A non-linear relationship between blood pressure and mild cognitive impairment in elderly individuals: A cohort study based on the Chinese longitudinal healthy longevity survey (CLHLS).

BACKGROUND: Hypertension is an established risk factor for mild cognitive impairment (MCI) in elderly individuals. Nevertheless, the impact of different levels of blood pressure on the progression of MCI remains uncertain. This study aims to investigate the non-linear relationship between blood pressure and MCI in the elderly and detect the critical blood pressure threshold, thus, improving blood pressure management for individuals at high risk of MCI. METHODS: Data was obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) cohort. We chose normal cognitive elderly individuals who entered the cohort in 2014 for a 5-year follow-up to observe the progression of MCI. Subsequently, we utilized the Cox regression model to identify risk factors for MCI and conducted a Cox-based restricted cubic spline regression (RCS) model to examine the non-linear relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) with MCI, determining the critical blood pressure threshold for MCI progression. RESULTS: In the elderly population, female (HR = 1.489, 95% CI: 1.017-2.180), lacking of exercise in the past (HR = 1.714, 95% CI: 1.108-2.653), preferring animal fats (HR = 2.340, 95% CI: 1.348-4.061), increased age (HR = 1.061, 95% CI: 1.038-1.084), increased SBP (HR = 1.036, 95% CI: 1.024-1.048), and increased DBP (HR = 1.056, 95% CI: 1.031-1.081) were associated with MCI progression. After adjusting factors such as gender, exercise, preferred types of fats, and age, both SBP (P non-linear < 0.001) and DBP (P non-linear < 0.001) in elderly individuals exhibited a non-linear association with MCI. The risk of MCI rose when SBP exceeded 135 mmHg and DBP was in the range of 80-88 mmHg. However, when DBP exceeded 88 mmHg, there was a declining trend in MCI progression, although the HR remained above 1. The identified critical blood pressure management threshold for MCI was 135/80 mmHg. CONCLUSION: In this study, we discovered that risk factors affecting the progression of MCI in elderly individuals comprise gender (female), preferring to use animal fat, lack of exercise in the past, increased age, increased SBP, and increased DBP. Additionally, a non-linear relationship between blood pressure levels and MCI progression was confirmed, with the critical blood pressure management threshold for MCI onset falling within the prehypertensive range.

Constitutive Overexpression of an NB-ARC Gene from Wild Chinese Vitis quinquangularis in Arabidopsis thaliana Enhances Resistance to Phytopathogenic Oomycete and Bacteria.

Resistance (R) genes were used to recognize pathogen effectors directly or indirectly in plants and activate defense signal pathways. Most of these R proteins consist of a nucleotide-binding adaptor (NB-ARC) domain, a leucine-rich repeat (LRR) domain and some also have a coiled-coil (CC) structure. In this study, we cloned a gene which encodes the CC-NB-ARC-LRR R protein (VqCNL) from Chinese wild grapevine Vitis. quinquangularis accession 'Dan-2'. The transcript of VqCNL was obviously induced by inoculation with Plasmopara viticola and the salicylic acid (SA) treatment. The results of sequence analysis showed that the VqCNL gene contained a CC domain at the N-terminus, along with an NB-ARC and an LRR domain at the C-terminus. We transferred this gene into wildtype Arabidopsis and treated transgenic lines with Hyaloperonospora arabidopsidis (Hpa) and Pseudomonas syringae pv. tomato DC3000 (Pst DC3000); the results demonstrated that VqCNL promotes broad spectrum resistance to pathogens. Furthermore, qPCR analysis displayed that VqCNL may display a significant function in disease resistance via activating SA signaling pathways. In general, these conclusions primarily demonstrated that VqCNL enhances the disease resistance level in plants and contributes to future research of the R gene identification for grape breeding biotechnology.

Inhibiting von Hippel‒Lindau protein-mediated Dishevelled ubiquitination protects against experimental parkinsonism.

