Rapamycin Nano-Micelle Ophthalmic Solution Reduces Corneal Allograft Rejection by Potentiating Myeloid-Derived Suppressor Cells' Function

Allograft rejection is the major cause of corneal allograft failure. Rapamycin (RAPA) has been reported as an effective and novel immunosuppressive agent for patients undergoing corneal transplantation. However, its high water insolubility and low bioavailability have strongly constrained its clinical application. In this study, we successfully developed a RAPA nano-micelle ophthalmic solution and found that corneal allograft survival in recipients treated with RAPA nano-micelle ophthalmic solution was significantly prolonged for more than 2 months, with less inflammatory infiltration, decreased production of pro-inflammatory factors, and elevated recruitment of myeloid-derived suppressor cells (MDSCs). MDSCs from mice treated with RAPA nano-micelle ophthalmic solution could significantly inhibit the proliferation of CD4+T cells through increased expressions of inducible nitric oxidase (iNOS) and arginase-1 (Arg-1). The activity blockade of Arg-1 and iNOS pharmacologically reversed their immunosuppressive ability. Moreover, the effects of RAPA were antagonized by the administration of anti-Gr-1 antibody or by inhibiting the activity of iNOS pharmacologically. In addition, RAPA nano-micelle also effectively alleviated allograft rejection in high-risk rabbit penetrating keratoplasty (PKP) models with corneal vascularization. Collectively, our results demonstrate that RAPA nano-micelle ophthalmic solution could improve the immunosuppressive activity of MDSCs through elevated expression of Arg-1 and iNOS, which highlights the possible therapeutic applications of RAPA against corneal allograft rejection

Seasonal Total Nitrogen and Phosphorus Variation, Speciation, and Composition in the Maowei Sea Affected by Riverine Flux Input, South China Sea

Human activities have altered global nutrient cycling and have significantly changed marine systems. This is evidenced by the significant changes in nitrogen and phosphorus availability. The Maowei Sea (MWS) is the largest oyster culture bay in southwest China. From August 2018 to May 2019, the spatial and temporal nutrient concentrations and fluxes in MWS using system-wide scale seasonal data were assessed from river estuaries and adjacent coastal waters. The annual average concentrations of total nitrogen (TN) and total phosphorus (TP) in the three estuaries of Maolingjiang River (MLJR), Dalanjiang River (DLJR) and Qinjiang River (QJR) were 3.00 mg/L and 0.183 mg/L, respectively. Therein, the highest TN and TP concentrations were in DLJR, the lowest TN concentration was in MLJR, and the lowest TP concentration was in QJR. DIN and DIP were the main forms of TN and TP, accounting for 80.9% and 59.4%, respectively. The main form of DIN in MLJR and QJR was NO3−, accounting for 86.8% and 84.4%, respectively, while the main form of DIN in DLJR was NH4+, accounting for 55.9%. The annual flux of pollutants discharged into MWS from the three estuaries is 10,409.52 t for TN and 556.21 t for TP. The month with the largest contribution to the annual load was July, accounting for 29.2% and 24.2% of TN and TP, respectively, and the fluxes of TN and TP were significantly different among the three seasons (p < 0.05). The annual average concentrations in the surface waters of the MWS were 1.07 mg/L for TN and 0.129 mg/L for TP, and there were significant differences (p < 0.05) in the concentrations of TN and TP among the three seasons. The annual average N/P ratios of the river water and seawater were 43 and 18, respectively, which were higher than the Redfield ratio (N/P = 16), indicating that the growth of phytoplankton in MWS may be limited by phosphorus. Eutrophication owing to nutrient pollution in the three estuaries may be persistent in adjacent coastal waters, and land–ocean integrated mitigation measures should be taken to effectively improve the water quality in the river estuary and coastal water

Preparation of a Solvent-Resistant Nanofiltration Membrane of Liquefied Walnut Shell Modified by Ethylenediamine

