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The toxicological effects of p-cresol have primarily been attributed to its metabolism products; however, very little human data are available in the key organ (i.e., liver) responsible for the generation of these metabolites. Experiments were conducted in HepaRG cells utilizing the following markers of cellular toxicity: 2′-7′-dichlorofluorescein (DCF; oxidative stress) formation, total cellular glutathione (GSH) concentration, and lactate dehydrogenase (LDH; cellular necrosis) release. Concentrations of p-cresol, p-cresol sulfate, and p-cresol glucuronide were determined using validated assays. p-Cresol exposure resulted in concentration- and time-dependent changes in DCF (EC50 = 0.64 ± 0.37 mM at 24 h of exposure) formation, GSH (EC50 = 1.00 ± 0.07 mM) concentration, and LDH (EC50 = 0.85 ± 0.14 mM) release at toxicologically relevant conditions. p-Cresol was also relatively more toxic than 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, indole-3-acetic acid, indoxyl sulfate, kynurenic acid, and hippuric acid on all markers. Although the exogenous administration of p-cresol sulfate and p-cresol glucuronide generated high intracellular concentrations of these metabolites, both metabolites were less toxic compared to p-cresol at equal-molar conditions. Moreover, p-cresol glucuronide was the predominant metabolite generated in situ from p-cresol exposure. Selective attenuation of glucuronidation (without affecting p-cresol sulfate formation, while increasing p-cresol accumulation) using independent chemical inhibitors (i.e., 0.75 mM l-borneol, 75 µM amentoflavone, or 100 µM diclofenac) consistently resulted in further increases in LDH release associated with p-cresol exposure (by 28.3 ± 5.3%, 30.0 ± 8.2% or 27.3 ± 6.8%, respectively, compared to p-cresol treatment). These novel data indicated that p-cresol was a relatively potent toxicant, and that glucuronidation was unlikely to be associated with the manifestation of its toxic effects in HepaRG cells.

The energy router composed of double active bridge (DAB) can interconnect multiple voltage level AC distribution network through DC lines to form AC/DC hybrid distribution network. The fault types of the system are diverse and the fault characteristics are complex. This paper studies the fault characteristics of the system in detail. The single-phase grounding fault of AC network side and single-phase grounding fault of AC valve side occurred in the system. This paper explored the impact of the AC side of the system after the above failure, and make a detailed comparative analysis. The results show that DAB can isolate the influence of AC side fault, and provide theoretical basis for the selection of grounding mode and the design of protection system for AC/DC hybrid distribution network.

Compared with the direct access to the main power grid and diesel generators, this paper puts forward the scheme of using electric ships to shuttle between islands to transport electric energy, analyzes the limitations and defects of its application in offshore islands; and then puts forward a comprehensive energy supply system of offshore islands. The comprehensive energy supply system can make full use of the rich renewable energy of the islands, and realize the optimal allocation of the overall resources of the islands. At the same time, the energy supply system can break the isolated development pattern of island power grid and connect the island group power exchange ship. This paper analyzes the connotation and characteristics of the system, puts forward the key technology for building the integrated energy supply system of ocean island group, and gives the design and operation analysis example of power exchange ship.

When planning the power grid, it is necessary to obtain the optimal decision scheme according to the market behavior of different stakeholders. In this paper, the virtual game player "nature" is introduced to realize the deep integration of game theory and robust optimization, and a source network load collaborative planning method considering uncertainty and multi-agent game is proposed. Firstly, the planning decision-making models of different stakeholders of DG investment operators, power grid investment operators and power users are constructed respectively; then, the static game behavior between distributed generation (DG) investment operators and power grid investment operators is analyzed according to the transmission relationship of the three; at the same time, robust optimization is used to deal with DG. In this paper, we introduce the virtual game player "nature" to study the dynamic game behavior between the virtual game player and the power grid investment operator. On this basis, the dynamic static joint game planning model is proposed.

With the strengthening of external supervision and the management requirements of internal quality and efficiency improvement of power grid, it is particularly important to improve the lean level of power grid investment. However, the accuracy and scientificity of the current grid infrastructure project investment plan adjustment need to be further improved, and the basis for the completion of investment submission is the on-site construction progress. Therefore, this topic carries out the analysis of the factors affecting the construction progress, including the types of the factors affecting the construction, the depth and breadth of the impact, and the impact of the milestone stage, and takes the analysis results of the shutdown factors as the reference basis for the adjustment of the investment plan, so as to improve the investment management level of the company.

In order to deal with the severe external supervision and challenges, and improve the scientific rationality of internal investment structure decision-making, this study explored the idea of voltage level investment structure decision-making considering the power grid development and operation benefits. Firstly, based on the study of the relationship between historical investment scale and power grid indicators, the investment demand of power grid is determined; secondly, the influence path of investment on business efficiency is sorted out, and the differences of investment, capital transfer and depreciation of different voltage levels are studied and determined, and the operation benefit level of the company under different investment schemes is calculated. Finally, the index system of investment structure optimization is constructed to quantify the power grid and benefit status of the company under different investment structures, so as to optimize the company’s investment scheme and promote the high-quality development of the company and power grid.

With the rapid development of the Internet of Things (IoT), autonomous vehicles have been receiving more and more attention because they own many advantages compared with traditional vehicles. A robust and accurate vehicle localization system is critical to the safety and the efficiency of autonomous vehicles. The global positioning system (GPS) has been widely applied to the vehicle localization systems. However, the accuracy and the reliability of GPS have suffered in some scenarios. In this paper, we present a robust and accurate vehicle localization system consisting of a bistatic passive radar, in which the performance of localization is solely dependent on the accuracy of the proposed off-grid direction of arrival (DOA) estimation algorithm. Under the framework of sparse Bayesian learning (SBL), the source powers and the noise variance are estimated by a fast evidence maximization method, and the off-grid gap is effectively handled by an advanced grid refining strategy. Simulation results show that the proposed method exhibits better performance than the existing sparse signal representation-based algorithms, and performs well in the vehicle localization system.

Finding out how many parameters are necessary to explain and describe complex and various phenomena of nature has been a challenge in modern physics. This paper introduces a new formal system of units, which maintain compatibility with SI units, to express all seven SI base units by dimensionless numbers with acceptable uncertainties and to establish the number one as the fundamental parameter of everything. All seven SI base units are converted successfully into the unified dimensionless numerical values via normalization of s, c, h, k, e/me, NA, and b by unity (1). In the proposed system of units, even the unlike-dimensioned physical quantities can be convertible and hence added, subtracted, or compared to one another. It is very simple and easy to analyze and validate physical equations by substituting every unit with the corresponding number. Furthermore, it is expected to find new relationships among unlike-dimensioned physical quantities, which is extremely difficult or even impossible in SI units.

Abstract Background Gankyrin was originally purified and characterized as the p28 component of the 26S proteasome, and later identified as an oncogenic protein in hepatocellular carcinomas (HCC). It has recently been found to be highly expressed in several other malignancies, and compelling evidence show gankyrin plays important roles in tumorigenesis. However, its mechanism of action remains unclear. Methods In order to further clarify the functions of gankyrin and better understand its molecular mechanisms, we generated a gankyrin null cell line, HCT116 gankyrin−/− , by targeted homologous recombination in human colon cancer cells, and then employed two-dimensional electrophoresis (2-DE) based proteomic approaches followed by MS identification to investigate alterations in the proteome due to the gankyrin knockout. Western blot and qRT-PCR assays were also used to examine the protein and mRNA levels of some identified proteins. Results Compared with wild-type control cells, gankyrin null cells were impaired in terms of their proliferation, migration and anchorage-independent growth. A total of 21 altered proteins were identified, which included 18 proteins that had not previously been reported to be related to gankyrin. Notably, eight metastasis-related proteins were identified. Western blot analyses confirmed that the changes in three examined proteins were consistent with 2-DE gel analysis. Conclusions In summary, we have generated a useful cell tool to clarify the functions of gankyrin. Our proteomic data provide novel information to better understand the roles and underlying mechanisms by which gankyrin is involved in tumorigenesis and cancer metastasis.

Abstract Background Herb mixtures are widely used as an alternative to hormonal therapy in China for treatment of the menopausal syndrome. However, composition of these herb mixtures are complex and their working mechanism is often unknown. This study investigated the effect of Tiáo-Gēng-Tāng (TG-decoction), a Chinese herbal mixture extract, in balancing female hormones, regulating expression of estrogen receptors (ERs), and preventing aging-related tissue damage. Methods Ovariectomized 5-month-old female rats were used to model menopause and treated with either TG-decoction or conjugated estrogen for 8 weeks. Estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in serum and in the hypothalamus. Hypothalamic expression of estrogen receptor (ER) alpha and beta were studied by real-time PCR and western blotting. Total antioxidant capacity (T-AOC), oxidation indicator superoxide dismutase (SOD) activity and tissue damage parameter malondialdehyde (MDA) were measured using standard assays. Aging-related ultrastructural alterations in mitochondria were studied in all animals by transmission electron microscopy. Results TG-decoction-treatment elevated E2 and lowered FSH in serum of ovariectomized rats. The potency and efficacy of TG-decoction on the hypothalamus was generally weaker than that of conjugated estrogens. However, TG-decoction was superior in upregulating expression of ERα and β. TG-decoction increased hypothalamic SOD and T-AOC levels and decreased MDAlevels and mitochondrial damage in hypothalamic neurons. Conclusions TG-decoction balances female hormones similarly to conjugated estrogens but less effectively. However, it is superior in up regulating ERα and β and exhibits antioxidative antiaging activities. Whilst it shares similar effects with estrogen, TG-decoction also seems to have distinctive and more complex functions and activities.

Controllable engineering of thin lithium (Li) metal is essential for increasing the energy density of solid-state batteries and clarifying the interfacial evolution mechanisms of a lithium metal negative electrode. However, fabricating a thin lithium electrode faces significant challenges due to the fragility and high viscosity of Li metal. Herein, through facile treatment of Ta-doped Li 7 La 3 Zr 2 O 12 (LLZTO) with trifluoromethanesulfonic acid, its surface Li 2 CO 3 species is converted into a lithiophilic layer with LiCF 3 SO 3 and LiF components. It enables the thickness control of Li metal negative electrodes, ranging from 0.78 μm to 30 μm. Quasi-solid-state lithium-metal battery with an optimized 7.54 μm-thick lithium metal negative electrode, a commercial LiNi 0.83 Co 0.11 Mn 0.06 O 2 positive electrode, and a negative/positive electrode capacity ratio of 1.1 shows a 500 cycles lifespan with a final discharge specific capacity of 99 mAh g -1 at 2.35 mA cm -2 and 25 °C. Through multi-scale characterizations of the thin lithium negative electrode, we clarify the multi-dimensional compositional evolution and failure mechanisms of lithium-deficient and -rich regions (0.78 μm and 7.54 μm), on its surface, inside it, or at the Li/LLZTO interface., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Electrochemical synthesis of hydrogen peroxide (H 2 O 2 ) via the two-electron oxygen reduction reaction (2e - -ORR) provides an alternative method to the energy-intensive anthraquinone method. Metal macrocycles with precise coordination are widely used for 2e - -ORR electrocatalysis, but they have to be commonly loaded on conductive substrates, thus exposing a large number of 2e - -ORR-inactive sites that result in poor H 2 O 2 production rate and efficiency. Herein, guided by first-principle predictions, a substrate-free and two-dimensional conductive metal-organic framework (Ni-TCPP(Co)), composed of CoN 4 sites in porphine(Co) centers and Ni 2 O 8 nodes, is designed as a multi-site catalyst for H 2 O 2 electrosynthesis. The approperiate distance between the CoN 4 and Ni 2 O 8 sites in Ni-TCPP(Co) weakens the electron transfer between them, thus ensuring their inherent activities and creating high-density active sites. Meanwhile, the intrinsic electronic conductivity and porosity of Ni-TCPP(Co) further facilitate rapid reaction kinetics. Therefore, outstanding 2e - -ORR electrocatalytic performance has been achieved in both alkaline and neutral electrolytes (>90 %/85 % H 2 O 2 selectivity within 0-0.8 V vs. RHE and >18.2/18.0 mol g -1  h -1 H 2 O 2 yield under alkaline/neutral conditions), with confirmed feasibility for water purification and disinfection applications. This strategy thus provides a new avenue for designing catalysts with precise coordination and high-density active sites, promoting high-efficiency electrosynthesis of H 2 O 2 and beyond., (© 2024 Wiley-VCH GmbH.)

The intrinsic reversibility of dynamic covalent bonding, such as the furan-maleimide Diels-Alder (DA) cycloaddition reactions, enables reprocessable, self-healing polymer materials that can be reconfigured via the mechanism of solid-state plasticity. In this work, the temperature-dependent exchange rates of stereochemically distinct endo and exo DA bonds are leveraged to achieve tunable, temperature- and stress-activated shape morphing in Diels-Alder polymer (DAP) networks. Through thermal annealing, ≈35% of endo DA isomers are converted in neat DAP networks to the thermodynamically favored exo form, achieving ≈97% exo after complete annealing at 60 °C. This conversion results in a ≈1.7 fold increase in elastic modulus, from 1.7 to 3.0 MPa, and significantly alters the stress relaxation and shape recovery behavior. Spatially resolved annealing, is further showcased enabling the precise control of spatial distributions of endo and exo DA bonds across planar geometries. The locally distinct concentrations of endo/exo isomers, achieved by temperature-induced conversion of endo DA isomers to the thermodynamically stable exo DA isomers, gave rise to the spatial distributions of stress relaxation rates and elastic strain recovery mismatch to enable controlled stereochemical shape morphing. This approach provides a simplified, thermally driven method for shape morphing, with potential applications in soft robotics and flexible electronics., (© 2024 Wiley‐VCH GmbH.)

Electroencephalography (EEG) microstates are canonical voltage topographies that reflect the temporal dynamics of brain networks on a millisecond time scale. Abnormalities in broadband microstate parameters have been observed in subjects with psychiatric symptoms, indicating their potential as clinical biomarkers. Considering distinct information provided by specific frequency bands of EEG, we hypothesized that microstates in decomposed frequency bands could provide a more detailed depiction of the underlying neuropathological mechanism. In this study, with a large open access resting-state dataset (n = 203), we examined the properties of frequency-specific microstates and their relationship with anxiety and depression symptoms. We conducted clustering on EEG topographies in decomposed frequency bands (delta, theta, alpha and beta), and determined the number of clusters with a meta-criterion. Microstate parameters, including global explained variance (GEV), duration, coverage, occurrence and transition probability, were calculated for eyes-open and eyes-closed states, respectively. Their ability to predict the severity of depression and anxiety symptoms were systematically identified by correlation, regression and classification analyses. Distinct microstate patterns were observed across different frequency bands. Microstate parameters in the alpha band held the best predictive power for emotional symptoms. Microstates B (GEV, coverage) and parieto-central maximum microstate E (coverage, occurrence, transitions from B to E) in the alpha band exhibited significant correlations with depression and anxiety, respectively. Microstate parameters of the alpha band achieved predictive R-square of 0.100 for anxiety scores, which is much higher than those of broadband (R-square = -0.026, p < 0.01). Similar results were found in classification of participants with high and low anxiety symptom scores (68% accuracy in alpha vs. 52% in broadband). These results suggested the value of frequency-specific microstates in predicting emotional symptoms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Daptomycin (DAP), a novel cyclic lipopeptide antibiotic produced by Streptomyces roseosporus, is clinically important for treatment of infections caused by multidrug-resistant Gram-positive pathogens, but the low yield hampers its large-scale industrial production. Here, we describe a combination metabolic engineering strategy for constructing a DAP high-yielding strain. Initially, we enhanced aspartate (Asp) precursor supply in S. roseosporus wild-type (WT) strain by separately inhibiting Asp degradation and competitive pathway genes using CRISPRi and overexpressing Asp synthetic pathway genes using strong promoter kasOp*. The resulting strains all showed increased DAP titre. Combined inhibition of acsA4, pta, pyrB, and pyrC increased DAP titre to 167.4 μg/mL (73.5% higher than WT value). Co-overexpression of aspC, gdhA, ppc, and ecaA led to DAP titre 168 μg/mL (75.7% higher than WT value). Concurrently, we constructed a chassis strain favourable for DAP production by abolishing by-product production (i.e., deleting a 21.1 kb region of the red pigment biosynthetic gene cluster (BGC)) and engineering the DAP BGC (i.e., replacing its native dptEp with kasOp*). Titre for the resulting chassis strain reached 185.8 μg/mL. Application of our Asp precursor supply strategies to the chassis strain further increased DAP titre to 302 μg/mL (2.1-fold higher than WT value). Subsequently, we cloned the engineered DAP BGC and duplicated it in the chassis strain, leading to DAP titre 274.6 μg/mL. The above strategies, in combination, resulted in maximal DAP titre 350.7 μg/mL (2.6-fold higher than WT value), representing the highest reported DAP titre in shake-flask fermentation. These findings provide an efficient combination strategy for increasing DAP production and can also be readily applied in the overproduction of other Asp-related antibiotics., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

