Interfacial engineering of Ti3C2 MXene/CdIn2S4 Schottky heterojunctions for boosting visible-light H2 evolution and Cr(VI) reduction.

Developing efficient heterojunction photocatalysts that have a high charge carrier separation rate and improved light-harvesting capacity is a crucial step in solving energy crisis and reducing environmental pollution. Herein, we synthesized few-layered Ti3C2 MXene sheets (MXs) by a manual shaking process, and combined with CdIn2S4 (CIS) to construct novel Ti3C2 MXene/CdIn2S4 (MXCIS) Schottky heterojunction through a solvothermal method. The strong interface between two-dimensional (2D) Ti3C2 MXene and 2D CIS nanoplates led to enhanced light-harvesting capacity and promoted charge separation rate. Additionally, the presence of S vacancies on the MXCIS surface helped to trap free electrons. The optimal sample, 5-MXCIS (with 5 wt% MXs loading), exhibited outstanding performance for photocatalytic hydrogen (H2) evolution and Cr(VI) reduction under visible light due to the synergistic effect of enhanced light-harvesting capacity and charge separation rate. The charge transfer kinetics was thoroughly studied using multiple techniques. The reactive species of •O2-, •OH and h+ were generated in 5-MXCIS system, and e- and •O2- radicals were found to be the main contributors to Cr(VI) photoreduction. Based on the characterization results, a possible photocatalytic mechanism for H2 evolution and Cr(VI) reduction was proposed. On the whole, this work provides new insights into the design of 2D/2D MXene-based Schottky heterojunction photocatalysts for boosting photocatalytic efficiency.

Self-Assembled Core-Shell Nanoscale Coordination Polymer Nanoparticles Carrying a Sialyltransferase Inhibitor for Cancer Metastasis Inhibition.

Despite hypersialylation of cancer cells together with a significant upregulation of sialyltransferase (ST) activity contributes to the metastatic cascade at multiple levels, there are few dedicated tools to interfere with their expression. Although transition state-based ST inhibitors are well-established, they are not membrane permeable. To tackle this problem, herein, we design and construct long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles carrying a transition state-based ST inhibitor, which make the inhibitor transmembrane and potently strip diverse sialoglycans from various cancer cells. In the experimental lung metastasis and metastasis prevention models, the nanoparticle device (NCP/STI) significantly inhibits metastases formation without systemic toxicity. This strategy enables ST inhibitors to be applied to cells and animals by providing them with a well-designed nanodelivery system. Our work opens a new avenue to the development of transition state-based ST inhibitors and demonstrates that NCP/STI holds great promise in achieving metastases inhibition for multiple cancers.

Government environmental protection subsidies, environmental tax collection, and green innovation: evidence from listed enterprises in China.

The government has issued a series of environmental laws and regulations to solve ecological problems, regulate environmental pollution, and drive enterprises to carry out green innovations. This paper constructs a theoretical framework of environmental protection subsidies, environmental tax collection, and enterprise green innovation by taking the China A-share manufacturing listed enterprises as a research sample. Further, we explore the contingency impact of the market-expected performance gap and market competition on the enterprise green innovation. The empirical results show that there is a linear positive driving relationship between environmental protection subsidies and enterprise green innovation. The relationship between environmental tax collection and enterprise green innovation is a U-shaped relationship that first inhibits and then promotes. The market expectation performance gap moderates between environmental subsidy and enterprise green innovation. Market competition plays a reinforcing role in environmental subsidy, environmental tax collection, and enterprise green innovation. These research findings are conducive to providing theoretical support and reference for the government to encourage enterprises to actively carry out green innovation in practice, thereby helping to promote green development in the country.

Chloroquine and Hydroxychloroquine Are Novel Inhibitors of Human Organic Anion Transporting Polypeptide 1A2.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used to treat malaria and inflammatory diseases, long-term usage of which often causes severe side effects, especially retinopathy. Solute carrier transporters (SLCs) are important proteins responsible for the cellular uptake of endogenous and exogenous substances. Inhibitors competing with transporter substrates for SLCs often results in unfavorable toxicities and unsatisfactory therapeutic outcomes. We investigated the inhibitory effect of CQ and HCQ on substrate uptake mediated through a range of important SLC transporters in overexpressing human embryonic kidney (HEK293) cells. Our data revealed that both CQ and HCQ potently inhibit the uptake activity of organic anion transporting polypeptide 1A2 (OATP1A2). We recently reported OATP1A2 to be expressed in human retinal pigment epithelium (RPE), where it mediates cellular uptake of all-trans-retinol (atROL), a key step in the classical visual cycle. In this study, we demonstrate that CQ and HCQ could markedly impair atROL uptake in OATP1A2-expressing HEK293 cells and more importantly, in primary human RPE cells. Our study shows that CQ and HCQ are novel inhibitors of OATP1A2 and significantly impair OATP1A2-mediated substrate uptake, particularly transport of atROL into the RPE. This effect may compromise the function of the classic visual cycle leading to vision impairment and contribute to the retinopathy observed clinically in patients using CQ or HCQ.

Human oligopeptide transporter 2 (PEPT2) mediates cellular uptake of polymyxins.

