Causal relationship between mitochondrial-associated proteins and cerebral aneurysms: a Mendelian randomization study.

Background: Cerebral aneurysm is a high-risk cerebrovascular disease with a poor prognosis, potentially linked to multiple factors. This study aims to explore the association between mitochondrial-associated proteins and the risk of cerebral aneurysms using Mendelian randomization (MR) methods. Methods: We used GWAS summary statistics from the IEU Open GWAS project for mitochondrial-associated proteins and from the Finnish database for cerebral aneurysms (uIA, aSAH). The association between mitochondrial-associated exposures and cerebral aneurysms was evaluated using MR-Egger, weighted mode, IVW, simple mode and weighted median methods. Reverse MR assessed reverse causal relationship, while sensitivity analyses examined heterogeneity and pleiotropy in the instrumental variables. Significant causal relationship with cerebral aneurysms were confirmed using FDR correction. Results: Through MR analysis, we identified six mitochondrial proteins associated with an increased risk of aSAH: AIF1 (OR: 1.394, 95% CI: 1.109-1.752, p = 0.0044), CCDC90B (OR: 1.318, 95% CI: 1.132-1.535, p = 0.0004), TIM14 (OR: 1.272, 95% CI: 1.041-1.553, p = 0.0186), NAGS (OR: 1.219, 95% CI: 1.008-1.475, p = 0.041), tRNA PusA (OR: 1.311, 95% CI: 1.096-1.569, p = 0.003), and MRM3 (OR: 1.097, 95% CI: 1.016-1.185, p = 0.0175). Among these, CCDC90B, tRNA PusA, and AIF1 demonstrated a significant causal relationship with an increased risk of aSAH (FDR q < 0.1). Three mitochondrial proteins were associated with an increased risk of uIA: CCDC90B (OR: 1.309, 95% CI: 1.05-1.632, p = 0.0165), tRNA PusA (OR: 1.306, 95% CI: 1.007-1.694, p = 0.0438), and MRM3 (OR: 1.13, 95% CI: 1.012-1.263, p = 0.0303). In the reverse MR study, only one mitochondrial protein, TIM14 (OR: 1.087, 95% CI: 1.004-1.177, p = 0.04), showed a causal relationship with aSAH. Sensitivity analysis did not reveal heterogeneity or pleiotropy. The results suggest that CCDC90B, tRNA PusA, and MRM3 may be common risk factors for cerebral aneurysms (ruptured and unruptured), while AIF1 and NAGS are specifically associated with an increased risk of aSAH, unrelated to uIA. TIM14 may interact with aSAH. Conclusion: Our findings confirm a causal relationship between mitochondrial-associated proteins and cerebral aneurysms, offering new insights for future research into the pathogenesis and treatment of this condition.

Pyrrole adducts mediated mitochondrial dysfunction activates SARM1-dependent axon degeneration in 2,5-hexanedione-induced neuropathy.

2,5-hexanedione (HD) is the γ-diketone metabolite of industrial organic solvent n-hexane, primarily responsible for n-hexane neurotoxicity. Previous studies have shown that the formation of pyrrole adducts (PAs) is crucial for the toxic axonopathy induced by HD. However, the exact mechanism underlying PAs-induced axonal degeneration remains unclear. Recently, Sterile α and toll/interleukin 1 receptor motif-containing protein 1 (SARM1) has been identified as the central executor of axon degeneration. This study was designed to investigate the role of SARM1-mediated axon degeneration in rats exposed to HD. Furthermore, the causal relationship between PAs and SARM1-mediated axon degeneration was further explored using Sarm1 KO mice. Our findings suggest that HD causes axon degeneration and neuronal loss in animals. Mechanistic studies revealed that HD activates SARM1-dependent axonal degeneration machinery. In contrast, Sarm1 KO attenuates motor dysfunction and rescues neuron loss following HD exposure. Interestingly, the PAs formed by the binding of HD to proteins primarily accumulate on mitochondria, leading to mitochondrial dysfunction. This dysfunction serves as an upstream event in HD-induced nerve injuries. Our findings highlight the crucial role of PAs formation in the major pathological changes during n-hexane poisoning, providing a potential therapeutic target for n-hexane neuropathy.

