d-Galactose induces the senescence and phenotype switch of corpus cavernosum smooth muscle cells.

Studies regarding age-related erectile dysfunction (ED) based on naturally aging models are limited by their high costs, especially for the acquisition of primary cells from the corpus cavernosum. Herein, d-galactose ( d-gal) was employed to accelerate cell senescence, and the underlying mechanism was explored. As predominant functional cells involved in the erectile response, corpus cavernosum smooth muscle cells (CCSMCs) were isolated from 2-month-old rats. Following this, d-gal was introduced to induce cell senescence, which was verified via ß-galactosidase staining. The effects of d-gal on CCSMCs were evaluated by terminal deoxynucleoitidyl transferase dUTP nick-end labeling (TUNEL), immunofluorescence staining, flow cytometry, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, RNA interference (RNAi) was carried out for rescue experiments. Subsequently, the influence of senescence on the corpus cavernosum was determined via scanning electron microscopy, qRT-PCR, immunohistochemistry, TUNEL, and Masson stainings. The results revealed that the accelerated senescence of CCSMCs was promoted by d-gal. Simultaneously, smooth muscle alpha-actin (alpha-SMA) expression was inhibited, while that of osteopontin (OPN) and Krüppel-like factor 4 (KLF4), as well as fibrotic and apoptotic levels, were elevated. After knocking down KLF4 expression in d-gal-induced CCSMCs by RNAi, the expression level of cellular alpha-SMA increased. Contrastingly, the OPN expression, apoptotic and fibrotic levels declined. In addition, cellular senescence acquired partial remission. Accordingly, in the aged corpus cavernosum, the fibrotic and apoptotic rates were increased, followed by downregulation in the expression of alpha-SMA and the concurrent upregulation in the expression of OPN and KLF4. Overall, our results signaled that d-gal-induced accelerated senescence of CCSMCs could trigger fibrosis, apoptosis and phenotypic switch to the synthetic state, potentially attributed to the upregulation of KLF4 expression, which may be a multipotential therapeutic target of age-related ED.

Increased level of RAB39B leads to neuronal dysfunction and behavioural changes in mice.

Duplications of the Xq28 region are a common cause of X-linked intellectual disability (XLID). The RAB39B gene locates in Xq28 and has been implicated in disease pathogenesis. However, whether increased dosage of RAB39B leads to cognitive impairment and synaptic dysfunction remains elusive. Herein, we overexpressed RAB39B in mouse brain by injecting AAVs into bilateral ventricles of neonatal animals. We found that at 2 months of age, neuronal overexpression of RAB39B impaired the recognition memory and the short-term working memory in mice and resulted in certain autism-like behaviours, including social novelty defect and repetitive grooming behaviour in female mice. Moreover, overexpression of RAB39B decreased dendritic arborization of primary neurons in vitro and reduced synaptic transmission in female mice. Neuronal overexpression of RAB39B also altered autophagy without affecting levels and PSD distribution of synaptic proteins. Our results demonstrate that overexpression of RAB39B compromises normal neuronal development, thereby resulting in dysfunctional synaptic transmission and certain intellectual disability and behavioural abnormalities in mice. These findings identify a molecular mechanism underlying XLID with increased copy numbers of Xq28 and provide potential strategies for disease intervention.

Caveolin-1 scaffolding domain peptide prevents corpus cavernosum fibrosis and erectile dysfunction in bilateral cavernous nerve injury-induced rats.

