20-Deoxyingenol Activates Mitophagy Through TFEB and Promotes Functional Recovery After Spinal Cord Injury.

Spinal cord injury (SCI) can lead to permanent paralysis and various motor, sensory and autonomic nervous system dysfunction. The complex pathophysiological processes limit the effectiveness of many clinical treatments. Mitochondria has been reported to play a key role in the pathogenesis of SCI; while mitophagy is a protective mechanism against mitochondrial dysfunction. However, there is recently little drugs that may targeted activate mitophagy to treat SCI. In this study, we evaluated the role of 20-Deoxyingenol (20-DOI) in SCI and explored its potential mechanisms. We used a SCI rat model and evaluated the functional outcomes after the injury. Western blotting and immunofluorescence techniques were used to analyze the levels of mitophagy, apoptosis, and TFEB-related signaling pathways. Our research results show that 20-DOI significantly improves the apoptosis of neural cells after TBHP stimulation and functional recovery after spinal cord injury. In addition, mitophagy, TFEB levels, and apoptosis are related to the mechanism of 20-DOI treatment for spinal cord injury. Specifically, our research results indicate that 20-DOI restored the autophagic flux after injury, thereby inducing mitophagy, eliminating the accumulation of Cyto C, and inhibiting apoptosis. Further mechanism research suggests that 20-DOI may regulate mitophagy by promoting TFEB nuclear translocation. These results indicate that 20-DOI can significantly promote recovery after spinal cord injury, which may be a promising treatment method for spinal cord injury.

MpoxNet: dual-branch deep residual squeeze and excitation monkeypox classification network with attention mechanism.

While the world struggles to recover from the devastation wrought by the widespread spread of COVID-19, monkeypox virus has emerged as a new global pandemic threat. In this paper, a high precision and lightweight classification network MpoxNet based on ConvNext is proposed to meet the need of fast and safe detection of monkeypox classification. In this method, a two-branch depth-separable convolution residual Squeeze and Excitation module is designed. This design aims to extract more feature information with two branches, and greatly reduces the number of parameters in the model by using depth-separable convolution. In addition, our method introduces a convolutional attention module to enhance the extraction of key features within the receptive field. The experimental results show that MpoxNet has achieved remarkable results in monkeypox disease classification, the accuracy rate is 95.28%, the precision rate is 96.40%, the recall rate is 93.00%, and the F1-Score is 95.80%. This is significantly better than the current mainstream classification model. It is worth noting that the FLOPS and the number of parameters of MpoxNet are only 30.68% and 31.87% of those of ConvNext-Tiny, indicating that the model has a small computational burden and model complexity while efficient performance.

Pure separation of acetylene based on a sulfonic acid and amino group functionalized Zn-MOF.

The dual-ligand strategy was employed to synthesize a new microporous material, [Zn3(SNDC)(AmTAZ)3(H2O)]·H2O·CH3CN (1), incorporating sulfonic acid and amino groups for enhancing gas adsorption and separation. The activated 1 (named 1a) exhibited selective adsorption of acetylene over carbon dioxide and methane. Hence, the dual-ligand strategy optimized the pore environment and provided an effective approach for pure separation of gases.

Underlying mechanisms governing on distribution and stratification of DOM during seasonal freeze-thaw cycles.

During the freeze-thaw cycles of ice-covered lakes, DOM undergoes a series of transformations including enrichment, dispersion, and filtration. However, the mechanisms and influence factors on lake pollution processes remain unclear. Therefore, this study investigates the distribution of DOM components and elucidate the role of ice-layer sieving its mechanisms within ice-water-sediments. Study identifies significant variations in the characteristics of DOM, protein-like substances tend to migrate towards the ice layer, while humic-like substances predominantly remain in water. This selective distribution is primarily influenced by the physical and chemical properties of DOM during the freezing process. The ice layer acts as a sieve, allowing smaller molecules such as protein-like substances to pass through more easily, while larger molecules like humic-like substances are retained in the water. Additionally, Temperature plays a pivotal role in affecting the contents of DOM. As the temperature decreases, the solubility of DOM decreases, leading to its precipitation and enrichment in sediments. Conversely, an increase in temperature can facilitate the release of DOM from sediments into the water. Furthermore, high content of total dissolved solids can affect the solubility and stability of DOM, potentially leading to changes in its composition and distribution. These insights provide a deeper understanding of the complex interplay between thermal processes and chemical dynamics within ice-covered aquatic environments. They offered valuable insights into the behavior of organic pollutants in frozen lake systems. The findings have potential implications for environmental management strategies aimed at mitigating the effects of climate.