Investigating the role of MAB_1915 in intrinsic resistance to multiple drugs in Mycobacterium abscessus.

The increasing clinical significance of Mycobacterium abscessus is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat M. abscessus infections. This study is inspired by the drug-hypersensitive profile of a mutant M. abscessus (U14) with transposon insertion in MAB_1915. We validated the role of MAB_1915 in intrinsic drug resistance in M. abscessus by constructing a selectable marker-free in-frame deletion in MAB_1915 and complementing the mutant with the same or extended version of the gene and then followed by drug susceptibility testing. Judging by the putative function of MAB_1915, cell envelope permeability was studied by ethidium bromide accumulation assay and susceptibility testing against dyes and detergents. In this study, we established genetic evidence of the role of MAB_1915 in intrinsic resistance to rifampicin, rifabutin, linezolid, clarithromycin, vancomycin, and bedaquiline. Disruption of MAB_1915 has also been observed to cause a significant increase in cell envelope permeability in M. abscessus. Restoration of resistance is observed to depend on at least 27 base pairs upstream of the coding DNA sequence of MAB_1915. MAB_1915 could therefore be associated with cell envelope permeability, and hence its role in intrinsic resistance to multiple drugs in M. abscessus, which presents it as a novel target for future development of effective antimicrobials to overcome intrinsic drug resistance in M. abscessus. IMPORTANCE: This study reports the role of a putative fadD (MAB_1915) in innate resistance to multiple drugs by M. abscessus, hence identifying MAB_1915 as a valuable target and providing a baseline for further mechanistic studies and development of effective antimicrobials to check the high level of intrinsic resistance in this pathogen.

Health Impacts of Fine Particulate Matter Shift Due to Urbanization in China.

Rapid urbanization and industrialization have resulted in diverse anthropogenic activities and emissions between urban and non-urban regions, leading to varying levels of exposure to air pollutants and associated health risks. However, endeavors to mitigate air pollution and health benefits have displayed considerable heterogeneity across different regions. Therefore, comprehending the changes in air pollutant concentrations and health impacts within an urbanization context is imperative for promoting environmental equity. This paper uses gross domestic product (GDP)- and population-weighted methods to distinguish anthropogenic emissions from urban and non-urban areas in China and quantified their contributions to fine particulate matter (PM2.5) using the Community Multiscale Air Quality (CMAQ) model in 2010 and 2019. Anthropogenic emissions from urban and non-urban (outside urban) regions decreased by 26 and 44% from 2010 to 2019, respectively, resulting in 31 and 28% reductions of PM2.5 in China. PM2.5-related premature mortality attributed to non-urban and urban anthropogenic emission decreases by 8%. Non-urban anthropogenic activities are the main contributor to PM2.5 (56% in 2010 and 2019) and its associated premature mortality (59%), which also predominantly affects non-urban premature mortality (37-42% in 2010-2019). Population changes increase the proportion of premature mortality in urban populations (7-19%) from 2010 to 2019. This study emphasizes the shift of affected populations due to urbanization and population changes.

Dilated cardiomyopathy caused by mutation of the PNPLA2 gene: a case report and literature review.

Deficiency of adipose triglyceride lipase (ATGL) due to mutation in PNPLA2 causes neutral lipid storage disease with myopathy (NLSDM), an autosomal recessive disorder (MIM: #610717). NLSDM patients are mainly affected by progressive myopathy, cardiomyopathy, and hepatomegaly. Cardiac involvement was reported in 40%-50% of NLSDM patients. Patients with cardiac involvement have adult-onset progressive heart failure, mimicking dilated or hypertrophic cardiomyopathy. The clinical characteristics, genotype-phenotype correlation, and prognosis of cardiomyopathy secondary to PNPLA2 mutation are not understood. We reported two male patients carrying a homozygous splicing mutation NM_020376.4 (c.757 + 1G>T) in PNPLA2, presenting with severe dilated cardiomyopathy and mild skeletal muscle involvement. Through the literature review, the ECG and imaging features and the prognosis of 49 previously reported cases of cardiomyopathy caused by the PNPLA2 mutation were summarized. This study suggests that NLSDM should be considered a cause of cardiomyopathy, especially in those with elevated creatine kinase (CK) levels, regardless of whether symptoms such as muscle weakness or atrophy are present.