BACKGROUND: Corpus cavernosum (CC) fibrosis significantly contributes to post-radical prostatectomy erectile dysfunction (pRP-ED). Caveolin-1 scaffolding domain (CSD)-derived peptide has gained significant concern as a potent antagonist of tissue fibrosis. However, applying CSD peptide on bilateral cavernous nerve injury (BCNI)-induced rats remains uninvestigated. AIM: The aim was to explore the therapeutic outcome and underlying mechanism of CSD peptide for preventing ED in BCNI rats according to the hypothesis that CSD peptide may exert beneficial effects on erectile tissue and function following BCNI through limiting collagen synthesis in CC smooth muscle cells (CCSMCs) and CC fibrosis. METHODS: After completing a random assignment of male Sprague Dawley rats (10 weeks of age), BCNI rats received either saline or CSD peptide treatment, as opposed to sham-operated rats. The evaluations of erectile function (EF) and succedent collection and histological and molecular biological examinations of penile tissue were accomplished 3 weeks postoperatively. In addition, the fibrotic model of CCSMCs was used to further explore the mechanism of CSD peptide action in vitro. OUTCOMES: The assessments of EF, SMC/collagen ratio, α-smooth muscle actin, caveolin-1 (CAV1), and profibrotic indicators expressions were conducted. RESULTS: BCNI rats exhibited significant decreases in EF, SMC/collagen ratio, α-SMA, and CAV1 levels, and increases in collagen content together with transforming growth factor (TGF)-ß1/Smad2 activity. However, impaired EF, activated CC fibrosis, and Smad2 signaling were attenuated after 3 weeks of CSD peptide treatment in BCNI rats. In vitro, TGF-ß1-induced CCSMCs underwent fibrogenetic transformation characterized by lower expression of CAV1, higher collagen composition, and phosphorylation of Smad2; then, the delivery of CSD peptide could significantly block CCSMC fibrosis by inactivating Smad2 signaling. CLINICAL IMPLICATIONS: Based on available evidence of CSD peptide in the prevention of ED in BCNI rats, this study can aid in the development and clinical application of CSD peptide targeting pRP-ED. STRENGTHS AND LIMITATIONS: This study provides data to suggest that CSD peptide protects against BCNI-induced deleterious alterations in EF and CC tissues. However, the available evidence still does not fully clarify the detailed mechanism of action of CSD peptide. CONCLUSION: Administration of CSD peptide significantly retarded collagen synthesis in CCSMCs, limited CC fibrosis, and prevented ED via confrontation of TGF-ß1/Smad signaling in BCNI rats.

Enhanced triacyclglycerols and starch synthesis in Chlamydomonas stimulated by the engineered biodegradable nanoparticles.

Microalgae are promising feedstock for renewable fuels. The accumulation of oils in microalgae can be enhanced by nanoparticle exposure. However, the nanoparticles employed in previous studies are mostly non-biodegradable, which hinders nanoparticles developing as promising approach for biofuel production. We recently reported the engineered resin nanoparticles (iBCA-NPs), which were found to be biodegradable in this study. When the cells of green microalga Chlamydomonas reinhardtii were exposed to the iBCA-NPs for 1 h, the cellular triacyclglycerols (TAG) and starch contents increased by 520% and 60% than that in the control. The TAG production improved by 1.8-fold compared to the control without compromised starch production. Additionally, the content of total fatty acids increased by 1.3-fold than that in control. Furthermore, we found that the iBCA-NPs addition resulted in increased cellular reactive oxygen species (ROS) content and upregulated the activities of antioxidant enzymes. The relative expressions of the key genes involved in TAG and starch biosynthesis were also upregulated. Overall, our results showed that short exposure of the iBCA-NPs dramatically enhances TAG and starch accumulation in Chlamydomonas, which probably resulted from prompt upregulated expression of the key genes in lipid and starch metabolic pathways that were triggered by over-accumulated ROS. This study reported a useful approach to enhance energy-rich reserve accumulation in microalgae. KEY POINTS: 1. The first attempt to increase oil and starch in microalgae by biodegradable NPs. 2. The biodegradability of iBCA-NPs by the BOD test was more than 50% after 28 days. 3. The iBCA-NPs induce more energy reserves than that of previously reported NPs.

Theranostic Quercetin Nanoparticle for Treatment of Hepatic Fibrosis.

The progression of hepatic fibrosis can lead to cirrhosis and hepatic failure, but the development of antifibrotic drugs have faced the challenges of poor effectiveness and targeted specificity. Herein, a theranostic strategy was carried to encapsulate a natural medicine (Quercetin, QR) into hepatitis B core (HBc) protein nanocages (NCs) for imaging and targeted treatment of hepatic fibrosis. It was noted that nanoparticles (RGD-HBc/QR) with surface-displayed RGD targeting ligand exhibit a rather high selectivity toward activated HSCs via the binding affinity with integrin αvß3, and an efficient inhibition of proliferation and activation of hepatic stellate cells (HSCs) in vitro and in vivo. Once encapsulated in quercetin-gadolinium complex and/or labeled with the NIR fluorescent probes (Cy5.5), the resulting nanoparticles (RGD-HBc/QGd) show great potential as NIR fluorescent and magnetic resonance imaging contrast agents for hepatic fibrosis in vivo. Therefore, the multifunctional integrin-targeted nanoparticles could selectively deliver QR to the activated HSCs, and may provide an effective antifibrotic theranostic strategy.

