Pectin from Citrus unshiu Marc. Alleviates Glucose and Lipid Metabolism by Regulating the Gut Microbiota and Metabolites.

The effects of pectin from Citrus unshiu Marc. on glycolipid metabolism, the morphologies of the pancreas and epididymal fat, the gut microbiota, and the metabolites of short-chain fatty acids (SCFAs) in db/db mice were investigated in this study. The results indicated that pectin reduced the levels of fasting blood glucose, glycated serum protein, triglycerides, total cholesterol, and low-density lipoprotein cholesterol while increasing the levels of high-density lipoprotein cholesterol. Meanwhile, pectin could improve the morphology of islet cells and inhibit the hypertrophy of adipocytes. Additionally, pectin not only regulated the intestinal flora dysbiosis in db/db mice, as shown by the increasing proportion of Firmicutes/Bacteroidetes and the relative abundance of Ligilactobacillus, Lactobacillus, and Limosilactobacillus, but also remedied the metabolic disorder of SCFAs in db/db mice. These results suggest that pectin could promote glucose and lipid metabolism by regulating the intestinal flora with changes in SCFA profile. This study proves that pectin might serve as a new prebiotic agent to prevent the disorder of glycolipid metabolism.

Efficient Reinforcement Learning from Demonstration via Bayesian Network-Based Knowledge Extraction.

Reinforcement learning from demonstration (RLfD) is considered to be a promising approach to improve reinforcement learning (RL) by leveraging expert demonstrations as the additional decision-making guidance. However, most existing RLfD methods only regard demonstrations as low-level knowledge instances under a certain task. Demonstrations are generally used to either provide additional rewards or pretrain the neural network-based RL policy in a supervised manner, usually resulting in poor generalization capability and weak robustness performance. Considering that human knowledge is not only interpretable but also suitable for generalization, we propose to exploit the potential of demonstrations by extracting knowledge from them via Bayesian networks and develop a novel RLfD method called Reinforcement Learning from demonstration via Bayesian Network-based Knowledge (RLBNK). The proposed RLBNK method takes advantage of node influence with the Wasserstein distance metric (NIW) algorithm to obtain abstract concepts from demonstrations and then a Bayesian network conducts knowledge learning and inference based on the abstract data set, which will yield the coarse policy with corresponding confidence. Once the coarse policy's confidence is low, another RL-based refine module will further optimize and fine-tune the policy to form a (near) optimal hybrid policy. Experimental results show that the proposed RLBNK method improves the learning efficiency of corresponding baseline RL algorithms under both normal and sparse reward settings. Furthermore, we demonstrate that our RLBNK method delivers better generalization capability and robustness than baseline methods.

Polysaccharide-based nanomedicines for cancer immunotherapy: A review.

Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics. However, direct administration of "naked" immunotherapeutic agents (such as nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target) efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, as they could interact with immune system to stimulate an enhanced immune response. Their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.

Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.

Recent advances in development of nanomedicines for multiple sclerosis diagnosis.

Multiple sclerosis (MS) is a neurodegenerative disease with a high morbidity and disease burden. It is characterized by the loss of the myelin sheath, resulting in the disruption of neuron electrical signal transmissions and sensory and motor ability deficits. The diagnosis of MS is crucial to its management, but the diagnostic sensitivity and specificity are always a challenge. To overcome this challenge, nanomedicines have recently been employed to aid the diagnosis of MS with an improved diagnostic efficacy. Advances in nanomedicine-based contrast agents in magnetic resonance imaging scanning of MS lesions, and nanomedicine-derived sensors for detecting biomarkers in the cerebrospinal fluid biopsy, or analyzing the composition of exhaled breath gas, have demonstrated the potential of using nanomedicines in the accurate diagnosis of MS. This review aims to provide an overview of recent advances in the application of nanomedicines for the diagnosis of MS and concludes with perspectives of using nanomedicines for the development of safe and effective MS diagnostic nanotools.

Functional gadolinium-based nanoscale systems for cancer theranostics.

Cancer theranostics is a new strategy for combating cancer that integrates cancer imaging and treatment through theranostic agents to provide an efficient and safe way to improve cancer prognosis. Design and synthesis of these cancer theranostic agents are crucial since these agents are required to be biocompatible, tumor-specific, imaging distinguishable and therapeutically efficacious. In this regard, several types of gadolinium (Gd)-based nanomaterials have been introduced to combine different therapeutic agents with Gd to enhance the efficacy of therapeutic agents. At the same time, the entire treatment procedure could be monitored via imaging tools due to incorporation of Gd ions, Gd chelates and Gd/other imaging probes in the theranostic agents. This review aims to overview recent advances in the Gd-based nanomaterials for cancer theranostics and perspectives for Gd nanomaterial-based cancer theranostics are provided.

Recent Advances in Nanomedicines for Multiple Sclerosis Therapy.

Multiple sclerosis (MS) is a neurological disorder characterized by loss of the myelin sheath. Since the myelin sheath could insulate nerve fibers from the surrounding environment, its loss would result in dysfunction of the affected neurons in transmitting electrical signals, thus leading to sensation and motor disabilities. The treatment of MS is accompanied by a low treatment efficacy due to the existence of the blood-brain barrier (BBB) and occurrence of side effects due to a poor targeting efficacy. To overcome these obstacles of traditional MS treatment methods, nanomedicines have recently been employed to deliver MS therapeutic agents to the lesions. With deep BBB penetration and specific targeting, these nano-based interventions have received positively encouraging results and become another potential MS treatment method with better therapeutic outcomes. This review will focus on recent advances in nanomedicines for the treatment of MS by critically analyzing their strengths and weaknesses. We will propose perspectives on the development of these MS therapeutic nanomaterials.