Stable gullies provide a suitable habitat for functional insects and reduce the threat of pests on crops in farmland of Northeast China.

Gullies with lower altitudes compared to the surrounding environment are widely distributed in farmland of the watershed and their numbers are still expanding. However, it is still unclear how these gullies regulate the functional insects in farmland. In this study, land use types combined with the herbaceous plant, herbicide application, soil moisture, topography and climatic factors during crop growth were considered to understand how gullies influence the dynamics of functional insects in farmland from a watershed (240 ha) of Northeast China. The primary findings demonstrate that the richness and abundance of functional insects are generally greatest in gullies, particularly in stable gullies, and decrease in the following order: forest belts, grasslands, and farmlands within the watershed. Notably, the ratios of beneficial insects to pests (BI/Pest) in terms of richness and abundance were lower in gullies before July but reversed after July, in comparison to farmland. Stable gullies exhibited higher BI/Pest abundance and diversity ratios than developing gullies. The richness and abundance of functional insects were higher in the middle sections of gullies compared to their heads and tails. Furthermore, the ratios of BI/Pest were generally lower in farmlands than in any gully position. Functional insect dynamics were mainly determined by season, followed by plant abundance and biomass in the gullies, and rarely by soil moisture in the both watershed and single gullies scales. Generally, the richness and abundance of functional insects in farmland were mainly influenced by gullies, especially influenced by the gully middle position. Insect composition in farmland influenced by stable gullies was stronger than by developing gullies, and stable gullies were more beneficial in reducing the threat of pests to crops in the farmland of the watershed.

[Imaging for displaying lymphatic vessels in whole-mount aorta adventitia of ApoE-/- mice by immunofluorescent histochemical staining].

Objective To explore a simple and feasible method for whole-mount immunofluorescence staining of lymphatic vessels in the ApoE-/- mouse model of atherosclerosis. Methods Aortic specimens were carefully excised from the ApoE-/- mouse model. Following immunostaining with specific antibodies against smooth muscle actin (SMA) and lymphatic vessel endothelial receptor 1 (LYVE1), the aortas, including the aortic root, were subjected to a 30-minute treatment with 5 g/L Sudan Black B solution. This step was instrumental in minimizing the autofluorescent background of the tissue. Thereafter, the aortas were processed through a clearing protocol and imaged within a purpose-built chamber under a fluorescence microscope. Results The pretreatment with 5 g/L Sudan Black B effectively suppressed the autofluorescent signals emanating from the vascular structures, thereby enhancing the contrast and clarity of the specific fluorescence signals associated with the lymphatic vessels. This enhancement in signal quality did not compromise the integrity or specificity of the immunofluorescent markers. Conclusion A facile, highly specific, and effective approach for the visualization of lymphatic vessels in whole-mount aortic preparations from ApoE-/- mice is established.

Rapamycin circumvents anti PD-1 therapy resistance in colorectal cancer by reducing PD-L1 expression and optimizing the tumor microenvironment.

The unresectable or postoperative recurrence of advanced metastatic colorectal cancer (CRC) is the difficulty of its clinical management, and pharmacological therapy is the main source of benefit. Immune checkpoint inhibitors are therapeutic options but are effective in approximately 5 % of patients with deficient mismatch repair (MMR)/microsatellite instability CRC and are ineffective in patients with MMR-proficient (pMMR)/microsatellite stable (MSS) CRCs, which may be associated with the tumor microenvironment (TME). Here, we propose a new combination strategy and evaluate the efficacy of rapamycin (Rapa) combined with anti-PD-1 (αPD-1) in CT26 tumor-bearing mice, azoxymethane (AOM)/dextran sodium sulfate (DSS) inflammation-associated CRC mice, CT26-Luc tumor-bearing mice with postoperative recurrence, and CT26 liver metastasis mice. The results revealed that Rapa improved the therapeutic effect of αPD-1 and effectively inhibited colorectal carcinogenesis, postoperative recurrence, and liver metastasis. Mechanistically, Rapa improved the anticancer effect of αPD-1, associated with Rapa reprograming of the immunosuppressive TME. Rapa effectively depleted α-SMA+ cancer-associated fibroblasts and degraded collagen in the tumor tissue, increasing T lymphocyte infiltration into the tumor tissue. Rapa induced the downregulation of programed cell death 1 ligand 1 (PD-L1) protein and transcript levels in CT26 cells, which may be associated with the inhibition of the mTOR/P70S6K signaling axis. Furthermore, co-culture of tumor cells and CD8+ T lymphocytes demonstrated that Rapa-induced PD-L1 downregulation in tumor cells increased spleen-derived CD8+ T lymphocyte activation. Therefore, Rapa improves the anti-tumor effect of αPD-1 in CRCs, providing new ideas for its use to improve combinatorial strategies for anti-PD-1 immunotherapy.