OBJECTIVES: Polymyxins are a last-line therapy to treat MDR Gram-negative bacterial infections. Nephrotoxicity is the dose-limiting factor for polymyxins and recent studies demonstrated significant accumulation of polymyxins in renal tubular cells. However, little is known about the mechanism of polymyxin uptake into these cells. Oligopeptide transporter 2 (PEPT2) is a solute carrier transporter (SLC) expressed at the apical membrane of renal proximal tubular cells and facilitates drug reabsorption in the kidney. In this study, we examined the role of PEPT2 in polymyxin uptake into renal tubular cells. METHODS: We investigated the inhibitory effects of colistin and polymyxin B on the substrate uptake mediated through 15 essential SLCs in overexpressing HEK293 cells. The inhibitory potency of both polymyxins on PEPT2-mediated substrate uptake was measured. Fluorescence imaging was employed to investigate PEPT2-mediated uptake of the polymyxin fluorescent probe MIPS-9541 and a transport assay was conducted with MIPS-9541 and [(3)H]polymyxin B1. RESULTS: Colistin and polymyxin B potently inhibited PEPT2-mediated [(3)H]glycyl-sarcosine uptake (IC50 11.4 ± 3.1 and 18.3 ± 4.2 µM, respectively). In contrast, they had no or only mild inhibitory effects on the transport activity of the other 14 SLCs evaluated. MIPS-9541 potently inhibited PEPT2-mediated [(3)H]glycyl-sarcosine uptake (IC50 15.9 µM) and is also a substrate of PEPT2 (Km 74.9 µM). [(3)H]polymyxin B1 was also significantly taken up by PEPT2-expressing cells (Km 87.3 µM). CONCLUSIONS: Our study provides the first evidence of PEPT2-mediated uptake of polymyxins and contributes to a better understanding of the accumulation of polymyxins in renal tubular cells.

The altered renal and hepatic expression of solute carrier transporters (SLCs) in type 1 diabetic mice.

Diabetes mellitus is a chronic metabolic disorder that significantly affects human health and well-being. The Solute carrier transporters (SLCs), particularly the Organic anion/cation transporters (Oats/Octs/Octns), Organic anion transporting polypeptides (Oatps) and Oligopeptide transporters (Pepts) are essential membrane proteins responsible for cellular uptake of many endogenous and exogenous substances such as clinically important drugs. They are widely expressed in mammalian key organs especially the kidney and liver, in which they facilitate the influx of various drug molecules, thereby determining their distribution and elimination in body. The altered expression of SLCs in diabetes mellitus could have a profound and clinically significant influence on drug therapies. In this study, we extensively investigated the renal and hepatic expression of twenty essential SLCs in the type 1 diabetic Ins2Akita murine model that develops both hyperglycemia and diabetes-related complications using real-time PCR and immunoblotting analysis. We found that the renal expression of mOatp1a1, mOatp1a6, mOat1, mOat3, mOat5, mOct2 and mPept2 was decreased; while that of mPept1 was increased at the mRNA level in the diabetic mice compared with non-diabetic controls. We found up-regulated mRNA expression of mOatp1a4, mOatp1c1, mOctn2, mOct3 and mPept1 as well as down-regulation of mOatp1a1 in the livers of diabetic mice. We confirmed the altered protein expression of several SLCs in diabetic mice, especially the decreased renal and hepatic expression of mOatp1a1. We also found down-regulated protein expression of mOat3 and mOctn1 in the kidneys as well as increased protein expression of mOatp1a4 and mOct3 in the livers of diabetic mice. Our findings contribute to better understanding the modulation of SLC transporters in type 1 diabetes mellitus, which is likely to affect the pharmacokinetic performance of drugs that are transported by these transporters and therefore, forms the basis of future therapeutic optimization of regimens in patients with type 1 diabetes mellitus.

Identification and crude protein extract of endophytic bacteria strain KLXD06 antagonistic against MRSA isolated from Hemsleya sinesis.

Hemsleya sinesis Cogn has a variety of medicinal value. Strain KLXD06 is an endophytic bacteria isolated from H. sinesis exhibited significant inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA). This strain was identified by methods including 16S rDNA sequence homology and phylogenetic analysis morphological, biochemical and physiological characteristics analysis. Ccrude protein from KLXD06 was extracted by ammon ium sulfate salting-out. The results showed that strain KLXD06 was identified as Serratia marcescens. Antibacterial crude protein from KLXD06 was extracted by ammon ium sulfate salting-out, has a thermal stability.

[Correlation of length of vascular segment in vitro with endothelin-1 metabolism of endothelial cells--study on accumulative effect of tensile stress in the upper endothelial cell membrane. III].

A few of flow experiments were utilized to verify a theoretical hypothesis proposed by Fung and coworker which showed that the tensile stress in the upper cell membrane of the vascular endothelium could accumulate upstream against the direction of blood flow. Endothelial cells from replicate human umbilical vein segment (HUVSEC) in vitro with length of 11 cm and 21 cm were exposed to the same pulsatile laminar shear stress averaged of 0.12 N/m2 for 42 hours. The average production rate of endothelin-1(ET-1), at 11 cm segment is 50% lower than that at 21 cm segment(16.93 +/- 0.89) vs. (26.13 +/- 1.79) pg/cm2.h respectively. The average production rate of ET-1 under pulsatile laminar flow was significantly higher than that under steady laminar flow. It showed that, high correlation of the length of HUVSEC with their ET-1 metabolism exists, suggesting that the tensile stress in the upper endothelial cell membrane could accumulate.