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.

Surface Charge Density Gradient Printing To Drive Droplet Transport: A Numerical Study.

Traditional strategies, such as morphological or chemical gradients, struggle to realize the high-velocity and long-distance transport for droplets on a solid surface because of the pinning hydrodynamic equilibrium. Thus, there is a continuing challenge for practical technology to drive droplet transport over the last decades. The surface charge density (SCD) gradient printing method overcame the theoretical limit of traditional strategies and tackled this challenge [Nat. Mater. 2019, 18: 936], which utilized the asymmetric electric force to realize the high-velocity and long-distance droplet transport along a preprinted SCD gradient pathway. In the present work, by coupling the electrostatics and the hydrodynamics, we developed an unexplored numerical model for the water droplet transporting along the charged superhydrophobic surface. Subsequently, the effects of SCD gradients on the droplet transport were systematically discussed, and an optimized method for SCD gradient printing was proposed according to the numerical results. The present approach can provide early guidance for the SCD gradient printing to drive droplet transport on a solid surface.

CX3CL1 in the red bone marrow promotes renal cell carcinoma to metastasize to the spine by involving the Src-related pathway.

Spinal metastasis (SM) frequently occurs in renal cell carcinoma (RCC) patients. Our preliminary work showed that CX3CL1 plays a positive role in SM. The objective of the present study was to verify whether CX3CL1 activates the downstream pathway by binding to CX3CR1 in RCC cells, ultimately promoting RCC to metastasize to the spine. The expression of CX3CL1 and CX3CR1 in tissue samples was detected by immunohistochemistry and western blotting. ELISA was used to quantify the concentration of CX3CL1 in the serum. The expression level of CX3CR1 in RCC cell lines was also detected. The CellTiter-Glo assay and flow cytometry were used to analyze cell viability and apoptosis of RCC cells. Transwell and wound healing assay were used to analyze the effect of CX3CL1 on the invasion and migration ability of RCC cells. Specific inhibitors were used to interfere with key molecules in the signaling pathway to further explore the signal transduction in RCC cells after CX3CL1 stimulation. The expression of CX3CR1 in SM from RCC was higher than that in limb bone metastases. Among the five RCC cell lines, 786O cells expressed the highest level of CX3CR1. CX3CL1 neither inhibited the proliferation of 786O cells nor promoted the apoptosis of 786O cells. However, it promoted the migration and invasion of RCC cells. After CX3CL1 stimulation, Src and Focal adhesion kinase (FAK) phosphorylation levels increased in RCC cells. Bosutinib and PF-00562271 inhibited Src/FAK phosphorylation and cell motility and invasion triggered by CX3CL1 stimulation. CX3CL1 in the red bone marrow of spinal cancellous bone enhances migration and invasion abilities of RCC cells, thereby promoting RCC metastasize to the spine. The migration and invasion of RCC cells activated by CX3CL1 are at least partially dependent on Src/FAK activation.

Prediction of overall survival based upon a new ferroptosis-related gene signature in patients with clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common and lethal renal cell carcinoma (RCC) histological subtype. Ferroptosis is a newly discovered programmed cell death and serves an essential role in tumor occurrence and development. The purpose of this study is to analyze ferroptosis-related gene (FRG) expression profiles and to construct a multi-gene signature for predicting the prognosis of ccRCC patients. METHODS: RNA-sequencing data and clinicopathological data of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed FRGs between ccRCC and normal tissues were identified using 'limma' package in R. GO and KEGG enrichment analyses were conducted to elucidate the biological functions and pathways of differentially expressed FRGs. Consensus clustering was used to investigate the relationship between the expression of FRGs and clinical phenotypes. Univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis were used to screen genes related to prognosis and construct the optimal signature. Then, a nomogram was established to predict individual survival probability by combining clinical features and prognostic signature. RESULTS: A total of 19 differentially expressed FRGs were identified. Consensus clustering identified two clusters of ccRCC patients with distinguished prognostic. Functional analysis revealed that metabolism-related pathways were enriched, especially lipid metabolism. A 7-gene ferroptosis-related prognostic signature was constructed to stratify the TCGA training cohort into high- and low-risk groups where the prognosis was significantly worse in the high-risk group. The signature was identified as an independent prognostic indicator for ccRCC. These findings were validated in the testing cohort, the entire cohort, and the International Cancer Genome Consortium (ICGC) cohort. We further demonstrated that the signature-based risk score was highly associated with the ccRCC progression. Further stratified survival analysis showed that the high-risk group had a significantly lower overall survival (OS) rate than those in the low-risk group. Moreover, we constructed a nomogram that had a strong ability to forecast the OS of the ccRCC patients. CONCLUSIONS: We constructed a ferroptosis-related prognostic signature, which might provide a reliable prognosis assessment tool for the clinician to guide clinical decision-making and outcomes research.

