Nitrogen utilisation, energy utilisation and methane emissions of sheep grazing in two types of pasture.

Livestock grazing plays a significant role in maintaining grasslands and promoting animal production globally. To understand the livestock performance in sown pasture (SP) vs native pasture (NP) is important to ensure more effective grassland-livestock interactions with minimal environmental impact. A 2 (treatment) * 2 (period) Latin Square design experiment was conducted with 10 growing Hu sheep ♂ × thin-tailed Han sheep ♀ rams grazed perennially SP vs NP in an inland arid region of China. The objectives were to evaluate the effects of grazing management on nutrient digestibility, nitrogen (N) and energy utilisation and methane (CH4) emission. The N intake, N retained and energy intake (gross energy (GE), and digestible and metabolisable energy) of sheep grazing in SP were significantly increased compared with those grazing in NP. There were significant linear relationships between DM intake (DMI) (g/kg BW or g/kg BW0.75) or CH4 (g/kg BW or g/kg BW0.75) emissions and forage nutrient and GE concentrations within each grassland type. The linear regression analysis indicated that forage CP or ether extract concentration was a good predictor for DMI (g/kg BW or g/kg BW0.75) (R2 = 0.756 or 0.752), and CH4 emission could be predicted using forage nutrient and GE concentrations (R2 = 0.381-0.503). These results suggest that DMI and CH4 emissions per unit metabolic BW were accurately predicted by multiple-factor combinations of forage nutrients, including ether extract and CP paired with GE. The present output could provide useful information for the development of sustainable sheep grazing systems in the inland arid regions of the world.

Pharmacodynamic evaluation of the XOR inhibitor WN1703 in a model of chronic hyperuricemia in rats induced by yeast extract combined with potassium oxonate.

Hyperuricemia is a common disease caused by a disorder of purine metabolism, which often causes hyperlipidemia and other metabolic diseases. WN1703 was demonstrated to be an effective xanthine oxidoreductase (XOR) inhibitor in our previous study. Here, we evaluated the pharmacodynamic effect of WN1703 on rats suffering from chronic hyperuricemia accompanied by disorders of lipid metabolism. We discovered that WN1703 was an efficacious uric acid (UA)-lowering compound. Simultaneously, it had effect on relieving renal injury, regulating lipid metabolism by reducing levels of triglycerides and low-density lipoprotein-cholesterol, increasing levels of high-density lipoprotein-cholesterol, and improving renal and liver lesions. WN1703 also exhibited anti-inflammatory and antioxidant activity by alleviating the increasing trend of levels of tumor necrosis factor-α, interleukin-1ß, monocyte chemoattractant protein-1, and malondialdehyde, and improving the activity of superoxide dismutase and glutathione peroxidase. WN1703 appeared to be more effective than febuxostat in inhibiting XOR and had higher antioxidant activity. In general, the pharmacologic action of WN1703 showed a clear dose-effect relationship.

Vessel-Targeting Nanoclovers Enable Noninvasive Delivery of Magnetic Hyperthermia-Chemotherapy Combination for Brain Cancer Treatment.

Despite being promising, the clinical application of magnetic hyperthermia for brain cancer treatment is limited by the requirement of highly invasive intracranial injections. To overcome this limitation, here we report the development of gallic acid-coated magnetic nanoclovers (GA-MNCs), which allow not only for noninvasive delivery of magnetic hyperthermia but also for targeted delivery of systemic chemotherapy to brain tumors. GA-MNCs are composed of clover-shaped MNCs in the core, which can induce magnetic heat in high efficiency, and polymerized GA on the shell, which enables tumor vessel-targeting. We demonstrate that intravenous administration of GA-MNCs following alternating magnetic field exposure effectively inhibited brain cancer development and preferentially disrupted tumor vasculature, making it possible to efficiently deliver systemic chemotherapy for further improved efficacy. Due to the noninvasive nature and high efficiency in killing tumor cells and enhancing systemic drug delivery, GA-MNCs have the potential to be translated for improved treatment of brain cancer.

Anti-edema and antioxidant combination therapy for ischemic stroke via glyburide-loaded betulinic acid nanoparticles.

