Response Surface Optimization of Polysaccharides from Jaboticaba (Myrciaria cauliflora [Mart.] O.Berg) Fruits: Ultrasound-Assisted Extraction, Structure Properties, and Antioxidant/Hypoglycemic Activities.

Ultrasound-assisted extraction (UAE) method proves to be more effective compared to traditional extraction methods. In the present study, response surface methodology (RSM) was used to determine the optimal process parameters for extracting polysaccharides (U-MCP) from jaboticaba fruit using UAE. The optimum extraction conditions were ultrasonic time 70 min, extraction temperature 60 °C, and power 350 W. Under these conditions, the sugar content of U-MCP was 52.8 %. The molecular weights of the ultrasound-assisted extracted U-MCP ranged from 9.52×102 to 3.27×103  Da, and consisted of five monosaccharides including mannose, galacturonic acid, glucose, galactose, and arabinose. Moreover, in vitro antioxidant and hypoglycaemic assay revealed that U-MCP has prominent anti-oxidant activities (1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals, hydroxyl radicals and 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulfonic Acid Ammonium Salt) (ABTS) radicals scavenging activities) and hypoglycemic activities (α-amylase and α-glucosidase inhibition activities).

Drug delivery nanoparticles for preventing implant bacterial infections based on the bacteria and immunity mechanisms.

Implant dysfunction and failure during medical treatment can be attributed to bacterial infection with Staphylococcus aureus and Enterococcus faecalis, which are the prevalent strains responsible for implant infections. Currently, antibiotics are primarily used either locally or systemically to prevent and treat bacterial infections in implants. However, the effectiveness of this approach is unsatisfactory. Therefore, the development of new antimicrobial medications is crucial to address the clinical challenges associated with implant infections. In this study, a nanoparticle (ICG+RSG) composed of indocyanine green (ICG) and rosiglitazone (RSG), and delivered using 1,2-dipalmitoyl-snglycero-3-phosphocholine (DPPC) was prepared. ICG+RSG has photothermal and photodynamic properties to eliminate bacteria at the infection site by releasing reactive oxygen species and increasing the temperature. Additionally, it regulates phagocytosis and macrophage polarization to modulate the immune response in the body. ICG+RSG kills bacteria and reduces tissue inflammation, showing potential for preventing implant infections.

Microenvironment-Regulating Drug Delivery Nanoparticles for Treating and Preventing Typical Biofilm-Induced Oral Diseases.

The oral cavity comprises an environment full of microorganisms. Dysregulation of this microbial-cellular microenvironment will lead to a series of oral diseases, such as implant-associated infection caused by Staphylococcus aureus (S. aureus) biofilms and periodontitis initiated by Streptococcus oralis (S. oralis). In this study, a liposome-encapsulated indocyanine green (ICG) and rapamycin drug-delivery nanoparticle (ICG-rapamycin) is designed to treat and prevent two typical biofilm-induced oral diseases by regulating the microbial-cellular microenvironment. ICG-rapamycin elevates the reactive oxygen species (ROS) and temperature levels to facilitate photodynamic and photothermal mechanisms under near-infrared (NIR) laser irradiation for anti-bacteria. In addition, it prevents biofilm formation by promoting bacterial motility with increasing the ATP levels. The nanoparticles modulate the microbial-cellular interaction to reduce cellular inflammation and enhance bacterial clearance, which includes promoting the M2 polarization of macrophages, upregulating the anti-inflammatory factor TGF-ß, and enhancing the bacterial phagocytosis of macrophages. Based on these findings, ICG-rapamycin is applied to implant-infected and periodontitis animal models to confirm the effects in vivo. This study demonstrates that ICG-rapamycin can treat and prevent biofilm-induced oral diseases by regulating the microbial-cellular microenvironment, thus providing a promising strategy for future clinical applications.

Lighting up metastasis process before formation of secondary tumor by phosphorescence imaging.

Metastasis is the leading cause of cancer-related deaths; until now, the detection of tumor metastasis is mainly located at the period that secondary tumors have been formed, which usually results in poor prognosis. Thus, fast and precise positioning of organs, where tumor metastases are likely to occur at its earliest stages, is essential for improving patient outcomes. Here, we demonstrated a phosphorescence imaging method by organic nanoparticles to detect early tumor metastasis progress with microenvironmental changes, putting the detection period ahead to the formation of secondary tumors. In the orthotopic and simulated hematological tumor metastasis models, the microenvironmental changes could be recognized by phosphorescence imaging at day 3, after tumor implantation in liver or intravenous injection of cancer cells. It was far ahead those of other reported imaging methods with at least 7 days later, providing a sensitive and convenient method to monitor tumor metastases at the early stage.

