O-GlcNAc Modification Is a Promising Therapeutic Target for Diabetic Retinopathy.

Diabetic retinopathy (DR) is a very serious diabetes complication. Changes in the O-linked N-acetylglucosamine (O-GlcNAc) modification are associated with many diseases. However, its role in DR is not fully understood. In this research, we explored the effect of O-GlcNAc modification regulation by activating AMP-activated protein kinase (AMPK) in DR, providing some evidence for clinical DR treatment in the future. Bioinformatics was used to make predictions from the database, which were validated using the serum samples of diabetic patients. As an in vivo model, diabetic mice were induced using streptozotocin (STZ) injection with/without an AMPK agonist (metformin) or an AMPK inhibitor (compound C) treatment. Electroretinogram (ERG) and H&E staining were used to evaluate the retinal functional and morphological changes. In vitro, 661 w cells were exposed to high-glucose conditions, with or without metformin treatment. Apoptosis was evaluated using TUNEL staining. The protein expression was detected using Western blot and immunofluorescence staining. The angiogenesis ability was detected using a tube formation assay. The levels of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in the serum changed in the DR patients in the clinic. In the diabetic mice, the ERG wave amplitude and retinal thickness decreased. In vitro, the apoptotic cell percentage and Bax expression were increased, and Bcl2 expression was decreased in the 661 w cells under high-glucose conditions. The O-GlcNAc modification was increased in DR. In addition, the expression of GFAT/TXNIP O-GlcNAc was also increased in the 661 w cells after the high-glucose treatment. Additionally, the Co-immunoprecipitation(CO-IP) results show that TXNIP interacted with the O-GlcNAc modification. However, AMPK activation ameliorated this effect. We also found that silencing the AMPKα1 subunit reversed this process. In addition, the conditioned medium of the 661 w cells may have affected the tube formation in vitro. Taken together, O-GlcNAc modification was increased in DR with photoreceptor cell degeneration and neovascularization; however, it was reversed after activating AMPK. The underlying mechanism is linked to the GFAT/TXNIP-O-GlcNAc modification signaling axis. Therefore, the AMPKα1 subunit plays a vital role in the process.

An Integrated Arterial Remodeling Hydrogel for Preventing Restenosis After Angioplasty.

The high incidence of restenosis after angioplasty has been the leading reason for the recurrence of coronary heart disease, substantially increasing the mortality risk for patients. However, current anti-stenosis drug-eluting stents face challenges due to their limited functions and long-term safety concerns, significantly compromising their therapeutic effect. Herein, a stent-free anti-stenosis drug coating (denoted as Cur-NO-Gel) based on a peptide hydrogel is proposed. This hydrogel is formed by assembling a nitric oxide (NO) donor-peptide conjugate as a hydrogelator and encapsulating curcumin (Cur) during the assembly process. Cur-NO-Gel has the capability to release NO upon ß-galactosidase stimulation and gradually release Cur through hydrogel hydrolysis. The in vitro experiments confirmed that Cur-NO-Gel protects vascular endothelial cells against oxidative stress injury, inhibits cellular activation of vascular smooth muscle cells, and suppresses adventitial fibroblasts. Moreover, periadventitial administration of Cur-NO-Gel in the angioplasty model demonstrate its ability to inhibit vascular stenosis by promoting reendothelialization, suppressing neointima hyperplasia, and preventing constrictive remodeling. Therefore, the study provides proof of concept for designing a new generation of clinical drugs in angioplasty.

Predication of the post mining land use based on random forest and DBSCAN.

Mine reclamation is one of the most important stages of the mining activities in line with the basic principles of sustainable development. In this study, different post-mining land uses are evaluated in the Hongliulin mining area, which is located in Shen mu country of China. 145 soil samples were collected in the May,2021 by using the soil auger, and the sampling depths were 0-20 cm. The sampling points contains 45 to be reclaimed samples and 100 existing classification land use types. 14 environmental factors including soil organic matter (SOM), total nitrogen (TN), available phosphate (AP), available potassium (AK), K, Slope steepness, curvatures, aspect, length, Topographic Wetness Index (TWI), NDVI and elevation were extracted and calculated based on laboratory test and digital elevation map. The random forest classier showed a great prediction capability, with only 1 miss-classified sample in the validation data-set, the accuracy of the classification model was 95%. The content of TN of C1 is 5 times more than C2 and 4 times more than C3. Also, the K value of C1 column is maximum and over 0.4, which means the soil particle is relatively smaller and the soil texture of it is sandy loam. In terms of the 45 to be reclaimed samples, 15 samples were classified into C1, 23 samples were classified into C2, 5 samples were classified into C3, 2 samples were classified into C4. The value of K and content of soil nutrients of the samples classified to be C1 column(C1-C) is maximum. The soybean and murphy were suggested based on the soil nutrients index and with the mining disturbance on cluster 2 of C1, the ground subsidence filling as well as soil nutrients increased strategy should be applied. The result may contribute to the land use planning and idle land utilization strategy.

Diabetic and nondiabetic BMSC-derived exosomes affect bone regeneration via regulating miR-17-5p/SMAD7 axis.

