Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma.

O6-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed a framework nucleic acid-based nanoparticles (FNN), which is constructed from a six-helix DNA bundle, to encapsulate and protect siMGMT for improving TMZ sensitivity in GBM treatment. For better blood-brain barrier (BBB) penetration and GBM targeting, we conjugated Angiopep-2 (ANG) targeting modules to each end of the FNN. Nucleolin (NCL)-responsive locks were engineered along the sides of the six-helix DNA bundle, which safeguard siMGMT before tumor entry. Upon interaction with tumor-overexpressed NCL, these locks unlock, exposing siMGMT, this allows for effective suppression of MGMT, resulting in a significant improvement of TMZ therapeutic efficacy in GBM. This innovative strategy has the potential to transform the current treatment landscape for GBM.

DNA-Engineered Degradable Invisibility Cloaking for Tumor-Targeting Nanoparticles.

Nanoparticle (NP) delivery systems have been actively exploited for cancer therapy and vaccine development. Nevertheless, the major obstacle to targeted delivery lies in the substantial liver sequestration of NPs. Here we report a DNA-engineered approach to circumvent liver phagocytosis for enhanced tumor-targeted delivery of nanoagents in vivo. We find that a monolayer of DNA molecules on the NP can preferentially adsorb a dysopsonin protein in the serum to induce functionally invisibility to livers; whereas the tumor-specific uptake is triggered by the subsequent degradation of the DNA shell in vivo. The degradation rate of DNA shells is readily tunable by the length of coated DNA molecules. This DNA-engineered invisibility cloaking (DEIC) is potentially generic as manifested in both Ag2S quantum dot- and nanoliposome-based tumor-targeted delivery in mice. Near-infrared-II imaging reveals a high tumor-to-liver ratio of up to ∼5.1, approximately 18-fold higher than those with conventional nanomaterials. This approach may provide a universal strategy for high-efficiency targeted delivery of theranostic agents in vivo.

Association between dietary vitamin intake and mortality in US adults with diabetes: A prospective cohort study.

AIMS: To explore the association of dietary vitamin intake from food and/or supplement with mortality in US adults with diabetes. MATERIALS AND METHODS: This prospective cohort study was conducted on 5418 US adults with diabetes from the National Health and Nutrition Examination Survey 1999-2018. Vitamin intake from food and supplements was estimated via dietary recall. Sufficient intake from food or food + supplement was defined as ≥ estimated average requirement (EAR) and ≤ tolerable upper intake level (UL), insufficient intake, < EAR; and excess intake, > UL. Medium supplementary intake was classified as > median level and ≤75th percentile; low intake, ≤ median level; and high intake, >75th percentile, as reported by supplement users. RESULTS: A total of 1601 deaths occurred among the participants over a median follow-up of 11.0 years. Cox regression analysis of the single-vitamin model demonstrated that sufficient vitamin A and folate intake from food and food + supplement and medium vitamin A and folate intake from supplement; sufficient riboflavin, niacin, and vitamin B6 intake from food and food + supplement; and sufficient thiamin and vitamin E intake from food + supplement were significantly associated with reduced all-cause mortality (all p < 0.05). In the multivitamin model, sufficient vitamin A and folate intake from food and food + supplement, medium vitamin A and folate intake from the supplement, and sufficient niacin intake from food and food + supplement were inversely associated with mortality (all p < 0.05). CONCLUSIONS: Vitamin A and folate intake from food or supplement and niacin intake from food were significantly associated with reduced mortality in US adults with diabetes.

RNA-binding protein YBX1 promotes brown adipogenesis and thermogenesis via PINK1/PRKN-mediated mitophagy.

Promoting the thermogenic function of brown adipose tissue (BAT) is a promising strategy to combat obesity and metabolic disorders. While much is known about the transcriptional regulation of BAT activation, however, the underlying mechanism of post-transcriptional control by RNA binding proteins remains largely unknown. Here, we found that RNA binding protein Y-box binding protein 1 (YBX1) expression was abundant in BAT and induced by cold exposure and a ß-adrenergic agonist in mice. Loss-of-function experiments showed that YBX1 deficiency inhibited mouse primary brown adipocyte differentiation and thermogenic function. Further study showed that YBX1 positively regulates thermogenesis through enhancing mitophagy. Mechanistically, RNA immunoprecipitation identified that YBX1 directly targeted the transcripts of PTEN-induced kinase 1 (Pink1) and parkin RBR E3 ubiquitin-protein ligase (Prkn), two key regulators of mitophagy. RNA decay assay proved that loss of YBX1 decreased mRNA stability of Pink1 and Prkn, leading to reduced protein expression, thereby alleviating mitophagy and inhibiting thermogenic program. Importantly, in vivo experiments demonstrated that YBX1 overexpression in BAT promoted thermogenesis and mitophagy in mice. Collectively, our results reveal novel insight into the molecular mechanism of YBX1 in post-transcriptional regulation of PINK1/PRKN-mediated mitophagy and highlight the critical role of YBX1 in brown adipogenesis and thermogenesis.