Dopaminergic neuron degeneration is a hallmark of Parkinson's disease (PD). We previously reported that the inactivation of von Hippel‒Lindau (VHL) alleviated dopaminergic neuron degeneration in a C. elegans model. In this study, we investigated the specific effects of VHL loss and the underlying mechanisms in mammalian PD models. For in vivo genetic inhibition of VHL, AAV-Vhl-shRNA was injected into mouse lateral ventricles. Thirty days later, the mice received MPTP for 5 days to induce PD. Behavioral experiments were conducted on D1, D3, D7, D14 and D21 after the last injection, and the mice were sacrificed on D22. We showed that knockdown of VHL in mice significantly alleviated PD-like syndromes detected in behavioral and biochemical assays. Inhibiting VHL exerted similar protective effects in MPP+-treated differentiated SH-SY5Y cells and the MPP+-induced C. elegans PD model. We further demonstrated that VHL loss-induced protection against experimental parkinsonism was independent of hypoxia-inducible factor and identified the Dishevelled-2 (DVL-2)/ß-catenin axis as the target of VHL, which was evolutionarily conserved in both C. elegans and mammals. Inhibiting the function of VHL promoted the stability of ß-catenin by reducing the ubiquitination and degradation of DVL-2. Thus, in vivo overexpression of DVL-2, mimicking VHL inactivation, protected against PD. We designed a competing peptide, Tat-DDF-2, to inhibit the interaction between VHL and DVL-2, which exhibited pharmacological potential for protection against PD in vitro and in vivo. We propose the therapeutic potential of targeting the interaction between VHL and DVL-2, which may represent a strategy to alleviate neurodegeneration associated with PD.

Heterologous VvDREB2c Expression Improves Heat Tolerance in Arabidopsis by Inducing Photoprotective Responses.

Extreme temperatures limit grape production and sustainability. Dehydration-responsive element-binding (DREB) transcription factors affect plant responses to temperature related stresses. Therefore, we investigated the role of VvDREB2c, a DREB-coding gene, found in grapes (Vitis vinifera L.). Protein characterization revealed that VvDREB2c is localized to the nucleus and that its AP2/ERF domain contains three ß-sheets and one α-helix sheet. Analysis of the VvDREB2c promoter region revealed the presence of light-, hormone-, and stress-related cis-acting elements. Furthermore, we observed that the heterologous expression of VvDREB2c in Arabidopsis improved growth, drought tolerance, and heat tolerance. Furthermore, it improved the leaf quantum yield of regulated energy dissipation [Y(NPQ)], elevated the activities of RuBisCO, and phosphoenolpyruvate carboxylase and reduced the quantum yield of non-regulated energy dissipation [Y(NO)] in plants exposed to high temperatures. VvDREB2c-overexpressing lines also specifically upregulated several photosynthesis-related genes (CSD2, HSP21, and MYB102). In addition, VvDREB2c-overexpressing lines reduced light damage and enhanced photoprotective ability by dissipating excess light energy and converting it into heat, which eventually improves tolerance to high temperature. The contents of abscisic acid, jasmonic acid, and salicylic acid and differentially expressed genes (DEGs) in the mitogen-activated protein kinase (MAPK) signaling pathway were affected by heat stress in VvDREB2c-overexpressing lines, which indicated that VvDREB2c positively regulates heat tolerance via a hormonal pathway in Arabidopsis. VvDREB2c promotes heat tolerance in Arabidopsis by exerting effects on photosynthesis, hormones, and growth conditions. This study may provide useful insights into the enrichment of the heat-tolerance pathways in plants.

Optimization of In Vitro Embryo Rescue and Development of a Kompetitive Allele-Specific PCR (KASP) Marker Related to Stenospermocarpic Seedlessness in Grape (Vitis vinifera L.).