Influence of Trapezoidal Cavity on the Wettability of Hydrophobic Surface: A Molecular Dynamics Study.

In this study, the behaviors of water droplets on hydrophobic surfaces with different cavities are studied by molecular dynamics. Hydrophobic surfaces with different cavities are designed and simulated: trapezoidal cavity with the same lower width, upside down trapezoidal cavity with the same lower width, and so on. The results show that the influence of the upper width and the depth of the cavity on the contact state and contact angle is different for different trapezoidal cavities. For example, for the trapezoidal cavity with the same lower width, the upper width decreases with the increase of the cavity depth. In such a scenario, the upper width and depth of the cavity collectively promote the droplet transition into the Cassie state from the Wenzel state, but the effect of the upper width and depth on the contact angle is opposite, and the decrease of the upper width of the cavity is the dominant factor, which leads to a decrease in the contact angle. Then, we have built trapezoidal cavities with different base angles. The influence of different base angles on wettability is also discussed, and it is found that an increase in base angle can significantly delay the transition from Cassie state into the Wenzel state.

Development of novel TPI/HDPE/CNTs ternary hybrid shape memory nanocomposites.

In order to make up for the defects of trans-1,4-polyisoprene (TPI) shape memory polymer, TPI/high density polyethylene (HDPE) hybrid shape memory matrix was prepared from the perspective of matrix composition. The carbon nanotubes (CNTs) with excellent mechanical properties were introduced into the hybrid shape memory matrix. Due to the difference of the inherent properties and geometry of nano-fillers, the change of the content of nano-fillers directly affects the bonding state within the composites. Therefore, it is very important to choose the appropriate content. In order to give full play to the potential of thermodynamics of nano-filler, the TPI/HDPE/CNTs ternary hybrid shape memory nanocomposites were prepared by mechanical melt blending technology combined with dynamic vulcanization and hot-pressing forming technology. The addition of CNTs promotes the formation of the crystal structure of TPI and HDPE, and facilitates the energy transfer between different interface, which greatly improves the thermal conductivity and mechanical properties of the nanocomposites at the same time. The effect of the changes of filler content on the thermodynamic properties of the composite materials were revealed by series of tests. The results show that the CNTs act as nucleating agents in the crystallization region of TPI and HDPE. However, the excessive addition of CNTs can inhibit the formation of HDPE crystal structure. Meanwhile, the crystallinity of nanocomposites is also an important factor affecting its thermal conductivity. The specimens with the CNTs content of 0.5 wt% have excellent tensile resistance and cyclic recovery ability, and it can improve the shape recovery properties. Therefore, the nanocomposite with the CNTs content of 0.5 wt% has the best thermodynamic and shape memory properties.

Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal.

The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.

The effect of physical exercise on rheumatoid arthritis: An overview of systematic reviews and meta-analysis.

AIMS: To determine which outcomes will be improved by different exercise interventions and the evidence quality for each intervention. DESIGN: Overview of systematic reviews and meta-analysis. DATA SOURCES: PubMed, Cochrane, Web of Science, CINAHL, and Embase. Published from the establishment of the database to 3 September 2019. REVIEW METHODS: AMSTAR 2 and PRISMA were used to evaluate methodological and reporting quality. Evidence quality of the effect of each intervention was assessed according to GRADE guidelines. Meta-analysis of original studies was conducted for comparison of systematic reviews and to explore the effect of different exercise interventions on the same outcome. RESULTS: Ten systematic reviews were included in the overview. A significant improvement was seen in: aerobic exercise for aerobic capacity; strength training for erythrocyte sedimentation rate and 50-foot walking time; aerobic exercise combined with strength training for aerobic capacity, physical function, and fatigue; hand exercise for hand function. CONCLUSIONS: For the maximum benefit of rheumatoid arthritis (RA) patients, different exercise methods should be selected according to the symptoms. For RA patients, any exercise is better than no exercise, but the intensity, frequency, and period of exercise for better results are not determined. IMPACT: What problem did the study address is which outcomes will be improved by different exercise interventions. For maximum benefit for RA patients, different exercise methods should be selected according to symptoms. The research summarized the evidence of exercise rehabilitation of RA and will help RA patients or their caregivers choose the appropriate type of exercise, which will play a positive role on the rehabilitation of patients with RA.

