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Ethnopharmacological Relevance: Traditional Chinese medicine (TCM) has shown notable effectiveness and safety in managing illnesses linked to cytokine storm(CS). Bailixiang tea (BLX), an herbal medicine formula, which is a compound Chinese medicine composed of Thymus mongolicus (Ronniger) Ronniger (Bailixiang), Glycyrrhiza uralensis Fisch. (Gancao), Citrus reticulata Blanco (Chenpi), Cyperus rotundus L. (Xiangfu), and Perilla frutescens (L.) Britton (Zisu). The objective of this study was to explore the capacity of BLX in improving LPS-induced CS., Aim of the Study: This study aimed to validate the mitigating effect of BLX on CS and to further investigate its mechanism., Materials and Methods: mice were orally administered BLX for 24 h after being treated with 5 mg/kg lipopolysaccharide (LPS). Histopathological observations further confirmed the significant protective effect of BLX treatment against LPS-induced lung and spleen damage. Additionally, we aimed to explore the molecular mechanism underlying its effects through blood proteomics and transcriptomics analyses. Real-Time Quantitative PCR (RT-qPCR) was utilized to detect the levels of Toll-like receptor 2 (TLR2), Matrix metalloproteinase 8 (MMP8), Matrix metalloproteinase 9 (MMP9), Integrin beta 2 (ITGB2), Mitogen-activated protein kinase 8 (MAPK8), Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon (NFKBIE), Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), and Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)expressions in the lung tissue., Results: The results demonstrated that BLX effectively down-regulated the overproduction of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in both the serum and lung and spleen tissues. Furthermore, BLX effectively mitigated the overproduction of monocyte chemoattractant protein-1 (MCP-1) in the serum. Through comprehensive multi-omics analysis, it was revealed that BLX specifically targeted and regulated TLR2/MAPK8 and TLR2/NF-κB signaling pathways, which play a crucial role in the production of key cytokines., Conclusions: The findings of this study demonstrate that Bailixiang tea possesses the ability to alleviate lung tissue damage and inhibit the development of LPS-induced cytokine storm in mice. These effects are attributed to the tea's ability to suppress the TLR2/MAPK8 and TLR2/NF-κB pathways. Consequently, this research highlights the potential application of Bailixiang tea as a treatment option for cytokine storm., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Heavy metals and organic pollutants are prevalent in water bodies, causing great damage to the environment and human beings. Hence, it is urgent to develop a kind of adsorbent with good performance. Anion interlacing layered double hydroxides (LDHs) are a promising adsorbent for the sustainable removal of heavy metal ions and dyes from wastewater. Using aluminum chloride, zinc chloride and ammonium pentaborate tetrahydrate (NH 4 B 5 O 8 · 4H 2 O, BA) as raw materials, the LDHs complex (BA-LDHs) of B 5 O 8 - intercalation was prepared by one-step hydrothermal method. The BA-LDHs samples were characterized by a X-ray powder diffractometer (XRD), scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR) and the Brunauer-Emmett-Teller (BET) method. The results showed that B 5 O 8 - was successfully intercalated. Adsorption experimental results suggested that BA-LDHs possess a maximum adsorption capacity of 18.7, 57.5, 70.2, and 3.12 mg·g -1 for Cd(II), Cu(II), Cr(VI) and Methylene blue (MB) at C s = 2 g·L -1 , respectively. The adsorption experiment conforms to the Langmuir and Freundlich adsorption models, and the kinetic adsorption data are well fitted by the pseudo-second-order adsorption kinetic equation. The as-prepared BA-LDHs have potential application prospects in the removal of heavy metals and dyes in wastewater. More importantly, they also provide a strategy for preparing selective adsorbents.

The surge in non-grain production on farmland (NGPF) poses significant threats to food security and land sustainability, particularly in hilly regions. However, there remains a lack of clarity on how to effectively balance grain and non-grain production in relation to land remediation. Using Wannian County as a case study, we investigate the evolution of this by leveraging high-precision land surveys and satellite imagery. Through the application of bootstrapped partial linear regression models, we identify key influencers behind each type of NGPF. In proposing land remediation solutions, we integrate the results of NGPF and land quality evaluations to identify mismatches between non-grain production and land attributes (i.e., topography, geology, soil, and land use). Our findings reveal a substantial growth in NGPF, expanding from 3838.72 ha to 5659.64 ha (2010-2020), and predominantly occurring on farmland with favorable natural conditions and connected locations such as proximity to roads, town centers, and industrial plants. Surprisingly, the basic farmland protection policy shows limited effectiveness in curbing NGPF, except for garden operations. We identify 1674 NGPF patches suitable for conversion to grain production and provide land remediation suggestions tailored to low-quality farmland with specific natural barriers, thus complementing the demand for regional non-grain production. This study thereby innovatively proposes nature-based land remediation strategies to address the non-grain production dilemma by tailoring NGPF and land quality, offering valuable insights for sustainable farmland management in China and beyond., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Insufficient endosomal escape presents a major hurdle for successful nucleic acid therapy. Here, for the first time, a chemical electron transfer (CET) system was integrated into small interfering RNA (siRNA) lipid nanoparticles (LNPs). The CET acceptor can be chemically excited using the generated energy between the donor and hydrogen peroxide, which triggers the generation of reactive oxygen species (ROS), promoting endosomal lipid membrane destabilization. Tetra-oleoyl tri-lysino succinoyl tetraethylene pentamine was included as an ionizable lipopeptide with a U-shaped topology for effective siRNA encapsulation and pH-induced endosomal escape. LNPs loaded with siRNA and CET components demonstrated a more efficient endosomal escape, as evidenced by a galectin-8-mRuby reporter; ROS significantly augmented galectin-8 recruitment by at least threefold compared with the control groups, with a p value of 0.03. Moreover, CET-enhanced LNPs achieved a 24% improvement in apoptosis level by knocking down the tumor-protective gene nuclear factor erythroid 2-related factor 2, boosting the CET-mediated ROS cell killing.