Stroke is a deadly disease without effective pharmacotherapies, which is due to two major reasons. First, most therapeutics cannot efficiently penetrate the brain. Second, single agent pharmacotherapy may be insufficient and effective treatment of stroke requires targeting multiple complementary targets. Here, we set to develop single component, multifunctional nanoparticles (NPs) for targeted delivery of glyburide to the brain for stroke treatment. Methods: To characterize the brain penetrability, we radiolabeled glyburide, intravenously administered it to stroke- bearing mice, and determined its accumulation in the brain using positron emission tomography-computed tomography (PET/CT). To identify functional nanomaterials to improve drug delivery to the brain, we developed a chemical extraction approach and tested it for isolation of nanomaterials from E. ulmoides, a medicinal herb. To assess the therapeutic benefits, we synthesized glyburide-loaded NPs and evaluated them in stroke- bearing mice. Results: We found that glyburide has a limited ability to penetrate the ischemic brain. We identified betulinic acid (BA) capable of forming NPs, which, after intravenous administration, efficiently penetrate the brain and significantly reduce ischemia-induced infarction as an antioxidant agent. We demonstrated that BA NPs enhance delivery of glyburide, leading to therapeutic benefits significantly greater than those achieved by either glyburide or BA NPs. Conclusion: This study suggests a new direction to identify functional nanomaterials and a simple approach to achieving anti-edema and antioxidant combination therapy. The resulting glyburide- loaded BA NPs may be translated into clinical applications to improve clinical management of stroke.

Single small molecule-assembled nanoparticles mediate efficient oral drug delivery.

Oral drug delivery, which requires surviving the harsh environment in the gastrointestinal (GI) tract and penetrating the intestinal epithelium, has not been achieved using simple formulation nanoparticles (NPs). Medicinal natural products (MNPs) have been widely used in traditional medicine for disease management through oral consumption. However, most pharmacologically active compounds within MNPs do not have the properties suitable for oral applications. We hypothesize that some MNPs contain natural nanomaterials that can convert those compounds into oral formulations by forming NPs. After screening 66 MNPs, we identified five classes of small molecules that form NPs, many of which are capable of efficient drug encapsulation and GI penetration. We show that one of them, dehydrotrametenolic acid (DTA), is capable of mediating oral delivery for effective disease treatment. We determine that DTA NPs assemble through hydrogen bonding and penetrate the GI tract via apical sodium-dependent bile acid transporter. Our study reveals a novel class of single component, small molecule- assembled NPs for oral drug delivery, and suggests a novel approach to modernizing MNPs through nanomaterial discovery.

Facile preparation of doxorubicin-loaded upconversion@polydopamine nanoplatforms for simultaneous in vivo multimodality imaging and chemophotothermal synergistic therapy.

The development of biosafe nanoplatforms with diagnostic and therapeutic multifunction is extremely demanded for designing cancer theranostic medicines. Here, a facile methodology is developed to construct a multifunctional nanotheranostic that gathers five functions, upconversion luminescence (UCL) imaging, T1-weighted magnetic resonance imaging (MRI), X-ray computed tomography (CT) imaging, photothermal therapy (PTT), and chemotherapy, into one single nanoprobe (named as UCNP@PDA5-PEG-DOX). For generating the UCNP@PDA5-PEG-DOX, a near-infrared light (NIR)-absorbing polydopamine (PDA) shell is directly coated on oleic-acid-capped ß-NaGdF4:Yb(3+),Er(3+)@ß-NaGdF4 upconverting nanoparticle (UCNP) core for the first time to form monodisperse, ultrastable, and noncytotoxic core-shell-structured nanosphere via water-in-oil microemulsion approach. When combined with 808 nm NIR laser irradiation, the UCNP@PDA5-PEG-DOX shows great synergistic interaction between PTT and the enhanced chemotherapy, resulting in completely eradicated mouse-bearing SW620 tumor without regrowth. In addition, leakage study, hemolysis assay, histology analysis, and blood biochemistry assay unambiguously reveal that the UCNP@PDA5-PEG has inappreciable cytotoxicity and negligible organ toxicity. The results provide explicit strategy for fabricating multifunctional nanoplatforms from the integration of UCNP with NIR-absorbing polymers, important for developing multi-mode nanoprobes for biomedical applications.