Mask-Guided Target Node Feature Learning and Dynamic Detailed Feature Enhancement for lncRNA-Disease Association Prediction.

Identifying new relevant long noncoding RNAs (lncRNAs) for various human diseases can facilitate the exploration of the causes and progression of these diseases. Recently, several graph inference methods have been proposed to predict disease-related lncRNAs by exploiting the topological structure and node attributes within graphs. However, these methods did not prioritize the target lncRNA and disease nodes over auxiliary nodes like miRNA nodes, potentially limiting their ability to fully utilize the features of the target nodes. We propose a new method, mask-guided target node feature learning and dynamic detailed feature enhancement for lncRNA-disease association prediction (MDLD), to enhance node feature learning for improved lncRNA-disease association prediction. First, we designed a heterogeneous graph masked transformer autoencoder to guide feature learning, focusing more on the features of target lncRNA (disease) nodes. The target nodes were increasingly masked as training progressed, which helps develop a more robust prediction model. Second, we developed a graph convolutional network with dynamic residuals (GCNDR) to learn and integrate the heterogeneous topology and features of all lncRNA, disease, and miRNA nodes. GCNDR employs an interlayer residual strategy and a residual evolution strategy to mitigate oversmoothing caused by multilayer graph convolution. The interlayer residual strategy estimates the importance of node features learned in the previous GCN encoding layer for nodes in the current encoding layer. Additionally, since there are dependencies in the importance of features of individual lncRNA (disease, miRNA) nodes across multiple encoding layers, a gated recurrent unit-based strategy is proposed to encode these dependencies. Finally, we designed a perspective-level attention mechanism to obtain more informative features of lncRNA and disease node pairs from the perspectives of mask-enhanced and dynamic-enhanced node features. Cross-validation experimental results demonstrated that MDLD outperformed 10 other state-of-the-art prediction methods. Ablation experiments and case studies on candidate lncRNAs for three diseases further proved the technical contributions of MDLD and its capability to discover disease-related lncRNAs.

Analytical method for studying acoustic fields radiated by general spherical sound sources in thermoviscous fluids.

The study of acoustic radiation from spherical sound sources plays a crucial role in understanding the thermoviscous effects in practical acoustic problems. However, finding a general solution of acoustic radiation from spherical sound sources in thermoviscous fluids remains a formidable challenge. To advance this issue, an analytical method is developed in this paper to calculate the acoustic field radiated by spherical sound sources with the isothermal boundary condition and arbitrary velocity boundary condition. The developed method is utilized to present the solutions of the acoustic field generated by an oscillating sphere and a general spherical sound source, and the accuracy and validity of these solutions are verified through analytical and numerical methods.

[Pollution Characteristics and Source Apportionment of VOCs in Urban Areas of Shijiazhuang in Spring].

Samples of ambient volatile organic compounds （VOCs） were collected using SUMMA canisters at three Country Control Sites in Shijiazhuang during the spring of 2019, 2021, and 2022, which were detected using gas chromatography/mass spectrometry （GC/MS）. To investigate the characteristics and temporal variations of VOCs mass concentration levels, the online monitoring data of ozone （O3） and PM2.5 at the same site were also collected. Subsequently, the ozone formation potential （OFP） and secondary organic aerosol formation potential （SOAFP） were utilized to assess the chemical activity of VOCs. Additionally, the potential source areas of VOCs in spring in Shijiazhuang were further identified using the potential source contribution factor （PSCF） method and concentration weight trajectory analysis （CWT）. Hence, the major VOCs sources were evaluated with the VOCs initial mixing ratio. The results demonstrated that the averaged concentration of VOCs during the polluted period and clean period of spring in Shijiazhuang were 191.17 µg·m-3 and 122.18 µg·m-3, respectively. Meanwhile, the OFP was 361.23 µg·m-3 during the polluted period and 266.96 µg·m-3 during the clean period, whereas the SOAFP was 1.98 µg·m-3 and 1.61 µg·m-3, respectively. Therefore, effective control of benzene, toluene, ethylbenzene, and xylene （BTEX） is crucial for reducing PM2.5 and O3 pollution. Based on the results obtained from weight PSCF and CWT, the potential source areas of VOCs were further identified to be primarily located in the eastern Yuhua District, the high-tech district, and the northern Luancheng District of Shijiazhuang. These areas were influenced not only by local emissions but also by transport from neighboring regions, in which consistency between the CWT and PSCF results further supported these findings. Furthermore, the results obtained from the benzene/toluene/ethylbenzene （B/T/E） and xylene/benzene （X/B） ratios indicated that the main sources of VOCs in Shijiazhuang in spring were vehicle exhaust sources and burning sources, leading to a more serious air mass aging phenomenon. Hence, controlling vehicle emissions and implementing regional cooperative measures are the effective strategies for optimizing the air quality of Shijiazhuang.

