Superior Safety Research Articles

Feasibility, safety, and efficacy of endovascular treatment of anterior cranial fossa dural arteriovenous fistulas: a systematic review and meta-analysis with a subanalysis for Onyx.

Dural Arteriovenous Fistulas (dAVFs) of the anterior cranial fossa (ACF) are uncommon but carry a high risk of hemorrhage and pose substantial treatment challenges. Recent advancements in endovascular treatment (EVT), including the introduction of novel liquid embolic agents, have markedly bolstered EVT's role in managing ACF-dAVFs, with notable series published in the last five years. We aimed to assess the feasibility, safety, and efficacy of EVT for ACF-dAVFs. We searched Medline, Scopus, Web of Science, and Cochrane Library databases following PRISMA guidelines. Eligible studies included those with ≥ 5 patients undergoing embolization of ACF-dAVFs, detailing both angiographic and clinical outcomes. We used single proportion analysis with 95% confidence intervals under a random-effects model, I2 to assess heterogeneity, and Baujat and sensitivity analysis to address high heterogeneity. Publication bias was assessed by funnel-plot analysis and Egger's test. Outcomes included complete occlusion following embolization, unsuccessful endovascular embolization attempts, incomplete occlusion following embolization, symptom resolution or clinical improvement following embolization, recurrence; procedure-related complications, morbidity, and mortality. Additionally, a subanalysis for studies exclusively utilizing Onyx™ embolic system was done. Eighteen studies comprising 231 ACF-dAVF were included. Unsuccessful endovascular embolization attempts rate was 2%. Complete occlusion rate was 85%, with 4% of complications. Incomplete occlusion rate was 10%. Successfully embolized patients experienced either symptom resolution or clinical improvement in 94% of cases. Morbidity and mortality rates were 1% and 0%, respectively. Onyx subanalyses showed an overall rate of 0% for unsuccessful attempts, 95% for complete occlusion, and 5% for incomplete occlusion. Symptom resolution or clinical improvement was 98% and recurrence rate was 0%. EVT for ACF-dAVF is highly feasible, effective, and safe, with a low rate of complications, morbidity, and mortality. The subanalyses focusing on Onyx embolizations revealed superior efficacy and safety outcomes compared to the findings of the primary analyses involving all included studies.

Three-dimensional electrochemical-magnetic-thermal coupling model for lithium-ion batteries and its application in battery health monitoring and fault diagnosis

Storage batteries with elevated energy density, superior safety and economic costs continues to escalate. Batteries can pose safety hazards due to internal short circuits, open circuits and other malfunctions during usage, hence real-time surveillance and error diagnosis of the battery’s operational state is imperative. In this paper, a three-dimensional model of electrochemical-magnetic field-thermal coupling is formulated with lithium-ion pouch cells as the research focus, and the spatial distribution pattern of the physical field such as magnetic field and temperature when the battery is operational is acquired. Furthermore, this manuscript also investigates the diagnostic methodology for defective batteries with internal short circuits and fissures, that is, the operational state of the battery is evaluated and diagnosed by the distribution of the magnetic field surrounding the battery. To substantiate the method’s practical viability, the present study extends its examination to the 18650-battery pack. We obtained the magnetic field images of the normal operation of the battery pack and the failure state of some batteries and analyzed the relationship between the magnetic field distribution characteristics and the performance of the battery pack, providing a new method for the health monitoring and fault diagnosis of the battery pack. This non-contact method incurs no damage to the battery, concurrently exhibiting elevated sensitivity and extremely rapid response time. Meanwhile, it provides an effective means for non-destructive research on the batteries and can be applied to areas such as battery safety screening and non-destructive testing. This research not only helps to facilitate our understanding of the battery’s operating mechanism, but also provides robust support for safe operation and optimal battery design.

Metabolites of traditional Chinese medicine targeting PI3K/AKT signaling pathway for hypoglycemic effect in type 2 diabetes

Type 2 diabetes mellitus is a chronic metabolic disease characterized by insulin resistance, with high morbidity and mortality worldwide. Due to the tightly intertwined connection between the insulin resistance pathway and the PI3K/AKT signaling pathway, regulating the PI3K/AKT pathway and its associated targets is essential for hypoglycemia and the prevention of type 2 diabetes mellitus. In recent years, metabolites isolated from traditional Chinese medicine has received more attention and acceptance for its superior bioactivity, high safety, and fewer side effects. Meanwhile, numerous in vivo and in vitro studies have revealed that the metabolites present in traditional Chinese medicine possess better bioactivities in regulating the balance of glucose metabolism, ameliorating insulin resistance, and preventing type 2 diabetes mellitus via the PI3K/AKT signaling pathway. In this article, we reviewed the literature related to the metabolites of traditional Chinese medicine improving IR and possessing therapeutic potential for type 2 diabetes mellitus by targeting the PI3K/AKT signaling pathway, focusing on the hypoglycemic mechanism of the metabolites of traditional Chinese medicine in type 2 diabetes mellitus and elaborating on the significant role of the PI3K/AKT signaling pathway in type 2 diabetes mellitus. In order to provide reference for clinical prevention and treatment of type 2 diabetes mellitus.

Role of a National Health Service Electronic Prescriptions Database in the Detection of Prescribing and Dispensing Issues and Adherence Evaluation of Direct Oral Anticoagulants

Background: Anticoagulation therapy plays a crucial role in the management of atrial fibrillation (AF) by significantly reducing the risk of stroke. Direct oral anticoagulants (DOAC) became preferred over warfarin due to their superior safety and efficacy profile. Assessing adherence to anticoagulation therapy is necessary in clinical practice for optimising patient outcomes and treatment efficacy, thus emphasising its significance. Methods: A retrospective study utilised the Latvian National Health Service reimbursement prescriptions database, covering prescriptions for AF and flutter from January 2012 to December 2022. The proportion of days covered method was selected for adherence assessment, categorising it into three groups: (1) below 80%, (2) between 80% and 90%, and (3) above 90%. Results: A total of 1,646,648 prescriptions were analysed. Dabigatran prescriptions started declining after 2020, coinciding with a decrease in warfarin prescriptions since 2018. The total adherence levels to DOAC therapy were 69.4%. Only 44.2% of users achieved an adherence level exceeding 80%. The rate of paper prescriptions decreased from 98.5% in 2017 to 1.3% in 2022. Additionally, the utilisation of international non-proprietary names reached 79.7% in 2022. Specifically, 16.7% of patients selected a single pharmacy, whereas 27.7% visited one or two pharmacies. Meanwhile, other patients obtained medicines from multiple pharmacies. Conclusions: The total adherence level to DOAC therapy is evaluated as low and there was no significant difference in age, gender, or “switcher” status among adherence groups. Physicians’ prescribing habits have changed over a decade.

Design of FK866-Based Degraders for Blocking the Nonenzymatic Functions of Nicotinamide Phosphoribosyltransferase.

Nicotinamide phosphoribosyltransferase (NAMPT) is an attractive therapeutic target for treating select cancers. There are two forms of NAMPT: intracellular NAMPT (iNAMPT, the rate-limiting enzyme in the mammalian NAD+ main synthetic pathway) and extracellular NAMPT (eNAMPT, a cytokine with protumorigenic function). Reported NAMPT inhibitors only inhibit iNAMPT and show potent activities in preclinical studies. Unfortunately, they failed to show efficacy due to futility and toxicity. We developed a series of FK866-based NAMPT-targeting PROTACs and identified LYP-8 as a potent and effective NAMPT degrader that simultaneously diminished iNAMPT and eNAMPT. Importantly, LYP-8 demonstrated superior efficacy and safety in mice when compared to the clinical candidate, FK866. This study highlights the importance and feasibility of applying PROTACs as a superior strategy for interfering with both the enzymatic function of NAMPT (iNAMPT) and nonenzymatic function of NAMPT (eNAMPT), which is difficult to achieve with conventional NAMPT inhibitors.

Pressure Tuning and Sn Particle Size Optimization for Enhanced Performance in PbSnF4-Based All-Solid-State Fluoride Ion Batteries.