Density functional theory (DFT) was employed to elucidate the mechanisms for ozonolysis reaction of p-nitrophenol (PNP) and its anion form aPNP. Thermodynamic data, coupled with Average Local Ionization Energies (ALIE) analysis, reveal that the ortho-positions of the OH/O - groups are the most favorable reaction sites. Moreover, rate constant calculations demonstrate that the O 3 attack on the C2-C3 bond is the predominant process in the reaction between neutral PNP and O 3 . For the aPNP + O 3 reaction, the most favorable pathways involve O 3 attacking the C1-C2 and C6-C1 bonds. The rate constant for PNP ozonolysis positively correlates with pH, ranging from 5.47 × 10 8 to 2.86 × 10 9  M -1  s -1 in the natural aquatic environment. In addition, the formation of hydroxyl radicals in the ozonation process of PNP and the mechanisms of its synergistic reaction of PNP with ozone were investigated. Furthermore, the ozonation and hydroxylation processes involving the intermediate OH-derivatives were both thermodynamically and kinetic analyzed, which illustrate that OH radicals could promote the elimination of PNP. Finally, the toxic of PNP and the main products for fish, daphnia, green algae and rat were assessed. The findings reveal that certain intermediates possess greater toxicity than the original reactant. Consequently, the potential health risks these compounds pose to organisms warrant serious consideration., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Blast furnace slag (BFS) is a kind of waste produced in industrial production, as well as a valuable secondary resource. In this paper, layered double hydroxides composites (BFS/LDHs) were prepared by aqueous polymerization, with industrial waste BFS as modifier and magnesium nitrate, aluminium nitrate, and urea as raw materials. BFS/LDHs have been characterized by using scanning electron microscopy (SEM), fourier infrared spectrometer (FT IR), x-ray diffraction (XRD), and the specific surface area analyser (BET). The adsorption of BFS/LDHs on Cu (II) and methylene blue (MB) was investigated by batch experiments. The results showed that the adsorption capacity of BFS/LDHs to Cu (II) is stronger than that of MB. What's more, the solid concentration effect was found in the process of sorption kinetics and sorption isotherms. The sorption kinetics curves of Cu (II) and MB on BFS/LDHs were well fitted by the quasi-second-order kinetics under different adsorbent concentrations. Langmuir and Freundlich sorption isotherm models were used to analyse the adsorption. It showed that the adsorption conforms to Langmuir and Freundlich's adsorption isotherm models. The BFS/LDHs composites have good recycling availability in this adsorption process of Cu (II) and MB, the removal capacity of which was reduced by 16.1% and 3.8% after being recycled for six times, respectively. More importantly, BFS/LDHs composites are not only expected to become a sewage treatment agent, but also to solve the problem of industrial waste treatment, which is a win-win strategy.

An iodoform-promoted functionalization of ether with secondary sulfonyl amides under visible-light irradiation was developed toward synthesis of hemiaminal skeleton with good to excellent isolated yields. The characterization of the isolated ether and iodoform complex revealed regioselective hydrogen atom transfer to initiate carbon radical formation and enabled the amination reaction with the sulfonamide.

Carbon nanodots present resistance to photobleaching, bright photoluminescence, and superior biocompatibility, making them highly promising for bioimaging applications. Herein, nanoprobes were caged with four-armed oligomers and subsequently modified with a novel DBCO-PEG-modified retro-enantio peptide ligand reL57, enhancing cellular uptake into U87MG glioma cells highly expressing low-density lipoprotein receptor-related protein 1 (LRP1). A key point in the development of the oligomers was the incorporation of ε-amino-linked lysines instead of standard α-amino-linked lysines, which considerably extended the contour length per monomer. The four-armed oligomer 1696 was identified as the best performer, spanning a contour length of ~8.42 nm for each arm, and was based on an altering motive of two cationic ε-amidated lysine tripeptides and two tyrosine tripeptides for electrostatic and aromatic stabilization of the resulting formulations, cysteines for disulfide-based caging, and N-terminal azidolysines for click-modification. This work highlights that well-designed four-armed oligomers can be used for noncovalent coating and covalent caging of nanoprobes, and click modification using a novel LRP1-directed peptide ligand facilitates delivery into receptor-expressing target cells.

Traditional Chinese medicine offer unique advantages in mitigating and preventing early or intermediate stage for treating heart failure (HF). The purpose of this study was to assess the in vivo therapeutic efficacy of Xin-shu-bao (XSB) at different stages of HF following induction of a myocardial infarction (MI) in mice and use mass spectrometry-based proteomics to identify potential therapeutic targets for different stages of HF based on the molecular changes following XSB treatment. XSB had high cardioprotective efficacy in the pre-HF with reduced ejection fraction (HFrEF) stages, but had a weak or no effect in the post-HFrEF stages. This was supported by echocardiographic measurements showing that XSB decreased ejection fraction and fractional shortening in HF. XSB administration improved cardiac function in the pre- and post-HFrEF mouse model, ameliorated deleterious changes to the morphology and subcellular structure of cardiomyocytes, and reduced cardiac fibrosis. Proteomics analysis showed that XSB intervention exclusively targeted thrombomodulin (THBD) and stromal interaction molecule 1 (STIM1) proteins when administered to the mice for both 8 and 6 weeks. Furthermore, XSB intervention for 8, 6, and 4 weeks after MI induction increased the expression of fibroblast growth factor 1 (FGF1) and decreased arrestin β1 (ARRB1), which are classic biomarkers of cardiac fibroblast transformation and collagen synthesis, respectively. Overall, the study suggests that early intervention with XSB could be an effective strategy for preventing HFrEF and highlights potential therapeutic targets for further investigation into HFrEF remediation strategies., Competing Interests: Declaration of Competing Interest There are no any financial and personal relationships with other people or organizations interests conflicts to declare., (Copyright © 2023. Published by Elsevier Masson SAS.)

