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Inspired by the natural phenomenon of phenolic-protein interactions, we translate this "naturally evolved interaction" to a "phenolic acid derivative based albumin bound" technology, through the synthesis of phenolic acid derivatives comprising a therapeutic cargo linked to a phenolic motif. Phenolic acid derivatives can bind to albumin and form nanocomplexes after microfluidic mixing. This strategy has been successfully applied to different types of anticancer drugs, including taxanes, anthraquinones, etoposides, and terpenoids. Paclitaxel was selected as a model drug for an in-depth study. Three novel paclitaxel-phenolic acid conjugates have been synthesized. Molecular dynamics simulations provide insights into the self-assembled mechanisms of phenolic-protein nanocomplexes. The nanocomplexes show improved pharmacokinetics, elevated tolerability, decreased neurotoxicity, and enhanced anticancer efficacies in multiple murine xenograft models of breast cancer, in comparison with two clinically approved formulations, Taxol (polyoxyethylated castor oil-formulated paclitaxel) and Abraxane (nab-paclitaxel). Such a robust system provides a broadly applicable platform for the development of albumin-based nanomedicines and has great potential for clinical translation.

Glyphosate-based herbicides (GBHs) are widely used worldwide. Glyphosate (GLP) is the main active component of GBHs. The presence of GBH residues in the environment has led to the exposure of animals to GBHs, but the mechanisms of GBH-induced nephrotoxicity are not clear. This study investigated the effects of GBHs on piglet kidneys. Twenty-eight healthy female hybrid weaned piglets (Duroc × Landrace × Yorkshire) with an average weight of 12.24 ± 0.61 kg were randomly divided into four treatment groups (n=7 piglets/group) that were supplemented with Roundup® (equivalent to GLP concentrations of 0, 10, 20, and 40 mg/kg) for a 35-day feeding trial. The results showed that the kidneys in the 40-mg/kg GLP group suffered slight damage. Roundup® significantly decreased the activity of catalase (CAT) (P=0.005) and increased the activity of superoxide dismutase (SOD) (P=0.029). Roundup® increased the level of cystatin-C (Cys-C) in the plasma (linear, P=0.002 and quadratic, P=0.015). The levels of neutrophil gelatinase-associated lipocalin (NGAL) in plasma increased linearly (P=0.007) and quadratically (P=0.003) as the dose of GLP increased. The mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1) in the 20-mg/kg GLP group was increased significantly (P

Therapeutic efficacy against cancer relies heavily on the ability of the therapeutic agents to reach their final targets. The optimal targets of most cancer therapeutic agents are usually biological macromolecules at the subcellular level, which play a key role in carcinogenesis. Therefore, to improve the therapeutic efficiency of drugs, researchers need to focus on delivering not only the therapeutic agents to the target tissues and cells but also the drugs to the relevant subcellular structures. In this review, we discuss the most recent construction strategies and release patterns of various cancer cell subcellular-targeting nanoformulations, aiming at providing guidance in the overall design of precise nanomedicine. Additionally, future challenges and potential perspectives are illustrated in the hope of enhancing anticancer efficacy and accelerating the translational progress of precise nanomedicine.

Some chemotherapy can damage tumor cells, releasing damage-related molecular patterns including ATP to improve immunological recognition against the tumor by immunogenic cell death (ICD). However, the immune-stimulating ATP may be rapidly degraded into immunosuppressive adenosine by highly expressed CD39 and CD73 in the tumor microenvironment, which leads to immune escape. Based on the above paradox, a liposome nanoplatform combined with ICD inducer (oxaliplatin) and CD39 inhibitor (POM-1) is designed for immunochemotherapy. The liposomes efficiently load the phospholipid-like oxaliplatin prodrug, and the cationic charged surface could adsorb POM-1. Rationally designed DSPE-PEG

Cancer has become one of the major threats to human survival. Because of antibodies specificity and low toxicity, it is the primary choice to diagnose and treat cancer. It is easy to be cleared from the blood circulation or distributing throughout the body and causes unnecessary side effects. It is necessary to delivery antibodies to the tumour region in a stable, safe and effective manner. In this review, we discuss the latest studies that aimed to delivery antibodies to tumour sites via several vector forms, such as liposomes, carbon nanomaterials, and gold nanomaterials. How to deliver antibodies to the target site is a difficulty for antibody therapy. This review summarises the antibody's therapeutic forms and carrier materials in recent years, and to explore how antibodies can be safely and stably delivered to the target site.

