Imagine before you leap: Episodic future thinking combined with transcranial direct current stimulation training for impulsive choice in repetitive negative thinking.

Background: Immediate reward preference in repetitive negative thinking (RNT) has a high clinical correlation with a variety of maladaptive behaviors, whereas episodic future thinking (EFT) may be conducive to dealing with non-adaptive thinking and decision-making. Objectives: This study aimed to evaluate the efficacy of EFT training combined with transcranial direct current stimulation (tDCS) stimulation over the ventromedial PFC (vmPFC) in inhibiting impulsive choice of RNT individuals. Method: Study 1 explored the effects of EFT on immediate reward preference of participants with high and low RNT (N = 48). Study 2 conducted a randomized controlled trial (RCT) to examine the treatment effect of the EFT-neural training on impulsive choice of high RNT individuals (N = 103). Results: In study 1, individuals with high RNT were more likely to choose smaller and sooner (SS) rewards, however, there were no significant differences between the high-RNT group and the low-RNT group under the positive EFT condition. In study 2, a significant decrease was shown in the proportion of choosing SS rewards under the 8-week EFT-neural training, and the effect was maintained at 1 month follow-up. Conclusion: RNT is a vulnerability factor for short-sighted behaviors, and EFT-neural training could be suitable for reducing RNT and improving immediate reward preference.

Complexes of Soluble Dietary Fiber and Polyphenols from Lotus Root Regulate High-Fat Diet-Induced Hyperlipidemia in Mice.

In this paper, complexes of soluble dietary fiber (SDF) and polyphenols (PPs) isolated from lotus roots were prepared (SDF-PPs), as well as physical mixtures (SDF&PPs), which were given to high-fat-diet (HFD)-fed mice. The results demonstrated that SDF-PPs improve lipid levels and reverse liver injury in hyperlipidemic mice. Western blotting and real-time quantitative Polymerase Chain Reaction (RT-qPCR) results showed that SDF-PPs regulated liver lipids by increasing the phosphorylation of Adenine monophosphate activated protein kinase (AMPK), up-regulating the expression of Carnitine palmitoyltransferase1 (CPT1), and down-regulating the expression of Fatty acid synthase (FAS) and 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA), as well as the transcription factor sterol-regulatory element binding protein (SPEBP-1) and its downstream liposynthesis genes. Additionally, the intervention of SDF-PPs could modulate the composition of intestinal gut microbes, inducing an increase in Lachnospiraceae and a decrease in Desulfovibrionaceae and Prevotellaceae in high-fat-diet-fed mice. Thus, the research provides a theoretical basis for the application of lotus root active ingredients in functional foods and ingredients.

α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata.

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4ß2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-ß-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure.

Effects of Dietary Selenium Yeast Supplementation on Lactation Performance, Antioxidant Status, and Immune Responses in Lactating Donkeys.

Donkey milk is a traditional medicinal food with various biological activities. However, its production is very low, and lactating donkeys often experience oxidative stress, leading to a further decline in milk yield. In this study, we supplemented the diets of lactating donkeys with yeast selenium (SY) to investigate its effects on lactation performance, antioxidant status, and immune responses, and we expected to determine the optimum additive level of SY in the diet. For this study, 28 healthy lactating Dezhou donkeys with days in milk (DIM, 39.93 ± 7.02 d), estimated milk yield (EMY, 3.60 ± 0.84 kg/d), and parity (2.82 ± 0.48) were selected and randomly divided into 4 groups of 7 donkeys in each: Group SY-0 (control), Group SY-0.15, Group SY-0.3, and Group SY-0.5, with selenium supplementation of 0, 0.15, 0.3, and 0.5 mg of Se/kg DM (in form of SY) to the basal diet, respectively. The results showed a dose-dependent increase in milk yield, milk component yield, milk protein production efficiency, milk production efficiency, the activities of glutathione peroxidases (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC), as well as the content of serum interleukin-10 (IL-10), white blood cells (WBC), lymphocytes (LYM), red blood cells (RBC), hematocrit, plasma selenium, and milk selenium. Conversely, it presented a dose-dependent decrease in the activity of nitric oxide synthase (iNOS) and the contents of malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interferon-γ (IFN-γ). In conclusion, the results confirmed that dietary supplementation with SY can improve lactation performance, antioxidant status, and immune responses in lactating donkeys, and the recommended dose of SY was 0.3 mg/kg.

