A bioinspired supramolecular nanoprodrug for precision therapy of B-cell non-Hodgkin's lymphoma.

Fludarabine (FA) is still considered as a first-line chemotherapy drug for hematological tumors related to B lymphocytes. However, it is worth noting that the non-specific distribution and non-different cytotoxicity of FA may lead to irreversible consequences such as central nervous system damage such as blindness, coma, and even death. Therefore, it is very important to develop a system to targeting delivery FA. In preliminary studies, it was found that B lymphoma cells would specific highly expressing the sialic acid-binding immunoglobulin-like lectin 2 (known as CD22). Inspired by the specific recognition of sialic acid residues and CD22, we have developed a supramolecular prodrug based on polysialic acid, an endogenous biomacromolecule, achieving targeted-therapy of B-cell non-Hodgkin's lymphoma (B-NHL). Specifically, the prepared hydrophobic reactive oxygen species-responsive FA dimeric prodrug (F2A) interacts with the TPSA, which polysialic acid were modified by the thymidine derivatives, through non-covalent intermolecular interactions similar to "Watson-Crick" base pairing, resulting in the formation of nanoscale supramolecular prodrug (F@TPSA). Cell experiments have confirmed that F@TPSA can be endocytosed by CD22+ B lymphoma cells including Raji and Ramos cells, and there is a significant difference of endocytosis in other leukocytes. Furthermore, in B-NHL mouse model, compared with FA, F@TPSA is determined to have a stronger tumor targeting and inhibitory effect. More importantly, the distribution of F@TPSA in vivo tends to be enriched in lymphoma tissue rather than nonspecific, thus reducing the leukopenia of FA. The targeted delivery system based on PSA provides a new prodrug modification strategy for targeted treatment of B-NHL.

Macrocycle-Based Supramolecular Drug Delivery Systems: A Concise Review.

Efficient delivery of therapeutic agents to the lesion site or specific cells is an important way to achieve "toxicity reduction and efficacy enhancement". Macrocycles have always provided many novel ideas for drug or gene loading and delivery processes. Specifically, macrocycles represented by crown ethers, cyclodextrins, cucurbit[n]urils, calix[n]arenes, and pillar[n]arenes have unique properties, which are different cavity structures, good biocompatibility, and good stability. Benefited from these diverse properties, a variety of supramolecular drug delivery systems can be designed and constructed to effectively improve the physical and chemical properties of guest molecules as needed. This review provides an outlook on the current application status and main limitations of macrocycles in supramolecular drug delivery systems.

Photovoltaic panel waste assessment and embodied material flows in China, 2000-2050.

Solar photovoltaics (PV) is one of the most promising renewable energy sources for climate change mitigation. However, not all green energy installations may not continue to be sustainable after their service life. With the largest installed solar capacity in the world, China is expected to face significant challenges in managing the end-of-life (EoL) PV panels in the coming decades, which have not been well addressed yet.Further, the massive deployment and planning of solar energy systems in China has led to a dramatic increases in demand for raw materials, which places more pressure on the available resources. In this study, we have developed a dynamic, technology-based material flow analysis model to clarify the stock, flow and secondary supply potential of waste PV panel materials in China from 2000 to 2050. The waste generation and circular flow characteristics of the component materials in PV panels are comprehensively investigated, which set important boundary conditions for the recovery and recycling of key materials. The results show that approximately 134 million metric tons (Mt) and 72 Mt of waste PV panels will be cumulatively generated in China up to 2050 under the early loss and regular loss scenarios, respectively. Polysilicon glass accounts for the largest share of PV waste, nearly 64% by weight, followed by aluminum (16%) and steel (11%). Precious metals such as Ag, Ga, In, and Te, account for less than 1% of the total PV waste, but can provide considerable economic benefits if recycled wisely. The potential of secondary resources from PV waste may reduce the supply pressure on the natural materials to some extent, but they could not fully mitigate the material supply resks. We suggest that stakeholders in the solar energy industry should take urgent actions, including recycling technology innovations, effective collection systems and incentive measures, to address the growing challenge of waste PV panels in China.

Extraction of Polysaccharides from Root of Pseudostellaria heterophylla (Miq.) Pax. and the Effects of Ultrasound Treatment on Its Properties and Antioxidant and Immune Activities.