Nanoliposomes Encapsulated Rapamycin/Resveratrol to Induce Apoptosis and Ferroptosis for Enhanced Colorectal Cancer Therapy.

OBJECTIVES: Monotherapy is often ineffective for treating colorectal cancer. In this study, we developed PEG-modified liposomes loaded with rapamycin (Rapa) and resveratrol (Res) (Rapa/Res liposomes, or RRL) to investigate their therapeutic potential in colorectal cancer. METHODS: RRL were constructed using the reversed-phase evaporation method. We assessed the cytotoxicity, apoptosis, and ferroptotic effects of RRL on colorectal cancer HCT116 cells. The anti-tumor efficacy of RRL was evaluated in HCT116 xenograft mice. RESULTS: RRL had a particle size of 86.67 ± 1.10 nm and a zeta potential of -33.13 ± 0.49 mV. The coloaded formulation demonstrated satisfactory performance both in vitro and in vivo, resulting in increased cytotoxicity to HCT116 cells and significant suppression of HCT116 xenografts tumor growth. Mechanically, RRL significantly increased the apoptosis rate of HCT116 cells, induced ROS accumulation in tumor cells, and effectively downregulated the expression of the ferroptosis-associated proteins GPX4 and SLC7A11, demonstrating its superior efficacy compared to that of Rapa liposomes (Rapa/Lps) or Res liposomes (Res/Lps) alone. CONCLUSION: Coloading Rapa and Res into liposomes to promote apoptosis and ferroptosis in tumor cells represents a promising strategy for the treatment of colorectal cancer.

Stromal and tumor immune microenvironment reprogramming through multifunctional cisplatin-based liposomes boosts the efficacy of anti-PD-1 immunotherapy in pancreatic cancer.

The dense stromal barrier in pancreatic cancer tissues blocks intratumoral delivery and distribution of chemotherapeutics and therapeutic antibodies, causing poor chemoimmunotherapy responses. We designed a multi-targeted pH-sensitive liposome which encapsulates cisplatin (Pt) in its water core (denoted as ATF@Pt Lps) and shows high affinity for uPAR receptors in pancreatic cancer cells, tumor-associated macrophages, and cancer-associated fibroblasts. Systemic administration of ATF@Pt Lps enabled overcoming the central stromal cellular barrier and effective drug delivery into tumor cells, resulting in a strong therapeutic response in a Panc02 cell derived transplanted tumor mouse model. More importantly, ATF@Pt Lps degradation of collagen contributes to the infiltration of CD8+ T cells into tumors as well as an enhanced accumulation of anti PD-1 monoclonal antibodies. Furthermore, the killing of tumor cells by Pt also leads to the release of tumor antigens, which promote the proliferation of immune cells, especially CD83+ cells, Th1 CD4+ cells, and CD8+ cytotoxic T cells, that converted an immunoscore "cold" pancreatic cancer into a pro-immune "hot" tumor. A further combination with an immune checkpoint agent, anti PD-1 antibodies that inhibit PD-1, can enhance tumor specific cytotoxic T cell response. Accordingly, ATF@Pt Lps displays multi-targeting, controlled drug release, stromal disruption, enhanced penetration, killing of cancer cells, modification of the immunosuppressive microenvironment, and enhancement of immunity. This study provides important mechanistic information for the further development of a combination of ATF@Pt Lps and anti PD-1 antibodies for the effective treatment of pancreatic cancer.