Impact on sexual function of plasma button transurethral vapour enucleation versus plasmakinetic resection of the large prostate >90 ml: Results of a prospective, randomized trial.

To compare the impact of plasma button transurethral vapour enucleation of the prostate (PVEP) and plasmakinetic resection of the prostate (PKRP) on lower urinary tract symptoms and sexual function in patients with benign prostatic enlargement (BPE) >90 ml. Between July 2017 and August 2018, 101 patients with symptomatic BPE were randomly, prospectively assigned to either PKRP or PVEP in our department. The clinical characteristics and sexual function were evaluated before and after surgery. Post-void residual volume, IPSS and QoL were all significantly decreased compared with baseline data in each group, while Qmax was significantly increased. The IIEF-5 score showed a slight but nonsignificant increase in both groups at 3 and 6 months after surgery, and there was no significant difference between the two groups. The post-operative rate of reduced ejaculate volume was significantly higher than the pre-operative rate in PKRP group, while there was no significant difference in PVEP group. PVEP had an attenuated effect on no ejaculate compared with PRKP, and they both had a significantly negative effect on no ejaculate. PVEP is an effective and minimally invasive procedure for large prostate. Compared with PKRP, PVEP has no effect on erectile dysfunction and has a lower negative impact on ejaculation.

Development of functionalized core-shell nanohybrid/synthetic rubber nanocomposites with enhanced performance.

Regulating the interfacial interaction between fillers and matrices is crucial for fabricating high-performance polymer composites. In this research, a functionalized core-shell hybrid silica@graphene oxide was produced by the charge attraction method, and then added to a trans-1,4-polyisoprene matrix as a neoteric filler to obtain a brand-new silica@graphene oxide/trans-1,4-polyisoprene polymer nanocomposite. The hybrid incorporation simultaneously improved the fracture toughness, mechanical strength and heat resistance of the nanocomposites. We examined the thermal, mechanical and shape memory properties of the nanocomposites via methodical measurements from the microscale to the macroscale. The experimental results demonstrated that, compared with other samples, the nanocomposite sample with 1.0 wt% silica@graphene oxide exhibited the best mechanical and thermal performance, and the fabricated nanocomposites showed good shape memory properties. This new and feasible approach is likely to enable a new strategy for the design of interfaces for developing nanocomposites with high performance.

A novel graphene oxide/trans-1,4-polyisoprene (GO/TPI) shape memory polymer nanocomposite and its multifunctional properties.

In this work, we have synthesized a novel graphene oxide/trans-1,4-polyisoprene (GO/TPI) shape memory polymer (SMP) nanocomposite by adding GO (0.0-1.5 phr) to bulk TPI polymer to enhance its mechanical properties. We have studied and examined its mechanical, thermal and thermomechanical properties through systematic tests from microscale to macroscale. The shape memory properties and the effect of the GO content on the thermal and mechanical properties of the manufactured SMP nanocomposites were studied by differential scanning calorimetry, dynamic mechanical analysis, thermogravimetric analysis, thermal conductivity, and static tensile and mechanical as well as thermomechanical cyclic loading tests. The experimental results indicate that the SMP nanocomposite with 0.9 phr GO has superior thermal and mechanical properties compared to all other cases, and good shape memory was obtained in the GO/TPI nanocomposites.

Experimental and analytical studies on the flexible, low-voltage electrothermal film based on the multi-walled carbon nanotube/polymer nanocomposite.

