.05) in a strong diathesis-stress model. Susceptibility for depression symptoms was associated with alcohol dependence in RETN rs1477341 A carriers. Specifically, those that showed more alcohol dependence and the A allele of RETN rs1477341 exhibited more depression symptoms. However, RETN rs3745368 had no significant interaction with alcohol dependence. CONCLUSIONS: The A allele of RETN rs1477341 may correlate with susceptibility to depression symptoms in alcohol-dependent individuals during acute alcohol withdrawal.

Regulatory T cells mediate insomnia-related psychotic symptoms and cognitive impairment in chronic schizophrenia patients.

Insomnia occurs frequently in schizophrenia patients and is often accompanied with severe psychotic symptoms and cognition impairment. Moreover, chronic insomnia is associated with immune alterations. This study explored the correlations between insomnia and clinical manifestations of schizophrenia and analyzed mediation effects of regulatory T cells (Tregs) on these correlations. In a total of 655 chronic schizophrenia patients, 70 persons (10.69%) had an ISI (Insomnia Severity Index) score >7 and were referred to as Insomnia group. Compared to non-Insomnia group, Insomnia group presented more severe psychotic symptoms (assessed by PANSS) and cognitive impairment (assessed by RBANS). The total effect of ISI on PANSS/RBANS total score was not significant due to the mediation effects by Tregs, in which Tregs strongly mediated the effect of ISI on PANSS total score in negative direction but mediated the effect of ISI on RBANS total score in positive direction. Pearson Correlation Coefficient revealed negative correlations between Tregs and PANSS total score or disorganization subscale of PANSS. Positive correlations existed between Tregs and RBANS total score, between Tregs and the subscales of attention, delayed memory, or language of RBANS. These mediation effects of Tregs on insomnia-related psychotic symptoms and cognitive impairment in chronic schizophrenia patients point to a potential therapeutic strategy of modulating Tregs for the patients.

Discovery of a Series of Potent, Selective, and Orally Bioavailable Nucleoside Inhibitors of CD73 That Demonstrates In Vivo Antitumor Activity.

CD73 (ecto-5'-nucleotidase) has emerged as an attractive target for cancer immunotherapy of many cancers. CD73 catalyzes the hydrolysis of adenosine monophosphate (AMP) into highly immunosuppressive adenosine that plays a critical role in tumor progression. Herein, we report our efforts in developing orally bioavailable and highly potent small-molecule CD73 inhibitors from the reported hit molecule 2 to lead molecule 20 and then finally to compound 49. Compound 49 was able to reverse AMP-mediated suppression of CD8+ T cells and completely inhibited CD73 activity in serum samples from various cancer patients. In preclinical in vivo studies, orally administered 49 showed a robust dose-dependent pharmacokinetic/pharmacodynamic (PK/PD) relationship that correlated with efficacy. Compound 49 also demonstrated the expected immune-mediated antitumor mechanism of action and was efficacious upon oral administration not only as a single agent but also in combination with either chemotherapeutics or checkpoint inhibitor in the mouse tumor model.

Differences in meat quality between Angus cattle and Xinjiang brown cattle in association with gut microbiota and its lipid metabolism.