Seedlessness is one of the highest valued agronomic traits in grapes. Embryo rescue in combination with marker-assisted selection have been widely applied in seedless grape breeding due to the advantages of increasing the ratio of seedless progenies and shortening the breeding cycle. However, the large number of deformed seedlings produced during embryo rescue and the lack of fast, efficient, and low-cost markers severely inhibit the process of seedless grape breeding. In this study, a total of eighty-three grape cultivars (51 seedless and 32 seeded) with diverse genetic backgrounds and two populations derived from embryo rescue, including 113 F1 hybrid individuals (60 seedless and 53 seeded), were utilized. We screened suitable media for converting malformed seedlings into normal seedlings, analyzed the association between the SNP in VviAGL11 and seeded/seedless phenotype, and developed a KASP marker related to stenospermocarpic seedlessness. Our results indicated that the transformation rate of 37.8% was obtained with MS medium supplemented with 2.0 mg·L-1 of 6-BA and 0.5 mg·L-1 of IBA. The presence of an A nucleotide allele at position chr18:26889437 was further confirmed to be fully associated with the stenospermocarpic seedlessness phenotype. The developed KASP marker, based on the verified SNP locus in VviAGL11, successfully distinguished the seedless and seeded genotypes with high precision and throughput. The results will contribute to enhancing the efficiency of embryo rescue and facilitate parent selection and early selection of seedless offspring with molecular markers, thereby accelerating the breeding process in seedless table grapes.

NUCKS Promotes the Proliferation, Migration and Invasion of Lung Cancer Cells Through Pi3k/Akt Signalling Pathway.

PURPOSE: Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) overexpression has been reported in various types of cancers. The purpose of this study is to clarify the role of NUCKS, underlying the involvement of non-small-cell lung cancer, in the progression of lung cancer. METHODS: The small interfering ribonucleic acid (siRNA) of NUCKS was transfected into a lung cancer cell line (NCI-H460, A549, NCI-H1299 and NCI-H1975). Functional experiments (MTT assay, Annexin V-FITC/PI double staining assay, colony formation assay, wound healing assay and Transwell assay) were performed to measure the effects of NUCKS on lung cancer cell viability, migration, invasion and apoptosis. RESULTS: NUCKS was found to be up-regulated in lung cancer cells. Knockdown of NUCKS significantly altered lung cancer cell apoptosis, proliferation colony formation, invasion and migration. Moreover, knockdown of NUCKS attenuated the activation of the PI3K/AKT pathway in lung cancer cells. CONCLUSION: NUCKS was overexpressed in lung cancer cells and played an important role in lung cancer by increasing cell growth through the PI3K/AKT signalling pathway. This in vitro study suggested NUCKS should be evaluated in a clinical setting as a novel biomarker and potential therapeutic target for lung cancer.

Ectopic expression of a grape nitrate transporter VvNPF6.5 improves nitrate content and nitrogen use efficiency in Arabidopsis.

BACKGROUND: Nitrate plays an important role in grapevines vegetative and reproductive development. However, how grapevines uptake, translocate and utilize nitrate and the molecular mechanism still remains to be investigated. RESULTS: In this study, we report the functional characterization of VvNPF6.5, a member of nitrate transporter 1/peptide transporter family (NRT1/PTR/NPF) in Vitis vinifera. Subcellular localization in Arabidopsis protoplasts indicated that VvNPF6.5 is plasma membrane localized. Quantitative RT-PCR analysis indicated that VvNPF6.5 is expressed predominantly in roots and stems and its expression is rapidly induced by nitrate. Functional characterization using cRNA-injected Xenopus laevis oocytes showed that VvNPF6.5 uptake nitrate in a pH dependent way and function as a dual-affinity nitrate transporter involved in both high- and low-affinity nitrate uptake. Further ectopic expression of VvNPF6.5 in Arabidopsis resulted in more 15NO3- accumulation in shoots and roots and significantly improved nitrogen use efficiency (NUE). Moreover, VvNPF6.5 might participate in the nitrate signaling by positively regulating the expression of primary nitrate response genes. CONCLUSION: Our results suggested that VvNPF6.5 encodes a pH-dependent, dual-affinity nitrate transporter. VvNPF6.5 regulates nitrate uptake and allocation in grapevines and is involved in primary nitrate response.

Transcriptome and coexpression network analysis reveals properties and candidate genes associated with grape (Vitis vinifera L.) heat tolerance.