This paper presents multi-walled carbon nanotube (MWCNT)/poly(m-phenylene isophthalamide) (PMIA) nanocomposite films as electrothermal elements, which offer advantages in flexibility, low energy consumption and rapid temperature growth. The electrical properties, electrothermal behavior and thermal stability of the films were investigated as a function of MWCNT content. The percolation behavior analysis revealed MWCNTs built a continuously conductive network in PMIA matrix at the corresponding percolation threshold of ∼0.06 wt%. The electrothermal behavior of the MWCNT/PMIA film was investigated by considering temperature response rapidity and electrothermal efficiency under different ambient conditions. For the film with 7.0 wt% MWCNTs under different ambient conditions, the film worked at a high heating rate of 1.0-8.2 °C s-1 and cooling rate of 0.75-7.0 °C s-1 under a low voltage of 3-12 V, due to the low electrical resistivity (4.5 Ω cm) of the film. The prepared MWCNT/PMIA films supported more outstanding heating performance than conventional PI-Kanthal film, including good heating uniformity, higher electrothermal efficiency and heating/cooling rate. Moreover, the improved thermomechanical properties of the nanocomposite were observed by dynamic thermomechanical analysis.

miR-34b Alleviates High Glucose-Induced Inflammation and Apoptosis in Human HK-2 Cells via IL-6R/JAK2/STAT3 Signaling Pathway.

BACKGROUND It is well established that inflammation and apoptosis of renal tubular epithelial cells caused by hyperglycemia contribute to the development of diabetic nephropathy (DN). Although microRNAs (miRNAs) are known to have roles in inflammation-related disorders, the exact role of miR-34b in DN has not been defined, and the regulatory mechanism has been unclear. This study aimed to clarify the role of miR-34b in DN pathogenesis. MATERIAL AND METHODS Expression of miR-34b, IL-6R, and other key factors of inflammation, apoptosis (TNF-alpha, IL-1ß, IL-6, caspase-3) in high glucose (HG)-induced HK-2 cells were measured by real-time PCR, Western blot, and flow cytometric cell apoptosis assays. We used luciferase reporter assay to detect the target of miR-34b. Moreover, the targeting gene of miR-34b and its downstream JAK2/STAT3 signaling pathway were explored. RESULTS It was demonstrated that miR-34b overexpression inhibited apoptosis and expression levels of TNF-alpha, IL-1ß, IL-6, and caspase-3 in HG-treated HK-2 cells. We also found that IL-6R is a direct target of miR-34b, which could rescue inflammation and apoptosis in HG-treated HK-2 cells transfected with miR-34b mimic. Furthermore, we showed that overexpression of miR-34b inhibited the IL-6R/JAK2/STAT3 signaling pathway in HG-treated HK-2 cells. CONCLUSIONS Our data suggest that overexpression of miR-34b improves inflammation and ameliorates apoptosis in HG-induced HK-2 cells via the IL-6R/JAK2/STAT3 pathway, indicating that miR-34b could be a promising therapeutic target in DN.

Effect of a Roughness Element on the Hypersonic Boundary Layer Receptivity Due to Different Types of Free-Stream Disturbance with a Single Frequency.

The hypersonic flow field around a blunt cone was simulated using a high-order finite difference method. Fast acoustic waves, slow acoustic waves, entropy waves, and vortical waves were introduced into the free-stream to determine the influence of a free-stream with disturbances on the hypersonic flow field and boundary layer. The effect of disturbance type on the evolution of perturbations in the hypersonic boundary layer was analyzed. Fast Fourier Transform was adopted to analyze the effect of the disturbance type on the evolution of different modes in the boundary layer. A roughness element was introduced into the flow field to reveal the impact of the roughness element on hypersonic boundary layer receptivity. The results showed that a free-stream with disturbances affected the hypersonic flow field and boundary layer; acoustic waves had the greatest influence. The impact of slow acoustic waves on the flow field was mainly concentrated in the region between the shock and the boundary layer, whereas the influence of fast acoustic waves was mainly concentrated in the boundary layer. Multi-mode perturbations formed in the boundary layer were caused by the free-stream with disturbances, wherein the fundamental mode was the dominant mode of the perturbations in the boundary layer caused by fast acoustic waves, entropy waves, and vortical waves. The dominant modes of the perturbations in the boundary layer caused by slow acoustic waves were both the fundamental mode and the second harmonic mode. The roughness element changed the propagation process of different modes of perturbations in the boundary layer. In the downstream region of the roughness element, perturbations in the boundary layer caused by the slow acoustic waves had the greatest influence. The second harmonic mode in the boundary layer was significantly suppressed, and the fundamental mode became the dominant mode. The effects of fast acoustic waves and entropy waves on the boundary layer receptivity were similar, except the amplitude of the perturbations in the boundary layer caused by the fast acoustic waves was larger.