Middle concentration of microplastics decreasing soil moisture-temperature and the germination rate and early height of lettuce (Lactuca sativa var. ramosa Hort.) in Mollisols.

Microplastics (MPs) have been widely found in soils, however, the mechanism of MPs influencing plant growth is still debated and possibly attributed to the soil environment changed by MPs. In this study, 0.0 %, 0.1 %, 0.5 %, 1.0 %, 2.0 %, and 5.0 % (w/w) content of low-density polyethylene MPs (LDPE-MPs) with the particle sizes of 75-2000 µm was used to test how MPs alter the germination and the early growth of lettuce (Lactuca sativa var. ramosa Hort.) in Mollisols under both natural condition and regular incubation condition. Soil temperature (ST), soil moisture (SM) and the ratio of cracks area to surface soil area (CA) and cracks length to surface soil area (CL) were monitored. As well, the dynamics of water and nutrient infiltration reported by our previous publication were combined to analyze the relationship between soil properties and crop growth influenced by MP concentration. The main results showed that: (1) compared with CK (0.0 %), the germination and plant height of lettuce were lowest in treatments with the middle concentration of MPs (0.5 % and 1 %, w/w), but was highest in treatments of high concentration of MPs (5.0 %, w/w) during the whole 14 days of incubation; (2) increasing MP concentration weakened the influence of SM on ST in Mollisols; (3) the average of SM and ST were highest at 5 % of MP concentration, while was lowest at 0.5 % and 1 % of MP concentration from the 2nd to the 9th day; (3) compared with CK and other treatments, the CA and CL were lowest in 1.0 % MP concentration, but were highest in 0.1 % and 5.0 % of MP concentration. This study provides insight that middle, rather than high and low levels of MP concentration, significantly decrease the SM and ST and increase nitrogen leaching which further leads to negative impacts on emergent and early growth of crops in soils with heavy texture (Mollisols).

Multi-targeting liposomal codelivery of cisplatin and rapamycin inhibits pancreatic cancer growth and metastasis through stromal modulation.

Pancreatic cancer treatment faces challenges due to drug resistance as well as liver metastasis. As a new strategy for treating pancreatic cancer, combination therapy is now available, but the dense mesenchymal barrier in the tumor tissue blocks drug delivery and impairs its therapeutic efficacy. To address this issue, we prepared an ATF peptide-decorated liposomal co-loaded with cisplatin and rapamycin (ATF@Pt/Rapa Lps), which targets both tumor cells and cancer-associated fibroblasts that express uPAR receptors. In tumor sphere penetration experiments, ATF peptide modified liposomes significantly enhanced deep penetration. More importantly, the ATF@Pt/Rapa Lps disrupted the stroma, as demonstrated by the downregulation of ɑ-SMA, I collagen, and fibronectin protein in vivo and in vitro. In this way, highly effective drug delivery to tumor cells can be achieved. As expected, there was a stronger inhibition of cell proliferation and migration by ATF@Pt/Rapa Lps in vitro compared to free Pt/Rapa and Pt/Rapa Lps. Furthermore, ATF@Pt/Rapa Lps showed greater therapeutic effects in PANC02 transplanted tumor mice and liver metastasis mice models. Ultimately, multi-targeting nanomedicines co-loaded with Rapa and cisplatin may provide a new approach to treating metastatic pancreatic cancer.

Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes.