Mitochondrial Transfer Regulates Cell Fate Through Metabolic Remodeling in Osteoporosis.

Mitochondria are the powerhouse of eukaryotic cells, which regulate cell metabolism and differentiation. Recently, mitochondrial transfer between cells has been shown to direct recipient cell fate. However, it is unclear whether mitochondria can translocate to stem cells and whether this transfer alters stem cell fate. Here, mesenchymal stem cell (MSC) regulation is examined by macrophages in the bone marrow environment. It is found that macrophages promote osteogenic differentiation of MSCs by delivering mitochondria to MSCs. However, under osteoporotic conditions, macrophages with altered phenotypes, and metabolic statuses release oxidatively damaged mitochondria. Increased mitochondrial transfer of M1-like macrophages to MSCs triggers a reactive oxygen species burst, which leads to metabolic remodeling. It is showed that abnormal metabolism in MSCs is caused by the abnormal succinate accumulation, which is a key factor in abnormal osteogenic differentiation. These results reveal that mitochondrial transfer from macrophages to MSCs allows metabolic crosstalk to regulate bone homeostasis. This mechanism identifies a potential target for the treatment of osteoporosis.

GFNet: Automatic segmentation of COVID-19 lung infection regions using CT images based on boundary features.

In early 2020, the global spread of the COVID-19 has presented the world with a serious health crisis. Due to the large number of infected patients, automatic segmentation of lung infections using computed tomography (CT) images has great potential to enhance traditional medical strategies. However, the segmentation of infected regions in CT slices still faces many challenges. Specially, the most core problem is the high variability of infection characteristics and the low contrast between the infected and the normal regions. This problem leads to fuzzy regions in lung CT segmentation. To address this problem, we have designed a novel global feature network(GFNet) for COVID-19 lung infections: VGG16 as backbone, we design a Edge-guidance module(Eg) that fuses the features of each layer. First, features are extracted by reverse attention module and Eg is combined with it. This series of steps enables each layer to fully extract boundary details that are difficult to be noticed by previous models, thus solving the fuzzy problem of infected regions. The multi-layer output features are fused into the final output to finally achieve automatic and accurate segmentation of infected areas. We compared the traditional medical segmentation networks, UNet, UNet++, the latest model Inf-Net, and methods of few shot learning field. Experiments show that our model is superior to the above models in Dice, Sensitivity, Specificity and other evaluation metrics, and our segmentation results are clear and accurate from the visual effect, which proves the effectiveness of GFNet. In addition, we verify the generalization ability of GFNet on another "never seen" dataset, and the results prove that our model still has better generalization ability than the above model. Our code has been shared at https://github.com/zengzhenhuan/GFNet.

[Construction strategies and prospect of the Global Medicinal Plant Stem Cell Bank].

Medicinal plant stem cells are separated from the meristem and vascular cambium of medicinal plants, which can produce active components for preventing and treating diseases and improving body physical functions under certain conditions. Medicinal plant stem cells come from a broad category of medicinal plants, including ethnic medicinal plants, folk medicinal plants, original plants of health products, vegetables, fruits, and other potential medicinal plants. At present, the techniques for the isolation, identification, preservation and culture of medicinal plant stem cells have become increasingly mature, and the mechanism of stem cell differentiation, growth and regulation of secondary metabolites has been studied in depth. Medicinal plant stem cells have a broad application prospect in medicine, health food, food and medical beauty products. As a strategic resource, the construction of the "Global Medicinal Plant Stem Cell Bank" was first proposed to preserve various kinds of medicinal plant resources in the world, and it will go global relying on the internationalization strategy of traditional Chinese medicine. The bank should follow safety, environmental protection, advanced and practical design principles. The main construction contents include the original plant bank, stem cell bank, component resource bank, gene bank, database and resource sharing system, with genetic and data resources incorporated into the scope of protection and utilization. The bank will establish a new strategy for medicinal plant resources protection and regeneration, and provide a new resource for natural products drug discovery and a technology sharing platform for various medicinal plant stem cells. As a resource treasury, a source of innovative technologies and a center of cooperation, it will become the core driving force of the global medicinal plant stem cell industry.

Nanoparticles Promote Bacterial Antibiotic Tolerance via Inducing Hyperosmotic Stress Response.