A double inducible cell ablation system for eliminating senescent astrocytes via apoptosis.

PURPOSE: Cell senescence stands as a principal risk factor for various neurodegenerative diseases, with astrocytic senescence emerging as a potentially pivotal player in the pathogenesis of aging and neurodegenerative disorders. Clearing senescent astrocytes holds promise as a potential therapeutic approach for senescence-related diseases. METHODS: In this study, we designed and constructed two plasmids aimed at inducing apoptosis in senescent astrocytes. This was achieved through the ligation of FKBP (FK506-binding protein) and FRB (FKBP and FKBP rapamycin binding domain) and the formation of caspase8 dimers, thereby achieving the purpose of eliminating senescent astrocytes. RESULTS: The developed vector system demonstrates a specifically capability to induce apoptosis in aging astrocytes, offering a targeted approach to eliminate these cells. CONCLUSION: The utilization of the double -inducible suicide gene system provides a versatile tool forstimulating cell apoptosis and inhibiting cellular senescence. This system proves valuable in exploring the intrinsic roles and molecular mechanisms of senescent cells in the occurrence and development of aging-related diseases. Ultimately, it offers a potential avenue for developing an efficient treatment system for such conditions.

Fisetin suppresses ferroptosis through Nrf2 and attenuates intervertebral disc degeneration in rats.

Low back pain, primarily caused by intervertebral disc degeneration (IVDD), lacks effective pharmacological treatments. Oxidative stress has been identified as a significant contributor to IVDD. This study aims to establish an in vitro model of IVDD induced by oxidative stress and identify potential therapeutic agents and their underlying mechanisms. By screening the natural product library, fisetin emerged as the most promising compound in suppressing cell death induced by oxidative stress in nucleus pulposus cells (NPCs). Furthermore, our investigation revealed that the cell death induced by oxidative stress was predominantly associated with ferroptosis, and fisetin demonstrated the ability to inhibit ferroptosis in NPCs. Mechanistic exploration suggested that the impact of fisetin on ferroptosis may be mediated through the Nrf2/HO-1 (Nuclear factor erythroid 2-related factor 2/heme oxygenase-1) axis. Notably, the in vivo study demonstrated that fisetin could alleviate IVDD in rats. These findings highlight fisetin as a potential therapeutic option for IVDD and implicate the involvement of the Nrf2/HO-1 pathway in its mechanism of action.

A novel adhesive dual-sensitive hydrogel for sustained release of exosomes derived from M2 macrophages promotes repair of bone defects.

The repair of bone defects remains a huge clinical challenge. M2 macrophage-derived exosomes (M2-Exos) can act as immunomodulators to promote fracture healing; however, how to retain the sustained release of exosomes to the target area remains a challenge. Here, we report a composite hydrogel loaded with M2-Exos aiming to accelerate bone defect healing. It was verified that the F127/HA-NB hydrogel had a dense network structure, tissue adhesiveness, and dual sensitivity to temperature and light. F127/HA-NB loaded with M2-Exos (M2-Exos@F127/HA-NB) exhibited good biocompatibility and achieved sustained release of exosomes for up to two weeks. The study showed that both M0-Exos and M2-Exos@F127/HA-NB significantly promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. The mechanism study implied that M2-Exos activates the Wnt/ß-catenin signaling pathway to promote osteogenic differentiation of BMSCs. Finally, we evaluated the osteogenetic effects of M2-Exos@F127/HA-NB in a rat cranial defect model, and the results showed that M2-Exos@F127/HA-NB had superior bone regeneration-promoting effects. This study provides a new strategy for cell-free treatment of bone defects.

