Mediating effect of gestational weight gain on the preventive effect of exercise during pregnancy on macrosomia: a randomized clinical trial.

OBJECTIVE: We sought to investigate the impact of individualized exercise guidance during pregnancy on the incidence of macrosomia and the mediating effect of gestational weight gain (GWG). DESIGN: A prospective randomized clinical trial. SETTING: A Hospital in Xingtai District, Hebei Province. POPULATION: Older than 20 years of age, mid-pregnancy, and singleton pregnant women without contraindications to exercise during pregnancy. METHODS: A randomized clinical trial was conducted from December 2021 to September 2022 to compare the effects of standard prenatal care with individualized exercise guidance on the incidence of macrosomia. MAIN OUTCOME MEASURE: Incidence of macrosomia. RESULTS: In all, 312 singleton women were randomized into an intervention group (N = 162) or a control group (N = 150). Participants who received individualized exercise guidance had a significantly lower incidence of macrosomia (3.73% vs. 13.61%, P = 0.002) and infants large for gestational age (9.94% vs. 19.73%, P = 0.015). However, no differences were observed in the rate of preterm birth (1.86% vs. 3.40%, P = 0.397) or the average gestational age at birth (39.14 ± 1.51 vs. 38.69 ± 1.85, P = 0.258). Mediation analysis revealed that GWG mediated the effect of exercise on reducing the incidence of macrosomia. CONCLUSION: Individualized exercise guidance may be a preventive tool for macrosomia, and GWG mediates the effect of exercise on reducing the incidence of macrosomia. However, evidence does not show that exercise increases the rate of preterm birth or affects the average gestational age at birth. TRIAL REGISTRATION: The trial is registered at www.clinicaltrails.gov [registration number: NCT05760768; registration date: 08/03/2023 (retrospectively registered)].

The soil microbial necromass carbon and the carbon pool stability drive a stronge priming effect following vegetation restoration.

The priming effect stands as a critical factor influencing the balance of soil organic carbon (SOC). Following vegetation restoration, the carbon (C) pool stability in Platycladus orientalis forests (PO) varies, and the priming effect resulting from exogenous C addition also differs significantly. Here, we selected PO with restoration ages of 10, 15, and 30 years in the rocky mountainous area in northern China and conducted measurements of soil properties, microbial communities, microbial necromass C (MNC), SOC fractions, and the priming effect characteristics to explore the main influencing factors of the priming effect, especially the microbiological mechanisms. Our results showed that the ratio of mineral-associated organic C to particulate organic C increased. The characteristics of the priming effect showed the same pattern, and there was a significant positive correlation between the C pool stability and the priming effect. The diversity of the fungal communities increased with increasing vegetation restoration age, and the content and proportion of fungal necromass C (FNC) also increased synchronously, reaching the maximum value in the soil of PO that had been restored for 30 years. In addition, the soil water content and total nitrogen indirectly affected the priming effect by influencing the microbial communities. In summary, the results suggested that vegetation restoration can enhance the C pool stability by promoting an increase in soil FNC, thereby producing a positive priming effect. This can help deepen our understanding of the SOC mineralization changes induced by fresh C input following vegetation restoration and provides a theoretical basis for better explaining the C cycle between soil and atmosphere under the vegetation restoration models in the future.

Study on the relationship between the fitness of three types of N95 respirators and facial dimensions.

N95 respirators are the core equipment used by healthcare workers to prevent the spread of respiratory diseases. The protective effect of N95 against infection spread depends on the fit of the N95 to the wearer, which is related to the wearer's facial dimensions. The purpose of this cross-sectional study was to assess the relationship between the fit of three types of N95 and facial dimensions. A total of 305 healthcare workers from ten hospitals in Beijing were recruited for this study. Facial dimensions of workers were measured using Intel RealSense Depth Camera D435. Fit testing was conducted on three types of N95 using the TSI-8038 Porta Count Pro + Respirator Fit Tester. Possible associations between the fit test results and facial dimension data were examined. A Porta Count reading of 100 was used as the criterion for an acceptable fit. The fit of the folding respirators was positively correlated with nose length (r = 0.13, p = 0.02), nose height (r = 0.14, p = 0.02), and face width (r = 0.12, p = 0.03), whereas that of flat respirators was correlated with nose width (r = 0.16, p < 0.01), chin length (r = 0.18, p < 0.01), and pro-face width (r = 0.13, p = 0.02), and that of arched respirators was correlated with the nose length (r = 0.13, p = 0.03). The fit of N95 for wearers depends on their facial features. The results of this study can provide advice for medical workers to choose the appropriate N95. Medical staff should fully consider their facial dimensions when choosing an appropriate N95 to improve the protective efficacy of respirators and to reduce the risk of infection by respiratory diseases.

Control of the electron dynamics in solid-state high harmonic generation on ultrafast time scales by a polarization-skewed laser pulse.

Since high-order harmonic generation (HHG) from atoms depends sensitively on the polarization of the driving laser field, the polarization gating (PG) technique was developed and applied successfully to generate isolated attosecond pulses from atomic gases. The situation is, however, different in solid-state systems as it has been demonstrated that due to collisions with neighboring atomic cores of the crystal lattice strong HHG can be generated even by elliptically- and circularly-polarized laser fields. Here we apply PG to solid-state systems and find that the conventional PG technique is inefficient for the generation of isolated ultrashort harmonic pulse bursts. In contrast, we demonstrate that a polarization-skewed laser pulse is able to confine the harmonic emission to a time window of less than one-tenth of the laser cycle. This method provides a novel way to control HHG and to generate isolated attosecond pulses in solids.

Boosting the Cell Performance of the SiO/Cu and SiO/PPy Anodes via In-Situ Reduction/Oxidation Coating Strategies.

Silicon monoxide (SiO) has attracted great attention due to its high theoretical specific capacity as an alternative material for conventional graphite anode, but its poor electrical conductivity and irreversible side reactions at the SiO/electrolyte interface seriously reduce its cycling stability. Here, to overcome the drawbacks, the dicharged SiO anode coated with Cu coating layer is elaborately designed by in-situ reduction method. Compared with the pristine SiO anode of lithium-ion battery (293 mAh g-1 at 0.5 A g-1 after 200 cycles), the obtained SiO/Cu composite presents superior cycling stability (1206 mAh g-1 at 0.5 A g-1 after 200 cycles). The tight combination of Cu particles and SiO significantly improves the conductivity of the composite, effectively inhibits the side-reaction between the active material and electrolyte. In addition, polypyrrole-coated SiO composites are further prepared by in-situ oxidation method, which delivers a high reversible specific capacity of 1311 mAh g-1 at 0.5 A g-1 after 200 cycles. The in-situ coating strategies in this work provide a new pathway for the development and practical application of high-performance silicon-based anode.

Extracellular vesicles derived from mouse adipose-derived mesenchymal stem cells promote diabetic corneal epithelial wound healing through NGF/TrkA pathway activation involving dendritic cells.

Diabetic keratopathy (DK) is a common ocular complication of diabetes in which the dendritic cells (DCs)-mediated inflammatory response plays an important role. Nerve growth factor (NGF)/Tropomyosin receptor kinase A (TrkA)-mediated inhibition of the nuclear factor kappa B (NF-κB) pathway can reduce inflammatory cytokine production. Extracellular vesicles (EVs) derived from mouse adipose-derived mesenchymal stem cells (mADSC-EVs) have been explored extensively as treatments for degenerative eye disease. However, mADSC-EVs is poorly studied in the DK models. In this study, we investigated the anti-inflammatory effects of mADSC-EVs and explored the underlying mechanisms in vitro and in vivo DK models. Our results showed that mADSC-EVs have significant therapeutic effects including increasing tear volume and the ratio of lacrimal gland/body weight, promoting corneal nerve regeneration, and sensation recovery in streptozotocin (STZ)-induced DK mice. In addition, mADSC-EVs significantly reduced the inflammatory response involving DCs, consistently up-regulated protein expression of the NGF/TrkA pathway, and importantly, reduced lipopolysaccharide (LPS)-mediated IL-6 and TNF-α expression and directly dependent on TrkA in the induced culture of bone marrow-derived DCs (BMDCs). Taken together, our findings revealed that mADSC-EVs promoted diabetic corneal epithelial wound healing through NGF/TrkA pathway activation involving DCs. Given the significant therapeutic efficacy of mADSC-EVs and its clinical application, mADSC-EVs appears to be a promising new therapy for DK.

Microenergy acoustic pulse therapy restores urethral wall integrity and continence in a rat model of female stress incontinence.

OBJECTIVE: To determine the outcomes and mechanisms of microenergy acoustic pulse (MAP) therapy in an irreversible rat model of female stress urinary incontinence. MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats were randomly assigned into four groups: sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + ß-aminopropionitrile (BAPN), and VBDO + ß-aminopropionitrile treated with MAP (MAP). MAP therapy was administered twice per week for 4 weeks. After a 1-week washout period, all 24 rats were evaluated with functional and histological studies. The urethral vascular plexus was examined by immunofluorescence staining with antibodies against collagen IV and von Willebrand factor (vWF). The urethral smooth muscle stem/progenitor cells (uSMPCs) were isolated and functionally studied in vivo and in vitro. RESULTS: Functional study with leak point pressure (LPP) measurement showed that the MAP group had significantly higher LPPs compared to VBDO and BAPN groups. MAP ameliorated the decline in urethral wall thickness and increased the amount of extracellular matrix within the urethral wall, especially in the urethral and vaginal elastic fibers. MAP also improved the disruption of the urethral vascular plexus in the treated animals. In addition, MAP enhanced the regeneration of urethral and vaginal smooth muscle, and uSMPCs could be induced by MAP to differentiate into smooth muscle and neuron-like cells in vitro. CONCLUSION: MAP appears to restore urethral wall integrity by increasing muscle content in the urethra and the vagina and by improving the urethral vascular plexus and the extracellular matrix.

Effect of PRECEDE-PROCEED-Model-Based Health Education on the Life Quality and 5-HTT Gene Expression of Patients with Gastric Cancer after Surgery.

This study aimed to investigate the effect of PRECEDE-PROCEED-Model-based health education on the life quality of patients with gastric cancer after surgery. Also, the effect of this model was evaluated on 5-HTT gene expression as a gene related to depression. For this purpose, a total of 32 gastric cancer patients who were hospitalized in this hospital between March 2019 and September 2020 were enrolled in this study after surgery and, according to the time of admission, were divided into the control group and observation group, with 16 patients in each group. Patients in the control group were nursed regularly, while those in the observation group, in addition to the regular nursing, would receive the PRECEDE-PROCEED-Model-based health education. Post-surgery life quality of patients in two groups was compared from the following aspects: Rehabilitation process, pain assessment, rate of complications and The Short-Form (SF-36) Health Survey. The expression of the 5-HTT gene was performed by the Real-time qPCR technique. The results of this study showed that after surgery, the extubation time and the time of hospital discharge of patients in the observation group were all earlier than those in the control group, while the score of pain assessment and rate of complication was much lower in the observation group, and the SF-36 score of patients was much higher (all P < 0.05). The results of 5-HTT gene expression showed that there was no significant difference between the control and observation groups before the intervention. But one month after the intervention, gene expression in the observation group was significantly reduced compared to the control group (p <0.01). This significant decrease was also seen two months after the intervention (p <0.05). As mentioned before, the expression of the 5-HTT gene increases during the depression, therefore improvement of the patient's condition and quality of life decreased the expression of this gene. Hence, PRECEDE-PROCEED-Model-Based Health Education plays an influential role in reducing the expression of this gene. However, the passage of time has not been ineffective in lowering 5-HTT expression. In general, PRECEDE-PROCEED-Model-based health education could help patients establish a good system of health knowledge, which could encourage the patients to avoid the negative mood, optimize the rehabilitation process, improve the post-surgery rehabilitation and, finally, ameliorate the life quality of patients after surgery.

Exosomes Derived from Mouse Adipose-Derived Mesenchymal Stem Cells Alleviate Benzalkonium Chloride-Induced Mouse Dry Eye Model via Inhibiting NLRP3 Inflammasome.

PURPOSE: The objective of the study was to investigate efficacy and mechanisms of mouse adipose-derived mesenchymal stem cell-derived exosomes (mADSC-Exos) in the benzalkonium chloride (BAC)-induced mouse dry eye model. METHODS: Exosomes in the mADSC culture supernatant were isolated by ultracentrifugation. Western blotting, nanoparticle tracking analysis, and transmission electron microscopy were used to characterize mADSC-Exos. An experimental mouse model of dry eye was established by instillation of 0.2% BAC. mADSC-Exos were administered following BAC treatment. The positive control group was treated with commercial eye drops (0.1% pranoprofen). Corneal fluorescein staining, tear secretion, and tear film break-up time (BUT) were evaluated, and histologic analysis of the cornea and conjunctiva was performed by hematoxylin and eosin and periodic acid-Schiff staining. Apoptosis in the corneal epithelium was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and by Western blotting. Levels of pro-inflammatory cytokines in the cornea and conjunctiva were evaluated by flow cytometry, and mRNA and protein levels of NLR family pyrin domain-containing 3 (NLRP3) pathway components were assessed by quantitative real-time PCR and Western blotting, respectively. RESULTS: mADSC-Exos were characterized as vesicles with a bilayer membrane. The particle size distribution peak was at 134 nm. mADSC-Exos specifically expressed cluster of differentiation (CD)9, CD63, and CD81. mADSC-Exos treatment repaired ocular surface damage. Additionally, mADSC-Exos inhibited cell apoptosis, decreased the levels of interleukin (IL)-1ß, IL-6, IL-1α, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, and increased levels of the anti-inflammatory cytokine IL-10. Meanwhile, NLRP3 inflammasome activation and upregulation of caspase-1, IL-1ß, and IL-18 were reversed by mADSC-Exos. CONCLUSIONS: mADSC-Exos alleviate ocular surface inflammation, suggesting that it is a promising treatment for dry eye.

Rapid postmortem ventilation improves donor lung viability by extending the tolerable warm ischemic time after cardiac death in mice.

Uncontrolled donation after cardiac death (uDCD) contributes little to ameliorating donor lung shortage due to rapidly progressive warm ischemia after circulatory arrest. Here, we demonstrated that nonhypoxia improves donor lung viability in a novel uDCD lung transplant model undergoing rapid ventilation after cardiac death and compared the evolution of ischemia-reperfusion injury to mice that underwent pulmonary artery ligation (PAL). The tolerable warm ischemia time at 37°C was initially determined in mice using a modified PAL model. The donor lung following PAL was also transplanted into syngeneic mice and compared with those that underwent rapid ventilation or no ventilation at 37°C before transplantation. Twenty-four hours following reperfusion, lung histology, [Formula: see text]/[Formula: see text] ratio, and inflammatory mediators were measured. Four hours of PAL had little impact on [Formula: see text]/[Formula: see text] ratio and acute lung injury score in contrast to significant injury induced by 5 h of PAL. Four-hour PAL lungs showed an early myeloid-dominant inflammatory signature when compared with naïve lungs and substantially injured 5 h PAL lungs. In the context of transplantation, unventilated donor lungs showed severe injury after reperfusion, whereas ventilated donor lungs showed minimal changes in [Formula: see text]/[Formula: see text] ratio, histologic score, and expression of inflammatory markers. Taken together, the tolerable warm ischemia time of murine lungs at 37°C can be extended by maintaining alveolar ventilation for up to 4 h. Nonhypoxic lung undergoing warm ischemia-reperfusion injury shows an early transcriptional signature of myeloid cell recruitment and extracellular matrix proteolysis before blood-gas barrier dysfunction and significant tissue damage.

Simultaneous removal of Zn2+ and p-nitrophenol from wastewater using nanocomposites of montmorillonite with alkyl-ammonium and complexant.

Three types of alkyl-ammonium with different branching chains and three complexants with different functional groups were used to prepare alkyl-ammonium or complexant intercalated montmorillonite nanocomposite (A-Mt or C-Mt). In addition, synergistic intercalated montmorillonite nanocomposites (A/C-Mt) with alkyl-ammonium along with complexant were also prepared. The adsorption performance of the various nanocomposites toward Zn2+ and p-nitrophenol (PNP) from simulated binary wastewater containing both Zn2+ and PNP were systematically investigated. Characterization of Mt nanocomposites showed that both alkyl-ammoniums and complexants were successfully intercalated into the interlayers of Mt. The surfactant loading amounts of the various nanocomposites were also determined and correlated with the resulting expansion of the interlayer spacing. It was found that intercalation of alkane (OTAC) and -SH (CSH) were conducive to the adsorption of Zn2+ while -C2H4NH (TETA) and all alkyl-ammoniums were beneficial for PNP adsorption. The extent of adsorption was found to be controlled primarily by pH, i.e., the higher pH had a good effect on the adsorption of both Zn2+ and PNP. The adsorption process of Zn2+ onto Mt nanocomposites was more in line with the Freundlich model (R2 = 0.99), while the Langmuir model described the adsorption of PNP well (R2 = 0.99). The adsorption kinetics could be well described by the Elovich equation (R2 = 0.98) and the double-constant model (R2 = 0.89). Chemical adsorption was determined to be the dominant process between the contaminant and Mt nanocomposite surfaces.

EphA2 overexpression reduces H2O2-induced damage of lens epithelial cells.

Age-related cataract (ARC) is a progressive lens opacification that occurs from middle to old age. Eph-receptor tyrosinekinase-type A2 (EphA2) has been reported to be associated with ARC. This work aims to investigate the molecular mechanism of EphA2 in ARC. We treated human lens epithelial cells (SRA01/04) with different concentration of H2O2 to induce lens epithelial cell damage. Then, we found that H2O2 treatment significantly suppressed cell viability and enhanced the expression of EphA2 in the SRA01/04 cells. H2O2 treatment repressed cell viability and enhanced the levels of reactive oxygen species (ROS) in SRA01/04 cells, which was partly abolished by EphA2 up-regulation. Moreover, EphA2 overexpression reduced H2O2-induced apoptosis of SRA01/04 cells. EphA2 up-regulation caused an up-regulation of Bcl-2, and repressed the expression of Bax and Cleaved-caspase-3 in the SRA01/04 cells following H2O2 treatment. In conclusion, our data confirm that EphA2 overexpression enhances cell viability and inhibits apoptosis in the H2O2-treated SRA01/04 cells, thereby reducing H2O2-induced damage of lens epithelial cells. Thus, this work provides new insights into the mechanism of EphA2 in ARC.

Overexpression of PpSnRK1α in tomato enhanced salt tolerance by regulating ABA signaling pathway and reactive oxygen metabolism.

BACKGROUND: SNF-related Kinase 1 (SnRK1) is a key component of the cell signaling network. SnRK1 is known to respond to a wide variety of stresses, but its exact role in salt stress response and tolerance is still largely unknown. RESULTS: In this study, we reported that overexpression of the gene encoding the α subunit of Prunus persica SnRK1 (PpSnRK1α) in tomato could improve salt stress tolerance. The increase in salt stress tolerance in PpSnRK1α-overexpressing plants was found to correlate with increased PpSnRK1α expression level and SnRK1 kinase activity. And PpSnRK1α overexpression lines exhibited a lower level of leaf damage as well as increased proline content and reduced malondialdehyde (MDA) compared with wild-type (WT) lines under salt stress. Furthermore, PpSnRK1α enhanced reactive oxygen species (ROS) metabolism by increasing the expression level of antioxidase genes and antioxidant enzyme activities. We further sequenced the transcriptomes of the WT and three PpSnRK1α overexpression lines using RNA-seq and identified about 1000 PpSnRK1α-regulated genes, including many antioxidant enzymes, and these genes were clearly enriched in the MAPK signaling pathway (plant), plant-pathogen interactions and plant hormone signaling transduction and can respond to stimuli, metabolic processes, and biological regulation. Furthermore, we identified the transcriptional levels of several salt stress-responsive genes, SlPP2C37, SlPYL4, SlPYL8, SlNAC022, SlNAC042, and SlSnRK2 family were altered significantly by PpSnRK1α, signifying that SnRK1α may be involved in the ABA signaling pathway to improve tomato salt tolerance. Overall, these findings provided new evidence for the underlying mechanism of SnRK1α conferment in plant salt tolerance phenotypes. CONCLUSIONS: Our findings demonstrated that plant salt stress resistance can be affected by the regulation of the SnRK1α. Further molecular and genetic approaches will accelerate our knowledge of PpSnRK1α functions, and inform the genetic improvement of salt tolerance in tomato through genetic engineering and other related strategies.

MnS@N,S Co-Doped Carbon Core/Shell Nanocubes: Sulfur-Bridged Bonds Enhanced Na-Storage Properties Revealed by In Situ Raman Spectroscopy and Transmission Electron Microscopy.

Rational structure and morphology design are of great significance to realize excellent Na storage for advanced electrode materials in sodium-ion batteries (SIBs). Herein, a cube-like core/shell composite of single MnS nanocubes (≈50 nm) encapsulated in N, S co-doped carbon (MnS@NSC) with strong CSMn bond interactions is successfully prepared as outstanding anode material for SIBs. The carbon shell significantly restricts the expansion of the MnS volume in successive sodiation/desodiation processes, as demonstrated by in situ transmission electron microscopy (TEM) of one single MnS@NSC nanocube. Moreover, the in situ generated CSMn bonds between the MnS core and carbon shell play a significant role in improving the Na-storage stability and reversibility of MnS@NSC, as revealed by in situ Raman and TEM. As a result, MnS@NSC exhibits a high reversible specific capacity of 594.2 mAh g-1 at a current density of 100 mA g-1 and an excellent rate performance. It also achieves a remarkable cycling stability of 329.1 mAh g-1 after 3000 charge/discharge cycles at 1 A g-1 corresponding to a low capacity attenuation rate of 0.0068% per cycle, which is superior to that of pristine MnS and most of the reported Mn-based anode materials in SIBs.

Exosome Released From Schwann Cells May Be Involved in Microenergy Acoustic Pulse-Associated Cavernous Nerve Regeneration.

BACKGROUND: Neurogenic erectile dysfunction (ED) is often refractory to treatment because of insufficient functional nerve recovery after injury or insult. Noninvasive mechano-biological intervention, such as microenergy acoustic pulse (MAP), low-intensity pulsed ultrasound, and low-intensity extracorporeal shockwave treatment, is an optimal approach to stimulate nerve regeneration. AIM: To establish a new model in vitro to simulate nerve injury in neurogenic ED and to explore the mechanisms of MAP in vitro. METHODS: Sprague-Dawley rats were used to isolate Schwann cells (SCs), major pelvic ganglion (MPG), and cavernous nerve with MPG (CN/MPG). SCs were then treated with MAP (0.033 mJ/mm2, 1 Hz, 100 pulses), and SC exosomes were isolated. The MPG and CN/MPG were treated with MAP (0.033 mJ/mm2, 1 Hz) at different dosages (25, 50, 100, 200, or 300 pulses) or exosomes derived from MAP-treated SCs in vitro. OUTCOMES: Neurite growth from the MPG fragments and CN was photographed and measured. Expression of neurotropic factors (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) was checked. RESULTS: Neurite outgrowth from MPG and CN/MPG was enhanced by MAP in a dosage response manner, peaking at 100 pulses. MAP promoted SC proliferation, neurotropic factor (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) expression, and exosome secretion. SC-derived exosomes significantly enhanced neurite outgrowth from MPG in vitro. CLINICAL IMPLICATIONS: MAP may have utility in the treatment of neurogenic ED by SC-derived exosomes. STRENGTH & LIMITATIONS: We confirmed that MAP enhances penile nerve regeneration through exsomes. Limitations of this study include that our study did not explore the exact mechanisms of how MAP increases SC exosome secretion nor whether MAP modulates the content of exosomes. CONCLUSION: This study revealed that neurite outgrowth from MPG was enhanced by MAP and by SC-derived exosomes which were isolated after MAP treatment. Our findings indicate that one mechanism by which MAP induces nerve regeneration is by stimulation of SCs to secrete exosomes. Peng D, Reed-Maldonado AB, Zhou F, et al. Exosome Released From Schwann Cells May Be Involved in Microenergy Acoustic Pulse-Associated Cavernous Nerve Regeneration. J Sex Med 2020;17:1618-1628.

Efficacy and Safety of Mechanical Thrombectomy for Acute Mild Ischemic Stroke with Large Vessel Occlusion.

BACKGROUND The suitability of mechanical thrombectomy (MT) for patients with acute mild ischemic stroke (AMIS) caused by large vessel occlusion (LVO) is controversial. This study evaluated MT in patients with AMIS and LVO. MATERIAL AND METHODS Forty-seven patients diagnosed as AMIS with LVO received MT or intravenous thrombolysis (IVT). Primary outcomes were National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale scores. Secondary outcomes were incidence of systemic complications and symptomatic intracranial hemorrhage. RESULTS There were no significant differences between IVT and MT groups for gender, age, risk factors of cerebrovascular disease, past history, NIHSS score at admission, blood pressure, and LVO sites. For all patients, the NIHSS scores at discharge were lower than those at admission. Patients with excellent outcomes were 66.6% (16/24) in the IVT group and 60.8% (14/23) in the MT group; favorable outcome rates were 75% (18/24) in the IVT group and 69.6% (16/23) in the MT group, with no significant differences between groups. Twelve patients (52.2%) in the MT group and 5 (20.8%) in the IVT group had systemic complications. Symptomatic intracranial hemorrhage was not detected in the IVT group, but manifested in 2 (8.7%) patients in the MT group. During 90-day follow-up, 1 patient died in each of the IVT and MT groups, with 4.2% and 4.4% mortality rates, respectively. CONCLUSIONS The efficacy of MT and IVT was comparable in AMIS patients with LVO. While MT had a higher incidence of systemic complications, its short- and long-term effects were equivalent to IVT.

