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The purpose of this study is to clarify the roles of thermophilic bacteria in humification during hyperthermophilic composting (HTC) of organic wastes mainly composed of mushroom residue. Results showed that HTC with a long hyperthermophilic (>80°C) period lasting for 18 days produced 83 mg/g of humus in compost on day 27, significantly higher than that of thermophilic composting (TC, 9.7 mg/g). Machine learning models identified that the dominant thermophiles belonging to Bacillaceae, Sporolactobacillaceae, Thermaerobacteraceae, Paenibacillaceae families and the unique thermophiles (Thermus and Calditerricola) in HTC played important roles in accumulating stubborn and soluble humus including humic acid and fulvic acid. Hyperthermophilic fermentation not only recruited and enriched these thermophilic bacteria to rapidly degrade organic matter into bioavailable nutrients, but also upregulated the metabolic pathways relevant to the generation and oxidation of precursors including amino acids that would be polymerized into humus, thus efficiently converting organic waste into humus-rich compost., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Kale is rich in various essential trace elements and phytochemicals, including glucosinolate and its hydrolyzed product isothiocyanate, which have significant anticancer properties. Nowadays, new types of pollutant microplastics (MP) pose a threat to global ecosystems due to their high bioaccumulation and persistent degradation. Silicon (Si) is commonly used to alleviate abiotic stresses, offering a promising approach to ensure safe food production. However, the mechanisms through which Si mitigates MP toxicity are unknown. In this study, a pot culture experiments was conducted to evaluate the morphogenetic, physiological, and biochemical responses of kale to Si supply under MP stress. The results showed that MP caused the production of reactive oxygen species, inhibited the growth and development of kale, and reduced the content of phytochemicals by interfering with the photosynthetic system, antioxidant defense system, and endogenous hormone regulation network. Si mitigated the adverse effects of MP by enhancing the photosynthetic capacity of kale, regulating the distribution of substances between primary and secondary metabolism, and strengthening the ascorbate-glutathione (AsA-GSH) cycling system., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaoqin Yao reports financial support was provided by National Natural Science Foundation of China. Xiaoqin Yao reports financial support was provided by Natural Science Foundation of Hebei Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Probing magnetic susceptibility of a microsized ferromagnet is a long-standing problem in condensed matter physics. Among various measuring methods for magnetic susceptibility including vibrating sample magnetometry and superconducting quantum interference device magnetometry, almost all require large-scale bulk samples or thick films. However, the quantitative measurement for magnetic susceptibility on a microscale nanoflake is a great challenge. Here, we demonstrate a new analysis method to quantitatively evaluate the magnetic susceptibility of a microscale ferromagnetic nanoflake. Based on the Arrott plot of magnetization isotherms obtained from anomalous Hall resistance, we achieve an in situ evaluation of the value of magnetic susceptibility of a microscale ferromagnetic Fe 5 GeTe 2 nanoflake, identification of the out-of-plane and in-plane magnetization, and investigation of the magnetic anisotropy transition with quantifying critical exponents. Our method reveals critical information on magnetic phase transition in microscale ferromagnetic materials, providing deep insight into spin dynamics of correlated electron systems.

Pulmonary fibrosis (PF) is a progressive, irreversible disease characterized by heterogeneous interstitial lung tissue damage. It originates from persistent or repeated lung epithelial injury and leads to the activation and differentiation of fibroblasts into myofibroblasts. Interleukins (ILs) are a group of lymphokines crucial for immunomodulation that are implicated in the pathogenesis of PF. However, different types of ILs exert disparate effects on PF. In the present review, based on the effect on PF, ILs are classified into three categories: i) Promotors of PF; ii) inhibitors of PF; and iii) those that exert dual effects on PF. Several types of ILs can promote PF by provoking inflammation, initiating proliferation and transdifferentiation of epithelial cells, exacerbating lung injury, while other ILs can inhibit PF through suppressing expression of inflammatory factors, modulating the Th1/Th2 balance and autophagy. The present review summarizes the association of ILs and PF, focusing on the roles and mechanisms of ILs underlying PF., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 He et al.)

Monitoring mercury (Hg) is critical for environmental and public health. Metal-organic framework (MOF)-based sensors demonstrate the advantage of high sensitivity and rapid response. We summarize the advances of MOF sensors for Hg 2+ detection from the perspective of MOF type and role in the sensors. First, we introduce three MOFs used in Hg sensors-UIO, ZIF, and MIL-that have demonstrated superior performance. Then, we discuss the specifics of MOF-based sensors for Hg 2+ detection in terms of the recognition and signal elements. Currently, the recognition elements include T-rich aptamers, noble metal nanoparticles, central metal ions, and organic functional groups inherent to MOFs. Sensors with fluorescence and colorimetric signals are the two main types of optical MOF sensors used for Hg detection. Electrochemical sensors have also been fabricated, but these are less frequently reported, potentially due to the limited conductivity and cycling stability of MOFs. Notably, dual-signal sensors mitigate background signals interference and enhance the accuracy of Hg 2+ detection. Furthermore, to facilitate portability and user-friendliness, portable devices such as microfluidics, paper-based devices, and smartphones have been developed for Hg 2+ detection, showcasing potential applications. We also address the challenges related to MOF-based sensors for Hg 2+ and future outlook., (© 2024 Wiley-VCH GmbH.)

Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are semi-crystalline elastomers with a low melting point and high elongation at break, allowing for a wide range of applications in domestic, agricultural, industrial, and mainly medical fields. Utilizing low-cost cellulose hydrolyzed sugar as a carbon source and metabolic engineering to enhance synthesis in Pseudomonas putida is a promising strategy for commercializing mcl-PHAs, but little has been attempted to improve the utilization of glucose for synthesizing mcl-PHAs. In this study, a multi-pathway modification was performed to improve the utilization of substrate glucose and the synthesis capacity of PHAs. To enhance glucose metabolism to flow to acetyl-CoA, which is an important precursor of mcl-PHA, multiple genes in glucose metabolism were inactive (branch pathway and negative regulatory) and overexpressed (positive regulatory) in this study. The two genes, gcd (encoding glucose dehydrogenase) and gltA (encoding citrate synthase), involved in glucose peripheral pathways and TCA cycles were separately and jointly knocked out in Pseudomonas putida QSRZ6 ( ΔphaZΔhsdR ), and the mcl-PHA synthesis was improved in the mutants; particularly, the mcl-PHA titer of QSRZ603 ( ΔgcdΔgltA ) was increased by 33.7%. Based on the glucose branch pathway truncation, mcl-PHA synthesis was further improved with hexR -inactivation (encoding a negative regulator in glucose metabolism). Compared with QSRZ603 and QSRZ6, the mcl-PHA titer of QSRZ607 ( ΔgcdΔgltAΔhexR ) was increased by 62.8% and 117.5%, respectively. The mutant QSRZ609 was constructed by replacing the endogenous promoter of gltB encoding a transcriptional activator of the two-component regulatory system GltR/GltS with the ribosome subunit promoter P 33 . The final mcl-PHA content and titers of QSRZ609 reached 57.3 wt% and 2.5 g/L, an increase of and 20.9% and 27.3% over that of the parent strain QSRZ605 and an increase of 110.4% and 159.9% higher as compared to QSRZ6, respectively. The fermentation was optimized with a feeding medium in shaker flacks; then, the mcl-PHA contents and titer of QSRZ609 were 59.1 wt% and 6.8 g/L, respectively. The results suggest that the regulation from glucose to acetyl-CoA by polygenic modification is an effective strategy for enhancing mcl-PHA synthesis, and the mutants obtained in this study can be used as chassis to further increase mcl-PHA production., Competing Interests: The authors declare no conflicts of interest.