Diabetes mellitus and hearing loss.

Diabetes mellitus (DM) is a major disease threatening human health and its incidence is increasing year on year. As a chronic complication of DM, hearing loss mostly occurs undetectably. However, the mechanism of this diabetes-related hearing loss (DRHL) remains unclear and there is no effective clinical treatment. Studies of animal or human pathology show that DM causes damage to the blood vessels, spiral ganglion neurons, afferent nerve fibers, the organ of Corti, and the stria vascularis of the inner ear. In recent years, more advances in pathological research have revealed the possible mechanism of DRHL. In addition, a large number of clinical studies suggest that the duration and severity of DM are closely related to the incidence and severity of DRHL. This review focuses on the relationship between DM and hearing loss. The clinical audiological characteristics of diabetic patients, risk factors for DRHL, typical pathology, and potential interventions of DRHL are summarized. This will help reveal the pathogenesis and intervention approaches for DRHL.

20-Deoxyingenol alleviates intervertebral disc degeneration by activating TFEB in nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is a prevalent degenerative disease with significant adverse implications for patients' quality of life and socioeconomic status. Although the precise etiology of IVDD remains elusive, the senescence of nucleus pulposus cells is recognized as the primary pathogenic factor of IVDD; however, drugs that may targetedly inhibit senescence are still lacking. In the current study, we evaluated the small-molecule active drug 20-Deoxyingenol(20-DOI) for its effects on combating senescence and delaying the progression of IVDD. In vitro experiments revealed that the administration of 20-DOI displayed inhibitory effects on senescence and the senescence-related cGAS-STING pathway of nucleus pulposus cells. Additionally, it exhibited the ability to enhance lysosome activity and promote autophagy flux within nucleus pulposus cells. Subsequent investigations elucidated that the inhibitory impact of 20-DOI on nucleus pulposus cell senescence was mediated through the autophagy-lysosome pathway. This effect was diminished in the presence of transcription factor EB (TFEB) small hairpin RNA (shRNA), thereby confirming the regulatory role of 20-DOI on the autophagy-lysosome pathway and senescence through TFEB. In vivo experiments demonstrated that 20-DOI effectively impeded the progression ofIVDD in rats. These findings collectively illustrate that 20-DOI may facilitate the autophagy-lysosomal pathway by activating TFEB, thereby suppressing the senescence in nucleus pulposus cells, thus suggesting 20-DOI as a promising therapeutic approach for IVDD.

Effect and environmental behaviour of microplastics in soil.

Soil microplastic pollution is currently a worldwide concern. Microplastics are organic pollutants that are abundant in the natural environment, are persistent and difficult to degrade and may endanger human health while harming the environment. This article offers a bibliometric analysis of the environmental behaviour of microplastics in soils, as well as a thorough statistical analysis of research goals and trends in this field. We conducted a thorough search of all relevant literature from 2012 to 2022 in the Web of Science core database. The data analysis shows that, starting in 2012, there has been an upward trend in the number of articles about soil microplastic pollution. It can also be seen that China is relatively ahead of the curve in this area of research, followed by the United Kingdom and the United States. This article also systematically describes the research hotspots in this field. The results show that the current research on soil microplastics is mainly focused on their identification, enrichment and toxicity, whereas studies on the migration and transformation of soil microplastics and the mechanism of interaction with other pollutants are still lacking. Our results provide ideas and prospects for future research in this field.

Hepatic epithelioid angiomyolipoma is scattered and unsuitable for surgery: a case report.