In the livestock husbandry compensatory growth may be explored as a means to improve nutrient utilization, to reduce gut health problems due to excess protein intake, to simplify feeding strategies and thus to improve production efficiencies. This study investigated the effects of early protein restriction (EPR) and early antibiotic intervention (EAI) on growth performance, intestinal morphology, colonic bacteria, metabolites and mucosal gene expressions during the restriction phase and re-alimentation phase. A total of 64 piglets (10.04 ± 0.73 kg) were randomly divided into four treatment groups according to a 2 × 2 factorial arrangement with two levels of proteins (14% v. 20%) and two levels of antibiotics (0 v. 50 mg/kg kitasamycin and 20 mg/kg colistin sulphate). After a 30-day restriction phase with four kinds of diets, all groups were fed the same diets for another 74 days. The results showed that EPR decreased BW, average daily gain (ADG), average daily feed intake in the restriction phase (P < 0.01) and increased ADG on days 66 to 104 of the late re-alimentation phase. Early protein restriction could decrease the villus height in the jejunum (P < 0.05), while shifting to the same diets restored the villus height. Meanwhile, during the re-alimentation phase, pigs in the protein restriction groups had increased concentrations of total short chain fatty acids (P < 0.05), and modified the abundances of Firmicutes and Bacteroidetes in the colon. Furthermore, the lower microbial diversity caused by EPR was improved, and gene expression analysis indicated a better barrier function in the colon. During the whole trial, EAI had no interaction with EPR and played a dispensable role in compensatory growth. Collectively, the retardation of growth caused by EPR can be compensated for in the later stages of pig raising, and accompanied by altered intestinal morphology, microbial composition.

To realize the controlled mass production of microspheres prepared by a high-pressure homogenizer and solve the problem of protein structure damage caused by very high pressure and overheating. This study established a numerical model based on the high-pressure homogenizer and performed simulation calculations using computational fluid dynamics (CFD). Through multipressure gradient microsphere preparation experiments, the particle size obtained by experiment and numerical calculation were compared and analyzed. According to the principle of conservation of energy, the speed was established as the optimization reference target, the structure of homogenizer was optimized and designed, and the corner spacing, corner radian, and corner taper of the homogeneous cavity were determined as the optimization objects. The ternary and cubic relationship equations of the optimized structure were fitted, and the continuous optimization of multi factor relations were realized. The results show that the optimal structural parameters are 0.496 mm corner spacing, 0.493 mm corner radian and 1.86 degrees corner taper, the fluid motion velocity of the high-pressure homogenizer increases from 234 m/s to 297 m/s under 30 MPa, and the velocity increases by 26.9%, and the particle size of the microsphere reaches the treatment effect of 50 MPa. The increase in kinetic energy indicates that the friction is overcome, the heat generation is reduced. The research has solved the problems of high pressure and overheating encountered in the process of homogeneous production, realized the social needs of efficient and green production, and provided support for the further development of homogenizer technology.