Background: The activation of lymphatic vessel function is the crux to resolving atherosclerosis (AS), a chronic inflammatory disease. Rapamycin (RAPA) recently has attracted considerable attention as a potent drug to induce atherosclerotic plaque attenuation. The objective of this work was to develop a ligand-decorated, RAPA-loaded liposome for lymphatic-targeted delivery of drugs to improve abnormal lymphatic structure and function, resulting in highly effective regression of atherosclerotic plaques. Methods: Hyaluronic acid-decorated, RAPA-loaded liposomes (HA-RL) were fabricated by emulsion-solvent evaporation. The average size, zeta potential, entrapment efficiency were characterized, and the stability and drug release in vitro were investigated. Furthermore, the in vitro and in vivo lymphatic targeting ability were evaluated on lymphatic endothelial cells and LDLR-/- mice, and the efficiency of this nano-system in inducing the attenuation of atherosclerotic plaques was confirmed. Results: HA-RL had a size of 100 nm, over 90% drug encapsulation efficiency, the storage stability was distinguished, demonstrating a slow release from the lipid nano-carriers. The mean retention time (MRT) and elimination half-life (t1/2ß) achieved from HA-RL were 100.27±73.08 h and 70.74±50.80 h, respectively. HA-RL acquired the most prominent efficacy of lymphatic-targeted delivery and atherosclerotic plaques attenuation, implying the successful implementation of this novel drug delivery system in vivo. Conclusion: HA-RL exhibited the most appreciable lymphatic targeting ability and best atherosclerotic plaques attenuation efficiency, opening a new paradigm and promising perspective for the treatment of arteriosclerosis.

Extraction and decontamination of microplastics from high organic matter soils: A simple, cost-saving and high efficient method.

This article introduces a simple, cost-saving and high efficient for the extraction and separation of microplastics (MPs) from soil with a high organic matter (SOM) content. In this study, MP with particle sizes of 154-600 µm of polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC) and polyethylene terephthalate (PET) were artificially added into the five Mollisols with the high SOM. Three flotation solutions were used to extract these MPs from soils, and four digestion solutions were used to digest the SOM. As well, their destruction effects on MPs were also examined. The results showed that the flotation recovery rates of PE, PP, PS, PVC and PET were 96.1%-99.0% by ZnCl2 solution, while were 102.0%-107.2% by rapeseed oil, were 100.0%-104.7% by soybean oil. The digestion rate of SOM was 89.3% by H2SO4:H2O2 (1:40, v:v) at 70 °C for 48 h, and this was higher than by H2O2 (30%), NaOH and Fenton's reagent. However, the digestion rate of PE, PP, PS, PVC and PET were 0.0%-0.54% by H2SO4:H2O2 (1:40, v:v), and this was lower than by H2O2 (30%), NaOH and Fenton's reagent. As well, the factors influencing on MP extraction was also discussed. Generally, the best flotation solution was ZnCl2 (ρ > 1.6 g cm-3) and the best digestion method was H2SO4:H2O2 (1:40, v:v) at 70 °C for 48 h. The optimal extraction and digestion method were verified by the known concentrations of MPs (recovery rate of MPs was 95.7-101.7%), and this method was also used to extract MPs from long-term mulching vegetable fields in Mollisols of Northeast China.

Isoorientin reverses lung cancer drug resistance by promoting ferroptosis via the SIRT6/Nrf2/GPX4 signaling pathway.

Cisplatin, or DDP, is a highly successful and well-known chemotherapy drug used to treat cancer. Acquired resistance to chemotherapy is a major clinical concern, yet the mechanisms of this resistance are still unknown. Ferroptosis is a type of cell death distinct from other forms, fueled by a buildup of iron-associated lipid reactive oxygen species (ROS). Gaining insight into the process of ferroptosis could lead to novel treatments for overcoming cancer resistance. In this study, the combination of isoorientin (IO) and DDP treatment resulted in a significant decrease in the viability of drug-resistant cells, a substantial increase in intracellular iron, malondialdehyde (MDA) and ROS concentrations, a notable decrease in glutathione concentration, and the occurrence of ferroptosis in cells, as revealed by in vitro and in vivo experiments. Additionally, there was a decrease in the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and sirtuin 6 (SIRT6) proteins, and an increase in cellular ferroptosis. Isoorientin acts as a mediator to regulate cellular ferroptosis and reverse drug resistance in lung cancer cells by controlling the SIRT6/Nrf2/GPX4 signaling pathway. The findings of this study suggest that IO can promote ferroptosis and reverse drug resistance in lung cancer through the SIRT6/Nrf2/GPX4 signaling pathway, thus offering a theoretical basis for its potential clinical application.