Association of dietary protein intake, inflammation with muscle mass, physical performance and incident sarcopenia in Chinese community-dwelling older adults.

OBJECTIVES: Inflammation and impaired muscle synthesis are important factors of sarcopenia. Plant protein may reduce inflammation but may not be as efficient as animal protein in providing essential amino acids. We therefore examined the associations between dietary protein intake and changes in muscle mass and physical performance, incident sarcopenia, and the interaction effect of inflammation. DESIGN: Prospective cohort study. SETTING: The Mr. OS and Ms. OS (Hong Kong) cohort. PARTICIPANTS: A total of 2,811 sarcopenia-free participants and 569 sarcopenia participants aged ≥65 years were recruited from communities. MEASUREMENTS: Dietary protein intake was assessed using a validated food frequency questionnaire. Serum high-sensitivity C-reactive protein (hs-CRP) was measured. Linear regression examined the associations between dietary protein intake and 4-year changes in muscle mass and physical performance. Cox regression examined the association between dietary protein intake and incident sarcopenia. RESULTS: Higher plant protein intake, but not total and animal protein, was associated with less decline in muscle mass and gait speed among sarcopenia-free participants. Conversely, higher ratio of animal-to-plant protein was associated with reduced muscle mass loss among participants with sarcopenia. The highest tertile of plant protein intake was associated with lower incident sarcopenia risk (HR: 0.75, 95% CI: 0.57-0.98; P-trend = 0.034) compared to the lowest tertile. Notably, this association was observed among participants with higher serum hs-CRP levels (HR: 0.57, 95% CI: 0.34-0.95), but not in those with lower hs-CRP levels. CONCLUSION: Dietary animal and plant protein intake have differential associations with muscle mass and physical performance in older adults with and without sarcopenia. The role of plant protein in preventing sarcopenia involves modulation of inflammation.

Blue light photoreceptor cryptochrome 1 promotes wood formation and anthocyanin biosynthesis in Populus.

Blue light photoreceptor cryptochrome 1 (CRY1) in herbaceous plants plays crucial roles in various developmental processes, including cotyledon expansion, hypocotyl elongation and anthocyanin biosynthesis. However, the function of CRY1 in perennial trees is unclear. In this study, we identified two ortholog genes of CRY1 (PagCRY1a and PagCRY1b) from Populus, which displayed high sequence similarity to Arabidopsis CRY1. Overexpression of PagCRY1 substantially inhibited plant growth and promoted secondary xylem development in Populus, while CRISPR/Cas9-mediated knockout of PagCRY1 enhanced plant growth and delayed secondary xylem development. Moreover, overexpression of PagCRY1 dramatically increased anthocyanin accumulation. The further analysis supported that PagCRY1 functions specifically in response to blue light. Taken together, our results demonstrated that modulating the expression of blue light photoreceptor CRY1 ortholog gene in Populus could significantly influence plant biomass production and the process of wood formation, laying a foundation for further investigating the light-regulated tree growth.

Osteogenically committed hUCMSCs-derived exosomes promote the recovery of critical-sized bone defects with enhanced osteogenic properties.

Low viability of seed cells and the concern about biosafety restrict the application of cell-based tissue-engineered bone (TEB). Exosomes that bear similar bioactivities to donor cells display strong stability and low immunogenicity. Human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-Exos) show therapeutic efficacy in various diseases. However, little is known whether hUCMSCs-Exos can be used to construct TEB to repair bone defects. Herein, PM-Exos and OM-Exos were separately harvested from hUCMSCs which were cultured in proliferation medium (PM) or osteogenic induction medium (OM). A series of in-vitro studies were performed to evaluate the bioactivities of human bone marrow mesenchymal stem cells (hBMSCs) when co-cultured with PM-Exos or OM-Exos. Differential microRNAs (miRNAs) between PM-Exos and OM-Exos were sequenced and analyzed. Furthermore, PM-Exos and OM-Exos were incorporated in 3D printed tricalcium phosphate scaffolds to build TEBs for the repair of critical-sized calvarial bone defects in rats. Results showed that PM-Exos and OM-Exos bore similar morphology and size. They expressed representative surface markers of exosomes and could be internalized by hBMSCs to promote cellular migration and proliferation. OM-Exos outweighed PM-Exos in accelerating the osteogenic differentiation of hBMSCs, which might be attributed to the differentially expressed miRNAs. Furthermore, OM-Exos sustainably released from the scaffolds, and the resultant TEB showed a better reparative outcome than that of the PM-Exos group. Our study found that exosomes isolated from osteogenically committed hUCMSCs prominently facilitated the osteogenic differentiation of hBMSCs. TEB grafts functionalized by OM-Exos bear a promising application potential for the repair of large bone defects.