Multi-omics integration has demonstrated promising performance in complex disease prediction. However, existing research typically focuses on maximizing prediction accuracy, while often neglecting the essential task of discovering meaningful biomarkers. This issue is particularly important in biomedicine, as molecules often interact rather than function individually to influence disease outcomes. To this end, we propose a two-phase framework named GREMI to assist multi-omics classification and explanation. In the prediction phase, we propose to improve prediction performance by employing a graph attention architecture on sample-wise co-functional networks to incorporate biomolecular interaction information for enhanced feature representation, followed by the integration of a joint-late mixed strategy and the true-class-probability block to adaptively evaluate classification confidence at both feature and omics levels. In the interpretation phase, we propose a multi-view approach to explain disease outcomes from the interaction module perspective, providing a more intuitive understanding and biomedical rationale. We incorporate Monte Carlo tree search (MCTS) to explore local-view subgraphs and pinpoint modules that highly contribute to disease characterization from the global-view. Extensive experiments demonstrate that the proposed framework outperforms state-of-the-art methods in seven different classification tasks, and our model effectively addresses data mutual interference when the number of omics types increases. We further illustrate the functional- and disease-relevance of the identified modules, as well as validate the classification performance of discovered modules using an independent cohort.

Pathogens constantly evolve and can develop mutations that evade host immunity and treatment. Addressing these escape mechanisms requires targeting evolutionarily conserved vulnerabilities, as mutations in these regions often impose fitness costs. We introduce adaptive multi-epitope targeting with enhanced avidity (AMETA), a modular and multivalent nanobody platform that conjugates potent bispecific nanobodies to a human immunoglobulin M (IgM) scaffold. AMETA can display 20+ nanobodies, enabling superior avidity binding to multiple conserved and neutralizing epitopes. By leveraging multi-epitope SARS-CoV-2 nanobodies and structure-guided design, AMETA constructs exponentially enhance antiviral potency, surpassing monomeric nanobodies by over a million-fold. These constructs demonstrate ultrapotent, broad, and durable efficacy against pathogenic sarbecoviruses, including Omicron sublineages, with robust preclinical results. Structural analysis through cryoelectron microscopy and modeling has uncovered multiple antiviral mechanisms within a single construct. At picomolar to nanomolar concentrations, AMETA efficiently induces inter-spike and inter-virus cross-linking, promoting spike post-fusion and striking viral disarmament. AMETA's modularity enables rapid, cost-effective production and adaptation to evolving pathogens., Competing Interests: Declaration of interests Y.X. and Y.S. are co-inventors on a provisional patent of AMETA technology filed by Icahn School of Medicine at Mount Sinai. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories, and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer, and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and AstraZeneca. A.G.-S. is an inventor of patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. Y.X. and Y.S. are co-inventors on a patent of Nbs filed by Univ. of Pittsburgh. Y.S. is a co-founder of Antenna Biotech Inc., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The performance of detectors is key for a PET scanner to achieve high spatial resolution and high sensitivity. This work aims to develop flood histogram generating algorithms to reduce the edge effect and improve the crystal identification of a PET detector consisting of two optically coupled pixelated scintillator detectors., Methods: The PET detector consists of two optically coupled detectors, each consisting of a 23×23 LYSO crystal array with a crystal size of 1.0×1.0×20 mm 3 read out by an 8×8 SiPM array with a pixel size of 3.0×3.0 mm 2 . The SiPM array is read out with a resistor network circuit to obtain four position encoding energy signals. A novel center of gravity (COG) positioning algorithm using six signals from the two detectors was proposed and compared to the traditional COG algorithms using either four or eight signals from the detectors. The raised-to-the-power (RTP) method was applied to the three COG algorithms for the PET detector. Different powers of the RTP from 1.0 to 2.5 were evaluated., Results: The proposed COG algorithm significantly improves the crystal identification at the junction of the two detectors as compared to the COG algorithm using four signals of each detector, and improves the crystal identification at the center of the two detectors as compared to the COG algorithm using eight signals from both detectors. The RTP method significantly improves the overall flood histogram qualities of the two COG algorithms using either eight or six signals from the two detectors, and the two COG algorithm provide similar flood histogram quality when a power of 1.5 is used., Conclusion: The novel positioning algorithms reduce the edge effect and improve the flood histogram quality for a PET detector consisting of two optically coupled detectors, each consisting of a pixelated scintillator crystal array and a SiPM array with highly multiplexed four signal readout. The positioning algorithms can be used in a PET scanner to improve the spatial resolution and sensitivity., (© 2024 American Association of Physicists in Medicine.)

Objective: In ophthalmic surgery, different materials and fixation methods are employed for bone flap repositioning after lateral orbitotomy approach (LOA), yet there is no unified standard. This study aims to investigate the impact of different fixation strategies on orbital stability through Finite Element Analysis (FEA) simulations of the biomechanical environment for orbital rim fixation in LOA., Methods: A Finite Element Model (FEM) was established and validated to simulate the mechanical responses under various loads in conventional lateral orbitotomy approach (CLOA) and deep lateral orbital decompression (DLOD) using single titanium plate, double titanium plates, and double absorbable plates fixation methods. The simulations were then validated against clinical cases., Results: Under similar conditions, the maximum equivalent stress (MES) on titanium alloy fixations was greater than that on absorbable plate materials. Both under static and physiological conditions, all FEM groups ensured structural stability of the system, with material stresses remaining within safe ranges. Compared to CLOA, DLOD, which involves the removal of the lateral orbital wall, altered stress conduction, resulting in an increase of MES and maximum total deformation (MTD) by 1.96 and 2.62 times, respectively. Under a horizontal load of 50 N, the MES in FEM/DLOD exceeded the material's own strength, with an increase in MES and MTD by 3.18 and 6.64 times, respectively, compared to FEM/CLOA. Under a vertical force of 50 N, the MES sustained by each FEM was within safe limits. Bone flap rotation angles remained minimally varied across scenarios. During follow-up, the 12 patients validated in this study did not experience complications related to the internal fixation devices., Conclusion: Under static or physiological conditions, various fixation methods can effectively maintain stability at the orbitotomy site, and absorbable materials, with their smoother stress transmission properties, are more suited for application in CLOA. Among titanium plate fixations, single titanium plates can better withstand vertical stress, while double titanium plates are more capable of handling horizontal stress. Given the change in the orbital mechanical behavior due to DLOD, enhanced fixation strength should be considered for bone flap repositioning., 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 Masson SAS. All rights reserved.)

