Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

Aggregation-Induced Catalysis: Asymmetric Catalysis with Chiral Aggregates.

So far, there have been 4 methods to control chirality including the use of chiral auxiliaries, reagents, solvents, and catalysts documented in literature and textbooks. Among them, asymmetric catalysts are normally divided into homogeneous and heterogeneous catalysis. In this report, we present a new type of asymmetric control-asymmetric catalysis via chiral aggregates that would not belong to the above categories. This new strategy is represented by catalytic asymmetric dihydroxylation reaction of olefins in which chiral ligands are aggregated by taking advantage of typical aggregation-induced emission systems containing tetrahydrofuran and H2O cosolvents. It was proven that the chiral induction can be enhanced from er of 78:22 to 97:3 simply by changing the ratios of these 2 cosolvents. The formation of chiral aggregates of asymmetric dihydroxylation ligands, (DHQD)2PHAL and (DHQ)2PHAL, has been proven by aggregation-induced emission and a new analytical tool-aggregation-induced polarization established by our laboratory. In the meanwhile, chiral aggregates were found to be formed either by adding NaCl into tetrahydrofuran/H2O systems or by increasing concentrations of chiral ligands. The present strategy also showed promising reverse control of enantioselectivity in the Diels-Alder reaction. This work is anticipated to be extended broadly to general catalysis, especially to asymmetric catalysis in the future.

Aggregation-induced polarization (AIP) of derivatives of BINOL and BINAP.

The relationship between optical rotations of small chiral molecules with water% in THF has been established. The typical aggregation co-solvent systems resulted in optical rotation amplification and adjustment, defined as aggregation-induced polarization (AIP). The AIP work can serve as a new tool to determine molecular aggregation, especially for those that cannot display aggregation-induced emission (AIE). Therefore, AIP and AIE are anticipated to complement each other. In addition, AIP can also serve as a new transmission tool providing adjusting right- or left-hand polarized lights of a series of individual wavelengths. Since chiral phosphine derivatives are among the most important ligands, this work would benefit research using chiral aggregates to control asymmetric synthesis and catalysts. Therefore, it will find many applications in chemical and materials sciences.

Aggregation-Induced Synthesis (AIS): Asymmetric Synthesis via Chiral Aggregates.

A new chiral aggregate-based tool for asymmetric synthesis has been developed by taking advantage of chiral aggregates of GAP (Group-Assisted Purification) reagents, N-phosphonyl imines. This tool was proven to be successful in the asymmetric GAP synthesis of functionalized 2,3-dihydrobenzofurans by reacting salicyl N-phosphonyl imines with dialkyl bromomalonates in various cosolvent systems. The chiral induction can be controlled by differentiating between two asymmetric directions simply by changing the ratios of cosolvents which are commonly adopted in AIE (aggregation-induced emission) systems. The formation of chiral aggregates was witnessed by a new analytical tool-aggregation-induced polarization (AIP). The present synthetic method will be broadly extended for general organic synthesis, particularly, for asymmetric synthesis and asymmetric catalysis in the future.

Aggregation-Induced Polarization (AIP): Optical Rotation Amplification and Adjustment of Chiral Aggregates of Folding Oligomers and Polymers.

The phenomenon of aggregation-induced polarization (AIP) was observed showing optical rotation amplification and adjustment. The relationship between optical rotations of chiral aggregates of multilayered chiral folding oligomers and polymers with water% in THF (f w) has been established accordingly. New multilayered chiral oligomers were synthesized under the asymmetric catalytic systems established by our laboratory recently. These products were well-characterized by UV-vis, NMR, and MALDI-TOF spectra. Absolute stereochemistry (enantio- and diastereochemistry) was assigned by comparison with similar asymmetric induction by the same catalyst in our previous reactions. The present AIP work can serve as a new tool to determine chiral aggregates, especially for those that cannot display emission. AIP would also complement AIE-based CPL since AIP serves as a new tool providing enhanced right- or left-hand polarized lights with individual wavelengths. It will find many applications in chemical and materials science in the future.

PM2.5 induces the distant metastasis of lung adenocarcinoma via promoting the stem cell properties of cancer cells.