Kawasaki disease coronary artery lesions prediction with monocyte-to-high-density lipoprotein ratio.

OBJECTIVE: The aim of this study was to evaluate the predictive value of the monocyte-to-high-density lipoprotein ratio (MHR) in Kawasaki disease (KD) complicated with coronary artery lesions (CALs) and to construct a nomogram prediction model. METHODS: The medical records of KD inpatients diagnosed in the Department of Pediatrics of Lanzhou University Second Hospital from May 2015 to September 2021 were retrospectively analyzed. ROC curves were applied to evaluate the predictive value of MHR in KD complicated with CALs, and logistic regression analysis was used to screen independent risk factors. We constructed a nomogram model and performed internal validation. RESULTS: A total of 568 KD patients were enrolled in the study. MHR was significantly higher in KD patients complicated with CALs and was identified as an independent risk factor for CALs (OR: 1.604, 95% CI: 1.292-1.990). The area under the ROC curve for MHR in predicting CALs was 0.661. The C-index of the nomogram model constructed by incorporating MHR was 0.725 (95% CI: 0.682-0.768), and the calibration curve revealed good agreement between the predicted and actual probabilities. CONCLUSIONS: MHR may not be suitable as a single biomarker to predict the occurrence of CALs, but the nomogram model constructed in combination with other independent risk factors had acceptable predictive performance. IMPACT: The inflammatory response plays an important role in the pathogenesis of Kawasaki disease. The monocyte-to-high-density lipoprotein ratio is a novel systemic inflammation marker. The monocyte-to-high-density lipoprotein ratio is an independent risk factor for Kawasaki disease complicated with coronary artery lesions. The nomogram established by incorporating the monocyte-to-high-density lipoprotein ratio has satisfactory predictive performance for coronary artery lesion formation.

Factors influencing catastrophic health expenditure of households with people with diabetes in Northwest China-an example from Gansu Province.

BACKGROUND: Diabetes is a chronic non-communicable disease that causes a substantial economic burden on diabetic suffers and their households. The aim of this study was to explore the prevalence, equity, and determinants of catastrophic health expenditure (CHE) among households with people with diabetes in Northwest China. METHODS: A total of 3,000 households were included in the 6th Health services survey in Gansu Province, China of which 270 households with people with diabetes. The equity of CHE was evaluated by concentration curve and concentration index (CI). We adopted the Pareto chart to analyze the main economic intervals of the occurrence of CHE. Finally, we combined the decision tree and logistic model and analyzed the determinants of the occurrence of CHE. RESULTS: The incidence of CHE at 15%, 25% and 40% were 75.19%, 58.89% and 35.19%, respectively. CHE tended to occur in households with a lower economic level, with the phenomenon being more pronounced at Z = 40%. The Pareto chart showed that households in the group with an annual per capita income of 0-740 USD (0-5,000 Chinese Yuan) were most likely to experience CHE. Both decision tree and logistic models suggested that economic level, comorbidities, and small household size were potential risk factors. In addition, the decision tree model also suggested the interaction between the influencing factor of health checks in the past 12 months and the number of chronic diseases. CONCLUSIONS: In summary, Households with people with diabetes were more likely to incur CHE. It is essential to focus on low- and middle-income households with people with diabetes, strengthen the management of patients with diabetes, and provide timely health interventions to reduce the occurrence of chronic comorbidity and the risk of CHE in households.

Associations of sleep duration with neurocognitive development in the first 2†years of life.