All-solid-state fluoride ion batteries (ASSFIBs) show remarkable potential as energy storage devices due to their low cost, superior safety, and high energy density. However, the poor ionic conductivity of F- conductor, large volume expansion, and the lack of a suitable anode inhibit their development. In this work, PbSnF4 solid electrolytes in different phases (β- and γ-PbSnF4) are successfully synthesized and characterized. The ASSFIBs composed of β-PbSnF4 electrolytes, a BiF3 cathode, and micrometer/nanometer size (µ-/n-) Sn anodes, exhibit substantial capacities. Compared to the μ-Sn anode, the n-Sn anode with nanostructure exhibits superior battery performance in the BiF3/β-PbSnF4/Sn battery. The optimized battery delivers a high initial discharge capacity of 181.3 mAh g-1 at 8mA g-1 and can be reversibly cycled at 40mA g-1 with a high discharge capacity of over 100.0 mAh g-1 after 120 cycles at room temperature. Additionally, it displays high discharge capacities over 90.0 mAh g-1 with excellent cyclability over 100 cycles under -20°C. Detailed characterization has confirmed that reducing Sn particle size and boosting external pressure are crucial for achieving good defluorination/fluorination behaviors in the Sn anode. These findings pave the way to designing ASSFIBs with high capacities and superior cyclability under different operating temperatures.

Self-assembly Fe-Co MOF@BN and epoxy resin nano composites with highly enhanced flame retardancy and smoke suppression properties

A shuttle-shaped Fe-Co bimetallic metal organic frameworks (MOFs) on sheet-like hexagonal boron nitride (h-BN) was fabricated via an organic-inorganic hybrid strategy, forming a novel Fe-Co MOF@BN flame retardant, and the hybrids together with ammonium polyphosphate (APP) were incorporated into epoxy resins to explore their flame retardancy and smoke suppression effects. When combining 0.5 % Fe-Co MOF@BN with 9.5 % APP, the peak heat release rate, peak smoke release rate, CO production rate, and peak CO2 production rate of the EP composite (EP/APP/Fe-Co MOF@BN) were reduced by 73.7 %, 71.4 %, 70 %, and 80 % respectively, compared to epoxy. The limiting oxygen index increases to 30.2 %, indicating the EP/APP/Fe-Co MOF@BN composites have superior fire safety performance. The excellent fire performance of EP/APP/Fe-Co MOF@BN composites benefiting from the barrier effect of Fe-Co MOF@BN lamellar structure, the catalytic carbonization of Fe and Co, the gas phase dilution of APP and the enhancement of the cross-linking degree of the char layer. Meanwhile, Fe-Co MOF@BN improves the dispersion of APP in the EP composites, which broadens the application range of MOF and h-BN. Herein, the EP/APP/Fe-CoMOF@BN composites with high flame retardancy, low smoke production rate, and excellent mechanical properties provide a feasible solution for the use of EP under high temperatures.

Flexible Ultrasonic‐Induced Wireless Energy Conversion Technology in Implantable Biomedicine

AbstractNumerous associated challenges arise with the advancement and continuous improvement of implantable medical devices, such as the frequent requirement for battery replacement. The flexible ultrasonic‐induced wireless energy conversion (UWEC) technology has garnered significant interest due to its superior energy transmission efficiency, safety, and biocompatibility compared to traditional electromagnetic wireless energy conversion technology. This paper provides a comprehensive review of the recent advancements in two types of flexible UWEC technologies, triboelectric nanogenerators, and piezoelectret nanogenerators, with a focus on their applications in implantable medical treatments. First, the energy conversion principles and general materials of flexible UWEC are presented. Then, the research and application of flexible UWEC devices are introduced in detail based on their medical functions. At the end of this review, perspectives and opportunities are discussed.

The immune response to systemically administered endotoxin in the murine intestinal microcirculation under pentobarbital versus isoflurane anesthesia.