Hepatic epithelioid angiomyolipoma (HEAML) is a rare tumour of mesenchymal tissue with a malignant tendency. Occurring most frequently in women, the relative incidence in men and women, according to incomplete statistics, is approximately 1:5. In rare cases, disease occurrence and development is hidden. Lesions are generally discovered as chance findings by patients; abdominal pain is the first symptom, and imaging has no specificity in diagnosing the disease. Therefore, great difficulties exist in the diagnosis and treatment of HEAML. Here, the case of a 51-year-old female patient with a history of hepatitis B, and abdominal pain over 8 months as the initial symptom, is described. The patient was found to have multiple intrahepatic angiomyolipoma. Due to the small and scattered foci, complete resection was impossible, and because of her history of hepatitis B, conservative treatment was undertaken, with the patient undergoing regular follow-up. When hepatic cell carcinoma could not be excluded, the patient was treated with transcatheter arterial chemoembolization. No tumour neogenesis or metastasis was detected at the 1-year follow-up.

Long noncoding RNA UCA1 promotes the expression and function of P-glycoprotein by sponging miR-16-5p in human placental BeWo cells.

Investigations on placental P-glycoprotein (P-gp) regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. The role of long noncoding RNA (lncRNA) on placental P-gp regulation is lacking. The present study was carried out to investigate the regulation and underlying mechanisms of lncRNA urothelial carcinoma associated 1 (UCA1) on P-gp in Bewo cells. lncRNA UCA1 inhibition or overexpression could decrease or increase ABCB1 mRNA expression, P-gp expression and its cellular efflux function, respectively. RNA-FISH revealed that lncRNA UCA1 was mainly located in the cytoplasm of Bewo cells. MicroRNA array was applied and 10 significant miRNAs was identified after lncRNA UCA1 inhibition. Databases of LncTarD, LncRNA2Target, and miRcode were further used to search potential target miRNAs of lncRNA UCA1 and miR-16-5p was screened out. Thereafter, we confirmed that miR-16-5p expression was significantly upregulated or reduced after lncRNA UCA1 knockdown or overexpression, respectively. Furthermore, we also proved that ABCB1 mRNA expression, P-gp expression and its cellular efflux function was enhanced or reduced after miR-16-5p inhibition or overexpression, respectively. The rescue experiment further indicated that miR-16-5p was involved in the positive regulation of lncRNA UCA1 on the expression and function of P-gp. Lastly, dual-luciferase reporter system, RNA-binding protein immunoprecipitation and RNA pull-down assays were performed to explore the relationships among lncRNA UCA1, miR-16-5p, and ABCB1. It was found that lncRNA UCA1(1103-1125) could directly interact with miR-16-5p and miR-16-5p could directly target ABCB1 coding DNA sequence region (882-907). In conclusion, LncRNA UCA1 could promote the expression and function of P-gp by sponging miR-16-5p in BeWo cells.

Modification mechanism of protein in rice adjuncts upon extrusion and its effects on nitrogen conversion during mashing.

The traditional production of wort with adjunct-introduced was achieved by double mashing procedure, which hindered the utilization of proteins in adjunct and led to a deficiency of nitrogen in wort. In this study, the modification mechanism of the extrusion pretreatment on the structure characterization of rice flour protein was investigated. The decoction mashing procedure was performed to enhance the nitrogen conversion of the extruded rice adjunct. Decreased solubility along with disrupted secondary and tertiary structures of rice protein were observed after extrusion. As a result, the total nitrogen, free amino nitrogen, and free amino acids content of wort with extruded rice adjunct-introduced were improved by 23.28 %, 34.67 %, and 7.33 %, respectively, which could be verified by the electrophoretic patterns of the wort protein. The application of extrusion as a pretreatment of adjuncts can promote the protein availability of adjuncts in the decoction mashing stage.

Calibration experiments based on a CO2 absorption cell for the 1.57-µm spaceborne IPDA LIDAR.