Lung cancer is the most common cancer in China and second worldwide, of which the incidence of lung adenocarcinoma is rising. As an independent factor, air pollution has drawn the attention of the public. An increasing body of studies has focused on the effect of PM2.5 on lung adenocarcinoma; however, the mechanism remains unclear. We collected the PM2.5 in two megacities, Beijing (BPM) and Shijiazhuang (SPM), located in the capital of China, and compared the different components and sources of PM2.5 in the two cities. Vehicle emissions are the primary sources of BPM, whereas SPM is industrial emissions. We found that chronic exposure to PM2.5 promotes the tumorigenesis and metastasis of lung adenocarcinoma in patient-derived xenograft (PDX) models, as well as the migration and invasion of lung adenocarcinoma cell lines. SPM has more severe effects in vivo and in vitro. The underlying mechanisms are related to the stem cell properties of cancer cells, the epithelial-mesenchymal transition (EMT) process, and the corresponding miRNAs. It is hopeful to provide a theoretical basis for improving air pollution in China, especially in the capital area, and is of the significance of long-term survival of lung cancer patients.

A new chiral phenomenon of orientational chirality, its synthetic control and computational study.

A new type of chirality, orientational chirality, consisting of a tetrahedron center and a remotely anchored blocker, has been discovered. The key structural element of this chirality is characterized by multiple orientations directed by a through-space functional group. The multi-step synthesis of orientational chiral targets was conducted by taking advantage of asymmetric nucleophilic addition, Suzuki-Miyaura cross-coupling and Sonogashira coupling. An unprecedented catalytic species showing a five-membered ring consisting of C (sp2)-Br-Pd-C (sp2) bonds was isolated during performing Suzuki-Miyaura cross-coupling. X-ray diffraction analysis confirmed the species structure and absolute configuration of chiral orientation products. Based on X-ray structures, a model was proposed for the new chirality phenomenon to differentiate the present molecular framework from previous others. DFT computational study presented the relative stability of individual orientatiomers. This discovery would be anticipated to result in a new stereochemistry branch and to have a broad impact on chemical, biomedical, and material sciences in the future.

[Preliminary Application of Body Surface Theodolitic Puncture Localization Method in Thoracoscopic Surgery of Pulmonary Ground-glass Nodules].

BACKGROUND: How to locate pulmonary ground-glass nodules in thoracoscopic surgery is an important clinical topic in minimally invasive thoracic surgery. There is no unified localization method at present. This study intends to investigate the accuracy and security of body surface theodolitic puncture localization method in video-assisted thoracoscopic surgery for pulmonary ground-glass nodules. METHODS: The clinical data of 41 patients from August 2018 to December 2019 were analyzed retrospectively, including 28 males and 13 females. After anesthesia, the patient was located by body surface theodolitic puncture, and then partial lobectomy was performed under video-assisted thoracoscopy. The distance from the nodule to the marked suture and the distance from the nodule to the incisal margin were measured, and the accuracy of localization, the rate of complication and the success rate of surgical resection were calculated. RESULTS: A total of 51 nodules in 41 patients were located by body surface theodolitic puncture localization method. The accuracy rate was 96.1%, and the average location time was 8.3 min. Puncture bleeding occurred in 5 cases (12.2%), all of which were successfully stopped by video-assisted thoracoscopy, and there were no other complications. All patients underwent thoracoscopic partial lobectomy, including 33 cases of anatomical segmentectomy and 8 cases of wedge lobectomy. All the patients in operation process smoothly. The distance between nodule and incisal margin was measured, and all specimens were more than 2 cm, reaching a safe distance. The success rate of surgical resection was 100.0%. CONCLUSIONS: In video-assisted thoracoscopic surgery for ground glass nodules of lung, the body surface theodolitic puncture localization method can be accurate, safe and simple.

Improving Dissolution and Cytotoxicity by Forming Multidrug Crystals.

Both rosiglitazone and metformin have effects on blood glucose regulation and the proliferation of liver cancer cells. Combination therapy with these two drugs is common and effective for the treatment of diabetes in the clinic, however, the application of these two drugs is influenced by the poor dissolution of rosiglitazone and the gastrointestinal side-effect of metformin resulting from a high solubility. The formation of a multidrug crystal form (Rsg-Met) by a solvent evaporation method can solve the solubility issue. Crystal structure data and intramolecular hydrogen bonds were detected by X-ray diffraction and infrared spectroscopy. Surprisingly, Rsg-Met shortens the time spent in solubility equilibrium and multiplies the dissolution rate of Rsg. Finally, we found that a low concentration of Rsg-Met enhanced the proliferation inhibition effect on liver cancer cells (HepG2, SK-hep1) compared with rosiglitazone, without affecting the human normal cell line LO2.

Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma.

Lung cancer is a leading global cause of cancer-related death, and lung adenocarcinoma (LUAD) accounts for ~ 50% of lung cancer. Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real-time PCR (qRT-PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA-target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa-mir-486-1, hsa-mir-486-2, hsa-mir-153, hsa-mir-210, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-577, and hsa-mir-4732) as optimal LUAD-specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT-PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD.