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Ethylene is widely recognized as a positive regulator of leaf senescence. However, how plants coordinate the biosynthesis of ethylene to meet the requirements of senescence progression has not been determined. The rate-limiting enzyme in the ethylene biosynthesis pathway is ACC synthase. AtACS7 was previously considered one of the major contributors to the synthesis of "senescence ethylene" in Arabidopsis . However, the "brake signal" that fine-tunes the expression of AtACS7 to ensure optimal ethylene production during leaf development has yet to be identified. In the present study, the RING-H2 zinc-finger protein RIE1 was found to specifically interact with and ubiquitinate AtACS7, among all functional ACSs in Arabidopsis , to promote its degradation. Overexpression of RIE1 markedly decreased ethylene biosynthesis and delayed leaf senescence, whereas loss of function of RIE1 significantly increased ethylene emission and accelerated leaf senescence. The ethylene-related phenotypes of RIE1 overexpressing or knockout mutants were effectively rescued by the ethylene precursor ACC or the competitive inhibitor of ACS, respectively. In particular, AtACS7-induced precocious leaf senescence was strongly enhanced by the loss of RIE1 but was significantly attenuated by the overexpression of RIE1 . The specific regions of interaction between AtACS7 and RIE1, as well as the major ubiquitination sites of AtACS7, were further investigated. All results demonstrated that RIE1 functions as an important modulator of ethylene biosynthesis during leaf development by specifically targeting AtACS7 for degradation, thereby enabling plants to produce the optimal levels of ethylene needed., Competing Interests: Competing interests statement:The authors declare no competing interest.

Lacticaseibacillus rhamnosus grx10 (grx10) has shown promising potential in promoting intestinal health as predicted by genomic and metabolomic analyses. Given the increasing prevalence of ulcerative colitis (UC) and the limitations of existing treatments, exploring alternative therapeutic strategies is essential. This study explored the therapeutic effects and underlying mechanisms of grx10 and its derived postbiotic (P-grx10) in a mouse model of dextran sulfate sodium (DSS)-induced chronic UC. The intervention with grx10 and P-grx10 significantly alleviated clinical symptoms and improved biochemical markers in UC mice. These effects included reducing the disease activity index (DAI), improving colon length and histopathological damage, decreasing the secretion of inflammatory cytokines, and preventing the reduction of antioxidant enzymes. Additionally, grx10 and P-grx10 downregulated key proteins in the Mitogen-Activated Protein Kinase (MAPK)/myosin light chain kinase (MLCK)/myosin light chain (MLC) pathway, prevented the dissociation of tight junction (TJ) proteins and E-cadherin, reduced intestinal permeability, and restored the integrity of the intestinal barrier. Furthermore, both grx10 and P-grx10 modulated the composition and abundance of gut microbiota, helping to maintain intestinal microbiome homeostasis. In conclusion, this study provided evidence regarding the role of grx10 and P-grx10 in alleviating intestinal barrier dysfunction associated with UC and restoring gut microbiota balance. Notably, P-grx10 exhibited higher anti-inflammatory activity and better restoration of intestinal barrier function, whereas the live probiotic grx10 showed a stronger regulatory effect on the gut microbiota. These findings suggest that grx10 and P-grx10 could serve as promising nutritional adjunct therapies for UC, providing novel insights into the distinct roles of probiotic and its derived postbiotic in UC treatment., (© 2024 Institute of Food Technologists.)

Bacillus subtilis has been reported to maintain the homeostasis of intestinal flora. In this study, a mouse model of alcoholic liver injury (ALI) was constructed to study the ameliorative effect of B. subtilis C10 on ALI and to further clarify its mechanism of action. Significant correlations between intestinal flora and biochemical indicators of ALI were found by statistical correlation analysis. Supplementation with B. subtilis C10 modulated the equilibrium of gut flora by reducing the population of detrimental bacteria while enhancing the numbers of beneficial microorganisms, which resulted in an improvement in lipid metabolism and oxidative stress in the liver. The results of RT-qPCR showed that B. subtilis C10 intervention regulated the main regulatory factors of liver lipid metabolism (PPAR-α, SREBP-1c) and interfered with Nrf-2/Ho-1 signal pathway, which in turn ameliorated alcohol-induced lipid metabolism disorder and liver peroxidation stress. In addition, liver metabonomic analysis showed that B. subtilis C10 intervention reduced the production of harmful metabolites and increased beneficial metabolites in the liver, thereby reversing the metabolic disturbances caused by excessive alcohol consumption. KEGG analysis showed that B. subtilis C10 intervention modulated liver metabolic disorders and accelerated lipid metabolism by regulating glutathione metabolic pathway, purine metabolic pathway, pantothenic acid and CoA biosynthesis pathway, ABC transporter protein pathway, and HIF-1 signaling pathway. Taken together, these findings suggest that B. subtilis C10 ameliorates ALI by modifying the structure of intestinal flora and liver metabolic pathways to attenuate alcohol-exposure-induced liver oxidative damage and lipid metabolism abnormalities. PRACTICAL APPLICATION: Bacillus subtilis C10 is an effective probiotic intervention that significantly ameliorated alcoholic liver injury in mice through the gut-liver axis. B. subtilis C10 can be used as a dietary probiotic to develop functional foods with beneficial effects for the population of excessive alcohol consumption., (© 2024 Institute of Food Technologists.)

3'-Sialyllactose (3'-SL), a key component of human milk oligosaccharides, provides significant health benefits and immune modulation, and is increasingly used in infant formula and dietary supplements. This study presents a novel approach for the efficient biosynthesis of 3'-SL using Escherichia coli BL21star(DE3)Δ lacZ through genomic integration. We first addressed the issue of metabolic competition by deleting crucial genes, nanA , nanK , nanE , and nanT , that are involved in the degradation of N -acetylneuraminic acid. This strategic gene knockout minimized the flux through competing pathways. The engineered Escherichia coli strain was subsequently transformed with the exogenous genes neuBCA and nST , enabling the de novo synthesis of 3'-SL. A modular metabolic engineering strategy was utilized to optimize the expression of key enzymes within the MSU module, enhancing and balancing the carbon flux distribution. Additionally, a cofactor regeneration strategy was implemented to increase CTP availability, which improved cofactor recycling and fine-tuned the metabolic pathway for maximal 3'-SL production. Transport protein screening was incorporated to further increase the extracellular concentration of 3'-SL, resulting in an unprecedented yield of 56.8 g/L in a 5L bioreactor fermentation, setting a new benchmark in the field.

Biomass-derived biochar has enormous potential for sustainable and low-cost treatment of lead-contained wastewater. In this study, corncob and cow dung-derived biochar were prepared. The increase in pyrolysis temperature could improve the porous structures, surface area, functional groups and alkalinity, and further provide a higher Pb 2+ capacity in both biochars. Cow dung biochar performed better than corncob for its higher inorganic mineral content and more alkaline surface. Among them, CDB-600 performed the Langmuir maximum capacity of 357.1 mg/g, with a high surface area of 144.3 m 2 /g; ion exchange and precipitate were the main adsorption mechanisms. After further MgO modification, the M-CDB displayed a high surface area of 166 m 2 /g, and ion exchangeability and precipitate-promoting effects were improved. M-CDB performed a Langmuir maximum capacity of 833.3 mg/g. The pHpzc was found to be 10 and the adsorbents portray a very good Pb 2+ adsorption selectivity among coexisting ions in the solution. The adsorption process was found to be endothermic, feasible, spontaneous and chemisorption. The fixed lead on CDB-600 was stable in water. The immobilized lead could be desorbed by acid wash. CDB-600 performed better in terms of sustainability in use, which could support its continuous application ability., Competing Interests: Declarations. Ethical approval: This manuscript was only submitted to Environmental Science and Pollution Research. All the research protocols were observed. The authors make sure they have permission for the use of all the information and tools necessary for the accomplishment of this research. The authors confirmed that this research’s contents and conclusions do not violate moral ethics. Consent to participate: This manuscript was presented by all the authors with honesty and without fabrication, falsification or inappropriate data manipulation. Consent for publication: All the authors have conformed to the manuscript and have agreed to its submissions for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