N,N-dimethylformamide (DMF) has excellent chemical stability and is widely used as an aprotic polar solvent. In order to reduce production costs and reduce pollution to the surrounding environment, it is necessary to recycle and reuse DMF. Previous research has found that the thin film composite nanofiltration membrane prepared from liquefied walnut shells exhibited a high rejection rate in DMF, but relatively low permeance and mechanical strength. In order to increase permeance without compromising the separation performance, ethylenediamine (EDA) is used as a modifier to graft onto the structure of liquefied walnut shell through the Mannich reaction. Then, modified liquefied walnut shell as an aqueous monomer reacts with trimesoyl chloride (TMC) via the interfacial polymerization method on the EDA-crosslinked polyetherimide (PEI) membrane. The results show that the permeance of the prepared membrane is significantly improved by an order of magnitude, demonstrating a rejection rate of 98% for crystal violet (CV), and a permeance of 3.53 L m−2 h−1 bar−1 in DMF. In conclusion, this study reveals the potential of utilizing liquefied walnut shells as raw materials for preparing high-performance separation membranes and demonstrates that surface modification is a feasible approach to enhance permeance of membranes without sacrificing the rejection rate

Metal Content and Enrichment in Bivalves within the Drainage Area of Seawater Used for a Desulfurization Process in Zhanjiang Bay, China

As heavy metals are easy to accumulate and have strong biological toxicity, they pose a potential threat to human health by entering the human body through the cumulative effect of marine life. Land-based input is an important source of heavy metals in the ocean, which has a great influence on coastal water quality. In this study, the spatial distribution characteristics of heavy metals (Zn, Cu, Cd, Pb, Cr, As) in the coastal waters of the desulfurization process outlet of a power plant in Zhanjiang Bay were investigated, and the enrichment behavior of heavy metals by organisms (oysters and barnacles) were also studied. The results showed that, before the seawater desulfurization system was closed, there were high concentrations of heavy metals (Cu, Zn, Cd, Pb and Cr) in the surface seawater near the drainage outlet. The concentrations of these heavy metals in the surface seawater were higher than those in the bottom seawater within 100 m of the drainage outlet. After the seawater desulfurization system was closed, the average concentrations of Cu, Cr and As in seawater at each station decreased by 17.04%, 37.52% and 29.53%, respectively, while the average concentrations of Zn, Cd and Pb increased by 17.05%, 32.87% and 48.77%, respectively. Single factor pollution index (SFI) and bio-concentration factor (BCF) showed that there was a potential high accumulation risk of Zn in oysters and barnacles near the drainage outlet of desulfurization wastewater (0.5 < SFI < 1 and BCF > 1000). The SFI and BCF of each metal in oysters and barnacles decreased with the increase in distance from the drainage outlet. Generally, the coastal water quality of desulfurization process drainage area in Zhanjiang Bay were below the class Ⅱof the “Seawater quality standard” (GB 3097-1997) of China. However, the heavy metals content in seawater and organisms near the drainage outlet is slightly higher. This suggested that if the seawater desulfurization process runs for a long time, it will have a negative impact on the coastal water and organisms

Generation of a squamous cell carcinoma mouse model for lineage tracing of BMI1+ cancer stem cells

Summary: BMI1-expressing cancer stem cells (CSCs) play a key role in the development, progression, therapy resistance, recurrence, and metastasis of head and neck squamous cell carcinoma (HNSCC). Here, we present a chemically-induced HNSCC mouse model, genetically and pathologically similar to human HNSCC. This protocol describes how to use genetic lineage tracing based on the Cre-loxP recombination strategy, which allows us to study the regulation and targeting of BMI1+ CSCs in primary tumors and lymph node metastases.For complete details on the use and execution of this protocol, please refer to Chen et al. (2017) and Jia et al. (2020

AWdpCNER: Automated Wdp Chinese Named Entity Recognition from Wheat Diseases and Pests Text