Industrial heavy metal-contaminated wastewater is one of the main water pollution problems. Adsorbents are a promising method for the removal of heavy metal contaminants. Herein, polyaspartic acid/carboxymethyl poplar sawdust hydrogels (PASP/CMPP) and ascorbic acid/carboxymethyl poplar sawdust hydrogels (VC/CMPP) were prepared by aqueous polymerization using alkalized poplar sawdust (CMPP) as the substrate and PASP and vitamin C (VC) as modifiers. The effective results, provided by the characterization analysis of SEM and BET, indicate that the surface of the PASP/CMPP hydrogel has a larger number of loose pores and a larger pore volume than the VC/CMPP hydrogel. The treatment effects of the two hydrogels on simulated wastewater containing Cd(II) were investigated by a batch of experiments. The results showed that PASP/CMPP had a better adsorption effect than VC/CMPP under the same adsorption conditions. Interestingly, the solid concentration effect was found in the process of sorption kinetics and sorption isotherms. The sorption kinetic curves of Cd(II) on PASP/CMPP were well-fitted by the quasi-second-order kinetics under different adsorbent concentrations. The adsorption conforms to Langmuir and Freundlich adsorption isotherm models. More importantly, PASP/CMPP composites are expected to be used as a new kind of environmental adsorbent for wastewater treatment.

Symbiotic nitrogen fixation boosts legume growth and production in nitrogen-poor soils. It has long been assumed that fixed nitrogen increases reproductive success, but until now, the regulatory mechanism was unknown. Here, we report a symbiotic flowering pathway that couples symbiotic and nutrient signals to the flowering induction pathway in legumes. We show that the symbiotic microRNA-microRNA172c (miR172c) and fixed nitrogen systemically and synergistically convey symbiotic and nutritional cues from roots to leaves to promote soybean ( Glycine max ) flowering. The combinations of symbiotic miR172c and local miR172c elicited by fixed nitrogen and development in leaves activate florigen-encoding FLOWERING LOCUS T ( FT ) homologs ( GmFT2a/5a ) by repressing TARGET OF EAT1-like 4a ( GmTOE4a ). Thus, FTs trigger reproductive development, which allows legumes to survive and reproduce under low-nitrogen conditions.

Objective: We aimed to identify the active ingredients and elucidate the underlying mechanism of action of Atractylodes lancea (Thunb.) DC (namely, Cangzhu) for the treatment of gouty arthritis (GA) based on network pharmacology methods. These findings are expected to provide a theoretical basis for the clinical treatment of GA., Methods: We used monosodium urate (MSU)-induced GA rats as a model to test the overall efficacy of Cangzhu in vivo. Then, the components of the Cangzhu decoction were analyzed and identified, and we screened the active ingredients and their targets. The GA disease targets were predicted by GeneCards and Disgenet databases and found to overlap in both databases. The STRING database was used to construct a protein-protein interaction network, followed by identification of the hub genes using Network Analyzer. Thereafter, Cytoscape software (version 3.8.2) was applied to construct a network for drug-active ingredient-key targets. Next, we applied cluego, a plug-in of Cytoscape, to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analyses. Additionally, molecular docking was used to verify the characteristics of the key candidate components interacting with the hub therapeutic targets. Finally, we established an inflammatory injury model of LPS using RAW264.7 macrophages and used it to experimentally validate the critical active ingredients., Results: Cangzhu effectively protected against gouty arthritis in vivo, and network pharmacology results revealed various active ingredients in Cangzhu, such as wogonin, atractylenolide I and atractylenolide II. These compounds were found to act on 16 hub targets, including tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL-1β), prostaglandin-endoperoxide synthase 2 (PTGS2), recombinant mitogen-activated protein kinase 14 (MAPK14) and transcription factor p65 (RELA), which have significant effects on regulating inflammatory factors and apoptosis-related pathways to improve the proinflammatory or anti-inflammatory imbalance in the body, and this may be one of the underlying mechanisms of Cangzhu in anti-GA., Conclusion: Our findings revealed that Cangzhu comprises multiple active components that exert various targeted effects during GA treatment. These findings provide relevant insights to illuminate the mechanism of Cangzhu in the treatment of GA and provide a reference for further experimental research., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

A soybean protein-based adhesive with desired adhesion properties and low processing cost is prepared by a simple and practical method, which is of great significance to the sustainable utilization of resources and human health. Nevertheless, the protein of high-temperature soybean meal (HSM) has a high degree of denaturation and low solubility, endowing the resultant soybean-based adhesive with a high viscosity and unstable bonding performance. Herein, we propose the strategy of protein molecular recombination to improve the bonding properties of the adhesive. First, chemical denaturation was carried out under the combined action of sodium sulfite, sodium dodecyl sulfate, sodium hydroxide, urea, or sodium dodecyl sulfate/sodium hydroxide to reshape the structure of the protein to release active groups. Then, thermal treatment was employed to facilitate the protein repolymerization and protein-carbohydrate Maillard reaction. Meanwhile, the epichlorohydrin-modified polyamide (PAE) as a crosslinking agent was introduced to recombine unfolded protein and the products from Maillard reaction to develop an eco-friendly soy protein-based adhesive with an excellent and stable bonding performance. As expected, the highest cycle wet bond strength of the adhesive sample of 1.20 MPa was attained by adding a combination of 2% SDS and 0.5% sodium hydroxide, exceeding the value required for structural use (0.98 MPa) of 22.44% according to the JIS K6806-2003 commercial standard. Moreover, the adhesive possessed the preferable viscosity and viscosity stability accompanied by good wettability. Noteworthily, the adhesive had a short time of dry glue, which could be solved by combining it with soybean meal (SM) at the ratio of 30:10., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

An efficient three-component radical iodosulfonylative cyclization of enynes is described. The visible-light irradiation of iodoform with sulfinates enables sulfonyl radical generation under catalyst- and oxidant-free conditions and triggers the radical addition, cyclization and iodination cascade reactions, giving various vinyl iodide containing sulfones in moderate to good yields.