Integration of phospholipid-complex nanocarrier assembly with endogenous N-oleoylethanolamine for efficient stroke therapy.

BACKGROUND: Leading to more and more deaths and disabilities, stroke has become a serious threat to human health. What's more, few effective drugs are available in clinic till now. RESULTS: In this research, we prepared a novel neuroprotective nanoformation (OEA-SPC NPs) via the combination of the nanoparticle drug delivery system with the endogenous N-oleoylethanolamine (OEA). By forming hydrogen bond between OEA and the carrier-soybean phosphatidylcholine (SPC), the form of OEA was turned into amorphus state when loading to the nanoparticles, which greatly improved its bioavailability. Then the following systematic experiments revealed the efficient neuroprotective effect of OEA-SPC NPs in vivo. Compared with the MCAO group, the cerebral infarct volume was reduced by 81.1%, and the edema degree by 78.4% via the oral administration of OEA-SPC NPs. And the neurological deficit scores illustrated that the MCAO rats treated with OEA-SPC NPs exhibited significantly less neurological dysfunction. The Morris water maze test indicated that the spatial learning and memory of cerebral ischemia model rats were almost recovered to the normal level. Besides, the OEA-SPC NPs could inhibit the inflammation of reperfusion to a very slight level. CONCLUSIONS: These results suggest that the OEA-SPC NPs have a great chance to be a potential anti-stroke formation for clinic application and actually bring hope to thousands of stroke patients.

Residual learning-based robotic image analysis model for low-voltage distributed photovoltaic fault identification and positioning.

With the fast development of large-scale Photovoltaic (PV) plants, the automatic PV fault identification and positioning have become an important task for the PV intelligent systems, aiming to guarantee the safety, reliability, and productivity of large-scale PV plants. In this paper, we propose a residual learning-based robotic (UAV) image analysis model for low-voltage distributed PV fault identification and positioning. In our target scenario, the unmanned aerial vehicles (UAVs) are deployed to acquire moving images of low-voltage distributed PV power plants. To get desired robustness and accuracy of PV image detection, we integrate residual learning with attention mechanism into the UAV image analysis model based on you only look once v4 (YOLOv4) network. Then, we design the sophisticated multi-scale spatial pyramid fusion and use it to optimize the YOLOv4 network for the nuanced task of fault localization within PV arrays, where the Complete-IOU loss is incorporated in the predictive modeling phase, significantly enhancing the accuracy and efficiency of fault detection. A series of experimental comparisons in terms of the accuracy of fault positioning are conducted, and the experimental results verify the feasibility and effectiveness of the proposed model in dealing with the safety and reliability maintenance of low-voltage distributed PV systems.

Caveolin-1 scaffolding domain-derived peptide enhances erectile function by regulating oxidative stress, mitochondrial dysfunction, and apoptosis of corpus cavernosum smooth muscle cells in rats with cavernous nerve injury.

AIM: Increased corpus cavernosum smooth muscle cells (CCSMCs) apoptosis in the penis due to cavernous nerve injury (CNI) is a crucial contributor to erectile dysfunction (ED). Caveolin-1 scaffolding domain (CSD)-derived peptide has been found to exert potential antiapoptotic properties. However, whether CSD peptide can alleviate CCSMCs apoptosis and ED in CNI rats remains unknown. The study aimed to determine whether CSD peptide can improve bilateral CNI-induced ED (BCNI-ED) by enhancing the antiapoptotic processes of CCSMCs. MAIN METHODS: Fifteen 10-week-old male Sprague-Dawley (SD) rats were randomly classified into three groups: sham surgery (Sham) group and BCNI groups that underwent saline or CSD peptide treatment respectively. At 3 weeks postoperatively, erectile function was assessed and the penis tissue was histologically examined. Furthermore, an in vitro model of CCSMCs apoptosis was established using transforming growth factor-beta 1 (TGF-ß1) to investigate the mechanism of CSD peptide in treating BCNI-ED. KEY FINDINGS: In BCNI rats, CSD peptide significantly prevented ED and decreased oxidative stress, the Bax/Bcl-2 ratio, and the levels of caspase3. TGF-ß1-treated CCSMCs exhibited severe oxidative stress, mitochondrial dysfunction, and apoptosis. However, CSD peptide partially reversed these alterations. SIGNIFICANCE: Exogenous CSD peptide could improve BCNI-ED by inhibiting oxidative stress, the Bax/Bcl-2 ratio, and caspase3 expression in penile tissue. The underlying mechanism might involve the regulatory effects of CSD peptide on oxidative stress, mitochondrial dysfunction, and apoptosis of CCSMCs following CNI. This study highlights CSD peptide as an effective therapy for post-radical prostatectomy ED (pRP-ED).