Temperature is one of the most important environmental factors affecting grape season growth and geographical distribution. With global warming and the increasing occurrence of extreme high-temperature weather, the impact of high temperatures on grape production has intensified. Therefore, identifying the molecular regulatory networks and key genes involved in grape heat tolerance is crucial for improving the resistance of grapes and promoting sustainable development in grape production. In this study, we observed the phenotypes and cellular structures of four grape varieties, namely, Thompson Seedless (TS), Brilliant Seedless (BS), Jumeigui (JMG), and Shine Muscat (SM), in the naturally high-temperature environment of Turpan. Heat tolerance evaluations were conducted. RNA-seq was performed on 36 samples of the four varieties under three temperature conditions (28°C, 35°C, and 42°C). Through differential expression analysis revealed the fewest differentially expressed genes (DEGs) between the heat-tolerant materials BS and JMG, and the DEGs common to 1890 were identified among the four varieties. The number of differentially expressed genes within the materials was similar, with a total of 3767 common DEGs identified among the four varieties. KEGG enrichment analysis revealed that fatty acid metabolism, starch and sucrose metabolism, plant hormone signal transduction, the MAPK signaling pathway, and plant-pathogen interactions were enriched in both between different temperatures of the same material, and between different materials of the same temperature. We also conducted statistical and expression pattern analyses of differentially expressed transcription factors. Based on Weighted correlation network analysis (WGCNA), four specific modules highly correlated with grape heat tolerance were identified by constructing coexpression networks. By calculating the connectivity of genes within the modules and expression analysis, six candidate genes (VIT_04s0044g01430, VIT_17s0000g09190, VIT_01s0011g01350, VIT_01s0011g03330, VIT_04s0008g05610, and VIT_16s0022g00540) related to heat tolerance were discovered. These findings provide a theoretical foundation for further understanding the molecular mechanisms of grape heat tolerance and offer new gene resources for studying heat tolerance in grapes.

Colored Shade Nets Can Relieve Abnormal Fruit Softening and Premature Leaf Senescence of "Jumeigui" Grapes during Ripening under Greenhouse Conditions.

High temperature causes premature grape leaf senescence, abnormal berry softening, and shortening of the fruiting period. Furthermore, the fruit quality and yield are severely affected. Here, the "Jumeigui" grape quality and leaf senescence were evaluated under shading; green, blue, black, and gray nets were used for shading, and their spectra were measured. At the same density, the shade-net color significantly affected cooling and shading efficiencies, with gray nets showing the best light transmission and cooling effect. Shading significantly alleviated abnormal heat-induced grape softness. The total soluble solids (TSS) content and grape coloration were affected under gray, blue, and green shade nets. Nonetheless, TSS exceeded 18 °Brix under gray, blue, and green nets, as required of first-class high-quality fruit. The peel color was not significantly affected under gray or blue shade nets, whereas unshaded grapes showed clear heat-stress damage, especially on the edges of unshaded bottom leaves, in which the net photosynthesis rate was significantly lower than that under shading, indicating that high light intensity and heat caused premature leaf senescence. Colored shade nets reduced greenhouse temperature and light intensity, thereby alleviating the premature senescence of grape plants. Grape quality under black shade nets was poor, whereas superior quality was achieved using gray or blue shade nets.

Interaction of VvbZIP60s and VvHSP83 in response to high-temperature stress in grapes.

The occurrence of frequent, extreme high temperatures affects agriculture and causes irreversible damage during the ripening period of grapes. Breeding high-temperature-tolerant varieties of grapes is the main way to deal with this challenge, thus necessitating research on the regulatory mechanism of high-temperature tolerance. Extreme high temperature causes the mismatch of proteins in the endoplasmic reticulum in plant cells and initiates the unfolded protein response (UPR). The transcription factor bZIP60 participates in the UPR process. In the present study, VvbZIP60 and VvbZIP60s (unconventional splicing of VvbZIP60) were cloned and expressed in a transgenic system to verify heat tolerance. VvbZIP60s was found to be a key gene in adapting to heat stress. VvbZIP60s/60u interacted with VvHSP83 as observed in two yeast hybrids, with bimolecular fluorescence complementation and pull-down assays. VvHSP83 is also a key gene for plants to adapt to heat stress by participating in the renaturation and degradation of denatured proteins under adversity, causing plants to resist high temperatures. This study provides a basis for analyzing the mechanism of high-temperature tolerance in grapes.