With the rapid development of nanotechnology, nanoparticles (NPs) are widely used in all fields of life. Nowadays, NPs have shown extraordinary antimicrobial activities and become one of the most popular strategies to combat antibiotic resistance. Whether they are equally effective in combating bacterial persistence, another important reason leading to antibiotic treatment failure, remains unknown. Persister cells are a small subgroup of phenotypic drug-tolerant cells in an isogenic bacterial population. Here, various types of NPs are used in combination with different antibiotics to destroy persisters. Strikingly, rather than eradicating persister cells, a wide range of NPs promote the formation of bacterial persistence. It is uncovered by PCR, thermogravimetric analysis, intracellular potassium ion staining, and molecular dynamics simulation that the persister promotion effect is achieved through exerting a hyperosmotic pressure around the cells. Moreover, protein mass spectrometry, fluorescence microscope images, and SDS-PAGE indicate NPs can further hijack cell osmotic regulatory circuits by inducing aggregation of outer membrane protein OmpA and OmpC. These findings question the efficacy of using NPs as antimicrobial agents and raise the possibility that widely used NPs may facilitate the global emergence of bacterial antibiotic tolerance.

Mobile Phone Flashlight-Excited Red Afterglow Bioimaging.

Organic room temperature phosphorescence (RTP) materials with ultralong lifetime possess the remarkable advantage in bioimaging for elimination of background noise by characteristic time scale. However, most of RTP luminogens need to be excited by the harmful ultraviolet (UV) lamp, and exhibit green or yellow emission with shallow tissue penetration, constraining the in vivo bioimaging for further application in clinical diagnosis and pathological study. In this text, the much safer excitation process by sunlight and mobile phone flashlight is realized by organic luminogens with various electronic pull-push systems. Moreover, the bright red RTP emission with lifetime up to 344 ms is achieved by optimizing molecular geometry and electronic property. Especially, the mobile phone flashlight-excited red afterglow imaging of lymph nodes in living mice has been realized for the first time, affording a safe and conventional approach to achieve the afterglow imaging of living mice with deep issue penetration and high signal-to-noise ratios.

Photothermal therapy may be a double-edged sword by inducing the formation of bacterial antibiotic tolerance.

Photothermal nanoparticles are thought to be the most suitable candidates against infectious disease by disrupting the cell membrane or inhibiting cellular metabolism. However, cells with low-metabolic activity states may be endowed with greater ability against harsh environments including antibiotic treatment. For now, it remains unexplored whether and how photothermal therapy (PTT) gives rise to bacterial antibiotic tolerance. In this study, we showed that although it exhibits excellent bactericidal ability, PTT with typical photothermal nanoparticle gold nanocages (AuNCs) can give rise to a subpopulation of cells with great ability of antibiotic tolerance. The subpopulation exhibits delayed growth and decreased cellular ATP levels, indicating a low metabolic state. Specifically, after AuNCs attach to the surface of a bacterial cell, photothermal manipulation can induce cell membrane shrinkage and block the bacterial respiratory chain. Besides, heat shock induces protein aggregation and leads to the dysfunction of a number of important proteins. The heat shock protein DnaK is closely associated with protein aggregation and plays a vital role in modulating antibiotic tolerance, providing a potential therapeutic target.

Cell-Membrane-Display Nanotechnology.

Advances in material science have set the stage for nanoparticle-based research with potent applications for the diagnosis, bioimaging, and precise treatment of diseases. Despite the wide range of biomaterials developed, the rational design of biomaterials with predictable bioactivity and safety remains a critical challenge. In recent years, the field of cell-membrane-based therapeutics has emerged as a promising platform for addressing unmet medical needs. The utilization of natural cell membranes endows biomaterials with a remarkable ability to serve as biointerfaces that interact with the host environment. To improve the function and efficacy of cell-membrane-based therapeutics, a series of novel strategies is developed as cell-membrane-display nanotechnology, which utilizes various methods to selectively display therapeutic molecules of cell membranes on nanoparticles. Although cell-membrane-display nanotechnology remains in the early phases, considerable work is currently being conducted in the field. This review discusses details of innovative strategies for displaying cell-membrane molecules, including the following: 1) displaying molecules of cell membranes on biomaterials, 2) pretreating cell membranes to induce increased expression of inherent molecules of cell membranes and enhance their function, and 3) inserting additional functional molecules on cell membranes. For each area, the theoretical basis, application scenarios, and potential development are highlighted.