Neddylation of RhoA impairs its protein degradation and promotes renal interstitial fibrosis progression in diabetic nephropathy.

Diabetic nephropathy (DN) is a common and serious complication of diabetes, characterized by chronic fibro-inflammatory processes with an unclear pathogenesis. Renal fibrosis plays a significant role in the development and progression of DN. While recent research suggests that the neddylation pathway may influence fibrotic processes, its specific dysregulation in DN and the underlying mechanisms remain largely unexplored.

A digestive system microphysiological platform for assessment of internal-exposure risks and metabolic disease mechanisms induced by multi-size nano-plastics.

Nano-plastics (NPs) are emerging hazardous environmental contaminants that pose health risks with size-dependent toxic effects and are potential risk factors for hepatocellular carcinoma (HCC) and lipid metabolism disorders including non-alcoholic fatty liver disease (NAFLD). However, their underlying molecular mechanisms remain unclear. To shed more light on the causes of these risks, we developed a digestive system microphysiological platform (DS-MPP) for simulating dynamic internal-exposure of multi-size NPs in the gastrointestinal tract and liver.

Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Nonstructural Protein Inhibitors.

The COVID-19 pandemic, exacerbated by persistent viral mutations, underscored the urgent need for diverse inhibitors targeting multiple viral proteins. In this study, we utilized covalent DNA-encoded libraries to discover innovative triazine-based covalent inhibitors for the 3-chymotrypsin-like protease (3CL, Nsp5) and the papain-like protease (PL) domains of Nsp3, as well as novel non-nucleoside covalent inhibitors for the nonstructural protein 12 (Nsp12, RdRp). Optimization through molecular docking and medicinal chemistry led to the development of , a nonpeptide 3CL inhibitor with an IC of 0.

Study on the mechanisms of defective spermatogenesis induced by TiO NPs based on 3D blood-testis barrier microfluidic chip.

Titanium dioxide nanoparticles (TiO NPs) can reduce sperm number, but the mechanisms of defective spermatogenesis induced by TiO NPs have not been studied through cell-cell interactions at present. A kind of biomimetic three-dimensional blood-testis barrier microfluidic chip capable of intercellular communication was constructed with soft lithography techniques, including Sertoli cell (TM4), spermatogonia (GC-1) and vascular endothelial cell units, to study the mechanisms of TiO NPs-induced defective spermatogenesis. TM4 and GC-1 cells cultured in TiO NPs exposure and control chips were collected for transcriptomics and metabonomics analysis, and key proteins and metabolites in changed biological processes were validated.

Air-Liquid Interface Microfluidic Monitoring Sensor Platform for Studying Autophagy Regulation after PM2.5 Exposure.

Undoubtedly, a deep understanding of PM-induced tumor metastasis at the molecular level can contribute to improving the therapeutic effects of related diseases. However, the underlying molecular mechanism of fine particle exposure through long noncoding RNA (lncRNA) regulation in autophagy and, ultimately, lung cancer (LC) metastasis remains elusive; on the other hand, the related monitoring sensor platform used to investigate autophagy and cell migration is lacking. Herein, this study performed an air-liquid interface microfluidic monitoring sensor (AIMMS) platform to analyze human bronchial epithelial cells after PM stimulation.

Comparison of the Watson formula and bioimpedance spectroscopy for measuring body volume and calculating kt/V in patients with peritoneal dialysis.

There were significant differences between Vwat and Vbis and between Kt/Vwat and Kt/Vbis. Kt/Vwat may underestimate small-solute dialysis adequacy in most cases. Kt/Vbis instead of Kt/Vwat could be accounted for in creating individualized dialysis prescriptions if the patient has no obvious clinical symptoms.

FGF1 ameliorates retinal inflammation via suppressing TSPO signal in a type 2 diabetes mouse model.

Translocator protein (18 kDa) (TSPO) plays an important role in retinal neuroinflammation in the early stage of diabetic retinopathy (DR). Studies have found that a FGF1 variant (FGF1) with reduced proliferative potency exerts excellent anti-inflammatory effects and potential therapeutic value for diabetic complications. In this study, intravitreal injection of FGF1 was administrated every week for one month in db/db mice, which are genetically predisposed to develop type 2 diabetes mellitus and early retinopathy.

ABPP-CoDEL: Activity-Based Proteome Profiling-Guided Discovery of Tyrosine-Targeting Covalent Inhibitors from DNA-Encoded Libraries.

DNA-encoded chemical library (DEL) has been extensively used for lead compound discovery for decades in academia and industry. Incorporating an electrophile warhead into DNA-encoded compounds recently permitted the discovery of covalent ligands that selectively react with a particular cysteine residue. However, noncysteine residues remain underexplored as modification sites of covalent DELs.

Modular Click Assembly DNA-Encoded Glycoconjugate Libraries with on-DNA Functional Group Transformations.

Carbohydrates are an important class of naturally active products and play vital roles in regulating various physiological activities. To meet the demand for carbohydrate-based libraries used for the identification of potential drug candidates for pharmaceutical-related targets, we developed a set of on-DNA protocols to construct the DNA-encoded glycoconjugates, including Seyferth-Gilbert homologation, anomeric azidation, and CuAAC cyclization. These on-DNA chemistries enable the generation and modification of DNA-linked glycosyl compounds with good conversions and broad substrate scope.

