Key roles of autophagosome/endosome maturation mediated by Syntaxin17 in methamphetamine-induced neuronal damage in mice.

BACKGROUND: Autophagic defects are involved in Methamphetamine (Meth)-induced neurotoxicity. Syntaxin 17 (Stx17), a member of the SNARE protein family, participating in several stages of autophagy, including autophagosome-late endosome/lysosome fusion. However, the role of Stx17 and potential mechanisms in autophagic defects induced by Meth remain poorly understood. METHODS: To address the mechanism of Meth-induced cognitive impairment, the adenovirus (AV) and adeno-associated virus (AAV) were injected into the hippocampus for stereotaxis to overexpress Stx17 in vivo to examine the cognitive ability via morris water maze and novel object recognition. In molecular level, the synaptic injury and autophagic defects were evaluated. To address the Meth induced neuronal damage, the epidermal growth factor receptor (EGFR) degradation assay was performed to evaluate the degradability of the "cargos" mediated by Meth, and mechanistically, the maturation of the vesicles, including autophagosomes and endosomes, were validated by the Co-IP and the GTP-agarose affinity isolation assays. RESULTS: Overexpression of Stx17 in the hippocampus markedly rescued the Meth-induced cognitive impairment and synaptic loss. For endosomes, Meth exposure upregulated Rab5 expression and its guanine-nucleotide exchange factor (GEF) (immature endosome), with a commensurate decreased active form of Rab7 (Rab7-GTP) and impeded the binding of Rab7 to CCZ1 (mature endosome); for autophagosomes, Meth treatment elicited a dramatic reduction in the overlap between Stx17 and autophagosomes but increased the colocalization of ATG5 and autophagosomes (immature autophagosomes). After Stx17 overexpression, the Rab7-GTP levels in purified late endosomes were substantially increased in parallel with the elevated mature autophagosomes, facilitating cargo (Aß42, p-tau, and EGFR) degradation in the vesicles, which finally ameliorated Meth-induced synaptic loss and memory deficits in mice. CONCLUSION: Stx17 decrease mediated by Meth contributes to vesicle fusion defects which may ascribe to the immature autophagosomes and endosomes, leading to autophagic dysfunction and finalizes neuronal damage and cognitive impairments. Therefore, targeting Stx17 may be a novel therapeutic strategy for Meth-induced neuronal injury.

Management of Isolated Abdominal Aortic Dissection: Indications and Strategies for Treatment.

BACKGROUND: The aim of this paper was to report our experience in the management of isolated abdominal aortic dissection with endovascular aortic repair and conservative treatment. METHODS: A cohort of 22 consecutive patients with isolated abdominal aortic dissection was treated between January 2016 and December 2021. We reviewed the demographics, clinical features, therapeutic modalities and follow-up results. Retrospective data analysis from patient charts was performed. RESULTS: Twenty-two patients were enrolled in this study from 2 centers. The mean age was 66.2 ± 13.3 years. Hypertension was the primary risk factor. Seventeen (72.7%) patients were asymptomatic, and 18 patients were subrenal artery type (type II). A total of 12 patients had successful endovascular repair (EVAR), and 10 patients underwent conservative treatment. In the group receiving conservative treatment, no patients required EVAR during follow-up, and 4 patients died. However, none of them had aortic causes: 2 patients had cardiac causes, the other 2 had cancer, and the others remained symptom-free. The latest computed tomographic angiography images showed that abdominal aortic dissection still existed, and the extent of the false lumen did not increase significantly. CONCLUSIONS: Both conservative treatment and EVAR are effective treatment options. Appropriate treatment needs to be performed according to different patients' clinical manifestations and doctors' experience.

Adhesion Coefficient Identification of Wheeled Mobile Robot under Unstructured Pavement.