Knockdown of programmed cell death factor 4 restores erectile function by attenuating apoptosis in rats with bilateral cavernous nerve crush injury.

BACKGROUND: Apoptosis is an important pathologic mechanism of erectile dysfunction after radical prostatectomy. Studies have shown that programmed cell death factor 4 is connected to the modulation of apoptosis in many cells. However, the programmed cell death factor 4 function in the cavernous nerve injury erectile dysfunction is unclear. OBJECTIVE: This investigation aimed to explore the programmed cell death factor 4 function in erectile dysfunction in rats with bilateral cavernous nerve crush. MATERIALS AND METHODS: The experiment used 30 male Sprague Dawley rats (18 months old) that were screened for normal erectile function by the apomorphine test. Ten rats were randomized into Sham and bilateral cavernous nerve crush groups to detect changes in programmed cell death factor 4 expression. The remaining 20 rats were distributed at random to four groups: the Sham group treated by sham surgery, the phosphate-buffered saline group, the lentivirus containing negative control short hairpin RNA group, and the lentivirus containing short hairpin RNA targeting programmed cell death factor 4 group underwent bilateral cavernous nerve crush and were afterward administered intracavernous injections of phosphate-buffered saline, lentivirus containing negative control short hairpin RNA, or lentivirus containing short hairpin RNA targeting programmed cell death factor 4. Electrical stimulation of the cavernous nerve was conducted 2 weeks later for penile erectile function assessment. The cavernous tissue was collected for histological analysis and western blotting. RESULTS: The apoptosis level in rat corpus cavernosum was elevated, and programmed cell death factor 4 expression was increased after bilateral cavernous nerve crush. Knockdown of programmed cell death factor 4 significantly improved erectile function in bilateral cavernous nerve crush rats. Furthermore, lentivirus containing short hairpin RNA targeting programmed cell death factor 4 treatment raised smooth muscle content and attenuated cavernous fibrosis and apoptotic levels. Additionally, programmed cell death factor 4 was found to mediate the PI3K/AKT pathway. DISCUSSION AND CONCLUSION: Elevated programmed cell death factor 4 expression may be an important pathogenetic mechanism for erectile dysfunction after bilateral cavernous nerve crush, and the knockdown of programmed cell death factor 4 enhanced erectile function in 18-month-old rats after cavernous nerve damage. The potential mechanism may be the stimulation of the PI3K/AKT pathway to attenuate the cavernous apoptosis level.

MicroRNA-145 Gene Modification Enhances the Retention of Bone Marrow-Derived Mesenchymal Stem Cells within Corpus Cavernosum by Targeting Krüppel-Like Factor 4.

PURPOSE: The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. MATERIALS AND METHODS: The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. RESULTS: In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2'-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. CONCLUSIONS: Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

Poly-L-lactic acid/gelatin electrospun membrane-loaded bone marrow-derived mesenchymal stem cells attenuate erectile dysfunction caused by cavernous nerve injury.