In Vivo Stimulation of Therapeutic Antigen-Specific T Cells in an Artificial Lymph Node Matrix.

T cells are critical mediators of antigen-specific immune responses and are common targets for immunotherapy. Biomaterial scaffolds have previously been used to stimulate antigen-presenting cells to elicit antigen-specific immune responses; however, structural and molecular features that directly stimulate and expand naïve, endogenous, tumor-specific T cells in vivo have not been defined. Here, an artificial lymph node (aLN) matrix is created, which consists of an extracellular matrix hydrogel conjugated with peptide-loaded-MHC complex (Signal 1), the co-stimulatory signal anti-CD28 (Signal 2), and a tethered IL-2 (Signal 3), that can bypass challenges faced by other approaches to activate T cells in situ such as vaccines. This dynamic immune-stimulating platform enables direct, in vivo antigen-specific CD8+ T cell stimulation, as well as recruitment and coordination of host immune cells, providing an immuno-stimulatory microenvironment for antigen-specific T cell activation and expansion. Co-injecting the aLN with naïve, wild-type CD8+ T cells results in robust activation and expansion of tumor-targeted T cells that kill target cells and slow tumor growth in several distal tumor models. The aLN platform induces potent in vivo antigen-specific CD8+ T cell stimulation without the need for ex vivo priming or expansion and enables in situ manipulation of antigen-specific responses for immunotherapies.

Field-Induced Non-BEC Transitions in Frustrated Magnets.

Frustrated spin systems have traditionally proven challenging to understand, owing to a scarcity of controlled methods for their analyses. By contrast, under strong magnetic fields, certain aspects of spin systems admit simpler and universal description in terms of hardcore bosons. The bosonic formalism is anchored by the phenomenon of Bose-Einstein condensation (BEC), which has helped explain the behaviors of a wide range of magnetic compounds under applied magnetic fields. Here, we focus on the interplay between frustration and externally applied magnetic field to identify instances where the BEC paradigm is no longer applicable. As a representative example, we consider the antiferromagnetic J_{1}-J_{2}-J_{3} model on the square lattice in the presence of a uniform external magnetic field, and demonstrate that the frustration-driven suppression of the Néel order leads to a Lifshitz transition for the hardcore bosons. In the vicinity of the Lifshitz point, the physics becomes unmoored from the BEC paradigm, and the behavior of the system, both at and below the saturation field, is controlled by a Lifshitz multicritical point. We obtain the resultant universal scaling behaviors, and provide strong evidence for the existence of a frustration and magnetic-field driven correlated bosonic liquid state along the entire phase boundary separating the Néel phase from other magnetically ordered states.

Photodegradation of polycyclic aromatic hydrocarbons on soil surface: Kinetics and quantitative structure-activity relationship (QSAR) model development.

Polycyclic aromatic hydrocarbons (PAHs) have attracted much attention because of their widespread existence and toxicity. Photodegradation is the main natural decay process of PAHs in soil. The photodegradation kinetics of benzopyrene (BaP) on 16 kinds of soils and 10 kinds of PAHs on Hebei (HE) soil were studied. The results showed that BaP had the highest degradation rate in Shaanxi (SN) soil (kobs = 0.11 min-1), and anthracene (Ant) was almost completely degraded after 16 h of irradiation in HE soil. Two quantitative structure-activity relationship (QSAR) models were established by the multiple linear regression (MLR) method. The developed QSAR models have good stability, robustness and predictability. The model revealed that the main factors affecting the photodegradation of PAHs are soil organic matter (SOM) and the energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital (Egap). SOM can function as a photosensitizer to induce the production of active species for photodegradation, thus favoring the photodegradation of PAHs. In addition, compounds with lower Egap are less stable and more reactive, and thus are more prone to photodegradation. Finally, the QSAR model was optimized using machine learning approach. The results of this study provide basic information on the photodegradation of PAHs and have important significance for predicting the environmental behavior of PAHs in soil.

Noncovalent Conjugates of Anthocyanins to Wheat Gluten: Unraveling Their Microstructure and Physicochemical Properties.

Intake of polyphenol-modified wheat products has the potential to reduce the incidence of chronic diseases. In order to determine the modification effect of polyphenols on wheat gluten protein, the effects of grape skin anthocyanin extract (GSAE, additional amounts of 0.1%, 0.2%, 0.3%, 0.4%, and 0.5%, respectively) on the microstructure and physicochemical properties of gluten protein were investigated. The introduction of GSAE improves the maintenance of the gluten network and increases viscoelasticity, as evidenced by rheological and creep recovery tests. The tensile properties of gluten protein were at their peak when the GSAE level was 0.3%. The addition of 0.5% GSAE may raise the denaturation temperature of gluten protein by 6.48 °C-9.02 °C at different heating temperatures, considerably improving its thermal stability. Furthermore, GSAE enhanced the intermolecular hydrogen bond of gluten protein and promoted the conversion of free sulfhydryl groups to disulfide bonds. Meanwhile, the GSAE treatment may also lead to protein aggregation, and the average pore size of gluten samples decreased significantly and the structure became denser, indicating that GSAE improved the stability of the gluten spatial network. The positive effects of GSAE on gluten protein properties suggest the potential of GSAE as a quality enhancer for wheat products.

A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia.

BACKGROUND: t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30-50% of patients experience drug resistance and subsequent relapse. N6-methyladenosine (m6A) is demonstrated to be involved in the development of AML. However, the regulatory mechanisms between AML1-ETO and m6A-related enzymes and the roles of dysregulated m6A modifications in the t(8;21)-leukemogenesis and chemoresistance remain elusive. METHODS: Chromatin immunoprecipitation, dual-luciferase reporter assay, m6A-qPCR, RNA immunoprecipitation, and RNA stability assay were used to investigate a regulatory loop between AML1-ETO and FTO, an m6A demethylase. Gain- and loss-of-function experiments both in vitro and in vivo were further performed. Transcriptome-wide RNA sequencing and m6A sequencing were conducted to identify the potential targets of FTO. RESULTS: Here we show that FTO is highly expressed in t(8;21) AML, especially in patients with primary refractory disease. The expression of FTO is positively correlated with AML1-ETO, which is attributed to a positive regulatory loop between the AML1-ETO and FTO. Mechanistically, AML1-ETO upregulates FTO expression through inhibiting the transcriptional repression of FTO mediated by PU.1. Meanwhile, FTO promotes the expression of AML1-ETO by inhibiting YTHDF2-mediated AML1-ETO mRNA decay. Inactivation of FTO significantly suppresses cell proliferation, promotes cell differentiation and renders resistant t(8;21) AML cells sensitive to Ara-C. FTO exerts functions by regulating its mRNA targets, especially IGFBP2, in an m6A-dependent manner. Regain of Ara-C tolerance is observed when IGFBP2 is overexpressed in FTO-knockdown t(8;21) AML cells. CONCLUSION: Our work reveals a therapeutic potential of targeting AML1-ETO/FTO/IGFBP2 minicircuitry in the treatment for t(8;21) patients with resistance to Ara-C.

Systematic comparison of rAAV vectors manufactured using large-scale suspension cultures of Sf9 and HEK293 cells.

Recombinant adeno-associated virus (rAAV) vectors could be manufactured by plasmid transfection into human embryonic kidney 293 (HEK293) cells or baculovirus infection of Spodoptera frugiperda (Sf9) insect cells. However, systematic comparisons between these systems using large-scale, high-quality AAV vectors are lacking. rAAV from Sf9 cells (Sf9-rAAV) at 2-50 L and HEK293 cells (HEK-rAAV) at 2-200 L scales were characterized. HEK-rAAV had ∼40-fold lower yields but ∼10-fold more host cell DNA measured by droplet digital PCR and next-generation sequencing, respectively. The electron microscope observed a lower full/empty capsid ratio in HEK-rAAV (70.8%) than Sf9-rAAV (93.2%), while dynamic light scattering and high-performance liquid chromatography analysis showed that HEK-rAAV had more aggregation. Liquid chromatography tandem mass spectrometry identified different post-translational modification profiles between Sf9-rAAV and HEK-rAAV. Furthermore, Sf9-rAAV had a higher tissue culture infectious dose/viral genome than HEK-rAAV, indicating better infectivity. Additionally, Sf9-rAAV achieved higher in vitro transgene expression, as measured by ELISA. Finally, after intravitreal dosing into a mouse laser choroidal neovascularization model, Sf9-rAAV and HEK-rAAV achieved similar efficacy. Overall, this study detected notable differences in the physiochemical characteristics of HEK-rAAV and Sf9-rAAV. However, the in vitro and in vivo biological functions of the rAAV from these systems were highly comparable. Sf9-rAAV may be preferred over HEK293-rAAV for advantages in yields, full/empty ratio, scalability, and cost.