The effect of sleep duration on neurocognitive development in infants and toddlers remains unclear. We aimed to investigate the relationship between sleep duration and neurocognitive development in infancy. Based on a prospective birth cohort, 2220 mother-infant pairs were enrolled in Wuhan, China, between January 2014 and October 2017. Sleep duration was evaluated at 1, 6, 12 and 24 months via parent-report questionnaires. To assess the children's neurocognitive development at 2 years old, the Bayley Scales of Infant Development of China Revision was used to assess the Mental Development Index (MDI) and Psychomotor Development Index (PDI). A group-based semiparametric mixture model was used to estimate the developmental trajectories of the total, nighttime and daytime sleep duration. The associations of sleep duration at each age and sleep duration trajectories with Mental Development Index scores and Psychomotor Development Index scores were analysed using generalized linear models. Daytime sleep duration (≥ 10.0 hr) at 1 month was associated with lower Mental Development Index scores (ß = -3.55, 95% confidence interval: -6.02, -1.08) and lower Psychomotor Development Index scores (ß = -2.87, 95% confidence interval: -4.94, -0.81). Nighttime sleep duration (≤ 7.0 hr) at 6 months was associated with lower Mental Development Index scores (ß = -7.02, 95% confidence interval: -11.02, -3.01). Daytime sleep duration (> 4 hr) and nighttime sleep duration (< 8 hr) at 12 months were associated with lower Mental Development Index scores (ß = -9.17, 95% confidence interval: -15.35, -2.98) and lower Psychomotor Development Index scores (ß = -8.14, 95% confidence interval: -13.56, -2.71), respectively. In further sleep duration trajectories analyses, lower Mental Development Index scores were significantly associated with the "decreased and then increased nighttime sleepers" trajectory (ß = -4.39, 95% confidence interval: -8.02, -0.76), and "long and decreased daytime sleepers" trajectory (ß = -2.44, 95% confidence interval: -4.58, -0.30). These results showed that short nighttime sleep duration and long daytime sleep duration in infancy were detrimental to children's neurocognitive development.

Effects of early sub-therapeutic antibiotic administration on body tissue deposition, gut microbiota and metabolite profiles of weaned piglets.

BACKGROUND: This study aimed to evaluate the effects of sub-therapeutic antibiotic (STA) administration and its subsequent withdrawal on the body tissue deposition, gut microbiota, and metabolite profiles of piglets. The piglets in the experimental group were fed with STA (30 mg kg-1 bacitracin methylene disalicylate, 75 mg kg-1 chlortetracycline, 300 mg kg-1 calcium oxytetracycline) for 14 days and the target bodyweight of the withdrawal period was 25 kg. RESULTS: The experiment was divided into two periods: the administration period and the withdrawal period. The results showed that STA did not improve piglets' growth performance during the two periods. Piglets treated with STA had lower body water deposition during the withdrawal period and tended to increase body lipid deposition during the withdrawal period and the whole period in comparison with the piglets in the control group. It was found that STA markedly altered the colonic microbiota and their metabolites in the piglets. Sub-therapeutic antibiotics were initially effective in decreasing the abundance of pathogenic bacteria during the administration period; however, STA could not continue the effect during the withdrawal period, leading to a rebound of pathogenic bacteria such as Alloprevotella and the increased abundance of other pathogenic bacteria like Oscillibacter. Remarkably, STA treatment decreased Blautia abundance. This bacterium plays a potential protective role against obesity. Metabolomic analysis indicated that STA mainly altered amino acid metabolism, lipid metabolism, and carbohydrate metabolism during the two periods. Spearman's correlation analysis showed that the gut microbiota was highly correlated with microbial metabolite changes. CONCLUSION: These results suggest that early STA administration may alter body tissue deposition later in life by reshaping the gut microbiota and their metabolite profiles. © 2022 Society of Chemical Industry.

Directing Multivalent Aptamer-Receptor Binding on the Cell Surface with Programmable Atom-Like Nanoparticles.

Multivalent interactions of biomolecules play pivotal roles in physiological and pathological settings. Whereas the directionality of the interactions is crucial, the state-of-the-art synthetic multivalent ligand-receptor systems generally lack programmable approaches for orthogonal directionality. Here, we report the design of programmable atom-like nanoparticles (aptPANs) to direct multivalent aptamer-receptor binding on the cell interface. The positions of the aptamer motifs can be prescribed on tetrahedral DNA frameworks to realize atom-like orthogonal valence and direction, enabling the construction of multivalent molecules with fixed aptamer copy numbers but different directionality. These directional-yet-flexible aptPAN molecules exhibit the adaptability to the receptor distribution on cell surfaces. We demonstrate the high-affinity tumor cell binding with a linear aptPAN oligomer (≈13-fold improved compared to free aptamers), which leads to ≈50 % suppression of cell growth.