The Peierls distortion plays an essential role in governing the in-plane ferroelectricity and nonlinear optical characteristics of anisotropic niobium oxide dihalides, such as NbOCl 2 and NbOI 2 . Despite its significance, experimental investigation into the structural, optical, and ferroelectric properties of NbOBr 2 has been lacking. Here, the successful fabrication of centimeter-sized, high-quality NbOBr 2 single crystals, enabling direct observation of Peierls distortion using aberration-corrected scanning transmission electron microscopy, is reported. Notably, the magnitude of Peierls distortion in NbOBr 2 falls between that observed in NbOCl 2 and NbOI 2 . Furthermore, the existence of giant linear dichroism absorption and second-harmonic generation (SHG) phenomena associated with Peierls distortion is confirmed. Exfoliated NbOBr 2 flakes exhibit single-domain ferroelectricity, with the polarization switchable by an electric field. Temperature-dependent SHG measurements reveal a Curie temperature of ≈502 K for ferroelectric NbOBr 2 . This work demonstrates that NbOBr 2 holds promise for polarized nonlinear optical devices, as well as for nonvolatile information processing and storage devices., (© 2024 Wiley‐VCH GmbH.)

To enhance the fast and accurate detection of pollution-free green apples for food safety, this paper uses the DETR network as a framework to propose a new method for pollution-free green apple detection based on a multidimensional feature extraction network and Transformer module. Firstly, an improved DETR network main feature extraction module adopts the ResNet18 network and replaces some residual layers with deformable convolutions (DCNv2), enabling the model to better adapt to pollution-free fruit changes at different scales and angles, while eliminating the impact of microbial contamination on fruit testing; Subsequently, the extended spatial pyramid pooling model (DSPP) and multiscale residual aggregation module (FRAM) are integrated, which help reduce feature noise and minimize the loss of underlying features during the feature extraction process. The fusion of the two modules enhances the model's ability to detect objects of different scales, thereby improving the accuracy of near-color fruit detection. At the same time, in order to solve the problems of slow convergence speed and large calculation amount of the basic network model, the convergence speed of the overall network model is improved by replacing the attention mechanism of Transformer. Experimental results show that compared with the original DETR model, the proposed algorithm has improved in AP, AP50, and AP75 indicators, especially in the AP50 indicator, which has the most obvious improvement reaching a detection accuracy of 97.12%. In the meantime, the trained network model is deployed on the picking robot. Compared with the original DETR network model, its average detection accuracy is as high as 96.58%, and the detection speed is increased by about 51%. Mixed sample detection tests were carried out before and after the model deployment, and the detection rate of the proposed method for nonpolluted fruits reached more than 0.95. enabling the picking robot to efficiently complete the task of picking green apples. The test results show that the algorithm proposed in this article exhibits great potential in the task of detecting pollution-free near-color fruits by the picking robot. It ensures pollution-free fruit picking and the application of AI in food safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Plants employ cell-surface receptors to perceive non- or altered-self, including the integrity of their cell wall. Here we identify a specific ligand-receptor module responsive to cell wall damage that potentiates immunity in Arabidopsis. Disruption of cell wall integrity by inhibition of cellulose biosynthesis promotes pattern-triggered immunity transcriptionally in a manner dependent on the receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2). Notably, while MIK2 can perceive peptides of the large SERINE RICH ENDOGENOUS PEPTIDE family, a single member of this family, SCOOP18, is transcriptionally induced upon cell wall damage and is required for subsequent responses such as lignification and immunity potentiation. Collectively, our results identify the SCOOP18-MIK2 ligand-receptor module as an important central hub, connecting plant cell wall integrity sensing with immunity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Soybean protein isolate (SPI) cannot meet the needs of modern food production due to various shortcomings. By change of its structural characteristics, its application in the food field may be increased. This study explored the impact of ultrasonic treatment on the structural and gelation properties of the SPI dispersions. By subjecting SPI to ultrasonic treatment at 0-800 W for 10 min, it was found that this treatment significantly reduced the particle size of SPI to 196 nm and caused an increase in its solubility, surface hydrophobicity, and sulfhydryl content as well as significant changes in the protein structure. At an optimal ultrasonic power of 200 W, SPI gels demonstrated an enhanced gelling ability, strength, and water-holding capacity, forming a more uniform and compact structure. Application in Chiba tofu showed that water retention, elasticity, and sensory quality were optimized at 200 W. The findings highlight that a sonication power of 200 W significantly improves the physicochemical and structural properties of SPI, resulting in a denser and more functional gel suitable for Chiba tofu production., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In addition to the pressurized high-temperature superconductivity, bilayer and trilayer nickelate superconductors La n +1 Ni n O 3 n +1 (n = 2 and 3) exhibit many intriguing properties at ambient pressure, such as orbital-dependent electronic correlation, non-Fermi liquid behavior, and density-wave transitions. Here, using ultrafast reflectivity measurement, we observe a drastic difference between the ultrafast dynamics of the bilayer and trilayer nickelates at ambient pressure. We observe a coherent phonon mode in La 4 Ni 3 O 10 involving the collective vibration of La, Ni, and O atoms, which is absent in La 3 Ni 2 O 7 . Temperature-dependent relaxation time diverges near the density-wave transition temperature of La 4 Ni 3 O 10 above ∼150 K, suggesting a non-Fermi liquid behavior of La 3 Ni 2 O 7 above ∼150 K, suggesting a non-Fermi liquid behavior of La 3 Ni 2 O 7 . Moreover, we estimate the electron-phonon coupling constants to be 0.05-0.07 and 0.12-0.16 for La 3 Ni 2 O 7 and La 4 Ni 3 O 10 , respectively, suggesting a relatively minor role of electron-phonon coupling in the electronic properties of La n +1 Ni n O 3 n +1 at ambient pressure. The relevant microscopic interaction and dynamic information are essential for further studying the interplay between superconductivity and density-wave transitions in nickelate superconductors., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Patients with brain metastases (BM) face a 90% mortality rate within one year of diagnosis and the current standard of care is palliative. Targeting BM-initiating cells (BMICs) is a feasible strategy to treat BM, but druggable targets are limited. Here, we apply Connectivity Map analysis to lung-, breast-, and melanoma-pre-metastatic BMIC gene expression signatures and identify inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo GTP synthesis pathway, as a target for BM. We show that pharmacological and genetic perturbation of IMPDH attenuates BMIC proliferation in vitro and the formation of BM in vivo. Metabolomic analyses and CRISPR knockout studies confirm that de novo GTP synthesis is a potent metabolic vulnerability in BM. Overall, our work employs a phenotype-guided therapeutic strategy to uncover IMPDH as a relevant target for attenuating BM outgrowth, which may provide an alternative treatment strategy for patients who are otherwise limited to palliation., Competing Interests: Declaration of interests A.M.K., J.W.J., C.V., J.M., and S.K.S. are listed as co-inventors for a PCT patent that has been filed, relating to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Interest is growing in investigating the ability of children with autism spectrum disorder (ASD) to process social information under conflicting and complex environments. However, few studies have employed objective behavioral measures to directly explore the underlying profile of social-emotional interference control., Methods: In the current study, 53 children with ASD and 53 typically developing (TD) control, aged 6-12 years, completed a set of modified flanker tasks involving arrows, schematic faces, same real faces (with facial interference by the same person), and different real faces (with facial interference by different people), respectively. Response time in incongruent (RT Inc ) and congruent conditions (RT Con ), percentage of errors in incongruent (%Error Inc ) and congruent conditions (%Error Con ), and flanker effect calculated by ΔRT = (RT Inc - RT Con )/RT Con and Δ%Error = %Error Inc - %Error Con were used as outcome metrics., Results: We obtained three major results: (1) the ASD group had longer RT Inc and RT Con compared to the TD group in the arrow, schematic-face, and same real-face tasks; (2) compared with the performance in the arrow flanker task, both groups exhibited longer RTs and reduced ΔRTs in the same real-face task; however, in the schematic-face task, longer RT and reduced ΔRT were exhibited in the TD group, but not in the ASD group; and (3) in the different real-face task, ASD group had higher %Error than the TD group, and %Error was negatively correlated with RT only in the ASD group., Conclusion: The current study delineates the inefficient processing of social-emotional interference in school-aged children with ASD and further suggests that these children might adopt a relatively optimized strategy like symbolization when dealing with emotional conflict. However, such compensatory cognitive strategies may be exhausted along with the increase in information load. These findings provide new perspectives of considering the difference more than difficulty in the cognitive profile of ASD, which will benefit the development of targeted behavioral interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Chen, Zhai, Chen, Wu, Liu and Jin.)