Gut microbiota plays important roles in mediating fat metabolic events in humans and animals. However, the differences of meat quality traits related to the lipid metabolism (MQT-LM) in association with gut microbiota involving in lipid metabolism have not been well explored between Angus cattle (AG) and Xinjiang brown cattle (BC). Ten heads of 18-month-old uncastrated male AG and BC (5 in each group) raised under the identical conditions were selected to test MQT-LM, i.e., the backfat thickness (BFT), the intramuscular fat (IMF) content, the intramuscular adipocyte areas (IAA), the eye muscle area (EMA), the muscle fiber sectional area (MFSA) and the muscle shear force after sacrifice. The gut microbiota composition and structure with its metabolic function were analyzed by means of metagenomics and metabolomics with rectal feces. The correlation of MQT-LM with the gut microbiota and its metabolites was analyzed. In comparison with AG, BC had significant lower EMA, IMF content and IAA but higher BFT and MFSA. Chao1 and ACE indexes of α-diversity were lower. ß-diversity between AG and BC were significantly different. The relative abundance of Bacteroidetes, Prevotella and Blautia and Prevotella copri, Blautia wexlerae, and Ruminococcus gnavus was lower. The lipid metabolism related metabolites, i.e., succinate, oxoglutaric acid, L-aspartic acid and L-glutamic acid were lower, while GABA, L-asparagine and fumaric acid were higher. IMF was positively correlated with Prevotella copri, Blautia wexlerae and Ruminococcus gnavus, and the metabolites succinate, oxoglutaric acid, L-aspartic acid and L-glutamic acid, while negatively with GABA, L-asparagine and fumaric acid. BFT was negatively correlated with Blautia wexlerae and the metabolites succinate, L-aspartic acid and L-glutamic acid, while positively with GABA, L-asparagine and fumaric acid. Prevotella Copri, Blautia wexlerae, and Ruminococcus gnavus was all positively correlated with succinate, oxoglutaric acid, while negatively with L-asparagine and fumaric acid. In conclusion, Prevotella copri, Prevotella intermedia, Blautia wexlerae, and Ruminococcus gnavus may serve as the potential differentiated bacterial species in association with MQT-LM via their metabolites of oxoglutaric acid, succinate, fumaric acid, L-aspartic acid, L-asparagine, L-glutamic acid and GABA between BC and AG.

Metabolomic and transcriptomic exploration of the uric acid-reducing flavonoids biosynthetic pathways in the fruit of Actinidia arguta Sieb. Zucc.

Flavonoids from Actinidia arguta Sieb. Zucc. can reduce uric acid in mice. However, the molecular basis of its biosynthesis is still unclear. In this paper, we used a combination of extensively targeted metabolomics and transcriptomics analysis to determine the types and differences of flavonoids in the fruit ripening period (August to September) of two main cultivated varieties in northern China. The ethanol extract was prepared, and the potential flavonoids of Chrysin (Flavone1), Rutin (Flavone2), and Daidzein (Flavone3) in Actinidia arguta Sieb. Zucc. were separated and purified by HPD600 macroporous adsorption resin and preparative liquid chromatography. The structure was identified by MS-HPLC, and the serum uric acid index of male Kunming mice was determined by an animal model test.125 flavonoids and 50 differentially regulated genes were identified. The contents of UA (uric acid), BUN (urea nitrogen), Cr (creatinine), and GAPDH in mouse serum and mouse liver glycogen decreased or increased in varying degrees. This paper reveals the biosynthetic pathway of uric acid-reducing flavonoids in the fruit of Actinidia arguta Sieb. Zucc., a major cultivar in northern China, provides valuable information for the development of food and drug homologous functional foods.

Comparative Genomics and Pan-Genome Driven Prediction of a Reduced Genome of Akkermansia muciniphila.

Akkermanisia muciniphila imparts important health benefits and is considered a next-generation probiotic. It is imperative to understand the genomic diversity and metabolic potential of the species for safer applications as probiotics. As it resides with both health-promoting and pathogenic bacteria, understanding the evolutionary patterns are crucial, but this area remains largely unexplored. Moreover, pan-genome has previously been established based on only a limited number of strains and without careful strain selection. The pan-genomics have become very important for understanding species diversity and evolution. In the current study, a systematic approach was used to find a refined pan-genome profile of A. muciniphila by excluding too-diverse strains based on average nucleotide identity-based species demarcation. The strains were divided into four phylogroups using a variety of clustering techniques. Horizontal gene transfer and recombination patterns were also elucidated. Evolutionary patterns revealed that different phylogroups were expanding differently. Furthermore, a comparative evaluation of the metabolic potential of the pan-genome and its subsections was performed. Lastly, the study combines functional annotation, persistent genome, and essential genes to devise an approach to determine a minimal genome that can systematically remove unwanted genes, including virulent factors. The selection of one strain to be used as a chassis for the prediction of a reduced genome was very carefully performed by analyzing several genomic parameters, including the number of unique genes and the resistance and pathogenic potential of the strains. The strategy could be applied to other microbes, including human-associated microbiota, towards a common goal of predicting a minimal or a reduced genome.