Effect of Short-Time High-Temperature Treatment on the Photosynthetic Performance of Different Heat-Tolerant Grapevine Cultivars.

To explore the photosynthetic response of short-term high-temperature treatments to the leaves of different grape varieties (Shenyue and Shenfeng), we performed 45°C treatments on annual potted grapes in an artificial climate chamber to simulate the summer high-temperature period. We measured the rapid A-Ci response curve, 1,5-ribulose bisphosphate carboxylase/oxygenase (Rubisco) activity and chlorophyll a fluorescence. Photosynthetic performance-related parameters of grapevine leaves were found to be adversely affected by high temperature; the maximum rates of carboxylation of Rubisco and ribulose diphosphate regeneration and Rubisco activity were all significantly reduced. The JI of the JIP-test curve disappeared under high-temperature treatment, and the K peak appeared, indicating that the oxygen-evolving complex (OEC) had been destroyed. Principal component analysis showed that PSII activity (Fv /Fm , DFABS , φEo , ABS/RC) was greatly affected by high temperature. It was also found that the Rubisco activity and OEC destruction strength were greater in one of the cultivars, and we were able to determine heat resistance based on the phenotype and photosynthetic performance. It can be seen from the above that Shenyue leaves have higher heat tolerance and stronger photosynthetic performance than Shenfeng leaves. This shows that photosynthetic performance is strongly correlated with a grapevine's tolerance to abiotic stress.

The complete chloroplast genome sequence of Vitis vinifera × Vitis labrusca 'Shenhua'.

Vitis vinifera × Vitis labrusca 'Shenhua' is a tetraploid grape, a Franco-american species. This study first published the complete chloroplast genome of Vitis vinifera × Vitis labrusca 'Shenhua' was assembled. The chloroplast genome is 160928 bp in length, including a large single copy region (89,148 bp), a small single-copy region (19,072 bp) and a pair of inverted repeats of 26,354 bp. The chloroplast genome encodes 133 genes, comprising 88 CDSs, 37 tRNA genes and 8 rRNA genes. The phylogenetic tree demonstrated that Vitis vinifera × Vitis labrusca 'Shenhua' is different from the other 16 varieties.

Influence of cluster thinning and girdling on aroma composition in 'Jumeigui' table grape.

Cluster thinning and girdling are common and simple practices applied to improve berry quality in table grape cultivation. However, there is limited information about the accumulation and biosynthesis of the entire aromatic profile under cluster thinning and girdling, notably in table grapes. This research investigated the influences of cluster thinning and girdling (alone or in combination) on aroma profiles, particularly the changes in biosynthesis and accumulation of Muscat-flavored related compounds from véraison to harvest in 'Jumeigui' grape. Cluster thinning and girdling (alone or in combination) significantly increased the concentrations of total soluble solids (TSS) and key aromatic compounds at harvest, with higher concentrations of both under cluster thinning than girdling. Berry weight and titratable acidity (TA) were unaffected by cluster thinning, girdling, or in combination at harvest. Linalool, the most abundant and active odorant related to Muscat flavor, accumulated in 28.6% and 20.2% higher concentrations from cluster thinning than control and girdling at maturity, respectively. Furthermore, higher DXS3 transcript abundance in cluster thinning groups might contribute to the increased accumulation of terpenes and linalool in 'Jumeigui' grape. The results will contribute to further understand the mechanism of source/sink ratio modulation on aroma accumulation and better apply cluster thinning and girdling for grape production.

Potential therapeutic role of fibroblast growth factor 21 in neurodegeneration: Evidence for ameliorating parkinsonism via silent information regulator 2 homolog 1 and implication for gene therapy.