Simvastatin Treatment Protects Myocardium in Noncoronary Artery Cardiac Surgery by Inhibiting Apoptosis Through miR-15a-5p Targeting.

Simvastatin treatment is cardioprotective in patients undergoing noncoronary artery cardiac surgery. However, the mechanisms by which simvastatin treatment protects the myocardium under these conditions are not fully understood. Seventy patients undergoing noncoronary cardiac surgery, 35 from a simvastatin treatment group and 35 from a control treatment group, were enrolled in our clinical study. Simvastatin (20 mg/d) was administered preoperatively for 5-7 days. Myocardial tissue biopsies were taken before and after surgery. Apoptosis was detected by TUNEL staining. The expressions of Bcl-2 and Bak in myocardial tissue were detected by immunoblotting. The expressions of miRNA and Bcl-2 mRNA were detected by quantitative real-time polymerase chain reaction assays. Cardiomyocytes were isolated from rat and cultured cells. MiR-15a-5p mimic was transfected into cardiomyocytes, and the Bcl-2 was detected by immunoblotting. TUNEL staining showed significantly less myocardial apoptosis in the simvastatin treatment group when compared with the control treatment group. Protein expression of Bcl-2 was increased in the simvastatin treatment group before surgery, and Bak expression was increased in the control treatment group after surgery. Further comparisons showed that Bcl-2/Bak ratios were reduced in the control treatment group but were not significantly changed in the simvastatin treatment group after surgery. Furthermore, microarray assays revealed that miR-15a-5p was significantly decreased by simvastatin treatment. This was validated by quantitative real-time polymerase chain reaction analysis. MiR-15a-5p was predicted to target Bcl-2 mRNA at nucleotide positions 2529-2536. This was validated by luciferase binding assays. Coincident with the change in miR-15a-5p, the mRNA expression of Bcl-2 was increased in the simvastatin treatment group. MiR-15a-5p mimic significantly inhibited Bcl-2 expression in cardiomyocytes. Our findings strongly suggest that simvastatin treatment preoperatively protected the myocardium in patients undergoing noncoronary artery cardiac surgery, at least in part, by inhibiting apoptosis via suppressing miR-15a-5p expression, leading to increasing expression of Bcl-2 and decreasing expression of Bak.

Effect of a Roughness Element on the Receptivity of a Hypersonic Boundary Layer over a Blunt Cone Due to Pulse Entropy Disturbance with a Single Frequency.

A high-order finite difference method was used to simulate the hypersonic flow field over a blunt cone with different height roughness elements. The unsteady flow field induced by pulse disturbances was analyzed and compared with that under continuous disturbances. The temporal and spatial evolution characteristics of disturbances in the boundary layer were investigated and the propagation of different disturbance modes in the boundary layer was researched through the fast Fourier transform (FFT) method. The effect of the roughness element on the receptivity characteristic of the hypersonic boundary layer under pulse entropy disturbances was explored. The results showed that the different mode disturbances near roughness in the boundary layer were enlarged in the upstream half of the roughness element and suppressed in the downstream half. However, the effect of roughness weakened gradually as the disturbance frequency increased in the boundary layer. A phenomenon of mode competition in the downstream region of the roughness element exited. As the disturbances propagated downstream, the fundamental mode gradually became the dominant mode. A certain promotion effect on the mode competition was induced by the roughness element and the effect was enhanced with the increase in the roughness element height.

Response of a hypersonic boundary layer to freestream pulse acoustic disturbance.