The hydrophilic polysaccharides (PS) were isolated and purified from the tuberous roots of Pseudostellaria heterophylla. The extraction process of PS from Pesudostellariae radix was optimized by single-factor experiments and orthogonal design. The extract was purified by DEAE cellulose column to obtain the pure polysaccharide PHP. Then PHP was treated with different intensities of sonication to study the effect of sonication on PHP's characteristics and its biological activity in vitro and in vivo. The results of this study revealed that ultrasound treatment did not significantly change the properties of PHP. Further, with the increase of ultrasound intensity, PHP enhanced the proliferation and phagocytosis of macrophage RAW264.7. Meanwhile, it could also significantly improve the body's antioxidant activity and immune function. The results of this study demonstrated that PHP has the potential as a food additive with enhanced antioxidant and immune functions, and its biological activities could be enhanced by sonication.

Mannose Receptor-Mediated Carbon Nanotubes as an Antigen Delivery System to Enhance Immune Response Both In Vitro and In Vivo.

Carbon nanotubes (CNTs) are carbon allotropes consisting of one, two, or more concentric rolled graphene layers. These can intrinsically regulate immunity by activating the innate immune system. Mannose receptors (MR), a subgroup of the C-type lectin superfamily, are abundantly expressed on macrophages and dendritic cells. These play a crucial role in identifying pathogens, presenting antigens, and maintaining internal environmental stability. Utilizing the specific recognition between mannose and antigen-presenting cells (APC) surface mannose receptors, the antigen-carrying capacity of mannose-modified CNTs can be improved. Accordingly, here, we synthesized the mannose-modified carbon nanotubes (M-MWCNT) and evaluated them as an antigen delivery system through a series of in vitro and in vivo experiments. In vitro, M-MWCNT carrying large amounts of OVA were rapidly phagocytized by macrophages and promoted macrophage proliferation to facilitate cytokines (IL-1ß, IL-6) secretion. In vivo, in mice, M-MWCNT induced the maturation of dendritic cells and increased the levels of antigen-specific antibodies (IgG, IgG1, IgG2a, IgG2b), and cytokines (IFN-γ, IL-6). Taken together, M-MWCNT could induce both humoral and cellular immune responses and thereby can be utilized as an efficient antigen-targeted delivery system.

Enhancement of immune responses using ovalbumin-conjugated Eucommia ulmoides leaf polysaccharides encapsulated in a cubic liquid-crystalline phase delivery system.

BACKGROUND: To improve the adjuvant activity of polysaccharides from Eucommia ulmoides leaves (PsEUL) in inducing an effective immune response against ovalbumin (OVA), PsEUL were conjugated to OVA using the N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) method. The synthesized PsEUL-OVA was encapsulated using phytantriol and F127 to produce PsEUL-OVA cubosomes (Cubs), a novel delivery system. The physicochemical properties and immune modulation effects of this novel delivery system were explored. RESULTS: In vitro, PsEUL-OVA/Cubs carrying large amounts of OVA were rapidly phagocytized by macrophages and upregulated macrophage proliferation, thereby stimulating cytokine production (interleukin (IL)-6 and IL-4). In vivo, PsEUL-OVA/Cubs increased the titer of OVA-specific antibodies (immunoglobulin (Ig)G, IgG2b, IgG2a and IgG1) and cytokine levels (IL-2, IL-6, IL-4 and interferon-γ). In addition, the cubosomes promoted the differentiation of CD8+ and CD4+ T cells in the spleen and the maturation of dendritic cells (DCs). These results indicated that PsEUL-OVA/Cubs stimulated both cellular and humoral immune responses by enhancing the phagocytic activity of DCs and macrophages and increasing the antigen presentation efficiency. CONCLUSION: Collectively, the findings demonstrate that PsEUL-antigen/Cubs can be a useful delivery vehicle with immune response-promoting effects. Therefore, this study lays the foundation for the development of novel adjuvant-antigen delivery systems with potential applications in vaccine design. © 2022 Society of Chemical Industry.

Study on Extraction Process of Root of Henry Wood Betony Polysaccharides and Their Antitumor Activity against S180.