New mitogenomes from the genus Cricotopus (Diptera: Chironomidae, Orthocladiinae): Characterization and phylogenetic implications.

Cricotopus is a large and diverse genus of non-biting midges composed of several subgenera. Complete mitogenome sequences are available for very few Cricotopus species. The subgenus Pseudocricotopus unites species with unusual morphological structures in adult male and pupal stages, however, molecular methods are needed to verify the placement of this subgenus within Cricotopus. We obtained mitogenomes of C. (Pseudocricotopus) cf. montanus and nine other Cricotopus species for phylogenetic analysis, coupled with two Rheocricotopus species and one Synorthocladius species as outgroups. The structure of the mitogenome was similar among these Cricotopus species, exhibiting A+T bias and retaining ancestral gene order. Mutation rate, estimated as Ka/Ks, varied among genes, and was highest for ATP8 and lowest for COI. The phylogenetic relationships among species of Cricotopus, Rheocricotopus and Synorthocladius was reconstructed using Bayesian inference and maximum likelihood estimation. The phylogenetic trees confirmed placement of subgenus Pseudocricotopus, represented by Cricotopus cf. montanus, within Cricotopus. Our study increases the library of chironomid mitogenomes and provides insight into the properties of their constituent genes.

Complete Suppression of Phase Segregation in Mixed-Halide Perovskite Nanocrystals under Periodic Heating.

Under continuous light illumination, it is known that localized domains with segregated halide compositions form in semiconducting mixed-halide perovskites, thus severely limiting their optoelectronic applications due to the negative changes in bandgap energies and charge-carrier characteristics. Here mixed-halide perovskite CsPbBr1.2 I1.8 nanocrystals are deposited onto an indium tin oxide substrate, whose temperature can be rapidly changed by ≈10 °C in a few seconds by applying or removing an external voltage. Such a sudden temperature change induces a temporary transition of CsPbBr1.2 I1.8 nanocrystals from the segregated phase to the mixed phase, the latter of which can be permanently maintained when the light illumination is coupled with periodic heating cycles. These findings mark the emergence of a practical solution to the detrimental phase-segregation problem, given that a small temperature modulation is readily available in various fundamental studies and practical devices of mixed-halide perovskites.

Enhanced cartilage regeneration by icariin and mesenchymal stem cell-derived extracellular vesicles combined in alginate-hyaluronic acid hydrogel.

OBJECTIVE: Osteoarthritis (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs. MATERIALS AND METHODS: MSC-EVs were isolated from sodium alginate (SA) and hyaluronic acid (HA) composite hydrogel (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo. RESULTS: EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers. CONCLUSION: The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.

Effects of Chinese heart-healthy diet on blood lipids, glucose, and estimated 10-y cardiovascular disease risk among Chinese adults: results on secondary outcomes of a randomized controlled trial.

BACKGROUND: Healthy diet is essential for cardiovascular disease risk management, but its effects among Chinese patients, whose diets differ from Western diets, remain largely unknown. METHODS: In this multicenter, patient- and outcome assessor-blind, randomized controlled feeding trial, 265 Chinese adults with baseline systolic blood pressure 130 to 159 mmHg were randomly assigned into Chinese heart-healthy (CHH) diet or usual diet for a 28-d intervention after a 7-d run-in period on usual diet. Blood lipids and glucose were measured from overnight fasting blood samples before and after the intervention. Ten-year cardiovascular disease risk was estimated using models previously developed and validated in Chinese. The changes in secondary outcomes of serum total cholesterol (TC), blood glucose, and 10-y cardiovascular disease risk over the intervention period were compared between intervention groups, adjusting for center, among participants with baseline and follow-up blood samples available. Sensitivity analyses were done with further adjustment for baseline values and covariables; missing data imputed; and among per-protocol population. RESULTS: Among 256 eligible participants (130 on CHH diet, 126 on control diet), 42% had hypercholesterolemia and 15% had diabetes at baseline. In the control group, TC and 10-y cardiovascular disease risk decreased after the intervention by 0.16 mmol/L and 0.91%, respectively, but blood glucose increased by 0.25 mmol/L. Compared with usual diet, the CHH diet lowered TC (-0.14 mmol/L, P = 0.017) and 10-y cardiovascular disease risk (-1.24%, P = 0.001) further. No effect on blood glucose was found. All sensitivity analyses confirmed the results on TC and 10-y cardiovascular disease risk, and analysis with multiple variables adjusted showed a borderline significant effect on blood glucose (-0.17 mmol/L, P = 0.051). The differences in intake of nutrients and food groups between intervention groups explained the results. CONCLUSIONS: The CHH diet reduced TC and 10-y cardiovascular disease risk and was likely to reduce blood glucose among Chinese adults with mild hypertension. Further studies with longer terms are warranted. This trial was registered at clinicaltrials.gov as NCT03882645.