Poly-Adenine-Based Spherical Nucleic Acids for Efficient Live-Cell MicroRNA Capture.

Direct delivery of exogenous non-coding nucleic acids into living cells has attracted intense interest in biological applications. However, the cell entry efficiency and target capture ability remain to be improved. Herein, we report a method for compartmenting the nucleic acids on the surface of poly-adenine-based spherical nucleic acids (polyA-SNAs) for efficient capture of oncogenic microRNAs (miRNAs) in living cells. We find that polyA-SNAs exhibit high cell entry efficiency, which is insensitive to the configuration of the anti-miRNA sequences. By programming the length of polyAs, we precisely engineered the spatial configuration of the anti-miRNA sequences in polyA-SNAs. Compartmentalized polyA-SNAs bind to miRNAs with improved capture ability as compared to densely compacted SNAs. We further demonstrate that polyA-SNAs serve as high-efficacy miRNA sponges for capturing oncogenic miRNAs both in living cells and in mice. The efficient inhibition of miRNAs results in significant suppression of tumor growth.

Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-ß1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge.

Whey protein concentrate (WPC) has been reported to have protective effects on the intestinal barrier. However, the molecular mechanisms involved are not fully elucidated. Transforming growth factor-ß1 (TGF-ß1) is an important component in the WPC, but whether TGF-ß1 plays a role in these processes is not clear. The aim of this study was to investigate the protective effects of WPC on the intestinal epithelial barrier as well as whether TGF-ß1 is involved in these protection processes in a piglet model after lipopolysaccharide (LPS) challenge. In total, eighteen weanling pigs were randomly allocated to one of the following three treatment groups: (1) non-challenged control and control diet; (2) LPS-challenged control and control diet; (3) LPS+5 %WPC diet. After 19 d of feeding with control or 5 %WPC diets, pigs were injected with LPS or saline. At 4 h after injection, pigs were killed to harvest jejunal samples. The results showed that WPC improved (P<0·05) intestinal morphology, as indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function, which was reflected by increased transepithelial electrical resistance and decreased mucosal-to-serosal paracellular flux of dextran (4 kDa), compared with the LPS group. Moreover, WPC prevented the LPS-induced decrease (P<0·05) in claudin-1, occludin and zonula occludens-1 expressions in the jejunal mucosae. WPC also attenuated intestinal inflammation, indicated by decreased (P<0·05) mRNA expressions of TNF-α, IL-6, IL-8 and IL-1ß. Supplementation with WPC also increased (P<0·05) TGF-ß1 protein, phosphorylated-Smad2 expression and Smad4 and Smad7 mRNA expressions and decreased (P<0·05) the ratios of the phosphorylated to total c-jun N-terminal kinase (JNK) and p38 (phospho-JNK:JNK and p-p38:p38), whereas it increased (P<0·05) the ratio of extracellular signal-regulated kinase (ERK) (phospho-ERK:ERK). Collectively, these results suggest that dietary inclusion of WPC attenuates the LPS-induced intestinal injury by improving mucosal barrier function, alleviating intestinal inflammation and influencing TGF-ß1 canonical Smad and mitogen-activated protein kinase signalling pathways.

Urinary polycyclic aromatic hydrocarbon metabolites in Chinese pregnant women: Concentrations, variability, predictors, and association with oxidative stress biomarkers.