Recognition layer materials play a crucial role in the functionality of chemical sensors. Although advancements in two-dimensional (2D) materials have promoted sensor development, the controlled fabrication of large-scale recognition layers with highly active sites remains crucial for enhancing sensor sensitivity, especially for trace detection applications. Herein, we propose a strategy for the controlled preparation of centimeter-scale non-layered ultrathin β-In 2 S 3 materials with tailored high-active sites to design ultrasensitive Hg 2+ sensors. Our results reveal that the highly active sites of non-layered β-In 2 S 3 materials are pivotal for achieving superior sensing performance. Selective detection of Hg 2+ at the 1 aM level is achieved via selective Hg-S bonding. Additionally, we evaluate that this sensor exhibits excellent performance in detecting Hg 2+ in the tap water matrix. This work provides a proof-of-concept for utilizing non-layered 2D films in high-performance sensors and highlights their potential for diverse analyte sensing applications.

Defect engineering offers a promising approach to enhance the sensitivity of biosensing materials by creating abundant chemically active sites. Despite its potential, achieving precise control and modification of these defects remains a significant challenge. Herein, we propose atomic-level defect engineering in GeP two-dimensional (2D) layered materials, following precise in situ growing Au nanoparticles on the single defect active sites for the design of ultrasensitive biosensors. The GeP-based biosensor exhibits notable capabilities for miRNA detection with excellent chemical stability, sensitivity, selectivity, and an extremely low detection limit of 28.6 aM. When applied to clinical tissue samples from gastric cancer patients, the biosensor effectively quantified the miR378c biomarker, enabling accurate stage-specific monitoring. This research not only represents a crucial advancement in the field of biosensing materials through defect engineering but also provides a promising avenue for early cancer diagnosis, staging, and monitoring.

In this paper, a highly sensitive method for sulfur ion (S 2- ) detection was developed based on a four-color fluorescence probe constructed from copper-containing metal-organic framework (CuBDC) and four dye-labeled single-strand DNA (ssDNA). In the absence of S 2- , dye-labeled ssDNA can be adsorbed on the surface of CuBDC, and the dyes are close to copper ion on the CuBDC surface, their fluorescence is quenched by copper ion, and their fluorescence signals are weak. In the presence of S 2- in the system, S 2- reacts with copper ion in CuBDC to form CuS, which has a more stable structure than complex CuBDC, resulting in the decomposition of CuBDC. In this case, dye-labeled ssDNA are detached from the CuBDC surface and dissolved in the solution, and the fluorescence of the dyes is restored. Under the optimized conditions, there is a good linear relationship between the total fluorescence intensity of four dyes and the concentration of S 2- in the range of 2 × 10 -9 to 5 × 10 -8  mol/L; the detection limit is 2.2 × 10 -10  mol/L. The method has a good selectivity and accuracy, and it can be applied to the analysis and detection of S 2- in actual water samples., (© 2024 John Wiley & Sons Ltd.)

Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers of post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived GBM models and independent lines of validation. Specific genetic dependencies were found consistent across recurrent tumor models, accompanied by increased mutational burden and differential transcript and protein expression compared to its primary GBM predecessor. Our observations suggest a multi-layered genetic response to drive tumor recurrence and implicate PTP4A2 (protein tyrosine phosphatase 4A2) as a modulator of self-renewal, proliferation and tumorigenicity in recurrent GBM. Genetic perturbation or small-molecule inhibition of PTP4A2 acts through a dephosphorylation axis with roundabout guidance receptor 1 (ROBO1) and its downstream molecular players, exploiting a functional dependency on ROBO signaling. Because a pan-PTP4A inhibitor was limited by poor penetrance across the blood-brain barrier in vivo, we engineered a second-generation chimeric antigen receptor (CAR) T cell therapy against ROBO1, a cell surface receptor enriched across recurrent GBM specimens. A single dose of ROBO1-targeted CAR T cells doubled median survival in cell-line-derived xenograft (CDX) models of recurrent GBM. Moreover, in CDX models of adult lung-to-brain metastases and pediatric relapsed medulloblastoma, ROBO1 CAR T cells eradicated tumors in 50-100% of mice. Our study identifies a promising multi-targetable PTP4A-ROBO1 signaling axis that drives tumorigenicity in recurrent GBM, with potential in other malignant brain tumors., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The electrodeposition process confronts significant challenges arising from mass transfer limitation and residual stress. To address these issues, an innovative method, combining megasonic agitation with coaxial jet electrodeposition, is introduced. This approach aims to enhance mass transfer and mitigate residual stress. First, an electrodeposition nozzle device was designed, and the liquid-phase mass transfer during electrodeposition was analyzed through finite element simulation. Simulation results indicate that the mass transfer coefficient increases with rising megasonic power density. Notably, when the megasonic power density reached 20 W/cm 2 , the mass transfer coefficient increased from 0.45 × 10 -7 m/s to 18.63 × 10 -7 m/s, compared to electrodeposition without megasonic agitation. Secondly, electrodeposition experiments were conducted both with and without megasonic assistance. X-ray diffraction (XRD) was employed to measure the residual stress values of the electrodeposited layers. The results reveal that samples processed with megasonic assistance exhibit lower residual stress values compared to those without. Specifically, at a megasonic power density of 10 W/cm 2 , the residual stress was 94.3 MPa, representing a 37.7 % reduction compared to the residual stress of 151.5 MPa observed in samples without megasonic agitation. Overall, the findings demonstrate that coaxial megasonic agitation can effectively enhance the liquid-phase mass transfer capability during electrodeposition and reduce the residual stress of the electroplated layer. This innovative method presents a promising avenue for improving electrodeposition processes and achieving superior material properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We propose and demonstrate a photonic-assisted approach for generating arbitrary microwave waveforms based on a dual-polarization dual-parallel Mach-Zehnder modulator, offering significant advantages in terms of tunability of repetition rates and anti-dispersion capability. In order to generate diverse microwave waveforms, two sinusoidal radio frequency signals with distinct frequency relationships are applied to the dual-polarization dual-parallel Mach-Zehnder modulator. By adjusting the power of the applied sinusoidal radio frequency signal, the power ratio between these orthogonal polarized optical sidebands can be changed, and thereby desired radio frequency waveforms can be obtained after photoelectric conversion. In our proof-of-concept experiment, we systematically varied the repetition rate of triangular, rectangular and sawtooth waveforms. Meanwhile, we calculated the Root Mean Square Error (RMSE) to assess the approximation error in each waveform. The RMSEs are 0.1089, 0.2182 and 0.1185 for the triangular, rectangular and sawtooth microwave waveforms with repetition rate of 8 GHz, respectively. Furthermore, after passing through 25 km single mode fiber, the optical power decreased by approximately 5.6 dB, which verifies the anti-dispersion transmission capability of our signal generator.