CT is crucial for diagnosing chest diseases, with image quality affected by spatial resolution. Thick-slice CT remains prevalent in practice due to cost considerations, yet its coarse spatial resolution may hinder accurate diagnoses. Our multicenter study develops a deep learning synthetic model with Convolutional-Transformer hybrid encoder-decoder architecture for generating thin-slice CT from thick-slice CT on a single center (1576 participants) and access the synthetic CT on three cross-regional centers (1228 participants). The qualitative image quality of synthetic and real thin-slice CT is comparable (p = 0.16). Four radiologists' accuracy in diagnosing community-acquired pneumonia using synthetic thin-slice CT surpasses thick-slice CT (p < 0.05), and matches real thin-slice CT (p > 0.99). For lung nodule detection, sensitivity with thin-slice CT outperforms thick-slice CT (p < 0.001) and comparable to real thin-slice CT (p > 0.05). These findings indicate the potential of our model to generate high-quality synthetic thin-slice CT as a practical alternative when real thin-slice CT is preferred but unavailable., Competing Interests: Competing interests: P.Y. and D.W. are employed by Infervision Medical Technology Co. Ltd. All other authors declare no competing interests., (© 2024. The Author(s).)

Puccinia striiformis f. sp. tritici (Pst), the airborne fungal pathogen of wheat stripe rust, causes a decline in wheat quality and severe yield loss. Effective field management of wheat stripe rust heavily relies on timely and accurate monitoring of incoming fungal sources. Therefore, rapid and accurate detection of Pst is invaluable in disease control programs. In this study, three assays using recombinase polymerase amplification (RPA) combined with different visualization methods, including RPA followed by agarose gel electrophoresis, RPA lateral-flow dipstick (RPA-LFD) technology, and real-time RPA, were developed for rapidly and sensitively detecting Pst. The RPA and RPA-LFD assays were conducted at an isothermal temperature of 39 °C within 30 min. The real-time RPA assay required only a 20-min reaction at 39 °C. The specificities of the three assays were determined based on the lack of cross-reactivity with the other seven control wheat pathogens. The detection limits of RPA and real-time RPA were 10 5  fg/μL, and that of RPA-LFD was 10 4  fg/μL. Additionally, the three RPA assays detected Pst in field leaf samples. Among the 73 samples examined, 44 (60.3 %), 45 (61.6 %), and 60 (82.2 %) tested positive in the RPA, real-time RPA, and RPA-LFD assays, respectively. The result suggested that RPA-LFD was the most sensitive in detecting Pst from field samples. Giving the simple, rapid, and practical nature of RPA assays, this method can serve as a promising molecular diagnostic tools for accurate and rapid detection of Pst., 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.)

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Currently, the medical diagnosis of SLE mainly relies on the clinical experience of physicians, and there is no universally accepted objective method for diagnosing SLE. Therefore, there is an urgent need to design an intelligent approach to accurately diagnose SLE to assist physicians in formulating appropriate treatment plans. With the rapid development of intelligent medical diagnostic technology, medical data is becoming increasingly multimodal. Multimodal data fusion can provide richer information than single-modal data, and the fusion of multiple modalities can effectively enhance the richness of data features to improve modeling performance., Results: In this paper, a cross-modal specific transfer fusion technique based on infrared spectra and metabolomics is proposed to effectively integrate infrared spectra and metabolomics by fully exploiting the intrinsic relationships between features across different modalities, thus achieving the diagnosis of SLE. In this research, a Decision Level Fusion module is also proposed to fuse the representations of two specific transfers further, obtaining the final prediction scores. Comprehensive experimental results demonstrate that the proposed method significantly improves the performance of SLE prediction, with accuracy and Area Under Curve (AUC) reaching 94.98 % and 97.13 %, respectively, outperforming existing methods., Significance: Our framework effectively integrates infrared spectra and metabolomics to achieve a more accurate prediction of SLE. Our research indicates that prediction methods based on different modalities outperform those using single-modality data. The Cross-modal Specific Transfer Fusion module effectively captures the complex relationships within each single modality and models the complex relationships between different modalities., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glucose oxidases (GODs) induce the catalyzation from β-d-glucose to gluconic acid in an oxygen-consuming process, providing a potential antibiotic substitution strategy. However, the inadequate properties of existing GODs in parallel hinder the antimicrobial capacity for industrial applications. In this study, PaGOD (WT) from Penicillium amagasakiense was enzymatically improved through computer-aided design based on energy optimization. Two thermostable variants A263P and K424F were selected and combined to generate variant A263P/K424F, superior in both thermostability (t 1/2 at 60 °C increased 2.6-fold) and catalytic efficiency (2.1-fold increase in catalytic efficiency), in comparison with the WT. The molecular dynamics simulations revealed the improved rigidity of A263P/K424F is attributed to the formation of hydrogen bonds within the flexible region and the newly-formed salt bridge Lys473: Asp477, following the increased ΔΔG. For improvement of antibacterial capacity, A263P/K424F impressively lower the half maximal inhibitory concentrations (IC 50 ) to 12 and 11 mg/L respectively for Escherichia coli and Staphylococcus aureus (86.4 % and 78.8 % lower than the WT, 65.7 % and 50 % lower than erythromycin). The results indicated that the antibacterial effects of GOD can be improved through in vitro molecular modification, which could be an effective strategy to address antibacterial requirements with antibiotic-free agents., 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.)

We present a two-dimensional (2D) electrically conductive metal-organic framework (EC-MOF)-based artificial synapse. The intrinsic electronic conductivity and subnanometer channels of the EC-MOF facilitate efficient ion diffusion, enable a high density of active redox centers, and significantly enhance capacitance within the artificial synapse. As a result, the synapse operates at an ultralow voltage of 10 mV and exhibits a remarkably low power consumption of approximately 1 fW, along with the longest retention time recorded for two-terminal electrolyte-type artificial synapses to date. The alignment of the quantum size of the subnanometer pores in the EC-MOF with various cations allows for versatile synaptic plasticity. This capability is applied to image refresh, classification, and efferent signal transmission for controlling artificial muscles, thereby offering a methodology for achieving tunable neuromorphic properties. These findings suggest the potential application of metal-organic frameworks in artificial nervous systems for future brain-inspired computation, peripheral interfaces, and neurorobotics.

In this study, four lactic acid bacteria (LAB) strains demonstrating ciprofloxacin, bile salt, gastric fluid, and intestinal fluid tolerance as well as adhesion ability to Caco-2 and HT-29 cells were used to improve and recover the intestinal flora disorders caused by ciprofloxacin, among which, Lactobacillus brevis 505 exhibited excellent adhesion ability to two kinds of cells and colonization ability to mouse intestinal. After ciprofloxacin treatment, certain recovery effect on cecum caused by ciprofloxacin in the mice was found during natural recovery (group 5C2), but it was challenging to fully restore the intestinal integrity to the initial level. After L. brevis 505 intervention (group 5C5), the intestinal damage to the colon and ileum caused by ciprofloxacin in mice was significantly alleviated; the recovery effect was better than that of natural recovery. Additionally, L. brevis 505 could effectively regulate INF-γ, sIgA, and RegIIIγ increase induced by ciprofloxacin. Shannon and Simpson index of the intestinal flora of mice in 5C5 group were higher than those in other group, the relative abundance of Bifidobacterium and Lactobacillus in the mice in 5C5 group was increased, indicating that LAB can better restore the structure and abundance of intestinal microflora. Consequently, L. brevis 505 shows promise as a probiotic for gut microbiota restoration and rebuilding during antibiotic therapy., Competing Interests: Declarations. Ethics Approval: All the animal all the relevant ethical procedures were complied with and were approved by the northwest A&F University Animal Care Committee (xn2024-0321). Competing Interest: The authors confirm that they have no conflicts of interest with respect to the work described in this manuscript., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Rh(III)-catalyzed indole C4-H bond addition to nitroalkenes is disclosed under mild and redox-neutral reaction conditions, offering straightforward access to various 4-(2-nitroalkyl)indoles (34 examples) with excellent chemo- and regioselectivity. Furthermore, late-stage diversifications and mechanistic studies were also performed.

