Molecular mechanism of GSDMD mediated glomerular endothelial cells pyroptosis: An implying in the progression of diabetic nephropathy.

Diabetic nephropathy (DN), a chronic progressive kidney disease, is the most prevalent microvascular complication associated with diabetes which causes the end-stage renal disease. Glomerular endothelial cells (GECs) are one of the inherent cells of the glomerulus and are particularly susceptible to be damaged by glucose, lipids and inflammatory factors. Numerous studies indicated that GECs injury was a critical pathological event in the early stages of DN. Previous studies have shown that podocyte pyroptosis occurred through the classical caspase-1 pathway, leading to kidney injury. However, the occurrence of pyroptosis in GECs and the underlying mechanism remain unclear. In this study, we investigated the pyroptosis of GECs during DN and its underlying mechanism. Upon stimulation with high glucose (HG), we observed the upregulation of GSDMD and cleaved N-terminus, disruption of cell membrane integrity, and an increase in IL-18 inflammatory cytokines. Also, we found that the expression of caspase-11, GSDMD and GSDMD-N were increased in C57BL/6J mice induced by STZ combined with high sugar and fat. In addition, the pathological results of kidney showed a significant thickening of the glomerular basement membrane, abnormal increasement of extracellular matrix and hyperplasia with blurred boundaries of glomerulus. Furthermore, interfering the expression of GSDMD improved the pathological degree of kidney. These findings indicated that the pyroptosis of GECs during DN was facilitated by the non-classical pathway of caspase-11/GSDMD, ultimately leading to GECs injury and further aggravating the progression of DN. This work highlights the potential of GSDMD as a therapeutic target for the treatment of DN.

VEGF aptamer/i-motif-grafted multi-functional SPION nanocarrier for chemotherapeutic/phototherapeutic synergistic research.

Chemotherapeutic agents and photosensitizers often suffer from poor tumor selectivity, high side toxicity, or low water solubility. To address these problems, various drug delivery systems (DDS) have been explored but most of them are toxic, difficult to synthesize, or of single function. In order to design a highly biocompatible, conveniently prepared, multi-functional drug delivery system, herein, an aptamer of vascular endothelial growth factor (VEGF) and a cytosine (C)-DNA fragment were grafted on the surface of superparamagnetic iron oxide nanoparticles (SPION), and then a chemotherapeutic agent daunomycin (DNM) and a photosensitizer 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP) were self-assembled with the hybridized VEGF-based DNA structure. By loading DNM and TMPyP, the DDS displayed strong chemotherapeutic/phototherapeutic capability against cancer cells via mechanisms such as mitochondrial dysfunction and ROS elevation, which triggered the apoptosis of the tumor cells. The dual delivery of chemotherapeutical agents and photosensitizers with aptamer/C-rich DNA successfully integrated the functions of pH stimuli-responsive drug release and chemotherapeutic/phototherapeutic modalities into one single system and thus could be considered as an ideal drug delivery vehicle with great potential in clinic.

Triboelectric Nanogenerator-Based Sensor Systems for Chemical or Biological Detection.

The rapid advances in the Internet of things and wearable devices have created a massive platform for sensor systems that detect chemical or biological agents. The accelerated development of these devices in recent years has simultaneously aggravated the power supply problems. Triboelectric nanogenerators (TENGs) represent a thriving renewable energy technology with the potential to revolutionize this field. In this review, the significance of TENG-based sensor systems in chemical or biological detection from the perspective of the development of power supply for biochemical sensors is discussed. Further, a range of TENGs are classified according to their roles as power supplies and/or self-powered active sensors. The TENG powered sensor systems are further discussed on the basis of their framework and applications. The working principles and structures of different TENG-based self-powered active sensors are presented, along with the classification of the sensors based on these factors. In addition, some representative applications are introduced, and the corresponding challenges are discussed. Finally, some perspectives for the future innovations of TENG-based sensor systems for chemical/biological detection are discussed.

High rotational speed hand-powered triboelectric nanogenerator toward a battery-free point-of-care detection system.

The timely biochemical detection of environmental pollutants or infectious disease is a predominant challenge for global health and people living in remote areas. However, the energy supply is still difficult for both the pretreatment and test steps, especially for diagnostics in resource-limited environments or outdoor point-of-care testing. Herein, we demonstrate a hand-powered triboelectric nanogenerator (TENG) system, which can simultaneously accomplish centrifugal pretreatment and analysis without an additional power supply. The complete separation of plasma from red blood cells can be achieved within 1.5 min at an operation frequency of 1 Hz. Besides, according to the impressive high rotational speed of 7500 rpm, the rotating mechanical energy can be efficiently recycled by the TENG to power different electronic devices, such as an electronic watch or thermometer. As a demonstration, the pretreatment of lake water and the detection of hydrogen peroxide contained in it has been realized. The combination of the system with different types of sensors will further promote its applications in multifarious biochemical detections. Moreover, this TENG system is effective, field-portable and ultra-low cost, and is promising for battery-free point-of-care diagnostic systems for outdoor or harsh environments.

Aptamer-assisted superparamagnetic iron oxide nanoparticles as multifunctional drug delivery platform for chemo-photodynamic combination therapy.

Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.

The Bio-Safety Concerns of Three Domestic Temporary Hair Dye Molecules: Fuchsin Basic, Victoria Blue B and Basic Red 2.

Hair-coloring products include permanent, semi-permanent and temporary dyes that vary by chemical formulation and are distinguished mainly by how long they last. Domestic temporary hair dyes, such as fuchsin basic, basic red 2 and Victoria blue B, are especially popular because of their cheapness and facile applications. Despite numerous studies on the relationship between permanent hair dyes and disease, there are few studies addressing whether these domestic temporary hair dyes are associated with an increased cancer risk. Herein, to ascertain the bio-safety of these temporary hair dyes, we comparatively studied their percutaneous absorption, hemolytic effect and cytotoxic effects in this paper. Furthermore, to better understand the risk of these dyes after penetrating the skin, experimental and theoretical studies were carried out examining the interactions between the dyes and serum albumins as well as calf thymus (CT)-DNA. The results showed that these domestic temporary hair dyes are cytotoxic with regard to human red blood cells and NIH/3T3 cell lines, due to intense interactions with bovine serum albumin (BSA)/DNA. We conclude that the temporary hair dyes may have risk to human health, and those who use them should be aware of their potential toxic effects.

Spiradiclislonganensis, a new species of Rubiaceae from China.

A new species of Spiradiclis (Rubiaceae) was found during our field trip to Guangxi, China, and is described here as Spiradiclislonganensis R. J. Wang. This species is readily distinguishable from other prostrate and decumbent species of the genus described previously by dense pubescence all over the plant, 5-20 small flowers per cymose, linear calyx lobes, and tubular corolla. The conservation status of VU was preliminarily assessed according to IUCN categories and criteria.