Background: Metronidazole is a first-line antibiotic to treat Helicobacter pylori infections. However, the Clinical Laboratory Standards Institute guidelines recommend against using antimicrobial susceptibility test (AST) to test metronidazole resistance, due to the unreliable predictive power which can result in treatment failure., Objectives: The aim of this study was to establish an 8-h, metabolic-phenotype based AST for H. pylori metronidazole susceptibility using D 2 O-probed Raman microspectroscopy., Methods: Minimal inhibitory concentration (MIC) measured by conventional AST (E-test) were compared with expedited MIC via metabolic activity (eMIC-MA) for 10 H. pylori isolates. Raman barcodes of cellular-response to stress (RBCS) incorporating protein and carbohydrate Raman bands, were utilized to identify a biomarker to distinguish metronidazole susceptibility., Results: Specifically, eMIC-MA produces metronidazole susceptibility results showing 100% agreement with E-test, and determines the bactericidal dosage for both high- and low-level resistant H. pylori strains. In addition, RBCS not just reliably distinguish between metronidazole-susceptible and -resistant strains, but reveal their distinct mechanisms in bacterial responses to metronidazole., Conclusion: The speed, accuracy, low cost, and rich information content that reveals the mode-of-action of drugs suggest the method's value in guiding metronidazole prescriptions for H. pylori eradication and in rapid screening based on drug-resistance mechanism., (© 2024 John Wiley & Sons Ltd.)

2D van der Waals (vdW) magnets have recently emerged as a promising material system for spintronic device innovations due to their intriguing phenomena in the reduced dimension and simple integration of magnetic heterostructures without the restriction of lattice matching. However, it is still challenging to realize Curie temperature far above room temperature and controllable magnetic anisotropy for spintronics application in 2D vdW magnetic materials. In this work, the pressure-tuned dome-like ferromagnetic-paramagnetic phase diagram in an iron-based 2D layered ferromagnet Fe 3 GaTe 2 is reported. Continuously tunable magnetic anisotropy from out-of-plane to in-plane direction is achieved via the application of pressure. Such behavior is attributed to the competition between intralayer and interlayer exchange interactions and enhanced DOS near the Fermi level. The study presents the prominent properties of pressure-engineered 2D ferromagnetic materials, which can be used in the next-generation spintronic devices., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Little is known about the synergistic effects of abiotic aging and biodegradation on microplastics (MPs) transformation in the environment. Herein, a hybrid process of MPs degradation was proposed by analyzing the effect of microorganisms and abiotic aging on aging MPs and non-aging MPs degradation during composting. The results showed that composting facilitated the oxidation and depolymerization of aging MPs, and its degradation efficiency was about three times that of non-aging MPs. Further investigation revealed that aging MPs contained higher abundance of plastic-degrading bacteria and enzyme activity than non-aging MPs. In addition, free radicals also influenced the degradation of MPs. However, path model and shielding experiments confirmed that free radicals mainly facilitated the non-aging MPs degradation (contribution was 68.8 %), while aging MPs was easily degraded by microorganisms (contribution was 72.6 %). This study provides promising strategies for scaling up plastic treatment in bioreactors through a hybrid collaboration of biological and abiotic processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

In order to address the problem of poor localization in electrochemical machining (ECM), a coaxial megasonic assisted jet ECM method was proposed. Based on theoretical analysis, experiments were conducted to compare the effects of various electrolyte flow rates, electrolytic voltage and megasonic power levels on pit ECM. The results indicate that, in the range of experimental parameters, the increase of electrolyte flow rate and megasonic power can increase the machining depth, so as to improve the depth-diameter ratio of ECM pits. The use of coaxial megasonic-assisted jet ECM can enhance the depth-diameter ratio of etched pits compared to the without megasonic one. When applying a megasonic power of 22 W, the dimensions of the ECM pit were measured as 0.81 mm in depth and 5.73 mm in diameter, resulting in an depth-diameter ratio of 0.140. Under the same conditions, without megasonic assistance, the pit diameter is reduced to 0.65 mm while the pit depth increases to 6.36 mm, resulting in a depth-diameter ratio of 0.102. Additionally, The results also demonstrate that, the increase of electrolytic voltage makes the depth to diameter ratio of pit further increase on the original basis. With an electrolyte flow rate of 0.9 L/min and a megasonic power of 22 W, the use of electrolysis voltage of 50 V increased the depth-diameter ratio of etched pits to 0.173. Using the above preferred parameters, electrolytic milling of the wide groove is carried out. The depth-diameter ratio of the wide groove is increased from 0.039 to 0.059 by appending coaxial megasonic. This further verified the effectiveness of the coaxial megasonic-assisted jet ECM method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Kale is a functional food with anti-cancer, antioxidant, and anemia prevention properties. The harmful effects of the emerging pollutant microplastic (MP) on plants have been widely studied, but there is limited research how to mitigate MP damage on plants. Numerous studies have shown that Se is involved in regulating plant resistance to abiotic stresses. The paper investigated impact of MP and Se on kale growth, photosynthesis, reactive oxygen species (ROS) metabolism, phytochemicals, and endogenous hormones. Results revealed that MP triggered a ROS burst, which led to breakdown of antioxidant system in kale, and had significant toxic effects on photosynthetic system, biomass, and accumulation of secondary metabolites, as well as a significant decrease in IAA and a significant increase in GA. Under MP supply, Se mitigated the adverse effects of MP on kale by increasing photosynthetic pigment content, stimulating function of antioxidant system, enhancing secondary metabolite synthesis, and modulating hormonal networks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The extraction of total flavonoids from Hylotelephium spectabile (Boreau) H. Ohba ( H. spectabile ) leaves was studied through the use of a double enzyme-assisted ultrasonic method, and the extraction process was optimized using the Box-Behnken design. Eight different macroporous resins were screened for purification in single-factorial experiments, and the flavonoid compounds in the extract of H. spectabile leaves were identified using HPLC-MS. Through the evaluation of the total reducing capacity and capacity for reducing 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH), hydroxyl radicals (·OH), and 2,2'-biazobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), the in vitro antioxidant activities of the crude extracts of the total flavonoids and purified total flavonoids of H. spectabile leaves were investigated. The results showed that the most efficient conditions for flavonoid extraction were an ultrasonic extraction time of 60 min, an ethanol concentration of 35%, a liquid-to-material ratio of 20:1 mL/g, and an amount of enzyme (cellulose/pectinase = 1:1) of 1.5%, forming H. spectabile powder. Under these conditions, the total flavonoid extraction rate in the H. spectabile leaf extract was 4.22%. AB-8 resin showed superior performance in terms of purification, and the optimal adsorption and desorption times were 1.5 h and 3 h, respectively. The recommended parameters for purification included a liquid volume of 5.5 BV, a flow rate of 1.2 BV/min, a pH of 5, and a concentration of 0.8 mg/mL. The observed order for reducing capacity was ascorbic acid (VC) > rutin > purified total flavonoids > crude extract of total flavonoids. The purified total flavonoid extract from H. spectabile showed a good scavenging ability against DPPH, ·OH, and ABTS ·+ , suggesting strong antioxidant activity. Therefore, this study can serve as technical support and reference data for the further development and utilization of H. spectabile resources.