Because of its uneven and large slope, unstructured pavement presents a great challenge to obtaining the adhesion coefficient of pavement. An estimation method of the peak adhesion coefficient of unstructured pavement on the basis of the extended Kalman filter is proposed in this paper. The identification accuracy of road adhesion coefficients under unstructured pavement is improved by introducing the equivalent suspension model to optimize the calculation of vertical wheel load and modifying vehicle acceleration combined with vehicle posture data. Finally, the multi-condition simulation experiments with Carsim are conducted, the estimation accuracy of the adhesion coefficient is at least improved by 3.6%, and then the precision and effectiveness of the designed algorithm in the article are verified.

Modeling the feasibility of Se-rich corn cultivation in Se-deficient agricultural fields using random forest algorithm.

Selenium constitutes an essential trace element for the human body. Moderate Se intake plays a pivotal role in preserving overall health. The absorption of Se by plants is primarily influenced by the available Se levels in soils, rather than by the soil total Se content, offering potential for exploring Se-rich crops in Se-deficient regions. In this study, we explore the factors influencing the Se bioaccumulation coefficient in corn based on a land quality geochemical survey at a 1:50,000 scale and establish predictive models for corn seed Se content using random forest and multiple linear regression approaches. The results indicate that the surface soil in the study area is deficient in Se (0.18-1.21 mg/kg), but 54% of the corn grain samples met the standards for Se-rich products (0.02-0.30 mg/kg). The factors influencing the Se biological enrichment coefficient in corn seeds are soil pH and CaO and MgO content, with impact levels of 0.54, 0.42, and 0.35, respectively. Compared to multiple linear regression models, the RF model provides more accurate and reliable predictions of corn Se content. The random forest model indicates that approximately 41% of the farmland within the study area is conducive to the cultivation of naturally Se-rich corn, which is a 26% increase in the planting area compared to recommendations based solely on soil Se content. In this research, we introduce an innovative methodological framework for organically cultivating naturally Se-rich corn within regions affected by Se deficiency.

Experimental investigation of nanosecond laser-induced shock waves in water using multiple excitation beams.

Revealing the expansion and interaction dynamics of multiple shock waves induced by a nanosecond laser is important for controlling laser surgery. However, the dynamic evolution of shock waves is a complex and ultrafast process, making it difficult to determine the specific laws. In this study, we conducted an experimental investigation into the formation, propagation, and interaction of underwater shock waves that are induced by nanosecond laser pulses. The effective energy carried by the shock wave is quantified by the Sedov-Taylor model fitting with experimental results. Numerical simulations with an analytic model using the distance between adjacent breakdown locations as input and effective energy as fit parameters provide insights into experimentally not accessible shock wave emission and parameters. A semi-empirical model is used to describe the pressure and temperature behind the shock wave taking into account the effective energy. The results of our analysis demonstrate that shock waves exhibit asymmetry in both their transverse and longitudinal velocity and pressure distributions. In addition, we compared the effect of the distance between adjacent excitation positions on the shock wave emission process. Furthermore, utilizing multi-point excitation offers a flexible approach to delve deeper into the physical mechanisms that cause optical tissue damage in nanosecond laser surgery, leading to a better comprehension of the subject.

Endovascular Repair for Abdominal Aortic Aneurysm in Mainland China: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study was to evaluate the safety, applicability, and outcomes of the endovascular aneurysm repair (EVAR) technique for patients in mainland China with abdominal aortic aneurysm (AAA) by performing a systematic review. METHODS: We conducted a systematic search using the PubMed, Embase, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases to identify Chinese studies on the management of AAAs using the EVAR technique published in English between January 2000 and December 2020. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The included studies investigated the clinical outcomes and postprocedural complications of using EVAR techniques. RESULTS: Sixteen studies reported a total of 3,024 AAA patients. The follow-up period ranged from 1 to 133 months. The mean follow-up time was 38.5 months, the mean age was 69.2 years, and the mean aneurysm diameter was 56.1 mm. The pooled technical success rate was 95% (95% confidence interval [CI]: 92-96%). The endoleak rate was 7% (95% CI: 6-8%). The rate of endoleak requiring reintervention was 3% (95% CI: 3-4%). The 30-day morbidity rate was 9% (95% CI: 6-14%). The 30-day mortality rate was 2% (95% CI: 1-3%). The follow-up mortality was 5% (95% CI: 3-8%). CONCLUSIONS: The results of the study showed that using the EVAR technique for treating patients in mainland China with AAAs produced encouraging mid-term outcomes. Long-term outcomes should be examined in future research.