Radical prostatectomy (RP) can cause neurogenic erectile dysfunction (ED), which negatively affects the quality of life of patients with prostate cancer. Currently, there is a dearth of effective therapeutic strategies. Although stem cell therapy is promising, direct cell transplantation to injured cavernous nerves is constrained by poor cell colonization. In this study, poly-L-lactic acid (PLLA)/gelatin electrospun membranes (PGEM) were fabricated to load bone marrow-derived mesenchymal stem cells (BM-MSCs) as a patch to be placed on injured nerves to alleviate ED. This study aimed to establish a promising and innovative approach to mitigate neurogenic ED post-RP and lay the foundation for modifying surgical procedures. Electrospinning and molecular biotechnology were performed in vitro and in vivo, respectively. It was observed that PGEM enhanced the performance of BM-MSCs and Schwann cells due to their excellent mechanical properties and biocompatibility. The transplanted PGEM and loaded BM-MSCs synergistically improved bilateral cavernous nerve injury-related ED and the corresponding histopathological changes. Nevertheless, transplantation of BM-MSCs alone has been verified to be ineffective. Overall, PGEM can serve as an ideal carrier to supply a more suitable survival environment for BM-MSCs and Schwann cells, thereby promoting the recovery of injured cavernous nerves and erectile function.

An animal model induced by bilateral cavernous nerve crushing mimics post-radical prostatectomy erectile dysfunction in old rats.

AIM: Over the years, the cavernous nerve (CN) crushing injury rat model has been frequently used for studying post-radical prostatectomy erectile dysfunction (pRP-ED). However, models based on young and healthy rats reportedly exhibit spontaneous recovery of erectile function. Our investigation purpose was to evaluate bilateral CN crushing (BCNC) effects on erectile function besides penile corpus cavernosum pathology in young and old rats and verify whether the BCNC modeling in old rats is more suitable to mimic pRP-ED. MATERIALS AND METHODS: Thirty young and old male Sprague-Dawley (SD) rats had been divided into three groups in a random manner: sham-operated group (Sham), CN-injured 2-week group (BCNC-2W), and CN-injured 8-week group (BCNC-8W). At 2 and 8 weeks postoperatively, mean arterial pressure (MAP) along with intracavernosal pressure (ICP) had been determined, respectively. Then, the penis was harvested for histopathological studies. KEY FINDING: We found that young rats exhibited erectile function spontaneous recovery 8 weeks following BCNC, while old ones failed to recover erectile function. After BCNC, the abundance of nNOS-positive nerve and smooth muscle were reduced, whereas apoptotic levels and collagen I content increased. These pathological modifications gradually resumed over time in young rats, unlike in old rats. SIGNIFICANCE: Our findings demonstrate that 18-month-old rats do not spontaneously regain erectile function at 8 weeks after BCNC. Therefore, CN-injury ED modeling in 18-month-old rats may be more suitable for studying pRP-ED.

Overexpression of a MYB1 Transcription Factor Enhances Triacylglycerol and Starch Accumulation and Biomass Production in the Green Microalga Chlamydomonas reinhardtii.

Microalgae are promising platforms for biofuel production. Transcription factors (TFs) are emerging as key regulators of lipid metabolism for biofuel production in microalgae. We previously identified a novel TF MYB1, which mediates lipid accumulation in the green microalga Chlamydomonas under nitrogen depletion. However, the function of MYB1 on lipid metabolism in microalgae under standard growth conditions remains poorly understood. Here, we examined the effects of MYB1 overexpression (MYB1-OE) on lipid metabolism and physiological changes in Chlamydomonas. Under standard growth conditions, MYB1-OE transformants accumulated 1.9 to 3.2-fold more triacylglycerols (TAGs) than that in the parental line (PL), and total fatty acids (FAs) also significantly increased. Moreover, saturated FA (C16:0) was enriched in TAGs and total FAs in MYB1-OE transformants. Notably, starch and protein content and biomass production also significantly increased in MYB1-OE transformants compared with that in PL. Furthermore, RT-qPCR results showed that the expressions of key genes involved in TAG, FA, and starch biosynthesis were upregulated. In addition, MYB1-OE transformants showed higher biomass production without a compromised cell growth rate and photosynthetic activity. Overall, our results indicate that MYB1 overexpression not only enhanced lipid content but also improved starch and protein content and biomass production under standard growth conditions. TF MYB1 engineering is a promising genetic engineering tool for biofuel production in microalgae.

A new porosity evaluation parameter based on neutron porosity logging.