Background : Extracorporeal life support echniques as an Adjunct to Advanced Cardiac Life Support is usually suitable for complex heart surgery such as cardiopulmonary bypass (CPB). Cerebral perfusion is a clinically feasible neuroprotective strategy; however, the lack of a reliable small animal model. Methods : Based on the rat model of ECLS we evaluate the effects of ECLS-CP using HE staining, Nissl staining, TUNEL staining and ELISA. Result : We found that ECLS combined with the cerebral perfusion model did not cause brain injury and immune inflammation. There was no difference between the two by a left carotid artery or right carotid artery CP. Conclusion : These experimental results can provide the experimental basis for selecting blood vessels for ECLS patients and clinical CP to offers a trustworthy animal model for future exploration of applying brain perfusion strategies during ECLS-CP., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The surface of three-dimensional materials provides an ideal and versatile platform to explore quantum-confined physics. Here, we systematically investigate the electronic structure of Na-intercalated CrTe 2 , a van der Waals antiferromagnet, using angle-resolved photoemission spectroscopy and ab initio calculations. The measured band structure deviates from the calculation of bulk NaCrTe 2 but agrees with that of ferromagnetic monolayer CrTe 2 . Consistently, we observe unexpected exchange splitting of the band dispersions, persisting well above the Néel temperature of bulk NaCrTe 2 . We argue that NaCrTe 2 features a quantum-confined 2D ferromagnetic state in the topmost surface layer due to strong ferromagnetic correlation in the CrTe 2 layer. Moreover, the exchange splitting and the critical temperature can be controlled by surface doping of alkali-metal atoms, suggesting the feasibility of tuning the surface ferromagnetism. Our work not only presents a simple platform for exploring tunable 2D ferromagnetism but also provides important insights into the quantum-confined low-dimensional magnetic states.

Introduction: Exosome-miR-146a is significantly increased in patients with Atherosclerosis (AS), but its mechanism and effect on AS have not been fully elucidated., Objectives: To explore the change rule and mechanism of exosomes release, and the role and molecular mechanism of exosome-miR-146a in AS., Methods: We isolated and identified exosomes from THP-1 macrophages after treating them with ox-LDL. Then used co-immunoprecipitation and silver staining to identify the proteins involved in regulating exosome release. PKH67 was used to label exosomes to confirm that cells can absorb them, and then co-culture with HVSMCs for cell proliferation and migration detection. The target genes of miR-146a were screened and identified through bioinformatics and luciferase activity assay, and the expression of miR-146a and related proteins was detected through qRT-PCR and Western blot in HUVECs. An AS model in LDLR -/- mice induced by a high-fat diet was developed to investigate the impact of exosome-miR-146a on AS., Results: The results showed that experimental foam cells from AS showed higher expression of miR-146a. It was observed that NMMHC IIA and HSP70 interacted to regulate the release of exosomes. And HUVECs can absorb exosomes derived from macrophages. In addition, we also found that miR-146a directly targeted the SMAD4 gene to modulate the p38 MAPK signaling pathway, thereby mediating HUVECs damage. Furthermore, exosome-miR-146a induced abnormal proliferation and migration of HVSMCs. The expression of miR-146a was significantly reduced in miR-146a-mimics mice and increased in miR-146a inhibitor mice whereas the inhibition of miR-146a effectively reduced while increasing miR-146a worsened AS in mice., Conclusion: Our findings expressed the potential of miR-146a as a favorable therapeutic target for AS, however, further exploration is suggestive for deep understanding of the mechanisms regulating exosome-miR-146a release in vivo and to develop effective therapeutic strategies involving miR-146a., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Nanocomposites are sophisticated materials that incorporate nanostructures into matrix materials, such as polymers, ceramics and metals. Generally, the marine ecosystem exhibits severe variability in terms of light, temperature, pressure, and nutrient status, forcing the marine organisms to develop variable, complex and unique chemical structures to boost their competitiveness and chances of survival. Polymers sourced from marine creatures, such as chitin, chitosan, alginate, sugars, proteins, and collagen play a crucial role in the bioengineering field, contributing significantly to the development of nanostructures like nanoparticles, nanocomposites, nanotubes, quantum dots, etc. These nanostructures offer a wide array of features involving mechanical strength, thermal stability, electrical conductivity, barrier and optical characteristics compared to traditional composites. Notably, marine nanocomposites have distinctive roles in a wide spectrum of applications, among them anti-cancer, anti-microbial, antioxidant, cytotoxic, food packing, tissue engineering and catalytic actions. Sol-gel, hot pressing, chemical vapor deposition, catalytic decomposition, dispersion, melt intercalation, in situ intercalative polymerization, high-energy ball milling and template synthesis are common processes utilized in engineering nanocomposites. According to our literature survey and the Web of Science, chitosan, followed by cellulose, chitin and MAPs emerge as the most significant marine polymers utilized in the construction of nanocomposites. Taken together, the current manuscript underscores the biogenesis of nanocomposites, employing marine polymers using eco-friendly processes. Furthermore, significant emphasis in this area is needed to fully explore their capabilities and potential benefits. To the best of our knowledge, this manuscript stands as the first comprehensive review that discusses the role of marine-derived polymers in engineering nanocomposites for various applications., Competing Interests: Declaration of competing interest The author has no declaration of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The intratumoral microbiota can modulate the tumor immune microenvironment (TIME); however, the underlying mechanism by which intratumoral microbiota influences the TIME in urothelial carcinoma of the bladder (UCB) remains unclear. To address this, we collected samples from 402 patients with UCB, including paired host transcriptome and tumor microbiome data, from The Cancer Genome Atlas (TCGA). We found that the intratumoral microbiome profiles were significantly correlated with the expression pattern of epithelial-mesenchymal transition (EMT)-related genes. Furthermore, we detected that the genera Lachnoclostridium and Sutterella in tumors could indirectly promote the EMT program by inducing an inflammatory response. Moreover, the inflammatory response induced by these two intratumoral bacteria further enhanced intratumoral immune infiltration, affecting patient survival and response to immunotherapy. In addition, an independent immunotherapy cohort of 348 patients with bladder cancer was used to validate our results. Collectively, our study elucidates the potential mechanism by which the intratumoral microbiota influences the TIME of UCB and provides a new guiding strategy for the targeted therapy of UCB. NEW & NOTEWORTHY The intratumoral microbiota may mediate the bladder tumor inflammatory response, thereby promoting the epithelial-mesenchymal transition program and influencing tumor immune infiltration.

The sustained circulation of H9N2 avian influenza viruses (AIVs) poses a significant threat for contributing to a new pandemic. Given the temporal and spatial uncertainty in the antigenicity of H9N2 AIVs, the immune protection efficiency of vaccines remains challenging. By developing an antigenicity prediction method for H9N2 AIVs, named PREDAC-H9, the global antigenic landscape of H9N2 AIVs was mapped. PREDAC-H9 utilizes the XGBoost model with 14 well-designed features. The XGBoost model was built and evaluated to predict the antigenic relationship between any two viruses with high values of 81.1 %, 81.4 %, 81.3 %, 81.1 %, and 89.4 % in accuracy, precision, recall, F1 value, and area under curve (AUC), respectively. Then the antigenic correlation network (ACnet) was constructed based on the predicted antigenic relationship for H9N2 AIVs from 1966 to 2022, and ten major antigenic clusters were identified. Of these, four novel clusters were generated in China in the past decade, demonstrating the unique complex situation there. To help tackle this situation, we applied PREDAC-H9 to calculate the cluster-transition determining sites and screen out virus strains with the high cross-protective spectrum, thus providing an in silico reference for vaccine recommendation. The proposed model will reduce the clinical monitoring workload and provide a useful tool for surveillance and control of H9N2 AIVs., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. There is no financial/personal interest or belief that could affect their objectivity., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Ultrasensitive detection of biomarkers, particularly proteins, and microRNA, is critical for disease early diagnosis. Although surface plasmon resonance biosensors offer label-free, real-time detection, it is challenging to detect biomolecules at low concentrations that only induce a minor mass or refractive index change on the analyte molecules. Here an ultrasensitive plasmonic biosensor strategy is reported by utilizing the ferroelectric properties of Bi 2 O 2 Te as a sensitive-layer material. The polarization alteration of ferroelectric Bi 2 O 2 Te produces a significant plasmonic biosensing response, enabling the detection of charged biomolecules even at ultralow concentrations. An extraordinary ultralow detection limit of 1 fm is achieved for protein molecules and an unprecedented 0.1 fm for miRNA molecules, demonstrating exceptional specificity. The finding opens a promising avenue for the integration of 2D ferroelectric materials into plasmonic biosensors, with potential applications spanning a wide range., (© 2024 Wiley‐VCH GmbH.)