In eggs, there are several components: eggshell (ES), eggshell membrane (ESM), egg white (EW), and egg yolk (EY). Many modification methods exist, such as thermal treatment, high pressure, freeze-thaw cycles, ultrasonic treatment, ozonation, phosphorylation, and acylation, all aimed at improving the functional properties of EW and EY. Additionally, microorganism and enzyme modifications have proven effective in enhancing the functional properties of EW and EY. ES and ESM are unique components of eggs. The eggshell is rich in calcium carbonate, while the eggshell membrane is rich in protein. The effective utilization of ES and ESM can help promote economic income in the poultry industry and benefit the environment. Research on the modification of ES and ESM has shown that microorganisms and enzymes have the potential to improve their functional properties. After modification, egg components can be utilized in the production of egg-based and other food products for improved performance. Furthermore, enzyme modification of egg components can produce bioactive peptides, which have the potential to treat specific diseases and may even be used in the biomedical field. This review primarily focuses on the effects of microorganisms and enzymes on the modification of egg components and summarizes the roles of microbial and enzymatic modifications in this context.

Yinchenhao Decoction (YCHD), a classic formula in traditional Chinese medicine, is believed to have the potential to treat liver diseases by modulating the Toll-like receptor 4 (TLR4) target. Therefore, a thorough exploration of the effective components and therapeutic mechanisms targeting TLR4 in YCHD is a promising strategy for liver diseases. In this study, the AIGO-DTI deep learning framework was proposed to predict the targeting probability of major components in YCHD for TLR4. Comparative evaluations with four machine learning models (RF, SVM, KNN, XGBoost) and two deep learning models (GCN, GAT) demonstrated that the AIGO-DTI framework exhibited the best overall performance, with Recall and AUC reaching 0.968 and 0.991, respectively.This study further utilized the AIGO-DTI model to identify the potential impact of Isoscopoletin, a major component of YCHD, on TLR4. Subsequent wet experiments revealed that Isoscopoletin could influence the maturation of Dendritic Cells (DCs) induced by Lipopolysaccharide (LPS) through TLR4, suggesting its therapeutic potential for liver diseases, especially hepatitis. Additionally, based on the AIGO-DTI framework, this study established an online platform named TLR4-Predict to facilitate domain experts in discovering more compounds related to TLR4. Overall, the proposed AIGO-DTI framework accurately predicts unique compounds in YCHD that interact with TLR4, providing new insights for identifying and screening lead compounds targeting TLR4., Competing Interests: Declarations Conflicts of Interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. International Association of Scientists in the Interdisciplinary Areas.)

Solid Earth tide represents the response of solid Earth to the lunar (solar) gravitational force. The yielding solid Earth due to the force has been thought to be a prolate ellipsoid since the time of Lord Kelvin, yet the ellipsoid's geometry such as major semi-axis's length, minor semi-axis's length, and flattening remains unresolved. Additionally, the tidal displacement of reference point is conventionally resolved through a combination of expanded potential equations and given Earth model. Here we present a geometric model in which both the ellipsoid's geometry and the tidal displacement of reference point can be resolved through a rotating ellipse with respect to the Moon (Sun). We test the geometric model using 23-year gravity data from 22 superconducting gravimeter (SG) stations and compare it with the current model recommended by the IERS (International Earth Rotation System) conventions (2010), the average Root Mean Square (RMS) deviation of the gravity change yielded by the geometric model against observation is 6.47 µGal (equivalent to 2.07 cm), while that yielded by the current model is 30.77 µGal (equivalent to 9.85 cm). The geometric model will greatly contribute to many application fields such as geodesy, geophysics, astronomy, and oceanography., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Brown sugar grade discrimination method using a three-electrode electrochemical scanning system was proposed in this paper. Copper foam, nickel foam, and copper film were utilized as the working electrodes, respectively. Platinum electrode was used as the counter electrode, and saturated calomel electrode functioned as the reference electrode. Cyclic voltammetry (CV) and chronoamperometry (i-t) were used to scan brown sugar samples of different brands and grades in the aqueous environment. An evaluation method was constructed to discriminate the brown sugar samples using the detection data. Results revealed unique characteristics of different brown sugar samples when using different working electrodes. Logistic regression model was utilized to establish the relationship between the current density and variety of brown sugars utilizing i-t scanning data. Validation testing results demonstrated that the average relative error between theoretical and actual current densities was within ±9.27 %, confirming its effectiveness for the discrimination of different grades of brown sugar., 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.)

Pseudorabies virus (PRV), known to infect pigs and found in various species, including humans, shows zoonotic potential. This study identified vimentin (VIM), a highly conserved intermediate filament protein expressed in multiple mammalian species and tissues, as a universal receptor for PRV infections in human and porcine cells. The adsorption of PRV is positively correlated with the level of VIM expressed in different cells. Overexpression and knockdown of VIM significantly increase and decrease PRV adsorption in cells, respectively. Dot blot assay and VOPBA showed that purified VIM can directly bind to PRV virions efficiently in a dose-dependent manner. PRV and VIM are co-localized at the cell membrane of PRV-infected cells. Moreover, PRV mainly binds to host VIM via its conserved amino acid residues in PRV gD (W 98 , G 162 , Y 164 , C 205 ) and gH (C 439 ) and the Rod domain (residues 96-404) of VIM. In addition, regulating the expression of VIM also influences the entry, replication, and release of PRV, which has a similar result to the adsorption. These results demonstrate that VIM, as a universal receptor, can facilitate PRV infection in multiple stages in human and porcine cells, highlighting the zoonosis characteristics of PRV and the need for more attention., 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.)

Variants in HSPB8 are predominantly associated with peripheral neuropathies, but their occurrence in myopathies remains exceedingly rare. The genetic and clinical spectrum of HSPB8-related myopathy is not yet complete. Herein, we not only described the first Chinese case of HSPB8-related myopathy characterized by a novel heterozygous frameshift variant (c.576&#95;579delinsCAG, p.Glu192Aspfs*55) in the C-terminal region of HSPB8, but also established the first association between this specific HSPB8 variant and pediatric-onset axial and limb-girdle myopathy. Muscle pathology revealed myofibrillar myopathy features and the novel pathological findings of inflammatory responses and vacuoles with sarcolemmal features pathology. Functional studies demonstrated significant colocalization of HSPB8 with autophagy markers and upregulation of autophagy-related proteins, which suggested that autophagic dysregulation may contribute to the pathological process of this disease. Furthermore, comprehensive bioinformatics analysis and molecular dynamics simulations revealed an increased propensity for aggregation, as well as altered structural and biochemical properties in the mutant HSPB8. Our study highlights the importance of considering HSPB8 mutations in early-onset axial and limb-girdle myopathy, expanding the genetic and phenotypic spectrum of the disease. Notably, our results underscore the critical role of autophagy dysregulation and aberrant protein aggregation in the pathogenesis, providing novel insights into potential therapeutic targets., Competing Interests: Competing interests The authors declare no competing interests. Ethics Written informed consent was obtained from the patient and her legal guardians for the utilization of clinical data and biological materials for research purposes. The study protocol was reviewed and approved by the Ethics Committee of Qilu Hospital of Shandong University (KYLL-2023(ZM)-017)., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

PIWI-interacting RNAs (piRNAs), which associate with PIWI clade Argonaute proteins to form piRNA-induced silencing complexes (piRISCs) in germline cells, are responsible for maintaining genomic integrity and reproductive function through transcriptional or post-transcriptional suppression of transposable elements and regulation of protein-coding genes. Recent discoveries of crucial PIWI-piRNA functions in oogenesis and embryogenesis in golden hamsters suggest an indispensable role in female fertility that has been obscured in the predominant mouse model of PIWI-piRNA pathway regulation. In particular, studies of piRNA expression dynamics, functional redundancies, and compositional variations across mammal species have advanced our understanding of piRNA functions in male and, especially, female reproduction. These findings further support the use of hamsters as a more representative model of piRNA biology in mammals. In addition to discussing these new perspectives, the current review also covers emerging directions for piRNA research, its implications for female fertility, and our fundamental understanding of reproductive mechanisms.