Cigarette smoke triggers calcium overload in mouse hippocampal neurons via the ΔFOSB-CACNA2D1 axis to impair cognitive performance.

A growing body of evidence shows that cigarette smoking impairs cognitive performance. The 'Calcium Hypothesis' theory of neuronopathies reveals a critical role of aberrant calcium signaling in compromised cognitive functions. However, the underlying implications of abnormalities in calcium signaling in the neurotoxicity induced by cigarette smoke (CS) have not yet been identified. CACNA2D1, an important auxiliary subunit involved in the composition of voltage-gated calcium channels (VGCCs), was reported to affect the calcium signaling in neurons by facilitating VGCCs-mediated Ca2+ influx. ΔFOSB, an alternatively-spliced product of the Fosb gene, is an activity-dependent transcription factor induced robustly in the brain in response to environmental stimuli such as CS. Interestingly, our preliminary bioinformatics analysis revealed a significant co-expression between ΔFOSB and CACNA2D1 in brain tissues of patients with neurodegenerative diseases characterized by progressive cognitive decline. Therefore, we hypothesized that the activation of the ΔFOSB-CACNA2D1 axis in response to CS exposure might cause dysregulation of calcium homeostasis in hippocampal neurons via VGCCs-mediated Ca2+ influx, thereby contributing to cognitive deficits. To this end, the present study established a CS-induced mouse model of hippocampus-dependent cognitive impairment, in which the activation of the ΔFOSB-CACNA2D1 axis accompanied by severe calcium overload was observed in the mouse hippocampal tissues. More importantly, ΔFOSB knockdown-/overexpression-mediated inactivation/activation of the ΔFOSB-CACNA2D1 axis interdicted/mimicked CS-induced dysregulation of calcium homeostasis followed by severe cellular damage in HT22 mouse hippocampal neurons. Mechanistically speaking, a further ChIP-qPCR assay confirmed the physical interaction between transcription factor ΔFOSB and the Cacna2d1 gene promoter, suggesting a direct transcriptional regulation of the Cacna2d1 gene by ΔFOSB. Overall, our current work aims to deliver a unique insight into the neurotoxic mechanisms induced by CS to explore potential targets for intervention.

An Integrated Autonomous Dynamic Navigation Approach toward a Composite Air-Ground Risk Construction Scenario.

Unmanned transportation in construction scenarios presents a significant challenge due to the presence of complex dynamic on-ground obstacles and potential airborne falling objects. Consequently, the typical methodology for composite air-ground risk avoidance in construction scenarios holds enormous importance. In this paper, an integrated potential-field-based risk assessment approach is proposed to evaluate the threat severity of the environmental obstacles. Meanwhile, the self-adaptive dynamic window approach is suggested to manage the real-time motion planning solution for air-ground risks. By designing the multi-objective velocity sample window, we constrain the vehicle's speed planning instructions within reasonable limits. Combined with a hierarchical decision-making mechanism, this approach achieves effective obstacle avoidance with multiple drive modes. Simulation results demonstrate that, in comparison with the traditional dynamic window approach, the proposed method offers enhanced stability and efficiency in risk avoidance, underlining its notable safety and effectiveness.

Feasibility of Co-Targeting HER3 and EpCAM Using Seribantumab and DARPin-Toxin Fusion in a Pancreatic Cancer Xenograft Model.

Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets. Designed ankyrin repeat protein (DARPin) Ec1 fused with the low immunogenic bacterial toxin LoPE provides specific and potent cytotoxicity against EpCAM-expressing cancer cells. Here, we investigated whether the co-targeting of HER3 using the monoclonal antibody seribantumab (MM-121) and of EpCAM using Ec1-LoPE would improve the therapeutic efficacy in comparison to the individual agents. Radiolabeled 99mTc(CO)3-Ec1-LoPE showed specific binding with rapid internalization in EpCAM-expressing PC cells. MM-121 did not interfere with the binding of Ec1-LoPE to EpCAM. Evaluation of cytotoxicity indicated synergism between Ec1-LoPE and MM-121 in vitro. An experimental therapy study using Ec1-LoPE and MM-121 in mice bearing EpCAM- and HER3-expressing BxPC3 xenografts demonstrated the feasibility of the therapy. Further development of the co-targeting approach using HER3 and EpCAM could therefore be justified.