In this study, polysaccharides were extracted at a rate of 87.5% ± 1.5% from native dandelion roots, and the dandelion root polysaccharides (DRPs) were then chemically modified to obtain sulfated polysaccharides (SDRPs) with a degree of substitution of 1.49 ± 0.07. The effects of modification conditions, physicochemical characterizations, structural characteristics, antioxidant properties, hypoglycemic activity, and proliferative effects on probiotics of DRP derivatives were further investigated. Results showed that the optimum conditions for sulfation of DRPs included esterification reagents (concentrated sulfuric acid: n -butanol) ratio of 3:1, a reaction temperature of 0 °C, a reaction time of 1.5 h, and the involvement of 0.154 g of ammonium sulfate. The DRPs and SDRPs were composed of six monosaccharides, including mannose, glucosamine, rhamnose, glucose, galactose, and arabinose. Based on infrared spectra, the peaks of the characteristic absorption bands of S=O and C-O-S appeared at 1263 cm -1 and 836 cm -1 . Compared with DRPs, SDRPs had a significantly lower relative molecular mass and a three-stranded helical structure. NMR analysis showed that sulfated modification mainly occurred on the hydroxyl group at C6. SDRPs underwent a chemical shift to higher field strength, with their characteristic signal peaking in the region of 1.00-1.62 ppm. Scanning electron microscopy (SEM) analysis indicated that the surface morphology of SDRPs was significantly changed. The structure of SDRPs was finer and more fragmented than DRPs. Compared with DRPs, SDRPs showed better free radical scavenging ability, higher Fe 2+ chelating ability, and stronger inhibition of α-glucosidase and α-amylase. In addition, SDRPs had an excellent promotional effect on the growth of Lactobacillus plantarum 10665 and Lactobacillus acidophilus . Therefore, this study could provide a theoretical basis for the development and utilization of DRPs.

Atherosclerosis (AS) is a common cardiovascular disease that poses a major threat to health. Schisandra chinensis is a medicinal and edible plant that is commonly used to treat cardiovascular diseases. In this paper, HPLC was used to detect and analyze 5 different components in Schisandra chinensis . Network pharmacological predictions highlight the PI3K/AKT/mTOR pathway as an important pharmacological pathway. The effective ingredient Schisandrin C was screened by the molecular docking technique. ox-LDL-induced HUVECs were used to construct the atherosclerosis model for further experimental verification. The results showed that Schisandrin C interfered with the PI3K/AKT/mTOR autophagy pathway. This study lays a foundation for the further application of Schisandrin C in the prevention and treatment of atherosclerosis in the future., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Revision of tumor-type prosthetic fractures is very challenging in clinical work. Traditional repair methods may not be able to meet the needs of complex cases or cause greater bone damage. Therefore, more effective and reliable solutions need to be found., Case Presentation: This study presents a novel revision technique for managing fractures of tumor-type total elbow prostheses. A 57-year-old female patient was diagnosed with a left distal humeral bone tumor accompanied by pathological fracture and underwent customized tumor-type total elbow prosthesis arthroplasty. After 5 years, she experienced pain and encountered difficulty in flexing the left elbow while lifting heavy objects. The X-ray examination revealed a fracture of the distal humeral prosthesis. As a response, the elbow joint was initially explored, and the damaged component of the prosthesis was extracted. Subsequently, we utilized 3D printing technology to design a split-piece sleeve prosthesis and effectively restored the fractured left distal humerus implant. During the 2-year follow-up, The X-ray demonstrated satisfactory positioning of the prosthesis, which remained securely affixed without any indications of loosening. The Mayo Elbow Performance Score (MEPS) reached 80 points, the Musculoskeletal Tumor Society (MSTS) attained a score of 28 points, and the range of motion of the elbow was measured between 25° and 110°, revealing favorable functional outcomes., Conclusion: The utilization of a 3D printed split-piece sleeve prosthesis presents a viable clinical treatment strategy for addressing fractures in tumor-type elbow prostheses., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Microplastic (MP), as a new pollutant, not only affects the growth and development of plants but also may affect the secondary metabolites of plants. The anti-tumor role of Pinellia ternata is related to secondary metabolites. The role of brassinolide (BR) in regulating plant resistance is currently one of the research hotspots. The paper mainly explores the regulation of BR on growth and physiology of Pinellia ternata under MP stress. The experimental design includes two levels of MP (0, 1%) and two levels of BR (0, 0.1 mg/L). MP led to a marked reduction in plant height (15.0%), Fv/Fm (3.2%), SOD and APX activity (15.0%, 5.1%), whereas induced an evident raise in the rate of O 2 · - production (29.6%) and GSH content (4.4%), as well as flavonoids (6.8%), alkaloids (75%), and β-sitosterol (26.5%) contents. Under MP addition, BR supply significantly increased plant height (15.7%), aboveground and underground biomass (16.1%, 10.3%), carotenoid and GSH content (11.8%, 4.2%), Fv/Fm (2.9%), and activities of SOD, GR, and MDHAR (32.2%, 21.08%, 20.9%). These results indicate that MP suppresses the growth of P. ternata, although it promotes secondary metabolism. BR can alleviate the inhibitory effect of MP on growth by improving photosynthesis, redox homeostasis, and the AsA-GSH cycle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The H1N1pdm09 virus has been a persistent threat to public health since the 2009 pandemic. Particularly, since the relaxation of COVID-19 pandemic mitigation measures, the influenza virus and SARS-CoV-2 have been concurrently prevalent worldwide. To determine the antigenic evolution pattern of H1N1pdm09 and develop preventive countermeasures, we collected influenza sequence data and immunological data to establish a new antigenic evolution analysis framework. A machine learning model (XGBoost, accuracy = 0.86, area under the receiver operating characteristic curve = 0.89) was constructed using epitopes, physicochemical properties, receptor binding sites, and glycosylation sites as features to predict the antigenic similarity relationships between influenza strains. An antigenic correlation network was constructed, and the Markov clustering algorithm was used to identify antigenic clusters. Subsequently, the antigenic evolution pattern of H1N1pdm09 was analyzed at the global and regional scales across three continents. We found that H1N1pdm09 evolved into around five antigenic clusters between 2009 and 2023 and that their antigenic evolution trajectories were characterized by cocirculation of multiple clusters, low-level persistence of former dominant clusters, and local heterogeneity of cluster circulations. Furthermore, compared with the seasonal H1N1 virus, the potential cluster-transition determining sites of H1N1pdm09 were restricted to epitopes Sa and Sb. This study demonstrated the effectiveness of machine learning methods for characterizing antigenic evolution of viruses, developed a specific model to rapidly identify H1N1pdm09 antigenic variants, and elucidated their evolutionary patterns. Our findings may provide valuable support for the implementation of effective surveillance strategies and targeted prevention efforts to mitigate the impact of H1N1pdm09., (© 2024 Wiley Periodicals LLC.)