Achieving the Inhibition of Aluminum Corrosion by Dual-Salt Electrolytes for Sodium-Ion Batteries.

Sodium bis(fluorosulfonyl)imide (NaFSI) electrolytes are renowned for their superior physicochemical and electrochemical properties, making them ideal for high-performance sodium-ion batteries (SIBs). However, severe oxidative dissolution of aluminum current collectors (commonly known as Al corrosion) in NaFSI-based electrolytes occurs at high potentials. To address this challenge, aiming to understand the Al corrosion mechanism and develop strategies to inhibit corrosion, we propose dual-salt electrolytes using 0.8 mol L-1 (M) NaFSI and 0.2 M of a second fluorine-containing sodium salt dissolved in EC/PC solutions (1:1, v/v) to construct an insoluble deposits layer on the Al. Dual-salt electrolytes adopting a second sodium salt capable of passivating the Al collector have been extensively investigated through various techniques, such as cyclic voltammetry, scanning electron microscopy, chronoamperometry, X-ray photoelectron spectroscopy, and charge-discharge tests. Our findings demonstrate that introducing sodium difluoro(oxalato)borate (NaDFOB) into the NaFSI electrolytes inhibits Al corrosion, which is attributed to the formation of insoluble deposits of Al-F (AlF3) and B-F containing polymers. Moreover, the capacity retention of Na||Na3V2(PO4)3 (NVP) cells using the NaFSI-NaDFOB dual-salt electrolyte reaches 99.2% along with a Coulombic efficiency over 99.3% at a 1 C rate after 200 cycles. This research provides a practical solution for passivating Al collectors in SIBs with NaFSI electrolytes and promotes the development of sodium batteries with long calendar lifetimes.

Both TREM2-dependent macrophages and Kupffer cells play a protective role in APAP-induced acute liver injury.

The inflammatory response is a significant factor in acetaminophen (APAP)-induced acute liver injury. And it can be mediated by macrophages of different origins. However, whether Kupffer cells and mononuclear-derived macrophages play an injury or protective role in APAP hepatotoxicity is still unclear. In this study, C57/BL6N mice were performed to establish the APAP acute liver injury model. Intervention experiments were also carried out using clodronate liposomes or TREM2 knockout. We found that APAP overdose triggered the activation of inflammatory factors and enhanced the expression of the RIPK1-MLKL pathway in mice's livers. Moreover, our study showed that inflammation-related protein expression was increased after clodronate liposome administration or TREM2 knockout. The RIPK1-MLKL-mediated necroptosis was also significantly activated after the elimination of Kupffer cells or the inhibition of mononuclear-derived macrophages. More importantly, clodronate liposomes treatment and TREM2 deficiency all worsen APAP-induced liver damage in mice. In conclusion, the results indicate that Kupffer cells and mononuclear macrophages play a protective role in APAP-induced liver injury by regulating necroptosis. Therefore, macrophages hold as a potential therapeutic target for APAP-induced liver damage.

Potential Drivers for the Spatiotemporal Patterns of the Global Burden of Chronic Obstructive Pulmonary Disease Attributable to Ambient Ozone, 1990-2019.