Platycodin D protects cortical neurons against oxygen-glucose deprivation/reperfusion in neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxic-ischemic encephalopathy is one of the leading causes of death in infants. Increasing evidence indicates that oxidative stress and apoptosis are major contributors to hypoxic-ischemic injury and can be used as particularly promising therapeutic targets. Platycodin D (PLD) is a triterpenoid saponin that exhibits antioxidant properties. The aim of this study was to evaluate the effects of PLD on hypoxic-ischemic injury in primary cortical neurons. We found that oxygen-glucose deprivation/reperfusion (OGD/R) induced inhibition of cell viability and cytotoxicity, which were attenuated by PLD treatment. PLD treatment inhibited oxidative stress induced by OGD/R, which was evidenced by the reduced level of reactive oxygen species and increased activities of catalase, superoxide dismutase, and glutathione peroxidase. Histone-DNA enzyme-linked immunosorbent assay revealed that apoptosis was significantly decreased after PLD treatment in OGD/R-treated cortical neurons. The increased bax expression and decreased bcl-2 expression induced by OGD/R were reversed by PLD treatment. Furthermore, PLD treatment caused the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in OGD/R-stimulated cortical neurons. Suppression of this pathway blocked the protective effects of PLD on OGD/R-induced cell injury. These findings suggested that PLD executes its protective effects on OGD/R-induced cell injury via regulating the PI3K/Akt/mTOR pathway in cortical neurons.

Bone marrow-derived mesenchymal stem cells-derived exosomes prevent oligodendrocyte apoptosis through exosomal miR-134 by targeting caspase-8.

Ischemic stroke causes severe brain damage and remains one of the leading causes of morbidity and mortality worldwide. The microRNA-134 (miR-134) is involved in regulating the process of ischemia injury in neural cells and brain with ischemia stroke. The role of miR-134 in ischemic stroke remains poorly understood. The purpose of the current study was to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs)-derived exosomal miR-134 on rat oligodendrocytes (OLs) apoptosis and its underlying mechanism of action. The results demonstrated that levels of miR-134 in BMSCs-exosome decreased but increased incaspase-8 after oxygen-glucose deprivation (OGD) treatment. Exosomal miR-134 significantly inhibited apoptosis by decreasing caspase-8 expression and activity in OGD-treated group cultured with BMSCs-exosome and OLs. In addition, the miR-134 mimics decreased caspase-8 expression in OGD-treated OLs, whereas miR-134 inhibitors exacerbated the changes in the expression of the procaspase-8 and caspase-8 cleaved product proteins caused by OGD. The caspase-8 knockdown using caspase-8 small interfering RNA decreased OLs apoptosis, reversing the improvements that the miR-134 inhibited cells apoptosis by targeting caspase-8. Taken together, these results demonstrated that BMSCs-derived exosomes suppressed OLs apoptosis through exosomal miR-134 by negatively regulating the caspase-8-dependent apoptosis pathway and may, therefore, be a novel potential therapeutic target for ischemic stroke treatment.

Smooth Muscle Differentiation of Penile Stem/Progenitor Cells Induced by Microenergy Acoustic Pulses In Vitro.