The neutron porosity logging is one of the main methods for measuring the formation porosity. However, for the formation with complex mineral compositions and fluid properties, it is difficult to calculate the formation porosity accurately by the neutron porosity logging. In this paper, the relationship between the neutron slowing-down length and the neutron diffusion length and the formation hydrogen index is studied. Based on the thermal-neutron flux formula, a new parameter, apparent formation hydrogen index, is constructed by the neutron counting ratio and the formation density and the capture cross section. The apparent formation hydrogen index is close to the formation hydrogen index and is not affected by the excavation effect. The response characteristic of the apparent formation hydrogen index is more consistent with the volume physical model. The porosity calculated by the new parameter is closer to the formation porosity, especially in the gas-bearing formation.

[Tactic movement of microalgae and its application in targeted transport: a review].

Microalgae are a group of photosynthetic microorganisms, which have the general characteristics of plants such as photosynthesis, and some species have the ability of movement which resembles animals. Recently, it was reported that microalgae cells can be engineered to precisely deliver medicine-particles and other goods in microfluidic chips. These studies showed great application potential in biomedical treatment and pharmacodynamic analysis, which have become one of the current research hotspots. However, these developments have been rarely reviewed. Here, we summarized the advances in manageable movement exemplified by a model microalgae Chlamydomonas reinhardtii based on its characteristics of chemotaxis, phototaxis, and magnetotaxis. The bottlenecks and prospects in the application of microalgae-based tactic movement were also discussed. This review might be useful for rational design and modification of microalgal manageable movement to achieve targeted transport in medical and other fields.

Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction.

Aging has been deemed the primary factor in erectile dysfunction (ED). Herein, age-related changes in the erectile response and histomorphology were detected, and the relationship between aging and ED was investigated based on gene expression levels. Thirty male Sprague-Dawley (SD) rats were randomly divided into 6 groups, and intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured. Subsequently, the corpus cavernosum (CC) was harvested and prepared for histological examinations of apoptosis, oxidative stress (OS), and fibrosis. Then, the microarray dataset (GSE10804) was analyzed to identify differentially expressed genes (DEGs) in ED progression, and hub genes were selected. In addition, aged CC smooth muscle cells (CCSMCs) were isolated to evaluate the function of the hub gene by siRNA interference, qRT-PCR, immunofluorescence staining, enzyme-linked immunosorbent assay, western blot analysis, CCK-8 assay, EdU staining, and flow cytometry approaches. The ICP/MAP and smooth muscle cell (SMC)/collagen ratios declined with aging, while apoptosis and OS levels increased with aging. The enriched functions and pathways of the DEGs were investigated, and 15 hub genes were identified, among which IGFBP3 was significantly upregulated. The IGFBP3 upregulation was verified in the CC of aging rats. Furthermore, aged CCSMCs were transfected with siRNA to knock down IGFBP3 expression. The viability and proliferation of the CCSMCs increased, while apoptosis, OS, and fibrosis decreased. Our findings demonstrate that the erectile response of SD rats declines in parallel with enhanced CC apoptosis, OS, and fibrosis with aging. Upregulation of IGFBP3 plays an important role; furthermore, downregulation of IGFBP3 improves the viability and proliferation of CCSMCs and alleviates apoptosis, OS, and fibrosis. Thus, IGFBP3 is a potential therapeutic target for age-related ED.

Thermal Neutron Cross Section Logging based on compensated neutron logging.

In this paper, the compensated neutron logging is transformed into the Thermal Neutron Cross Section Logging (TNXS) to improve the application effect. Because the compensated neutron logging measures the neutron count, TNXS cannot be directly measured by the compensated neutron logging tool. Moreover, the thermal neutron ratio cannot be directly converted into the TNXS due to the influence of lithology and fluid. The ratio of thermal neutron count is related not only to the formation hydrogen index, but also to the formation density and the formation capture cross section. The density and the capture cross section of formations can be used to reduce the influence of lithology and fluid. Therefore, the thermal neutron counting ratio can be converted into the TNXS by density and the capture cross section of formations. The accuracy of the porosity calculated by the TNXS is studied based on the Monte Carlo method. The results show that the thermal neutron counting ratio can be accurately converted to the TNXS by density and the capture cross section of formations. The porosity calculated by TNXS is closer to the formation porosity than that calculated by the compensated neutron logging, especially in gas-bearing formations and complex lithologic formations.

Identification and Verification on Prognostic Index of Lower-Grade Glioma Immune-Related LncRNAs.