Parkinson's disease (PD) is one of the common complex neurodegenerative diseases and characterized by abnormal metabolic brain networks. Fibroblast growth factor 21 (FGF21), an endocrine hormone that belongs to the fibroblast growth factor superfamily, plays an extensive role in the regulation of metabolism. However, our understandings of the specific function and mechanisms of FGF21 on PD are still quite limited. Here we aimed to elucidate the actions and the underlying mechanisms of FGF21 on dopaminergic neurodegeneration using cellular and animal models of parkinsonism. To investigate the effects of FGF21 on dopaminergic neurodegeneration in vivo and in vitro, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine models of PD were utilized, and animals were treated with recombinant FGF21 protein or FGF21 gene delivered via an adeno-associated virus. In the present study, systemic and continuous intracerebroventricular recombinant FGF21 protein administration to mice both prevented behavioral deficits, protected dopaminergic neurons against degeneration, and ameliorated α-synuclein pathology in PD models; and in vivo gene delivery of FGF21 improved PD-like symptoms and pathologies suggesting a potential implication of FGF21 in gene therapy for PD. In vitro evidence confirmed FGF21 mediated neuroprotective benefits against PD pathologies. Further, our data suggested that enhanced autophagy was involved in the FGF21 neuroprotection in PD models, and silent information regulator 2 homolog 1 may play a crucial role in molecular mechanisms underlying anti-PD activities of FGF21.

Acid-degradable lactobionic acid-modified soy protein nanogels crosslinked by ortho ester linkage for efficient antitumor in vivo.

It remains a crucial challenge to achieve efficient cellular uptake and intracellular drug release in tumor cells for the nanoscale drug delivery systems. Herein, acid-degradable nanogels were prepared by cross-linking methacrylated soy protein with an acid-labile ortho ester cross-linker (NG1), and then modified with lactobionic acid (LA) to give tumor-targeted nanogels (NG2). Both NG1 and NG2 displayed excellent stability in neutral environment, while showed pH-triggered degradation behaviors under mildly acidic conditions resulting from the breakage of ortho ester bonds. Doxorubicin (DOX) was successfully loaded into nanogels, which exhibited an accelerated release at low pH. In vitro cell studies demonstrated that LA-modified nanogels could effectively improve cellular internalization, show higher cytotoxicity and apoptosis toward asialoglycoprotein receptor (ASGPR) over-expressed HepG2 cells. In vivo antitumor experimentproved that LA modification could significantly enhance the tumor-targeting ability of nanogels and increase DOX concentration in tumor site, leading to better therapeutic efficacy. Histological analysis further demonstrated that soy protein-based nanogels did not cause any damage to normal organs. Overall, these pH-sensitive and tumor-targeting soy protein-based nanogels can be potential drug carriers for efficient tumor treatment.

Systematic Identification and Analysis of Lysine Succinylation in Strawberry Stigmata.

The various post-translational modifications (PTMs) of plant proteins have important regulatory roles in development. We therefore examined various modified proteins from strawberry stigmata and found that succinylation of lysine residues was the most abundant type of modification. We then subjected proteins from strawberry stigmata to an efficient enrichment method for succinylated peptides and identified 200 uniquely succinylated lysines (Suks) in 116 proteins. A bioinformatics analysis revealed that these proteins are involved in important biological processes, including stress responses, vesicular transport, and energy metabolism. Proteomics, combined with immunoprecipitation and immunoblotting, revealed an obvious increase in succinylation of the assembly polypeptide 2 (AP2) and clathrin from 0.5 to 2 h after pollination, suggesting that succinylation is involved in the recognition of pollen-stigma signaling substances and vesicular transport. These results suggest that AP2/clathrin-mediated vesicular transport processes are regulated by lysine succinylation during pollen recognition.

Hyaluronic acid nanogels prepared via ortho ester linkages show pH-triggered behavior, enhanced penetration and antitumor efficacy in 3-D tumor spheroids.