Zn ion batteries (ZIBs) are promising for large-scale energy storage but their practical application is plagued by inhomogeneous Zn deposition. Despite much effort, the harm of simultaneous hydrogen evolution reaction (HER) during plating to Zn deposition, has not received sufficient studies. Herein, Sn-modified Cu nanowires (Sn@CuNWs) with Sn-Cu core-shell nanostructure to achieve uniform Zn deposition by zinc affinity-HER tendency trade-off are fabricated. Confirmed by both theoretical calculation and practical characterization, the nanowires with high zinc affinity and large deposition sites facilitate Zn deposition, while the enlarged HER tendency harmful to Zn plating is inhibited by Sn nanoshell. Therefore, the Zn deposited Sn@CuNWs anode delivers a long lifespan of 800 h at 5 mA cm -2 , and the full cell exhibits a high capacity of 294.4 mAh g -1 at 5 A g -1 and a high capacity retention of 97.8% after 2500 cycles. This work reveals the importance of HER regulation for reversible Zn deposition, which should be noticed in further research., (© 2024 Wiley‐VCH GmbH.)

Background: The correlation between heading date and flowering time significantly regulates grain filling and seed formation in barley and other crops, ultimately determining crop productivity. In this study, the transcriptome, hormone content detection, and metabolome analysis were performed systematically to analyze the regulatory mechanism of heading time in highland barley under different light conditions. The heading date of D18 (winter highland barley variety, Dongqing18) was later than that of K13 (vernal highland barley variety) under normal growth conditions or long-day (LD) treatment, while this situation will reverse with short-day (SD) treatment., Results: The circadian rhythm plant, plant hormone signaling transduction, starch and sucrose metabolism, and photosynthesis-related pathways are significantly enriched in barley under SD and LD to influence heading time. In the plant circadian rhythm pathway, the key genes GI (Gigantea), PRR (Pesudoresponseregulator), FKF1 (Flavin-binding kelch pepeat F-Box 1), and FT (Flowering locus T) are identified as highly expressed in D18SD3 and K13SD2, while they are significantly down-regulated in K13SD3. These genes play an important role in regulating the heading date of D18 earlier than that of K13 under SD conditions. In photosynthesis-related pathways, a-b binding protein and RBS were highly expressed in K13LD3, while NADP-dependent malic enzyme, phosphoenolpyruvate carboxylase, fructose-bisphosphate aldolase, and triosephosphate isomerase were significantly expressed in D18SD3. In the starch and sucrose metabolism pathway, 41 DEGs (differentially expressed genes) and related metabolites were identified as highly expressed and accumulated in D18SD3. The DEGs SAUR (Small auxin-up RNA), ARF (Auxin response factor), TIR1 (Transport inhibitor response 1), EIN3 (Ethylene-insensitive 3), ERS1 (Ethylene receptor gene), and JAZ1 (Jasmonate ZIM-domain) in the plant hormone pathway were significantly up-regulated in D18SD3. Compared with D18LD3, the content of N6-isopentenyladenine, indole-3-carboxylic acid, 1-aminocyclopropanecarboxylic acid, trans-zeatin, indole-3-carboxaldehyde, 1-O-indol-3-ylacetylglucose, and salicylic acid in D18SD3 also increased. The expression levels of vernalization genes (HvVRN1, HvVRN2, and HvVRN3), photoperiod genes (PPD), and PPDK (Pyruvate phosphate dikinase) that affect photosynthetic efficiency in barley are also analyzed, which play important regulatory roles in barley heading date. The WGCNA analysis of the metabolome data and circadian regulatory genes identified the key metabolites and candidate genes to regulate the heading time of barley in response to the photoperiod., Conclusion: These studies will provide a reference for the regulation mechanism of flowering and the heading date of highland barley., (© 2024. The Author(s).)

Ovarian cancer (OC) is one of the most common malignancies and a leading cause of death among women worldwide. The ubiquitin pathway plays an important role in OC development. Using the single nucleotide polymorphism data obtained using the prevalence and dominance strategies, four ubiquitin marker genes were identified according to their expression levels: BARD1, BRCA2, FANCA, and BRCA1. Based on these four genes, a consensus clustering of OC expression data was performed. The significant differences in the survival analysis, ESTIMATE, and CIBERSORT results among the clusters indicated the pivotal role of these four genes in OC development. Of the ubiquitin-representative genes in each cluster, two ubiquitin genes, TOP2A and MYLIP , were identified in the survival risk model after univariate survival, Least Absolute Shrinkage and Selection Operator regression, and multivariate survival analyses. The reliability and robustness of both the training and validation data were confirmed by comparing the significant survival difference between high- and low-risk patients. We further explored the association between our risk model and clinical outcomes as well as predicted potentially interacting drugs. The co-expression network showed clear interactions among the four marker genes and two model genes and between high- and low-risk differentially expressed genes. Significantly enriched genes were found in pathways associated with ion channels, channel activity, and neuroactive ligand-receptor interactions. Therefore, suggesting the involvement of ubiquitin genes in the survival and development of OC through neurohumoral regulation. Our results will provide valuable reference or supplementary information for studies investigating OC diagnosis and therapies., Competing Interests: 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., (© 2024 The Authors.)