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive contaminants having adverse health effects. Urinary monohydroxylated PAHs (OH-PAHs) are commonly employed as biomarkers to estimate PAH exposure levels in humans. However, little is understood about the variability in OH-PAHs among pregnant women across trimesters and their relationship with oxidative stress biomarkers (OSBs). Based on a prospective birth cohort study conducted in Wuhan, China, we selected 644 women who donated (spot) urine samples across different trimesters and measured the urinary concentrations of eight OH-PAHs and three selected OSBs (8-OHG, 8-OHdG, and HNEMA) to explore the relationship between the OH-PAHs and OSBs. Pregnant women were found to be ubiquitously exposed to the PAHs, with detection rates of the OH-PAHs ranging from 86.3% to 100%. 2-Hydroxynaphthalene (2-OH-Nap) had the highest urinary concentrations among the OH-PAHs during the three trimesters (specific gravity-adjusted median values for the first, second, and third trimesters: 1.86, 2.39, and 2.20 ng/mL, respectively). However, low reproducibility of the OH-PAHs was observed across the three trimesters with intraclass correlation coefficients ranged between 0.02 and 0.22. Most urinary OH-PAHs had the highest concentrations at the first trimester and the lowest at the third trimester. Some OH-PAH concentrations were higher in pregnant women with lower educational level [2-hydroxyphenanthrene (2-OH-Phen) and 3-hydroxyphenanthrene (3-OH-Phen)], those who were overweight [2-OH-Nap, 2/3-hydroxyfluorene (2/3-OH-Fluo), 2-OH-Phen, and 4-hydroxyphenanthrene (4-OH-Phen)], those who were unemployed during pregnancy [1-hydroxynaphthalene, 1/9-hydroxyphenanthrene, and 4-OH-Phen], and the samples donated in summer (most OH-PAHs, except for 2-OH-Nap). In multivariable linear mixed-effects model analyses, every OH-PAH was found to be significantly associated with increased levels of the three OSBs. For example, each interquartile range-fold increase in 2/3-OH-Fluo concentration was associated with the largest increase in 8-OHdG (65.4%) and 8-OHG (49.1%), while each interquartile range-fold increase in 3-OH-Phen concentration was associated with the largest increase in HNEMA (76.3%). Weighted quantile sum regression models, which were used to examine the joint effect of OH-PAH mixture on the OSBs, revealed positive associations between the OH-PAH mixture exposure and the OSBs. Specifically, 2/3-OH-Fluo and 2-OH-Nap were the major contributors in the association with oxidative damage of nucleic acids (8-OHdG and 8-OHG), while hydroxyphenanthrenes and 1-hydroxypyrene were the major contributors in the association with oxidative damage of lipid (HNEMA). Further work is required to examine the potential mediating role of oxidative stress in the relationship of adverse health outcomes with elevated PAH exposure among pregnant women.

Associations between maternal urinary rare earth elements during pregnancy and birth weight-for-gestational age: Roles of cord blood vitamin D levels.

Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord blood total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [ß = -0.092; 95 % confidence interval (CI): -0.149, -0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 µg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 µg/L) (all p-values for interaction < 0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.

Engineering Bacterial Biofilm Development and Structure via Regulation of Silver Nanoparticle Density in Graphene Oxide Composite Coating.

Graphene-based composites have shown significant potential in the treatment of biofilm infections in clinical settings due to their exceptional antimicrobial properties and specific mechanisms. Nevertheless, a comprehensive understanding of the influence exerted by nanoparticles embedded in the composites on the development and structure of biofilms is still lacking. Here, we fabricate different graphene oxide-silver nanoparticle (GAg) composite-modified substrates (GAgS) with varying densities of silver nanoparticles (AgNPs) and investigate their effects on planktonic bacterial adhesion, subsequent biofilm formation, and mature biofilm structure. Our findings indicate that the initial attachment of Pseudomonas aeruginosa cells during biofilm formation is determined by the density of AgNPs on the GAgS surface. In contrast, the subsequent transition from adherent bacteria to the biofilm is determined by GAgS's synergistic antimicrobial effect. There exists a threshold for the inhibitory performance of GAgS, where the 20 µg/cm2 GAg composite completely prevents biofilm formation; below this concentration, GAgS delays the development of the biofilm and causes structural changes in the mature biofilm with enhanced bacterial growth and increased production of extracellular polymeric substance. More importantly, GAgS have minimal impact on mammalian cell morphology and proliferation while not inducing hemolysis in red blood cells. These results suggest that GAg composites hold promise as a therapeutic approach for addressing medical devices and implant-associated biofilm infections.

Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.

Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?

Oxidative stress has been associated with a number of physiological problems in swine, including reduced production efficiency. Recently, although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production, it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors. Here, we discuss the dose and dose intensity of the causes of oxidative stress involving physiological, environmental and dietary factors, recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.

Effect of mixed meal replacement of soybean meal on growth performance, nutrient apparent digestibility, and gut microbiota of finishing pigs.