The accurate diagnosis of diabetic nephropathy relies on achieving ultrasensitive biosensing for biomarker detection. However, existing biosensors face challenges such as poor sensitivity, complexity, time-consuming procedures, and high assay costs. To address these limitations, we report a WS 2 -based plasmonic biosensor for the ultrasensitive detection of biomarker candidates in clinical human urine samples associated with diabetic nephropathy. Leveraging plasmonic-based electrochemical impedance microscopy (P-EIM) imaging, we observed a remarkable charge sensitivity in monolayer WS 2 single crystals. Our biosensor exhibits an exceptionally low detection limit (0.201 ag/mL) and remarkable selectivity in detecting CC chemokine ligand 2 (CCL2) protein biomarkers, outperforming conventional techniques such as ELISA. This work represents a breakthrough in traditional protein sensors, providing a direction and materials foundation for developing ultrasensitive sensors tailored to clinical applications for biomarker sensing.

Imaging the surface charge of biomolecules such as proteins and DNA, is crucial for comprehending their structure and function. Unfortunately, current methods for label-free, sensitive, and rapid imaging of the surface charge of single DNA molecules are limited. Here, we propose a plasmonic microscopy strategy that utilizes charge-sensitive single-crystal monolayer WS 2 materials to image the local charge density of a single λ-DNA molecule. Our study reveals that WS 2 is a highly sensitive charge-sensitive material that can accurately measure the local charge density of λ-DNA with high spatial resolution and sensitivity. The consistency of the surface charge density values obtained from the single-crystal monolayer WS 2 materials with theoretical simulations demonstrates the reliability of our approach. Our findings suggest that this class of materials has significant implications for the development of label-free, scanning-free, and rapid optical detection and charge imaging of biomolecules.

'Not in My Back Yard (NIMBY)' facilities are psychologically sensitive to urban and regional development. Multi-criteria evaluation (MCE) method has been widely used for the decision-making of optimum siting of urban NIMBY facilities which aim to improve residents' psychological satisfaction. However, the evaluation of qualitative criteria in siting analysis remains under researched, such as the insufficient focus on urban and regional spatial development, social public opinion, and psychological factors. Thus, the effective improvement of MCE method through an interdisciplinary view can optimise the decision process and advance the factor assessment system of siting, which helps to supplement qualitative criteria evaluation. The specific improvement steps are as follows. The first step is to introduce the mixed MCE method to improve the qualitative criteria evaluation method by pre-processing qualitative criteria with min-max standardisation and normalization. This process transfers all negative factors to positive ones and transforms the F function to linear functions. The second step is to optimise the existing two-phase siting decision-making including the feasibility evaluation phase and the MCE phase. The third step is to propose a modular criteria system composed of urban and regional spatial planning, social psychological factors and the corresponding improvement strategy of this system from three perspectives of composition, measure, and weight. We argue that the improved method could be broadly applied to optimum siting decision of urban NIMBY facilities and enhance the psychological satisfaction of residents., (© 2024. The Author(s).)

In recent years, concerns have been raised regarding the contamination of grapes with pesticide residues. As consumer demand for safer food products grows, regular monitoring of pesticide residues in food has become essential. This study sought to develop a rapid and sensitive technique for detecting two specific pesticides (phosmet and paraquat) present on the grape surface using the surface-enhanced Raman spectroscopy (SERS) method. Gold nanostars (AuNS) particles were synthesized, featuring spiky tips that act as hot spots for localized surface plasmon resonance, thereby enhancing Raman signals. Additionally, the roughened surface of AuNS increases the surface area, resulting in improved interactions between the substrate and analyte molecules. Prominent Raman peaks of mixed contaminants were acquired and used to characterize and quantify the pesticides. It was observed that the SERS intensity of the Raman peaks changed in proportion to the concentration ratio of phosmet and paraquat. Moreover, AuNS exhibited superior SERS enhancement compared to gold nanoparticles. The results demonstrate that the lowest detectable concentration for both pesticides on grape surfaces is 0.5 mg/kg. These findings suggest that SERS coupled with AuNS constitutes a practical and promising approach for detecting and quantifying trace contaminants in food. PRACTICAL APPLICATION: This research established a novel surface-enhanced Raman spectroscopy (SERS) method coupled with a simplified extraction protocol and gold nanostar substrates to detect trace levels of pesticides in fresh produce. The detection limits meet the maximum residue limits set by the EPA. This substrate has great potential for rapid measurements of chemical contaminants in foods., (© 2024 Institute of Food Technologists.)

Ethnopharmacological Relevance: Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy in China. Most tumors develop from chronic inflammation. Artemisia rupestris L. (ARL) has been found to have a significant effect on viral influenza and hepatitis, but the mechanism of action of ARL against liver cancer is unclear., Aim of the Study: The study objective was to explore the mechanism of action of ARL for the treatment of hepatocellular carcinoma (HCC) by ethanol extract and in vitro experimental design., Materials and Methods: Interactions between ARL and cellular target proteins against HCC were analyzed through network pharmacology and network topology with the utilization of the DAVID database. The rate of HepG2 cells' growth inhibition was assessed using the MTT assay in vitro cellular assay; hoechst33342 detects apoptosis of cells; the ability of HepG2 cells to migrate and invade was assessed using the transwell assay and the cell scratch experiment; and the levels of protein expression in HepG2 cells were assessed using the western blot assay., Results: Network pharmacology prediction results demonstrated that 22 active ingredients were tested, 176 possible action targets were discovered, and the PI3K/Akt signaling pathway was found to be the most pertinent action pathway for the treatment of hepatocellular carcinoma. In vitro results showed that it can effectively restrict HepG2 cell proliferation, apoptosis, migration, and invasion as well as the regulation of protein expressions., Conclusion: Conclusively, Quercetin, Linarin, and Kaempferol were found most essential active ingredients from ARL that regulate the antitumor effects against HCC through the PI3K/Akt signaling pathway. The study provides a fundamental basis for further comprehensive evaluation of ARL to treat tumor diseases in general and its therapeutic potential against hepatocellular carcinoma in particular., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Since 2020, clade 2.3.4.4b highly pathogenic avian influenza H5N8 and H5N1 viruses have swept through continents, posing serious threats to the world. Through comprehensive analyses of epidemiological, genetic, and bird migration data, we found that the dominant genotype replacement of the H5N8 viruses in 2020 contributed to the H5N1 outbreak in the 2021/2022 wave. The 2020 outbreak of the H5N8 G1 genotype instead of the G0 genotype produced reassortment opportunities and led to the emergence of a new H5N1 virus with G1's HA and MP genes. Despite extensive reassortments in the 2021/2022 wave, the H5N1 virus retained the HA and MP genes, causing a significant outbreak in Europe and North America. Furtherly, through the wild bird migration flyways investigation, we found that the temporal-spatial coincidence between the outbreak of the H5N8 G1 virus and the bird autumn migration may have expanded the H5 viral spread, which may be one of the main drivers of the emergence of the 2020-2022 H5 panzootic.IMPORTANCESince 2020, highly pathogenic avian influenza (HPAI) H5 subtype variants of clade 2.3.4.4b have spread across continents, posing unprecedented threats globally. However, the factors promoting the genesis and spread of H5 HPAI viruses remain unclear. Here, we found that the spatiotemporal genotype replacement of H5N8 HPAI viruses contributed to the emergence of the H5N1 variant that caused the 2021/2022 panzootic, and the viral evolution in poultry of Egypt and surrounding area and autumn bird migration from the Russia-Kazakhstan region to Europe are important drivers of the emergence of the 2020-2022 H5 panzootic. These findings provide important targets for early warning and could help control the current and future HPAI epidemics., Competing Interests: The authors declare no conflict of interest.