Compound 5p is a 4β-N-substituted podophyllotoxin derivative, which exhibited potent activity toward drug-resistant K562/A02 cells and decreased MDR-1 mRNA expression. Here, we further investigated its detail mechanism and tested its antitumor activity. 5p exerted catalytic inhibition of topoisomerase IIα, and didn't show the inhibitor of topoisomerase I. 5p exhibited the inhibitory effect on microtubule polymerization. 5p showed potent anti-proliferation against breast cancer, oral squamous carcinoma, and their drug-resistant cell lines, with resistance index of 0.61 and 0.86, respectively. 5p downregulated the expression levels of P-gp in KB V200  cells and BCRP in MCF7/ADR cells in dose-dependent manner. Moreover, 5p induced KB and KB V200  cells arrest at G 2 /M phase by up-regulating the expression of γ-H2AX, p-Histone H3 and cyclin B1. 5p induced apoptosis and pyroptosis by increased the expression levels of cleaved-PARP, cleaved-caspase3, N-GSDME as well as LDH release in KB and KB V200  cells. In addition, 5p efficiently impaired tumor growth in KB and KB V200 xenograft mice. Conclusively, this work elucidated the dual inhibitor of topoisomerase II and microtubule of 5p and its mechanism of overcoming the multidrug resistance, indicating that 5p exerts the antitumor potentiality., Competing Interests: Declaration of competing interest I, [Xing Lv], declare that there are no conflicts of interest in relation to the manuscript titled "[Dual inhibition of topoisomerase II and microtubule of podophyllotoxin derivative 5p overcomes cancer multidrug resistance]" submitted to [European journal of pharmacology]. I confirm that the results and interpretations reported in the manuscript are original and have not been plagiarized., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ozone (O 3 ) pollution is a severe environmental problem in China. The incomplete understanding of atmospheric photochemical reaction mechanisms prevents us from accurately understanding the chemistry of O 3 production. Here, we used an improved dual-channel reaction chamber technique to measure net photochemical O 3 production rate (P(O 3 ) net ) directly in Dongguan, a typical industrial city in China. The maximum P(O 3 ) net was 46.3 ppbv h -1 during the observation period, which is at a relatively high level compared to previous observations under different environment worldwide. We employed an observation-based box model coupled with the state-of-the-art atmospheric chemical mechanism (MCM v3.3.1) to investigate the chemistry of O 3 production. Under the base scenario, the modelling underestimates P(O 3 ) net by ~30 %. Additionally considering HO 2 uptake by ambient aerosols, inorganic deposition, and Cl chemistry only caused a small change (< 13 %) in the simulation of P(O 3 ) net . Further analysis indicates that unmeasured reactive volatile organic compounds (VOCs), such as oxygenated VOCs and branched alkenes are potential contributors to the underestimation of P(O 3 ) net . This study underscores the underestimation of P(O 3 ) net in conventional atmospheric modelling setups, providing a crucial scientific foundation for further investigation aimed at promoting our understanding of photochemical O 3 formation., 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.)

Cardiomyopathy is particularly common in septic patients. Our previous studies have shown that activation of the alpha 1 adrenergic receptor (α 1 -AR) on cardiomyocytes inhibits sepsis-induced myocardial dysfunction. However, the role of cardiac endothelial α 1 -AR in septic cardiomyopathy has not been determined. Here, we identified α 1 -AR expression in mouse and human endothelial cells and showed that activation of α 1 -AR with phenylephrine (PE) improved cardiac function and survival by preventing cardiac endothelial injury in septic mice. Mechanistically, activating α 1 -AR with PE decreased the expression of ICAM-1, VCAM-1, iNOS, E-selectin, and p-p38MAPK, while promoting PKC and ERK1/2 phosphorylation in LPS-treated endothelial cells. These effects were abolished by a PKC inhibitor or α 1 -AR antagonist. PE also reduced p65 nuclear translocation, but this suppression is not blocked by PKC inhibition. Treatment with U0126 (a specific ERK1/2 inhibitor) reversed the effects of PE on p38MAPK phosphorylation. Our results demonstrate that cardiac endothelial α 1 -AR activation prevents sepsis-induced myocardial dysfunction in mice by inhibiting the endothelial injury via PKC-ERK/p38MAPK signaling pathway and a PKC-independent inhibition of p65 nuclear translocation. These findings offer a new perspective for septic patients with cardiac dysfunction by inhibiting cardiac endothelial cell injury through α 1 -AR activation., 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 B.V. All rights reserved.)

Indole and pyridine, which are highly produced refractory compounds in the industrial wastewater, exhibit poor degradation capabilities in natural environments. In this study, we developed an anaerobic digestion system coupled with weak electric mediation (ED), and investigated the promoting effect of weak electricity on indole and pyridine biodegradation. The degradation characteristics were systematically explored, and the results showed that the degradation rate and mineralization of indole and pyridine were significantly enhanced, the production of CH 4 was increased 1.4-fold, and the optimal voltages were 1.0 V and 0.8 V in the ED, respectively. Moreover, simultaneous removal of carbon and nitrogen was achieved. Gas chromatography-mass spectrometry analysis verified the transformation products, and possible pathways were proposed. Several byproducts of indole and pyridine were identified, with oxindole and glutaric dialdehyde being the main metabolites, respectively. Additionally, density functional theory (DFT) analysis was performed to investigated the radical indices and stabilities of the molecules to further confirm the degradation pathway. Microbial structure analysis demonstrated that the electrically mediated enhanced metabolism and activity of functional microbes, led to the promotion of indole and pyridine mineralization. Moreover, such species as degrading bacteria (Alicycliphilus, Shinella) and electroactive bacteria (Achromobacter), anaerobic ammonia-oxidizing bacteria (SM1A02), and denitrifying bacteria (Thiobacillus) coexisted. This study demonstrates that weak electric mediation is a promising methodology for enhancing the removal of indole and pyridine from wastewater under anaerobic conditions., 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.)

Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that nonhematopoietic but not hematopoietic Opn depletion improved septic outcomes. When compared with wild type mice, cohoused Opn-/- mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation and OPN neutralization assay showed that Opn depletion could reduce bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in wild type organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN-deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Fetal growth restriction (FGR) is associated with various perinatal complications. Limited research has focused on the fetal heart in the context of FGR. This study aimed to investigate the application value of fetal heart quantification (HQ) technology in evaluating the size, morphology, and function of the heart in FGR., Methods: A total of 31 fetuses diagnosed with FGR in our hospital from April 2022 to May 2024 were included, alongside another 31 normal fetuses matched for gestational age as the control group. Ultrasound Doppler parameters of the middle cerebral artery (MCA), umbilical artery (UA), venous catheter, and fetal HQ parameters were collected for comparative analysis, and perinatal data were followed up., Results: Fetuses with FGR exhibited significant differences in various parameters of the MCA and UA compared to the control group (P < 0.05). The four-chamber view end-diastolic transverse width, end-diastolic area, left ventricular (LV) end-diastolic area, end-systolic area, end-systolic length, end-diastolic volume, end-systolic volume, and right ventricular (RV) end-systolic area in the FGR group were significantly lower than those in the control group (P < 0.05). In the 24-segment analysis, the LV fractional shortening in the FGR group was greater than in the control group at segments 12 to 14, while the end-diastolic diameter (ED) at segments 5 to 13 of the LV and segments 1 to 14 of the RV were smaller than those in the control group, with statistical significance (P < 0.05). Analysis of each subgroup indicated that fractional shortening (FS) in the early-onset group was significantly greater than in the late-onset group at RV segments 2 to 8. LV-ED at segments 1 to 15 and RV-ED at segments 1 to 16 were significantly smaller in the early-onset group than in the control group, and LV ED segments 20 to 21 were significantly smaller in the early-onset group compared to the late-onset group (P < 0.05). FS in the mild group was significantly larger than in the normal group at LV segments 10 to 16. The severe group exhibited significantly smaller LV segment 2 to 11 ED and the mild group showed smaller RV segments 1 to 13 compared to the control group (P < 0.05)., Conclusions: Fetal HQ is a promising technique for evaluating the cardiac function, size, and morphology in cases of FGR., Competing Interests: Declarations Ethics approval and consent to participate The study protocol was approved by the Ethics Committee of Shanghai First Maternity and Infant Hospital (No. KS22311). All the women recruited agreed to participate in the study and provided written informed consent. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The development of novel gel-mineral supplements is important for improving the health of patients with dysphagia. In this study, we used natural egg white protein (NEWP) and phosphorylated egg white protein (STEWP) as controls. We modified NEWP with succinic anhydride to produce varying degrees of succinylated egg white protein (SAEWP). The addition of 20 % (w/v) succinic anhydride increased the β-sheet content of SAEWP from 11.97 % to 50.60 %, which stabilized the gel structure and formed a uniformly ordered three-dimensional network, resulting in the average pore size of SAEWP could reach >80 μm. Compared to NEWP, SAEWP hydrogel with 20 % succinic anhydride showed a 22.27 % increase in water holding capacity, a 56.13 % increase in hardness, and a 173.01 % increase in elasticity. Immersion in a calcium chloride solution resulted in a 220 % increase in calcium content. This study provides new insights into the development of innovative gel mineral supplements., Competing Interests: Declaration of competing interest We declare that the work described was original research that has not been published previously. No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors to be published., (Copyright © 2024. Published by Elsevier B.V.)

A 14-metal Tb(III) nanocluster with four CO 3 2- anions as templates was constructed for the quantitative and qualitative detection of vanillylmandelic acid (VMA) with high sensitivity and selectivity. The luminescence response time to VMA is less than ten seconds, and the limit of detection is as low as 0.32 nM in CH 3 CN.

7-Dehydrocholesterol (7-DHC), a direct precursor of vitamin D3, has attracted increasing attention in microbial fermentation recently. In this study, 7-DHC biosynthesis in diploid Saccharomyces cerevisiae with robust ergosterol production was achieved by heterologous 24-dehydrocholesterol reductase expression, generating 44.1 mg/L 7-DHC, whereas the titer of ergosterol decreased by 40.5%. The ergosterol biosynthetic pathway was completely blocked by knocking out ERG6 and ERG5 , affording a 4.2-fold increase in the 7-DHC titer. Subsequently, the facilitation of the mevalonate and the postsqualene pathways accompanied by elimination of transcriptional repressors enhanced 7-DHC synthesis, and the 7-DHC titer reached 738.5 mg/L in a shake flask. Further validation in a 50 L fermenter demonstrated that the 7-DHC titer reached 3.80 g/L within just 24 h, with productivity reaching 158.3 mg/L/h, setting a new benchmark as the highest reported to date. This study paves the way toward a large-scale and cost-effective manufacture of 7-DHC.

Background: For critically ill patients with acute kidney injury (AKI), there remains controversy regarding the predictive factors affecting the discontinuation of continuous renal replacement therapy (CRRT). This study aims to explore factors associated with successful CRRT discontinuation in AKI patients and to develop predictive models for successful discontinuation., Methods: We conducted a retrospective study on adult patients with AKI who received CRRT, sourced from the Medical Information Mart for Intensive Care (MIMIC-IV) database. Successful discontinuation of CRRT was defined as no CRRT requirement within 72 h after stopping CRRT. Predictive factors for successful discontinuation of CRRT were analyzed. Additionally, we utilized machine learning algorithms to develop predictive models, including logistic regression (LR), decision tree (DT), random forest (RF), XGBoost, and K-nearest neighbor (KNN)., Results: A total of 599 patients were included, of whom 475 (79.3%) successfully discontinued CRRT. Urine output, non-renal SOFA score, bicarbonate, systolic blood pressure, and blood urea nitrogen were identified as risk factors for successful CRRT discontinuation. The KNN model exhibited the highest area under the receiver operating characteristic curve (AUC) (0.870), followed by LR (0.739), DT (0.691), RF (0.847), and XGBoost (0.830). When incorporating all available variables, the AUCs for the LR, DT, RF, XGBoost, and KNN models were 0.708, 0.674, 0.875, 0.866, and 0.816, respectively. Considering the performance of the models in both scenarios, the ensemble learning models (RF and XGBoost) were demonstrated superior performance., Conclusions: Our results identified factors associated with successful discontinuation of CRRT in AKI patients. Additionally, we developed promising machine learning models which provided a reference for future research., Competing Interests: Declarations Ethics approval and consent to participate The Institutional Review Board at the Beth Israel Deaconess Medical Center approved the collection of patient information and creation of the research resource and granted a waiver of informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

For settling the recycling problem of waste polyurethane sponges (PU) and environment pollution of oil spills simultaneously, this work exploited the multifunctional superhydrophobic PU materials via the dip-coating method, which were prepared by anchoring modified Fe 3 O 4 and expandable graphite (EG) on PU sponges under the adhesion effect of polydimethylsiloxane (PDMS). The water contact angle and sliding angle of as-prepared PU sponges reached 154.1 ± 1.6 and 8°, respectively. Most importantly, the superhydrophobic PU sponges were endowed with the multipath oil treatment ability, which consisted of magnetically driven, gravity-driven, peristaltic pump-driven, and photothermally driven modes. Besides, the light oil absorption capacity, separation flux, and efficiency for superhydrophobic PU sponges reached 23.9 g/g, 27779 L m -2 h -1 , and 99.5%, respectively. Owing to the photothermal conversion ability of Fe 3 O 4 and EG, the temperature of superhydrophobic PU sponges was raised to 71.5 °C within 233 s under 1.2 solar irradiation (1200 W/m 2 ), demonstrating its absorption potential for high-viscosity crude oils. In addition, the prepared sponges exhibited good chemical/mechanical stability, self-cleaning, and flame retardancy. In a nutshell, this article has evolved an environmentally benign and practical method for fabricating the multifunctional materials in oil spill treatment, which will efficiently accomplish the targets of low carbon and environmental management.

We present a universal preparation method for synthesizing a range of pure-phase IB-group Sn-based alloy catalysts (Cu 3 Sn, Ag 4 Sn, and AuSn) for electrochemical reduction of CO 2 to C 1 product. The selectivity can be widely adjusted by altering metal composition and potential, improving the understanding of the structure-activity relationship in various Sn-based alloys.

Reclaimed water recharge into rivers is an important supplementary approach to address water resource shortage in arid and semi-arid areas worldwide. However, the ecology impacts of reclaimed water recharge on the rivers are still unknown, especially for the microbial assemble and species coexistence in different seasons. Here, the evolution of microbiome and its response to different reasons in the Jialu River, which was subjected to long-term reclaimed water recharge, is investigated by using 16S rRNA gene sequencing and multivariate statistical methods. The results indicated that microbial communities exhibited significant temporal heterogeneity across different periods and were negatively correlated with river discharge. Their assembly was primarily influenced by stochastic processes such as dispersal limitation and drift. As the transition occurred from the dry season to the normal season, the role of drift diminished, while the deterministic effects of dispersal limitation and niche selection intensified. The relationships among planktonic bacterial species were primarily positive (cooperative), and the complexity and positive correlations within the ecological network showed a trend of first decreasing and then increasing with the change of seasons. Temperature, dissolved oxygen, and ammonia nitrogen were the main driving forces influencing the structure of microbial communities. In summary, these findings provided insights into the impact of seasonal variations on the microbial community patterns in reclaimed water-supplemented river ecosystems., 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.)