We optimized the hot water extraction of polysaccharides from the root of Henry wood betony (RHWPs) using a uniform test and explored their anti-tumor activities in vitro and in vivo. The optimal extraction conditions were as follows: 40 min extraction time, liquid/solid ratio 30 mL/g, 100 min soaking time, two extraction cycles, 100% ethanol concentration, and extraction temperature of 80 °C. The molecular weight distribution of RHWPs with MWs was 228,600 g/mol and 5001 g/mol. The IR spectrum further indicated that RHWPs are acidic polysaccharides containing pyranose and furan rings. The main monosaccharides found in RHWPs were mannose, ribose, l-rhamnose monohydrate, glucuronic acid, galacturonic acid, glucose, galactose, xylose, arabinose, and fucose. RHWPs inhibited the proliferation of S180 tumor cells and induced apoptosis in vitro. Oral administration of RHWPs to tumor-bearing mice significantly inhibited the growth of the S180 xenografts, accelerated apoptosis in tumor cells, and expanded the necrotic regions. Furthermore, RHWPs also markedly increased the levels of TNF-α, IFN-γ, and IL-2 in the sera of tumor-bearing mice, and activated immune cells such as lymphocytes, NK cells, and macrophages, thereby inducing tumor cell apoptosis. Taken together, RHWPs are a promising anti-tumor agent that ought to be explored further.

Spatial-temporal evolutions of groundwater environment in prairie opencast coal mine area: a case study of Yimin Coal Mine, China.

The interactions between groundwater and its environment was investigated in prairie mining area in this study, through the groundwater system evolutions in mining area before and after the mining actions (from 1973 to 2016) of Yimin coal mine. The results showed that (1) the mining activities of the open-pit coal changed the original reduction environment into the oxidizing environment in the mining area. The pyrite and sulfur-bearing coal in the stratum oxidized, produced acid and triggered a series of subsequent reactions, resulting in the decrease in the pH value of the groundwater in the mining area. The concentration of SO42-, Fe2+, Fe3+, Ca2+ and Mg2+ and the total hardness increased. The regional hydrochemical type evolved from HCO3-Na·Ca·Mg type before mining to the type of HCO3·SO4-Na·Ca·Mg after mining. (2) Coal mining strongly draining underground water accelerated the regional groundwater circulation, and then made the groundwater desalination. The concentrations of TDS, COD and Na++K+ in the mining area all showed a decreasing trend. (3) The coal mining activities made the calcite and dolomite in saturated state under the natural condition of underground water to be unsaturated again. The hydro-geochemical action evolves from double control (water-rock interaction and evaporation-concentration) to water-rock interaction control.

Immunomodulatory Effects of Phosphorylated Radix Cyathulae officinalis Polysaccharides in Immunosuppressed Mice.

This research aimed to investigate the immunomodulatory effects of phosphorylated Radix Cyathulae officinalis Kuan polysaccharides (pRCPS) in immunosuppressed mice, improving their cellular and humoral immune function. Our results showed that pRCPS increased serum immunoglobulin (IgG, IgA, IgM) concentrations significantly, enhanced splenocyte proliferation, and the thymus and spleen indices. pRCPS also promoted phagocytosis in peritoneal macrophages and enhanced cytokine (IFN-γ, IL-2, -4, -5, -6, and -10) serum levels. Importantly, pRCPS increased the proportions of selected T cell subpopulations (CD3+, CD4+, and the CD4+ to CD8+ ratio). Our results revealed that phosphorylation of the polysaccharides promoted their immune-enhancing effects. Thus, pRCPS can enhance cellular and humoral immunity and could be used as an immune-enhancing agent to overcome cyclophosphamide (CY)-induced immunosuppression.

Phosphorylated Radix Cyathulae officinalis Polysaccharides Act as Adjuvant via Promoting Dendritic Cell Maturation.