Objectives: To establish a three-dimensional finite element model of the upper palate, pharyngeal cavity, and levator veli palatini muscle in patients with unilateral complete cleft palate, simulate two surgical procedures that the two-flap method and Furlow reverse double Z method, observe the stress distribution of the upper palate soft tissue and changes in pharyngeal cavity area after different surgical methods, and verify the accuracy of the model by reconstructing and measuring the levator veli palatini muscle., Materials and Methods: Mimics, Geomagic, Ansys, and Hypermesh were applied to establish three-dimensional finite element models of the pharyngeal cavity, upper palate, and levator veli palatini muscle in patients with unilateral complete cleft palate. The parameters including length, angle, and cross-sectional area of the levator veli palatini muscle etc. were measured in Mimics, and two surgical procedures that two-flap method and Furlow reverse double Z method were simulated in Ansys, and the area of pharyngeal cavity was measured by hypermesh., Results: A three-dimensional finite element model of the upper palate, pharyngeal cavity, and bilateral levator veli palatini muscle was established in patients with unilateral complete cleft palate ; The concept of horizontal projection characteristics of the palatal dome was applied to the finite element simulation of cleft palate surgery, vividly simulating the displacement and elastic stretching of the two flap method and Furlow reverse double Z method during the surgical process; The areas with the highest stress in the two-flap method and Furlow reverse double Z method both occur in the hard soft palate junction area; In resting state, as measured, the two flap method can narrow the pharyngeal cavity area by 50.9%, while the Furlow reverse double Z method can narrow the pharyngeal cavity area by 65.4%; The measurement results of the levator veli palatini muscle showed no significant difference compared to previous studies, confirming the accuracy of the model., Conclusions: The finite element method was used to establish a model to simulate the surgical procedure, which is effective and reliable. The area with the highest postoperative stress for both methods is the hard soft palate junction area, and the stress of the Furlow reverse double Z method is lower than that of the two-flap method. The anatomical conditions of pharyngeal cavity of Furlow reverse double Z method are better than that of two-flap method in the resting state., Clinical Relevance: This article uses three-dimensional finite element method to simulate the commonly used two-flap method and Furlow reverse double Z method in clinical cleft palate surgery, and analyzes the stress distribution characteristics and changes in pharyngeal cavity area of the two surgical methods, in order to provide a theoretical basis for the surgeon to choose the surgical method and reduce the occurrence of complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid (CGA) treatment of acute kidney injury (AKI) in mice., Method: Twenty-four C57Bl/6J mice were randomized into sham-operated group, cecal ligation and puncture (CLP) group, CLP+dexamethasone group (CLP+DXM group), and CLP+CGA group ( n =6) and subjected to either sham operation (laparotomy only) or CLP. After modeling the mice received intravenous infusion of 10 mg/kg normal saline (in sham and CLP groups), 1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump. Eight hours after the infusion, renal morphology and histology, renal cell apoptosis, and the renal function parameters such as urea nitrogen (BUN), creatinine (Scr), and kidney injury molecule 1 (KIM-1) were compared among the 4 groups; the 7-day survival rates of the mice were recorded, and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected., Results: CGA treatment significantly improved the 7-day survival rate, reduced renal pathologies of the septic mice ( P < 0.05), and lowered the levels of BUN, Scr, KIM-1, NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway., Conclusion: CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

Colorectal cancer (CRC) and gastric cancer (GC) rank the top five common and lethal cancers worldwide. Early detection can significantly reduce the mortality of CRC and GC. However, current clinical screening methods including invasive endoscopic techniques and noninvasive fecal occult blood test screening tests/fecal immunochemical test have shown low sensitivity or unsatisfactory patient's compliance. Aberrant DNA methylation occurs frequently in tumorigenesis and cell-free DNA (cfDNA) methylation has shown the potential in multi-cancer detection. Herein, we aimed to explore the value of cfDNA methylation in the gastrointestinal cancer detection and develop a noninvasive method for CRC and GC detection. We applied targeted methylation sequencing on a total of 407 plasma samples from patients diagnosed with CRC, GC, and noncancerous gastrointestinal benign diseases (Non-Ca). By analyzing the methylation profiles of 34 CRC, 62 GC and 107 Non-Ca plasma samples in the training set (n=203), we identified 40,110 gastrointestinal cancer-specific markers and 63 tissue of origin (TOO) prediction markers. A new integrated model composed of gastrointestinal cancer detection and TOO prediction for three types of classification of CRC, GC and Non-Ca patients was further developed through logistic regression algorithm and validated in an independent validation set (n=103). The model achieved overall sensitivities of 83% and 81.3% at specificities of 81.5% and 80% for identifying gastrointestinal cancers in the test set and validation set, respectively. The detection sensitivities for GC and CRC were respectively 81.4% and 83.3% in the cohort of the test and validation sets. Among these true positive cancer samples, further TOO prediction showed accuracies of 95.8% and 95.8% for GC patients and accuracies of 86.7% and 93.3% for CRC patients, in test set and validation set, respectively. Collectively, we have identified novel cfDNA methylation biomarkers for CRC and GC detection and shown the promising potential of cfDNA as a noninvasive gastrointestinal cancer detection tool., Competing Interests: Ying Wen, Xixiang Tu, Hong Wang, Jinsheng Tao, Weimei Ruan, Zhiwei Chen and Jian-Bing Fan are/were employee of AnchorDx. Medical. Co., Ltd. or AnchorDx, Inc., (AJCR Copyright © 2024.)

Background: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited., Methods: In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45 + cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2 hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models., Results: Our results characterized the CD45 + cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C + monocytes and interacted with effector CD4 + T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2 hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP., Conclusion: Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP's cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets., (© 2024. The Author(s).)

Purpose: Brain metastases (BM) are mainly treated palliatively with an expected survival of less than 12 months after diagnosis. In many solid tumors, the human neural stem cell marker glycoprotein CD133 is a marker of a tumor-initiating cell population that contributes to therapy resistance, relapse, and metastasis., Experimental Design: Here, we use a variant of our previously described CD133 binder to generate second-generation CD133-specific chimeric antigen receptor T cells (CAR-T) to demonstrate its specificity and efficacy against multiple patient-derived BM cell lines with variable CD133 antigen expression., Results: Using both lung- and colon-BM patient-derived xenograft models, we show that a CD133-targeting CAR-T cell therapy can evoke significant tumor reduction and survival advantage after a single dose, with complete remission observed in the colon-BM model., Conclusions: In summary, these data suggest that CD133 plays a critical role in fueling the growth of BM, and immunotherapeutic targeting of this cell population is a feasible strategy to control the outgrowth of BM tumors that are otherwise limited to palliative care. See related commentary by Sloan et al., p. 477., (©2023 American Association for Cancer Research.)

Ferroptosis, a type of regulated cell death driven by iron-dependent lipid peroxidation, is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species. Ferroptosis is a prevalent and primitive form of cell death. Numerous cellular metabolic processes regulate ferroptosis, including redox homeostasis, iron regulation, mitochondrial activity, amino acid metabolism, lipid metabolism, and various disease-related signaling pathways. Ferroptosis plays a pivotal role in cancer therapy, particularly in the eradication of aggressive malignancies resistant to conventional treatments. Multiple studies have explored the connection between ferroptosis and bladder cancer, focusing on its incidence and treatment outcomes. Several biomolecules and tumor-associated signaling pathways, such as p53, heat shock protein 1, nuclear receptor coactivator 4, RAS-RAF-MEK, phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin, and the Hippo-tafazzin signaling system, exert a moderating influence on ferroptosis in bladder cancer. Ferroptosis inducers, including erastin, artemisinin, conjugated polymer nanoparticles, and quinazolinyl-arylurea derivatives, hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment. Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer. In this review, we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment., (© 2024. Huazhong University of Science and Technology.)