Superelastic conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of highly stretchable (up to 1320%) sheath-core ...conducting fibers created by wrapping carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber cores. The resulting structure exhibited distinct short- and long-period sheath buckling that occurred reversibly out of phase in the axial and belt directions, enabling a resistance change of less than 5% for a 1000% stretch. By including other rubber and carbon nanotube sheath layers, we demonstrated strain sensors generating an 860% capacitance change and electrically powered torsional muscles operating reversibly by a coupled tension-to-torsion actuation mechanism. Using theory, we quantitatively explain the complementary effects of an increase in muscle length and a large positive Poisson's ratio on torsional actuation and electronic properties.
Patients with long duration of atrial fibrillation (AF), enlarged atria, or failed catheter ablation have advanced AF and may require more extensive treatment than pulmonary vein isolation.
The aim ...of this study was to investigate the efficacy and safety of additional ganglion plexus (GP) ablation in patients undergoing thoracoscopic AF surgery.
Patients with paroxysmal AF underwent pulmonary vein isolation. Patients with persistent AF also received additional lines (Dallas lesion set). Patients were randomized 1:1 to additional epicardial ablation of the 4 major GPs and Marshall's ligament (GP group) or no extra ablation (control) and followed every 3 months for 1 year. After a 3-month blanking period, all antiarrhythmic drugs were discontinued.
Two hundred forty patients with a mean AF duration of 5.7 ± 5.1 years (59% persistent) were included. Mean procedure times were 185 ± 54 min and 168 ± 54 min (p = 0.015) in the GP (n = 117) and control groups (n = 123), respectively. GP ablation abated 100% of evoked vagal responses; these responses remained in 87% of control subjects. Major bleeding occurred in 9 patients (all in the GP group; p < 0.001); 8 patients were managed thoracoscopically, and 1 underwent sternotomy. Sinus node dysfunction occurred in 12 patients in the GP group and 4 control subjects (p = 0.038), and 6 pacemakers were implanted (all in the GP group; p = 0.013). After 1 year, 4 patients had died (all in the GP group, not procedure related; p = 0.055), and 9 were lost to follow-up. Freedom from AF recurrence in the GP and control groups was not statistically different whether patients had paroxysmal or persistent AF. At 1 year, 82% of patients were not taking antiarrhythmic drugs.
GP ablation during thoracoscopic surgery for advanced AF has no detectable effect on AF recurrence but causes more major adverse events, major bleeding, sinus node dysfunction, and pacemaker implantation. (Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery AFACT; NCT01091389).
Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown.
To ...determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment.
Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020.
Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d.
The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group.
Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 interquartile range, 46-66 years; 227 39% women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care.
Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.
ClinicalTrials.gov Identifier: NCT04292730.
NiCo2S4 single-shelled hollow polyhedrons (SSHPs) and double-shelled hollow polyhedrons (DSHPs) were synthesized by the same metal-organic-framework-engaged strategy that took advantage of the unique ...reactions of zeolitic imidazolate framework-67 and Ni(NO3)2, H2O, thiacetamide. It was found by XRD, SEM, TEM that the synthesized NiCo2S4 materials showed the hollow polyhedron structure assembled with nanocrystalline (the size was around 10–15 nm), and numerous mesopores existed among these nanocrystalline. As anode materials for lithium-ion batteries, NiCo2S4 SSHPs and DSHPs exhibited excellent cycling stability, but DSHPs were remarkably superior to SSHPs in terms of capacity performance and rate capability. At 0.1C, DSHPs could deliver the discharge capacity of 770.3 mAh g−1 at the 100th cycle, and the average discharge capacity over 100 cycles reached 745.5 mAh g−1. When the current came back to 0.1C after rate measurements, NiCo2S4 DSHPs could stably deliver the discharging capacity of 712.0 mAh g−1, reaching 92.1% of that at the initial 0.1C. The superior Li-storage performance should be attributed to the nanocrystalline, mesopore, and multi-shelled hollow polyhedron structure. The unique NiCo2S4 multi-shelled hollow polyhedrons exhibit great potential as anode materials for high-performance lithium-ion batteries.
Although synaptic behaviours of memristors have been widely demonstrated, implementation of an even simple artificial neural network is still a great challenge. In this work, we demonstrate the ...associative memory on the basis of a memristive Hopfield network. Different patterns can be stored into the memristive Hopfield network by tuning the resistance of the memristors, and the pre-stored patterns can be successfully retrieved directly or through some associative intermediate states, being analogous to the associative memory behaviour. Both single-associative memory and multi-associative memories can be realized with the memristive Hopfield network.
Corrosion behaviour of N80 carbon steel in formation water containing CO2 was studied by polarization curve technique, electrochemical impedance spectroscopy, weight loss test, scanning electron ...microscope, and X-ray diffraction. Effects of temperature and acetic acid concentration on the corrosion behaviour of N80 carbon steel were discussed. The results showed that increasing temperature not only enhanced the dissolution of steel substrate, but also promoted the precipitation of FeCO3, the addition of acetic acid enhanced localized corrosion attack on N80 carbon steel. FeCO3 was the main corrosion product. And there was a transition region between CO2 corrosion control and HAc corrosion control.