Objectives: To identify the long-term spatiotemporal trend of ozone-related chronic obstructive pulmonary disease (COPD) burden by sex and country and to explore potential drivers. Methods: We retrieved data of ozone-related COPD death and disability adjusted life year (DALY) from the Global Burden of Disease 2019. We used a linear regression of natural logarithms of age-standardized rates (ASRs) with calendar year to examine the trends in ASRs and a panel regression to identify country-level factors associated with the trends. Results: Global ozone-attributable COPD deaths increased from 117,114 to 208,342 among men and from 90,265 to 156,880 among women between 1990 and 2019. Although ASRs of ozone-related COPD death and DALY declined globally, they increased in low and low-middle Socio-demographic Index (SDI) regions, with faster rise in women. Elevated average maximum temperature was associated with higher ozone-attributable COPD burden, while more green space was associated with lower burden. Conclusion: More efforts are needed in low and low-middle SDI regions, particularly for women, to diminish inter-country inequality in ozone-attributable COPD. Global warming may exacerbate the burden. Expanding green space may mitigate the burden.

Performance Limits and Advancements in Single 2D Transition Metal Dichalcogenide Transistor.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) allow for atomic-scale manipulation, challenging the conventional limitations of semiconductor materials. This capability may overcome the short-channel effect, sparking significant advancements in electronic devices that utilize 2D TMDs. Exploring the dimension and performance limits of transistors based on 2D TMDs has gained substantial importance. This review provides a comprehensive investigation into these limits of the single 2D-TMD transistor. It delves into the impacts of miniaturization, including the reduction of channel length, gate length, source/drain contact length, and dielectric thickness on transistor operation and performance. In addition, this review provides a detailed analysis of performance parameters such as source/drain contact resistance, subthreshold swing, hysteresis loop, carrier mobility, on/off ratio, and the development of p-type and single logic transistors. This review details the two logical expressions of the single 2D-TMD logic transistor, including current and voltage. It also emphasizes the role of 2D TMD-based transistors as memory devices, focusing on enhancing memory operation speed, endurance, data retention, and extinction ratio, as well as reducing energy consumption in memory devices functioning as artificial synapses. This review demonstrates the two calculating methods for dynamic energy consumption of 2D synaptic devices. This review not only summarizes the current state of the art in this field but also highlights potential future research directions and applications. It underscores the anticipated challenges, opportunities, and potential solutions in navigating the dimension and performance boundaries of 2D transistors.

Phytic acid inhibits Cr(VI) reduction on Fe(II)-bearing clay minerals: Changing reduction sites and electron transfer pathways.

The presence of organic phosphorus may influence the characteristics of Cr(VI) reduction and immobilization on Fe(II)-bearing clay minerals under anoxic conditions, as the organic phosphorus tends to bind strongly to clay minerals in soil. Herein, reduced nontronite (rNAu-2) was used to reduction of Cr(VI) in the presence of phytic acid (IHP) at neutral pH. With IHP concentration from 0 to 500 µM, Cr(VI) reduction decreased obviously (17.8%) within first 5 min, and then preferred to stagnate during 4-12 h (≥50 µM). After that, Cr(VI) was reduced continuously at a slightly faster rate. Density functional theory (DFT) calculations revealed that IHP primarily absorbed at the edge sites of rNAu-2 to form Fe-IHP complexes. X-ray diffraction (XRD), scanning transmission electron microscopy (STEM), and Fourier transform infrared spectroscopy (FTIR) results demonstrated that IHP hindered the ingress of CrO42- into the interlayer space of rNAu-2 and impeded their reduction by trioctahedral Fe(II) and Al-Fe(II) at basal plane sites in the initial stage. Additionally, Fe(II) extraction results showed that IHP promoted the electron from interior transfer to near-edge, but hindered it further transfer to surface, resulting in the inhibition on Cr(VI) reduction at edge sites during the later stage. Consequently, IHP inhibits the reduction and immobilization of Cr(VI) by rNAu-2. Our study offers novel insights into electron transfer pathways during the Cr(VI) reduction by rNAu-2 with coexisting IHP, thereby improve the understanding of the geochemical processes of chromium within the iron cycle in soil.

Nacre-Inspired Structure Enables Ultrahigh "Strong-Tough" Design of Phosphorus Anode.