Pentobarbital and isoflurane are commonly used veterinary anesthetics. Due to the dangers of overdose by repeat-bolus regimen of pentobarbital, isoflurane has been recommended. However, literature suggests isoflurane-induced inhibition of cytokine and adhesion molecule release, impacting leukocyte adhesion. This study aims to characterize the impacts of pentobarbital versus isoflurane on leukocyte interactions within the intestinal microcirculation with and without endotoxin challenge. Female BALB/c mice were subjected to pentobarbital or isoflurane (N = 20) and challenged with endotoxin or saline by intraperitoneal injection. The mice were kept under anesthesia for 2 hours. Fluorochromes, rhodamine-6 G and fluorescein isothiocyanate, were injected intravenously. To visualize leukocyte adhesion within the intestinal microcirculation, laparotomy and intravital microscopy was performed. Leukocyte rolling and adhesion was quantified offline in a blinded fashion. Within collecting venules, leukocyte rolling and adhesion showed no significant differences between pentobarbital and isoflurane anesthesia under basal conditions. Endotoxin challenge caused a similar response in both anesthetic groups. Within postcapillary venules, no statistical differences between the two anesthetics were found for adhering leukocytes under basal conditions or following endotoxin challenge either. However, leukocyte rolling after LPS-challenge was significantly decreased in postcapillary venules during isoflurane anesthesia compared to pentobarbital anesthesia. Isoflurane anesthesia showed only minor differences in the immune response to endotoxin within the intestinal microcirculation compared to pentobarbital anesthesia. Due to the superior safety profile of volatile anesthetics, immunological studies may choose isoflurane over pentobarbital as the veterinary anesthetic of choice.

Emerging Innate Immune Cells in Cancer Immunotherapy: Promises and Challenges.

Immune checkpoint inhibitor (ICI)-based therapy has made an unprecedented impact on survival benefit for a subset of cancer patients; however, only a subset of cancer patients is benefiting from ICI therapy if all cancer types are considered. With the advanced understanding of interactions of immune effector cell types and tumors, cell-based therapies are emerging as alternatives to patients who could not benefit from ICI therapy. Pioneering work of chimeric antigen receptor T (CAR-T) therapy for hematological malignancies has brought encouragement to a broad range of development for cellular-based cancer immunotherapy, both innate immune cell-based therapies and T-cell-based therapies. Innate immune cells are important cell types due to their rapid response, versatile function, superior safety profiles being demonstrated in early clinical development, and being able to utilize multiple allogeneic cell sources. Efforts on engineering innate immune cells and exploring their therapeutic potential are rapidly emerging. Some of the therapies, such as CD19 CAR natural killer (CAR-NK) cell-based therapy, have demonstrated comparable early efficacy with CD19 CAR-T cells. These studies underscore the significance of developing innate immune cells for cancer therapy. In this review, we focus on the current development of emerging NK cells, γδ T cells, and macrophages. We also present our views on potential challenges and perspectives to overcome these challenges.

Conformation inversion of succinonitrile towards long-life solid-state lithium metal batteries

Solid-state lithium metal batteries are considered as the next-generation energy storage devices, but their application is significantly hindered by poor interfacial compatibility between Li anodes and solid-state electrolytes, especially for succinonitrile (SN) based electrolyte. Herein, this issue is addressed by a conformation inversion strategy via introducing a PE separator grafted with poly-(lithium 2-acrylamido-2-methylpropanesulfonic acid) (PAMPSLi) brushes into a SN-based electrolyte. The PAMPSLi brushes inverse the conformation of SN molecules through the multiple interactions between −SO3Li and cyanide groups, alleviating the corrosion reactions of SN on Li anodes. Significantly, the PAMPSLi brushes regulate Li+ transport pathway with the inversed SN molecules at the anode/electrolyte interface to achieve uniform Li deposition. Notably, the PAMPSLi brushes contribute to a solid electrolyte interphase (SEI) film rich in LiF and Li3N. Consequently, the solid-state Li||LiFePO4 batteries with the resulting electrolyte exhibit a specific discharge capacity of 115.0 mAh/g and a considerably long cycle life of 1500 cycles at 3 C. A pouch cell with a high-loading LiFePO4 cathode (18 mg cm−2) also exhibits a high areal capacity and superior safety. This study provides a novel strategy for achieving a stable electrolyte/anode interface in SN-based electrolytes, which facilitates the practical application of solid-state batteries with long life and high energy density.