INTRODUCTION: Modulating tissue-resident stem and progenitor cells with a non-invasive, mechanobiological intervention is an optimal approach for tissue regeneration. Stem cell antigen-1 (Sca-1) has been identified as a stem cell marker within many organs but never within the penis. AIM: To localize and isolate penile stem/progenitor cells (PSPCs) and to evaluate cellular differentiation after exposure to induction medium and microenergy acoustic pulse (MAP) therapy. METHODS: Six male Sprague-Dawley rats were used to isolate PSPCs. Isolation was followed by stem cell characterization and differentiation assays. The PSPCs were then treated with MAP (0.033 mJ/mm2, 1 Hz) at various dosages (25, 50, 100, and 200 pulses) and for different durations (1, 2, 4, 6, or 8 hours) in vitro. MAIN OUTCOME MEASURE: The PSPCs (Sca-1-positive cells) were isolated using the magnetic-activated cell sorting system. PSPC cellular differentiation was assessed after induction with induction medium and with MAP in vitro. Wnt/ß-catenin signaling was also assayed. RESULTS: The PSPCs were successfully localized within the penile subtunic and perisinusoidal spaces, and they were successfully isolated using magnetic-activated cell sorting. The stemness of the cells was confirmed by stem cell marker characterization and by multiple differentiation into smooth muscle cells, endothelial cells, adipocytes, and neurons. MAP-induced PSPCs differentiated into smooth muscle cells by activating the Wnt/ß-catenin signaling pathway in a time- and dosage-dependent manner. CLINICAL IMPLICATIONS: By modulating resident PSPCs, MAP may have utility in the treatment of erectile dysfunction (ED). STRENGTHS & LIMITATIONS: This study provides solid evidence in support of microenergy therapies, including both MAP and low-intensity extracorporeal shock wave therapy, for the treatment of ED. Additional studies are needed and should include additional stem cells markers. Furthermore, studies exploring the underling mechanisms for PSPC activation and differentiation are required. CONCLUSION: PSPCs were successfully identified, localized, and isolated. Additionally, MAP provoked PSPCs to differentiate into smooth muscle cells via the Wnt/ß-catenin signaling pathway. As such, MAP provides a novel method for activating endogenous tissue-resident stem/progenitor cells and might facilitate stem cell regenerative therapy targeting ED. Peng D, Yuan H, Liu T, et al. Smooth Muscle Differentiation of Penile Stem/Progenitor Cells Induced by Microenergy Acoustic Pulses In Vitro. J Sex Med 2019; 16:1874-1884.

Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury.

BACKGROUND: Erectile dysfunction (ED) caused by pelvic neurovascular injury (PNVI) is often refractory to treatment. In many cases, erectogenic therapy is administered in a delayed fashion. AIM: To evaluate penile hemodynamic effects and histologic changes associated with delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) after PNVI ED in a rat model. We visualized images using immunofluorescence and 3-dimensional imaging of solvent-cleared organs (3DISCO), a novel imaging technique. METHODS: A total of 32 Sprague-Dawley male rats aged 12 weeks were divided equally into 4 groups: sham surgery as normal controls (NC), PNVI controls (PC), PNVI with very-low-energy Li-ESWT (PVL), and PNVI with low-energy Li-ESWT (PL). Bilateral cavernous nerve crush and internal pudendal bundle ligation were performed in the 3 PNVI groups. Li-ESWT was administered twice a week for 4 weeks in the PL and PVL groups starting at 4 weeks after PNVI. OUTCOMES: Intracavernous pressure (ICP) studies (normalized to mean arterial pressure [MAP]) were conducted in all subject animals. After testing, tissue was harvested for immunofluorescence staining and 3DISCO analysis. RESULTS: Mean ICP/MAP was lower in PC animals compared with NC animals (0.37 ± 0.03 vs 0.91 ± 0.03, respectively; P = .001). The ICP/MAP ratio was significantly higher in PVL and PL animals (0.66 ± 0.07 and 0.82 ± 0.05, respectively) compared with PC animals (P = .002 and .001, respectively). Detailed microstructures and trajectories of nerves and vessels were identified with immunofluorescence and 3DISCO. The PC group had lower density of nerves, axons, neuronal nitric oxide synthase-positive nerves, and Schwann cells in the dorsal penis. Animals in the PL group had significantly higher expression of all of these markers compared with PC animals. CLINICAL IMPLICATIONS: Li-EWST may have utility in the management of severe ED related to PNVI from severe pelvic injury or radical pelvic surgeries, even when administered in a delayed fashion. STRENGTH & LIMITATIONS: This study of a severe ED phenotype involved treatment administered in a delayed fashion, which is more consistent with how therapy likely would be delivered in a real-world clinical context. Moreover, because the treatment commenced at 4 weeks after injury, when nerve and tissue atrophy have already occurred, the results imply that Li-ESWT can be used for regenerative therapy. Additional studies on dose optimization and treatment interval are needed to inform the design of human clinical trials. CONCLUSION: Li-ESWT ameliorates the negative functional and histologic effects of severe pelvic neurovascular injury in a rat model system. 3DISCO provides high-resolution images of neuroanatomy and neural regeneration. Wang HS, Ruan Y, Banie L, et al. Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury. J Sex Med 2019;16:17-26.