Microplastics change the leaching of nitrogen and potassium in Mollisols.

Nowadays, the dynamics of nutrients leaching from the soils and their driving mechanism have been focused on, however, it is still unclear how microplastics (MPs) influence the nutrients' leaching in soils. In this study, five concentrations (w/w, 0.0 %, 0.5 %, 1 %, 2 %, 3 %) and three sizes of MPs of polyethylene (PE) (0.15-0.36 mm, 0.36-0.60 mm and 0.60-1.00 mm) influencing the leaching of NO3--N and water-soluble potassium (WSK) was simulated by a column method in Mollisols, and both the pre-fertilization and post-fertilization were considered. The results showed that, before KNO3 addition, there was a negative power function relationship between the NO3--N concentration and the leaching solution volume/leaching time. The amount and concentration of NO3--N leaching was higher in the early leaching stage. Compared with the CK, PE0.5% significantly reduced the leaching amount of WSK, while increased the leaching amount of NO3--N but not significantly. The leaching amount of WSK decreased with the increasing size of PEMP when the PEMP concentration was the same, while NO3--N was opposite. PE0.60-1.00 increased the leaching amount of NO3--N, while reduced the leaching amount of WSK. After KNO3 addition, compared with CK, PE1% significantly reduced the leaching amount of NO3--N, and PE1% had the lowest leaching amount of WSK. However, when the PEMP concentration in the soil reached a certain threshold (w/w, >1 %), the leaching amount of NO3--N and WSK increased gradually with PEMP increasing. PE0.60-1.00 reduced the leaching amount of NO3--N and WSK most obviously. In general, low concentrations (w/w, <1 %) and large sizes (0.60-1.00 mm) of PEMP promoted NO3--N leaching and inhibited the WSK leaching from the soil before the addition of KNO3, however, they both inhibited the leaching of NO3--N and WSK from the soil after addition of KNO3.

Microplastic migration and distribution in the terrestrial and aquatic environments: A threat to biotic safety.

Plastics production has been increasing over years, while their recycling rate is lower, resulting in huge amounts of microplastics (MP) accumulating in the environment. Although the environmental behaviors of MPs have been focused on in recent years, the migration, distribution and adverse effects of MPs in terrestrial and aquatic environments are still not systematically understood. In this review, based on the newest publications from the core database of the Web of Science, both the migration and distribution of MPs were summarized, as well as MPs transfer in biota and their biological effects were also focused on. Generally, the complicated and numerous pathways of MPs migration lead to their distribution throughout or nearly all environments on a global scale. However, the migration mechanisms of MPs with various sizes, shapes, and colors by physicochemical and biological processes, and the prediction models of MP migration and distribution, are deficient, despite these properties being highly related to MPs migration and bio-safety. Although MPs have already invaded microorganisms, plants, animals, and even human beings, the biological effects still need more study, so far as their sizes and shapes and also their composition and adsorption are concerned. Moreover, based on the highlights and deficiencies of current studies, further studies have also been proposed. This review aims to help people re-evaluate the uncertain behaviors of MPs in various environments, and could be helpful to fully understand their biological effects in different environmental conditions.

Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC (Min/+) Mice and AOM/DSS-Induced Colorectal Cancer Mice.