Praeruptorin A (PA) is a natural coumarin compound from the roots of Radix Peucedani and is commonly used in the treatment of certain respiratory diseases and hypertension. Although previous studies identified relaxant effects of PA on tracheal and arterial preparations, little is known about its vasodilative effects and underlying mechanisms. Here, an organ bath system and tension recording methods were used to prepare and analyze isolated rat thoracic aorta artery rings. Aorta artery rings were pre-contracted with phenylephrine and then incubated with PA, and the possible mechanism of relaxation was investigated by adding inhibitors of nitric oxide synthase (NG-nitro-L-arginine methyl ester, L-NAME), endothelial nitric oxide synthase (L-NG-nitroarginine, L-NNA), cyclooxygenase (indomethacin), guanylyl cyclase (1 H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one, ODQ), and KCa channels (tetraethylammonium, TEA). Our study showed that PA-induced vasodilation was blocked by L-NAME, L-NNA, and ODQ, while CaCl 2 -induced vasoconstriction was countered by PA. Thus, PA may exert a vasodilatory effect by influencing the amounts of endothelium-derived relaxing factors through endothelial-dependent NO-cGMP and prostacyclin pathways (such as NO and prostacyclin 2). In the rat thoracic aorta, PA reduces vasoconstriction by inhibiting Ca 2+ inflow.

Symbiotic nodulation is initiated in the roots of legumes in response to low nitrogen and rhizobial signal molecules and is dynamically regulated by a complex regulatory network that coordinates rhizobial infection and nodule organogenesis. It has been shown that the miR156-SPL module mediates nodulation in legumes; however, conclusive evidence of how this module exerts its function during nodulation remains elusive. Here, we report that the miR156b-GmSPL9d module regulates symbiotic nodulation by targeting multiple key regulatory genes in the nodulation signalling pathway of soybean. miR156 family members are differentially expressed during nodulation, and miR156b negatively regulates nodulation by mainly targeting soybean SQUAMOSA promoter-binding protein-like 9d (GmSPL9d), a positive regulator of soybean nodulation. GmSPL9d directly binds to the miR172c promoter and activates its expression, suggesting a conserved role of GmSPL9d. Furthermore, GmSPL9d was coexpressed with the soybean nodulation marker genes nodule inception a (GmNINa) and GmENOD40-1 during nodule formation and development. Intriguingly, GmSPL9d can bind to the promoters of GmNINa and GmENOD40-1 and regulate their expression. Our data demonstrate that the miR156b-GmSPL9d module acts as an upstream master regulator of soybean nodulation, which coordinates multiple marker genes involved in soybean nodulation., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

Sonodynamic therapy (SDT) is a non-invasive and highly penetrating treatment strategy under ultrasound irradiation. However, uncertainty in the mechanism of SDT has seriously hindered its future clinical application. Here, the mechanism of SDT enhanced by the wettability of nanoparticles is investigated. Nanoparticles can adsorb and stabilize nanobubbles in liquid, thus enhancing SDT efficiency. The stability of the nanobubbles is positively correlated with the desorption energy of the nanoparticles, which is determined by the wettability of the nanoparticles. This conclusion is verified for mesoporous silica and polystyrene nanoparticles and it is found that nanoparticles with a water contact angle of about 90° possess the largest desorption energy. To further apply this conclusion, thrombus models are constructed on rats and the experimental results demonstrate that nanoparticles with the largest desorption energy have the highest thrombolytic efficiency. It is believed that these findings will help to better understand the SDT mechanism and guide new strategies for rational design of nanoparticles adopted in SDT., (© 2021 Wiley-VCH GmbH.)

As a fundamental resource for human beings, cultivated land contributes significantly to the sustainable development of society. Investigating cultivated land stability in semiarid areas with a fragile ecology is essential for stabilizing agricultural production and preserving environmental security. The objective of this study was to evaluate cultivated land stability by combining the growth root normalized difference vegetation index (GRNDVI) and precipitation during the crop growing season from 2015 to 2019 in the Horqin Zuoyihou Banner. The productivity of cultivated land was categorized into five levels by the relative criterion, and the minimum productivity level was chosen to represent the stability level. The results showed that a variation in precipitation was evident across both years and crop growing seasons; approximately 66.78% of the cultivated land was classified as moderately stable, 6.55% was classified as highly stable, 22.14% was classified as marginally stable, 0.91% was classified as extremely stable, and 3.62% was classified as unstable. Extremely and highly stable cultivated lands were dominant at the eastern and southern ends of the region, and marginal and unstable cultivated lands were principally present in the west and north while moderately stable land was distributed extensively. Cultivated land stability was affected substantially by water availability and topography, indicating that cultivated land with high levels of stability was distributed more in areas with abundant water and flat terrain. Marginally stable and unstable cultivated lands should be returned to their previous vegetation covers, with priority given to planting appropriate sandy plants to restore ecological integrity. Such evaluation outcomes are meaningful for optimizing the distribution of cultivated land and facilitating the sustainable utilization of land resources., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Sechang-Zhixie-San (SCZX) is an ancient prescription used for pediatric diarrhea by the Yi people in China, which consists of Rodgersia sambucifolia Hemsley (known as Yantuo and abbreviated as YT) and Bentonite (BN). Now, it is also a Chinese patent medicine used in the clinic to treat infantile diarrhea. Besides evaluating the antidiarrheal effect of SCZX on diarrhea mice induced by Folium Sennae, the purpose of this study is to outline the characteristics of the antidiarrheal effect and reveal the potential mechanisms of SCZX through the analysis of the mechanism and active components of YT via network pharmacology and molecular docking, combined with the research progress of BN obtained from the literature. SCZX (3.12 and 12.48 g/kg) effectively inhibited diarrhea in mice, significantly lowering the loose stool rate (LSR), loose stool level (LSL), and loose stool index (LSI). Using network pharmacology, the "herb-compound-target-pathway-pharmacological action" network was mapped to indicate the antidiarrheal mechanism of YT. And the docking results revealed that 4 components of YT including quercetin, geranyl-1-O- α -L-arabinopyranosyl-(1 ⟶ 6)- β -D-glucopyranoside, 3 α -O-(E)-p-hydroxy-cinnamoyl-olean-12-en-27-oic acid, and daucosterol showed significant docking activities with STAT3, EGFR, and SLC10A2, involving 11 pathways such as Th17 cell differentiation, Jak-STAT signaling pathway, ErbB signaling pathway, and HIF-1 signaling pathway. According to our research results and literature reports, the antidiarrheal could be summarized into five aspects: inhibiting intestinal inflammation, acting as a barrier to the intestinal mucosal, regulating water and ion transport, involving the purification of intestinal microorganisms, and intestinal transmission, which might be dependent on multiple proteins and intervention in multiple pathways., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Zhiyong Li et al.)