Abstract
STUDY QUESTION
Can human pre-antral follicles isolated enzymatically from surplus medulla tissue survive and grow in vitro during long-term 3D culture?
SUMMARY ANSWER
Secondary human ...follicles can develop to small antral follicles and remain hormonally active in an alginate-encapsulation culture system for more than 30 days.
WHAT IS KNOWN ALREADY
Ovarian tissue cryopreservation followed by transplantation is a promising fertility preservation approach for cancer patients. However, transplantation of cryopreserved tissue to patients may carry the risk of re-implanting malignant cells. Grafting of follicles enzymatically isolated from ovarian tissue or developing a method for follicular culture and maturation in vitro may provide fertility to such patients without the risk of reintroducing the malignancy. However, the growth of pre-antral follicles isolated by enzymatic digestion from medulla tissue during long-term culture has received only little attention.
STUDY DESIGN, SIZE, DURATION
Two to ten human pre-antral follicles were encapsulated together within an alginate bead and cultured with or without ovarian interstitial tissue for either 7 days or >30 days. Follicles were cultured in either 20% oxygen or 5% oxygen or encapsulated in a lower concentration of alginate together with a lower concentration of FSH in high oxygen.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 395 pre-antral follicles from 16 cancer patients, aged 9–37 years, were co-cultured for either 7 days or >30 days. A proportion of follicle (64) were removed from culture on Day 7 and assessed for viability using confocal fluorescence microscopy following calcein-AM and ethidium homodimer-1 staining or histology. The remaining follicles (331) were continued in culture for >30 days then assessed for survival and growth. Anti-Müllerian hormone (AMH) and estradiol levels were quantified in the medium.
MAIN RESULTS AND THE ROLE OF CHANCE
An optimized protocol for isolation of intact healthy pre-antral follicles from ovarian medulla was developed. After 7 days of culture, secondary follicles had a significantly higher survival rates compared with primary and primordial follicles (70 versus <38%). Primordial and primary follicles did not develop into the antral follicle stage. In contrast, secondary follicles continued to develop in all culture conditions examined. Based on growth rate and morphology, four distinct cohorts of surviving follicles, ‘fast growth’, ‘slow growth’, ‘no growth’ and ‘extruded oocyte’ were identified. From Day 1 to Day 30, the mean diameter of follicles increased from 184 ± 35 to 661 ± 120 μm (significant from Day 18), 145 ± 19 to 318 ± 68 μm and 136 ± 15 to 162 ± 25 μm (mean ± SD) in the ‘fast growth’, ‘slow growth’ and ‘no growth’ patterns, respectively. The fast growth follicles also contained a larger diameter oocyte than other follicle groups. From the pre-antral follicle to antral stage, follicles became steroidogenically active and secretion of AMH and estradiol increased. No significant difference between the follicles cultured with or without ovarian interstitial tissue was observed.
LIMITATIONS, REASONS FOR CAUTION
The number of surviving follicles at the end of study was low in each of the culture conditions therefore whether there is a benefit with any of the conditions is difficult to ascertain. Multiple pre-antral follicles were cultured within the same alginate bead which may affect the in vitro development of the secondary follicles.
WIDER IMPLICATIONS OF THE FINDINGS
These findings show that pre-antral follicles, isolated enzymatically from surplus medulla tissue that is normally discarded, possess a developmental potential which may be used to devise safer fertility preservation methods for patients who are at high risk of malignant contamination of their ovarian tissue.
STUDY FUNDING/COMPETING INTEREST(S)
The Child Cancer Foundation in Denmark (2012–26) and the EU interregional project ReproHigh are thanked for having funded this study; and the Key Program of Medical Science and Technology Innovation of Nanjing Military Area Command in China (14ZX06; 11Z010). They had no role in the study design, collection and analysis of data, data interpretation or in writing the report. The authors have no conflicts of interest to disclose.