The response of hypersonic boundary layer over a blunt wedge to freestream pulse acoustic disturbance was investigated. The stability characteristics of boundary layer for freestream pulse wave and continuous wave were analyzed comparatively. Results show that freestream pulse disturbance changes the thermal conductivity characteristics of boundary layer. For pulse wave, the number of main disturbance clusters decreases and the frequency band narrows along streamwise. There are competition and disturbance energy transfer among different modes in boundary layer. The dominant mode of boundary layer has an inhibitory action on other modes. Under continuous wave, the disturbance modes are mainly distributed near fundamental and harmonic frequencies, while under pulse wave, the disturbance modes are widely distributed in different modes. For both pulse and continuous waves, most of disturbance modes slide into a lower-growth or decay state in downstream, which is tending towards stability. The amplitude of disturbance modes in boundary layer under continuous wave is considerably larger than pulse wave. The growth rate for the former is also considerably larger than the later the disturbance modes with higher growth are mainly distributed near fundamental and harmonic frequencies for the former, while the disturbance modes are widely distributed in different frequencies for the latter.

Temporal and spatial evolution characteristics of disturbance wave in a hypersonic boundary layer due to single-frequency entropy disturbance.

By using a high-order accurate finite difference scheme, direct numerical simulation of hypersonic flow over an 8° half-wedge-angle blunt wedge under freestream single-frequency entropy disturbance is conducted; the generation and the temporal and spatial nonlinear evolution of boundary layer disturbance waves are investigated. Results show that, under the freestream single-frequency entropy disturbance, the entropy state of boundary layer is changed sharply and the disturbance waves within a certain frequency range are induced in the boundary layer. Furthermore, the amplitudes of disturbance waves in the period phase are larger than that in the response phase and ablation phase and the frequency range in the boundary layer in the period phase is narrower than that in these two phases. In addition, the mode competition, dominant mode transformation, and disturbance energy transfer exist among different modes both in temporal and in spatial evolution. The mode competition changes the characteristics of nonlinear evolution of the unstable waves in the boundary layer. The development of the most unstable mode along streamwise relies more on the motivation of disturbance waves in the upstream than that of other modes on this motivation.

In Situ-Sprayed Bioinspired Adhesive Conductive Hydrogels for Cavernous Nerve Repair.

Cavernous nerve injury (CNI), resulting in erectile dysfunction (ED), poses a significant threat to the quality of life for men. Strategies utilizing conductive hydrogels have demonstrated promising results for the treatment of peripheral nerves with a large diameter (>2 mm). However, integrating convenient minimally invasive operation, antiswelling and immunomodulatory conductive hydrogels for treating small-diameter injured cavernous nerves remains a great challenge. Here, a sprayable adhesive conductive hydrogel (GACM) composed of gelatin, adenine, carbon nanotubes, and mesaconate designed for cavernous nerve repair is developed. Multiple hydrogen bonds provide GACM with excellent adhesive and antiswelling properties, enabling it to establish a conformal electrical bridge with the damaged nerve and aiding in the regeneration process. Additionally, mesaconate-loaded GACM suppresses the release of inflammatory factors by macrophages and promotes the migration and proliferation of Schwann cells. In vivo tests demonstrate that the GACM hydrogel repairs the cavernous nerve and restores erectile function and fertility. Furthermore, the feasibility of sprayable GACM in minimally invasive robotic surgery in beagles is validated. Given the benefits of therapeutic effectiveness and clinical convenience, the research suggests a promising future for sprayable GACM materials as advanced solutions for minimally invasive nerve repair.

Stem Leydig cells support macrophage immunological homeostasis through mitochondrial transfer in mice.

As testicular mesenchymal stromal cells, stem Leydig cells (SLCs) show great promise in the treatment of male hypogonadism. The therapeutic functions of mesenchymal stromal cells are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs remain unclear. Here, we observe that SLCs transplantation restore male fertility and testosterone production in an ischemia‒reperfusion injury mouse model. SLCs prevent inflammatory cascades through mitochondrial transfer to macrophages. Reactive oxygen species (ROS) released from activated macrophages inducing mitochondrial transfer from SLCs to macrophages in a transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated manner. Notably, knockdown of TRPM7 in transplanted SLCs compromised therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. These findings reveal a new mechanism of SLCs transplantation that may contribute to preserve testis function in male patients with hypogonadism related to immune disorders.