Introduction: A local microneedle patch loaded with 5-aminolevulinic acid (ALA) was constructed to improve the efficiency of ALA photodynamic treatment of oral leukoplakia, reduce local photosensitivity reactions, and promote the healing of lesions., Methods: The microneedle patch loaded with ALA was constructed with the hyaluronic acid (HA) solution (ALA-HAMN), and its morphology, strength, mucosal penetration, and biocompatibility were tested., Results: In vivo safety and permeability tests confirmed that ALA-HAMN had good biocompatibility and could penetrate the mucosal barrier and quickly dissolve and release ALA for in situ transdermal administration. The 4-nitroquinoline oxide (NQO) rat model experiment showed that ALA-HAMN can significantly improve photodynamic therapy (PDT) efficiency and has no damage to mucosal tissue compared with the commonly used ALA cotton ball dressing., Conclusions: The ALA-loaded microneedle patch was successfully constructed for the photodynamic treatment of oral leukoplakia, and the photodynamic efficiency and comfort of oral leukoplakia were improved, which provided an effective delivery mode to improve clinical ALA-PDT treatment of oral leukoplakia (OLK)., 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.)

Designing non-noble metal single-atom catalysts (M-SACs) for two-electron oxygen reduction reaction (2e-ORR) is attractive for the hydrogen peroxide (H 2 O 2 ) electrosynthesis, in which the coordination configuration of the M-SACs essentially affects the reaction activity and product selectivity. Though extensively investigated, a generalized coordination engineering strategy has not yet been proposed, which fundamentally hinders the rational design of M-SACs with optimized catalytic capabilities. Herein, a generalized coordination engineering strategy is proposed for M-SACs toward H 2 O 2 electrosynthesis via introducing heteroatoms (e.g., oxygen or sulfur atoms) with higher or lower electronegativity than nitrogen atoms into the first sphere of metal-N 4 system to tailor their electronic structure and adjust the adsorption strength for * OOH intermediates, respectively, thus optimizing their electrocatalytic capability for 2e-ORR. Specifically, the (O, N)-coordinated Co SAC (Co-N 3 O) and (S, N)-coordinated Ni SAC (Ni-N 3 S) are precisely synthesized, and both present superior 2e-ORR activity (E onset : ≈0.80 V versus RHE) and selectivity (≈90%) in alkaline conditions compared with conventional Co-N 4 and Ni-N 4 sites. The high H 2 O 2 yield rates of 14.2 and 17.5 moL g -1  h -1 and long-term stability over 12 h are respectively achieved for Co-N 3 O and Ni-N 3 S. Such favorable 2e-ORR pathway of the catalysts is also theoretically confirmed by the kinetics simulations., (© 2024 Wiley‐VCH GmbH.)

This study aimed to explore the influence of excess iodine on the articular cartilage and epiphyseal growth plate in rats. Wistar rats (n = 200) were randomly divided into five groups with 40 rats in each: normal iodine (NI), 5-fold high iodine group (5HI), 10-fold high iodine group (10HI), 50-fold high iodine group (50HI), and 100-fold high iodine group (100HI). The rats were executed in 6 and 12 months. 24-h urinary iodine concentration (UIC) was monitored by arsenic-cerium catalytic spectrophotometry. The chemiluminescence method was used to determine the thyroid function. The pathological changes in the epiphyseal plate, articular cartilage, and thickness of the epiphyseal plate were observed. The mRNA expression of collagen II (ColII), collagen X, matrix metalloproteinase-13 (MMP-13), and fibroblast growth factor receptor 1 in articular chondrocytes was detected by RT-PCR. 24-h UIC increased as iodine intake increased. In the 12th month, there was a significant increase in serum sTSH and a decrease in serum FT 4 in HI groups, compared to the NI group. There was a decrease in the number of proliferating cells in the epiphyseal plate and an increase in the number of mast cell layers. The chondrocytes appeared disorganized, and the tidal lines were disturbed or even broken. Growth plate thickness decreased with increasing iodine intake. Compared with the NI group, ColII and MMP-13 mRNA expression in chondrocytes in all HI groups significantly increased. Chronic iodine overdose increases the risk of hypothyroidism. Chronic iodine overdose leads to abnormal morphology of epiphyseal growth plates and articular cartilage, increasing the risk of osteoarthritis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Magnolia wufengensis , a newly discovered ornamental species in the Magnoliaceae family, is susceptible to salinity. Moreover, Ca 2+ is an essential element for plant growth and is receiving increasing attention for its ability to mitigate the negative effects of environmental stress on plants. In the present study, we investigated the effect of Ca 2+ on the growth and transcriptome of M. wufengensis under salt stress. The treatments used here were as follows: control, NaCl (150 mmol/L), CaCl 2 (5 mmol/L), and NaCl (150 mmol/L) + CaCl 2 (5 mmol/L). After a 60-day treatment period, plant growth indices were determined, and leaves were collected for physiological analysis and transcriptome investigation. The combined application of NaCl and CaCl 2 alleviated phenotypic damage and restored seedling growth. Moreover, RNA sequencing data revealed that in the Na vs. control group and the NaCa vs. Na group, there were 968 and 2632 differentially expressed genes, respectively, which were both primarily enriched in secondary metabolism, glutathione metabolism, signaling hormone metabolism, glucose metabolism, and amino acid metabolism. These pathways were analyzed to screen key genes: the adenosine triphosphate (ATP)-binding cassette efflux transporter G1 (ABCG1) genes, which are related to transmembrane transport; the calmodulin genes, which are related to signal transmission; and the glutathione S-transferase (GST), glutathione peroxidase (GPX), and peroxidase (POD) genes related to antioxidant enzymes. Lastly, we constructed a hypothesis model of Ca 2+ -enhanced salt tolerance in M. wufengensis . This study reveals the potential mechanisms by which Ca 2+ enhances the salt tolerance of M. wufengensis and provides a theoretical reference for its cultivation in saline areas.