Background: Transgenic C57BL/6-APC(Min/+) spontaneous cancer mouse model and the Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS) chemically induced orthotopic colorectal cancer mouse model represented distinct pathogenesis of colorectal cancers. Our previous study revealed that the combination of Rapamycin liposomes (Rapa/Lps) and 5-Fluorouracil (5-FU) has anti-colorectal cancer effects. However, the therapeutic efficacy of Rapa/Lps and 5-FU in other colorectal cancer mice models is yet to be thoroughly explored. The purpose of this study was to investigate the anti-tumor effect of Rapa/Lps combined with 5-FU in vivo and in vitro. Methods: In this study, we evaluated the effect of Rapa/Lps and 5-FU on APC (Min/+) mice and AOM/DSS-induced colorectal cancer mice. The small intestine, colorectum, serum, and plasma of mice in each group were collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to intestine tissues. Tube formation assay, Transwell assay, wound healing assay, Western Blot were used to explore the anti-angiogenesis effect of drugs in HUVECs. Results: As expected, Rapa/Lps and 5-FU significantly suppressed tumor formation, decreased the number of tumors, and tumor load both in two mouse models, and had no influence on mouse weight. Mechanically, the anti-tumor effect of the drug also was associated in inhibiting angiogenesis and proliferation. Furthermore, we found that Rapa/Lps obviously inhibited HUVECs tube formation and migration. Conclusion: Altogether, we revealed the Rapa/Lps synergism with 5-FU decreased colon and small intestinal tumorigenesis in AOM/DSS-treated and APC (Min/+) mice, respectively, and correlated with anti-angiogenesis.

Heterogeneity of plastic residue was determined by both mulch film and external plastic pollutants in the farmland of Northeast China.

Plastic pollution in farmland ecosystems has been widely concerned. However, the heterogeneity and driving mechanisms of plastic residue (PR) remain unclear in the farmland surrounded by complex pollution points. In this study, the abundance, mass, and accumulation areas of PR of mulch film (MF) and non-MF (NMF) were investigated in a large area of the vegetable field covered by plastic mulching in a long-term in Northeast China. Geostatistics combined with classical statistics were used to clarify how pollution source and migration factors change the PR heterogeneity in the farmlands. Results indicated that the MF type was only polyethylene (PE) (79.1 % of total PR), while NMF accounted for 20.9 % of total PR. As well, NMF-polypropylene (PP) and NMF-PE accounted for 45.3 % and 39.7 % of total NMF respectively, followed by polystyrene accounting for 7.5 %. In the 0-20 cm soil layer, the spatial autocorrelation of mass and accumulation areas of MF were significantly (p < 0.05) positive, and their spatial pattern tended to cluster. The accumulation areas of MF was predoniment in northwest and southeast near the roadside in all soil layers, while the accumulation areas of NMF was higher near the landfill in the 0-20 cm soil layer. Landfill and residential areas were critical sources of PR for the farmland. Southwest wind and southeast wind were the main driving force of PR migration and their annual migration rates were 23.7 and 19.8 m·year-1. The functional groups on the surface of plastics were different after degradation (including different types and different utilization methods), and PR was oxidized could release or adsorb toxic substances from the soils. Generally, in order to reduce PR pollution, in addition to source control and recycling, farmland tillage should be avoided in the weather when the wind speed is strong, especially near the PR pollution source.

Field management changes the distribution of mesoplastic and macroplastic in Mollisols of Northeast China.

