Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Mechanistic Understanding of Surface Migration Dynamics with DNA Walkers

Dynamic DNA walkers can move cargoes on a surface through various mechanisms including enzymatic reactions and strand displacement. While they have demonstrated high processivity and speed, their motion dynamics are not well understood. Here, we utilize an enzyme-powered DNA walker as a model system and adopt a random walk model to provide new insight on migration dynamics. Four distinct migration modes (ballistic, Lévy, self-avoiding, and diffusive motions) are identified. Each mode shows unique step time and velocity distributions which are related to mean squared displacement (MSD) scaling. Experimental results are in excellent agreement with the theoretical predictions. With a better understanding of the dynamics, we performed a mechanistic study, elucidating the effects of cargo types and sizes, walker sequence designs, and environmental conditions. Finally, this study provides a set of design principles for tuning the behaviors of DNA walkers. The DNA walkers from this work could serve as a versatile platform for mathematical studies and open new opportunities for bioengineering.</p

Amorphous/crystalline Zn60Zr40 alloys lattice structures with improved mechanical properties fabricated by mechanical alloying and selective laser melting

In the present study, mechanical alloying (MA) was employed for synthesising non-equilibrium Zn60Zr40 amorphous powders, and then consolidated into amorphous/crystalline Zn60Zr40 alloys using selective laser melting (SLM). The results showed that the MA process destabilised the atomic periodicity of Zn and Zr powders and induced crystalline-to-amorphous transformation due to atomic size mismatch and negative heat of mixing. Moreover, the amorphisation trend of as-milled powders was intensified with increasing milling time and attained almost fully amorphous structure after 30 h of milling. During SLM, the ultra-high cooling rate restricted the long-range atomic diffusion of the amorphous powders and enabled successful survival of amorphous phase, leading to amorphous/crystalline Zn60Zr40 alloys. The alloys exhibited a maximum compressive yield strength and microhardness of 160.9 ± 9.1 MPa and 3.73 ± 0.8 GPa, respectively. These findings demonstrated that the developed MA-SLM process might be a promising strategy for the preparation of amorphous/crystalline alloys with superior properties

PDA-BPs integrated mussel-inspired multifunctional hydrogel coating on PPENK implants for anti-tumor therapy, antibacterial infection and bone regeneration

Currently, many cancer patients with bone defects are still threatened by tumor recurrence, postoperative bacterial infection, and massive bone loss. Many methods have been studied to endow bone implants with biocompatibility, but it is difficult to find an implant material that can simultaneously solve the problems of anticancer, antibacterial and bone promotion. Here, a multifunctional gelatin methacrylate/dopamine methacrylate adhesive hydrogel coating containing 2D black phosphorus (BP) nanoparticle protected by polydopamine (pBP) is prepared by photocrosslinking to modify the surface of poly (aryl ether nitrile ketone) containing phthalazinone (PPENK) implant. The multifunctional hydrogel coating works in conjunction with pBP, which can deliver drug through photothermal mediation and kill bacteria through photodynamic therapy at the initial phase followed by promotion of osteointegration. In this design, photothermal effect of pBP control the release of doxorubicin hydrochloride loaded via electrostatic attraction. Meanwhile, pBP can generate reactive oxygen species (ROS) to eliminate bacterial infection under 808 nm laser. In the slow degradation process, pBP not only effectively consumes excess ROS and avoid apoptosis induced by ROS in normal cells, but also degrade into PO43− to promote osteogenesis. In summary, nanocomposite hydrogel coatings provide a promising strategy for treatment of cancer patients with bone defects

Application of Improved Random Forest Variables Importance Measure to Traditional Chinese Chronic Gastritis Diagnosis

Many machine learning approaches have been proposed to establish the chronic gastritis diagnostic models. But till now, most of the machine-learning classifiers do not give any insight as to which features play key roles with respect to the derived classifier as well as the individual class. Recently, the variables importance measure yielded by random forest (RF) has been proposed in many applications. However, in multi-label classifications RF attempts to yield a common feature ranking for all classes, which fail in identifying the distinct predictive structures for individual class, This paper developed an improved random forest variables importance measure to evaluate the importance of features according to each individual class in multi-classification problem, and then applied a wrapper method for feature selection to construct the key features sets referring to each subtype of the chronic gastritis. Experiment results show that, compared with the previous studies, the selected features are more close to expert knowledge and contribute to better understanding of the underlying process that characterize the chronic gastritis