Spanish mackerel is an important economic fish species in China, but corruption undermines its overall economic value. Fermentation serves as a crucial technique for preserving perishable fish in developing countries. This study aimed to examine the dynamic changes in the gel properties, physicochemical properties, microbial diversity, and volatile flavor compounds (VFCs) of Spanish mackerel sausages inoculated with Lactiplantibacillus plantarum CY1-2 during fermentation. The correlation between key microorganisms and VFCs was explored using a two-way orthogonal partial least squares analysis. The results showed that the group inoculated with strain CY1-2 exhibited significant improvements compared with the control group after 40 h of fermentation. Specifically, gel strength increased by 207.7%, total free amino acids increased by 37.49%, DPPH and ABTS radical scavenging rates increased by 34.12% and 58.73%, and TVB-N levels decreased by 54.2%, respectively. In addition, using gas chromatography-mass spectrometry, 36 VFCs were detected in fermented sausages, including 9 aldehydes, 9 hydrocarbons, 7 alcohols, 4 acids, 2 ketones, and 5 esters. High-throughput sequencing demonstrated that the bacterial profiles were altered in sausages inoculated with strain CY1-2 during fermentation. Enhydrobacter dominated initially but was quickly replaced by Macrococcus after 8 h of fermentation, while Lactobacillus became the dominant genus after 40 h. Correlation analysis revealed that Lactobacillus and Staphylococcus played important roles in the production of VFCs in the fermented sausages. Notably, Lactobacillus was positively associated with 2-undecanone, pentadecane, and hexanal. This study confirmed that strain CY1-2 inoculation could enable the production of high-quality fermented fish sausages.

Alkaline methanol-water electrolysis system is regarded as an appealing strategy for electro-reforming methanol into formate and producing hydrogen with low energy-consumption compared with alkaline water electrolysis. However, stability and selectivity under high current densities for practical application remain challenging. Herein, a CeF3@Ni3N nanosheets array anchored on carbon cloth (CeF3@Ni3N/CC) was fabricated. The gradual extrusion of F species from Ni(OH)2 lattices can stabilize hierarchical structure and construct abundant heterostructure interfaces. Moreover, CeF3 can modulate electron distribution of Ni3N, thus simultaneously enhancing the surface adsorption kinetics and capability of methanol and OH-, which is conducive to enhanced methanol oxidation reaction (MOR) activity and selectivity. Therefore, bifunctional CeF3@Ni3N/CC exhibits low potential of 1.43 V at 500 mA cm-2, along with high stability over 72 h and high faradaic efficiency (FEs) in MOR, as well as an overpotential of 76 mV to achieve 50 mA cm-2 for hydrogen evolution reaction (HER). Furthermore, membrane-free CeF3@Ni3N/CC||CeF3@Ni3N/CC cell for MOR||HER delivers high electrocatalytic activity, long-term stability and FEs at high current density of 300 mA cm-2. This study highlights the importance of optimizing surface adsorption behavior of active species, as well as rational design of highly efficient heterostructure electrocatalysts for methanol upgrading coupled with hydrogen production., (© 2024 Wiley‐VCH GmbH.)

Allergic rhinitis (AR), which presents symptoms like sneezing and a runny nose, is categorized as an upper respiratory condition of type 2. Recent progress in comprehending AR has revealed the significant role played by type 2 cytokines, specifically interleukin (IL)-13, IL-4, and IL-5. These cytokines are released by helper T cells 2 (Th2) and innate lymphoid cells (ILC2s). ILC2s have the ability to interact with various immune cells and are essential in promoting both type 2 immune response and tissue repair, contributing to normal homeostatic functions within the body. This article presents a summary of the latest advancements in comprehending the activity of ILC2s, with particular emphasis on their potential role involvement in AR. It explores how they collaborate with Th2 cells to exacerbate nasal inflammation and interact with regulatory T cells (Tregs) to counteract the suppressive role mediated by Tregs during allergic inflammation. The significance of ILC2s in allergen-specific therapy is highlighted. A comprehensive understanding of ILC2s biology establishes a robust foundation for unraveling the pathogenesis of AR and devising innovative therapeutic approaches for its management., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

Targeting tumor-specific neoantigens holds promise for cancer immunotherapy, but their ultra-low expression on tumor cells poses challenges for T cell therapies. Here, we found that chimeric antigen receptors (CARs) exhibit 10-100 times lower sensitivity than T cell receptors (TCRs) when targeting human leukocyte antigen (HLA) class I-presented p53 R175H neoantigen. To enhance CAR functionality, we introduced T cell receptor fusion constructs (TRuCs) and synthetic TCRs and antigen receptors (STARs). Our data show that STARs optimally reproduce TCR antigen sensitivity, outperforming CARs and TRuCs in redirecting CD8 + and CD4 + T cells to recognize HLA class I neoantigens. STAR-T cells demonstrate superior killing of cancer cell lines with low neoantigen density in vitro and improved tumor control in mouse models compared to CAR-T and TRuC-T cells. These findings highlight CAR sensitivity limitations and present STARs as more effective synthetic receptors for T cell-based immunotherapy against tumors with low neoantigen density., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Osteonecrosis of the femoral head (ONFH) is a common complication of glucocorticoid (GC) therapy. Recent advances demonstrate that sympathetic nerves regulate bone homeostasis, and GCs lower the sympathetic tone. Here, we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH. GCs activate the glucocorticoid receptor (GR) but hinder the activation of the mineralocorticoid receptor (MR) on neurons in the hypothalamic paraventricular nucleus (PVN). This disrupts the balance of corticosteroid receptors (GR/MR) and subsequently reduces the sympathetic outflow in the PVN. Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone (MPS) daily for 3 days, and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice. Importantly, treatment with a GR inhibitor (RU486) in the PVN promotes the activation of MR and rebalances the ratio of GR and MR, thus effectively boosting sympathetic outflow, as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice. Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head, while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2 (Adrb2) knockout. Furthermore, activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype. Mechanistically, norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) via Adrb2-cyclic AMP response element-binding protein (CREB) signaling. Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice. Thus, GC inhibits sympathetic tone via the hypothalamic descending pathway, which, in turn, acts as a mediator of GC-induced ONFH., (© 2024. The Author(s).)

Competing Interests: We declare no competing interests.

Objective: NOTES gallbladder-preserving surgery (N-GPS) has been heralded as a new paradigm shift in minimally invasive surgery for chronic cholecystitis patients. The objective of this research was to evaluate the impact of N-GPS on the intestinal microbiota of patients. Methods: The study selected patients with benign gallbladder disease (BG group) within 1 week preoperative (BG&#95;DPR stage) and followed up over 1 year postoperative (BG&#95;YPO stage) and selected healthy controls (HC group) whose sex, age, and BMI index matched with patients at BG&#95;YPO stage, too. Accordingly, stool samples from healthy controls and two stages of patients with benign gallbladder disease were collected; among them, the selected samples were sent for 16S rDNA sequencing with Illumina MiSeq platform, and then, the combined samples were sent for short-chain fatty acid (SCFA) analysis with GC-MS platform. Results: The result of alpha diversity of Shannon index showed that the difference among the two stages of BG group and HC group wasn't statistically significant, while the result of beta diversity based on the weighted UniFrac distance suggested that the structure of intestinal microbiota of BG group at YPO stage was closer to HC group. LEfSe analysis suggested that BG&#95;YPO stage enriched genus, such as Enterocloster and Hungatella&#95;A&#95;128155 , which improved bile acid metabolism. Compared with BG&#95;DPR stage, BG&#95;YPO stage and HC group enriched Faecalibacterium and Roseburia , but depleted Streptococcus , while fecal SCFA concentrations increased. Conclusion: Patients with benign gallbladder disease and chronic cholecystitis after N-GPS treatment for over 1 year improved gut microbial community structure. With the improving bile acid metabolism, SCFA-producing bacteria increased and pathobionts decreased, which helped the intestinal microbiota structure of BG group at YPO stage restore and close to HC group. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR1900028267., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Lixin Deng et al.)