A deep learning-aided multi-objective optimization of a downstream process for production of monoclonal antibody products

Monoclonal antibodies (mAbs) have emerged as the dominant class of therapeutic moieties due to their superior therapeutic potential and safety profile. Downstream processing plays a pivotal role in ensuring the purity, yield, and quality of these therapeutic products. The biopharmaceutical industry generates a significant amount of data, making it an attractive target for creating machine learning (ML) and deep learning (DL) applications. This paper reports a DL-based 2D-convolutional neural network (2D-CNN) to predict: (i) Protein A mAb elute concentration, (ii) Cation exchange (CEX) mAb elute concentration, (iii)% Acidic variant, (iv) Aggregate (%), and (v)% Basic variant from process data that is routinely collected during biopharma manufacturing, including Protein A elution UV, CEX elution UV, CEX elution conductivity, and post viral inactivation pH profiles. Further, interpretation of predicted outputs using the SHAPLEY technique and optimization through multi-objective Bayesian optimization methods have been attempted so as to match the biosimilar to the reference molecule with respect to the critical quality attributes. It is observed that the proposed model outperforms other published approaches in prediction. The optimum results were experimentally validated by performing three consecutive runs, and a mean percentage deviation of less than 3% was reported. The proposed approach demonstrates the feasibility of real-time prediction and optimization in biopharmaceutical product manufacturing using CNN-aided modeling and multi-objective weighted sum optimization.

Three-Dimensional Metal-Organic Framework@Cellulose Skeleton-Reinforced Composite Polymer Electrolyte for All-Solid-State Lithium Metal Battery.

High-safety and high-energy-density solid-state lithium metal batteries (SSLMBs) attract tremendous interest in both academia and industry. Especially, composite polymer electrolytes (CPEs) can overcome the limitations of single-component solid-state electrolytes. In this work, a strategy of combining a rigid functional skeleton with a soft polymer electrolyte to prepare reinforced CPEs was adopted. The in situ grown zeolitic imidazolate frameworks (ZIFs) with three-dimensional cellulose fiber skeleton (ZIF-67@CF) and succinonitrile (SN) plasticizer into poly(ethylene oxide) (PEO) together form ZIF-67@CF/PEO-SN CPEs. The addition of ZIF-67@CF and SN to PEO synergistically enhanced the physical and electrochemical properties of CPEs. Furthermore, the conduction mechanism of lithium-ion (Li+) in CPEs was studied using density functional theory. It is impressive that the ZIF-67@CF/PEO-SN CPEs at 30 °C exhibit a high ionic conductivity of 1.17 × 10-4 S cm-1, a competitive Li+ transference number of 0.40, a wide electrochemical window of 5.0 V, a notable tensile strength of 18.7 MPa, and superior lithium plating/stripping stability (>550 h at 0.1 mA cm2). Such favorable features endowed LiFePO4/(ZIF-67@CF/PEO-SN)/Li cell at 30 °C with a high discharging capacity (152.5 mA h g-1 at 0.2 C), a long cycling lifespan (>150 cycles with 99% capacity retention), and superior operating safety. This work provides insights and promotes the application of functionalized CPEs for SSLMBs.

Nanosuspension-Loaded Dissolving Microneedle Patches for Enhanced Transdermal Delivery of a Highly Lipophilic Cannabidiol.

Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum's barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility. Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance. The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action's duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1β compared with the methotrexate subcutaneous injection method. NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration.

Enhancing Zinc Electrode Stability Through Pre-Desolvation and Accelerated Charge Transfer via a Polyimide Interface for Zinc-Ion Batteries.