The aim of this study was to investigate whether phosphorylated Radix Cyathulae officinalis Kuan polysaccharides (pRCPS) used as adjuvant with foot-and-mouth disease vaccine (FMDV) can stimulate specific humoral and cellular immune responses in ICR mice. The results demonstrated that pRCPS significantly up-regulated FMDV-specific IgG, IgG1, IgG2b and IgG2a antibody levels and splenocyte proliferation. pRCPS also promoted the killing activities of cytotoxic T lymphocytes (CTL) and natural killer cells (NK). In addition, pRCPS enhanced the expression levels of IL-2, IL-4, and IFN-γ in CD4⁺ T cells and the level of IFN-γ in CD8⁺ T cells. Importantly, pRCPS enhanced the expression of MHCII, CD40⁺, CD86⁺, and CD80⁺ in dendritic cells (DCs). This study indicated that phosphorylation modification could increase immune-enhancing activities of RCPS, and pRCPS could promote humoral and cellular immune responses through facilitating DC maturation.

[The Development of the Supermicroinvasive Magnetic Anchoring Laparoscopic System].

A magnetic anchoring supermicroinvasive laparoscopic system, including in vitro magnetic navigation handle and in vivo magnetic anchor laparoscopy is introduced. The magnetic anchor laparoscopic comprises an outer cannula, two data lines, a camera, a high color temperature LED light and two inner magnets. It is tiny enough to enter the abdominal cavity through conventional laparoscopic trocar and achieve orientation, navigation as wel as adjustment thefi eld of view within the abdominal cavity by attracting with the in vitro magnetic handle, thus it does not take up space of the laparoscopic trocar in working state. The system which can not only apply in single-port laparoscopic surgery based on a single traditional laparoscopic trocar but also apply in traditional laparoscopic surgery with less trocar, wil enhance the extent of minimaly invasive surgery and reduce the operation diffi culty at the same time. The clinical application of the system wil optimize the minimaly invasive techniques and benefi t the patients.

Sulfated radix Cyathulae officinalis polysaccharides act as adjuvant via promoting the dendritic cell maturation and suppressing Treg frequency.

This study was conducted to evaluate the adjuvant potential of sulfated Radix Cyathulae officinalis Kuan polysaccharides (sRCPS) and their effects on specific cellular and humoral immune responses to hepatitis B subunit vaccine in mice. Our data demonstrated that sRCPS significantly promoted the rHBsAg-specific IgG, IgG1, IgG2a, and IgG2b antibody titers, the activities of natural killer cells (NK) and cytotoxic T lymphocytes (CTL), T cells proliferation, and phagocytic capacity of peritoneal macrophages. Furthermore, sRCPS increased the levels of IL-4, IL-2, and IFN-γ in CD4(+)T cells and the level of IFN-γ in CD8(+)T cells. In addition, sRCPS enhanced the expression of CD40(+), CD80(+), CD86(+), MHC I and MHC II in dendritic cells (DCs) and upregulated the mRNA levels of MHC I, MHC II. sRCPS downregulated the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells. sRCPS increased both cellular and humoral immune responses by upregulating DC maturation, and suppressing the frequency of Treg cells.

Mucosal and systemic immunity in mice after intranasal immunization with recombinant Lactococcus lactis expressing ORF6 of PRRSV.

The purpose of the study was to construct mucosal vaccine of a recombinant Lactococcus lactis expressing PRRSV ORF6 gene and evaluate mucosal and systemic immune response against PRRSV in mice after intranasal immunization. The result show that the vaccine can stimulate mice to produce specific IgG in serum and remarkable special s-IgA in lung lavage fluid, at the same time, the contents of cytokines IL-2 and IFN-γ of the experimental group were significant higher than those of the control group (P < 0.01), however, the contents of cytokines IL-4 was not different to the all groups. In summary, the constructed mucosal vaccine can significantly induce mucosal immune, humoral immunity and cellular immunity involved Th1 type cytokines, which will lay a theoretical foundation on immune mechanism and new efficient vaccines for PRRSV.

Self-assembly of nano/micro-structured Fe3O4 microspheres among 3D rGO/CNTs hierarchical networks with superior lithium storage performances.