Heparan sulfate 3‐O‐sulfotransferase 2 (HS3ST2), an enzyme mediating 3‐O‐sulfation of heparan sulfate (HS), is silenced by hypermethylation in breast cancer. As HS has an important co‐receptor ...function for numerous signal transduction pathways, the phenotypical changes due to HS3ST2 reexpression were investigated in vitro using high and low invasive breast cancer cell lines. Compared to controls, highly invasive HS3ST2‐expressing MDA‐MB‐231 cells showed enhanced Matrigel invasiveness, transendothelial migration and motility. Affymetrix screening and confirmatory real‐time PCR and Western blotting analysis revealed increased expression of several matrix metalloproteinases, cadherin‐11, E‐cadherin and CEACAM‐1, while protease inhibitor and annexin A10 expression were decreased. Low invasive HS3ST2 ‐expressing MCF‐7 cells became even less invasive, with no change in gelatinolytic MMP activity. HS3ST2 expression increased HS‐dependent basal and FGF2‐specific signaling through the constitutively active p44/42 MAPK pathway in MDA‐MB‐231 cells. Increased MAPK activation was accompanied by upregulation of ß‐catenin in MDA‐MB‐231, and of the transcription factor Tcf4 in both cell lines. Dysregulation of Tcf4‐regulated ion transporters and increased cytosolic acidification were observed in HS3ST2‐expressing MDA‐MB‐231 cells, which is a possible underlying cause of increased chemosensitivity towards doxorubicine and paclitaxel in these cells. This study provides the first in vitro evidence of the involvement of HS3ST2 in breast cancer cell invasion and chemosensitivity.
What's New?
Heparan sulfate is present in all cell types and tissues and is involved in the modulation of cell adhesion, proliferation, and motility. While HS3ST2—an enzyme mediating 3‐O‐sulfation of heparan sulfate—is known to be epigenetically silenced in breast cancer, its mechanistic role has yet to be characterized. This study reveals a novel role of HS3ST2 in modulating breast cancer cell invasiveness and chemoresistance via MAP kinase‐ and Tcf7l2/Tcf4‐dependent regulation of protease and cadherin expression. The findings demonstrate the importance of specific sulfation patterns in heparan sulfate and pave the way for new heparinoid‐based therapeutic approaches.
Abstract In the context of this study, we leverage a hierarchical deep reinforcement learning algorithm to address challenges in the integration of renewable energy sources within smart grid ...environments. The primary focus is on enhancing the efficiency of large-scale renewable energy integration while ensuring grid stability and reliability. The algorithm builds on the principles of hierarchical deep reinforcement learning, aiming to optimize energy utilization, reduce operational costs, and decrease reliance on conventional energy sources within the smart grid framework. Rigorous experimentation in authentic smart grid settings validates the efficacy of the proposed algorithm, demonstrating notable improvements in grid performance and increased utilization of renewable energy sources. The mathematical outcomes underscore the algorithm’s superior performance across diverse conditions. This research contributes a practical solution for seamlessly incorporating renewable energy sources into smart grids, providing valuable insights for the optimization and sustainability of future smart grid systems. Future research directions may involve further refinement of the algorithm to adapt to evolving electricity network environments, fostering broader applications of renewable energy technologies in power systems.
Currently, antimicrobial peptides (AMPs) are of growing interest as potential substitutes for antibiotic growth promoters in animal production. The present study was conducted to evaluate the effects ...of dietary supplementation of bioengineering artificial Parasin I protein (API) and artificial plectasin protein (APL) (named as compound bioengineering protein, CBP) on growth performance and intestinal health of broilers. A total of 450 one-day-old Arbor Acres male healthy broilers were randomly allotted to 5 dietary groups with 10 replicates of 9 individuals in each replicate and supplemented with 0, 250, 500, 750, and 1,000 mg/kg CBP for 6 wk. Dietary CBP supplementation increased (P < 0.01) body weight (6 wk), average daily gain (0–6 wk), and average daily feed intake (3–6 wk and 0–6 wk). CBP addition enhanced antioxidant capacity, which was accompanied by the higher (P < 0.05) activity of serum total antioxidant capacity (T-AOC) (750 mg/kg), jejunal glutathione peroxidase (750 mg/kg), and T-AOC (500 and 1,000 mg/kg). Dietary CBP addition improved intestinal health, reflecting by the increased (P < 0.05) villus height to crypt depth ratio in the duodenum, the upregulated (P < 0.01) mRNA levels of claudin-1 (500 and 750 mg/kg) in the ileum, the downregulated (P < 0.01) mRNA expression of occludin (500 mg/kg) in the duodenum and claudin-1 (500 mg/kg) and occludin (500 and 750 mg/kg) in the jejunum, and the upregulated mRNA expression of (P < 0.01) mucin2 (MUC2) (1,000 mg/kg) in the duodenum. In addition, CBP upregulated (P < 0.01) IL-10 (1,000 mg/kg) in duodenum and ileum, and downregulated (P < 0.05) the mRNA expression of IL-6 (750 and 1,000 mg/kg), interferon-γ (1,000 mg/kg) in the jejunum and TNF-α (250 mg/kg) in the ileum. Furthermore, dietary CBP increased (P < 0.01) the abundance of total bacteria and Lactobacillus (500 and 750 mg/kg), and reduced (P < 0.05) the abundance of Escherichia coli (750 mg/kg) in the cecum. In conclusion, CBP supplementation enhances the antioxidant capacity, intestinal health, immune function, and ameliorates the gut microflora population, thus improving the growth performance of broilers. Dietary supplementation of 750 mg/kg CBP exhibits a better beneficial effect.
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