A new type of pH-triggered hyaluronic acid nanogel system (HA-NGs) was successfully developed for tumor-targeted delivery of drugs. HA-NGs were obtained by copolymerization between methacrylate HA and a new cross-linker containing ortho ester groups in an aqueous solution. The therapeutic drug (DOX) was loaded into the HA-NGs (DOX@HA-NGs) and exhibited appropriate loading of about 17.3% with a size of around 200nm. Such new pH-triggered HA-NGs are found to be highly desirable for targeted cancer therapy because it could significantly minimize the amount of premature drug release in neutral pH, and also provide a sufficient amount of drug to effectively kill the cancer cells caused by the degradation of ortho ester groups at acid pH values. Results from the cellular uptake and cytotoxicity of DOX@HA-NGs performed in two-dimensional (2D) cell culture demonstrated that DOX@HA-NGs exhibit excellent tumor homing and higher cytotoxicity. Importantly, the penetration and inhibition against three-dimensional (3D) tumor spheroids demonstrated that DOX@HA-NGs could fully penetrate into HepG2 tumor spheroids, thus leading to higher inhibition. So, such new tumor-targeting DOX@HA-NGs prepared via ortho ester linkages will exhibit excellent stability in a neutral environment, pH-triggered drug release, as well as enhanced penetration and destruction against 3D tumor spheroids, thereby making targeted cancer therapy possible.

Folic acid-conjugated soybean protein-based nanoparticles mediate efficient antitumor ability in vitro.

In this study, soy protein isolate was hydrolyzed by compound enzymes to give aqueous soy protein with low molecular weights. Folic acid modified and free soy protein nanoparticles were successfully prepared by a desolvation method as target-specific drug delivery, respectively. Ultraviolet spectrophotometry demonstrated that folic acid was successfully grafted onto soy protein. The shape and size of folic acid modified soy protein nanoparticles were detected by transmission electron microscopy, scanning electron microscope, and dynamic light scattering. In addition, a series of characteristics including kinetic stability, pH stability, and time stability were also performed. Doxorubicin was successfully loaded into folic acid modified soy protein nanoparticles, and the encapsulation and loading efficiencies were 96.7% and 23%, respectively. Doxorubicin-loaded folic acid modified soy protein nanoparticles exhibited faster drug release rate than soy protein nanoparticles in PBS solution (pH = 5). The tumor penetration and antitumor experiments were done using three-dimensional multicellular tumor spheroids as the in vitro model. The results proved that folic acid modified soy protein nanoparticles display higher penetration and accumulation than soy protein nanoparticles, therefore possessing efficient growth inhibitory ability against multicellular tumor spheroids.

Acid-degradable carboxymethyl chitosan nanogels via an ortho ester linkage mediated improved penetration and growth inhibition of 3-D tumor spheroids in vitro.

This work describes an acid-degradable and tumor-targeted nanogels prepared by the copolymerization between lactobionic acid-modified methacrylated carboxymethyl chitosan and acid-labile methacrylated orthoester-based monomers. The size distribution and micromorphology of the prepared nanogels were observed by dynamic light scattering, transmission electron microscopy and scanning electron microscopy. The stability of nanogels in various environments was then investigated. Doxorubicin as a model drug was successfully encapsulated into nanogels. In vitro cellular uptake and MTT results indicate that the tumor-targeting and pH-sensitive nanogels display higher cellular internalization and cytotoxicity than non-target nanogels and free DOX. The improved penetration and growth inhibition against 3-D multicellular spheroids further demonstrate that the dual-functional nanogels may be a potential nano-carrier for drug delivery in cancer therapy.

High Temperature Affects Photosynthetic and Molecular Processes in Field-Cultivated Vitis vinifera L. × Vitis labrusca L.

High-temperature stress markedly influences grape growth and development. However, how high-temperature stress response differs between controlled and field-cultivated grape is poorly understood. In this study, the effects of heat treatment on grapevines were studied for changes in photosystem II (PSII) activity and expression levels of heat-responsive genes and heat shock protein HSP21. July 31st, 2015 was considered as the post high-temperature treatment ("42°C"; temperatures above 40°C for a period of time each day ranging from 1-7 h) under field cultivation in our experiment. The recovery of chlorophyll fluorescence indicators and the increasing expression of heat-responsive genes and the heat shock protein HSP21 suggested the development of heat tolerance in the form of acclimation in grape. Changes in various parameters of photosynthetic pigment fluorescence and of the electron transport chain (Fv/Fm, PIABS , Wk , RCQA , ΦPo , and ΦEo ) between "42°C" and the 45°C treatment demonstrated that the donor side, reaction center, and acceptor side of PSII were influenced by a critical high temperature. Furthermore, the difference between the two cultivation conditions studied was attributed to other environmental factors and inherent tree vigor.