Nano/micro-structured Fe3O4 microspheres among three-dimensional (3D) reduced graphene oxide (rGO)/carbon nanotubes (CNTs) hierarchical networks (the ternary composite is denoted as rGCFs) have been synthesized using a facile, self-assembled and one-pot hydrothermal approach. The rGCFs composite exhibits superior lithium storage performances: initial discharge and charge capacities of 1452 and 1036 mAh g(-1), respectively, remarkable rate capability at current densities from 100 mA g(-1) to 10 A g(-1) and outstanding cycling performance up to 200 cycles. The highly enhanced electrochemical performances of rGCFs depend heavily on the robust 3D rGO/CNTs hierarchical networks, the stable nano/microstructures of active Fe3O4 microspheres and the positive synergistic effects of building components. The systematic structure characterizations and electrochemical investigations provide insightful understanding towards the relationship between structure/morphology and lithium storage performances, which may pave the way for the rational design of composite materials with desirable goals.

Network pharmacology and molecular docking to explore the treatment potential and molecular mechanism of Si-Miao decoction against gouty arthritis.

Gouty arthritis (GA) is a common metabolic rheumatological disease. Si-Miao decoction has therapeutic effects on GA. In our study, we investigated the mechanism of Si-Miao decoction against GA using network pharmacology and molecular docking analytical methods. The Traditional Chinese Medicine Systems Pharmacology Database was used as the basis for screening the main targets and agents of the Si-Miao decoction, and the Genecards, OMIM, and Drugbank databases were used to screen GA-related targets. They were analyzed using Venn with the drug targets to obtain the intersection targets. We used Cytoscape 3.9.1 to draw the "Drugs-Compounds-Targets" network and the String database for creative protein-protein interaction networks of target genes and filtered core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze the core targets. Molecular docking was performed using AutoDockTools to predict the binding capacity between nuclear targets and active components in the Si-Miao decoction. A total of 50 chemically active components containing 53 common targets of Si-Miao decoction anti-GA and 53 potential drug target proteins were identified. Core targets, namely, TNF, STAT3, SRC, PPARG, TLR4, PTGS2, MMP9, RELA, TGFB1, and SIRT1, were obtained through PPI network analysis. GO and KEGG analyses showed that the mechanism of anti-GA in Si-Miao decoction may proceed by regulating biological processes such as inflammatory factor levels, cell proliferation, apoptosis, and lipid and glucose metabolism, and modulating the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, NF-kappa B signaling pathway, and Toll-like receptor signaling pathway. We further screened the core targets, including PTGS2, MMP9, and PPAGR, as receptor proteins based on their degree value and molecular docking with the main active compounds in Si-Miao decoction, and found that baicalein had high affinity. In conclusion, Si-Miao decoction, through anti-inflammatory, apoptosis-regulating, and anti-oxidative stress action mechanisms in the treatment of GA.

Study on Ce2Fe14B-based sintered magnets with Ce/RE> 80.

Up to now, the development of Ce/RE> 80% sintered permanent magnets still faces a challenge, owing to their seriously deteriorated microstructure. In this article, the Ce25.5∼31.5Nd0∼5Febal.B1.25M1.15 (wt.%) sintered magnets with Ce/RE > 80% were investigated, the roles of minor Nd substitution were explored. The typical island-like phase common existed in the grain-boundary (GB) regions of Ce2Fe14B-based SC alloys (which destroys the continuity of RE-rich GB phase), was confirmed as a tetragonal B-rich phase (fct-RE5Fe18B18), and probably generated by the peritectic reaction of "L + Ce2Fe14B → CeFe2 + B-rich" at 797 °C. It was found that: the deteriorated microstructures of high Ce sintered magnets were hardly improved (Nd element was not enriched in the main phase as it was expected), and the coercivity increments were far below expectations by directly adding 3-5% Nd in alloy designs. However, the GB phase distribution was more uniform and continuous, Nd-rich shells formed, and magnetic properties were remarkably promoted by blending 2% NdHx powders into the Ce27.5Nd3Febal.B1.25M1.15 (Ce27.5Nd3) magnet during JM milling, compared with the Ce25.5Nd5Febal.B1.25M1.15 (Ce25.5Nd5) magnet with similar composition. The good comprehensive magnetic properties of Hcj = 1.714 kOe, Br = 9.395 kG, and (BH)max = 11.16 MGOe have been reached in the Ce27.5Nd3+2% (NdHx) magnet (Ce accounted for 84.5 wt% of total rare earth). The present work deepens our understanding of metallurgical behavior, process/microstructure designing for Ce/RE> 80% sintered magnets, and shed a light on the large-scale utilization of Ce element in a permanent magnet.