A miR-15a related polymorphism affects NSCLC prognosis via altering ERCC1 repair to platinum-based chemotherapy.

Platinum-based chemotherapy is regarded as a preferential curative-intent option for non-small cell lung cancer (NSCLC), while the acquired drug resistance has become a major obstacle that limits its clinical application. Since the repair efficiency of tumour cells to platinum-DNA adducts plays a crucial role in chemotherapy resistance, we aimed to explore whether several meaningful polymorphisms of DNA repair genes were associated with the benefits of platinum-based chemotherapy in NSCLC patients. Firstly, six single nucleotide polymorphisms (SNPs) located in the 3'untranslated region (3'UTR) of three DNA repair genes were detected in 246 NSCLC patients receiving platinum-based chemotherapy and analysed the correlation of these candidate SNPs with the overall survival. Cox proportional hazard model showed that NSCLC patients carrying ERCC1 rs3212986 AA genotype had a shorter overall survival compared to those with CC. Mechanistically, we performed tumour chemosensitivity assay to observe the convincing linkage of rs3212986 polymorphism with ERCC1 expression and cisplatin sensitivity. The subsequent in vitro experiments identified that rs3212986 polymorphism altered the post-transcriptional regulation of ERCC1 via affecting the binding of miR-15a, and further changed the sensitivity to platinum analogue. It reminded that patients carrying ERCC1 rs3212986 CC homozygote were expected to respond better to platinum-based chemotherapy due to a lower expression of ERCC1. Compared with previous studies, our current comprehensive study suggested that rs3212986, a 3'UTR polymorphism in ERCC1, might have clinical relevance in predicting the prognosis of NSCLC patients receiving platinum-based chemotherapy.

Dynamic moist air monitor in a micro area with extremely high figure-of-merit.

In the rapidly changing moisture air, conventional relative humidity (RH) sensors are often difficult to respond in time and accurately due to the limitation of flow rate and non-uniform airflow distribution. In this study, we numerically demonstrate that humidity changes on micro-zones can be monitored in real time using a Bloch surface wave (BSW) ubiquitous in one-dimensional photonic crystals (1DPC). This phenomenon can be observed by leakage radiation microscope (LRM). After theoretically deriving the angular resolution limit of LRM, we obtained the minimum BSW angular change on a practical scheme that can be observed in the momentum space to complete the detection, and realized the dynamic real-time monitoring of small-scale humidity change in experiment for the first time. This monitoring method has extremely high figure of merit (FOM) without hysteresis, which can be used in humidity sensing and refractive index sensing as well as the research on turbulence.

Laser ultrasonic loading and optical interference detection of closed cracks in K9 glass.

The traditional optical detection method has a limitation in detecting closed cracks in optical elements. In this Letter, a novel, to the best of our knowledge, method has been developed for the detection of closed cracks in transparent samples. Firstly, behaviors of closed cracks under ultrasonic waves loading are demonstrated through the finite-element method (FEM). Simulation results show that the crack can be opened by the laser ultrasonic shear wave (S-wave). Then, a Mach-Zehnder interferometer system is experimentally established to detect closed cracks under ultrasonic waves loading in the sample. It is demonstrated that closed cracks which cannot be detected by interferometry become visible in interferogram images under ultrasonic waves loading. The width of the opened crack can also be quantitatively estimated. Thus the method would be a promising approach to detect initially closed cracks in optical elements.

Environmental benefits of remanufacturing mechanical products: a harmonized meta-analysis of comparative life cycle assessment studies.