Mesoplastic (MaP) and macroplastic (MeP) coming from plastic mulching tend to cause negative effects on biota in ecosystems. However, it is still not clear how field management influences the distribution of MeP/MaP in soils. In this study, MeP/MaP was investigated in 0-20 and 20-30 cm soil layers of three vegetable fields (3.4-6.5 ha) after 13 years plastic-mulching in Mollisols of Northeast China under different management methods (MM) of fertilization and tillage frequency. The tillage frequency was MM2 > MM1 > MM3, while the fertilization was MM1 > MM2 > MM3. The results showed that polyethylene (PE), polypropylene (PP), polystyrene, polyvinyl chloride, polyethylene terephthalate (PET), polyamide, melamine-formaldehyde resin and polyether urethane were found in soil, and PE (>83.76%, from plastic mulching) was the predominant type of MeP/MaP. MeP abundance was significantly (p < 0.05) higher in MM1 and MM2 than that in MM3 in the 0-20 cm soil layer. MM1 and MM2 had the highest abundance of MeP/MaP of size <4 cm2 and 4-16 cm2, while MM3 had the highest abundance at the size >16 cm2. The broken index of MeP/MaP was significantly (p < 0.05) lower in MM2 compared with MM1 and MM3 in the 20-30 cm soil layer. Both tillage frequency and fertilization accelerate the breaking of plastics, especially since the influence was stronger from fertilization. Compared with original plastics, the PE, PP and PET's carbonyl index was significantly (p < 0.05) higher in the three MMs. Generally, fertilization and frequent tillage can reduce the physical effects of large-sized plastic debris on crop growth and increases the negative effects of small-sized plastic and new pollutants formed on biota in the agroecosystems. MeP/MaP recycling should be strengthened, and the irrigation and rotation of farmland should be carried out when the wind speed is weak to avoid plastic invasion.

Crops Change the Morphology, Abundance, and Mass of Microplastics in Mollisols of Northeast China.

Degradation of microplastics (MPs) by both physicochemical and biological processes in the natural environment is determined by the enzymes inside the soil, and which was severely influenced by crop growth and straw amendment (SA). However, it is still unclear how crop growth and SA influence degradation of MPs in soils. In this study, both catalase and sucrase were measured, and the stereomicroscope combined with microscopic infrared spectroscopy and scanning electron microscope (SEM) was used to detect the morphology and quantity of low-density polyethylene microplastic (LDPE-MP) and low-density polypropylene microplastic (LDPP-MP), after crop growth (maize and soybean, with and without SA, 1 and 2% MP) in an outdoor pot experiment, in the Mollisols. The results showed that the growth of the crops changed the morphology, functional groups (e.g., methylene, carbonyl), total mass, and abundance ratio of MPs of different sizes. These were possibly caused by enzymes that were significantly influenced by crop types, abundance, and types of MPs in the soils. Maize growth decreased the mass of LDPE-MP and LDPP-MP by 28.7 and 32.7%, respectively, and 2% (w/w) of LDPP-MP addition in soil decreased mass of 9%, which was higher than that in 1% (w/w) LDPP-MP addition in soil. Soybean growth with SA decreased the mass of LDPE-MP and LDPP-MP by 36.6 and 20.7%, respectively, than the control treatment (CK). Compared with CK, both crop growth and SA changed the abundance of MPs of different sizes and decreased the mean size of MPs. The LDPE-MP could be more easily degraded by enzymes in the soils compared to LDPP-MP when the MP size was smaller with surface roughness. Generally, both maize and soybean growth can accelerate MP change in soils, and MP change process was mainly determined by SA, MP types, and the dose effect of MP.

Molecularly Imprinted Polymers with Enzymatic Properties Reduce Cytokine Release Syndrome.

A core-shell molecularly imprinted polymer nanoparticle with biological enzyme functional characteristics was developed by oxidative polymerization of template protein and polydopamine on the surface of protease-copper phosphate hybrid nanoflowers by molecular imprinting technology and enzyme immobilization technology. The obtained molecularly imprinted polymer showed specific binding characteristics with the template protein. It recognized and enriched the target molecules through the surface molecularly imprinted sites of the shell structure. In addition, the bound target molecules were further degraded into fragments by nanozymes with biological enzyme characteristics in the core. In this study, molecular imprinting technology and biotechnology were combined to obtain bifunctional molecularly imprinted polymer nanoparticles that can not only enrich template molecules but also degrade them into fragments. Herein, we selected interleukin 6 (IL-6), the target molecule of cytokine release syndrome (CRS), as a template molecule, and reported a molecularly imprinted polymer with degrading enzyme properties that can rapidly reduce IL-6 levels in vivo, including a molecularly imprinted layer that can recognize and bind IL-6 and nanozymes that can degrade IL-6 and deactivate it. It is used to clear the excessive secretion of IL-6 in CRS and reduce the level of IL-6 in the body to achieve the purpose of adjuvant treatment of CRS.