Nanomaterials-based prodrug activation systems have been widely explored in cancer therapy, aiming at overcoming limited dosage formulation, systemic toxicity, and insufficient pharmacokinetic performance of parent drugs. For better delivery control, various stimuli systems, especially nanomaterials-based ones, have come to the forefront. Among them, near-infrared (NIR) light takes advantage of on-demand/site-specific regulation and non-invasiveness. In this review, we will address the developments of nanomaterials-based prodrug over the last decade, the activation mechanisms, and bioapplications under NIR light triggering. The advantages and limitations of NIR-triggered prodrug activation strategies and the perspectives of the next-generation prodrug nanomedicine will also be summarized. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2020 Wiley Periodicals LLC.)

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron-hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chemo-phototherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. However, the complex tumor microenvironment restricts the penetration depth of chemo-phototherapy agents in the tumor region. Here, biodegradable amphiphilic gelatin (AG) wrapped nanocomposite (PRDCuS@AG) composed of doxorubicin and copper sulfide (CuS)-loaded dendrimer is designed for deep tumor chemo-phototherapy. PR in PRDCuS@AG represents arginine-conjugated polyamidoamine dendrimer. PRDCuS@AG can rapidly biodegrade into PRDCuS by matrix metalloproteinases under near-infrared light irradiation. The resulted PRDCuS harbors dual cell-tissue penetration ability, which can effectively penetrate deep into the tumor tissue. In particular, PRDCuS@AG achieves photoacoustic imaging-guided synergistic chemo-phototherapy with 97% of tumor inhibition rate. Moreover, PRDCuS@AG can further degrade into 3 nm ultrasmall CuS, which can be eliminated from the body after treatment to avoid side effects. This strategy provides an insight that the development of chemo-phototherapy agents with high penetration ability to overcome the limitation of current deep tumor therapy., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Traditional Chinese medicine (TCM) formulae can be regarded as a source of new antistroke drugs. The aim of this study was to discover herbal pairs containing Gastrodia elata (Tianma, TM) from formulae based on data mining and the Delphi expert questionnaire. The proposed approach for discovering new herbal combinations, which included data mining, a clinical investigation, and a network pharmacology analysis, was evaluated in this study., Methods: A database of formulae containing TM was established. All possible herbal pairs were acquired by data mining association rules, and herbal pairs containing TM were screened according to the Support and Confidence levels. Taking stroke as the research object, the relationships between herbal pairs containing TM and stroke were explored by the Delphi expert questionnaire and statistical methods. To explore the effects of herbal pairs containing TM on stroke, a network pharmacology analysis was performed to predict core targets, biological functions, pathways, and mechanisms of action., Results: A total of 1903 formulae containing TM, involving 896 Chinese herbal medicines (CHMs) and 126 herbal pairs containing RG, were analyzed by association rules. A total of 27 herbal pairs were further screened according to the Support and Confidence levels. Twelve herbal pairs containing RG were added according to the expert questionnaires. Weightiness analysis showed that 9 groups of core herbal pairs contained RG, including TM-QX, TM-JH, TM-CX, TM-GG, TM-SJM, TM-JC, TM-SCP, TM-MJZ, and TM-GT. Two core herbal pairs, TM-JH and TM-CX, were randomly screened to explore their network pharmacological mechanisms in stroke. The important biological targets for network pharmacological analysis of TM-CX and TM-JH related to stroke were PTGS2, ACE, APP, NOS1, and NOS2. An herbal pair-compound-core target-pathway network (H-C-T-P network) was established, and arginine biosynthesis, arginine and proline metabolism, and the relaxin signaling pathway were identified by enrichment analysis., Conclusion: The herbal pairs of TM-CX and TM-JH obtained from data mining and the expert investigation were found to have effects of preventing and treating stroke through network pharmacology. This could be a viable approach to uncover hidden knowledge about TCM formulae and to discover herbal combinations with clinical and medicinal value based on data mining and questionnaires., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Rongrong Zhou et al.)

Carbon nanomaterials have flourished for cancer therapy for decades. However, their practical applications on clinical bases still pose a challenge to address the dilemma of metabolism in vivo . In this study, an attempt is made to design a degradable carbon-silica nanocomposite (CSN) with immunoadjuvant property, which could undergo an enzyme-free degradation process into small particles (∼5 nm) and facilitate its clinical application. CSN harbors photothermal and photodynamic properties and as an immunoadjuvant would help to generate tumor-associated antigens and mature dendritic cells (DCs). Potent antitumor effects have been achieved in both 4T1 and patient-derived xenograft tumor models with tumor inhibition efficiencies of 93.2% and 92.5%, respectively. We believe that this strategy will benefit the possible clinical translation and carbon-silica-nanomaterial-based cancer therapy.