Integrated system for rapid enrichment and detection of airborne polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are extremely toxic environmental pollutants, which are harmful to the human body. Direct collection and analysis of airborne PAHs is essential for air quality monitoring. Herein, we demonstrated an integrated system for airborne PAHs enrichment and detection.

Assessment of cancer-related signaling pathways in responses to polystyrene nanoplastics via a kidney-testis microfluidic platform (KTP).

As a new type of environmental pollutants, micro/nano plastics (MPs/NPs) derived from plastic products are commonly contact in daily life and lead to some serious health issues. The toxicity effects of MPs/NPs on the human body have aroused wide concerns. Although MPs/NPs have been reported to be transmitted into the kidney and reproductive organs, the molecular mechanisms of MPs/NPs toxicity remain unclear due to the lack of a physiologically relevant organ-organ linking platform in vitro.

Identification of RPGR ORF15 mutation for X-linked retinitis pigmentosa in a large Chinese family and in vitro correction with prime editor.

X-linked retinitis pigmentosa (XLRP) is the most severe form of Retinitis Pigmentosa (RP) and one of the leading causes of blindness in the world. Currently, there is no effective treatment for RP. In the present study, we recruited a XLRP family and identified a 4 bp deletion mutation (c.

Emerging roles of circRNAs in mice kidney with aging.

Circular RNA (circRNA) is a novel type of noncoding RNA expressed in different tissues and species. Up to now, little is known of the function and expression of circRNAs in kidney aging. In this research, we used RNA sequencing to identify 11,929 circRNAs in kidney from 3-, 12-, and 24-month-old mice, of which 12 circRNAs were validated by qPCR.

Noncontact Intraocular Pressure Measurement over Bandage Contact Lens and the Effect of Pentacam and Corvis ST's IOP Correction System.

Purpose: To evaluate the influence of intraocular pressure (IOP) measurement while wearing bandage contact lens (BCL) and the effect of Pentacam and Corvis ST's correction systems.

Methods: It was a prospective comparative study. Forty healthy subjects (40 eyes) were included in this study.

Renal-on-Chip Microfluidic Platform with a Force-Sensitive Resistor (ROC-FS) for Molecular Pathogenesis Analysis of Hydronephrosis.

Hydronephrosis is one of the most common diseases in urology. However, due to the difficulties in clinical trials and the lack of reliable platforms, the surgical indicators are not clear. Herein, the renal-on-chip with a force-sensitive resistor microfluidic platform was established to simulate the state of hydronephrosis.

A General Set of DNA-Compatible Reactions for Preparing DNA-Tagged Multisubstituted Pyrroles.

DNA-encoded library (DEL) technology provided a powerful screening platform for identifying potential bioactive small molecules with high affinity to biologically interesting targets. Essential to a successful DEL campaign are the drug-like small molecular moieties of DNA-encoded libraries with expanded chemical space. Our laboratory has been working on developing and producing novel DNA-encoded libraries that complement current reported DELs.

Association of PM with Insulin Resistance Signaling Pathways on a Microfluidic Liver-Kidney Microphysiological System (LK-MPS) Device.

Insulin resistance (IR) is a typical sign of metabolic dysregulation caused by fine particulate matter (PM), but the underlying signaling has not been clearly determined. Herein, a microfluidic liver-kidney microphysiological system (LK-MPS) is presented to assess the signaling pathways of IR generated by PM at 200 μg/mL for 24 h. The LK-MPS device consisted of a biomimetic liver-kidney architecture and reconstructed two circulation paths: the liver metabolism-kidney excretion (LM-KE) and kidney excretion-liver metabolism (KE-LM), by which PM is feasibly distributed in the two organs.

Diversified strategy for the synthesis of DNA-encoded oxindole libraries.

DNA-encoded library technology (DELT) employs DNA as a barcode to track the sequence of chemical reactions and enables the design and synthesis of libraries with billions of small molecules through combinatorial expansion. This powerful technology platform has been successfully demonstrated for hit identification and target validation for many types of diseases. As a highly integrated technology platform, DEL is capable of accelerating the translation of synthetic chemistry by using on-DNA compatible reactions or off-DNA scaffold synthesis.

The Effect of Peroral Endoscopic Myotomy in Achalasia Patients with Prior Endoscopic Intervention: A Systematic Review and Meta-Analysis.

Background: Peroral endoscopic myotomy (POEM) has been reported to be effective in achalasia patients with prior failed endoscopic intervention (PFI). We performed this meta-analysis to compare and summarize the clinical outcome of POEM in patients with or without prior endoscopic intervention.

Method: We searched relevant studies published up to March 2020.

Synthetic Studies toward DNA-Encoded Heterocycles Based on the On-DNA Formation of α,β-Unsaturated Ketones.

Taking advantage of the diversity-oriented synthesis strategy with α,β-unsaturated carbonyl compounds, we have successfully established the DNA-compatible transformations for various heterocyclic scaffolds. The ring-closure reactions for pyrrole, pyrrolidine, pyrazole, pyrazoline, isoxazoline, pyridine, piperidine, cyclohexenone, and 5,8-dihydroimidazo[1,2-]pyrimidine were elegantly demonstrated in a DNA-compatible format. These efforts paved the way for preparing DNA-encoded libraries with more extensive chemical space.