Myrothecol A, a new alkylresorcinol with cytotoxicity from Myrothecium sp.

A new alkylresorcinol, myrothecol A (1), along with two known ones (2 and 3), were isolated from a fungal strain Myrothecium sp. GY170016. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was determined by electronic circular dichroism experiment. This is the first case of the presence of alkylresorcinols in genus Myrothecium. All the isolates were evaluated for their cytotoxic activities against human cancer cell line MCF-7 with IC50 values of 16.7, 13.2, 21.3 µM, respectively.

Development of a novel ssDNA aptamer targeting cardiac troponin I and its clinical applications.

Cardiac troponin I (cTnI) is a specific biomarker of acute myocardial infarction (AMI). However, cTnI detection kits prepared with antibodies have many defects. Nucleic acid aptamers are sequences of single-strand DNA or RNA that can overcome the deficiency of antibodies. Herein, sandwich ELONA methods were established based on aptamers. Two selected ssDNA aptamers (Apt3 and Apt6) showed high binding affinity and sensibility (Apt3: Kd = 1.01 ± 0.07 nM, Apt6: k = 0.68 ± 0.05) and did not bind to the same domain of cTnI. Therefore, these two aptamers can be applied to the ELONA methods. The detection range of cTnI using the dual-aptamer sandwich ELONA method was 0.05-200 ng/mL, and the bioanalytical method verification results can meet the national standard of Chinese Pharmacopoeia (2020 Edition). There was no difference between results of the dual-aptamer sandwich ELONA method and the diagnostic results of serum obtained from 243 people (P = 0.39, P ˃ 0.05). The sensitivity and specificity of the ELONA with cTnI in serum were 96.46% and 93.85%, respectively. Compared with the FICA kit, which is clinically used, the consequences of ELONA method are closer to the diagnostic results. This study suggests that the aptamers Apt3 and Apt6 have high affinity and strong specificity and that the dual-aptamer sandwich ELONA method has a wide detection range and can be used to determine cTnI in serum, with potential applications in the diagnosis of AMIs.

Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer.

BACKGROUND: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer. METHODS: We prepared the rapamycin liposomes using the ethanol injection method. The cellular uptake and biodistribution were detected by LC-MS and in vivo imaging system. MTT assay, transwell migration experiment, flow cytometry, and Western blot analysis evaluated the antitumor effect of rapamycin liposomes in vitro. Furthermore, HCT-116 tumor-bearing mice were used to assess the therapeutic efficacy of rapamycin liposomes in vivo. RESULTS: The prepared rapamycin liposomes had a particle size of 100±5.5 nm and with a narrow size distribution. In vitro cellular uptake experiments showed that the uptake of rapamycin liposomes by colorectal cells was higher than that of free rapamycin. Subsequently, in vivo imaging experiments also demonstrated that rapamycin liposomes exhibited higher tumor accumulation. Therefore, the ability of rapamycin liposomes to inhibit tumor proliferation, migration and to induce tumor apoptosis is superior to that of free rapamycin. We also demonstrated in vivo good antitumor efficacy of the rapamycin liposomes in HCT-116 xenograft mice. In addition, rapamycin liposomes and 5-FU can synergistically improve the efficacy of colorectal cancer via the Akt/mTOR and P53 pathways. CONCLUSION: Collectively, rapamycin liposomes are a potential treatment for colorectal cancer, as it not only improves rapamycin's antitumor effect but also synergistically enhances 5-FU's chemotherapy effect.