Nanozymes have attracted extensive interest owing to their high stability, low cost and easy preparation, especially in the field of cancer therapy. However, the relatively low catalytic activity of nanozymes in the tumor microenvironment (TME) has limited their applications. Herein, we report a novel nanozyme (PtFe@Fe 3 O 4 ) with dual enzyme-like activities for highly efficient tumor catalytic therapy. PtFe@Fe 3 O 4 shows the intrinsic photothermal effect as well as photo-enhanced peroxidase-like and catalase-like activities in the acidic TME, thereby effectively killing tumor cells and overcoming the tumor hypoxia. Importantly, a possible photo-enhanced synergistic catalytic mechanism of PtFe@Fe 3 O 4 was first disclosed. We believe that this work will advance the development of nanozymes in tumor catalytic therapy., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Although near-infrared (NIR)-light-mediated photothermal thrombolysis has been investigated to overcome the bleeding risk of clinical clot-busting agents, the secondary embolism of post-phototherapy fragments (>10 µm) for small vessels should not be ignored in this process. In this study, dual-modality photothermal/photodynamic thrombolysis is explored using targeting nanoagents with an emphasis on improving biosafety as well as ameliorating the thrombolytic effect. The nanoagents can actively target glycoprotein IIb/IIIa receptors on thrombus to initiate site-specific thrombolysis by hyperthermia and reactive oxygen species under NIR laser irradiation. In comparison to single photothermal thrombolysis, an 87.9% higher re-establishment rate of dual-modality photothermal/photodynamic thrombolysis by one-time treatment is achieved in a lower limb thrombosis model. The dual-modality thrombolysis can also avoid re-embolization after breaking fibrin into tiny fragments. All the results show that this strategy is a safe and validated protocol for thrombolysis, which fits the clinical translational trend of nanomedicine., Competing Interests: The authors declare no conflict of interest.

Enzymes have been used to direct the conversion of prodrugs in cancer therapy. However, non-specific distribution of endogenous enzymes seriously hinders their bioapplications. Herein, we developed a near-infrared-triggered locoregional chemo-photothermal therapy based on the exogenous enzyme delivery and remolded tumor mivroenvironment. The catalytic efficiency of enzymes was enhanced by the hyperthermia, and the therapeutic efficacy of photothermal therapy (PTT) was improved owing to the inhibition of heat shock protein 90 by chemotherapeutics. The locoregional chemo-phototherapy achieved a one-time successful cure in 4T1 tumor-bearing mice model. Thus, a mutually reinforcing feedback loop between PTT and chemotherapy can be initiated by the irradiation, which holds a promising future in cancer therapy., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The Lhasa River basin is the economic and population center of Tibet and has abundant resources. Due to its harsh weather condition, high elevation, and inconvenient accessibility, few studies have focused on heavy metal distributions in this region. In the present study, to investigate the dissolved trace metal pollution and its controlling factors, 57 water samples from the Lhasa River and its tributaries were collected during three water flow regimes in 2016. The data on the dissolved fraction revealed that the Lhasa River basin appeared to have no to low pollution levels. However, the Lhasa River water showed alkaline characteristics which may affect the presence of heavy metal elements in a dissolved fraction. The concentration of heavy metal elements in colloidal or particulate matter therefore needs attention. Multivariate analyses were performed to determine the significant relationship between the data and to identify controlling factors for dissolved heavy metals in the study area. The results suggested that Mn, Cd, Cu, and Zn originated from a natural geological background, whereas Pb originated from mining drainage and As was influenced by geothermal flows. The concentration of dissolved heavy metals in the Meldromarchu tributary was greatly affected by the mining drainage water, while that in the Tölungchu tributary was greatly influenced by the geothermal water sources. This paper provides the first comprehensive analysis of dissolved heavy metal pollution characteristics and the controlling factors of pollution during the three different water flow regimes of the Lhasa River basin.

Photothermal-radiotherapy (PT-RT) is an effective strategy for relieving hypoxia-related radiotherapy resistance and inducing tumor-specific cell apoptosis/necrosis. Nevertheless, limited tissue penetration of near-infrared (NIR) laser and the serious side effects of high-dose radiation severely hinder its applications for deep tumors. An interventional photothermal-brachytherapy (IPT-BT) technology is proposed here for the internal site-specific treatment of deep tumors. This technology utilizes a kind of biodegradable honeycomb-like gold nanoparticles (HGNs) acting as both internal photothermal agents and radiosensitizers. A high tumor inhibition rate of 96.6% is achieved in SW1990 orthotopic pancreatic tumor-bearing mice by HGNs-mediated IPT-BT synergistic therapy. Interestingly, this approach effectively causes double-stranded DNA damage and improves the oxygen supply and the penetration of nanoparticles inside the tumor. Therefore, it is believed that this strategy may open up a new avenue for PT-RT synergistic therapy of deep malignant tumors and has a significant impact on the future clinical translation., Competing Interests: The authors declare no conflict of interest.

Glioblastoma (GBM) is the most malignant and highly aggressive brain tumor. In this study, four types of typical GBM cell lines (LN229, SNB19, U87, U251) were cultured in a microfabricated 3-D model to study their in vitro behaviors. The 3-D in vitro model provides hollow micro-chamber arrays containing a natural collagen interface and thus allows the GBM cells to grow in the 3-D chambers. The GBM cells in this model showed specific properties on the aspects of cell morphology, proliferation, migration, and invasion, some of which were rarely observed before. Furthermore, how the cells invaded into the surrounding ECM and the corresponding specific invasion patterns were observed in details, implying that the four types of cells have different features during their development in cancer. This complex in vitro model, if applied to patient derived cells, possesses the potential of becoming a clinically relevant predictive model.

In this paper, we study finite-time stability of fractional differential systems with variable coefficients, which includes the homogeneous and nonhomogeneous delayed cases. Based on the theories of fractional differential equations, we obtain three theorems on the finite-time stability, which give some sufficient conditions on finite-time stability, respectively, for homogeneous systems without and with time delay and for the nonhomogeneous system with time delay.