Introduction: This study was carried out to investigate the effects of mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacement soybean meal on growth performance, nutrient apparent digestibility, serum inflammatory factors and immunoglobulins, serum biochemical parameters, intestinal permeability, short-chain fatty acid content, and gut microbiota of finishing pigs. Methods: A total of 54 pigs with an average initial weight of 97.60 ± 0.30 kg were selected and randomly divided into 3 groups according to their initial weight, with 6 replicates in each group and 3 pigs in each replicate. The trial period was 26 days. The groups were as follows: control group (CON), fed corn-soybean meal type basal diet; Corn-soybean-mixed meal group (CSM), fed corn-soybean meal-mixed meal diet with a ratio of rapeseed meal, cotton meal, and sunflower meal of 1:1:1 to replace 9.06% soybean meal in the basal diet; Corn-mixed meal group (CMM), fed a corn-mixed meal diet with a ratio of Rapeseed meal, Cotton meal and Sunflower meal of 1:1:1 to replace soybean meal in the basal diet completely. The crude protein level of the three diets was maintained at 12.5%. Results: Our findings revealed no significant impact of replacing soybean meal with the mixed meal (rapeseed meal, cotton meal, and sunflower meal) on the ADG (Average daily gain), ADFI (Average daily feed intake), and F/G (Feed gain ratio) (P > 0.05), or crude protein, crude fat, and gross energy (P > 0.05) in the diet of finishing pigs. Compared with the CON group, the serum interleukin 6 (IL-6) and interleukin 10 (IL-10) concentrations were significantly decreased in the CMM group (P < 0.05). However, there is no significant effect of the mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacing soybean meal in the diet on the serum interleukin 1ß (IL-1ß), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF-α), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations (P > 0.05). Concordantly, there is no significant effect of mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacing soybean meal in the diet on the serum antioxidant capacity, such as total antioxidant capacity (T-AOC), catalase (CAT), and malondialdehyde (MDA) levels of finishing pigs. Moreover, compared with the CON group, serum low-density lipoprotein (LDL-C) levels were significantly lower in the CSM group (P < 0.05) and their total bilirubin (TBIL) levels were significantly lower in the CMM group (P < 0.05). There is not a significant effect on serum D-lactate and diamine oxidase (DAO) concentrations (P > 0.05). The next section of the survey showed that the replacement of soybean meal with a mixed meal (rapeseed meal, cotton meal, and sunflower meal) in the diet did not significantly influence the acetic acid, propionic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid in the colon contents (P > 0.05). Furthermore, compared with the CON group, the CMM group diet significantly increased the abundance of Actinobacteria at the phylum level (P < 0.05), U_Actinobacteria at the class level (P < 0.05), and U_Bacteria at the class level (P < 0.05). The result also showed that the CMM group significantly reduced the abundance of Oscillospirales at the order level (P < 0.05) and Streptococcaceae at the family level (P < 0.05) compared with the CON group. The Spearman correlation analysis depicted a statistically significant positive correlation identified at the class level between the relative abundance of U_Bacteria and the serum T. BILI concentrations (P < 0.05). Moreover, a significant negative correlation was detected at the order level between the relative abundance of Oscillospirales and the levels of acetic and propionic acids in the colonic contents (P < 0.05). Additionally, there was a significant positive correlation between the serum concentrations of IL-6 and IL-10 and the relative abundance of the family Streptococcaceae (P < 0.05). Discussion: This study demonstrated that the mixed meal (rapeseed meal, cotton meal, and sunflower meal) as a substitute for soybean meal in the diet had no significant negative effects on the growth performance, nutrient apparent digestibility, serum immunoglobulins, serum antioxidant capacity, intestinal permeability, short-chain fatty acid content, and diversity of gut microbiota of finishing pigs. These results can help develop further mixed meals (rapeseed meal, cotton meal, and sunflower meal) as a functional alternative feed ingredient for soybean meals in pig diets.

Effect of Miscellaneous Meals Replacing Soybean Meal in Feed on Growth Performance, Serum Biochemical Parameters, and Microbiota Composition of 25-50 kg Growing Pigs.