Aqueous zinc-based energy storage devices possess superior safety, cost-effectiveness, and high energy density; however, dendritic growth and side reactions on the zinc electrode curtail their widespread applications. In this study, these issues are mitigated by introducing a polyimide (PI) nanofabric interfacial layer onto the zinc substrate. Simulations reveal that the PI nanofabric promotes a pre-desolvation process, effectively desolvating hydrated zinc ions from Zn(H2O)6 2+ to Zn(H2O)4 2+ before approaching the zinc surface. The exposed zinc ion in Zn(H2O)4 2+ provides an accelerated charge transfer process and reduces the activation energy for zinc deposition from 40 to 21kJ mol-1. The PI nanofabric also acts as a protective barrier, reducing side reactions at the electrode. As a result, the PI-Zn symmetric cell exhibits remarkable cycling stability over 1200h, maintaining a dendrite-free morphology and minimal byproduct formation. Moreover, the cell exhibits high stability and low voltage hysteresis even under high current densities (20mA cm-2, 10 mAh cm-2) thanks to the 3D porous structure of PI nanofabric. When integrated into full cells, the PI-Zn||AC hybrid zinc-ion capacitor and PI-Zn||MnVOH@SWCNT zinc-ion battery achieve impressive lifespans of 15000 and 600 cycles with outstanding capacitance retention. This approach paves a novel avenue for high-performance zinc metal electrodes.

Transforming construction: The growing role of mechatronics in building our infrastructure

Mechatronics, the synergistic integration of mechanical engineering, electrical engineering, control engineering, and computer science, is progressively transforming the construction industry. This paper explores how mechatronic technologies are being applied across the construction lifecycle to enhance productivity, quality, safety, sustainability, and cost-effectiveness. Core mechatronic technologies changing construction include automated material handling systems, advanced construction robotics, sensor networks for monitoring, laser scanning for accurate modeling and control, and building information modeling (BIM) software. Mechatronics offers multifaceted benefits spanning from enhanced labor productivity and construction velocity to superior quality control, safety, and process optimization. However, realizing the immense potential of mechatronics in construction requires overcoming key challenges including high upfront costs, lack of technical skills, organizational resistance, integration difficulties, and reliability concerns. With thoughtful leadership and implementation, mechatronics promises to revolutionize construction, shifting it towards more automated, streamlined, and optimized techniques. This paper delineates the tremendous potential of mechatronics in construction regarding benefits, technologies, and challenges. The outlook is promising for intelligent mechatronic systems to profoundly enhance productivity, quality, and safety as construction progresses towards greater automation and optimization.

Dendrite-free Zn anodes enabled by interface engineering for non-alkaline Zn-air and Zn-ion batteries

Aqueous zinc-metal batteries hold immense promise for large-scale energy storage applications due to their cost-effectiveness and superior safety features. However, uncontrolled dendrite growth, corrosion and side reactions in aqueous environments destabilize the electrode/electrolyte, leading to Zn plating/striping irreversibility. Herein, a low-cost, non-toxic functional electrolyte additive, tetraethyl ammonium bromide (TEAB), addresses this challenge. The preferential adsorption of TEAB on the surface of the Zn anode endows the Zn/electrolyte interface with an optimized electric field distribution and abundant active sites for the uniform and dendrite-free Zn2+ deposition. Moreover, TEAB disrupts the H-bond network between the electrolytes, effectively suppressing water-induced side reactions and corrosion. Consequently, a Zn||Zn symmetric battery achieves a long cycle life of 4,950 h at 1 mA cm-2, and the average coulombic efficiency of the Zn||Cu battery reaches as high as 99.5%. Additionally, even after 2,000 cycles at 3 A g-1, the capacity retention of the Zn||MnO2 battery remains at 91.22%. The non-alkaline full Zn||air batteries deliver remarkable cycling stability up to 270 h.