A highly sensitive and selective label-free impedimetric immunosensor based on AuNPs@pDA@NiCo 2 S 4 @MoS 2 nanocomposite modified on the surface of a screen-printed electrode (SPE) was designed for the detection of interleukin-6 (IL-6). The distribution of NiCo 2 S 4 nanoparticles on MoS 2 nanosheets was able to prevent them from agglomerating. The polydopamine (pDA) layer was coated on the surface of NiCo 2 S 4 @MoS 2 nanosheets by self-polymerization, which improved the stability and biocompatibility of the nanomaterial. The excellent reduction ability of pDA promoted the synthesis of gold nanoparticles (AuNPs), which increased the amount of antibody adsorption and the conductivity of the material. Finally, the antibody (Ab) of IL-6 was immobilized on the surface of AuNPs@pDA@NiCo 2 S 4 @MoS 2 nanocomposite. Electrochemical impedance spectroscopy (EIS) was used to detect the change of impedance before and after the immune response between Ab and IL-6 antigen (IL-6). Under the optimal experimental conditions, the relative change in impedance and the logarithmic concentration of IL-6 showed a good linear relationship in the range 1.00 to 1.00 × 10 6  pg/mL, with a low detection limit of 0.97 pg/mL. In addition, the proposed immunosensor performed with good reproducibility, stability, and specificity. It was successfully applied to the determination of IL-6 in patient's serum samples of head and neck carcinoma with recoveries of 98.40% to 106.5%. To sum up, the proposed label-free impedimetric immunosensor was successfully constructed for IL-6 detection in real samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: The stress hyperglycemia ratio (SHR) is a new biomarker indicating acute hyperglycemia and predicting adverse outcomes in different conditions. Yet, its impact on metabolic syndrome (MetS) has not been studied. We explored the link between SHR and long-term all-cause and cardiovascular disease (CVD) mortality in MetS patients., Methods: We conducted a large prospective cohort study involving 9438 participants diagnosed with MetS, drawn from the 1999-2018 NHANES. MetS diagnosis was based on NCEP-ATPIII criteria. Participants were categorized into three groups based on SHR tertiles: T1 (SHR ≤ 0.890), T2 (SHR 0.890-0.992), and T3 (SHR ≥ 0.992). Cox regression and Kaplan-Meier curve analyses assessed the correlation between SHR and mortalities. Non-linear correlations were explored using restricted cubic splines, and stratification analysis was performed., Results: Out of 9438 MetS patients, 1929 deaths occurred during an average follow-up of 107 ± 64 months, including 541 CVD deaths. All-cause and CVD mortality rates were significantly higher with elevated SHR values (T3) than lower tertiles (23.4% vs. 19.5% and 18.3%, P < 0.001; 6.8% vs. 5.3% and 5.1%, P = 0.007, respectively). A U-shaped relationship was observed between SHR and all-cause and CVD mortality (all P for non-linear < 0.001). Kaplan-Meier analysis indicated higher SHR values associated with increased risk of all-cause and CVD mortality (all log-rank P < 0.001). After adjusting for confounders, multivariate Cox regression showed SHR remained associated with a 1.256-fold and 1.023-fold risk of all-cause and CVD mortality., Conclusions: SHR independently correlates with all-cause and CVD mortality in MetS patients, displaying a U-shaped relationship with clinical endpoints., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Dual-mode-based sensors have drawn a lot of interest due to their high accuracy and sensitivity compared to single-response systems. A simple electrochemical and colorimetric dual-mode sensor based on enzyme-linked immunosorbent assay (ELISA), without complex electrode surface modification, was developed for accurate and sensitive detection of carcinoembryonic antigen (CEA). The target CEA is recognized by an antibody coupled to horseradish peroxidase (HRP), which then oxidizes the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to generate both a colorimetric and an electrochemical signal. A paper-based analysis device (μPAD) with dual-mode homogeneous sensing microfluidic was created; three paper-based detection areas for colorimetric testing, and a two-electrode embedded detection area for electrochemical testing. When applying colorimetric analysis technology, the linear range of CEA detection is 0.6-40 ng mL -1 , and the limit of detection (LOD) is 0.2 ng mL -1 . The linear range is 0.1-40 ng mL -1 and the LOD is 0.03 ng mL -1 by applying electrochemical analysis. The visibility and intuitiveness of colorimetry provide a reference for higher sensitivity and quick response of the electrochemical method. A smartphone application (APP) was also developed to realize the dual extraction of colorimetric signals. The colorimetric detection system based on ELISA can provide a new path for the development of electrochemical sensing and makes it have inherent self-verification and self-correction functions and is expected to provide more reliable and accurate detection results.

Background: Upadacitinib, a specific JAK1 inhibitor, has minimal effect on other JAK subtypes. It influences the inflammatory process in various ways. Upadacitinib has been approved for conditions such as rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, and ulcerative colitis in various countries. The purpose of this study is to assess the clinical efficacy and safety of upadacitinib in patients with refractory palmoplantar pustulosis who have not responded to conventional treatments (e.g., Acitretin, Tripterygium wilfordii Hook F, cyclosporine, methotrexate)., Methods: We conducted a retrospective collection of clinical data from 28 patients who received upadacitinib treatment at the Department of Dermatology, First Affiliated Hospital of Suzhou University, from July 2022 to December 2023. We evaluated the Palmoplantar Pustulosis Area and Severity Index (PPPASI) scores, Dermatology Life Quality Index (DLQI) scores, and Physician's Global Assessment (PGA) scores before and after treatment. We also recorded any adverse events during the treatment process., Results: A total of 28 patients were diagnosed with PPP, including 10 males and 18 females, and 8 patients (3 males and 5 females) were diagnosed with SAPHO syndrome. The mean age was (36.3 ± 10.5) years. After 12 weeks of treatment, PPPASI scores decreased from baseline (13.86 ± 2.76) to (5.56 ± 1.08), with a statistically significant difference ( p < 0.05). DLQI scores decreased from (12.55 ± 4.56) to (2.03 ± 1.13), also showing a statistically significant difference ( p < 0.05). Additionally, 20 patients achieved a PGA score of 0/1. No severe adverse events were reported during the treatment and follow-up period., Conclusion: Upadacitinib could be an additional safe and effective treatment for treating refractory palmoplantar pustulosis with a potential benefit on patients' quality of life. Further studies are needed to assess its short-and long-term efficacy and safety in larger sample sizes in randomized double-blind controlled trials., 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 Du, Yang, Zhang, Lv, Cao and Min.)

Saikosaponin-b2 (SS-b2), an active ingredient derived from the root of Radix Bupleuri, possesses antitumour, anti-inflammatory, antioxidative and hepatoprotective properties. We investigated the inhibition of tumour proliferation by SS-b2 and the underlying molecular mechanisms, including the MACC1/p-c-Met/p-Akt pathway expression in HepG2 liver cancer cells and H22 tumour-bearing mice. Animal experiments showed that SS-b2 significantly decreased the levels of MACC1, p-c-MET and p-Akt in tumour tissue transplanted with H22 liver cancer cells in mice, while it increased the expression of p-BAD. The results also revealed a concentration-dependent suppression of MACC1, p-c-Met and p-Akt expression in the SS-b2 treatment group compared with the control group. Additionally, the suppression of MACC1 activation by SS-b2 resulted in a reduction in the viability and proliferation of HepG2 liver cancer cells, and this reduction was comparable to that by doxorubicin (DOX). This suggests that SS-b2 has significant efficacy in liver cancer, comparable to DOX. Meanwhile, Annexin V-FITC/PI staining and western blot analysis of cleaved caspase 9 and cleaved caspase 3 demonstrated that SS-b2 induced apoptosis of HepG2 liver cancer cells. These findings provide experimental evidence suggesting that SS-b2 is a promising anticancer agent for liver cancer., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Yanxue Zhu et al.)