Red phosphorus anode, attributed to its high specific capacity of 2596 mAh g-1, is expected to improve the energy density of Na-ion batteries. However, the P anode currently is unsatisfactory for practical usage due to the large volume expansion beyond 300%, which brings out uncontrolled brittle failure. To address this challenge, we here design a nacre-like phosphorus anode by resilient graphene oxide staggered together. The staggered structure simultaneously offers mechanical strength and interwoven toughness. Finite element modeling reveals that the sodiation stress from P nanoparticles will be transferred into interlayer pillars as the elastic medium to release sodiation stress. The prepared anode achieves an ultrahigh areal capacity of 13 mAh cm-2 at a mass loading of 5.8 mg cm-2. Notably, the volume change of the anode is limited to approximately 8.2% at full sodiation, significantly lower than that of the traditional phosphorus electrodes.

Blocking CX3CR1+ Tumor-associated Macrophages Enhances the Efficacy of Anti-PD-1 Therapy in Hepatocellular Carcinoma.

The efficacy of immune checkpoint inhibitors (ICI) in the treatment of hepatocellular carcinoma (HCC) remains limited, highlighting the need for further investigation into the underlying mechanisms. Accumulating evidence indicates that tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) are implicated in immune evasion and treatment resistance. This study aimed to explore the contribution of TAMs in the HCC TME. Our findings reveal the critical involvement of CX3C motif chemokine receptor 1 (CX3CR1)-positive TAMs in inducing T cell exhaustion through interleukin-27 (IL-27) secretion, providing valuable insights into the mechanisms underlying the suboptimal efficacy of anti-PD-1 therapy in HCC. Moreover, we identified prostaglandin E2 (PGE2), released by immune-attacked tumor cells, as a key regulator of CX3CR1+ TAM phenotype transition. To augment the therapeutic response to current anti-PD-1 therapy, we propose an innovative treatment strategy that incorporates targeting CX3CR1+ TAMs in addition to anti-PD-1 therapy. In conclusion, our study contributes to the understanding of TAMs' role in cancer immunotherapy and highlights potential clinical implications for HCC treatment. The combination of targeting CX3CR1+ TAMs with anti-PD-1 therapy holds promise for enhancing the efficacy of immunotherapeutic interventions in HCC patients.

Repeated postnatal sevoflurane exposure impairs social recognition in mice by disrupting GABAergic neuronal activity and development in hippocampus.

BACKGROUND: Repeated exposure to sevoflurane during early developmental stages is a risk factor for social behavioural disorders, but the underlying neuropathological mechanisms remain unclear. As the hippocampal cornu ammonis area 2 subregion (CA2) is a critical centre for social cognitive functions, we hypothesised that sevoflurane exposure can lead to social behavioural disorders by disrupting neuronal activity in the CA2. METHODS: Neonatal mice were anaesthetised with sevoflurane 3 vol% for 2 h on postnatal day (PND) 6, 8, and 10. Bulk RNA sequencing of CA2 tissue was conducted on PND 12. Social cognitive function was assessed by behavioural experiments, and in vivo CA2 neuronal activity was recorded by multi-channel electrodes on PND 60-65. RESULTS: Repeated postnatal exposure to sevoflurane impaired social novelty recognition in adulthood. It also caused a decrease in the synchronisation of neuronal spiking, gamma oscillation power, and spike phase-locking between GABAergic spiking and gamma oscillations in the CA2 during social interaction. After sevoflurane exposure, we observed a reduction in the density and dendritic complexity of CA2 GABAergic neurones, and decreased expression of transcription factors critical for GABAergic neuronal development after. CONCLUSIONS: Repeated postnatal exposure to sevoflurane disturbed the development of CA2 GABAergic neurones through downregulation of essential transcription factors. This resulted in impaired electrophysiological function in adult GABAergic neurones, leading to social recognition deficits. These findings reveal a potential electrophysiological mechanism underlying the long-term social recognition deficits induced by sevoflurane and highlight the crucial role of CA2 GABAergic neurones in social interactions.

Development and Validation of a Novel Multiplex Real-Time PCR Assay for Rapid Detection of Carbapenemase Genes in Carbapenem-Resistant Enterobacterales Isolates and Clinical Samples.