Diabetic bone disease (DBD) is a complication of diabetes mellitus (DM) and is characterized by impaired osteocyte function and delayed bone remodeling due to high blood glucose levels and sustained release of inflammatory factors. Recent studies show that the regulation of osteoblasts (OBs) by bone marrow stromal cells (BMSCs) is an important mechanism in alleviating DBD and that exosomes are recognized as the key medium. Mesenchymal stem cell-derived exosome (MSC-Exos) therapy is a promising approach to facilitate tissue repair. However, the influence of exosomes from diabetic conditioned BMSCs on OBs and bone regeneration, as well as the underlying mechanism, are still elusive. Here, we used high-glucose medium to mimic diabetic conditions and normal-glucose medium as control to mimic nondiabetic conditions in vitro and found that microRNA-17 (miR-17) was downregulated in diabetic-conditioned BMSC-derived exosomes (HG-Exos), HG-Exo-co-cultured osteoblasts, and the skull of rats with type 2 diabetes mellitus (T2DM). Further experiment concluded that nondiabetic conditioned BMSC-Exos (NG-Exos) promoted the osteogenesis of OBs and bone regeneration of rats with T2DM via upregulation of miR-17. Compare with NG-Exos, HG-Exos impeded osteogenesis of OBs in vitro and bone regeneration of rats in vivo by downregulation of miR-17. Moreover, miR-17 promoted bone regeneration by targeting SMAD7, which was further proved to have a negative effect on osteogenesis. Taken together, nondiabetic BMSC-derived exosomes greatly foster bone regeneration, whereas diabetic BMSC-derived exosomes undermine the promotion effect of MSC-Exos by regulating the miR-17/SMAD7 axis. These findings provide support for the miR-17-5p/SMAD7 axis as a promising therapeutic target to treat DBD.

Influence of the contact area of the sub-antral space with sinus bone and the Schneiderian membrane on osteogenesis in lateral window sinus elevation surgery: a prospective experiment.

BACKGROUND: Osteogenesis of lateral window sinus elevation surgery is the key to placement of the subsequent implant, excessive collapse of the sub-antral space may adversely affect long-term stability of implants. At present, few studies focus on the influence of the contact area of the sub-antral space on osteogenesis. This study evaluated whether the change in the contact area of the sub-antral space with maxillary sinus bone and the Schneiderian membrane can affect osteogenesis. METHODS: Cone beam computed tomography (CBCT) images were collected of patients requiring maxillary sinus floor elevation (residual bone height < 6 mm) for standard-length implant placement before surgery, after surgery, and at 6-month follow-up visits. The postoperative sub-antral space volume (V1) and surface area (S1), and the remaining volume after six months of healing (V2) were measured. Then, the contact area of sub-antral space with maxillary sinus bone (Sbc) and the Schneiderian membrane (Smc), the absorbed volume during healing (Va), and the percentage of remaining volume (V2%) and absorbed volume (Va%) were calculated. The correlation between anatomical parameters was analyzed using multiple linear regression. RESULTS: A total of 62 maxillary sinuses from 56 patients were augmented, of which 57 were considered for the final analysis (5 withdrew due to perforation). Multiple linear regression results demonstrated that Sbc was significantly positively correlated with Va (ß coefficient = 0.141, p < 0.01) without correlation between Smc and Va (ß coefficient = - 0.046, p = 0.470). There was a positive correlation between Sbc and V2% (ß coefficient = 2.269, p < 0.05). CONCLUSIONS: This study confirmed that the size of the Sbc in lateral window sinus elevation surgery affected osteogenesis after six months of healing. Clinicians should assess the sinus contour type preoperatively, then consider whether it is necessary to expand the range of the Schneiderian membrane elevation to avoid excessive collapse of the sub-antral space. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2200057924. Registered 22 March 2022-Retrospectively registered.

Mitochondria-Associated Endoplasmic Reticulum Membranes: Inextricably Linked with Autophagy Process.

Mitochondria-associated membranes (MAMs), physical connection sites between the endoplasmic reticulum (ER) and the outer mitochondrial membrane (OMM), are involved in numerous cellular processes, such as calcium ion transport, lipid metabolism, autophagy, ER stress, mitochondria morphology, and apoptosis. Autophagy is a highly conserved intracellular process in which cellular contents are delivered by double-membrane vesicles, called autophagosomes, to the lysosomes for destruction and recycling. Autophagy, typically triggered by stress, eliminates damaged or redundant protein molecules and organelles to maintain regular cellular activity. Dysfunction of MAMs or autophagy is intimately associated with various diseases, including aging, cardiovascular, infections, cancer, multiple toxic agents, and some genetic disorders. Increasing evidence has shown that MAMs play a significant role in autophagy development and maturation. In our study, we concentrated on two opposing functions of MAMs in autophagy: facilitating the formation of autophagosomes and inhibiting autophagy. We recognized the link between MAMs and autophagy in the occurrence and progression of the diseases and therefore collated and summarized the existing intrinsic molecular mechanisms. Furthermore, we draw attention to several crucial data and open issues in the area that may be helpful for further study.

Three new species of the genus Hexarhopalus Fairmaire, 1891 (Coleoptera, Tenebrionidae: Cnodalonini) from China.

Three new species of the genus Hexarhopalus Fairmaire, 1891 are described and figured from China: Hexarhopalus (Hexarhopalus) yunnanensis sp. nov. from Yunnan, Hexarhopalus (Hexarhopalus) zhuxiangi sp. nov. from Guangxi, and Hexarhopalus (Leprocaulus) nanlingensis sp. nov. from Guangdong. A revised key is provided to the species of Hexarhopalus from China.