Involvement of Porcine &beta;-Defensin 129 in Sperm Capacitation and Rescue of Poor Sperm in Genital Tract Infection

In mammals, &beta;-defensins have been reported to play pivotal roles in sperm protection and fertilization. However, the function and mechanism of porcine &beta;-defensin 129 (pBD129) in the sperm remain unclear. Here, we demonstrate that pBD129 is a glycosylated protein and broadly exists in accessory sex glands and coats the sperm surface. We inhibited the pBD129 protein on the sperm surface with an anti-pBD129 antibody and found that sperm motility was not significantly affected; however, sperm acrosome integrity and tyrosine phosphorylation levels increased significantly with time (p &lt; 0.05) during capacitation. These changes were accompanied by an increase in sperm Ca2+ influx, resulting in a significantly reduced in vitro fertilization cleavage rate (p &lt; 0.05). Further investigation revealed that treatment with recombinant pBD129 markedly restored the sperm motility in semen contaminated with Escherichia coli. The results suggest that pBD129 is not only associated with poor sperm motility after genital tract infection but can also protect the spermatozoa from premature capacitation, which may be beneficial for semen preservation

Improved Mechanical Properties of Copoly(Phthalazinone Ether Sulphone)s Composites Reinforced by Multiscale Carbon Fibre/Graphene Oxide Reinforcements: A Step Closer to Industrial Production

The properties of carbon fibre (CF) reinforced composites rely heavily on the fibre-matrix interface. To enhance the interfacial properties of CF/copoly(phthalazinone ether sulfone)s (PPBES) composites, a series of multiscale hybrid carbon fibre/graphene oxide (CF/GO) reinforcements were fabricated by a multistep deposition strategy. The optimal GO loading in hybrid fibres was investigated. Benefiting from the dilute GO aqueous solution and repeated deposition procedures, CF/GO (0.5%) shows a homogeneous distribution of GO on the hybrid fibre surface, which is confirmed by scanning electron microscopy, atomic force microscope, and X-ray photoelectron spectroscopy, thereby ensuring that its PPBES composite possesses the highest interlaminar shear strength (91.5 MPa) and flexural strength (1886 MPa) with 16.0% and 24.1% enhancements, respectively, compared to its non-reinforced counterpart. Moreover, the incorporation of GO into the interface is beneficial for the hydrothermal ageing resistance and thermo-mechanical properties of the hierarchical composite. This means that a mass production strategy for enhancing mechanical properties of CF/PPBES by regulating the fiber-matrix interface was developed

Effects of Structural Flexibility on the Kinetics of DNA Y‑Junction Assembly and Gelation

The kinetics of DNA assembly is determined not only by temperature but also by the flexibility of the DNA tiles. In this work, the flexibility effect was studied with a model system of Y-junctions, which contain single-stranded thymine (T) loops in the center. It was demonstrated that the incorporation of a loop with only one thymine prominently improved the assembly rate and tuned the final structure of the assembly, whereas the incorporation of a loop of two thymines exhibited the opposite effect. These observations could be explained by the conformation adjustment rate and the intermotif binding strength. Increasing DNA concentration hindered the conformational adjustment rate of DNA strands, leading to the formation of hydrogels in which the network was connected by ribbons. Therefore, the gel can be treated as a metastable state during the phase transition

Design Principles of DNA Enzyme-Based Walkers: Translocation Kinetics and Photoregulation

Dynamic DNA enzyme-based walkers complete their stepwise movements along the prescribed track through a series of reactions, including hybridization, enzymatic cleavage, and strand displacement; however, their overall translocation kinetics is not well understood. Here, we perform mechanistic studies to elucidate several key parameters that govern the kinetics and processivity of DNA enzyme-based walkers. These parameters include DNA enzyme core type and structure, upper and lower recognition arm lengths, and divalent metal cation species and concentration. A theoretical model is developed within the framework of single-molecule kinetics to describe overall translocation kinetics as well as each reaction step. A better understanding of kinetics and design parameters enables us to demonstrate a walker movement near 5 μm at an average speed of ∼1 nm s^–1. We also show that the translocation kinetics of DNA walkers can be effectively controlled by external light stimuli using photoisomerizable azobenzene moieties. A 2-fold increase in the cleavage reaction is observed when the hairpin stems of enzyme catalytic cores are open under UV irradiation. This study provides general design guidelines to construct highly processive, autonomous DNA walker systems and to regulate their translocation kinetics, which would facilitate the development of functional DNA walkers