Gold complexes can serve as efficient photothermal converters for cancer therapy, but their non-biodegradability hinders clinical bioapplications. Although enormous effort has been devoted, the conventionally adopted synthetic methods of biodegradation are characterized by high cost and complicated procedures, which delay the process of further clinical translation of gold complexes. Here, we report a multifunctional poly(amino acid)-gold-magnetic complex with self-degradation properties for synergistic chemo-photothermal therapy via simple and green chemistry methods. Nanoparticles of ∼3 nm in the biodegradation product were observed in simulated body fluid in 4 days. The biodegradability mainly benefits from the weakened internal electrostatic interaction of the poly(amino acid) by the ions in simulated body fluid. It is demonstrated that the poly(amino acid)-gold-magnetic complex has great cellular endocytosis by taking advantage of the guanidine group in arginine and possesses multimodal imaging and efficient tumor ablation (94%). This study reports a possibility for gold-magnetic complexes composed of poly(amino acid) to serve as a biodegradable nanotherapeutic for clinical applications.

Lithocholic acid (LCA) is known to kill glioma cells while sparing normal neuronal cells. However, the anti-glioma mechanism of LCA is unclear at present. Although malondialdehyde (MDA) is not specific to detect tumors, biologically active α,β-unsaturated aldehydes can be used to detect the outcome of gliomas, especially the mitochondria, as a research tool. The purpose of this research was to determine the optimum conditions for a lipid peroxidation model, according to changes in the aldehydes formed from the reaction between 2-thiobarbituric acid and biologically active α,β-unsaturated aldehydes. Experimental methods and procedures were successfully established for a model of lipid peroxidation induced by H2O2 in glioma mitochondria for glioma treatment and optimum conditions for LCA treatment were determined. The optimal conditions for the model were a glioma mitochondrial concentration of 1.5 mg/ml, H2O2 concentration of 0.3 mg/ml, duration of action of 30 min, and addition of 4.0 ml of 46 mM thiobarbituric acid. The effect of LCA, as determined by changes in the UV peaks at 450, 495, and 532 nm, was optimal at a concentration of 100 µM, a duration of action of 15 min, and in an acidic microenvironment. The study concluded that a suitable concentration of LCA has anti-glioma effects as determined by the effect on changes in the UV peaks at 450, 495 and 532 nm and the mitochondrial model developed should be conducive to further in-depth research.

Introduction: Nicotine is a key biologically active compound of cigarettes. Although nicotine is a risk factor for various health issues, it may also be beneficial when treated at moderate concentrations. Nicotine has been shown to bidirectionally regulate stem cell proliferation and differentiation depending on the doses applied. It is not clear whether or how nicotine regulates mouse embryonic stem cell (mESC) survival and proliferation., Methods: Mouse embryonic stem cells were cultured in the presence of 0.01, 0.1, 1, or 10 μM nicotine. The effects of nicotine on cell survival and proliferation were examined. The signaling pathway that mediated these effects was analyzed., Results: Cell viability was not affected by nicotine at all 4 concentrations examined. The proliferation of mESCs was promoted by 0.01 and 0.1 μM nicotine and suppressed by 1 and 10 μM. This dose-dependent regulation was mediated through the Wnt/β-catenin pathway. Modulation of Wnt/β-catenin activity either worsens or reverses the effects of nicotine., Conclusions: We have identified a bidirectional function of nicotine on mESC proliferation through regulation of the Wnt/β-catenin pathway and this is associated with different doses. This study suggests that concentration of nicotine is a crucial aspect for consideration when designing research or therapeutic strategies., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Although nanoparticle-based photothermal therapy (PTT) has been intensively investigated recently, its comparative efficiency with any clinical cancer treatments has been rarely explored. Herein for the first time we report a systematic comparative study of clinical iodine-125 ( 125 I) interstitial brachytherapy (IBT-125-I) and interventional PTT (IPTT) in an orthotopic xenograft model of human pancreatic cancer. IPTT, based on the nanoparticles composing of anti-urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) modified gold nanoshells (hereinafter uIGNs), is directly applied to local pancreatic tumor deep in the abdomen. In comparison to IBT-125-I, a 25% higher median survival rate of IPTT with complete ablation by one-time intervention has been achieved. The IPTT could also inhibit pancreatic tumor metastasis which can be harnessed for effective cancer immunotherapy. All results show that this IPTT is a safe and radical treatment for eradicating tumor cells, and may benefit future clinical pancreatic cancer patients., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A 3-D microfluidic system consisting of microchamber arrays embedded in a collagen hydrogel with tuneable biochemical gradients that mimics the tumour microenvironment of mammary glands was constructed for the investigation on the interactions between invasive breast cancer cells and stromal cells. The hollow microchambers in collagen provide a very similar 3-D environment to that in vivo that regulates collective cellular dynamics and behaviour, while the microfluidic channels surrounding the collagen microchamber arrays allow one to impose complex concentration gradients of specific biological molecules or drugs. We found that breast epithelial cells (MCF-10A) seeded in the microchambers formed lumen-like structures similar to those in epithelial layers. When MCF-10A cells were co-cultured with invasive breast cancer cells (MDA-MB-231), the formation of lumen-like structures in the microchambers was inhibited, indicating the capability of cancer cells to disrupt the structures formed by surrounding cells for further invasion and metastasis. Subsequent mechanism studies showed that down regulation of E-cad expression due to MMPs produced by the cancer cells plays a dominant role in determining the cellular behaviour. Our microfluidic system offers a robust platform for high throughput studies that aim to understand combinatorial effects of multiple biochemical and microenvironmental factors.