Previous studies have shown that the prognosis of patients with lower-grade glioma (LGG) is closely related to the infiltration of immune cells and the expression of long non-coding RNAs (lncRNAs). In this paper, we applied single-sample gene set enrichment analysis (ssGSEA) algorithm to evaluate the expression level of immune genes from tumor tissues in The Cancer Genome Atlas (TCGA) database, and divided patients into the high immune group and the low immune group, which were separately analyzed for differential expression. Venn analysis was taken to select 36 immune-related lncRNAs. To construct a prognostic model of LGG based on immune-related lncRNAs, we divided patients into a training set and a verification set at a ratio of 2:1. Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to select 11 immune-related lncRNAs associated with the prognosis of LGG, and based on these selected lncRNAs, the risk scoring model was constructed. Through Kaplan-Meier analysis, the overall survival (OS) of patients in the high-risk group was significantly lower than that of the low-risk group. Then, established a nomogram including age, gender, neoplasm histologic grade, and risk score. Meanwhile, the predictive performance of the model was evaluated by calculating the C-index, drawing the calibration chart, the clinical decision curve as well as the Receiver Operating Characteristic (ROC) curve. Similar results were obtained by utilizing the validation data to verify the above consequences. Based on the TIMER database, the correlation analysis showed that the 11 immune-related lncRNAs risk score of LGG were in connection with the infiltration of the subtypes of immune cells. Subsequently, we performed enrichment analysis, whose results showed that these immune-related lncRNAs played important roles in the progress of LGG. In conclusion, these 11 immune-related lncRNAs have the potential to predict the prognosis of patients with LGG, which may play a key role in the development of LGG.

Enhanced Water Solubility and Oral Bioavailability of Paclitaxel Crystal Powders through an Innovative Antisolvent Precipitation Process: Antisolvent Crystallization Using Ionic Liquids as Solvent.

Paclitaxel (PTX) is a poor water-soluble antineoplastic drug with significant antitumor activity. However, its low bioavailability is a major obstacle for its biomedical applications. Thus, this experiment is designed to prepare PTX crystal powders through an antisolvent precipitation process using 1-hexyl-3-methylimidazolium bromide (HMImBr) as solvent and water as an antisolvent. The factors influencing saturation solubility of PTX crystal powders in water in water were optimized using a single-factor design. The optimum conditions for the antisolvent precipitation process were as follows: 50 mg/mL concentration of the PTX solution, 25 °C temperature, and 1:7 solvent-to-antisolvent ratio. The PTX crystal powders were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, high-performance liquid chromatography-mass spectrometry, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Raman spectroscopy, solid-state nuclear magnetic resonance, and dissolution and oral bioavailability studies. Results showed that the chemical structure of PTX crystal powders were unchanged; however, precipitation of the crystalline structure changed. The dissolution test showed that the dissolution rate and solubility of PTX crystal powders were nearly 3.21-folds higher compared to raw PTX in water, and 1.27 times higher in artificial gastric juice. Meanwhile, the bioavailability of PTX crystal increased 10.88 times than raw PTX. These results suggested that PTX crystal powders might have potential value to become a new oral PTX formulation with high bioavailability.

Nanoparticle-based co-delivery of siRNA and paclitaxel for dual-targeting of glioblastoma.

Aim: To explore the therapeutic effect of nanoparticle-based dual-targeting delivery of antitumor agents for glioblastoma treatment. Materials & methods: A hepatitis B core protein-virus-like particle (VLP)-based dual-targeting delivery system was designed with the primary brain targeting peptide TGN for blood-brain barrier penetration and tumor vascular preferred ligand RGD (arginine-glycine-aspartic acid) for glioblastoma targeting. Chemo- and gene-therapeutic agents of paclitaxel and siRNA were co-packaged inside the vehicle. Results: The results demonstrated efficient delivery of the packaged agents to invasive tumor sites. The combination of chemo- and gene-therapies demonstrated synergistic antitumor effects through enhancing necrosis and apoptosis, as well as being able to inhibit tumor invasion with minimal cytotoxicity. Conclusion: Our hepatitis B core-VLP-based dual-targeting delivery of chemo- and gene-therapeutic agents possesses a synergistic antitumor effect for glioblastoma therapy.