The spaceborne IPDA LIDAR has the potential to measure the global atmosphere CO2 column concentrations with high accuracy. For this kind of LIDAR, system calibration experiments in the laboratory are of high importance. In this study, a specially-customized CO2 absorption cell is employed to simulate the CO2 column absorption of the spaceborne platform. Then calibration experiments are constructed for the receiving system and the entire LIDAR system. The absorption of several different XCO2 concentrations from 400 to 415 ppm in the atmosphere is equivalent to that of the absorption cell charged with different pressures of pure CO2. Under the zero pressure of the absorption cell, the calculated equivalent column average concentration (XCO2) is 12.53 ppm, which acts as system bias. In the calibration experiments, the absolute errors are all less than 1 ppm. And the standard deviations (STDs) are less than 1.1 ppm (148-shot averaging) and 0.8 ppm (296-shot averaging) for receiving system and less than 1.2 ppm and 0.9 ppm for the IPDA LIDAR system. All the results of different average times are close to each other and less than 1 ppm, which proves the high accuracy of the IPDA LIDAR system. In addition, the XCO2 concentrations Allan deviation of 0.25 ppm and 0.35 ppm at 100 s shows that the receiving system and IPDA LIDAR system function with long-term stability. Using a CO2 absorption cell as a standard calibration device in the laboratory validates the measurement accuracy and stability of the spaceborne IPDA LIDAR prototype. Furthermore, the proposed absorption cell may serve as a standard calibration device for related atmosphere trace gases sounding research.

High-Throughput Sequencing to Investigate lncRNA-circRNA-miRNA-mRNA Networks Underlying the Effects of Beta-Amyloid Peptide and Senescence on Astrocytes.

Astrocytes are widely distributed in the central nervous system and play an essential role in the function of neuronal cells. Associations between astrocytes and Alzheimer's disease (AD) have been noted, and recent work has implicated circular RNA (circRNA) and long non-coding RNA (lncRNA) in the development of AD. However, few reports have investigated which lncRNA and circRNA are involved in the influence of amyloid beta (Aß) and senescence on astrocytes. This study therefore examines changes at the transcriptome level to explore the effects of Aß and senescence on astrocytes. Primary cultured astrocytes were treated with Aß and cultured for 90 days in vitro, and high-throughput sequencing was performed to identify differentially expressed RNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that differentially expressed genes were associated with the focal adhesion signaling pathway, extracellular matrix receptor signaling pathway, and the extracellular matrix. The protein-protein interaction network was then constructed, and 103 hub genes were screened out; most of these were strongly associated with the expression of the extracellular matrix, extracellular matrix receptor signaling pathway, and focal adhesion. Two competing endogenous RNA networks were constructed based on the selected hub gene and differential RNAs, and we identified multiple competing endogenous RNA regulatory axes that were involved in the effects of Aß and senescence on astrocytes. This is the first study to explore the molecular regulation mechanism of Aß and senescence on primary astrocytes from the perspective of the whole transcriptome. In uncovering the signaling pathways and biological processes involved in the effects of Aß and senescence on astrocytes, this work provides novel insights into the pathogenesis of AD at the level of competing endogenous RNA network regulation.

Lanthanide-Organic Frameworks with Uncoordinated Lewis Base Sites: Tunable Luminescence, Antibiotic Detection, and Anticounterfeiting.

Several new isostructural lanthanide metal-organic frameworks (Ln-MOFs), {[Ln2(L)3DMA4]·2DMA}n (1-Ln, where Ln = Eu, Tb, or EuxTb1-x), were first constructed via the solvothermal reactions of 4,6-di(4-carboxyphenyl)pyrimidine and Ln3+ ions. 1-Ln exhibits a 4-connected two-dimensional framework endowed with uncoordinated Lewis base sites. An exploration of luminescence sensing demonstrated 1-Eu can be used for the selectivity detection of dimetridazole and metronidazole antibiotics in other antibiotics, blood plasma, and urine, acting as an exceptional recyclable luminescent probe. More importantly, the luminescent inks of 1-Ln are invisible, color adjustable, and stabilized, which may greatly improve their anticounterfeiting applications.