Chinese named entity recognition of wheat diseases and pests is an initial and key step in constructing knowledge graphs. In the field of wheat diseases and pests, there are problems, such as lack of training data, nested entities, fuzzy entity boundaries, diverse entity categories, and uneven entity distribution. To solve the above problems, two data augmentation methods were proposed to expand sentence semantic information on the premise of fully mining hidden knowledge. Then, a wheat diseases and pests dataset (WdpDs) for Chinese named entity recognition was constructed containing 21 types of entities and its domain dictionary (WdpDict), using a combination of manual and dictionary-based approaches, to better support the entity recognition task. Furthermore, an automated Wdp Chinese named entity recognition model (AWdpCNER) was proposed. This model was based on ALBERT-BiLSTM-CRF for entity recognition, and defined specific rules to calibrate entity boundaries after recognition. The model fusing ALBERT-BiLSTM-CRF and rules amendment achieved the best recognition results, with a precision of 94.76%, a recall of 95.64%, and an F1-score of 95.29%. Compared with the recognition results without rules amendment, the precision, recall, and F1-score was increased by 0.88 percentage points, 0.44 percentage points, and 0.75 percentage points, respectively. The experimental results showed that the proposed model could effectively identify Chinese named entities in the field of wheat diseases and pests, and this model achieved state-of-the-art recognition performance, outperforming several existing models, which provides a reference for other fields of named entities recognition such as food safety and biology

Alkyl Sulfoxides as Radical Precursors and Their Use in the Synthesis of Pyridine Derivatives

We report here the use of simple and readily available alkyl sulfoxides as precursors to radicals and their application in the preparation of pyridine derivatives. We show that alkyl sulfoxides form EDA complexes with N-methoxy pyridinium salts, which upon visible light irradiation, undergo a cascade of radical processes to afford pyridine derivatives smoothly. This method displays broad scope with respect to both reactants. The synthetic versatility of sulfoxides as a handle in chemistry adds to the power of this transformation. The method is further applied in the synthesis of various pyridyl C–glycosides that are previously difficult to access

Seasonal Total Nitrogen and Phosphorus Variation, Speciation, and Composition in the Maowei Sea Affected by Riverine Flux Input, South China Sea

Human activities have altered global nutrient cycling and have significantly changed marine systems. This is evidenced by the significant changes in nitrogen and phosphorus availability. The Maowei Sea (MWS) is the largest oyster culture bay in southwest China. From August 2018 to May 2019, the spatial and temporal nutrient concentrations and fluxes in MWS using system-wide scale seasonal data were assessed from river estuaries and adjacent coastal waters. The annual average concentrations of total nitrogen (TN) and total phosphorus (TP) in the three estuaries of Maolingjiang River (MLJR), Dalanjiang River (DLJR) and Qinjiang River (QJR) were 3.00 mg/L and 0.183 mg/L, respectively. Therein, the highest TN and TP concentrations were in DLJR, the lowest TN concentration was in MLJR, and the lowest TP concentration was in QJR. DIN and DIP were the main forms of TN and TP, accounting for 80.9% and 59.4%, respectively. The main form of DIN in MLJR and QJR was NO3−, accounting for 86.8% and 84.4%, respectively, while the main form of DIN in DLJR was NH4+, accounting for 55.9%. The annual flux of pollutants discharged into MWS from the three estuaries is 10,409.52 t for TN and 556.21 t for TP. The month with the largest contribution to the annual load was July, accounting for 29.2% and 24.2% of TN and TP, respectively, and the fluxes of TN and TP were significantly different among the three seasons (p p < 0.05) in the concentrations of TN and TP among the three seasons. The annual average N/P ratios of the river water and seawater were 43 and 18, respectively, which were higher than the Redfield ratio (N/P = 16), indicating that the growth of phytoplankton in MWS may be limited by phosphorus. Eutrophication owing to nutrient pollution in the three estuaries may be persistent in adjacent coastal waters, and land–ocean integrated mitigation measures should be taken to effectively improve the water quality in the river estuary and coastal water