The database of eye-movement measures on words in Chinese reading.

Eye movements are one of the most fundamental behaviors during reading. A growing number of Chinese reading studies have used eye-tracking techniques in the last two decades. The accumulated data provide a rich resource that can reflect the complex cognitive mechanisms underlying Chinese reading. This article reports a database of eye-movement measures of words during Chinese sentence reading. The database contains nine eye-movement measures of 8,551 Chinese words obtained from 1,718 participants across 57 Chinese sentence reading experiments. All data were collected in the same experimental environment and from homogenous participants, using the same protocols and parameters. This database enables researchers to test their theoretical or computational hypotheses concerning Chinese reading efficiently using a large number of words. The database can also indicate the processing difficulty of Chinese words during text reading, thus providing a way to control or manipulate the difficulty level of Chinese texts.

Metabolomic and Transcriptomic Analysis of Flavonoid Biosynthesis in Two Main Cultivars of Actinidia arguta Sieb.Zucc. Grown in Northern China.

Actinidia arguta Sieb.Zucc. is a fruit that is rich in flavonoids. Nevertheless, details of flavonoid formation and the potential mechanism behind flavonoid biosynthesis have not previously been reported. In order to explore the biosynthetic regulation mechanism of flavonoids in A. arguta Sieb.Zucc., we conducted a combination of extensive targeted metabolite analysis and analyzed transcriptomes to determine the flavonoids present and the genes bound up with flavonoid biosynthesis in the two main cultivated varieties of A. arguta Sieb.Zucc. in Northern China. The maturity period is from August to September. A total of 118 flavonoids were found in fruits. Among them, 39 flavonoids were accumulated at significant levels after fruit ripening. Transcriptome analysis indicated that most flavonoid biosynthesis structural genes and certain regulatory genes exhibited differential expression between the two varieties. Correlation analysis of transcriptome and metabolite profiles showed that the ways of expression of 21 differentially expressed genes related to structure and regulation between the 2 varieties were more highly correlated with 7 flavonoids after fruit ripening. These results contribute to the development of A. arguta Sieb.Zucc. as a food and drug homologous functional food.

Diselenide-crosslinked carboxymethyl chitosan nanoparticles for doxorubicin delivery: Preparation and in vivo evaluation.

In this paper, we report a simple approach to fabricate diselenide-crosslinked carboxymethyl chitosan nanoparticles (DSe-CMC NPs) for doxorubicin (DOX) delivery, with disulfide analogs (DS-CMC NPs) as control. DS-CMC NPs and DSe-CMC NPs featured a spherical morphology and narrow size distribution with the average size about 200 nm. Carboxymethyl chitosan (CMC) as the starting material not only improved the biocompatibility of the nanocarriers but also enhanced physiological stability. Due to electrostatic interactions between DOX and CMC, the nanoparticles had high drug encapsulation efficiency (∼25 %). The nanoparticles disintegration and drug release were accelerated by the cleavage of diselenide bonds through oxidation by H2O2 or reduction by GSH. In vitro cell experiments revealed that DOX-loaded DSe-CMC NPs possessed the highest drug accumulation and cytotoxicity in tumor cells. Moreover, DOX-loaded DSe-CMC NPs performed the enhanced growth inhibition in vivo than that of DS-CMC NPs. Thus, the diselenide-crosslinked nanoparticles possess great potentials for DOX delivery.