Objective: To identify the quantitative profiling of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) in cumulus cells (CCs) and to evaluate their roles in the early embryo development of polycystic ovary syndrome (PCOS) patients, in part, with obesity., Methods: Fifty-five subjects were divided into two groups according to the body mass index. Oocytes were further inseminated and only mature and normal fertilized oocytes (2PN) were included in this research. Real-time PCR and western blot were performed to identify adiponectin and its receptors in CCs., Results: Adiponectin and receptors were ubiquitously expressed in CCs of PCOS and non-PCOS patients. The level of AdipoR2 in CCs from the oocytes yielding blastocyst after 5/6 days in vitro culture was markedly higher than in those from oocytes could not develop to blastocyst stage after Day 6, for non-obese or obese PCOS patients (0.1647 ± 0.0161 versus 0.0783 ± 0.0385, 0.1948 ± 0.0307 versus 0.1057 ± 0.0236, respectively, p < 0.05). In addition, only in patients with PCOS and concurrent obesity the AdipoR1 in CCs was considerably increased in CC-B + compared with CC-B - subgroup (0.5162 ± 0.0371 versus 0.2448 ± 0.0333, p < 0.01)., Conclusion: The development of early embryo was associated with the up-regulation of AdipoR1 and AdipoR2 in PCOS patients. Our results suggested that adiponectin could positively modulate embryo development in humans. Further investigations should be carried out to unlock the crucial role that adiponectin plays in embryo development.

Objective Betatrophin is a newly identified circulating protein that is significantly associated with type 2 diabetes mellitus (T2DM), adiposity, and metabolic syndrome. The aim of this study was to investigate whether betatrophin levels and polycystic ovary syndrome (PCOS) were associated. Methods Circulating betatrophin levels were measured in 162 patients with PCOS and 156 matched control females using specific enzyme-linked immunosorbent assay kits. Correlations between betatrophin levels and PCOS incidence as well as multiple key endocrine PCOS parameters were analyzed using multiple statistical methods. Results Betatrophin levels were significantly increased in patients with PCOS (685.3 ± 27.7 vs. 772.6 ± 42.5 pg/ml). When sub-grouping all investigated subjects according to the presence of insulin resistance, women with PCOS and insulin resistance exhibited markedly higher betatrophin concentrations. Furthermore, betatrophin levels were significantly correlated with fasting insulin levels and homeostatic model assessment of insulin resistance only in females with PCOS ( r = 0.531 and r = 0.628, respectively). Conclusion We provide the first report that betatrophin is strongly associated with PCOS. This study suggests that betatrophin may potentially serve as an independent predictor for the development of PCOS in at-risk women, especially those with insulin resistance.

Magnetic composites consisting of magnetite (Fe3O4), graphene oxide (GO), and Mg3Al-OH layered double hydroxide (LDH), denoted as MGL composites, with varying GO contents (RGO) were synthesized by a mechano-hydrothermal (MHT) route using Fe3O4, Mg(OH)2, and Al(OH)3 as the inorganic starting materials. The application of the synthesized MGLs for removing the heavy-metal Pb(II) and the hydrophobic organic pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous solutions was investigated. Chemical bonding among the GO, Fe3O4, and LDH components was observed in the MGLs. The MGL composites showed good water-dispersity, strong magnetic response, and high sorption capacities and removal efficiencies for both Pb(II) and 2,4-D pollutants. The sorption capacities of the MGL for the pollutants significantly increased with an increase in RGO. Increasing pH could increase the removal efficiency for Pb(II) but decrease that for 2,4-D. The MGLs showed more affinity for Pb(II) than for 2,4-D in the competitive sorption. In addition, the MGLs could remain almost constant removal efficiency for the pollutants after reuse over six cycles, indicating their potential use as sorbents in wastewater treatment. Furthermore, a Cs effect was observed in the sorption equilibriums, which could be described using the Langmuir-SCA and Freundlich-SCA isotherms. The removal mechanisms of the MGL for Pb(II) and 2,4-D were discussed. The MHT method provided a simple and environmentally friendly route for synthesizing GO-LDH composite materials.

This paper presents a brief overview of recent developments in chaos synchronization in coupled fractional differential systems, where the original viewpoints are retained. In addition to complete synchronization, several other extended concepts of synchronization, such as projective synchronization, hybrid projective synchronization, function projective synchronization, generalized synchronization and generalized projective synchronization in fractional differential systems, are reviewed.

The equivalent system for a multiple-rational-order (MRO) fractional differential system is studied, where the fractional derivative is in the sense of Caputo or Riemann-Liouville. With the relationship between the Caputo derivative and the generalized fractional derivative, we can change the MRO fractional differential system with a Caputo derivative into a higher-dimensional system with the same Caputo derivative order lying in (0,1). The stability of the zero solution to the original system is studied through the analysis of its equivalent system. For the Riemann-Liouville case, we transform the MRO fractional differential system into a new one with the same order lying in (0,1), where the properties of the Riemann-Liouville derivative operator and the fractional integral operator are used. The corresponding stability is also studied. Finally, several numerical examples are provided to illustrate the derived results.

Regional modelling of soil organic carbon (SOC) dynamics is important for predicting large-scale patterns in carbon cycling and for assessing potential responses of soil carbon pools to land-use change. However, data uncertainties related to both spatial heterogeneity and small-scale differences in farming practice related to cropping systems affect the accuracy of regional models. A case study is presented from Quzhou County in the North China Plain, an area characterized by highly intensive farming. For this county, the DNDC model was validated using sampling data from 68 sites around the county under generalized farm practices. Unique modelling units based on soil type, soil texture and crop type were created and then used to model the spatial change of SOC under different farming practices. Considering the main factors affecting SOC sequestration, the results indicate that the DNDC model delivers acceptable modelling results at county level. The results show that there is a great potential for SOC sequestration in Quzhou County in its central, southern and eastern parts. Changes in farming practices show a strong effect on carbon sequestration. A very efficient and environmental friendly sequestration of SOC pools could be achieved even by decreasing nitrogen fertilizer inputs, when the amount of straw returned to the field is greatly increased.