The present study aims to determine the effect of miscellaneous meals (rapeseed meal, cottonseed meal, and sunflower meal) replacing soybean meal in feed on growth performance, apparent digestibility of nutrients, serum biochemical parameters, serum free amino acid content, microbiota composition and SCFAs content in growing pigs (25-50 kg). A total of 72 (Duroc × Landrace × Yorkshire) growing pigs with initial weights of 25.79 ± 0.23 kg were randomly divided into three treatments. The pigs were fed corn-soybean meal (CON), corn-soybean-miscellaneous meals (CSM), and corn-miscellaneous meals (CMM). Each treatment included six replicates with four pigs per pen (n = 24, 12 barrows and 12 gilts). Soybean meal accounted for 22.10% of the basal diet in the CON group. In the CSM group, miscellaneous meals partially replaced soybean meal with a mixture of 4.50% rapeseed meal, 3.98% cottonseed meal, and 4.50% sunflower meal. In the CMM group, miscellaneous meals entirely replaced soybean meal with a mixture of 8.50% rapeseed meal, 8.62% cottonseed meal, and 8.5% sunflower. The results showed that compared with the CON, the CSM and CMM groups significantly improved the average daily gain (ADG) of growing pigs during the 25-50 kg stage (p < 0.05) but had no effects on average daily feed intake (ADFI) and average daily feed intake/average daily gain (F/G) (p > 0.05). Moreover, the CMM group significantly reduced nutrient apparent digestibility of gross energy compared with the CON group. The serum biochemical parameters results showed that the CSM group significantly improved the contents of total protein (TP) compared with the CON group (p < 0.05). The CMM group significantly improved the contents of total protein (TP), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) compared with the CON group in serum (p < 0.05). In comparison with the CON group, the CMM group also significantly improved lysine (Lys), threonine (Thr), valine (Val), isoleucine (Ile), leucine (Leu), phenylalanine (Phe), arginine (Arg), and citrulline (Cit) levels in serum (p < 0.05). However, the CMM group significantly decreased non-essential amino acid content glycine (Gly) in serum compared with CON (p < 0.05), while compared with the CON group, the CSM and CMM groups had no significant effects on the relative abundance, the alpha-diversity, or the beta-diversity of fecal microbiota. Moreover, compared with the CON group, the CSM group significantly increased butyric acid and valeric acid contents of short-chain fatty acids (SCFAs) in feces (p < 0.05). In contrast to the CON group, the CMM group significantly reduced the contents of SCFAs in feces, including acetic acid, propionic acid, and isobutyric acid (p < 0.05). Collectively, the results of the present study indicate that miscellaneous meals (rapeseed meal, cottonseed meal, and sunflower meal) can partially replace the soybean meal and significantly improve the growth performance of growing pigs during the 25-50 kg stage. Thus, miscellaneous meals are a suitable protein source as basal diets to replace soybean meals for 25-50 kg growing pigs. These results can be helpful to further develop miscellaneous meals as a functional alternative feed ingredient to soybean meal.

Subcellular localization of DNA nanodevices and their applications.

The application of nanodevices based on DNA self-assembly in the field of cell biology has made significant progress in the past decade. In this study, the development of DNA nanotechnology is briefly reviewed. The subcellular localization of DNA nanodevices, and their new progress and applications in the fields of biological detection, subcellular and organ pathology, biological imaging, and other fields are reviewed. The future of subcellular localization and biological applications of DNA nanodevices is also discussed.

Nanoarchitectonics composite hydrogels with high toughness, mechanical strength, and self-healing capability for electrical actuators with programmable shape memory properties.

Hydrogel materials show promise in various fields, including flexible electronic devices, biological tissue engineering and wound dressing. Nevertheless, the inadequate mechanical properties, recovery performance, and self-healing speed still constrain the development of intelligent hydrogel materials. To tackle these challenges, we designed a composite hydrogel with high mechanical strength, rapid self-recovery and efficient self-healing ability based on multiple synergistic effects. With the synergistic effect of hydrogen bonds, metal coordination bonds and electrostatic interaction, the synthesized hydrogel could reach a maximum tensile strength of 6.2 MPa and a toughness of 50 MJ m-3. The interaction between the weak polyelectrolyte polyethyleneimine and polyacrylic acid aided in improving the elasticity of the hydrogel, thereby endowing it with prompt self-recovery attributes. The multiple reversible effects also endowed the hydrogel with excellent self-healing ability, and the fractured hydrogel could achieve 95% self-healing within 4 h at room temperature. By the addition of glycerol, the hydrogel could also cope with a variety of extreme environments in terms of moisture retention (12 h, maintaining 80% of its water content) and freeze protection (-36.8 °C) properties. In addition, the composite hydrogels applied in the field of shape memory possessed programmable and reversible shape transformation properties. The polymer chains were entangled at high temperatures to achieve shape fixation, and shape memory was eliminated at low temperatures, which allowed the hydrogels to be reprogrammed and achieve multiple shape transitions. In addition, we also assemble composite hydrogels as actuators and robotic arms for intelligent applications.