Remanufactured mechanical products with high-added value are generally claimed to gain environmental benefits. These claims were made based on different products and assessment methodologies. The variability of life cycle assessment (LCA) results precludes a meaningful comparison across products and studies. This paper aims to critically and systematically evaluate the lifecycle environmental performance of remanufactured products compared with their new counterparts and to identify the key factors, strengths, and limitations in the assessment procedure. Faced with the noteworthy variations, we closely examined and harmonized the unit function, allocation approach, system boundary, impact assessment method, and the underlying assumptions in screened 20 papers regarding 11 types of products. The environmental indicators adopted in this study were global warming potential (GWP) and primary energy consumption (PEC). In terms of these two indicators, the environmental burdens of remanufactured products relative to newly manufactured alternatives were harmonized to the comparison ratios. With these harmonized samples, descriptive statistics were calculated using Monte Carlo Simulation to disclose the variations of comparison results and identify the general tendency. Results of this meta-study showed that remanufacturing could contribute to over 50% reduction for GWP when usage and end-of-life stages were excluded from the life cycle. The GWP and PEC of remanufactured mechanical products account for 28.5% and 25.9% of the new counterparts, respectively, on average. This meta-analysis of comparative LCAs on new and remanufactured products would advance the understanding of the environmental advantages of remanufacturing.

Endovascular In Situ Fenestration Technique of Aortic Arch Pathology: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study was to evaluate the safety, applicability and outcomes of the endovascular in situ fenestration (ISF) technique for patients with aortic arch pathologies by performing a systematic review. METHODS: We conducted a systematic search using the PubMed, Embase, and Cochrane databases to identify English language articles between January 2004 and March 2019 on the management of aortic arch pathologies using an in situ fenestration technique. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The studies included all investigated the clinical outcomes and postprocedural complications of using ISF techniques. RESULTS: Seven studies reported on a total of 117 aortic arch pathologies patients. Including 52 dissection patients, 47 aneurysm patients, 18 intramural hematomas and penetrating ulcers patients. Needle fenestration and laser fenestration were performed in 62 and 45 patients respectively, and the rest 10 patients received radiofrequency fenestration. The follow-up period ranged from 1 to 55 months. The pooled technical success rates were 94% (95% confidence interval [CI]: 79-98%). The stroke rate was 6% (95% CI: 3-13%). The 30-day MAE was 11% (95% CI: 6-18%). CONCLUSION: The results of the study showed that using the in-situ fenestration technique for treating patients with aortic arch pathologies produced encouraging mid-outcomes. Long-term outcomes remain undefined.

Stable directional emission in active optical waveguides shielding external environmental influences.

The skillful confinement of light brought by the composite waveguide structure has shown great possibilities in the development of photonic devices. It has greatly expanded the application range of an on-chip system in dark-field imaging and confined the laser when containing an active medium. Here we experimentally proved a stable directional emission in an active waveguide composed of metal and photonic crystal, which is almost completely unaffected by the external environment and different from the common local light field that is seriously affected by the structure. When the refractive index of samples on the surface layer changes, it can ensure the constant emission intensity of the internal mode, while still retaining the external environmental sensitivity of the surface mode. It can also be used for imaging and sensing as a functional slide. This research of chip-based directional emission is very promising for various applications including quantitative detection of biological imaging, coupled emission intensity sensing, portable imaging equipment, and tunable micro lasers.

The usefulness of contrast-enhanced echocardiography in the diagnosis and management of intramural hematoma and aortic dissection: A case report.

Contrast-enhanced transthoracic echocardiography (cTTE) plays an important role in the diagnosis of intramural hematoma (IMH) and aortic dissection (AD), and is also necessary for the adequate management from the assessment of findings. We hereby present an interesting case in which cTTE provides additional value over contrast-enhanced computed tomography (CT) in the diagnosis and the morphological characterization of IMH and AD. A 58-year-old man presented to the emergency department with intermittent chest pain. After emergency consultation, an enhanced CT scan showed an acute aortic intramural hematoma involving aortic arch and descending aorta. Nevertheless, the entry tear and false lumen flow direction were identified by cTTE, which suggested an acute type B AD.