Targeting Senescent Cells in Atherosclerosis: Pathways to Novel Therapies.

Targeting senescent cells has recently emerged as a promising strategy for treating age-related diseases, such as atherosclerosis, which significantly contributes to global cardiovascular morbidity and mortality. This review elucidates the role of senescent cells in the development of atherosclerosis, including persistently damaging DNA, inducing oxidative stress and secreting pro-inflammatory factors known as the senescence-associated secretory phenotype. Therapeutic approaches targeting senescent cells to mitigate atherosclerosis are summarized in this review, which include the development of senotherapeutics and immunotherapies. These therapies are designed to either remove these cells or suppress their deleterious effects. These emerging therapies hold potential to decelerate or even alleviate the progression of AS, paving the way for new avenues in cardiovascular research and treatment.

Bibliometric and visualized analysis of hydrogels in organoids research.

Over the past decades, there has been ongoing effort to develop complex biomimetic tissue engineering strategies for in vitro cultivation and maintenance of organoids. The defined hydrogels can create organoid models for various organs by changing their properties and various active molecules. An increasing number of researches has been done on the application of hydrogels in organoids, and a large number of articles have been published on the topic. Although there have been existing reviews describing the application of hydrogels in the field of organoids, there is still a lack of comprehensive studies summarizing and analyzing the overall research trends in this field. The citation can be used as an indicator of the scientific influence of an article in its field. This study aims to evaluate the application of hydrogels in organoids through bibliometric analysis, and to predict the hotspots and developing trends in this field.

RBC-hitchhiking PLGA nanoparticles loading ß-glucan as a delivery system to enhance in vitro and in vivo immune responses in mice.

Red blood cells (RBCs) naturally trap some bacterial pathogens in the circulation and kill them by oxidative stress. Following neutralization, the bacteria are presented to antigen-presenting cells in the spleen by the RBCs. This ability of RBCs has been harnessed to develop a system where they play a crucial role in enhancing the immune response, offering a novel approach to enhance the body's immunity. In this work, a conjugate, G-OVA, was formed by connecting ß-glucan and OVA through a disulfide bond. Poly (lactic-co-glycolic acid) (PLGA) was then employed to encapsulate G-OVA, yielding G-OVA-PLGA. Finally, the nanoparticles were adsorbed onto RBCs to develop G-OVA-PLGA@RBC. The results demonstrated that the delivery of nanoparticles by RBCs enhanced the antibody response to antigens both in vitro and in vivo. The objective of this study was to investigate the increased immune activity of G-OVA-PLGA nanoparticles facilitated by RBCs transportation and to elucidate some of its underlying mechanisms. These findings are anticipated to contribute valuable insights for the development of efficient and safe immune enhancers.

Enhancement of the immune responses to foot-and-mouth disease vaccination in mice by oral administration of a novel polysaccharide from the roots of Radix Cyathulae officinalis Kuan (RC).

Foot-and-mouth disease (FMD) is a kind of the important animal infectious disease caused by the foot-and-mouth disease virus (FMDV). Thus, the aim of this study was to determine the effects of the polysaccharide from the Radix Cyathulae officinalis Kuan (RCPS) for its adjuvant potential on the FMDV-specific cellular and humoral immune responses in mice. In this study, our findings shows that oral administration of RCPS significantly enhanced the phagocytic capacity of peritoneal macrophage, splenocyte proliferation, the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) and IgG, IgG1, IgG2a, and IgG2b antibody titers. Furthermore, RCPS promoted the level of IL-2, IFN-γ and IL-4 in CD4(+)T cells and level of IFN-γ in CD8(+)T cells. In addition, RCPS enhanced the expression of CD40(+), CD80(+) and CD86(+) on DCs. Importantly, RCPS could up-regulated the mRNA level of MHC I, MHC II, TLR-2, TLR-4. Interestingly, RCPS down-regulated the frequency of CD4(+)CD25(+)Foxp3(+)Treg cells. Taken together, these results demonstrate that RCPS can enhance both cellular and humoral immune responses via up-regulating DCs maturation through TLR2, TLR4 signaling pathway, and suppressing Treg frequency.