The objective of this study was to investigate the effects of diets supplemented with sodium stearoyl-2-lactylate (SSL), polyglycerol fatty acid ester (PGFE), and combined emulsifiers (0.02% SSL and 0.08% PGFE) on growth performance, nutrient digestibility, and plasma lipid profiles in weaned piglets and to further evaluate the possible effects of feeding exogenous emulsifiers on digestive enzyme activities and liver bile acid (BA) metabolism. Twenty-eight barrows (age at 35 d, Duroc × Landrace × Yorkshire) with an initial BW of 10.13 ± 0.16 kg were randomly assigned to 4 dietary treatment groups (7 pigs/treatment). Dietary treatment groups included the following: 1) basal diet (Control, CTR); 2) basal diet with 0.1% SSL (SSL); 3) basal diet with 0.1% PGFE (PGFE); and 4) basal diet with 0.08% PGFE+0.02% SSL (PG-SL). SSL diet increased ADG and ADFI of piglets during day 0 to 17 (P < 0.05) compared with the CTR treatment. Piglets fed emulsifier diets experienced a significant improvement in the digestibility of nutrients (DM, CP, ether extract, energy, calcium, and phosphorus) during the first 17 d (P < 0.05). The level of low-density lipoprotein cholesterol (LDL-C) was lower in the PGFE and PG-SL treatment groups than in the CTR treatment group (P < 0.05). Feeding emulsifier diets increased the lipase activity of the pancreas when compared with the CTR diet (P < 0.05). Moreover, the emulsifier diets significantly increased the mRNA expression of FXR (P < 0.05) and decreased the mRNA expression of CYP27A1 (P < 0.05) in the liver. In conclusion, the addition of emulsifiers improved nutrient digestibility and increased the mRNA expression of FXR BA receptors while inhibiting the mRNA expression of BA biosynthesis by CYP27A1 in weanling piglets.

At present, glyphosate (GLP) is the most produced and used herbicide in the world. With the large-scale use of glyphosate-based herbicides (GBHs), their toxic effects on animals and plants have increasingly become a concern. Based on the Codex Alimentarius Commission (CODEX) dose (20 mg kg−1) and the dose set by the government (40 mg kg−1), four experimental groups in which Roundup® (R) herbicide was added to the feed of weaned piglets at GLP concentrations of 0, 10, 20, and 40 mg kg−1 were designed. The results showed that R had no significant effect on the vulvar size or index of reproductive organs but that it could affect the tissue morphology and ultrastructure of the uterus and ovary. With the increase in GLP concentration, the activities of antioxidant enzymes [SOD (P

The present study investigated the effects of protein restriction and antibiotics on the hypothalamus-pituitary-liver growth axis during the compensatory growth of growing and finishing pigs. Growth performance, serum hormones, and messenger RNA (mRNA) levels of hormones and their receptors in growth axis tissues were recorded for analyses. A total of 64 piglets (large white × Landrace × Duroc cross) with an initial weight of 10.07 ± 0.14 kg were randomly divided into 4 treatment groups of 16 piglets per group. The dietary treatments consisted of 2 protein levels (14% and 20%) and 2 antibiotic levels (no antibiotics and 20 mg/kg colistin sulfate with 50 mg/kg kitasamycin) in a 2 × 2 factorial arrangement. The study was performed over 30 d for the first stage (S1, restriction phase) and 74 d for the second stage (S2, realimentation phase). The 4 treatment diets were maintained throughout the duration in the restriction phase. The 4 groups were fed the same diet in the realimentation phase. The trial period totaled 104 d. Protein restriction decreased BW, average daily food intake, and ADG in weaning pigs (P0.01) and induced compensatory growth after feeding a normal diet during the growth of finishing pigs. Average daily gain increased during the last phase of compensatory growth (P0.01). Protein restriction increased serum GH and leptin (LEP) and the mRNA levels of liver IGF-1 receptor (IGF-1-R; P0.01) but decreased serum IGF-1 (P0.01) and the mRNA levels of liver GH receptor (GH-R; P0.01) and IGF-1 (P0.05) in weaning piglets. Serum GH was increased, but serum IGF-1 was decreased during the realimentation phase (P0.05). Antibiotics increased the mRNA levels of GHRH (P0.05) and decreased somatostatin (P0.01) in the hypothalamus of weaning pigs. Protein restriction and antibiotics had no interactions across the entire trial. In conclusion, the slowing of growth caused by early protein restriction may be compensated for in the later stages of pig raising, and the mechanism of compensation is related to the regulation of GH, IGF-1, GH-R, and IGF-1-R.