Spinal cord injury is a serious traumatic nervous system disorder characterized by extensive neuronal apoptosis. Oxidative stress, a key factor in neuronal apoptosis, leads to the accumulation of reactive oxygen species, making mitochondrial quality control within cells crucial. Previous studies have demonstrated zinc's anti-inflammatory and anti-apoptotic properties in protecting mitochondria during spinal cord injury treatment, yet the precise mechanisms remain elusive. Single-cell sequencing analysis has identified Lgals3 and Bax as core genes in apoptosis. This study aimed to investigate whether zinc ions protect intracellular mitochondria by inhibiting the apoptotic proteins Lgals3 and Bax. We elucidated zinc ions' key role in mitigating mitochondrial quality control dysfunction triggered by oxidative stress and confirmed this was achieved by targeting the Lgals3-Bax pathway. Zinc's inhibitory effect on this pathway not only preserved mitochondrial integrity but also significantly reduced PANoptosis after spinal cord injury. Under oxidative stress, zinc ion regulation of mitochondrial quality control reveals an organelle-targeted therapeutic strategy, offering a novel approach for more precise treatment of spinal cord injury., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Herein, we present a one-pot method for the direct cross-coupling of aryl diazonium salts and aryl bromides in an economical way that avoids the use of sensitive organometallic reagents. The reaction is accomplished with the assistance of nickel catalysts, ligands, magnesium turnings, lithium chloride, and triethylamine, avoiding the use of pre-activated organometallic reagents.

Background: Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) stand as pivotal diagnostic tools for brain disorders, offering the potential for mutually enriching disease diagnostic perspectives. However, the costs associated with PET scans and the inherent radioactivity have limited the widespread application of PET. Furthermore, it is noteworthy to highlight the promising potential of high-field and ultra-high-field neuroimaging in cognitive neuroscience research and clinical practice. With the enhancement of MRI resolution, a related question arises: can high-resolution MRI improve the quality of PET images?, Purpose: This study aims to enhance the quality of synthesized PET images by leveraging the superior resolution capabilities provided by high-field and ultra-high-field MRI., Methods: From a statistical perspective, the joint probability distribution is considered the most direct and fundamental approach for representing the correlation between PET and MRI. In this study, we proposed a novel model, the joint diffusion attention model, namely, the joint diffusion attention model (JDAM), which primarily focuses on learning information about the joint probability distribution. JDAM consists of two primary processes: the diffusion process and the sampling process. During the diffusion process, PET gradually transforms into a Gaussian noise distribution by adding Gaussian noise, while MRI remains fixed. The central objective of the diffusion process is to learn the gradient of the logarithm of the joint probability distribution between MRI and noise PET. The sampling process operates as a predictor-corrector. The predictor initiates a reverse diffusion process, and the corrector applies Langevin dynamics., Results: Experimental results from the publicly available Alzheimer's Disease Neuroimaging Initiative dataset highlight the effectiveness of the proposed model compared to state-of-the-art (SOTA) models such as Pix2pix and CycleGAN. Significantly, synthetic PET images guided by ultra-high-field MRI exhibit marked improvements in signal-to-noise characteristics when contrasted with those generated from high-field MRI data. These results have been endorsed by medical experts, who consider the PET images synthesized through JDAM to possess scientific merit. This endorsement is based on their symmetrical features and precise representation of regions displaying hypometabolism, a hallmark of Alzheimer's disease., Conclusions: This study establishes the feasibility of generating PET images from MRI. Synthesis of PET by JDAM significantly enhances image quality compared to SOTA models., (© 2024 American Association of Physicists in Medicine.)

Background: The impact of transcatheter closure of coronary artery fistula (CAF) and residual shunt after occlusion on improving blood flow in the donor vessel remains uncertain., Objectives: To evaluate the functional impact on the donor vessel following CAFs closure using QFR (Quantitative Flow Ratio) analysis., Methods: A total of 46 patients with 48 CAFs who underwent transcatheter closure at Shanghai Chest Hospital and Shuguang Hospital between March 2015 and August 2023 were included in the review. The clinical, angiographic details, and QFR data were subjected to analysis. The size of the fistulae was defined according to the ratio between the diameters of the fistulae and the largest diameter of the coronary vessel not feeding the coronary fistula., Results: Among 48 CAFs, the average diameter of the fistulae ostium was 3.19 ± 1.04 mm, while the mean diameter of the donor vessel segment following fistulae was 3.45 ± 1.01 mm. The mean QFR value of the donor vessels with medium CAFs was found to be significantly lower than those with small CAFs (0.93 ± 0.10 vs. 0.98 ± 0.03; p  < 0.05). Furthermore, the mean QFR value of donor vessels with medium CAFs was observed to be significantly improved after occlusion (0.99 ± 0.01 vs. 0.93 ± 0.10; p  = 0.01). However, there was no statistical difference in the mean QFR value of donor vessels with small CAFs before and after occlusion (0.98 ± 0.03 vs. 0.98 ± 0.02; p  > 0.05). Moreover, the changes in QFR were more pronounced in donor vessels with medium CAFs compared to those with small CAFs after occlusion (0.06 ± 0.10 vs. 0.005 ± 0.012; p  = 0.01). There is no statistical difference in the mean QFR variation and QFR variation rate between donor vessels with CAFs that occurred residual shunt and those without residual shunt after occlusion ( p  > 0.05)., Conclusions: The presence of medium CAFs has a significant impact on the blood flow of the donor vessel, as compared to small CAFs, and may benefit from occlusion. A small residual shunt has no significant impact on the effectiveness of CAFs occlusion in enhancing donor blood flow., 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., (© 2024 Sang, Ji, Tong, Shen, Wang and He.)