Inactivation of foodborne pathogens by the synergistic combinations of food processing technologies and food-grade compounds.

There is a need to develop food processing technologies with enhanced antimicrobial capacity against foodborne pathogens. While considering the challenges of adequate inactivation of pathogenic microorganisms in different food matrices, the emerging technologies are also expected to be sustainable and have a minimum impact on food quality and nutrients. Synergistic combinations of food processing technologies and food-grade compounds have a great potential to address these needs. During these combined treatments, food processes directly or indirectly interact with added chemicals, intensifying the overall antimicrobial effect. This review provides an overview of the combinations of different thermal or nonthermal processes with a variety of food-grade compounds that show synergistic antimicrobial effect against pathogenic microorganisms in foods and model systems. Further, we summarize the underlying mechanisms for representative combined treatments that are responsible for the enhanced microbial inactivation. Finally, regulatory issues and challenges for further development and technical transfer of these new approaches at the industrial level are also discussed.

Optical breakdown during femtosecond laser propagation in water cloud.

When a femtosecond laser pulse propagates through water clouds, optical breakdown can occur once the laser intensity exceeds a certain threshold. This photoionization process, along with the resultant laser-induced plasma, can strongly influence laser communications and laser-induced precipitation. However, the calculation model for the initial evolution of the laser field and its self-generated plasma remain insufficient. Here, we provide a theoretical transient coupling model to investigate the evolution of the laser-induced plasma in the water-cloud droplets, along with the nonlinear absorption occurring during optical breakdown. Agreement is achieved between the experimentally determined breakdown threshold and our calculated prediction. The calculation results indicate that the optical breakdown occurring in a water cloud has a considerable influence on the laser field. It is recommended that the laser intensity does not exceed the breakdown threshold for laser communications. We expect that our findings will also be helpful for weather control.

Environmental Benefits of Engine Remanufacture in China's Circular Economy Development.

China has recently implemented broad strategies aimed at achieving a circular economy by providing subsidies for the remanufacture industry and setting a target of 15% increase in energy efficiency in industrial production across sectors, among other strategies. Here, we examine the environmental implications of these policies in the context of engine remanufacture, using an environmental computable general equilibrium (CGE) model. Results indicate that both the subsidy policy and energy efficiency improvement target can contribute to economic growth and emission reductions, but the subsidy policy is estimated to have far greater impacts. The implementation of both can reinforce each other, generating higher economic and environmental benefits than the sum of each occurrence alone. Another major finding from our model is that an additional remanufactured engine only displaces 0.42 (90% confidence interval from 0.32 to 0.47) of a new engine (comprised of new parts), mainly because the lower prices of remanufactured engines lead to greater consumption. This ratio is much lower than the 1:1 perfect displacement commonly assumed in life cycle assessment (LCA) studies. Overall, our study suggests that the subsidizing of engine remanufacture in China can help promote the industry, improve overall economic welfare, and contribute to environmental targets. Our study also contributes to the estimation of more realistic product displacement ratios in LCA.

The Doping Effect of 13-Atom Iron Clusters on Water Adsorption and O-H Bond Dissociation.

Understanding the interactions between water and Fe-based clusters is necessary to unravel the micromechanics of the surface hydrophilic property and the corrosion process of iron-related materials. Herein, a theoretical study is conducted of water adsorption and dissociation on icosahedral Fe13 and Fe12X (X = Ti, V, Cr, Mn, Co, Ni) clusters. It is found that the doping atoms have significant influence on the geometric structures, magnetic moments, and electronic states of Fe12X clusters. The center-doped clusters X@Fe12 show higher stability than the shell-doped X-Fe12; Ni@Fe12 exhibits lower activation energy for the dissociation of H2O than all the others; Ti@Fe12 strikes a weak bonding energy and high activation energy for water dissociation. Also, a water dimer finds a decreased energy barrier for O-H dissociation, and the electronic states and metal-water interactions can be altered by the support effect. This information is helpful to those working on water chemistry, anticorrosion wading devices, and high-standard potable water utilization.