Compensatory growth that can enhance the growth rate of animals and has been used commonly in production. However, the underlying mechanism is largely unknown, and the long-term effects of early protein restriction (PR) on pigs mostly remain unclear. This study aimed to investigate the long-term effects of early dietary protein restriction maintaining levels of lysine, methionine, threonine, and tryptophan on protein absorption and metabolism in pigs during the grower phase. Sixty-four weaning piglets (10.0 ± 0.73 kg) were divided into two groups: a control (NP, 200 g/kg crude protein, CP) and a protein-restricted group (RP, 140 g/kg CP). After a 30-day PR, both groups were offered the same diets ad libitum for another 74 days. PR to day 30 inhibited the growth of pigs but tended to enhance growth rate (P = 0.076) and significantly improved feed: gain in the period 70−104 days. PR significantly decreased (P

Glyphosate (GLP), the most widely used and productive pesticide worldwide, which safety and reliability gradually become a social concern. It is important to explore the toxic of GLP on the limitation level by governments on piglets and the potential role of hepatic CAR/PXR and Keap1-Nrf2 pathways in low levels of glyphosate detoxification. Compared with the control group, the production performance and organ index of GLP group showed no significant change. However, the liver GLP residue of 40 mg/kg group was significantly higher than the control group. We also found that the activity of ALP increased linearly and DBIL content increased quadratically. Furthermore, GLP could significantly increase SOD and GSH-Px and decrease T-AOC and CAT activities and significantly increase MDA and H2O2 contents (P < 0.05); however, the genes expression of Keap1/Nrf2 pathway was not affected. Gene expression of CAR/PXR pathway showed that GLP could significantly stimulate the expression of CAR, but it could not affect the expression of phase Ⅰ (CYP1A1, CYP1A2, CYP2E1, CYP2A19, CYP3A29), phase Ⅱ (UGT1A6, GSTA1, GSTA2) detoxification enzymes and transporters (MDR1, MRP2, P-gp). Our study showed that although 10-40 mg/kg GLP would inevitably cause some liver damage and dysfunction, it can self-alleviating the toxic effect of GLP.

At present, the public is paying more attention to the adverse effects of pesticides on human and animal health and the environment. Glyphosate is a broad-spectrum pesticide that is widely used in agricultural production. In this manuscript, the effects of diets containing glyphosate on intestinal morphology, intestinal immune factors, intestinal antioxidant capacity and the mRNA expression associated with the Nrf2 signaling pathway were investigated in weaned piglets. Twenty-eight healthy female hybrid weaned piglets (Duroc × Landrace × Yorkshire) were randomly selected with an average weight of 12.24 ± 0.61 kg. Weaned piglets were randomly assigned into 4 treatment groups and fed a basal diet supplemented with 0, 10, 20, and 40 mg/kg glyphosate for a 35-day feeding trial. We found that glyphosate had no effect on intestinal morphology. In the duodenum, glyphosate increased the activities of CAT and SOD (linear, P 0.05) and increased the levels of MDA (linear and quadratic, P 0.05). In the duodenum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P 0.05) and NQO1 (linear and quadratic, P 0.05) and reduced the relative mRNA expression levels of GPx1, HO-1 and GCLM (linear and quadratic, P 0.05). In the jejunum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P 0.05) and decreased the relative mRNA expression levels of GCLM (linear and quadratic, P 0.05). Glyphosate increased the mRNA expression levels of IL-6 in the duodenum (linear and quadratic, P 0.05) and the mRNA expression levels of IL-6 in the jejunum (linear, P 0.05). Glyphosate increased the mRNA expression of NF-κB in the jejunum (linear, P = 0.05). Additionally, the results demonstrated that glyphosate linearly decreased the ZO-1 mRNA expression levels in the jejunum and the mRNA expression of claudin-1 in the duodenum (P 0.05). In the duodenum, glyphosate increased the protein expression levels of Nrf2 (linear, P = 0.025). Overall, glyphosate exposure may result in oxidative stress in the intestines of piglets, which can be alleviated by enhancing the activities of antioxidant enzymes and self-detoxification.