The fate and effects of sodium dodecyl benzene sulfonate (SDBS) in sewage treatment plants effluents on nutrients and submerged macrophytes are far from clear in wetlands. This study conducted a 24-day experiment to investigate changes in nutrients and epiphytic biofilm of Hydrilla verticillata in wetlands receiving effluents with 0.5, 2 and 5 mg L -1 SDBS. The decrease of SDBS in overlying water followed pseudo-first-order kinetic equation, with over 80 % of SDBS removal achieved. 2 and 5 mg L -1 SDBS decreased nutrient removal efficiency, induced oxidative stress response and damaged cells of H. verticillata. SDBS altered bacterial and eukaryotic community diversity. 0.5 mg L -1 SDBS can promote carbon fixation and methane oxidation of microorganisms. Network analysis revealed that 0.5 mg L -1 SDBS decreased the stability of epiphytic ecosystems. Mantel tests indicated significant influences of SDBS, temperature, and total nitrogen on epiphytic microbial communities., 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.)

This study aims to discover the association between serum osteocalcin, the Chinese visceral adiposity index (CVAI), and atherosclerotic cardiovascular disease (ASCVD) risk, and their impact on arterial stiffness in T2DM patients. We included 639 T2DM patients aged 30 and older who received the assessment of ASCVD risk using the China-PAR equation, Osteocalcin and arterial stiffness in this cross-sectional study. We found that osteocalcin and CVAI as independent risk factors for both medium-high-risk ASCVD (osteocalcin: men, OR,0.96, 95% CI 0.92, 1.00; women, OR, 0.93, 95% CI 0.8, 1.08, respectively)(CVAI: men, OR,1.01,95% CI 1.00,1.02; women: OR, 1.08, 95% CI 1.02,1.14, respectively) and arterial stiffness (osteocalcin: men, OR, 0.98, 95% CI 0.94,1.01; women, OR, 0.98, 95% CI 0.90,1.06, respectively)(CVAI: men, OR,1.0, 95% CI 0.99,1.01; women, OR, 1.02, 95% CI 1.00,1.04, respectively) in both men and women patients with T2DM. Combining osteocalcin levels and CVAI improved the prediction accuracy of arterial stiffness in men patients with T2DM (difference of AUC (Model 4 vs. Model 1) :1.5%, NRI: 0.06 [0.0,0.4]). All P-values were < 0.05. The results suggested that osteocalcin levels and CVAI are independent risk factors for ASCVD risk and arterial stiffness in T2DM. Combining osteocalcin and CVAI can enhance the early detection of atherosclerosis through male patients with T2DM., (© 2024. The Author(s).)

Background: Hyperuricemia is considered as an independent risk factor for acute ischemic stroke (AIS), and some AIS patients are accompanied by an increase in serum uric acid. Recent studies have highlighted the important role of gut microbiota in both hyperuricemia and AIS, but there is little available data on the relationship between gut microbiota and the pathogenesis of AIS with hyperuricemia (HAS)., Methods: Here we profiled the gut microbiota composition in 63 HAS patients and 269 non-HAS patients through 16s rRNA sequencing. Male rat with hyperuricemia were subjected to middle cerebral artery occlusion (MCAO) to establish HAS model and were then treated with Parabacteroides distasonis. Subsequently, the neurological deficit, pathological damages and blood-brain barrier disruption were evaluated. Moreover, the levels of ROS, inflammatory cytokines, NF-𝜿B pathway related protein, and vascular density markers were determined., Results: There were significant differences of gut microbiota composition between HAS patients and non-HAS patients, and a significant decrease in the abundance of Parabacteroides in HAS patients compared to non-HAS patients. Animal experiments showed that supplementation with P. distasonis increased beneficial commensal bacteria, significantly improved neurological deficits, pathological damages and BBB disruption, as well as reduced the level of serum uric acid in HAS rats. We further demonstrated that P. distasonis treatment decreased ROS level and increased SOD2 level, thereby reducing oxidative stress. Meanwhile, P. distasonis effectively inhibited NF-𝜿B signal pathway and reduced the production of inflammatory cytokines, including TNF-α and IL-1β, alleviating the inflammatory response. Notably, P. distasonis treatment increased the levels of vascular density markers including cluster of differentiation 31 (CD31) and alpha-smooth muscle actin (α-SMA), ameliorating vascular damage in HAS rats., Conclusions: Together, these findings highlighted the important role of P. distasonis in the pathogenesis of HAS, and its mechanism was involved in the regulation of gut microbiota-gut-brain axis, which implied a novel strategy against HAS., (© 2024. The Author(s).)

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple symptoms, and its rapid screening is the research focus of surface-enhanced Raman scattering (SERS) technology. In this study, gold@silver-porous silicon (Au@Ag-PSi) composite substrates were synthesized by electrochemical etching and in-situ reduction methods, which showed excellent sensitivity and accuracy in the detection of rhodamine 6G (R6G) and serum from SLE patients. SERS technology was combined with deep learning algorithms to model serum features using selected CNN, AlexNet, and RF models. 92 % accuracy was achieved in classifying SLE patients by CNN models, and the reliability of these models in accurately identifying sera was verified by ROC curve analysis. This study highlights the great potential of Au@Ag-PSi substrate in SERS detection and introduces a novel deep learning approach for SERS for accurate screening of SLE. The proposed method and composite substrate provide significant value for rapid, accurate, and noninvasive SLE screening and provide insights into SERS-based diagnostic techniques., 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.)

Objective: This study aimed to thoroughly explore the relationship between individual oral behavior and the differing numbers of temporomandibular disorder (TMD) symptom in the general population., Methods: A total of 565 participants were recruited and completed a questionnaire containing demographic characteristics, eight specific oral behaviors, and five major TMD symptoms (5Ts) checklist. Multivariate linear regression analysis was performed to assess the relationship between individual oral behavior and the number of TMD symptoms, after controlling for confounders., Results: The prevalence of TMD symptoms was up to 38.2% in the general population, with 64.6% of the participants engaging in one or more oral behaviors. Female participants showed a stronger positive association with most oral behaviors than males. Moreover, wake oral behaviors exhibited a higher correlation coefficient value with TMD symptom number than sleep oral behaviors. Among the eight oral behaviors, bruxism in sleep exhibited no significant correlation with the of TMD symptom number ( P >0.05). Seven other specific oral behaviors were significantly correlated with the number of TMD symptoms by multivariate linear regression analysis ( P <0.01). The associations between the seven oral behaviors and TMD symptom number remained significant in sleep posture pressuring jaw (β: 0.165, 95% CI: 0.080-0.250), bruxism in awake (β: 0.341, 95% CI: 0.132-0.550), teeth clenching (β: 0.422, 95% CI: 0.264-0.580), pressing, holding, or touching teeth together (β: 0.282, 95% CI: 0.169-0.395), holding or tightening muscles without clenching (β: 0.447, 95% CI0.304-0.589), holding jaw forward or to the side (β: 0.694, 95% CI0.526-0.861), and holding jaw in rigid or tense position (β: 0.571, 95% CI0.418, 0.724) after adjustment for demographic factors ( P <0.01)., Conclusion: There was a positive association between seven specific oral behaviors and TMD symptom number. Individuals with higher frequency of specific oral behaviors are more likely to suffer from more TMD symptoms. Sleep bruxism exhibited no association with TMD symptoms and symptom number., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 Tian et al.)