Experimental Study on Compression Failure of Type II Ballastless Track Slab Based on Optical Fiber Sensing

Ballastless track structures are widely employed in high-speed rail networks because of their superior safety and durability. Among the various types of ballastless track, the Type II slab is currently one of the most extensively used and mature technologies in practice. Over the course of its service life, the damage within the ballastless track structure gradually accumulates in response to increased external loads. Therefore, it is crucial to continuously monitor the health condition of the track structure. In this study, a quasi-distributed fiber optic sensing system is adopted to monitor the deformation capacity and force performance of a Type II ballastless track slab under vertical load. The investigation aims to analyze the damage mechanism of the track structure under vertical pressure by assessing the deformation differences among its different components. The findings reveal that the incorporation of vertical reinforcement can enhance the pressure bearing capacity of the cement asphalt mortar layer to a certain extent, subsequently affecting the stress dilation. The stress performance of the ballastless track slab can be effectively monitored using the quasi-distributed fiber optic sensing technology under pressure. The outcomes of this research offer valuable insights for controlling displacement and analyzing damage in ballastless railway systems subjected to compression.

Discovery of Urea Derivatives of Celastrol as Selective Peroxiredoxin 1 Inhibitors against Colorectal Cancer Cells.

Peroxiredoxin (PRDX1) is a tumor-overexpressed antioxidant enzyme for eliminating excessive reactive oxygen species (ROS) to protect tumor cells from oxidative damage. Herein, a series of celastrol urea derivatives were developed based on its cocrystal structure with PRDX1, with the aim of pursuing a PRDX1-specific inhibitor. Among them, derivative 15 displayed potent anti-PRDX1 activity (IC50 = 0.35 μM) and antiproliferative potency against colon cancer cells. It covalently bound to Cys-173 of PRDX1 (KD = 0.37 μM), which was secured by the cocrystal structure of PRDX1 with an analogue of 15 while exhibiting weak inhibitory effects on PRDX2-PRDX6 (IC50 > 50 μM), indicating excellent PRDX1 selectivity. Treatment with 15 dose-dependently decreased the mitochondria membrane potential of SW620 cells, probably due to ROS induced by PRDX1 inhibition, leading to cell apoptosis. In colorectal cancer cell xenograft model, it displayed potent antitumor efficacy with superior safety to celastrol. Collectively, 15 represents a promising PRDX1 selective inhibitor for the development of anticolorectal cancer agents.

Efficacy and Safety of Endoscopic Third Ventriculostomy Versus Ventriculoperitoneal Shunting for the Treatment of Hydrocephalus: A Meta-Analysis

<i>Introduction</i>: Hydrocephalus, characterized by abnormal cerebrospinal fluid (CSF) accumulation, presents significant challenges requiring timely intervention to prevent neurological complications. Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting (VPS) are primary surgical options, yet their relative efficacy and safety remain debated. This meta-analysis aims to compare ETV and VPS for hydrocephalus treatment, providing evidence-based insights to guide clinical decision-making. <i>Objectives</i>: To compare the efficacy of ETV and VPS in achieving symptom relief and radiological resolution of hydrocephalus. To evaluate the safety profiles of ETV and VPS by assessing perioperative and postoperative complication rates. To examine long-term outcomes following ETV or VPS placement. To conduct subgroup analyses based on patient characteristics influencing treatment effectiveness and safety. <i>Methods</i>: A comprehensive literature search was conducted in PubMed and Scopus databases to identify relevant studies comparing ETV and VPS for hydrocephalus treatment. Inclusion criteria encompassed comparative studies reporting efficacy and safety outcomes in pediatric and adult populations. Data extraction and quality assessment were performed using standardized protocols. Meta-analysis was conducted using appropriate statistical methods, with sensitivity and subgroup analyses conducted to assess robustness and variability. <i>Results</i>: Symptom improvement was comparable between ETV and VPS, with lower major complications associated with ETV. Mortality and postoperative complications favored ETV, although VPS exhibited lower CSF leakage risk. Overall success rates were similar, but ETV demonstrated superior safety profiles. Subgroup analyses revealed variations based on patient characteristics. <i>Conclusion</i>: ETV and VPS are effective in achieving symptomatic relief and radiological resolution of hydrocephalus, with ETV demonstrating superior safety profiles. Shared decision-making considering patient factors is crucial in selecting the most appropriate treatment approach. Further research is warranted to refine treatment algorithms and optimize outcomes for hydrocephalus patients.