Fabrication of ammonia and acetic acid-responsive intelligent films based on grape skin anthocyanin via adjusting the pH of film-forming solution.

pH-responsive intelligent films for food freshness monitoring have attracted great attentions recently. In this study, several intelligent films based on chitosan (CS), polyvinyl alcohol (PVA), and grape skin anthocyanin (GSA) were prepared, and the effect of film-forming solution pH on the properties of intelligent films was investigated. The results of SEM, FTIR, XRD and TGA displayed that the hydrogen bond between CS and GSA was strong at strong acidic conditions (2.0-2.5), and it weakened at weak acidic conditions (3.0-4.5). Meanwhile, the hydrogen bond between PVA and GSA was negligible under strong acidic conditions, and it appeared under weak acidic conditions. Consequently, the films fabricated under weak acidic conditions displayed lower water solubility, lower water vapor permeability, and higher elongation at break. The tensile strength of films increased firstly and subsequently decreased with pH increasing, reaching a maximum value of 31.44 MPa at pH 3.5. Additionally, the films prepared at pH 2.5 and 4.0 showed the best color responsiveness to ammonia and acetic acid, respectively. Overall, the intelligent films prepared under variant pH have the potential to realize the goal of monitoring the freshness of different types of food, thereby expanding the application subject of anthocyanins-based intelligent films.

Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity.

Lipid nanoparticles (LNPs) can be designed to potentiate cancer immunotherapy by promoting their uptake by antigen-presenting cells, stimulating the maturation of these cells and modulating the activity of adjuvants. Here we report an LNP-screening method for the optimization of the type of helper lipid and of lipid-component ratios to enhance the delivery of tumour-antigen-encoding mRNA to dendritic cells and their immune-activation profile towards enhanced antitumour activity. The method involves screening for LNPs that enhance the maturation of bone-marrow-derived dendritic cells and antigen presentation in vitro, followed by assessing immune activation and tumour-growth suppression in a mouse model of melanoma after subcutaneous or intramuscular delivery of the LNPs. We found that the most potent antitumour activity, especially when combined with immune checkpoint inhibitors, resulted from a coordinated attack by T cells and NK cells, triggered by LNPs that elicited strong immune activity in both type-1 and type-2 T helper cells. Our findings highlight the importance of optimizing the LNP composition of mRNA-based cancer vaccines to tailor antigen-specific immune-activation profiles.

Free and Bound Phenolic Profiles and Antioxidant Activities in Melon (Cucumis melo L.) Pulp: Comparative Study on Six Widely Consumed Varieties Planted in Hainan Province.

Bound phenolic compounds in the melon pulp have seldom been investigated. This study revealed considerable differences in the total phenolic content (TPC) and antioxidant activity of the free and bound phenolic extracts in the pulps of six melon varieties from Hainan Province, China. Naixiangmi and Yugu demonstrated the highest free TPC, while Meilong showed the highest bound and total TPC and antioxidant activity. UHPLC-QQQ-MS identified and quantified 30 phenolic compounds. The melon cultivars markedly differed in the amount and content of their free and bound phenolic compounds. Xizhoumi No. 25 and Meilong afforded the most phenolic compounds. Hongguan emerged with the highest free phenolic compound content and total content of phenolic compounds; however, Meilong possessed the highest bound phenolic compound content. Hierarchical cluster analysis divided the melon varieties into four different taxa. The present study provides a scientific basis for developing the health-promoting effects of melon pulp.