Purpose: Carbapenem-resistant Enterobacterales (CRE) infection is an urgent threat to human health. This study aimed to develop and validate a novel multiplex real-time PCR (multi-qPCR) assay for the detection of the blaKPC, blaNDM, blaIMP, blaOXA-48-like, and blaVIM genes in CRE isolates and clinical samples, as well as to compare it with three phenotypic methods. Methods: The reliability and limit of detection (LOD) of the multi-qPCR assay were evaluated. PCR and DNA sequencing were used as the reference methods to identify carbapenemase genes in CRE isolates and clinical samples. The accuracy of the multi-qPCR assay, modified carbapenem inactivation and EDTA-modified carbapenem inactivation method (mCIMandeCIM), carbapenemase inhibitor-based combined disk test (CDT), and colloidal gold-based immunochromatographic test was compared with the reference methods with 182 isolates of CRE. Furthermore, 112 clinical samples were collected to validate the efficacy of this multi-qPCR assay. Results: The standard deviations (CVs) of intra-assay and inter-assay of the multi-qPCR assay were ≤ 0.53% and ≤ 2.04% for detecting the five major carbapenemase genes, respectively; while the LOD ranged from 2×102 copies/mL to 8×102 copies/mL. PCR and DNA sequencing confirmed 168 out of 182 CRE isolates producing carbapenemase(s): KPC (n = 93), NDM (n = 46), IMP (n = 8), OXA-48-like (n = 14), VIM (n = 1), KPC&NDM (n = 5), and KPC&NDM&IMP (n = 1). The accuracy of mCIMandeCIM, CDT, Colloidal Gold, and the multi-qPCR assay was 96.2%, 89.6%, 100%, and 100% respectively for detecting carbapenemase(s) producers. Moreover, the sensitivity and specificity of the multi-qPCR assay were all 100% for the detection of each carbapenemase gene in clinical samples, compared with PCR and sequencing. Conclusion: For clinical isolate detection, the multi-qPCR assay is comparable to Colloidal Gold, and superior to mCIMandeCIM and CDT; while for clinical samples detection, it also shows excellent performance. Therefore, the multi-qPCR assay has great potential for clinical diagnosis.

Research and engineering application of layout optimization for lockbolt structures in railway wagons considering multidimensional failure modes based on MSNSGA-III.

The lockbolt structure is essential in railway wagons, and a scientific lockbolt layout can ensure uniform load distribution, thereby preventing failure. However, current engineering lacks layout optimization methods that address multidimensional failure modes. This paper presents a new lockbolt structure layout optimization method based on submodel, parametric models, and a multi-strategy integrated NSGA-III (MSNSGA-III), adhering to the DVS EFB 3435-2 standard. This method simultaneously optimizes the number and spacing of lockbolts to prevent tensile, bearing, shear, and other static failure modes under specified load conditions. The proposed method was applied during the design phase of a container flatcar. Optimization results indicate that, compared to NSGA-III, this method achieves the best IGD and HV values across multiple complex test functions, demonstrating superior performance in solving complex Pareto front optimization problems. Additionally, the optimized lockbolt structure's safety margins increased by a maximum of 59.81%, passing the full vehicle strength test and significantly enhancing resistance to multidimensional failure modes. These results highlight the method's significant practical application value in addressing the optimization of railway wagon lockbolt structures under complex multidimensional failure modes.

Superhydrophobic stretchable sensors based on interfacially self-assembled carbon nanotube film for self-sensing drag-reduction shipping.

Multifunctional flexible electronics integrated with superhydrophobicity and flexible sensing can greatly promote broader applications. However, the hierarchical roughness morphology of superhydrophobic surfaces is vulnerable to complex mechanical deformations of stretchable sensors leading to degradation of hydrophobic properties, so constructing robust superhydrophobic stretchable sensors remains challenging. Herein, we propose a facile strategy to fabricate superhydrophobic stretchable sensors based on self-assembled carbon nanotube (CNT) films at the air-water interface. The customizable functions of superhydrophobic stretchable sensors can be achieved by controlling the combination of the CNT film and polydimethylsiloxane (PDMS) through a simple and efficient interfacial transferring strategy. Even under large mechanical deformations, the developed sensors can present excellent robustness and superhydrophobicity with a water contact angle of 150.9° at 80% strain. As a proof-of-concept, this work demonstrates their potential application in self-sensing drag-reduction shipping, which is expected to realize greener, more sustainable and safer aquatic transportation.