Background: Stroke patients with coexisting intracranial artery stenosis (ICAS) and white matter lesions (WML) usually have a poor outcome. However, how WML affects stroke prognosis has not been determined., Objective: To investigate the quantitative forward flow at the middle cerebral artery in ICAS patients with different degrees of WML using 4D flow., Design: Single-center cross-sectional cohort study., Methods: Ischemic stroke patients with symptomatic middle cerebral artery (MCA) atherosclerosis were included, and they were divided into 2 groups based on Fazekas scale on Flair image (mild group = Fazekas 0-2, and severe group = Fazekas >2), TOF-MRA and 4D flow were performed to quantify the stenosis degree and forward flow at the proximal of stenosis. The flow parameters were compared between different white matter hyperintensity (WMH) groups, as well as in different MCA stenosis groups, logistic regression was used to validate the association between forward flow and WMH., Results: A total of 66 patients were included in this study (mean age 56 years old, 68.2% male). 77.3% of them presented with WMH (Fazekas 1-5). Comparison of flow index between mild and severe WMH groups found a significantly lower forward flow (2.34 ± 1.09 vs 3.04 ± 1.35), higher PI (0.75 ± 0.43 vs 0.66 ± 0.32), and RI (0.49 ± 0.19 vs 0.46 ± 0.15) at ipsilateral infarction MCA in the severe WMH group, all P -values <0.05. After adjusting for other covariates, forward mean flow at ipsilateral infarction MCA is still associated with severe WMH independently, OR = 0.537, 95% CI (0.294, 0.981), P = 0.043., Conclusion: Intracranial artery stenosis patients with coexisting severe WMH suffer from significantly decreased flow, which could explain the poor clinical outcome in this population, and also provide some insight into recanalization therapy in the future., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Advancing the high-voltage stability of the O3-type layered cathodes for sodium-ion batteries is critical to boost their progress in energy storage applications. However, this type of cathode often suffers from intricate phase transition and structural degradation at high voltages (i.e., >4.0 V vs Na + /Na), resulting in rapid capacity decay. Here, we present a Li/Ti cosubstitution strategy to modify the electronic configuration of oxygen elements in the O3-type layered oxide cathode. This deliberate modulation simultaneously mitigates the phase transitions and counteracts the weakening of the shielding effect resulting from the extraction of sodium ions, thus enhancing the electrostatic bonding within the TM layer and inducing and optimizing the O3-OP2 phase transition occurring in the voltage range of 2.0-4.3 V. Consequently, the cosubstituted NaLi 1/9 Ni 1/3 Mn 4/9 Ti 1/9 O 2 exhibits an astounding capacity of 161.2 mAh g -1 in the voltage range of 2.0-4.3 V at 1C, and stable cycling up to 100 cycles has been achieved. This work shows the impact mechanism of element substitution on interlayer forces and phase transitions, providing a crucial reference for the optimization of O3-type materials.

Background: Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis)., Results: In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P < 0.05, LDA > 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal., Conclusions: This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host's food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem., (© 2024. The Author(s).)

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly‑oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC 50 values ranging from 24.83 to 45.46 μM, while the IC 50 values of the positive control adriamycin was ranging from 1.11 to 1.44 μM., 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.)

Open science skills are increasingly important for a career in ecology and evolutionary biology (EEB) as efforts to make data and analyses publicly available continue to become more commonplace. While learning core concepts in EEB, students are also expected to gain skills in conducting open science to prepare for future careers. Core open science skills like programming, data sharing, and practices that promote reproducibility can be taught to undergraduate students alongside core concepts in EEB. Yet, these skills are not always taught in biology undergraduate programs, and a major challenge in developing open science skills and learning EEB concepts simultaneously is the high cognitive load associated with learning multiple disparate concepts at the same time. One solution is to provide students with easily digestible, scaffolded, pre-formatted code in the form of vignettes and interactive tutorials. Here, we present six open source teaching tutorials for undergraduate students in EEB. These tutorials teach fundamental ecological concepts, data literacy, programming (using R software), and analysis skills using publicly available datasets while introducing students to open science concepts and tools. Spanning a variety of EEB topics and skill levels, these tutorials serve as examples and resources for educators to integrate open science tools, programming, and data literacy into teaching EEB at the undergraduate level., Competing Interests: The authors declare that there are no competing interests., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, the hit compound CDI (IC 50  = 2.46 ± 0.33 μM) was identified by screening of an in-house compound library. And then novel potent benzimidazole derivatives were designed and synthesized as core assembly modulators, and their antiviral effects were evaluated in vitro and in vivo biological experiments. The results indicated that compound 26f displayed the most optimized modulator of HBV capsid assembly (IC 50  = 0.51 ± 0.20 μM, EC 50  = 2.24 ± 0.43 μM, CC 50  = 84.29 μM) and high selectivity index. Moreover, treatment with compound 26f for 14 days significantly decreased serum levels of HBV DNA levels in the Hydrodynamic-Injection (HDI) mouse model. Therefore, compound 26f could be considered as a promising candidate drug for further development of novel HBV CAMs with the desired potency and safety., Competing Interests: Declaration of competing interest The authors declared that there were no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Casein (CN) is the primary allergenic protein in cow's milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights. The unique internal and external structural characteristics of mCN were substantiated by disparities in surface microstructure, alterations in the secondary structure, variations in free amino acid contents, and modifications in functional molecular groups. Despite the lower digestibility of TCN and GCN compared to LCN, they significantly suppressed IL-8 production in Caco-2 cells without significantly promoting their proliferation. Moreover, GCN showed the weakest capacity to induce LAD2 cell degranulation. Despite the therapeutic effect of TCN, GCN-treated mice displayed the most prominent attenuation of allergic reactions and a remarkably restored Th1/Th2 imbalance, while LCN administration resulted in severe allergic phenotypes and endotypes in both cellular and murine models. This study highlighted the detrimental effect of linear modifications and underscored the significance of glycation in relation to CN allergenicity.